CURAGEN CORP, S-1/A, 1997-11-06

CURAGEN CORP
S-1/A, 1997-11-06
COMMERCIAL PHYSICAL & BIOLOGICAL RESEARCH

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AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON NOVEMBER 6, 1997

REGISTRATION NO. 333-38051
- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------

SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

---------------

AMENDMENT NO. 1

FORM S-1
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933

---------------

CURAGEN CORPORATION
(EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

DELAWARE 8731 06-1331400
(STATE OR OTHER (PRIMARY STANDARD (I.R.S. EMPLOYER
JURISDICTION OF INDUSTRIAL IDENTIFICATION NO.)
INCORPORATION OR CLASSIFICATION CODE
ORGANIZATION) NUMBER)

555 LONG WHARF DRIVE, 11TH FLOOR
NEW HAVEN, CONNECTICUT 06511
(203) 401-3330
(203) 401-3333 FACSIMILE
(ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER, INCLUDING AREA CODE, OF
REGISTRANT'S PRINCIPAL EXECUTIVE OFFICES)

---------------

JONATHAN M. ROTHBERG, PH.D.
CHIEF EXECUTIVE OFFICER, PRESIDENT AND
CHAIRMAN OF THE BOARD
CURAGEN CORPORATION
555 LONG WHARF DRIVE, 11TH FLOOR
NEW HAVEN, CONNECTICUT 06511
(203) 401-3330
(203) 401-3333 FACSIMILE
(NAME, ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER, INCLUDING AREA CODE,
OF AGENT FOR SERVICE)

---------------

COPIES TO:

JONATHAN L. KRAVETZ, ESQ. KEITH F. HIGGINS, ESQ.
STANFORD N. GOLDMAN, JR., ESQ. ROPES & GRAY
MINTZ, LEVIN, COHN, FERRIS, ONE INTERNATIONAL PLACE
GLOVSKY AND POPEO, P.C. BOSTON, MASSACHUSETTS 02110
ONE FINANCIAL CENTER (617) 951-7000
BOSTON, MASSACHUSETTS 02111 (617) 951-7050 FACSIMILE
(617) 542-6000
(617) 542-2241 FACSIMILE

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APPROXIMATE DATE OF COMMENCEMENT OF PROPOSED SALE TO THE PUBLIC: As soon as
practicable after this Registration Statement becomes effective.

If any of the securities being registered on this Form are to be offered on
a delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, as amended (the "Securities Act"), check the following box. [_]

If this Form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, check the following box and
list the Securities Act registration statement number of the earlier effective
registration statement for the same offering. [_]

If this Form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. [_]

If this Form is a post-effective amendment filed pursuant to Rule 462(d)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. [_]

If delivery of the prospectus is expected to be made pursuant to Rule 434,
please check the following box. [_]

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THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR
DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT
SHALL FILE A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS
REGISTRATION STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH
SECTION 8(A) OF THE SECURITIES ACT OF 1933 OR UNTIL THIS REGISTRATION
STATEMENT SHALL BECOME EFFECTIVE ON SUCH DATE AS THE SECURITIES AND EXCHANGE
COMMISSION, ACTING PURSUANT TO SAID SECTION 8(A), MAY DETERMINE.

- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------
<PAGE>

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
+INFORMATION CONTAINED HEREIN IS SUBJECT TO COMPLETION OR AMENDMENT. A +
+REGISTRATION STATEMENT RELATING TO THESE SECURITIES HAS BEEN FILED WITH THE +
+SECURITIES AND EXCHANGE COMMISSION. THESE SECURITIES MAY NOT BE SOLD NOR MAY +
+OFFERS TO BUY BE ACCEPTED PRIOR TO THE TIME THE REGISTRATION STATEMENT +
+BECOMES EFFECTIVE. THIS PROSPECTUS SHALL NOT CONSTITUTE AN OFFER TO SELL OR +
+THE SOLICITATION OF AN OFFER TO BUY NOR SHALL THERE BE ANY SALE OF THESE +
+SECURITIES IN ANY STATE IN WHICH SUCH OFFER, SOLICITATION OR SALE WOULD BE +
+UNLAWFUL PRIOR TO REGISTRATION OR QUALIFICATION UNDER THE SECURITIES LAWS OF +
+ANY SUCH STATE. +
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
PROSPECTUS (Subject to Completion)

Issued November 6, 1997

[Company Logo]

CuraGen Corporation

COMMON STOCK

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ALL OF THE SHARES OF COMMON STOCK ARE BEING SOLD BY CURAGEN CORPORATION
(THE "COMPANY"). PRIOR TO THIS OFFERING, THERE HAS BEEN NO PUBLIC MARKET
FOR THE COMMON STOCK OF THE COMPANY. IT IS CURRENTLY ESTIMATED THAT
THE INITIAL PUBLIC OFFERING PRICE PER SHARE WILL BE BETWEEN $
AND $ . SEE "UNDERWRITERS" FOR A DISCUSSION OF THE FACTORS
CONSIDERED IN DETERMINING THE INITIAL PUBLIC OFFERING
PRICE.

BIOGEN, INC. ("BIOGEN"), ONE OF THE COMPANY'S COLLABORATIVE PARTNERS AND AN
EXISTING STOCKHOLDER, HAS AGREED TO PURCHASE $5,000,000 OF THE
COMPANY'S COMMON STOCK IN A PRIVATE PLACEMENT CONCURRENT WITH THIS
OFFERING AT A PRICE PER SHARE EQUAL TO THE PRICE TO PUBLIC
BELOW. THE SALE OF SUCH SHARES OF COMMON STOCK WILL NOT
BE REGISTERED IN THIS OFFERING. SEE "BUSINESS--
RESEARCH COLLABORATIONS."

----------

APPLICATION HAS BEEN MADE TO LIST THE COMMON STOCK FOR QUOTATION ON THE
NASDAQ NATIONAL MARKET UNDER THE SYMBOL "CRGN."

----------

THIS OFFERING INVOLVES A HIGH DEGREE OF RISK. SEE "RISK FACTORS"
BEGINNING ON PAGE 8 OF THIS PROSPECTUS.

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THESE SECURITIES HAVE NOT BEEN APPROVED OR DISAPPROVED BY THE SECURITIES AND
EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION NOR HAS THE
SECURITIES AND EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION
PASSED UPON THE ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY
REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.

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PRICE $ A SHARE

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<TABLE>
<CAPTION>
UNDERWRITING
PRICE TO DISCOUNTS AND PROCEEDS TO
PUBLIC COMMISSIONS(1) COMPANY(2)
-------- -------------- -----------
<S> <C> <C> <C>
Per Share................................... $ $ $
Total(3).................................... $ $ $
</TABLE>
- -----
(1) The Company has agreed to indemnify the Underwriters against certain
liabilities, including liabilities under the Securities Act of 1933, as
amended.
(2) Before deducting expenses payable by the Company estimated at $ .
(3) The Company has granted to the Underwriters an option, exercisable within
30 days of the date hereof, to purchase up to an aggregate of
additional Shares at the price to public less underwriting discounts and
commissions for the purpose of covering overallotments, if any. If the
Underwriters exercise such option in full, the total price to public,
underwriting discounts and commissions and proceeds to Company will be
$ , $ and $ , respectively. See "Underwriters."

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The Shares are offered, subject to prior sale, when, as and if accepted by
the Underwriters named herein and subject to approval of certain legal matters
by Ropes & Gray, counsel for the Underwriters. It is expected that delivery of
the Shares will be made on or about , 1997 at the office of Morgan Stanley
& Co. Incorporated, New York, N.Y., against payment therefor in immediately
available funds.

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MORGAN STANLEY DEAN WITTER

LEHMAN BROTHERS

BEAR, STEARNS & CO. INC.

, 1997
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[GRAPHICAL DEPICTION OF THE COMPANY'S GENOMICS TECHNOLOGY PLATFORM]

<PAGE>

NO PERSON IS AUTHORIZED IN CONNECTION WITH ANY OFFERING MADE HEREBY TO GIVE
ANY INFORMATION OR TO MAKE ANY REPRESENTATION NOT CONTAINED IN THIS
PROSPECTUS, AND, IF GIVEN OR MADE, SUCH INFORMATION OR REPRESENTATION MUST NOT
BE RELIED UPON AS HAVING BEEN AUTHORIZED BY THE COMPANY OR BY ANY UNDERWRITER.
THIS PROSPECTUS DOES NOT CONSTITUTE AN OFFER TO SELL OR A SOLICITATION OF AN
OFFER TO BUY ANY SECURITY OTHER THAN THE SHARES OF COMMON STOCK OFFERED
HEREBY, NOR DOES IT CONSTITUTE AN OFFER TO SELL OR A SOLICITATION OF AN OFFER
TO BUY ANY OF THE SECURITIES OFFERED HEREBY TO ANY PERSON IN ANY JURISDICTION
IN WHICH IT IS UNLAWFUL TO MAKE SUCH AN OFFER OR SOLICITATION TO SUCH PERSON.
NEITHER THE DELIVERY OF THIS PROSPECTUS NOR ANY OFFER OR SALE MADE HEREBY
SHALL UNDER ANY CIRCUMSTANCE IMPLY THAT THE INFORMATION CONTAINED HEREIN IS
CORRECT AS OF ANY DATE SUBSEQUENT TO THE DATE HEREOF.

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UNTIL , 1997 (25 DAYS AFTER THE COMMENCEMENT OF THE OFFERING), ALL
DEALERS EFFECTING TRANSACTIONS IN THE COMMON STOCK, WHETHER OR NOT
PARTICIPATING IN THIS DISTRIBUTION, MAY BE REQUIRED TO DELIVER A PROSPECTUS.
THIS IS IN ADDITION TO THE OBLIGATION OF DEALERS TO DELIVER A PROSPECTUS WHEN
ACTING AS UNDERWRITERS AND WITH RESPECT TO THEIR UNSOLD ALLOTMENTS OR
SUBSCRIPTIONS.

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TABLE OF CONTENTS

<TABLE>
<CAPTION>
PAGE
----
<S> <C>
Prospectus Summary.................. 4
Risk Factors........................ 8
Use of Proceeds..................... 20
Dividend Policy..................... 20
Capitalization...................... 21
Dilution............................ 22
Selected Financial Data............. 23
Management's Discussion and Analysis
of Financial Condition and Results
of Operations...................... 24
Business............................ 29
</TABLE>
<TABLE>
<CAPTION>
PAGE
----
<S> <C>
Management............................................................ 50
Certain Transactions.................................................. 57
Principal Stockholders................................................ 59
Description of Capital Stock.......................................... 61
Shares Eligible for Future Sale....................................... 65
Underwriters.......................................................... 67
Legal Matters......................................................... 68
Experts............................................................... 68
Additional Information................................................ 69
Glossary.............................................................. 70
Index to Financial Statements......................................... F-1
</TABLE>

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The Company intends to furnish to its stockholders annual reports containing
audited financial statements and an opinion thereon expressed by independent
accountants and quarterly reports for the first three quarters of each fiscal
year containing interim financial information.

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CERTAIN PERSONS PARTICIPATING IN THE OFFERING MAY ENGAGE IN TRANSACTIONS
THAT STABILIZE, MAINTAIN OR OTHERWISE AFFECT THE PRICE OF THE COMMON STOCK.
SPECIFICALLY, THE UNDERWRITERS MAY OVERALLOT IN CONNECTION WITH THE OFFERING,
AND MAY BID FOR, AND PURCHASE, SHARES OF THE COMMON STOCK IN THE OPEN MARKET.
FOR A DESCRIPTION OF THESE ACTIVITIES, SEE "UNDERWRITERS."

----------------

In this Prospectus, the terms the "Company" or "CuraGen" shall mean CuraGen
Corporation. The Company's corporate headquarters are located at 555 Long
Wharf Drive, New Haven, Connecticut 06511, and its telephone number is (203)
401-3330.

GeneScape(R) is a trademark of the Company which has been registered with
the United States Patent and Trademark Office. GeneCalling(TM),
PathCalling(TM), HitCalling(TM), GeneShop(TM), QEA(TM), MIM(TM), CombiGen(TM),
OGI(TM), Niagara(TM), Niagara(TM), MicroNiagara(TM) and NanoNiagara(TM) are
trademarks or service marks of the Company for which registration applications
have been filed with the United States Patent and Trademark Office.

3
<PAGE>

PROSPECTUS SUMMARY

The following summary is qualified in its entirety by the more detailed
information, including "Risk Factors" and the Financial Statements and Notes
thereto, appearing elsewhere in this Prospectus. This Prospectus contains
forward-looking statements which involve risks and uncertainties. The Company's
actual results could differ materially from those anticipated in these forward-
looking statements as a result of certain factors, including those set forth
under "Risk Factors" and elsewhere in this Prospectus. A Glossary of technical
terms used in this Prospectus appears at page 70 of this Prospectus.

THE COMPANY

CuraGen Corporation ("CuraGen" or the "Company") is pioneering the systematic
application of genomics to accelerate the discovery and development of
therapeutic and agricultural products. CuraGen's fully-integrated genomics
technologies, processes and information systems are designed to rapidly
generate comprehensive information about gene expression, biological pathways
and the potential drugs that affect these pathways, each on a scale not
previously undertaken. The Company believes that it can overcome the
limitations of competing technologies, processes and databases and can condense
key steps in gene-based drug discovery and development. CuraGen believes its
technology platform will facilitate the development of highly specific and
effective drugs aimed at a variety of complex diseases such as cardiovascular
disease, stroke, cancer and metabolic disorders.

The Company's drug discovery platform has three primary systems, each
consisting of proprietary technologies, automated processes and a database: the
GeneCalling system for comprehensive gene expression analysis and gene
discovery; the PathCalling system for discovery of the roles of genes and the
proteins they encode in biological pathways; and the HitCalling system for
identification of small molecule drug candidates. The GeneCalling and
PathCalling systems are currently operational. The Company expects to complete
development of the HitCalling system in 1998. These systems are integrated to
enable gene discovery, drug target validation and high-throughput screening of
drug candidates in a highly efficient and cost-effective manner.

In addition to accelerating the discovery of new drug candidates, the Company
believes its GeneCalling and PathCalling systems are well-positioned to predict
the efficacy and safety of drug candidates currently in pharmaceutical
development pipelines and to review the performance and side effects of drugs
already on the market. This pharmacogenomics approach can aid in the
development of more effective, safer drugs and identify more appropriate
patient populations.

The Company's GeneCalling, PathCalling and HitCalling systems use proprietary
technologies to overcome current limitations of gene-based drug discovery. In
contrast to other gene expression methods used to identify disease-related
genes that may not detect previously undiscovered genes or genes expressed at
low levels, GeneCalling has been designed to measure 95% of the genes expressed
in any cell, including novel genes and those expressed at the level of a single
copy per cell. GeneCalling generates multiple fragments per gene for enhanced
reproducibility, precision and fault-tolerance. In order to validate proteins
as drug targets, PathCalling replaces cumbersome protein-by-protein research
methods with a process that tests simultaneously for interactions between
billions of combinations of proteins. PathCalling assembles these interactions
into a database of biological pathways to link a disease-related protein with
its biological role. HitCalling is designed to screen thousands of these
proteins simultaneously against hundreds of thousands of potential drugs,
building a database of targets and drug candidates to accelerate drug
discovery.

4
<PAGE>

technology platform, thereby allowing researchers interactive capabilities via
the internet for multiple sites to meet their individual discovery and
development needs. GeneScape also includes [GeneTools], a full-featured
bioinformatics software suite for further gene and protein characterization.

CuraGen's goal is to establish its fully-integrated technologies and
GeneScape operating system as the preferred platform for genomics and to
pursue, both internally and through collaborations, a broad portfolio of
research programs for drug discovery, drug development and pharmacogenomics.
During the next five years, the Company intends to analyze systematically the
genetic basis of many common diseases in order to identify potential
therapeutic proteins, targets and small molecule drug candidates. CuraGen is
marketing its genomics technology and information to pharmaceutical,
biotechnology and agricultural companies through research collaborations and
database subscriptions. Research collaborations will involve the application of
CuraGen's GeneCalling, PathCalling and HitCalling technologies to a
collaborator's projects and will include support services required to
characterize gene and target discoveries. Database subscriptions will provide
subscribers with access to CuraGen's GeneCalling, PathCalling and HitCalling
databases. The Company believes these collaborations and subscription
arrangements will establish milestone and royalty-based revenues from products
emerging from the drug development programs of multiple partners.

To date, CuraGen has entered into agreements with Pioneer Hi-Bred
International, Inc. ("Pioneer Hi-Bred") and Biogen. In May 1997, CuraGen and
Pioneer Hi-Bred established a research collaboration agreement. Under the terms
of the agreement, Pioneer Hi-Bred made a $7.5 million investment in the Company
and may fund up to $18.5 million in research at the Company to use GeneCalling
to identify genes responsible for agricultural seed product performance. In
October 1997, CuraGen and Biogen established a research collaboration and
database subscription arrangement to discover novel genes and therapeutics.
Under the terms of the agreement, Biogen agreed to invest $5 million in CuraGen
to purchase Common Stock (the "Biogen Shares") at the initial public offering
price and to provide a $10 million loan facility, convertible at CuraGen's
option into Common Stock. Biogen will additionally provide payments over five
years to support a research collaboration to generate project-specific
GeneCalling and PathCalling databases and for database subscription fees.
Payments could reach $18.5 million if the research collaboration and database
subscription arrangement both continue for the full five-year term. Biogen will
provide milestone payments up to $18.5 million for each therapeutic product
that attains certain development and commercialization milestones and will pay
royalties based on future product sales.

CuraGen has also used its GeneCalling and PathCalling systems in its internal
programs in areas including cardiovascular disease, stroke, cancer and
metabolic disorders, has discovered over disease-related genes and has filed
patent applications relating to these discoveries.

5
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THE OFFERING

<TABLE>
<S> <C>
Common Stock offered by the Company...... shares
Common Stock to be outstanding after the
Offering................................ shares(1)
Use of Proceeds.......................... The Company plans to use approxi-
mately $10 million of the net pro-
ceeds for capital expenditures and
$1,750,000 to redeem all of the Se-
ries B Preferred Stock. The balance
of the net proceeds will be used for
research and development, including
internal discovery programs, the
further development of its
GeneCalling, PathCalling and
HitCalling databases, and working
capital and general corporate pur-
poses. See "Use of Proceeds."
Proposed Nasdaq National Market Symbol... CRGN
</TABLE>

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(1) Based on 8,871,987 shares of Common Stock outstanding on September 30,
1997 and assuming the issuance of the Biogen Shares at a price equal
to the assumed initial public offering price of $ per share. Excludes
1,598,884 and 1,583,866 shares of Common Stock reserved for issuance upon
the exercise of stock options and warrants, respectively, outstanding on
September 30, 1997, at weighted average exercise prices of $3.75 and $4.12
per share, respectively. Also excludes an aggregate of 65,000 shares of
Common Stock issuable upon the exercise of stock options granted to non-
employee directors after September 30, 1997, at the initial public
offering price.

Unless otherwise indicated, all share and per share data in this Prospectus
have been adjusted to reflect: (i) the amendment and restatement of the
Company's Certificate of Incorporation (as amended and restated, the "Restated
Certificate"), to be filed and effective upon the closing of the Offering, to,
among other things, (a) increase the number of authorized shares of Common
Stock from 25,000,000 shares to 50,000,000 shares and (b) decrease the number
of authorized shares of Preferred Stock from 7,500,000 to 3,000,000 shares;
(ii) the conversion upon the closing of the Offering of all outstanding shares
of the Company's Series A Convertible Preferred Stock, Series C Convertible
Preferred Stock, Series D Convertible Preferred Stock and Series E Convertible
Preferred Stock into an aggregate of 3,418,635 shares of Common Stock (the
"Automatic Conversion"); (iii) the redemption upon the closing of the Offering
of all of the 175,000 outstanding shares of the Company's Series B Redeemable
Preferred Stock (the "Series B Preferred Stock"); (iv) the termination upon the
closing of the Offering of certain redemption rights relating to 394,031 shares
of Redeemable Common Stock (the "Redeemable Common Stock") described in Note 6
of Notes to Financial Statements; and (v) the issuance of the Biogen Shares
at a price per share equal to the assumed initial public offering price of $
per share. The information in this Prospectus assumes no exercise of the
Underwriters' over-allotment option. As used in this Prospectus, references to
"Biogen" include Biogen, Inc. and its wholly-owned subsidiary, Biotech
Manufacturing Limited.

6
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SUMMARY FINANCIAL DATA

The summary financial data set forth below should be read in conjunction
with, and are qualified by reference to, "Management's Discussion and Analysis
of Financial Condition and Results of Operations" and the Company's audited
financial statements and related notes appearing elsewhere in this Prospectus.

<TABLE>
<CAPTION>
NINE MONTHS ENDED
YEAR ENDED DECEMBER 31, SEPTEMBER 30,
----------------------------------- -----------------------
1994 1995 1996(1) 1996 1997(2)
--------- ----------- ----------- ---------- -----------
<S> <C> <C> <C> <C> <C>
STATEMENT OF OPERATIONS
DATA:
Revenue................. $ 257,536 $ 1,581,175 $ 4,422,947 $3,101,322 $ 4,171,750
--------- ----------- ----------- ---------- -----------
Operating expenses:
Research and
development.......... 647,640 1,466,375 3,516,035 2,192,740 6,431,139
General and
administrative....... 525,671 961,815 1,140,325 666,803 2,071,435
--------- ----------- ----------- ---------- -----------
Total operating
expenses........... 1,173,311 2,428,190 4,656,360 2,859,543 8,502,574
--------- ----------- ----------- ---------- -----------
Income (loss) from
operations............. (915,775) (847,015) (233,413) 241,779 (4,330,824)
Other income (expenses),
net.................... (40,254) (93,729) (162,746) (118,588) 217,979
--------- ----------- ----------- ---------- -----------
Net income (loss)....... (956,029) (940,744) (396,159) 123,191 (4,112,845)
Preferred dividends..... -- -- (17,106) -- (51,318)
--------- ----------- ----------- ---------- -----------
Net income (loss)
attributable to common
stockholders........... ($956,029) ($940,744) ($413,265) $123,191 ($4,164,163)
========= =========== =========== ========== ===========
Pro forma net loss per
share attributable to
common stockholders....
=========== ===========
Pro forma weighted
average number of
shares of common stock
outstanding............
=========== ===========
</TABLE>

<TABLE>
<CAPTION>
AS OF SEPTEMBER 30, 1997
---------------------------
ACTUAL AS ADJUSTED(3)
----------- --------------
<S> <C> <C>
BALANCE SHEET DATA:
Cash and cash equivalents........................... $20,781,115
Working capital..................................... 18,477,187
Total assets........................................ 26,944,446
Total long-term liabilities......................... 3,398,060
Redeemable Common Stock............................. 5,319,419
Series B Preferred Stock............................ 1,442,090
Accumulated deficit................................. (6,975,544)
Stockholders' equity................................ 15,060,353
</TABLE>
- --------

(1) During the year ended December 31, 1996, the Company completed its
development stage activities with the signing of its first collaborative
research agreement and commenced its planned principal operations.

(2) For an explanation of the calculation of pro forma weighted average number
of common shares outstanding, see Note 1 of Notes to Financial Statements.

(3) As adjusted to reflect the pro forma capitalization of the Company, giving
effect to the redemption of the 175,000 outstanding shares of Series B
Preferred Stock, the termination of certain redemption rights relating to
394,031 shares of Redeemable Common Stock and the sale of the shares of
Common Stock offered by the Company hereby and the Biogen Shares at an
assumed initial public offering price of $ per share and the receipt of
the estimated net proceeds therefrom.

7
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RISK FACTORS

An investment in the shares of Common Stock offered hereby involves a high
degree of risk. The following factors, in addition to the other information
contained in this Prospectus, should be carefully considered in evaluating the
Company and its business before purchasing the shares of Common Stock offered
hereby. This Prospectus contains forward-looking statements. For this purpose,
any statements contained herein that are not statements of historical fact may
be deemed to be forward-looking statements. Without limiting the foregoing,
the words "believes," "anticipates," "plans," "expects," "intends" and similar
expressions are intended to identify forward-looking statements. There are a
number of important factors that could cause the Company's actual results to
differ materially from those indicated by such forward-looking statements.
These factors include, without limitation, those set forth below and elsewhere
in this Prospectus.

EARLY STAGE OF DEVELOPMENT; HISTORY OF OPERATING LOSSES; UNCERTAINTY OF FUTURE
PROFITS

The Company has had a limited operating history and is at an early stage of
development. For the nine months ended September 30, 1997 and the years ended
December 31, 1996, 1995 and 1994, the Company had net losses attributable to
common stockholders of $4,164,163, $413,265, $940,744 and $956,029,
respectively, and as of September 30, 1997, the Company had an accumulated
deficit of $6,975,544. To date, a significant portion of the Company's revenue
has come from United States government grants. The development of the
Company's technologies, including the Company's expansion of its GeneCalling
and PathCalling database development efforts, together with the development of
its HitCalling database, will require substantial increases in expenditures
over the next several years. In addition, the Company expects to incur
substantial increases in expenditures in connection with its internal research
programs. As a result, the Company currently expects to incur operating losses
at least through 2000 and the Company may never achieve significant revenues
or profitability. The Company's ability to achieve significant revenues or
profitability will depend upon its ability to obtain research collaborators
and subscribers for its GeneCalling, PathCalling and HitCalling databases and
related products and services. The Company currently has two research
collaborations, one of which includes a database subscription arrangement, and
there can be no assurance that the Company will be able to obtain any
additional research collaborations or enter into any additional subscription
arrangements for such databases and related products and services.

There can be no assurance that the Company's technologies will continue to
be successfully developed, or that any therapeutic, agricultural or diagnostic
products discovered or developed through the utilization of such technologies
will prove to be commercially useful, meet applicable regulatory standards in
a timely manner or at all, successfully compete with other technologies and
products, avoid infringing the proprietary rights of others, be manufactured
in sufficient quantities or at reasonable costs or be marketed successfully.
The Company expects that it will be a number of years, if ever, before the
Company will recognize revenue from therapeutic, agricultural or diagnostic
product sales or royalties.

TECHNOLOGICAL UNCERTAINTY AND PRODUCT DEVELOPMENT RISK

The Company has developed and intends to continue to develop its
GeneCalling, PathCalling and HitCalling databases and related technology for
the identification of novel genes, biological pathways and drug candidates
useful for the discovery and development of therapeutic, agricultural and
diagnostic products. These technologies involve new and unproven approaches.
Failure to identify genes, biological pathways and drug candidates useful for
the discovery and development of therapeutic, agricultural and diagnostic
products could have a material adverse effect on the Company. The Company's
technology and development focus is primarily directed toward complex diseases
as well as agronomic traits. There is limited scientific understanding
generally relating to the role of genes in these diseases and traits, and few
products based on gene discoveries have been developed and commercialized.
Accordingly, even if the Company is successful in identifying genes,
biological pathways or drug candidates associated with specific diseases or in
identifying genes associated with certain agronomic traits, there can be no
assurance that these discoveries will lead to the development of therapeutic,
agricultural or diagnostic products. To date, the Company has not developed or
commercialized any such products based on its technological methods.

8
<PAGE>

In addition, the success of the Company's GeneCalling, PathCalling and
HitCalling databases and its related products and services will depend upon
the Company's ability to generate data concerning gene expression, biological
pathways and drug candidates using software tools. The Company's database
products are complex and sophisticated and could contain design defects or
software errors that are difficult to detect. There can be no assurance that
errors will not be found in the Company's current and future products, if any.

The Company's strategy of using a systematic analysis of the genome to
discover and develop novel therapeutic, agricultural and diagnostic products
is unproven. The Company's GeneCalling, PathCalling and HitCalling databases
and related products and services represent a business for which there is
little precedent. There can be no assurance that the Company's methods,
processes and related services will be accepted. To date, the Company has
entered into a research collaboration with Pioneer Hi-Bred and a research
collaboration and database subscription arrangement with Biogen. There can be
no assurance that the Company will be able to establish any additional
research collaborations or subscription arrangements. The Company's ability to
achieve and sustain profitability depends on attracting additional
collaborators and subscribers for its databases and related products and
services. In addition, the Company has limited experience in providing
software-based products or services. The specialized nature and price of the
Company's databases and related products and services are such that there are
a limited number of pharmaceutical, biotechnology and agricultural companies
that are potential customers for such products and services. Additional
factors that may affect demand for the Company's products and services include
the extent to which the Company's potential collaborators and subscribers
determine to conduct in-house gene research, the success of competitors
offering similar services at competitive prices, the ability of the Company to
service satisfactorily its collaborators and subscribers, the extent to which
the gene expression analyses, as well as the identification of biological
pathways, drug candidates and related information contained in the Company's
databases, are made public by or are the subject of patents issued to others,
and the emergence of technological innovations that are more advanced than
those used by and available to the Company.

The building of the Company's PathCalling database is still in its early
stages. In addition, the Company has not yet completed the development of its
CombiGen technology to enable it to conduct high-throughput screening of
protein targets, and has not yet started to develop its HitCalling database.
There can be no assurance that the Company will be able to populate its
PathCalling database in a timely manner or develop its CombiGen technology or
its HitCalling database successfully or that, if completed or developed
successfully, such technology or database will be accepted by, or useful to,
the Company's collaborators or subscribers.

FUTURE CAPITAL REQUIREMENTS; UNCERTAINTY OF ADDITIONAL FUNDING

The Company's comprehensive approach to developing therapeutic products
through the application of genomics has required it to establish a substantial
scientific infrastructure. The Company has used substantial amounts of cash to
date and expects capital and operating expenditures to increase over the next
several years as it expands its infrastructure and its research and
development activities, including the completion of its PathCalling database
and the development of its HitCalling database and CombiGen technology. The
Company's future capital requirements will depend on many factors, including
progress of its research programs, the number and breadth of these programs,
the ability of the Company to attract collaborators for or subscribers to its
products and services, achievement of milestones under the Company's existing
collaborations, the ability of the Company to establish and maintain
additional collaborations, and the progress of the Company's collaborators.
These factors also include the level of the Company's activities relating to
commercialization rights it has retained in its collaborations, competing
technological and market developments, the costs involved in enforcing patent
claims and other intellectual property rights and the costs and timing of
regulatory approvals. The Company expects that it will require significant
additional financing in the future, which it may seek to raise through public
or private equity offerings, debt financings or additional collaborations and
licensing arrangements. There can be no assurance that additional financing
will be available when needed, or, if available, that such financing will be
obtained on terms favorable to the Company or its stockholders. To the extent
that the Company raises additional capital by issuing equity securities,
ownership dilution to stockholders will result. To the extent that the Company
raises additional funds through collaborations and licensing arrangements, the

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Company may be required to relinquish rights to certain of its technologies or
product candidates, or to grant licenses on terms that are not favorable to
the Company, either of which could have a material adverse effect on the
Company's business, financial condition and results of operations. In the
event that adequate funds are not available, the Company's business, financial
condition and results of operations would be materially, adversely affected.
See "Use of Proceeds" and "Management's Discussion and Analysis of Financial
Condition and Results of Operations--Liquidity and Capital Resources."

RELIANCE ON RESEARCH COLLABORATIONS

The Company's strategy for development and commercialization of therapeutic,
agricultural and diagnostic products based upon its discoveries depends upon
the formation of various research collaborations and licensing arrangements.
To date, the Company has two research collaborations. The Company and Pioneer
Hi-Bred have entered into a research collaboration, which Pioneer Hi-Bred may
terminate after November 16, 1998 with three months' notice if the Company has
not identified any genes associated with certain traits of interest to Pioneer
Hi-Bred. The Company and Biogen have also entered into a research
collaboration that Biogen may terminate upon six months' written notice, with
the earliest possible termination date being April 2000. There can be no
assurance that these collaborations will not be terminated at such times or
earlier upon a material breach by the Company. Any such termination could have
a material adverse effect on the Company's business, financial condition and
results of operation. There can be no assurance that the Company will be able
to maintain or expand existing collaborations or establish additional research
collaborations or licensing arrangements necessary to develop and
commercialize therapeutic, agricultural or diagnostic products resulting from
the Company's technology, that any such collaborations or licensing
arrangements will be on terms favorable to the Company or that the current or
any future collaborations or licensing arrangements ultimately will be
successful. Under the Company's current strategy, and for the foreseeable
future, the Company does not expect to develop or market therapeutic,
agricultural or diagnostic products on its own. As a result, the Company will
be dependent on collaborators for the preclinical study and clinical
development of therapeutics and for regulatory approval, manufacturing and
marketing of therapeutic, agricultural and diagnostic products resulting from
the application of the Company's technology. The agreements with collaborators
typically will allow them significant discretion in electing whether to pursue
such activities. The Company cannot control the amount and timing of resources
its collaborators devote to the Company's programs or potential products. If
any of the Company's collaborators were to breach or terminate its agreement
with the Company or otherwise fail to conduct collaborative activities
successfully and in a timely manner, the preclinical or clinical development
or commercialization of product candidates or research programs would be
delayed or terminated. Any such delay or termination could have a material
adverse effect on the Company's business, financial condition and results of
operations.

The Company has structured and intends to continue to structure the
agreements with its collaborators so that, after a period of initial
exclusivity and unless a collaborator elects to pay for an extended period of
exclusivity, the research data developed during the collaboration will become
available for subscribers to the Company's general databases. There can be no
assurance that any additional collaborators of the Company will agree to such
provisions. If the Company is unable to obtain rights to this data, it may
have to change its collaboration strategy and rely more heavily on its own
internal discovery programs to fill its subscription databases.

The Company intends to rely on its collaborators for significant funding in
support of its research efforts. If funding from one or more of its
collaborative programs were reduced or terminated, the Company would be
required to devote additional internal resources to product development, scale
back or terminate certain research development programs or seek alternative
collaborators. See "--Future Capital Requirements; Uncertainty of Additional
Funding" and "Business--Research Collaborations." Disputes may arise in the
future with respect to the ownership of rights to any technology developed
with collaborators. These and other possible disagreements between
collaborators and the Company could lead to delays in the collaborative
research, development or commercialization of certain therapeutic,
agricultural or diagnostic products, or could require or result in litigation
or arbitration to resolve. Any such event could have a material adverse effect
on the Company's business, financial condition and results of operations.

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COMPETITION

The Company faces, and will continue to face, intense competition from
pharmaceutical, biotechnology and diagnostic companies, as well as academic and
research institutions and government agencies. The Company is subject to
significant competition from organizations that are pursuing technologies and
products that are the same as or similar to the Company's technology and
products. Many of the organizations competing with the Company have greater
capital resources, research and development staffs and facilities and marketing
capabilities than the Company. In addition, research in the field of genomics
generally is highly competitive. Competitors of the Company in the genomics
area include, among others, public companies such as Affymetrix, Inc., Human
Genome Sciences, Inc., Incyte Pharmaceuticals, Inc. and Millennium
Pharmaceuticals, Inc., as well as private companies and major pharmaceutical
companies. Universities and other research institutions, including those
receiving funding from the federally funded Human Genome Project, also compete
with the Company. The Company's future success will depend in large part on its
maintaining a competitive position in the genomics field. Rapid technological
development by the Company or others may result in products or technologies
becoming obsolete before the Company recovers the expenses it incurs in
connection with their development. Products offered by the Company could be
made obsolete by less expensive or more effective technologies. There can be no
assurance that the Company will be able to make the enhancements to its
technology necessary to compete successfully with newly emerging technologies.
See "Business--Competition."

A number of competitors are attempting to rapidly identify and patent genes
and gene fragments sequenced at random, typically without specific knowledge of
the function of such genes or gene fragments. The Company's competitors may
discover or characterize important genes or gene fragments in advance of the
Company, which events could have a material adverse effect on any related
disease research program of the Company. The Company expects competition to
intensify in genomics research as technical advances are made and become more
widely known. See "Business--Background" and "--Technology Platform."

PATENTS AND PROPRIETARY RIGHTS; THIRD PARTY RIGHTS

The Company's business and competitive position are dependent upon its
ability to protect its GeneCalling, PathCalling and HitCalling proprietary
databases, proprietary software and other proprietary methods and technology.
Despite the Company's efforts to protect its proprietary rights, unauthorized
parties may attempt to obtain and use information that the Company regards as
proprietary. The Company relies on patent, trade secret and copyright law and
nondisclosure and other contractual arrangements to protect such proprietary
information. The Company has filed patent applications for its proprietary
methods and devices for gene expression analysis, and for discovery of
biological pathways and for drug screening for pharmaceutical product
development. As of September 30, 1997, the Company had 14 patent applications
pending covering its technology with the United States Patent and Trademark
Office (the "USPTO"), and had filed several corresponding international and
foreign patent applications. To date, no patents have been issued to the
Company with respect to its technology and there can be no assurance that any
patents will issue. There can be no assurance that others will not
independently develop substantially equivalent proprietary information and
techniques or otherwise gain access to the Company's proprietary information,
that such information will not be disclosed or that the Company can effectively
protect its rights to unpatented trade secrets or other proprietary
information.

The Company's commercial success will also depend in part on obtaining patent
protection on gene and protein discoveries for which it or its collaborators or
subscribers discover utility and on products, methods and services based on
such discoveries. The Company has applied for patent protection on novel
mutants of known genes and their uses, partial sequences of novel proteins and
their gene sequences and uses, and novel uses for previously identified genes
discovered by third parties. The Company has sought and intends to continue to
seek patent protection for novel uses for genes and proteins which may have
been patented by third parties. In such cases, the Company would need a license
from the holder of the patent with respect to such gene or protein in order to
make, use or sell such gene or protein for such use. There can be no assurance
that the Company will be able to acquire such licenses on commercially
reasonable terms, if at all. The Company's patent application filings that
result from the identification of genes associated with the cause or effect of
a particular disease

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generally seek to protect the genes and encoded proteins if these genes and
encoded proteins are, among other things, novel and non-obvious, as well as
therapeutic, diagnostic and drug screening methods and products, and other
subject matter based upon a gene and its indication. Where information is
discovered on the specific biological pathway in which the protein encoded by
the gene participates, the Company also seeks to protect the newly identified
protein complex as well as the methods for identifying intervention strategies.
Each application typically contains multiple genes discovered for a particular
disease system.

The patent positions of pharmaceutical, biopharmaceutical and biotechnology
companies, including the Company, are generally uncertain and involve complex
legal and factual questions. There can be no assurance that any of the
Company's pending patent applications will result in issued patents, that the
Company will develop additional proprietary technologies that are patentable,
that any patents issued to the Company or its collaborative customers will
provide a basis for commercially viable products or will provide the Company
with any competitive advantages or will not be challenged or circumvented or
invalidated by third parties, or that the patents of others will not have an
adverse effect on the ability of the Company to do business. In addition,
patent law relating to the scope of claims in the technology fields in which
the Company operates is still evolving. The degree of future protection for the
Company's proprietary rights is uncertain. Furthermore, there can be no
assurance that others will not independently develop similar or alternative
technologies, duplicate any of the Company's technologies, or, if patents are
issued to the Company, design around the patented technologies developed by the
Company. In addition, the Company could incur substantial costs in litigation
if it is required to defend itself in patent suits brought by third parties or
if it initiates such suits.

There can be no assurance that patents for the Company's products or methods
will be obtained, or that, if issued, such patents will provide substantial
protection or be of commercial benefit to the Company. The issuance of a patent
is not conclusive as to its validity or enforceability, nor does it provide the
patent holder with freedom to operate without infringing the patent rights of
others. A patent could be challenged by litigation and, if the outcome of such
litigation were adverse to the patent holder, competitors could be free to use
the subject matter covered by the patent, or the patent holder may license the
technology to others in settlement of such litigation. The invalidation of key
patents owned by or licensed to the Company or non-approval of pending patent
applications could increase competition, and result in a material adverse
effect on the Company's business, financial condition and results of
operations. In addition, there can be no assurance that any application or
exploitation of the Company's technology will not infringe patents or
proprietary rights of others or that licenses that might be required as a
result of such infringement for the Company's processes or products would be
available on commercially reasonable terms, if at all.

The Company cannot predict whether its or its competitors' patent
applications will result in the issuance of valid patents. Litigation, which
could result in substantial cost to the Company, may also be necessary to
enforce the Company's patent and proprietary rights and/or to determine the
scope and validity of others' proprietary rights. The Company may participate
in interference proceedings that may in the future be declared by the USPTO to
determine priority of invention, which could result in substantial cost to the
Company. There can be no assurance that the outcome of any such litigation or
interference proceedings will be favorable to the Company, that the Company
will be able to obtain licenses to technology that it may require or that, if
obtainable, such technology can be licensed at a reasonable cost.

The public availability of expressed sequence tags ("ESTs") or other sequence
information prior to the time the Company applies for patent protection on a
corresponding full-length or partial gene could adversely affect the Company's
ability to obtain patent protection with respect to such gene or gene
sequences. In addition, certain other groups are attempting to rapidly identify
and characterize genes through the use of gene expression analysis and other
technologies. To the extent any patents issue to other parties on such partial
or full-length genes or uses for such genes, the risk increases that the sale
of potential products, including therapeutics, or processes developed by the
Company or its collaborators may give rise to claims of patent infringement.
Others may have filed and in the future are likely to file patent applications
covering genes or gene products that are similar or identical to those of the
Company. No assurance can be given that any such patent application will not

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have priority over patent applications filed by the Company. Any legal action
against the Company or its collaborators claiming damages and seeking to enjoin
commercial activities relating to the affected products and processes could, in
addition to subjecting the Company to potential liability for damages, require
the Company or its collaborators to obtain a license in order to continue to
manufacture or market the affected products and processes or could enjoin the
Company from continuing to manufacture or market the affected products and
processes. There can be no assurance that the Company or its collaborators
would prevail in any such action or that any license required under any such
patent would be made available on commercially acceptable terms, if at all. The
Company believes that there may be significant litigation in the industry
regarding patent and other intellectual property rights. If the Company becomes
involved in such litigation, it could consume a substantial portion of the
Company's managerial and financial resources.

There is substantial uncertainty concerning the extent to which supportive
data will be required for issuance of patents for human therapeutics. If data
additional to that available to the Company is required, the Company's ability
to obtain patent protection could be delayed or otherwise adversely affected.
Although the USPTO issued new utility guidelines in July 1995 that address the
requirements for demonstrating utility for biotechnology inventions,
particularly for inventions relating to human therapeutics, there can be no
assurance that the USPTO examiners will follow such guidelines or that the
USPTO's position will not change with respect to what is required to establish
utility for gene sequences and products and methods based on such sequences.
Furthermore, the enactment of the legislation implementing the General
Agreement on Tariffs and Trade has resulted in certain changes to United States
patent laws that became effective on June 8, 1995. Most notably, the term of
patent protection for patent applications filed on or after June 8, 1995 is no
longer a period of seventeen years from the date of grant. The new term of
United States patents will commence on the date of issuance and terminate
twenty years from the earliest filing date in the United States to which
priority is claimed for the application. Because the time from filing to
issuance of biotechnology patent applications is often more than three years, a
twenty-year term from the claimed United States priority date may result in a
substantially shortened term of patent protection, which may adversely affect
the Company's patent position. If this change results in a shorter period of
patent coverage, the Company's business could be adversely affected to the
extent that the duration and level of the royalties it is entitled to receive
from its strategic partners is based on the existence of a valid patent.

The Company also relies upon trade secret protection for some of its
confidential and proprietary information that is not subject matter for which
patent protection is being sought. The Company believes that it has developed
proprietary technology, processes and information systems for use in gene
expression and biological pathway discovery, as well as in the identification
of molecular targets for pharmaceutical development, including proprietary
biological protocols, instrumentation, robotics and automation, software and an
integrated bioinformatics system. In addition, the Company has developed a
database of proprietary gene expression patterns and biological pathways which
it updates on an ongoing basis and which can be accessed over the Internet. The
Company has taken security measures to protect its proprietary technologies,
processes, information systems and data and continues to explore ways to
enhance such security. There can be no assurance, however, that such measures
will provide adequate protection for the Company's trade secrets or other
proprietary information. While the Company requires employees, academic
collaborators and consultants to enter into confidentiality and/or non-
disclosure agreements where appropriate, there can be no assurance that
proprietary information will not be disclosed, that others will not
independently develop substantially equivalent proprietary information and
techniques or otherwise gain access to the Company's trade secrets or disclose
such technology, or that the Company can meaningfully protect its trade
secrets. See "Business--Intellectual Property."

UNCERTAINTIES RELATING TO COMMERCIALIZATION RIGHTS

In the Company's research collaborations, the Company will seek to retain
commercialization rights for the development and marketing of certain
pharmaceutical, agricultural and diagnostic products or services. There can be
no assurance that the Company will be successful in retaining such rights and
no such pharmaceutical, agricultural or diagnostic products or services have
been developed to date by the Company. The Company may

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seek to commercialize any such retained rights, as well as any products
developed in its internal development programs, directly or through
collaborations with others. To date, the Company has not initiated significant
activities with respect to the exploitation of any of its retained
commercialization rights or any products developed in its internal development
programs. The value of these rights and products, if any, will be largely
derived from the Company's gene expression, biological pathway and drug
screening efforts, the success of which is also uncertain. See "--Technological
Uncertainty and Product Development Risk." Even if the Company identifies and
characterizes relevant disease-related genes, biological pathways and/or drug
candidates, the commercialization of retained rights and products developed
internally requires, in addition to capital resources, technological, product
development, manufacturing, regulatory, marketing and sales resources that the
Company does not currently possess. There can be no assurance that the Company
will be able to develop or obtain such resources. To the extent that the
Company is required to rely on third parties for these resources, failure to
establish and maintain such relationships could have a material adverse effect
on the Company's ability to realize value from its retained commercialization
rights and products developed internally. If the Company seeks to commercialize
retained rights and products developed internally through joint ventures or
research collaborations, it may be required to relinquish material rights on
terms that may not be favorable to the Company. No agreements concerning any
such arrangements currently exist, and there can be no assurance that the
Company will be able to enter into any such agreements on acceptable terms, if
at all, or that the Company will be able to realize any value from any retained
commercialization rights and products developed internally. See "Business--
CuraGen's Strategy" and "--Research Collaborations."

GOVERNMENT REGULATION; NO ASSURANCE OF REGULATORY APPROVAL

Prior to marketing, any new drug developed by the Company or its
collaborative customers must undergo an extensive regulatory approval process
in the United States and other countries. This regulatory process, which
includes preclinical and clinical studies, as well as post-marketing
surveillance to establish a compound's safety and efficacy, can take many years
and require the expenditure of substantial resources. Data obtained from such
studies are susceptible to varying interpretations that could delay, limit or
prevent regulatory approval. The rate of completion of clinical trials is
dependent upon, among other factors, the enrollment of patients. Patient
accrual is a function of many factors, including the size of the patient
population, the proximity of patients to clinical sites, the eligibility
criteria for the study and the existence of competitive clinical trials. Delays
in planned patient enrollment in clinical trials may result in increased costs,
program delays or both, which could have a material adverse effect on the
Company. Delays or rejections may also be encountered based upon changes in
United States Food and Drug Administration ("FDA") policies for drug approval
during the period of product development and FDA regulatory review of each
submitted new drug application ("NDA") in the case of new pharmaceutical
agents, or product license application ("PLA") in the case of biologics.
Similar delays also may be encountered in the regulatory approval of any
diagnostic product and in obtaining regulatory approvals in foreign countries.
Under current guidelines, proposals to conduct clinical research involving gene
therapy at institutions supported by the National Institutes of Health ("NIH")
must be approved by the Recombinant DNA Advisory Committee and the NIH. There
can be no assurance that regulatory approval will be obtained for any drugs or
diagnostic products developed by the Company or its collaborative customers.
Furthermore, regulatory approval may impose limitations on the indicated use of
a drug. Because certain of the products likely to result from the Company's
disease research programs involve the application of new technologies and may
be based upon a new therapeutic approach, such products may be subject to
substantial additional review by various government regulatory authorities and,
as a result, regulatory approvals may be obtained more slowly than for products
using more conventional technologies.

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of criminal penalties against the manufacturer and NDA or PLA holder. The
Company has not submitted an investigational new drug application ("IND") for
any product candidate, and no product candidate has been approved for
commercialization in the United States or elsewhere. The Company intends to
rely primarily on its collaborators to file INDs and generally direct the
regulatory approval process. No assurance can be given that the Company or any
of its collaborators will be able to conduct clinical testing or obtain the
necessary approvals from the FDA or other regulatory authorities for any
products. Failure to obtain required governmental approvals will delay or
preclude the Company's collaborators from marketing drugs or diagnostic
products developed by the Company or limit the commercial use of such products
and could have a material adverse effect on the Company's business, financial
condition and results of operations.

The Company's research and development activities involve the controlled use
of hazardous materials and chemicals. The Company is subject to federal, state
and local laws and regulations governing the use, storage, handling and
disposal of such materials and certain waste products. Although the Company
believes that its safety procedures for handling and disposing of such
materials comply with the standards prescribed by federal, state and local laws
and regulations, the risk of accidental contamination or injury from these
materials cannot be completely eliminated. In the event of such an accident,
the Company could be held liable for any damages that result and any liability
could exceed the resources of the Company. See "Business--Government
Regulation."

ATTRACTION AND RETENTION OF KEY EMPLOYEES

The Company is highly dependent on the principal members of its management
and scientific staff, including Dr. Jonathan Rothberg, its Chief Executive
Officer, President and Chairman of the Board, Dr. Gregory Went, its Executive
Vice President, and certain other members of the Company's senior management.
The loss of services of any of these personnel could have a material adverse
effect on the Company's business, financial condition and results of
operations. The Company has not entered into employment agreements with Dr.
Rothberg, Dr. Went or any of the other principal members of its management and
scientific staff that bind any of them to a specific term of employment. The
Company maintains key person life insurance on the lives of each of Drs.
Rothberg and Went in the amount of $2,000,000. The Company's future success
also will depend in part on the continued services of its key scientific and
management personnel and its ability to attract, hire and retain additional
personnel. There is intense competition for such qualified personnel and there
can be no assurance that the Company will be able to continue to attract and
retain such personnel. Failure to attract and retain key personnel could have a
material adverse effect on the Company's business, financial condition and
results of operations. See "Management."

EXPANSION OF OPERATIONS; MANAGEMENT OF GROWTH

The Company has recently experienced significant growth in the number of its
employees, the extent of its genomics efforts and database development, its
research programs and collaborations and the scope of its operations. This
growth has placed, and may continue to place, a significant strain on the
Company's management and operations. The Company's ability to manage
effectively such growth will depend upon its ability to strengthen its
management team and its ability to attract and retain skilled employees. The
Company's success will also depend on the ability of its officers and key
employees to continue to implement and improve its operational, management
information and financial control systems and to expand, train and manage its
work force. In addition, the Company must continue to take steps to provide
resources to supports its collaborative customers and subscribers as their
numbers increase. The Company's inability to manage growth effectively could
have a material adverse effect on the Company's business, financial condition
and results of operations. See "Business--Employees" and "--Facilities."

DEPENDENCE UPON LICENSED TECHNOLOGIES; GOVERNMENT RIGHTS TO FUNDED TECHNOLOGIES

Certain components of the Company's technologies have been acquired or
licensed from third parties. Changes in such third party agreements, or
termination thereof, could materially adversely affect the Company's research
and development activities. There can be no assurance that the Company will be
able to acquire from third parties or develop new technologies, either alone or
with others. Failure to license or otherwise acquire

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necessary technologies could have a material adverse effect on the Company's
business, financial condition and results of operation. In addition, certain of
such licenses impose an obligation on the Company to market the licensed
technology to third parties. A breach by the Company of any such license or
other failure by the Company to maintain rights to such technology could have a
material adverse effect on the Company's business, financial condition and
results of operation.

Under the Company's government grants and agreements, the government has a
statutory right to practice or have practiced and, under certain circumstances
(including inaction on the part of the Company or its licensees to achieve
practical application of the invention or a need to alleviate public health or
safety concerns not reasonably satisfied by the Company or its licensees), to
grant to other parties licenses under, any inventions first reduced to practice
under the government grants and agreements.

DEPENDENCE ON ACADEMIC COLLABORATORS AND SCIENTIFIC ADVISORS

The Company has relationships with collaborators and consultants at academic
and other institutions who conduct research at the Company's request. Such
collaborators and consultants are not employees of the Company. Substantially
all of the Company's collaborators and consultants are employed by employers
other than the Company and may have commitments to, or consulting or advisory
contracts with, other entities that may limit their availability to the
Company. As a result, the Company has limited control over their activities
and, except as otherwise required by its collaboration and consulting
agreements, can expect only limited amounts of their time to be dedicated to
the Company's activities. The Company's ability to discover genes and
biological pathways involved in human disease and commercialize products based
on those discoveries may depend in part on continued collaborations with
researchers at academic and other institutions. There can be no assurance that
the Company will be able to negotiate additional acceptable collaborations with
collaborators or consultants at academic and other institutions or that its
existing collaborations will be successful.

The Company's academic collaborators, consultants and scientific advisors may
have relationships with other commercial entities, some of which could compete
with the Company. The academic collaborators, consultants and scientific
advisors sign agreements which provide for confidentiality of the Company's
proprietary information and of the results of studies. There can be no
assurance that the Company will be able to maintain the confidentiality of its
technology and other confidential information in connection with every academic
collaboration or advisory arrangement, and any unauthorized dissemination of
the Company's confidential information could have a material adverse effect on
the Company's business, financial condition and results of operations. Further,
there can be no assurance that any such collaborator, consultant or advisor may
not enter into an employment or consulting arrangement with a competitor of the
Company. See "Business--CuraGen Internal Programs."

LENGTHY SALES CYCLE

The ability of the Company to obtain collaborators and subscribers for its
products and services depends in significant part upon the perception that such
products and services can help accelerate drug discovery and development
efforts. The sales cycle is typically lengthy due to the education effort that
is required as well as the need to effectively sell the benefits of the
Company's products and services to a variety of constituencies within potential
collaborators and subscribers, including research and development personnel and
key management. In addition, each subscription and collaboration will involve
the negotiation of agreements containing terms that may be unique to each
subscriber or collaborator. The Company may expend substantial funds and
management effort with no assurance that a database subscription or a
collaboration will result.

VARIATION IN QUARTERLY OPERATING RESULTS

The Company's results of operations historically have fluctuated on a
quarterly basis and can be expected to continue to be subject to quarterly
fluctuations. The Company expects that losses will fluctuate from quarter to
quarter and the such fluctuations may be substantial. Quarterly operating
results can fluctuate as a result of a

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number of factors, including the commencement, delay, cancellation or
completion of contracts; the timing of option, license and milestone payments
under the Company's agreements; the mix of services provided; the timing of
start-up expenses for new services and facilities; the timing and integration
of acquisitions and changes in regulations related to the products and services
of the Company. The Company believes that quarterly comparisons of its
financial results are not necessarily meaningful and should not be relied upon
as an indication of future performance. In addition, fluctuations in quarterly
results could affect the market price of the Common Stock in a manner unrelated
to the longer term operating performance of the Company. See "Management's
Discussion and Analysis of Financial Condition and Results of Operations."

RISKS ASSOCIATED WITH COMMERCIALIZATION OF PROPRIETARY PRODUCTS

Although the Company is not currently developing any potential pharmaceutical
products, should the Company choose to do so, any such products will require
significant research and development and preclinical testing, and will require
extensive clinical testing prior to submission of any regulatory application
for commercial use. Such activities, if undertaken without the collaboration of
others, would require the expenditure of significant funds. Such potential
pharmaceutical products will be subject to the risks of failure inherent in the
development of pharmaceutical products based on new technologies. These risks
include the possibilities that such potential pharmaceutical products will be
found to be unsafe or ineffective or otherwise fail to receive necessary
regulatory clearances; that the products, if safe and effective, will be
difficult to manufacture on a large scale or uneconomical to market; that
proprietary rights of third parties will preclude the Company or its partners
from marketing such products; or that third parties will market superior or
equivalent products. As a result, there can be no assurance that the Company's
research and development activities will result in any commercially viable
products. Clinical trials or marketing of any such potential pharmaceutical
products may expose the Company to liability claims from the use of such
pharmaceutical products. There can be no assurance that the Company will be
able to obtain product liability insurance or, if obtained, that sufficient
coverage can be acquired at a reasonable cost. In addition, should the Company
choose to develop pharmaceutical products internally, it will have to make
significant investments in pharmaceutical product development, marketing, sales
and regulatory compliance resources, and it will have to establish or contract
for the manufacture of products under the Good Manufacturing Practices of the
FDA. There can be no assurance that the Company will be able to develop or
commercialize successfully any potential pharmaceutical products. Any potential
products developed by the Company's licensees will be subject to the same
risks. See "Business--Government Regulation."

UNCERTAINTY OF PHARMACEUTICAL PRICING, REIMBURSEMENT AND RELATED MATTERS

The Company's business, financial condition and results of operations may be
materially adversely affected by the continuing efforts of government and third
party payors to contain or reduce the costs of health care through various
means. In certain foreign markets, pricing and profitability of prescription
pharmaceuticals are subject to government control. In the United States, the
Company expects that there will continue to be a number of federal and state
proposals to implement similar government control. In addition, increasing
emphasis on managed care in the United States will continue to put pressure on
the pricing of pharmaceutical and diagnostic products. Cost control initiatives
could decrease the price that the Company or any of its subscribers and
collaborators receives for any products in the future and may have a material
adverse effect on the Company's business, financial condition and results of
operations. Further, to the extent that cost control initiatives have a
material adverse effect on the Company's subscribers or collaborators, the
Company's ability to commercialize its products and to realize royalties could
be adversely affected.

The ability of the Company and any subscriber or collaborative customer to
commercialize pharmaceutical or diagnostic products may depend in part on the
extent to which reimbursement for the products will be available from
government and health administration authorities, private health insurers and
other third party payors. Significant uncertainty exists as to the
reimbursement status of newly approved health care products. Third party
payors, including Medicare, increasingly are challenging the prices charged for
medical products and services. Government and other third party payors are
increasingly attempting to contain health care costs by limiting both coverage
and the level of reimbursement for new therapeutic products and by refusing in
some

17
<PAGE>

cases to provide coverage for uses of approved products for disease indications
for which the FDA has not granted labeling approval. There can be no assurance
that any third party insurance coverage will be available to patients for any
products discovered and developed by the Company or its subscribers or
collaborators. If adequate coverage and reimbursement levels are not provided
by government and other third party payors for the Company's products, the
market acceptance of these products may be reduced. Any such reduction may have
a material adverse effect on the Company's business, financial condition,
results of operations and cash flows.

CONTROL BY EXISTING STOCKHOLDERS

Following completion of this Offering, the Company's directors, executive
officers and principal stockholders and certain of their affiliates will
beneficially own approximately % of the Common Stock. Accordingly, they
collectively will have the ability to determine the election of all of the
Company's directors and to determine the outcome of most corporate actions
requiring stockholder approval, including the merger of the Company with or
into another company, a sale of substantially all of the Company's assets and
amendments to the Company's Certificate of Incorporation. See "Principal
Stockholders."

POTENTIAL ADVERSE EFFECT OF ANTI-TAKEOVER PROVISIONS

The Company's Board of Directors is authorized to issue up to 3,000,000
shares of Preferred Stock and to determine the price, rights, preferences and
privileges of those shares without any further vote or action by the Company's
stockholders. The rights of the holders of Common Stock will be subject to, and
may be adversely affected by, the rights of the holders of any shares of
Preferred Stock that may be issued in the future. While the Company has no
present intention to issue shares of Preferred Stock, such issuance, while
providing desirable flexibility in connection with possible acquisitions and
other corporate purposes, could have the effect of making it more difficult for
a third party to acquire a majority of the outstanding voting stock of the
Company. In addition, such Preferred Stock may have other rights, including
economic rights senior to the Common Stock, and, as a result, the issuance
thereof could have a material adverse effect on the market value of the Common
Stock. The Restated Certificate provides for a classified Board of Directors
and members of the Board of Directors may be removed only for cause upon the
affirmative vote of holders of at least a majority of the shares of capital
stock of the Company entitled to vote. Furthermore, the Company is subject to
the anti-takeover provisions of Section 203 of the Delaware General Corporation
Law (the "DGCL"), which prohibits the Company from engaging in a "business
combination" with an "interested stockholder" for a period of three years after
the date of the transaction in which such person first becomes an "interested
stockholder," unless the business combination is approved in a prescribed
manner. The application of these provisions could have the effect of delaying
or preventing a change of control of the Company. Certain other provisions of
the Restated Certificate could also have the effect of delaying or preventing
changes of control or management of the Company, which could adversely affect
the market price of the Company's Common Stock. See "Description of Capital
Stock."

NO PRIOR TRADING MARKET FOR COMMON STOCK; POSSIBLE VOLATILITY OF STOCK PRICE

Prior to this offering, there has been no public market for the Company's
Common Stock and there can be no assurance that an active public market for the
Common Stock will develop or be sustained after this offering. The initial
public offering price will be determined by negotiations between the Company
and the representatives of the Underwriters and may not be indicative of future
market prices. See "Underwriting" for a discussion of the factors to be
considered in determining the initial public offering price. The trading price
of the Company's Common Stock could be subject to significant fluctuations in
response to announcements of results of research activities, technological
innovations or new commercial products by the Company or its competitors,
changes in government regulations, regulatory actions, changes in patent laws,
developments concerning proprietary rights, quarterly variations in operating
results, litigation or other events. The stock market has from time to time
experienced extreme price and volume fluctuations that have affected
particularly the market prices for biotechnology companies and that often have
been unrelated to the operating performance of such companies. These broad
market fluctuations may adversely affect the market price of the Company's
Common Stock. See "Underwriters."

18
<PAGE>

SHARES ELIGIBLE FOR FUTURE SALE; POSSIBLE ADVERSE EFFECT ON FUTURE MARKET
PRICE

Sales of Common Stock (including Common Stock issued upon the exercise of
outstanding options and warrants) in the public market after this offering
could materially adversely affect the market price of the Common Stock. These
sales also might make it more difficult for the Company to sell equity
securities or equity-related securities in the future at a time and price that
the Company's management deems acceptable, or at all. Upon the completion of
this offering, the Company will have shares of Common Stock outstanding,
assuming no exercise of options or warrants after September 30, 1997 and
assuming no exercise of the Underwriters' overallotment option. Of these
outstanding shares of Common Stock, the shares sold in this offering will
be freely tradeable, without restriction under the Securities Act of 1933, as
amended (the "Securities Act"), unless purchased by "affiliates" of the
Company, as that term is defined in Rule 144 under the Securities Act. The
remaining 8,871,987 shares of Common Stock held by existing stockholders are
"restricted securities" as that term is defined in Rule 144 under the
Securities Act and were issued and sold by the Company in reliance on
exemptions from the registration requirements of the Securities Act. These
shares may be resold in the public market only if registered or pursuant to an
exemption from registration, such as Rule 144 under the Securities Act. All
officers, directors and certain holders of Common Stock owning, in the
aggregate, shares of Common Stock have agreed, pursuant to certain lock-up
agreements, that they will not offer, sell, contract to sell, grant any option
to sell, pledge, hypothecate or otherwise dispose of, directly or indirectly,
any shares of Common Stock owned by them, or that could be purchased by them
through the exercise of options or warrants to purchase Common Stock of the
Company, for a period of 180 days after the date of this Prospectus without
the prior written consent of Morgan Stanley & Co. Incorporated. Upon
expiration of the lock-up agreements, all shares of Common Stock currently
outstanding will be immediately eligible for resale, subject to the
requirements of Rule 144. Immediately following the completion of this
Offering, holders of 3,610,510 shares of Common Stock and warrants to purchase
388,005 shares of Common Stock, as well as Biogen with respect to the Biogen
Shares, 100,000 shares of Common Stock and any shares issued to it pursuant to
the conversion of the loan facility provided by Biogen to the Company, will be
entitled to certain registration rights. However, pursuant to the lock-up
agreements, no sale of such shares will be permitted for 180 days after the
date of this Prospectus without the prior written consent of Morgan Stanley &
Co. Incorporated. See "Shares Eligible for Future Sale" and "Description of
Capital Stock--Registration Rights." If such holders, by exercising their
demand rights, cause a large number of shares to be registered and sold on the
public market, such sales could have a material adverse effect on the market
price of the Company's Common Stock. The Company intends to file a
registration statement covering the shares of Common Stock issued or
reserved for issuance under its stock plans and, upon filing, any shares
subsequently issued under such plans will be eligible for sale in the public
market, subject to compliance with Rule 144 in the case of affiliates of the
Company. The Company is unable to predict the effect that sales may have on
the then prevailing market price of the Common Stock. See "Management--Stock
Option Plans," "Description of Capital Stock" and "Shares Eligible for Future
Sale."

DILUTION

Purchasers in the offering will experience immediate and substantial
dilution in the net tangible book value of the Common Stock from the initial
public offering price. Additional dilution is likely to occur upon exercise of
options and warrants granted by the Company. See "Dilution." The Company's
collaboration agreement with Biogen is structured such that amounts borrowed
by the Company from Biogen are, at the Company's option, convertible into
shares of Common Stock at the market price of the Common Stock at the time of
such conversion. If the Company converts such amounts into shares of Common
Stock at a time when the market price of the Common Stock is lower than the
initial public offering price, the Company's stockholders could experience
substantial dilution.

ABSENCE OF DIVIDENDS

The Company has never paid dividends on its capital stock and does not
intend to pay any cash dividends on its Common Stock for the foreseeable
future. See "Dividend Policy."

19
<PAGE>

USE OF PROCEEDS

The net proceeds to the Company from the sale of the shares of Common
Stock offered by the Company hereby are estimated to be $ million
($ million if the Underwriters' overallotment option is exercised in full),
assuming an initial public offering price of $ per share (the midpoint of
the range set forth on the cover page of this Prospectus) and after deducting
the underwriting discounts and commissions and estimated offering expenses
payable by the Company.

The Company expects to use approximately $10 million of the net proceeds for
capital expenditures and $1,750,000 (plus dividends of approximately $200,000)
to redeem, upon the closing of the Offering, all of the 175,000 outstanding
shares of the Series B Preferred Stock. See "Description of Capital Stock--
Preferred Stock." The Company expects to use the balance of the net proceeds
for research and development, including internal discovery programs, the
further development of its GeneCalling, PathCalling and HitCalling databases
and working capital and general corporate purposes. The amounts actually
expended for each purpose, other than the amount expended for the redemption
of the Series B Preferred Stock, may vary significantly depending upon
numerous factors, including progress of the Company's internal programs and
research and development projects, the number and breadth of these programs,
achievement of milestones under collaborative arrangements, the ability of the
Company to establish and maintain research collaborations and database
subscriptions, and the progress of the development efforts of the Company's
collaborators and subscribers. These factors also include the level of the
Company's activities relating to commercialization of rights it has retained
in its collaborative arrangements, competing technological and market
developments, the costs involved in the defense, prosecution and enforcement
of patent claims and other intellectual property rights and the costs and
timing of regulatory approvals.

From time to time in the ordinary course of business, the Company evaluates
the acquisition of products, businesses and technologies that complement the
Company's business, for which a portion of the net proceeds may be used.
Currently, however, the Company does not have any understandings, commitments
or agreements with respect to any such acquisitions.

Pending use of the net proceeds for the above purposes, the Company intends
to invest such funds in short- term, interest-bearing, investment-grade
securities.

DIVIDEND POLICY

The Company has never paid dividends on its capital stock and does not plan
to pay any cash dividends on its Common Stock for the foreseeable future. The
Company currently intends to retain earnings, if any, to finance the
development of its business.

20
<PAGE>

CAPITALIZATION

The following table sets forth, as of September 30, 1997, the actual
capitalization of the Company and the capitalization of the Company as
adjusted to reflect (i) the redemption of the 175,000 outstanding shares of
Series B Preferred Stock, (ii) the filing of the Restated Certificate, (iii)
the termination of certain redemption rights relating to 394,031 shares of
Redeemable Common Stock, (iv) the sale by the Company of the Biogen Shares,
based upon an assumed initial public offering price of $ , and application of
the net proceeds thereof, and (v) the sale by the Company of shares of
Common Stock offered hereby, based upon an assumed initial public offering
price of $ per share and after deducting underwriting discounts and
commissions and estimated offering expenses, and application of the estimated
net proceeds thereof. This table should be read in conjunction with the
Company's audited financial statements, including the notes thereto, which
appear elsewhere in this Prospectus.

<TABLE>
<CAPTION>
AS OF
SEPTEMBER 30, 1997
------------------------
ACTUAL AS ADJUSTED
----------- -----------
<S> <C> <C>
Obligations under capital leases, including current
portion.............................................. $ 4,315,808 $4,315,808
Other long-term liabilities........................... 194,869 194,869
----------- ----------
4,510,677 4,510,677
----------- ----------
Redeemable Common Stock(1)............................ 5,319,419 --
----------- ----------
Stockholders' equity(1)(2):
Preferred Stock, $0.01 par value; 7,500,000 shares
authorized, 175,000 shares issued and outstanding
actual; 3,000,000 shares authorized, no shares
issued and outstanding as adjusted................. 1,442,090
Common Stock, $0.01 par value; 25,000,000 shares
authorized, 8,477,956 shares issued and outstanding
actual; 50,000,000 shares authorized, shares
issued and outstanding as adjusted................. 84,779
Additional paid-in capital.......................... 20,509,028
Accumulated deficit................................. (6,975,544)
----------- ----------
Total stockholders' equity......................... 15,060,353
----------- ----------
Total capitalization.............................. $24,890,449 $
=========== ==========
</TABLE>
- --------
(1) See Notes 1, 4 and 6 of Notes to Financial Statements.

(2) Excludes 1,598,884 and 1,583,866 shares of Common Stock reserved for
issuance upon the exercise of stock options and warrants, respectively,
outstanding on September 30, 1997, at weighted average exercise prices of
$3.75 and $4.12 per share, respectively. Also excludes an aggregate of
65,000 shares of Common Stock issuable upon the exercise of stock options
granted to non-employee directors after September 30, 1997, at the initial
public offering price.

21
<PAGE>

DILUTION

As of September 30, 1997, the pro forma net tangible book value per share of
Common Stock, assuming the redemption of the Series B Preferred Stock and the
termination of certain redemption rights relating to 394,031 shares of
Redeemable Common Stock, was $2.08. After giving effect to the sale by the
Company of (i) the Biogen Shares, based upon an assumed initial public offering
price of $ , and application of the net proceeds thereof, and (ii) shares
of Common Stock offered hereby, based upon an assumed initial public offering
price of $ per share and after deducting underwriting discounts and
commissions and estimated offering expenses, the pro forma net tangible book
value of the Company at September 30, 1997 would have been $ or $ per
share, representing an immediate $ per share dilution of new investors
purchasing shares in the Offering. The following table illustrates such per
share dilution:

<TABLE>
<S> <C> <C>
Assumed initial public offering price per share................ $
----
Pro forma net tangible book value per share before the
Offering(1)................................................. $ 2.08
Increase per share attributable to new investors.............
-------
Pro forma net tangible book value per share after the
Offering......................................................
----
Dilution per share to new investors(2)......................... $
====
</TABLE>
- --------

(1) Pro forma net tangible book value per share of Common Stock is determined
by dividing the Company's pro forma net tangible book value at September
30, 1997 of $18,420,850, by the pro forma number of shares of Common Stock
outstanding, in each case assuming the redemption of the Series B Preferred
Stock and the termination of certain redemption rights relating to 394,031
shares of Redeemable Common Stock.

(2) Dilution per share to new investors is determined by subtracting pro forma
net tangible book value per share after the Offering from the assumed
initial public offering price per share.

The following table sets forth on a pro forma basis as of September 30, 1997,
assuming the redemption of the Series B Preferred Stock and the termination of
certain redemption rights relating to 394,031 shares of Redeemable Common
Stock, the number of shares of Common Stock purchased from the Company, the
total consideration paid and the average price per share paid by existing
stockholders and to be paid by new investors, based on an assumed initial
public offering price of $ per share and before deducting underwriting
discounts and commissions and estimated offering expenses payable by the
Company:

<TABLE>
<CAPTION>
SHARES PURCHASED TOTAL CONSIDERATION AVERAGE PRICE
----------------- ------------------- -------------
NUMBER PERCENT AMOUNT PERCENT PER SHARE
--------- ------- ----------- ------- -------------
<S> <C> <C> <C> <C> <C>
Existing stockholders....... 8,871,987 % $24,687,635 % $2.78
New investors...............
--------- --- ----------- ---
Total..................... 100% $ 100%
========= === =========== ===
</TABLE>

The foregoing tables assume no exercise of any outstanding stock options or
warrants to purchase Common Stock. At September 30, 1997, there were
outstanding options and warrants to purchase 1,598,884 shares and 1,583,866
shares of Common Stock, respectively, at weighted average exercise prices of
$3.75 and $4.12 per share, respectively. The foregoing tables also exclude an
aggregate of 65,000 shares of Common Stock issuable upon the exercise of stock
options granted to non-employee directors after September 30, 1997, at the
initial pubic offering price. To the extent such options and warrants are
exercised, there will be further dilution to the new investors. See
"Capitalization," "Management--Stock Option Plans," "Description of Capital
Stock" and Note 6 of Notes to Financial Statements.

22
<PAGE>

SELECTED FINANCIAL DATA

The selected financial data set forth below for each of the three years in
the period ended December 31, 1996 are derived from the Company's balance
sheets as of December 31, 1995 and 1996 and the related audited statements of
operations, of stockholders' equity (deficiency) and of cash flows for the
three years ended December 31, 1994, 1995 and 1996 and notes thereto, which
appear elsewhere in this Prospectus, as audited by Deloitte & Touche LLP,
independent auditors. The selected financial data as of September 30, 1997 and
for the nine months ended September 30, 1996 and 1997 and notes thereto, which
appear elsewhere in this Prospectus, have been derived from the Company's
unaudited financial statements and include, in the opinion of management, all
normal recurring adjustments necessary for a fair presentation of the data for
such periods. The operating results for the nine months ended September 30,
1997 are not necessarily indicative of the results that may be expected for
the full year ending December 31, 1997. The selected financial data for the
years ended December 31, 1992 and 1993 have been derived from the Company's
unaudited financial statements, which have not been included in this
Prospectus. The selected financial data set forth below should be read in
conjunction with, and are qualified by reference to, "Management's Discussion
and Analysis of Financial Condition and Results of Operations" and the
Company's audited financial statements and related notes appearing elsewhere
in this Prospectus.

<TABLE>
<CAPTION>
NINE MONTHS ENDED
YEAR ENDED DECEMBER 31, SEPTEMBER 30,
------------------------------------------------------- -----------------------
1992 1993 1994 1995 1996(1) 1996 1997(2)
-------- --------- ---------- ---------- ---------- ---------- -----------
<S> <C> <C> <C> <C> <C> <C> <C>
STATEMENT OF OPERATIONS
DATA:
Revenue:
Grant revenue.......... -- $ 21,903 $ 257,536 $1,581,175 $4,047,947 $2,901,322 $ 2,558,167
Collaboration revenue.. -- -- -- -- 375,000 200,000 1,613,583
-------- --------- ---------- ---------- ---------- ---------- -----------
Total revenue.......... -- 21,903 257,536 1,581,175 4,422,947 3,101,322 4,171,750
-------- --------- ---------- ---------- ---------- ---------- -----------
Operating expenses:
Research and
development........... -- 309,351 647,640 1,466,375 3,516,035 2,192,740 6,431,139
General and
administrative........ $ 12,281 250,729 525,671 961,815 1,140,325 666,803 2,071,435
-------- --------- ---------- ---------- ---------- ---------- -----------
Total operating
expenses.............. 12,281 560,080 1,173,311 2,428,190 4,656,360 2,859,543 8,502,574
-------- --------- ---------- ---------- ---------- ---------- -----------
Income (loss) from
operations............. (12,281) (538,177) (915,775) (847,015) (233,413) 241,779 (4,330,824)
-------- --------- ---------- ---------- ---------- ---------- -----------
Other income (expenses):
Interest income........ 366 2,786 20,544 12,306 20,848 2,587 525,021
Interest expense....... -- (22,484) (60,798) (106,035) (183,594) (121,175) (307,042)
-------- --------- ---------- ---------- ---------- ---------- -----------
Total other income
(expenses)............ 366 (19,698) (40,254) (93,729) (162,746) (118,588) 217,979
-------- --------- ---------- ---------- ---------- ---------- -----------
Net income (loss)....... (11,915) (557,875) (956,029) (940,744) (396,159) 123,191 (4,112,845)
Preferred dividends..... -- -- -- -- (17,106) -- (51,318)
-------- --------- ---------- ---------- ---------- ---------- -----------
Net income (loss)
attributable to common
stockholders........... ($11,915) ($557,875) ($956,029) ($940,744) ($413,265) $ 123,191 ($4,164,163)
======== ========= ========== ========== ========== ========== ===========
Net income (loss) per
share attributable to
common stockholders....
======== ========= ========== ========== ========== ========== ===========
Weighted average number
of shares of common
stock outstanding......
======== ========= ========== ========== ========== ========== ===========
Pro forma net loss per
share attributable to
common stockholders....
========== ===========
Pro forma weighted
average number of
shares of common stock
outstanding............
========== ===========
<CAPTION>
AS OF DECEMBER 31, AS OF SEPTEMBER 30,
------------------------------------------------------- -----------------------
1992 1993 1994 1995 1996 1996 1997
-------- --------- ---------- ---------- ---------- ---------- -----------
<S> <C> <C> <C> <C> <C> <C> <C>
BALANCE SHEET DATA:
Cash and cash
equivalents............ $ 14,579 $ 368,458 $ 276,890 $ 9,129 $3,298,642 $1,667,142 $20,781,115
Working capital
(deficiency)........... (14,421) 231,511 285,386 (625,015) 2,474,038 1,432,318 18,477,187
Total assets............ 18,108 722,898 795,161 1,006,816 5,653,391 3,711,396 26,944,446
Total long-term
liabilities............ -- 74,583 622,591 897,691 1,482,601 1,225,629 3,398,060
Redeemable Common
Stock.................. -- -- 731,250 914,063 1,142,579 1,083,894 5,319,419
Series B Preferred
Stock.................. -- -- -- -- 1,390,772 1,373,666 1,442,090
Accumulated deficit..... (11,892) (569,767) (1,525,796) (2,466,540) (2,862,699) (2,343,349) (6,975,544)
Stockholders' equity
(deficiency)........... (10,892) 528,233 (793,769) (1,772,107) 1,401,536 112,032 15,060,353
</TABLE>
- --------
(1) During the year ended December 31, 1996, the Company completed its
development stage activities with the signing of its first collaborative
research agreement and commenced its planned principal operations.

(2) For an explanation of the calculation of weighted average number of common
shares outstanding and pro forma weighted average number of common shares
outstanding, see Note 1 of Notes to Financial Statements.

<PAGE>

MANAGEMENT'S DISCUSSION AND ANALYSIS
OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

This Prospectus contains certain statements of a forward-looking nature
relating to future events or the future financial performance of the Company.
Prospective investors are cautioned that such statements are only predictions
and that actual events or results may differ materially. In evaluating such
statements, prospective investors should specifically consider the various
factors identified in this Prospectus, including the matters set forth under
the caption "Risk Factors," which could cause actual results to differ
materially from those indicated by such forward-looking statements.

OVERVIEW

The Company is a biotechnology company focusing on the application of
genomics to the systematic discovery of genes, biological pathways and drug
candidates in order to accelerate the discovery and development of the next
generation of therapeutic, agricultural and diagnostic products. The Company
was incorporated in November 1991 and, until March 1993, was engaged primarily
in organizational activities, research and development of the Company's
technology, grant preparation and obtaining financing. The Company has
incurred losses since inception, principally as a result of research and
development and general and administrative expenses in support of its
operations. As of September 30, 1997, CuraGen had an accumulated deficit of
$6,975,544. The Company anticipates incurring additional losses over at least
the next several years as it expands its internal and collaborative gene
discovery efforts, continues development of its technology and expands its
operations. The Company expects that losses will fluctuate from quarter to
quarter and that such fluctuations may be substantial.

In June 1996, the Company entered into a pilot collaborative agreement with
Genentech to evaluate the application of CuraGen's gene expression technology
to Genentech, pursuant to which the Company recorded $200,000. Based on its
successful pilot, in December 1996, the Company commenced an additional
collaborative agreement to provide research services to Genentech during 1997,
for a minimum research fee of $667,000. For the nine months ended September
30, 1997, the Company recorded revenues from Genentech of $500,250, or 12% of
total revenues. In connection with the execution of the pilot agreement,
Genentech made an equity investment in the Company of $1,800,000. See
"Business--Research Collaborations."

Effective June 1, 1997, the Company entered into a collaborative research
and development agreement with Pioneer Hi-Bred, whereby the Company is to
perform agricultural research that will be funded by Pioneer Hi-Bred. In
conjunction with the execution of this agreement, Pioneer Hi-Bred made an
equity investment of $7,500,000. In addition, Pioneer Hi-Bred agreed to pay
the Company an annual minimum fee of $2,500,000 based on an established number
of CuraGen employees devoted to Pioneer Hi-Bred research. For the nine months
ended September 30, 1997, the Company recorded revenues from Pioneer Hi-Bred
of $833,333, or 20% of total revenues. The agreement also includes provisions
for payments based on potential milestones, database subscriptions, licensing
of discoveries and royalties. See "Business--Research Collaborations."

In October 1997, CuraGen and Biogen entered into a research collaboration
and database subscription arrangement to discover novel genes and
therapeutics. Under the terms of the agreement, Biogen agreed to invest $5
million in CuraGen to purchase the Biogen Shares at the initial public
offering price and to provide a $10 million loan facility. At any time during
the term of the agreement, the loan is convertible at CuraGen's option into
Common Stock at the prevailing market price. Biogen will additionally provide
payments over five years to support a research collaboration to generate
project-specific GeneCalling and PathCalling databases and for database
subscription fees. Payments could reach $18.5 million if the research
collaboration and database subscription arrangement both continue for the full
five-year term. The agreement also provides for payments based on exclusive
licenses for discoveries, potential milestones and royalties. See "Business--
Research Collaborations" and "Business--Database Subscriptions."

The Company's revenue to date has primarily consisted of government grants
and ongoing payments for research and development under collaborative
agreements. Grant revenue is recognized as the related costs

24
<PAGE>

qualifying under the terms of the grants are incurred. Revenue on collaborative
agreements is recognized based upon work performed or upon the attainment of
certain benchmarks specified in the related agreement. Payments under
collaborative agreements that are received in advance, and are in excess of
amounts earned, are classified as deferred revenue.

The Company anticipates that collaborations will become an increasingly
important element of its business strategy and future revenues. The Company
also expects that government grant revenues will decrease, both in actual
dollar amounts and as a percentage of revenues, during the remainder of 1997
and in future years. Therefore, the loss of revenues from existing
collaborations would have a material adverse effect on the Company's business,
financial condition and results of operations. The Company's ability to
generate revenue growth and become profitable is dependent, in part, on the
ability of the Company to enter into additional collaborative arrangements, and
on the ability of the Company and its collaborative partners to successfully
commercialize products incorporating, or based on, the Company's technologies.
There can be no assurance that the Company will be able to maintain or expand
existing collaborations, enter into future collaborations to develop
applications of its GeneCalling, PathCalling or HitCalling technologies on
terms satisfactory to the Company, if at all, or that any such collaborative
arrangements will be successful.

Failure of the Company to successfully develop and market additional products
over the next several years, or to realize existing product revenues, would
have a material adverse effect on the Company's business, financial condition
and results of operations. Royalties or other revenue generated from commercial
sales of products developed by using the Company's technologies are not
expected for at least several years, if at all.

RESULTS OF OPERATIONS

NINE MONTHS ENDED SEPTEMBER 30, 1997 AND 1996

Revenue for the nine months ended September 30, 1997 of $4,171,750
represented an increase of $1,070,428, or 35%, compared to $3,101,322 for the
first nine months of 1996. The increase was largely due to additional
collaboration revenue of $1,413,583 recorded in 1997, primarily under the
Company's arrangements with Pioneer Hi-Bred and Genentech. The collaboration
revenue increase was offset by a decrease in grant revenue during the first
nine months of 1997 of $343,155, as the Company changed its revenue focus from
federal grants to research and development collaborations. Interest income
increased from $2,587 in the first nine months of 1996 to $525,021 in the same
period for 1997, primarily as a result of interest received on funds from sales
of the Company's preferred stock and warrants, and from research
collaborations.

Research and development expenses for the nine months ended September 30,
1997 were $6,431,139, an increase of $4,238,399 or 193%, compared to the same
period in 1996. The increase was primarily attributable to increased personnel
expenses as the Company hired additional research and development personnel,
increased purchases of laboratory supplies, increased equipment depreciation
and increased facilities expenses in connection with the expansion of the
Company's internal and collaborative research efforts. The Company expects
research and development expenses to increase as additional personnel are hired
and research and development facilities are expanded to accommodate the
Company's strategic collaborations and internal research.

General and administrative expenses for the first nine months of 1997, were
$2,071,435, an increase of $1,404,632 or 211%, compared to $666,803 for the
first nine months of 1996. The Company expects general and administrative
expenses will continue to increase in proportion to its revenue growth and
research and development expenses. Interest expense for the nine months ended
September 30, 1997 of $307,042 increased $185,867 or 153% compared to $121,175
for the same period in 1996. This increase was due to additional capital lease
obligations during the nine months ended September 30, 1997, to support
research and development activities, primarily through equipment acquisitions.

As of September 30, 1997, the Company had accumulated losses of $6,975,544
since inception and, therefore, has not paid any Federal income taxes.
Realization of deferred tax assets is dependent on future

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earnings, if any, the timing and amount of which are uncertain. Accordingly,
valuation allowances in amounts equal to the deferred income tax assets have
been established to reflect these uncertainties in all periods presented. See
Note 7 of Notes to Financial Statements.

YEARS ENDED DECEMBER 31, 1996 AND 1995

Revenue for the year ended December 31, 1996 was $4,422,947, an increase of
$2,841,772 or 180%, over 1995. The increase was primarily due to $2,466,772 of
increased grant revenue as the Company achieved certain research objectives
under certain federal grants, and $375,000 of collaboration revenue recorded in
1996 of which $200,000 was associated with the Genentech arrangement. Interest
income increased by $8,542 to $20,848, or 69%, in 1996, from $12,306 in 1995,
primarily as a result of interest received on funds received from private
placements of the Company's preferred stock and warrants and from research
collaborations.

Research and development expenses for the year ended December 31, 1996, were
$3,516,035, an increase of $2,049,660, or 140%, over 1995. The increase was
primarily attributable to increased personnel expenses as the Company hired
additional research and development personnel, increased purchases of
laboratory supplies, increased equipment depreciation and increased facilities
expenses in connection with the expansion of the Company's internal and
collaborative research efforts.

YEARS ENDED DECEMBER 31, 1995 AND 1994

Revenue for the year ended December 31, 1995 was $1,581,175, an increase of
$1,323,639 or 514%, compared to $257,536 in 1994. The increase was due entirely
to additional grant revenue as the Company was awarded several federal grants.
Interest income decreased to $12,306 in 1995, from $20,544 in 1994, as initial
funds received from private placements of securities were expended in support
of the Company's growth.

Research and development expenses totaled $1,466,375 for the year ended
December 31, 1995, an increase of $818,735, or 126% compared to $647,640 for
1994. The increase was primarily attributable to increased personnel expenses
as the Company hired additional research and development personnel, increased
purchases of laboratory supplies, increased equipment depreciation and
increased facilities expenses in connection with the expansion of the Company's
internal research efforts.

General and administrative expenses for 1995 were $961,815, an increase of
$436,144 or 83%, compared to $525,671 for 1994, in support of the Company's
growth, grant revenue and research and development. Interest expense for the
year ended December 31, 1995 of $106,035 increased $45,237 or 74% compared to
$60,798 for 1994, as capital lease obligations increased to support additional
research and development activities. The remainder of the Company's interest
expense in 1995 and 1994 was the result of a note payable to a Connecticut
state agency, borrowed in February 1994, that remained outstanding through
December 31, 1995.

LIQUIDITY AND CAPITAL RESOURCES

The Company's cash and cash equivalents totaled $20,781,115 at September 30,
1997. The Company has financed its operations since inception primarily through
private placements of equity securities, government grants, collaborative
research and development agreements and capital leases. As of September 30,
1997, the Company had recognized $10,455,311 of cumulative sponsored research
revenues from government grants and collaborative research agreements. The sale
by the Company of equity securities has provided the Company with gross
proceeds of approximately $26,500,000, including $7,500,000 from Pioneer Hi-
Bred, $1,800,000 from Genentech and $1,000,000 from Biogen. To date inflation
has not had a material effect on the Company's business.

The Company's investing activities, other than purchases and sales of cash
equivalent securities, have consisted entirely of acquisitions of equipment and
expenditures for leasehold improvements. At September 30, 1997, the Company's
gross investment in equipment and leasehold improvements since inception was
$6,362,717. At September 30, 1997 equipment with a gross book value of
$5,199,783 secures the Company's

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equipment financing facility. Although the Company had no material commitments
for capital expenditures at September 30, 1997, the Company expects capital
expenditures to increase over the next several years as it expands facilities
and purchases additional equipment to support expansion of its collaborative
agreements and internal research and development.

Net cash used in operating activities was $1,613,654 for the nine months
ended September 30, 1997, resulting primarily from the Company's net loss,
increased grants receivable balances and decreases in accrued expenses,
partially offset by increased accounts payable balances and deferred revenue.
The increase in deferred revenue on collaboration agreements during the nine
month period was due to the receipt of cash prior to completion of work to be
performed under the agreements. Net cash provided by operating activities was
$13,898 in 1996, compared to net cash used in operating activities of $222,029
in 1995 and $673,307 in 1994. The increase in net cash provided by operating
activities in 1996 compared to 1995 resulted from a decrease in the Company's
net loss, increases in accounts payable and accrued expenses, partially offset
by increases in grants receivable and accounts receivable, consistent with the
Company's growth in revenues. The decrease in net cash used in operating
activities in 1995 compared to 1994 was primarily due to increases in accrued
expenses and deferred revenue; partially offset by increases in grants
receivable.

As of September 30, 1997, the Company had net operating loss carryforwards
of approximately $6,200,000 to offset federal and state income taxes. If not
utilized, the federal and state net operating loss carryforwards will begin to
expire in 2008 and 1998, respectively. The Company also had research and
development tax credit carryforwards at September 30, 1997, estimated to be
approximately $1,293,000 for federal and state income tax purposes. An initial
public offering of the Company's securities will not result in any additional
limitation on the future utilization of these operating loss and tax credit
carryforwards.

The Company expects its cash requirements will increase significantly in
future periods because of planned expansion of its operations and its
technology platform. The planned expansion will be in support of expected
growth in collaborative agreements, database subscriptions and internal
research and development programs. The Company believes that the net proceeds
from this offering, together with existing cash and cash equivalents, and
anticipated cash flows from its current collaboration agreements, will be
sufficient to support the Company's operations through at least 1999. The
Company's belief is based on its current operating plan, which could change in
the future and require additional funding sooner than anticipated. Even if the
Company has sufficient cash for its current operating plan, it may also seek
to raise additional capital because of favorable market conditions or other
strategic factors. The Company can offer no assurance that it will be able to
establish additional collaborations or retain existing collaborators, or that
such collaborations will produce sufficient revenues, which together with cash
and cash equivalents will be adequate to fund the Company's cash requirements.
The Company has no credit facility or other sources of committed capital.

The Company's future capital requirements depend on numerous factors,
including: (i) the receipt of payments and the achievement of milestones under
existing and possible future collaborative agreements; (ii) the availability
of government research grant payments; (iii) the progress of internal research
and development projects; (iv) defense and enforcement of patent claims or
other intellectual property; (v) the purchase of additional capital equipment;
(vi) investments in complementary technologies; (vii) the development of
manufacturing, sales and marketing capabilities; and (viii) competing
technological and market demands.

The Company expects that it will require significant additional financing in
the future, which it may seek to raise, at any time, through public or private
equity offerings, debt financings or additional collaborations and licensing
arrangements. No assurance can be given that additional financing or
collaborations and licensing arrangements will be available when needed, or
that if available, such financing will be obtained on terms favorable to the
Company or its stockholders. If adequate funds are not available when needed,
the Company may have to curtail operations or attempt to raise funds on
unattractive terms. See "Risk Factors--Future Capital Requirements;
Uncertainty of Additional Funding."

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RECENTLY ENACTED PRONOUNCEMENTS

Statement of Financial Accounting Standards No. 128, Earnings Per Share, was
issued in March 1997, effective for periods ending after December 15, 1997.
Earlier application is not permitted. This pronouncement simplifies the
standards for computing earnings per share (EPS). When effective, this
statement will replace the presentation of primary EPS with presentation of
basic EPS and diluted EPS on the face of the Statement of Operations. For the
Company, basic and diluted EPS under this pronouncement would have equalled
reported EPS, as currently presented in the Company's Statement of Operations.

Statement of Financial Accounting Standards No. 130, Reporting Comprehensive
Income, was issued in June 1997 and is effective for fiscal years beginning
after December 15, 1997. This pronouncement establishes standards for
reporting and display of comprehensive income and its components in a full set
of general-purpose financial statements. The Company will adopt this
pronouncement in 1998 and does not expect its implementation will have a
material effect on the Company's financial statements as currently presented.

Statement of Financial Accounting Standards No. 131, Disclosures About
Segments of an Enterprise and Related Information, was also issued in June
1997 and is effective for fiscal periods beginning after December 15, 1997.
This pronouncement establishes the way in which publicly held business
enterprises report information about operating segments in annual financial
statements and interim reports to stockholders. As the Company operates in a
single business segment the implementation of this standard is not expected to
significantly impact the Company's financial statements as currently
presented.

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BUSINESS

CuraGen is pioneering the systematic application of genomics to accelerate
the discovery and development of therapeutic and agricultural products.
CuraGen's fully-integrated genomics technologies, processes and information
systems are designed to rapidly generate comprehensive information about gene
expression, biological pathways and the potential drugs that affect these
pathways, each on a scale not previously undertaken. The Company believes that
it can overcome the limitations of competing technologies, processes and
databases and can condense key steps in gene-based drug discovery and
development. CuraGen believes its technology platform will facilitate the
development of highly specific and effective drugs aimed at a variety of
complex diseases such as cardiovascular disease, stroke, cancer and metabolic
disorders.

The Company's drug discovery platform has three primary systems, each
consisting of proprietary technologies, automated processes and a database: the
GeneCalling system for comprehensive gene expression analysis and gene
discovery; the PathCalling system for discovery of the roles of genes and the
proteins they encode in biological pathways; and the HitCalling system for
identification of small molecule drug candidates. The GeneCalling and
PathCalling systems are fully operational, and the Company expects to
commercialize its HitCalling system in 1998. These systems are integrated to
enable gene discovery, drug target validation and high-throughput screening of
drug candidates in a highly efficient and cost-effective manner.

In addition to accelerating the discovery of new drug candidates, CuraGen's
GeneCalling and PathCalling systems are well-positioned to predict the efficacy
and safety of drug candidates currently in pharmaceutical development pipelines
and to review the performance and side effects of drugs already on the market.
This pharmacogenomics approach can aid in the development of more effective,
safer drugs and identify more appropriate patient populations.

The Company has unified its GeneCalling, PathCalling and HitCalling
technologies, processes and databases under its GeneScape bioinformatics
operating system that integrates all aspects of process management, data
analysis and visualization. GeneScape provides an easy-to-use, web-based
interface to its technology platform, thereby allowing researchers remote
Internet access and interactive capabilities from multiple sites to meet their
individual discovery and development needs. GeneScape also includes
[GeneTools], a full-featured bioinformatics software suite for further gene and
protein characterization.

BACKGROUND

Successful treatment of disease is often limited by a lack of understanding
of its initiation and progression at the level of genes, proteins and
biological pathways. Technologies and processes that have been used
successfully in the past to discover treatments for diseases with relatively
simple causes have been less effective against complex diseases that arise
through a combination of multiple genetic and environmental factors.
Cardiovascular disease, cancer, stroke and metabolic disorders are examples of
prevalent complex diseases. Treating these complex diseases requires an
understanding of how the body uses its genetic information, how disruptions in
this information can lead to disease and, in turn, how drugs can arrest or
reverse disease progression. As scientific advances improve our understanding
of the genetic basis of disease, the Company believes that the methods the
pharmaceutical industry uses to develop new drugs will undergo a fundamental
transformation. Companies that can anticipate this transformation and develop
and apply new technologies may have a unique opportunity to develop the next
generation of therapeutic products for important complex diseases.

In recent years, scientists have begun to analyze large portions of the
genetic information contained within the human genome. This discipline, termed
genomics, employs large-scale efforts catalyzed by the Human Genome Project. By
understanding the role of genes in the control and function of biological
pathways and cellular processes, scientists seek to understand more fully the
genetic basis of disease and develop more effective treatments. To date,
however, neither the pharmaceutical nor the agricultural industries have used
genomics extensively to develop new product opportunities. These industries
have used genomics to a limited extent for three primary reasons: technologies
have been inadequate; inefficient, non-automated discovery processes have
incompletely evaluated the influence of genetic and environmental factors; and
uniform information systems to drive the discovery process have been
unavailable.

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Treatment of complex diseases remains a major technical challenge and will
require an integrated set of genomic technologies and processes. CuraGen
believes that knowledge of genes, proteins, biological pathways and their
interplay with the environment, together with information systems to use this
knowledge, will accelerate drug discovery and development. CuraGen has
developed its technologies, processes and information systems to provide this
knowledge and is applying its integrated platform towards the discovery and
development of the next generation of genomics-based therapeutic, diagnostic
and agricultural products.

GENES, PATHWAYS AND DISEASE

The GENOME is the complete set of genetic information within each cell of an
organism. The information in the genome is stored in chromosomes, which are
long molecules of DNA. Sections of DNA contain discrete units of hereditary
information called GENES, each of which contains a set of instructions for the
cell to produce a particular protein. In GENE EXPRESSION, the instructions
encoded in the DNA are used by a cell to make a protein molecule. Initially,
the genetic information in the DNA is copied to a complementary molecule
called messenger RNA (MRNA). The information in the mRNA is then translated
into a PROTEIN with a precise sequence of AMINO ACID building blocks which
determine its structure and function. Although all genes are present in all
cells, each cell normally expresses only those genes it needs for the specific
functions it performs. The level of mRNA expressed for each gene dictates its
activity and the number of protein molecules produced.

Proteins carry out the biological functions of cells through a series of
highly specific, organized cascades of interactions with other proteins, genes
and chemicals. These carefully regulated, complex networks of protein
interactions are termed BIOLOGICAL PATHWAYS. These pathways are generally
classified as metabolic pathways, responsible for cellular metabolism such as
the production of energy from glucose, and SIGNAL TRANSDUCTION PATHWAYS, which
use secreted proteins, cell-surface receptor proteins, and intracellular
proteins to allow cells to communicate, coordinate, and regulate their
activities. The activities of biological pathways have many levels of control
and redundancy, and thus can be affected by many genes within a pathway. In
addition to the effects of inherited genetic differences in the genome, a
biological pathway is also affected by the EXPRESSION LEVELS of its key genes
and proteins. Many of the genes at control points along a biological pathway
are expressed at levels as low as one mRNA molecule in 100,000. Therefore,
very small changes in the expression levels of these genes can produce
substantial changes in the operation of the biological pathways under their
control.

It is now recognized that essentially all stages of disease and its
progression are caused by a sequence of changes in the expression levels of
genes and the activities of specific proteins and pathways in affected cells.
Although some diseases are caused by defects in a single gene, many prevalent
diseases involve multiple genetic factors that either cause disease directly
or predispose an individual to disease in conjunction with environmental
factors. The genes and biological pathways involved in complex diseases,
however, remain largely uncharacterized. This lack of knowledge has limited
the development of drugs to treat these diseases.

GENE-BASED DRUG DISCOVERY AND DEVELOPMENT

Most treatments for disease rely on drugs that modify the activities of
biological pathways by interacting with proteins expressed by genes in the
affected cells and tissues. In the search for safer and more effective drugs
to treat a wider range of diseases, pharmaceutical companies have begun to
explore the application of genomics to gene-based drug discovery and
development.

Modern gene-based drug discovery and development programs typically involve
the following steps: (i) GENE DISCOVERY, finding a disease-related gene; (ii)
TARGET IDENTIFICATION, ascertaining that the protein encoded by a disease-
related gene can potentially serve as a novel drug-discovery target; (iii)
TARGET VALIDATION, confirming that the potential target is at a control point
in a disease-related pathway and that a drug which interacts with the target
is expected to have a beneficial effect; (iv) ASSAY DEVELOPMENT, using the
target in a test that is designed to mimic aspects of the disease process; (v)
HIGH-THROUGHPUT SCREENING, using this assay to screen hundreds of thousands of
small organic compounds to identify compounds, or hits, which interact with
the target protein; and (vi) LEAD SELECTION AND OPTIMIZATION, identifying the
most promising hits as lead drug

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candidates according to expected efficacy, safety and bioavailability.
Typically, each step involves a laborious, time-consuming process which must
be completed before subsequent steps are undertaken. In addition, several of
the steps currently require highly skilled personnel to perform non-automated,
bench biology experiments on a single gene or target at a time. Consequently,
this has been a very costly and time-consuming approach to drug discovery and
development.

Gene Discovery. Gene discovery involves the identification of a gene related
to disease susceptibility, onset or progression. Although previous attempts to
identify disease-related genes have resulted in a better understanding of
certain diseases, they have discovered only a limited number of disease-
related genes and have led to relatively few new drugs due to limitations of
the technologies employed. The current methods for gene discovery include
genome sequencing, gene mapping, positional cloning and, more recently and
less widely used, gene expression.

GENOME SEQUENCING involves determining the sequence of large portions of
DNA. This technology identifies genes primarily at random, providing little
direct association of genes with disease. GENE MAPPING and POSITIONAL CLONING
are used together to identify disease-related genes. Gene mapping is a
laborious process that requires the extensive collection of tissue samples and
family histories in order to identify regions of the genome whose inheritance
correlates with the occurrence of disease. Positional cloning describes
efforts to find the gene within the region contributing to disease. Positional
cloning can take years to find the correct gene, is particularly difficult for
complex diseases, and has been limited in practice to identifying the genes
responsible for simple genetic disorders. Furthermore, gene mapping and
positional cloning do not directly identify additional proteins that are in
the same biological pathway as the disease-related gene and may be more
suitable targets for drugs.

GENE EXPRESSION methods are based upon comparisons of biological samples,
such as cells from human biopsies over the progression of a disease, to
identify genes whose expression levels correlate with the disease. The most
significant correlations involve genes that are expressed in disease-specific
tissues, change expression levels over the stages of a disease, and are
expressed at low levels consistent with the ability to regulate biological
pathways. In contrast to gene mapping and positional cloning, gene expression
can identify multiple disease-related genes. Even if these genes do not cause
disease directly, they are likely to encode proteins that participate in
disease-related biological pathways and can offer places to intervene in
disease progression. Some disease-related genes, such as secreted proteins,
can even serve directly as protein drugs.

CuraGen believes that gene expression methods will be the most efficient and
broadly applicable approach to identifying genes related to disease. To be
most useful, gene expression methods should be fault tolerant, measure the
expression levels for a majority of the expressed genes, including those
expressed at a single copy per cell, and be applicable to humans, animals,
plants and pathogens. Many current gene expression methods, however, face
significant limitations. Expression methods based on the repetitive sequencing
of small portions of mRNA molecules, termed expressed sequence tags (ESTS),
are inefficient. These methods cannot accurately measure genes expressed at
low levels and often miss genes that control important pathways.
Hybridization-based gene expression methods usually use portions of known
genes as probes to determine the expression levels of those genes in
biological samples. These methods are generally ineffective in discriminating
between genes with closely related sequences. Further, their application is
limited to the small set of known genes, often precluding their use for animal
models which are essential to human disease research. Methods such as
differential display generate patterns of fragments from expressed mRNA
molecules, attempt to detect changes in these patterns, and then attempt to
identify the genes responsible for these changes. These methods can be
imprecise and inefficient in measuring gene expression levels, are especially
problematic when each gene generates at most one gene fragment, and can
require time-consuming steps to confirm which genes are responsible for
particular changes in the patterns.

Target Identification and Validation. After a disease-related gene has been
identified, the next step is to decide whether the protein it encodes can
serve as a target for a drug. Part of TARGET IDENTIFICATION is determining
whether the protein is related structurally to proteins that have served
successfully as targets, including receptors and other proteins in biological
pathways.

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If a protein is not appropriate as a target, potential targets are then
sought among proteins in the same biological pathway as the disease-related
gene. Although other proteins in the same pathway can exhibit correlated
levels of gene expression, this information is often insufficient to sort
proteins into specific pathways or to show how proteins interact within a
pathway. Most research to understand biological pathways relies on non-
automated bench biology techniques able to identify only one protein at a
time. Despite the promise of this protein-by-protein approach, the associated
time, effort and expense have limited its use and, as a result, many
discoveries of disease-related genes have not led to suitable targets.

Once a protein target is identified, it must be validated in order to
provide evidence that it plays an important role in disease and that finding a
chemical compound that is active against it could lead to a drug. Alternative
techniques for TARGET VALIDATION can take months or years to complete because
it is not usually possible to view a given protein in the context of a
disease-related biological pathway.

Assay Development and High-Throughput Screening. Each validated target
usually requires the development of a specific assay or specialized
measurement technique to identify compounds that interact with it. Each assay
often requires months to develop. Potential drugs are identified by testing a
target against a chemical diversity library, usually comprising hundreds of
thousands of different small organic molecules, in HIGH-THROUGHPUT SCREENING.
Although screening a single target can be relatively rapid, screening multiple
targets can be time-consuming because most assays require that each target be
screened in a separate assay. The screening process often produces multiple
hits. To date, little progress has been made towards developing general assays
that do not require customization for each new disease-related gene and
validated target.

Drug Development. Hits that are suitable for development into potential
drugs are chosen for LEAD COMPOUND SELECTION AND OPTIMIZATION. Optimizing a
lead compound entails synthesizing and testing a series of closely related
organic compounds. The most promising leads are selected based on expected
efficacy, safety and bioavailability. This selection process typically does
not use detailed information of a candidate drug's MECHANISM OF ACTION, which
would show how a drug interacts with particular proteins and biological
pathways to achieve its desired therapeutic affect. The lack of information
often results in inaccurate predictions of efficacy and safety.

Following optimization, leads are entered into PRECLINICAL TRIALS to predict
their efficacy and safety based on animal testing. If preclinical trials are
promising, candidate drugs advance to CLINICAL TRIALS to determine their
efficacy and safety in human patients. Drug candidates have a high attrition
rate at this stage due to the lack of understanding of the mechanism of
action, poor predictions of efficacy and unexpected side effects. On average,
only one out of ten candidates that enter clinical trials gains FDA approval.
Failure at the later stages of drug development is especially significant as
it can account for half of the $360 million average cost to attain FDA
approval.

Pharmacogenomics. Even after a drug has been approved and marketed, there is
often limited knowledge of how it works. Consequently, many side effects are
observed only after use by a larger, more diverse population of patients who
may not have been adequately represented in the original trials, including
patients taking additional medications which can cause unanticipated adverse
effects. The study of the genes that determine the efficacy, pharmacology and
toxicity of a drug is referred to as PHARMACOGENOMICS. Unfortunately, previous
technologies have lacked the ability to show comprehensively what genes,
proteins and biological pathways are affected by a drug. This lack of
information has led to failures and FDA recalls of widely-prescribed drugs
such as thalidomide and dexfenfluramine.

TECHNOLOGY INTEGRATION AND INFORMATION SYSTEMS

Biotechnology companies have attempted to overcome limitations in the gene-
based drug discovery by focusing on single, isolated technologies. Major
pharmaceutical firms have been left with the challenge to integrate these
disparate components into a cohesive discovery and development pipeline. This
has created a great need for sophisticated bioinformatics systems to manage
what is now a disjointed process.

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CURAGEN'S APPROACH

CuraGen's integrated genomics technologies, processes and information
systems are designed to overcome significant technological limitations and
condense key steps in gene-based drug discovery and development. The Company
believes that its technology platform has the potential to rapidly generate
comprehensive information about gene expression, biological pathways and the
compounds affecting these pathways, each on a scale not previously undertaken.
CuraGen believes this will permit the comprehensive analysis of many diseases
and enable the discovery of disease-related genes, drug targets and potential
drugs.

[Graph showing the steps involved in both traditional gene-based drug discovery
and using CuraGen's approach to gene-based drug discovery]

CURAGEN'S APPROACH TO GENE-BASED DRUG DISCOVERY

GENE DISCOVERY (QEA AND GENECALLING)

CuraGen has developed its proprietary Quantitative Expression Analysis
("QEA") and GeneCalling technologies to overcome significant limitations of
existing gene discovery methods. QEA and GeneCalling enable the rapid, precise
measurement of substantially all of the differences in gene expression levels
between biological samples in order to discover disease-related genes. QEA and
GeneCalling are designed to detect genes expressed at the level of a single
mRNA molecule per cell, to measure comprehensively the expression levels of
95% of the genes expressed in any species and to be integrated into an
efficient, automated, high-throughput process in order to rapidly generate
large databases of gene expression profiles. These technologies permit the
Company to pursue research programs for many disease systems, process many
samples in parallel and potentially discover and seek patent protection for
commercially valuable disease-related genes.

TARGET IDENTIFICATION AND VALIDATION (MIM AND PATHCALLING)

The Company has developed its proprietary Multiplexed Interaction Method
("MIM") and PathCalling technologies to reduce the time and cost of target
identification and validation. MIM is an automated, high-throughput process
that simultaneously tests for interactions between billions of combinations of
proteins. PathCalling is the Company's proprietary software and database that
assembles the protein-protein interactions

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discovered by the MIM system into connected biological pathways. Although the
PathCalling database is still at a relatively early stage, the Company intends
to continue to populate the PathCalling database with as complete a set as
possible of the protein-protein interactions that constitute the pathways in
humans and model organisms that are relevant to disease. By identifying
protein-protein interactions with MIM and comparing them with pathways within
the PathCalling database, the role of these proteins within a given biological
pathway can be elucidated and the database further augmented. PathCalling is
designed to permit disease-related genes to be linked rapidly to specific
biological pathways, providing valuable biological context for gene
discoveries and additional targets for therapeutic intervention. The Company
believes that its PathCalling database has the potential to streamline target
identification and validation into a single, efficient, accelerated process.
The Company further believes that the number of pathway-related protein-
protein interactions currently in its proprietary PathCalling database is
greater than the total number of interactions previously described in the
scientific literature.

ASSAY DEVELOPMENT AND HIGH-THROUGHPUT SCREENING (COMBIGEN AND HITCALLING)

The Company is developing its proprietary CombiGen technology and HitCalling
database and information system to accelerate the identification of hits by
screening protein targets in parallel against small molecule diversity
libraries. The Company has designed CombiGen to avoid any need to develop a
specialized assay for each new target. With the ability to screen thousands of
targets simultaneously, the Company believes that its automated, high-
throughput screening assays will have the potential to screen more
combinations of targets and compounds than any competing technology of which
it is aware. The Company believes that this capacity enables a new approach to
drug discovery. The Company intends to pursue this approach by using CombiGen
to screen every protein that it discovers to participate in a protein-protein
interaction, including proteins both in disease-related pathways and in
pathways not yet associated with disease. The HitCalling database will store
the identities of proteins and hits. The Company anticipates that a newly-
identified disease-related gene can be linked into a pathway whose proteins
have already been screened. The identities of proteins and hits can then be
retrieved from the HitCalling database, reducing or eliminating the need for
further target identification, target validation, assay development or high-
throughput screening and thereby potentially accelerating a program by two to
three years following the first identification of a disease-related gene.

DRUG DEVELOPMENT AND PHARMACOGENOMICS (GENECALLING; PATHCALLING)

The Company believes that its GeneCalling and PathCalling technologies can
also be used to predict which drugs are more likely to succeed by analyzing
gene expression changes induced by drug treatment in humans and animal models
in preclinical and clinical trials. For drugs already on the market, the
Company has commenced generating GeneCalling databases with the objective of
selecting appropriate patient populations and accelerating the development of
an improved generation of drugs with fewer side effects. By providing a
precise correlation of gene expression levels and the activities of biological
pathways following treatment with specific drugs, the objective of the
Company's pharmacogenomics approach is to minimize the side effects of drugs,
to identify appropriate patient populations for existing drugs and to aid the
development of safer, more effective drugs.

TECHNOLOGY INTEGRATION AND INFORMATION SYSTEMS (GENESCAPE)

The Company has integrated its GeneCalling, PathCalling and HitCalling
process and databases under its GeneScape BIOINFORMATICS operating system that
unifies all aspects of process management, data analysis and visualization.
CuraGen's goal is to establish its fully-integrated technology and the
GeneScape operating system as the preferred platform for genomics and to apply
its platform to accelerate drug discovery, drug development and
pharmacogenomics. GeneScape provides a standardized, web-based interface to
its technology platform, thereby allowing researchers remote access and
interactive capabilities from multiple sites to meet their individual
discovery and development needs. Once the HitCalling database is established,
the Company expects that all three databases will be interrelated. Thus,
researchers who discover a disease-related gene through GeneCalling have the
potential to locate the relevant biological pathways in the PathCalling
database and to use the HitCalling database to identify hits active against
proteins in this pathway.

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CURAGEN'S STRATEGY

CuraGen's goal is to establish the first fully-integrated genomics business
providing comprehensive characterization of gene expression, biological
pathways and potential drugs for drug discovery and development. The Company
believes that its integrated approach can be the preferred alternative to
competitive methods employed today. The key elements of the Company's strategy
are as follows:

Provide fully-integrated, innovative technologies to overcome limitations in
drug discovery and development. The Company believes that its integrated
genomics platform provides enabling technologies at each of the three critical
levels of the genomics-based pharmaceutical development process:
identification of disease-related genes (gene discovery), elucidation of
biological pathways (target identification and validation) and identification
of compounds that interact with such pathways (assay development, high-
throughput screening, lead selection and optimization). These technologies
have the potential to advance the discovery and development of treatments for
complex diseases. The Company has designed these technologies to be (i)
applicable to a broad range of diseases; (ii) comprehensive in the analysis of
substantially all expressed genes, biological pathways and potential drugs;
(iii) standardized to enable the simultaneous processing of many combinations
of biological samples, proteins and drug candidates; (iv) integrated under a
single information system to facilitate the processing, analysis and use of
information generated from a variety of sources; and (v) readily used in
existing pharmaceutical development pipelines.

Apply its technology for drug discovery, drug development and
pharmacogenomics systematically to major diseases. The Company intends to
apply its technologies to address a wide range of diseases. CuraGen plans to
obtain biological samples from numerous models of disease (human tissue,
animal and cell-based models) in an effort to examine systematically the genes
and biological pathways involved in major diseases and to develop new drugs.
The Company believes that this broad-based approach will maximize its
opportunities to participate in the discovery and development of drugs either
alone or in collaboration with others. Through pharmacogenomics, the Company
believes it can help pharmaceutical companies develop more effective drugs
with fewer side effects by assessing the efficacy and safety of their
currently marketed drugs as well as drug candidates within their product
pipelines.

Generate revenue through research collaborations. The Company intends to
enter into research collaborations with pharmaceutical, biotechnology and
agricultural companies. The Company expects to receive revenues for applying
its proprietary technologies to a collaborator's own samples, for providing a
period of exclusivity for analyzing the data generated and from milestone and
royalty payments derived from licensed products. Data generated in
collaborations may become part of CuraGen's subscription databases. To date,
the Company has entered into collaborations with Pioneer Hi-Bred and Biogen.

Generate revenue through database subscriptions. The Company believes that
the information in its GeneCalling, PathCalling and HitCalling databases will
be a valuable resource for pharmaceutical and agricultural product
development. The Company intends to generate revenue by providing subscribers
with fee-based, non-exclusive access to its databases for defined periods. The
Company expects that its research collaborators will enter into subscriptions
as they seek to access the additional information available in the Company's
databases. To date, the Company has entered into a database subscription
arrangement with Biogen.

Retain product rights to select internal research and drug discovery
programs. The Company intends to devote a substantial portion of its resources
to its internal research programs. The initial programs selected by the
Company are expected to focus on disease systems which, the Company believes,
have the potential to result in the discovery of novel proteins as drug
candidates or targets for drug discovery. The Company also expects that its
internal research programs will be an ongoing source of data for its
GeneCalling, PathCalling and HitCalling databases.

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PRODUCTS AND SERVICES

CuraGen intends to market its genomics technology and information to the
pharmaceutical, biotechnology and agricultural industries through two
arrangements: research collaborations and subscriptions. RESEARCH
COLLABORATIONS currently involve the application of CuraGen's GeneCalling and
PathCalling technologies to a collaborator's projects, include those support
services required to characterize gene and target discoveries, and provide
ready integration with a collaborator's existing development pipeline. The
Company anticipates that collaborations will involve HitCalling when it becomes
available. DATABASE SUBSCRIPTIONS will provide subscribers with access to
CuraGen's GeneCalling, PathCalling and HitCalling databases. The Company does
not currently have any database subscribers. Both arrangements will use the
GeneScape operating system, the Company's web-based software that manages the
Company's processes, provides access to the Company's databases and includes
[GeneTools], a full-featured bioinformatics software suite.

QEA AND GENECALLING: GENE EXPRESSION SERVICES AND DATABASE

CuraGen developed its proprietary QEA and GeneCalling technology to overcome
significant limitations of competing gene discovery methods. QEA is the
Company's method for generating and analyzing gene expression profiles.
GeneCalling is the Company's information system and database that analyzes and
stores differences in these gene expression profiles to identify disease-
related genes. QEA and GeneCalling permit sensitive detection of genes that can
control biological pathways when expressed at very low levels, and unlike EST-
based methods, do not require repetitive sequencing to measure gene expression.
The Company's technology is comprehensive in detecting genes with novel
sequences and therefore applicable universally to humans, animals, plants, and
pathogens. In comparison, hybridization-based methods are primarily limited to
known genes and do not readily discriminate between many genes which share
related DNA sequences.

QEA and GeneCalling provide the ability to discover disease-related genes by
measuring expression levels and determining gene expression differences between
biological samples, such as diseased and normal human tissues. These samples
are usually processed within a month of receipt, and profiles of gene
expression levels are available immediately for inspection and analysis. The
Company's current capacity is 5,000 biological samples per year. The Company
detects multiple fragments for each gene in a sample and believes that it can
quantify accurately the expression levels of over 150 million gene fragments
per year. The Company believes that this capability exceeds the capacity of
competing technologies, can be up to 6,000 times faster than EST-based methods
for comprehensive expression profiling, and can observe a greater number of
genes than methods relying on the detection of a single fragment per gene.
Based upon its current capacity, the Company estimates that it could conduct
approximately 250 projects per year consisting of approximately 20 samples
each. The Company believes this is sufficient to support five collaborators
while meeting the needs of the Company's internal programs. See "--CuraGen
Internal Programs." The Company has designed its processes to be modular and
scalable in order to accommodate increases in the number of collaborations.

The Company's GeneCalling database stores data generated by QEA for exclusive
access for collaborations and internal programs. Through GeneScape, researchers
can access their projects and are able to select samples that have been
processed by QEA and use GeneCalling to analyze expression profiles to identify
those genes that are specific to a disease. The Company intends to structure
its collaborations such that, after the period of exclusivity has ended, data
generated from samples using QEA revert to CuraGen's GeneCalling subscription
database which currently contains gene expression data from normal human and
animal tissues.

Using QEA and GeneCalling, CuraGen has developed an innovative approach for
gene discovery for inherited diseases: POSITIONAL EXPRESSION CLONING. By
combining its gene expression analysis with existing gene mapping techniques,
the Company can rapidly discover genes associated with inherited diseases by
identifying candidate genes that both show altered expression and map to the
chromosomal locations known to contain underlying disease genes. The Company
believes its positional expression cloning approach will be particularly
effective in identifying and characterizing susceptibility and protective genes
in many common complex diseases.

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The Company believes that its technology for disease-related gene discovery
has significant advantages over genome sequencing, positional cloning and
competing gene expression technologies. CuraGen's methods permit the Company
to pursue research programs for many disease systems in parallel, with the
potential to identify rapidly a large number of commercially valuable disease-
related genes. As part of its internal programs, the Company seeks patent
protection for newly discovered disease-related genes and proteins, as well as
for novel uses of known genes and the proteins they encode. See "--
Intellectual Property" and "Risk Factors--Patents and Proprietary Rights;
Third-Party Rights."

MIM AND PATHCALLING: PATHWAY ANALYSIS SERVICES AND DATABASE

Once genes involved in a disease have been identified using GeneCalling, it
is important to be able to determine how the proteins they encode interact in
the complex pathways involved in the disease. Although a particular disease-
related protein might not be a potential protein drug or drug discovery
target, knowledge of the other proteins in the same pathway may lead to
promising protein drug or target candidates. CuraGen's MIM technology and
PathCalling database were developed to provide the link between disease-
related proteins and their biological pathways to aid in the identification
and validation of appropriate targets following the discovery of a disease-
related gene.

MIM consists of proprietary automated, high-throughput biological operations
that simultaneously test for interactions between billions of pairs of
proteins. By using MIM, CuraGen can routinely test 100,000 proteins against
100,000 other proteins, potentially identifying all interacting pairs.
PathCalling is the Company's proprietary software and database that assembles
protein-protein interactions discovered by the MIM system into connected
biological pathways, including pathways discovered previously by CuraGen or
previously described in the scientific literature. Although the PathCalling
database is still at a relatively early stage, the Company's objective is to
continue to build this database to contain as complete a set as possible of
the protein-protein interactions that constitute the pathways that are
relevant to disease. The PathCalling database permits the graphical display of
all pathways contained in the database involving any particular protein and
allows these pathways to be queried for information in much the same way gene
sequence databases are queried today. The Company believes that this will
facilitate the rapid linkage of disease-related genes to specific biological
pathways, providing the crucial biological context for gene discoveries, which
may lead to the identification of potential targets for therapeutic
intervention.

The Company seeks patent protection on the utility of specific proteins or
protein-protein interactions as drug targets based on information provided by
MIM and PathCalling, in addition to composition of matter claims based on the
sequences of novel and non-obvious proteins and the genes encoding them. There
can be no assurance, however, that such patents will be granted. See "--
Intellectual Property" and "Risk Factors--Patents and Proprietary Rights;
Third-Party Rights."

COMBIGEN AND HITCALLING: DRUG SCREENING SERVICES AND DATABASE

Traditionally, potential drugs have been screened against one target at a
time. Even with many of the advances in high-throughput screening, this
process remains inefficient, time-consuming and labor intensive. In an effort
to overcome these shortcomings, CuraGen is developing its proprietary CombiGen
technology and HitCalling database to identify simultaneously both novel
targets and hits. These technologies are based upon a combinatorial approach
for screening libraries of potential protein targets against libraries of
potential drugs.

CombiGen is being developed to use a biological assay system that will
permit the parallel processing of hundreds of drug discovery targets in the
form of single proteins or protein-protein interactions in a single high-
throughput screening assay. CombiGen has been designed to work efficiently
with the proteins in biological pathways which were identified by PathCalling.
The Company has designed this technology to avoid any need to develop a
specialized assay for each new target. With the ability to screen targets in
parallel, the Company believes that its automated, high-throughput screening
assays have the potential to screen more combinations of targets and compounds
than any competing technology of which the Company is aware.

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When CombiGen is fully operational, the Company intends to commence screening
of many of the proteins in its PathCalling database, both in disease-related
biological pathways and in pathways not yet associated with disease, to
generate its HitCalling database. In this new approach, the Company believes
that, when a disease-related gene is discovered, the HitCalling database may
accelerate drug discovery by displaying hits against other proteins in that
gene's pathway.

CuraGen expects that it will complete pilot studies of its CombiGen
technology and commercialize HitCalling in 1998. The Company intends to
generate a database containing a large collection of hits against many of the
proteins in its PathCalling database. Where appropriate, the Company plans to
file patent applications to protect targets, small organic compounds and their
utilities. There can be no assurance, however, that the Company will
successfully complete the development of CombiGen and HitCalling, that the
Company will discover hits through the use of this technology, that patent
applications will be filed or that patents on such hits will be granted. See
"Risk Factors--New and Uncertain Business" and "--Patents and Proprietary
Rights; Third-Party Rights."

GENESCAPE OPERATING SYSTEM FOR GENOMICS

CuraGen designed its GeneScape bioinformatics software to meet the needs of
researchers for a single operating system which integrates research requests,
project management, database access and data analysis and visualization. The
Company's GeneScape web-based bioinformatics operating system provides the user
with a standardized, Internet-enabled interface to its processes and databases
for GeneCalling, PathCalling and HitCalling. GeneScape operates on any computer
platform that supports a standard web browser. GeneScape is designed to be
modular and extendable to incorporate other processes. GeneScape currently
consists of three components: Discovery, Study Management, and [GeneTools].

Discovery. The Discovery component manages queries to the GeneCalling,
PathCalling and HitCalling databases. GeneScape provides data analysis and
visualization through a flexible, easy-to-use point-and-click interface
organized in three sections corresponding to GeneCalling, PathCalling, and
HitCalling. GeneScape provides the answers to queries in visual format,
organized according to preferences set by the end user: differential gene
expression; expression in particular samples, tissues, or disease stages;
participation in metabolic or signal transduction pathways; map position;
functional role; interactions with proteins or small molecules; or other custom
criteria. The Company believes that the ability to respond to direct queries
with the comprehensive analysis of gene expression and biological pathways may
make GeneScape a preferred platform for discovering disease-related genes and
drug discovery targets.

Study Management. CuraGen's collaborators can manage processes and resources
over the Internet to meet their individual research needs. Separate links on
the Study Management page provide direct, up-to-the-minute status reports for
projects, individual processes within projects, and resource allocation among
projects and processes. Study Management automates the operation of every
station in the QEA and MIM process and monitors quality control at each
processing step.

[GeneTools]. The GeneScape operating system also includes [GeneTools], an
easy-to-use, unified bioinformatics software package for DNA and protein
sequence analysis; sequence similarity to known genes, protein drugs and
protein targets; three-dimensional structure prediction; identification of
proteins participating in biological pathways; and custom literature searches.
[GeneTools] also provides users with access to publicly available sequence,
mapping and expression databases that the Company has imported, assembled, and
annotated for enhanced value. In addition, the Company has assembled
proprietary sequence and mapping databases for portions of the corn, mouse, rat
and human genomes. Collaborators can elect to have CuraGen link their own
proprietary or third-party sequence databases into GeneScape and [GeneTools]
for their own exclusive use.

GENESHOP

Through its GeneShop, the Company now offers its collaborators services that
will complement its proprietary GeneCalling, PathCalling, and HitCalling
technologies. GeneShop can provide high-throughput,

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efficient and essential research services including confirmation of gene
expression differences, gene sequencing, delivery of full-length clones of
genes, gene mapping and mutation detection. These services and materials can
all be requested, for a fee, directly through GeneScape.

RESEARCH COLLABORATIONS

The Company's business strategy includes the establishment of research
collaborations with pharmaceutical, biotechnology and agricultural companies.
The Company anticipates that such collaborations will generally provide
revenues in the form of fees for the generation of gene expression and
biological pathway data from samples provided by a collaborator. The
collaborator will have the ability to control how resources are allocated to
generate GeneCalling and PathCalling databases and to perform additional
research services through GeneShop, including the sequencing of gene fragments
and the generation of full-length clones. Fees will also give each such
partner exclusive access for a defined period of time to the GeneCalling or
PathCalling databases containing the information produced in the
collaboration. The Company expects that collaborators will have the right to
license, for an up-front fee, discoveries arising from a collaboration,
including rights to novel genes, novel uses of previously identified genes,
and protein targets and hits. Collaborations may also include milestone
payments and royalty payments on sales of products developed using discoveries
made through the use of the Company's technology. After the period of
exclusivity expires, rights to genes and portions of the data not licensed by
the collaborator are expected to revert to CuraGen. The Company intends to
include this data in its expanding subscription databases.

The Company intends to seek collaborations that will be non-exclusive with
respect to a given field or disease indication, for example stroke or
cardiovascular disease, but exclusive for a specific period of time for
certain disease models, such as a research project using a mouse model for
stroke or cardiovascular disease. To date, the Company has entered into
collaborations with Pioneer Hi-Bred and Biogen.

PIONEER HI-BRED

In May 1997, CuraGen and Pioneer Hi-Bred entered into a research
collaboration to identify genes responsible for agricultural seed product
performance, including crop yield, drought resistance and pest resistance (the
"Pioneer Agreement"). Pioneer Hi-Bred is a leader in the development of
genetically based agricultural crop seed products, with approximately 42% of
the North American corn seed market and a significant share of the market in
other major corn-growing areas of the world. Historically, Pioneer Hi-Bred has
developed new hybrid seed strains with favorable traits using traditional
cross breeding techniques with only limited knowledge of the genes responsible
for such traits. The Company believes that by applying QEA and GeneCalling
technologies, it will discover the genes responsible for these favorable
traits, thereby enabling Pioneer Hi-Bred to develop, faster and more
efficiently, new generations of seed products with superior traits.

Under the terms of the Pioneer Agreement, Pioneer Hi-Bred agreed to fund a
research program for up to five years in certain areas related to agricultural
crop seed research and product development, and the Company agreed not to
collaborate with any other parties within such areas. Payments by Pioneer Hi-
Bred to the Company in the form of research funding could reach $18.5 million
if the research program continues for its full five-year term, with minimum
annual payments of $2.5 million. In connection with the collaboration, Pioneer
Hi-Bred made a $7.5 equity million investment in the Company.

Pioneer Hi-Bred has the right, at any time after November 1998, to terminate
the research program on three months' notice if the Company has not identified
any genes associated with certain traits of interest to Pioneer. Pioneer Hi-
Bred may also terminate the research program at any time after May 2000 on six
months' notice. Unless earlier terminated in accordance with its terms, the
Pioneer Agreement will remain in effect until the expiration of the
obligations of Pioneer Hi-Bred to pay royalties under the Pioneer Agreement.

The Pioneer Agreement provides Pioneer Hi-Bred with exclusive, worldwide,
royalty-bearing rights to develop and commercialize products based on gene
discoveries made in the collaboration in certain areas related

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to seed products, non-seed plant products and agricultural chemicals. CuraGen
will receive specified royalties on the sale of seed products incorporating
trait-specific genes identified by CuraGen. Royalties with respect to non-seed
plant products and agricultural chemicals are to be negotiated. The Pioneer
Agreement provides the Company with a worldwide right to develop and
commercialize products in the fields of human healthcare, pharmaceuticals,
animal health and microbial applications based upon gene discoveries arising
from the collaboration.

The Company believes that this collaboration offers it significant discovery
benefits because Pioneer Hi-Bred has assembled one of the world's largest
collections of genetic materials, which contains a wide range of genes and
pathways responsible for important agricultural traits. Many of the genes and
pathways plant cells use to carry out biological processes have closely
related genes and pathways in human cells. CuraGen has retained all rights to
use the information gained in studies of plant genes for applications to the
Company's programs in human disease.

BIOGEN

In June 1997, CuraGen and Biogen entered into a stock purchase agreement,
pursuant to which Biogen made a $1 million equity investment in the Company in
anticipation of evaluating the application of CuraGen's technology to a
particular program of interest to Biogen.

The October 1997, CuraGen and Biogen entered into a research collaboration
and database subscription arrangement pursuant to a Research and Option
Agreement (the "Biogen Agreement"). Under the Biogen Agreement, CuraGen and
Biogen will collaborate in the discovery of novel therapeutics across a range
of Biogen-specified disease programs. The parties also expect to conduct
pharmacogenomic analysis of selected products and product candidates in
Biogen's portfolio. The collaboration will provide Biogen with access to
CuraGen's proprietary genomics platform, including the GeneScape
bioinformatics operating system in order to generate GeneCalling and
PathCalling databases from Biogen-specified disease systems. Biogen will also
gain non-exclusive access to CuraGen's GeneCalling and PathCalling
subscription databases.

Under the terms of the agreement, Biogen agreed to invest $5 million in
CuraGen to purchase Common Stock (the "Biogen Shares") at the initial public
offering price and to provide a $10 million loan facility. Interest under the
loans is payable semi-annually. The loan is convertible at any time at
CuraGen's option into Common Stock at its prevailing market price and the
principal is payable at the earlier of five years or one year after
termination by Biogen of the Biogen Agreement. Biogen will additionally
provide payments over five years to support the research collaboration and to
gain non-exclusive access to CuraGen's GeneCalling and PathCalling
subscription databases. Payments could reach $18.5 million if the research
collaboration and database subscription arrangement both continue for the full
five-year term. Biogen has an exclusive right during specified periods to
evaluate discoveries arising from the collaboration and to license discoveries
upon payment of an additional fee. After the period of exclusivity elapses,
rights to genes not licensed to Biogen and rights to the data will revert to
CuraGen for inclusion in its subscription databases. For each therapeutic
product which is developed under an exclusive license and attains certain
development and commercialization milestones, Biogen will provide milestone
payments of up to $18.5 million. Biogen will also pay royalties based on
future product sales.

Biogen may terminate the research collaboration upon six months' written
notice, with the earliest possible termination date being in April 2000.
Biogen may terminate its database subscription at any time upon three months'
written notice.

GENENTECH

In June 1996 and December 1996, CuraGen and Genentech entered into
exploratory programs to evaluate the application of CuraGen's integrated
genomics technologies to selected internal programs at Genentech. These
agreements are limited in scope and duration. Under the terms of these
agreements, CuraGen received a $1.8 million equity investment and will receive
research and development payments of a minimum of $667,000 to cover three
separate exploratory programs. The agreements call for milestone payments and
royalties on therapeutic product sales.

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DATABASE SUBSCRIPTIONS

As part of its business strategy, the Company intends to offer subscriptions
which will provide users with non-exclusive access to its GeneCalling,
PathCalling and HitCalling databases through the GeneScape operating system.
The Company will also provide subscribers access to its [GeneTools]
bioinformatics software. The Company anticipates updating its databases
regularly with selected data generated from internal programs, as well as data
from collaborations which have reverted to the Company. The Company intends to
structure its arrangements to receive initial fees and periodic maintenance
fees for each subscription. In addition, the Company may receive license fees,
milestone payments and royalties in connection with the licensing or use of
proprietary information in its databases for the development of products.
Certain subscribers may also seek to take advantage of the full range of the
Company's GeneCalling, PathCalling, HitCalling and GeneShop services by
entering into collaborations with the Company. To date, the Company has entered
into a subscription arrangement with Biogen as part of the Biogen Agreement.
See "--Research Collaborations--Biogen."

CURAGEN INTERNAL PROGRAMS

The Company intends to use its integrated genomics technology platform to
pursue a broad portfolio of research programs that encompass drug discovery,
drug development and pharmacogenomics. During the next five years, the
Company's objective is to analyze systematically the genetic basis of many
common diseases as well as the mechanisms of action and adverse side effects of
many commonly prescribed drugs. CuraGen is focusing its efforts on programs
that address unmet medical needs and that the Company believes have the
potential to yield products that can be commercialized in a relatively short
time. In particular, the Company selects human diseases and animal models of
human disease based on their potential to yield protein drugs, to identify
novel targets for common diseases that lack effective treatments or to aid
rational development or marketing of existing drugs. At each stage, the Company
plans to reevaluate the relative merits of continuing such programs through
internal efforts or through research collaborations.

DISCOVERY PROGRAMS

The Company currently has programs in cardiovascular disease, including
hypertension and stroke; endocrine and metabolic disorders, including obesity,
diabetes and osteoporosis; autoimmune disorders including arthritis; cancer;
and infectious diseases. In its internal programs, CuraGen has discovered over
disease-related genes and has filed patent applications relating to
these discoveries.

Certain of the genetic disease models selected by the Company are designed to
discover variations of genes that protect individuals from disease in addition
to finding mutations in genes that are involved in the susceptibility, onset or
progression of disease. The Company intends to explore the potential of the
proteins encoded by protective genes as protein drugs. The Company has already
identified gene variants that are potentially protective in stroke. These gene
variants were identified from animal models using QEA and GeneCalling within
months of project inception. The Company has also discovered mutations in genes
involved in diabetes and hypertension, one of which the Company believes may be
a suitable target for small molecule drug development.

Cardiovascular Disease and Stroke. Cardiovascular diseases such as stroke and
atherosclerosis are the leading cause of death in the United States. Treatments
for these diseases have limited efficacy. Using GeneCalling and PathCalling,
CuraGen is analyzing genetic models of hypertension and ischemic stroke to
identify disease-related genes. This strategy has led to the discovery of a
secreted protein variant that appears to protect against stroke and the
discovery of a gene that may contribute to hypertension.

Endocrine and Metabolic Diseases. Within the field of endocrine and metabolic
diseases, CuraGen is analyzing a variety of genetic models including obesity,
type II diabetes, osteoporosis, osteoarthritis and gall stone disease. The
Company believes that its technology platform is well-suited to identifying the
genes and

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pathways involved in these diseases, which are known to involve errors in
signal transduction and the regulation of metabolic pathways. To date, the
Company has used QEA and GeneCalling to discover over 40 genes associated with
these diseases and is using PathCalling in an attempt to identify disease-
related pathways and potential targets for drug discovery. The Company
believes that this information may also lead to the discovery of protein
drugs.

Autoimmunity, Arthritis, and Allergy. Although diseases of the immune
system, such as systemic lupus erythematosus and rheumatoid arthritis, are
among the most common and chronic, existing drugs for autoimmune diseases have
exhibited limited efficacy and debilitating side effects. The Company has used
QEA and GeneCalling in nine different genetic models of systemic autoimmune
disease to identify disease-related genes. CuraGen is using MIM and
PathCalling to identify pathways which incorporate these genes.

Cancer. Cancer encompasses disease processes of almost every organ system
and involves the loss of control of multiple, diverse mechanisms of signal
transduction and pathway regulation. CuraGen is applying GeneCalling and
PathCalling to identify the genes and pathways involved in the early
development of cancer and its step-wise progression to metastatic disease.
CuraGen has analyzed a number of models of cancer and has identified pathways
incorporating proteins common to many of the models.

Infectious Diseases. The Company believes that its program for pathogenic
diseases offers advantages over alternative approaches that primarily aim at
sequencing pathogen genomes with little characterization of the role of
specific pathogen proteins in biological pathways. CuraGen's research,
however, uses MIM and PathCalling to identify protein-protein interactions,
including both pathogen-pathogen and pathogen-host interactions, and
biological pathways to provide this characterization, which is valuable for
target identification and validation. The Company anticipates discovering
novel pathways specific to unique human infectious agents, including viruses,
bacteria and parasites, that are important during resting, vegetative, and
pathogenic states of infection. The Company believes its approach may
facilitate the development of diagnostic assays for infectious diseases and
improved vaccines and drugs. The Company has initiated a program for a
specific bacterial pathogen and has discovered novel protein-protein
interactions that tie into known pathways conferring pathogenicity.

DRUG DEVELOPMENT AND PHARMACOGENOMICS

The Company believes that the application of QEA and GeneCalling to identify
genes that are differentially expressed in response to treatment with drug
candidates and marketed drugs represents a significant commercial opportunity.
Using this approach, the tissues targeted by the drug, as well as the organs
that might exhibit side effects, including liver or kidney damage, can be
studied in animal models thought to be indicative of human response. The
Company believes that this information may help pharmaceutical companies
select and optimize drug candidates based on efficacy and reduced side
effects. In addition to reducing the time and cost of developing drugs, the
Company believes that such results may strengthen FDA applications. For drugs
already on the market, an understanding of the mechanism of action through
pharmacogenomics can help identify appropriate patient populations and lead to
an improved generation of drugs.

The Company has begun to analyze drugs whose commercial viability or
clinical indications are threatened either by a lack of understanding of
mechanism of action or by severe side effects. The Company's goal is to
generate GeneCalling databases for 20 to 50 drugs a year to provide
pharmacology and toxicology information, to understand the mechanism of drug
action, to identify patient populations that are likely to respond favorably
to a particular medication, and potentially to identify new indications or
more optimal targets.

TECHNOLOGY PLATFORM

CuraGen's integrated genomics technologies, processes and information
systems are designed to rapidly generate extensive and precise information
about gene expression, biological pathways and the chemicals that affect these
pathways, each on a scale not previously undertaken. CuraGen's GeneCalling,
PathCalling and HitCalling and related core technologies have been integrated
under its GeneScape operating system. The

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Company has 14 patent applications pending on its proprietary technologies.
CuraGen intends to continue to pursue a broad intellectual property position
with respect to its GeneCalling, PathCalling, HitCalling and related core
technologies.

QEA AND GENECALLING: CURAGEN'S TECHNOLOGY FOR GENE DISCOVERY

CuraGen's QEA technology and GeneCalling database, accessed over the
Internet through GeneScape, serve as the basis of the Company's collaborations
with Pioneer Hi-Bred and Biogen. The use of these technologies has led to
patent filings relating to over disease-related genes in internal programs
and research collaborations.

The QEA process starts with a biological sample from which mRNA molecules
are isolated. The gene expression information contained in the mRNA molecules
is copied back to DNA molecules, which are more chemically stable, to create a
pool of complementary DNA (CDNA). Each of 48 to 96 QEA reactions probes a
separate portion of the original cDNA pool with a unique pair of subsequences,
short stretches of bases. If a cDNA molecule contains both subsequences, it
produces a fluorescently-labeled gene fragment whose length is determined by
the number of bases between the subsequences as they occur in the gene. Each
QEA reaction produces approximately 200 different fragments. The QEA process
typically generates multiple fragments per gene to provide fault tolerance by
minimizing the possibility that a gene will not be detected.

The labeled fragments from each QEA reaction are loaded into individual
lanes of an electrophoresis gel and separated according to length. The
quantity of fragments of each length is determined by optical detection of the
fragment labels. The more copies of a given gene, the more fragments are
produced and the brighter the signal from that gene's fragments. The Company's
proprietary instrumentation and software has the sensitivity to detect
fragments at the level of 1 in 250,000, sufficient to detect a single mRNA
molecule per cell. The detection of 200 fragments in each lane contains
information on both the identities (from the lengths) and expression levels
(from the fluorescence intensities) of approximately 200 genes, as opposed to
alternative EST-sequencing approaches, where a single lane yields information
solely on the identity of a single gene. Analysis of 48 to 96 lanes from
different QEA reactions generates data for approximately 10,000 to 20,000
fluorescently labeled gene fragments. Gene fragment patterns are stored in the
Company's GeneCalling database.

After a sample has been processed by QEA to produce gene fragment patterns,
GeneCalling software uses the subsequence pair in a QEA reaction like an area
code, the fragment length like a phone number, and a database of known genes
like a phone book to identify the gene that generated each fragment. Fragments
which do not have any match in the database of known genes, and which
therefore may represent valuable novel genes, may also be observed. The
Company sequences just these unmatched fragments for inclusion in its
database.

QEA and GeneCalling are designed to be sufficiently sensitive to detect
genes expressed at the level of a single mRNA per cell, comprehensive by
measuring the expression levels of 95% of the genes expressed in a cell, and
efficient in processing samples, generating gene expression profiles, and
identifying genes whose expression levels correlate with disease. The
Company's technology is able to detect genes with novel sequences and
therefore is applicable broadly to humans, animals, plants and pathogens. The
Company believes that QEA and GeneCalling provide advantages over other
technologies that analyze gene fragment patterns but lack fault tolerance,
specificity or the ability to look up gene identity in a database.

MIM AND PATHCALLING: CURAGEN'S TECHNOLOGY FOR TARGET IDENTIFICATION AND
VALIDATION

CuraGen's MIM technology and PathCalling database were developed to provide
a link between disease-related genes and the biological pathways in which the
proteins encoded by such genes interact. The Company believes that these
technologies, accessed over the Internet through GeneScape, will serve as a
significant component of the Company's research collaborations and
subscriptions. The use of these technologies in internal programs has led to
patent filings on proteins that participate in disease-related biological
pathways.

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MIM uses genetically engineered cells to simultaneously test for interactions
between thousands of pairs of proteins. First, two cDNA libraries are produced
from the genes expressed in any biological sample, including human tissues,
animals or pathogens. Next, each cell in the MIM system is engineered to
contain a foreign protein encoded by a gene from one of the two cDNA libraries.
Each of these foreign proteins is connected to one half of an essential
activating protein that has been split in two and cannot function unless
reconstituted. Billions of these engineered cells are then fused,
simultaneously, to test for interactions between the majority of possible
combinations of foreign proteins from each library. If a cell contains two
foreign proteins which interact with each other, the essential activating
protein is reconstituted and permits the cell to live. Those cells that do not
contain interacting proteins die. The identities of the interacting proteins in
the surviving cells are then determined by sequencing the DNA encoding the
foreign proteins.

The Company believes its automated MIM technology is an advance over
technical approaches in which a single target protein is the same in all the
cells, while the second foreign protein is from a cDNA library. This approach
can identify only those proteins that interact with a single target protein of
interest. The Company has introduced proprietary advances that permit testing
of interactions using two protein libraries simultaneously, which eliminates
the need for a specific target protein and the protein-by-protein approach for
elucidating pathways. The Company believes that its proprietary advances in
biological methods and computer software also allow a significant reduction in
the error rate due to incorrect identification of protein-protein interactions.

COMBIGEN AND HITCALLING: CURAGEN'S TECHNOLOGY FOR MULTIPLEXED HIGH-THROUGHPUT
SCREENING ASSAYS

The Company is developing its CombiGen technology and HitCalling database to
accelerate high-throughput screening of novel protein targets. The Company's
CombiGen technology is designed to employ cells that have been engineered to
express foreign protein targets. Many of these cells, each potentially
expressing unique targets, are then introduced into each well of an assay
plate. The engineered cells in each well are then exposed to a small molecule
from a chemical diversity library as part of an automated, high-throughput
screen. In most cases, the small molecule does not bind to any of the foreign
proteins and all the cells in a well die. If the small molecule does bind to a
foreign protein target in one of the cells, however, that cell lives. This
selection step allows the assay to be multiplexed for many protein targets in
parallel: thousands or millions of cells, each expressing different targets,
can be introduced at once and assayed against the same small molecule. Growth
in a well implies that the small molecule is active against one or more of the
foreign protein targets. The identity of the targets can then be determined by
sequencing DNA from the surviving cells. The identities of the protein targets
and hits will be stored in the HitCalling database.

CombiGen technology leverages CuraGen's expertise with MIM technology and is
directly applicable to proteins discovered by MIM and PathCalling to
participate in protein-protein interactions. CombiGen also permits screening of
protein targets discovered through methods other than MIM.

CORE TECHNOLOGY DEVELOPMENT

The Company has historically reduced its reliance on equity financing for
developing its GeneCalling, PathCalling, HitCalling and related core
technologies by competing successfully for federal grants. Granting agencies
have included the National Cancer Institute (NCI) and the National Human Genome
Research Institute (NHGRI) of the National Institutes of Health (NIH) and the
National Institute of Standards and Technology (NIST) of the United States
Department of Commerce through its Advanced Technology Program (ATP). The
Company believes that these multiple awards, in particular the receipt of three
separate ATP awards in a highly competitive selection process, attest to
CuraGen's excellence in developing and applying innovative, commercially
valuable technology.

Bioinformatics. CuraGen's GeneScape operating system provides web-based
access to its technologies, processes and databases; full capabilities for
project management and discovery queries over the Internet or at a client's
site; and use of [GeneTools], a full-featured suite of bioinformatics software.
GeneScape uses JAVA and C programs to interact with an underlying Oracle
database. The Company plans to continue development of

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GeneScape as a modular, cross-platform system able to serve as a standardized
operating system for multiple genomic-based technologies.

Instrumentation. CuraGen has conducted extensive technology research and
development for the analysis of DNA fragments, which the Company considers to
be an important unit operation for genomics. The Company believes that there
is strategic value in developing in-house, proprietary technology and
instrumentation that offers higher performance than commercially-available DNA
electrophoresis and hybridization platforms.

The Company has developed its Niagara DNA analysis device to operate in
conjunction with QEA and GeneCalling. The Company believes that Niagara is
faster, more sensitive and flexible, and offers better resolution of closely-
spaced gene fragments than commercially available instruments. In addition,
the Company has developed its proprietary Open Genome Initiative ("OGI")
software for signal processing and data analysis in conjunction with its
Niagara device. OGI software is integrated with the GeneScape operating
system, but is also capable of stand-alone operation or for use with
commercially available DNA analysis instruments.

CuraGen is developing an upgrade path for the Niagara instrument that
includes MicroNiagara, combining features of slab-gel and capillary
electrophoresis, and NanoNiagara, a micromachined separation chip that uses a
non-electrophoretic, liquid-phase mechanism for DNA separation. The Company
believes that these advanced programs will help maintain its competitive
advantage in the separation, detection and analysis of DNA.

COMPETITION

The Company faces, and will continue to face, intense competition from
pharmaceutical, biotechnology and diagnostic companies, as well as academic
and research institutions and government agencies. The Company is subject to
significant competition from organizations that are pursuing technologies and
products that are the same as or similar to the Company's technology and
products. Many of the organizations competing with the Company have greater
capital resources, research and development staffs and facilities and
marketing capabilities than the Company. In addition, research in the field of
genomics generally is highly competitive. Competitors of the Company in the
genomics area include, among others, public companies such as Affymetrix,
Inc., Human Genome Sciences, Inc., Incyte Pharmaceuticals, Inc. and Millennium
Pharmaceuticals, Inc., as well as private companies and major pharmaceutical
companies. Universities and other research institutions, including those
receiving funding from the federally funded Human Genome Project, also compete
with the Company. The Company's future success will depend in large part on
its maintaining a competitive position in the genomics field. Rapid
technological development by the Company or others may result in products or
technologies becoming obsolete before the Company recovers the expenses it
incurs in connection with their development. Products offered by the Company
could be made obsolete by less expensive or more effective technologies. There
can be no assurance that the Company will be able to make the enhancements to
its technology necessary to compete successfully with newly emerging
technologies. See "Business--Competition."

A number of competitors are attempting to identify and patent genes and gene
fragments sequenced at random, typically without specific knowledge of the
function of such genes or gene fragments. The Company's competitors may
discover, characterize or develop important genes or gene fragments in advance
of the Company, which could have a material adverse effect on any related
disease research program of the Company. The Company expects competition to
intensify in genomics research as technical advances are made and become more
widely known. See "Risk Factors--Competition."

INTELLECTUAL PROPERTY

The Company's business and competitive position are dependent upon its
ability to protect its GeneCalling, PathCalling and HitCalling proprietary
technologies, processes, databases and information systems. Despite the
Company's efforts to protect its proprietary rights, unauthorized parties may
attempt to obtain and use information that the Company regards as proprietary.
The Company relies on patent, trade secret and copyright law and nondisclosure
and other contractual arrangements to protect such proprietary information.
The Company

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has filed patent applications for its proprietary methods and devices for gene
expression analysis, for discovery of biological pathways and for drug
screening for pharmaceutical product development. As of September 30, 1997,
the Company had 14 patent applications pending, with the United States Patent
and Trademark Office ("USPTO"), covering its technology and had filed several
corresponding international and foreign patent applications. To date, no
patents have been issued to the Company with respect to such technology and
there can be no assurance that any patents will issue. There can be no
assurance that others will not independently develop substantially equivalent
proprietary information and techniques or otherwise gain access to the
Company's proprietary information, that such information will not be disclosed
or that the Company can effectively protect its rights to unpatented trade
secrets or other proprietary information.

The Company's commercial success will also depend in part on obtaining
patent protection on gene and protein target discoveries for which it or its
collaborators or subscribers discover utility and on products, methods and
services based on such discoveries. The Company has applied for patent
protection for novel mutants of known genes and their uses, partial sequences
of novel proteins and their gene sequences and uses, and novel uses for
previously identified genes discovered by third parties. The Company has
sought and intends to continue to seek patent protection for novel uses for
genes and proteins which may have been patented by third parties. In such
cases, the Company would need a license from the holder of the patent with
respect to such gene or protein in order to make, use or sell such gene or
protein for such use. There can be no assurance that the Company will be able
to acquire such licenses on commercially reasonable terms, if at all. The
Company's patent application filings that result from the identification of
genes associated with the cause or effect of a particular disease generally
seek to protect the genes and encoded proteins if these genes and encoded
proteins are, among other things, novel and non-obvious, as well as
therapeutic, diagnostic and drug screening methods and products, and other
subject matter based upon a gene and its indication. Where information is
discovered on the specific biological pathway in which the protein encoded by
the gene participates, the Company also seeks to protect the newly identified
protein complex as well as the methods for identifying intervention
strategies. Each application typically contains multiple genes discovered for
a particular disease system.

The patent positions of pharmaceutical, biopharmaceutical and biotechnology
companies, including the Company, are generally uncertain and involve complex
legal and factual questions. There can be no assurance that any of the
Company's pending patent applications will result in issued patents, that the
Company will develop additional proprietary technologies that are patentable,
that any patents issued to the Company or its collaborative customers will
provide a basis for commercially viable products or will provide the Company
with any competitive advantages or will not be challenged or circumvented or
invalidated by third parties, or that the patents of others will not have an
adverse effect on the ability of the Company to do business. In addition,
patent law relating to the scope of claims in the technology fields in which
the Company operates is still evolving. The degree of future protection for
the Company's proprietary rights is uncertain. Furthermore, there can be no
assurance that others will not independently develop similar or alternative
technologies, duplicate any of the Company's technologies, or, if patents are
issued to the Company, design around the patented technologies developed by
the Company. In addition, the Company could incur substantial costs in
litigation if it is required to defend itself in patent suits brought by third
parties or if it initiates such suits.

There can be no assurance that patents for the Company's products or methods
will be obtained, or that, if issued, such patents will provide substantial
protection or be of commercial benefit to the Company. The issuance of a
patent is not conclusive as to its validity or enforceability, nor does it
provide the patent holder with freedom to operate without infringing the
patent rights of others. A patent could be challenged by litigation and, if
the outcome of such litigation were adverse to the patent holder, competitors
could be free to use the subject matter covered by the patent, or the patent
holder may license the technology to others in settlement of such litigation.
The invalidation of key patents owned by or licensed to the Company or non-
approval of pending patent applications could increase competition, and result
in a material adverse effect on the Company's business, financial condition
and results of operations. In addition, there can be no assurance that any
application or exploitation of the Company's technology will not infringe
patents or proprietary rights of others or that licenses that might be
required as a result of such infringement for the Company's processes or
products would be available on commercially reasonable terms, if at all.

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The Company cannot predict whether its or its competitors' patent
applications will result in valid patents being issued. Litigation, which
could result in substantial cost to the Company, may also be necessary to
enforce the Company's patent and proprietary rights and/or to determine the
scope and validity of others' proprietary rights. The Company may participate
in interference proceedings that may in the future be declared by the USPTO to
determine priority of invention, which could result in substantial cost to the
Company. There can be no assurance that the outcome of any such litigation or
interference proceedings will be favorable to the Company or that the Company
will be able to obtain licenses to technology that it may require or that, if
obtainable, such technology can be licensed at a reasonable cost.

The public availability of ESTs or other sequence information prior to the
time the Company applies for patent protection on a corresponding full-length
or partial gene could adversely affect the Company's ability to obtain patent
protection with respect to such gene or gene sequences. In addition, certain
other groups are attempting to rapidly identify and characterize genes through
the use of gene expression analysis and other technologies. To the extent any
patents issue to other parties on such partial or full-length genes or uses
for such genes, the risk increases that the sale of potential products,
including therapeutics, or processes developed by the Company or its
collaborators may give rise to claims of patent infringement. Others may have
filed and in the future are likely to file patent applications covering genes
or gene products that are similar or identical to those of the Company. No
assurance can be given that any such patent application will not have priority
over patent applications filed by the Company. Any legal action against the
Company or its collaborators claiming damages and seeking to enjoin commercial
activities relating to the affected products and processes could, in addition
to subjecting the Company to potential liability for damages, require the
Company or its collaborators to obtain a license in order to continue to
manufacture or market the affected products and processes or could enjoin the
Company from continuing to manufacture or market the affected products and
processes. There can be no assurance that the Company or its collaborators
would prevail in any such action or that any license required under any such
patent would be made available on commercially acceptable terms, if at all.
The Company believes that there may be significant litigation in the industry
regarding patent and other intellectual property rights. If the Company
becomes involved in such litigation, it could consume a substantial portion of
the Company's managerial and financial resources. Under the Company's
government grants and contracts, the federal government has a nonexclusive,
nontransferable, paid-up license to practice or have practiced for or on
behalf of the United States, throughout the world and, under certain
circumstances, to grant to other parties licenses under, any inventions
conceived or first actually reduced to practice under the government grants
and contracts.

There is substantial uncertainty concerning the extent to which supportive
data will be required for issuance of patents for human therapeutics. If data
additional to that available to the Company is required, the Company's ability
to obtain patent protection could be delayed or otherwise adversely affected.
Although the USPTO issued new utility guidelines in July 1995 that address the
requirements for demonstrating utility for biotechnology inventions,
particularly for inventions relating to human therapeutics, there can be no
assurance that USPTO examiners will follow such guidelines or that the USPTO's
position will not change with respect to what is required to establish utility
for gene sequences and products and methods based on such sequences.
Furthermore, the enactment of the legislation implementing the General
Agreement on Tariffs and Trade has resulted in certain changes to United
States patent laws that became effective on June 8, 1995. Most notably, the
term of patent protection for patent applications filed on or after June 8,
1995 is no longer a period of seventeen years from the date of grant. The new
term of United States patents will commence on the date of issuance and
terminate twenty years from the earliest filing date in the United States to
which priority is claimed for the application. Because the time from filing to
issuance of biotechnology patent applications is often more than three years,
a twenty-year term from the claimed United States priority date may result in
a substantially shortened term of patent protection, which may adversely
impact the Company's patent position. If this change results in a shorter
period of patent coverage, the Company's business could be adversely affected
to the extent that the duration and level of the royalties it is entitled to
receive from its strategic partners is based on the existence of a valid
patent.

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The Company also relies upon trade secret protection for some of its
confidential and proprietary information that is not subject matter for which
patent protection is being sought. The Company believes that it has developed
proprietary technology, processes and information systems for use in gene
expression and biological pathway discovery, as well as in the identification
of molecular targets for pharmaceutical development, including proprietary
biological protocols, instrumentation, robotics and automation, software and
an integrated bioinformatics system. In addition, the Company has developed a
database of proprietary gene expression patterns and biological pathways which
it updates on an ongoing basis and which can be accessed over the Internet.
The Company has taken security measures to protect its proprietary
technologies, processes, information systems and data and continues to explore
ways to enhance such security. There can be no assurance, however, that such
measures will provide adequate protection for the Company's trade secrets or
other proprietary information. While the Company requires employees, academic
collaborators and consultants to enter into confidentiality and/or non-
disclosure agreements where appropriate, there can be no assurance that
proprietary information will not be disclosed, that others will not
independently develop substantially equivalent proprietary information and
techniques or otherwise gain access to the Company's trade secrets or disclose
such technology, or that the Company can meaningfully protect its trade
secrets. See "Risk Factors--Patents and Proprietary Rights; Third Party
Rights."

GOVERNMENT REGULATION

Prior to marketing, any new drug developed by the Company or its
collaborative customers must undergo an extensive regulatory approval process
in the United States and other countries. This regulatory process, which
includes preclinical and clinical studies, as well as post-marketing
surveillance to establish a compound's safety and efficacy, can take many
years and require the expenditure of substantial resources. Data obtained from
such studies are susceptible to varying interpretations that could delay,
limit or prevent regulatory approval. The rate of completion of clinical
trials is dependent upon, among other factors, the enrollment of patients.
Patient accrual is a function of many factors, including the size of the
patient population, the proximity of patients to clinical sites, the
eligibility criteria for the study and the existence of competitive clinical
trials. Delays in planned patient enrollment in clinical trials may result in
increased costs, program delays or both, which could have a material adverse
effect on the Company. Delays or rejections may also be encountered based upon
changes in FDA policies for drug approval during the period of product
development and FDA regulatory review of each submitted NDA in the case of new
pharmaceutical agents, or PLA in the case of biologics. Similar delays also
may be encountered in the regulatory approval of any diagnostic product and in
obtaining regulatory approvals in foreign countries. Under current guidelines,
proposals to conduct clinical research involving gene therapy at institutions
supported by the NIH must be approved by the Recombinant DNA Advisory
Committee and the NIH. There can be no assurance that regulatory approval will
be obtained for any drugs or diagnostic products developed by the Company or
its collaborative customers. Furthermore, regulatory approval may impose
limitations on the indicated use of a drug. Because certain of the products
likely to result from the Company's disease research programs involve the
application of new technologies and may be based upon a new therapeutic
approach, such products may be subject to substantial additional review by
various government regulatory authorities and, as a result, regulatory
approvals may be obtained more slowly than for products using more
conventional technologies.

Even if regulatory approval is obtained, a marketed product and its
manufacturer are subject to continuing review. Discovery of previously unknown
problems with a product may have adverse effects on the Company's business,
financial condition and results of operations, including withdrawal of the
product from the market. Violations of regulatory requirements at any stage,
including preclinical studies and clinical trials, the approval process or
post-approval, may result in various adverse consequences to the Company,
including the FDA's delay in approval or refusal to approve a product,
withdrawal of an approved product from the market or the imposition of
criminal penalties against the manufacturer and NDA or PLA holder. The Company
has not submitted an IND for any product candidate, and no product candidate
has been approved for commercialization in the United States or elsewhere. The
Company intends to rely primarily on its collaborators to file INDs and
generally direct the regulatory approval process. No assurance can be given
that the Company or any of its collaborators will be

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able to conduct clinical testing or obtain the necessary approvals from the
FDA or other regulatory authorities for any products. Failure to obtain
required governmental approvals will delay or preclude the Company's
collaborators from marketing drugs or diagnostic products developed by the
Company or limit the commercial use of such products and could have a material
adverse effect on the Company's business, financial condition and results of
operations.

The Company's research and development activities involve the controlled use
of hazardous materials, chemicals and various radioactive materials. The
Company is subject to federal, state and local laws and regulations governing
the use, storage, handling and disposal of such materials and certain waste
products. Although the Company believes that its safety procedures for
handling and disposing of such materials comply with the standards prescribed
by federal, state and local laws and regulations, the risk of accidental
contamination or injury from these materials cannot be completely eliminated.
In the event of such an accident, the Company could be held liable for any
damages that result and any liability could exceed the resources of the
Company. See "Risk Factors--Government Regulation; No Assurance of Regulatory
Approval."

EMPLOYEES

At September 30, 1997, the Company had 150 full-time equivalent employees,
of whom 70 held Ph.D. or other doctoral degrees and 12 others held masters or
other post-graduate degrees. The employee group includes engineers,
physicians, molecular biologists, chemists and computer scientists. The
Company intends to expand its number of full-time equivalent employees and
affiliates prior to the end of 1997. The Company believes that its relations
with its employees are good. None of the Company's employees is represented by
a union.

FACILITIES

CuraGen's principal administrative offices are located in New Haven,
Connecticut in a 26,000 square foot leased facility. The Company also leases
an 8,000 square foot technology development laboratory at its original site in
Branford, Connecticut, and a 4,000 square foot facility in Alachua, Florida.
The Company also supports scientists at the University of California at
Berkeley MicroFabrication laboratory. CuraGen believes that its facilities are
adequate for the Company's operations and that suitable additional space will
be available in New Haven, Branford and Alachua as needed.

LEGAL PROCEEDINGS

The Company is not a party to any legal proceedings.

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MANAGEMENT

EXECUTIVE OFFICERS AND DIRECTORS

The executive officers and directors of the Company, their ages as of
November 1, 1997, and their positions with the Company are as follows:

<TABLE>
<CAPTION>
Name Age Position
- ---- --- --------
<S> <C> <C>
Jonathan M. Rothberg, Ph.D........... 34 Chief Executive Officer, President
and Chairman of the Board
Gregory T. Went, Ph.D................ 34 Executive Vice President and
Director
David M. Wurzer, C.P.A............... 39 Executive Vice President, Treasurer
and Chief Financial Officer
Elizabeth A. Whayland, C.P.A......... 37 Director of Financial Management and
Secretary
Peter A. Fuller, Ph.D................ 43 Vice President, Business Development
Stephen F. Kingsmore, M.B., Ch.B..... 37 Vice President, Research
Richard H. Booth, C.P.A., C.L.U.,
Ch.F.C. ............................ 50 Director
Vincent T. DeVita, Jr., M.D.......... 62 Director
Robert E. Patricelli................. 57 Director
James L. Vincent..................... 57 Director
</TABLE>
- --------

(1)Member of the Compensation Committee.

(2)Member of the Audit Committee.

Jonathan M. Rothberg, Ph.D. has served as Chief Executive Officer, President
and Chairman of the Board of Directors of the Company since its formation in
1991. From May 1991 to March 1993, he served as a Postdoctoral Fellow at the
Howard Hughes Medical Institute's Boyer Center for Molecular Medicine. Dr.
Rothberg received his B.S. in Chemical Engineering from Carnegie Mellon
University and his M.S., M. Phil. and Ph.D. in Biology from Yale University.

Gregory T. Went, Ph.D. has served as Executive Vice President of the Company
since February 1997 and as a Director of the Company since October 1997. From
September 1994 until February 1997, Dr. Went served as Vice President,
Business Development of the Company. From the Company's formation until
September 1994, Dr. Went served as Director of Structural Biology. Dr. Went
received his B.S. in Chemical Engineering from Carnegie Mellon University and
his Ph.D. in Chemical Engineering from the University of California, Berkeley.

David M. Wurzer, C.P.A. has served as Executive Vice President, Treasurer
and Chief Financial Officer of the Company since September 1997. From January
1991 to September 1997, Mr. Wurzer served as Senior Vice President and Chief
Financial Officer and in other senior managerial positions for Value Health,
Inc., a managed health care provider. Mr. Wurzer received his B.B.A. from the
University of Notre Dame.

Elizabeth A. Whayland, C.P.A. has served as Director of Financial Management
since November 1994 and as Secretary of the Company since September 1997. From
July 1982 to November 1994, Ms. Whayland served as a Senior Manager and in
other staff and management positions with Deloitte & Touche. Ms. Whayland
received her B.A. from Grove City College and her M.S.T. from the University
of Hartford.

Peter A. Fuller, Ph.D. has served as Vice President, Business Development of
the Company since October 1997. From September 1983 to October 1997, Dr.
Fuller served as Director, Technology Identification & Assessment, Director,
Technology Access, Director, Technology Acquisition Group and Soybean Research
Station Manager for Pioneer Hi-Bred, a leading supplier of agricultural
genetics. Dr. Fuller received his B.S. from California State University and
his M.S. and Ph.D. from the University of Nebraska.

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Stephen F. Kingsmore, M.B., Ch.B. has served as Vice President, Research of
the Company since October 1997. From July 1994 to October 1997, Dr. Kingsmore
served as Assistant Professor at the University of Florida in its Department
of Medicine, Division of Rheumatology and Clinical Immunology and at its
Center for Mammalian Genetics. He also served as an Affiliate Assistant
Professor at the University of Florida in its Department of Pathology and
Laboratory Medicine from July 1994 to October 1997, and in its Department of
Molecular Genetics and Microbiology from August 1996 to October 1997. From
March 1988 to July 1994, he served in the positions of Postdoctoral Fellow,
Intern, Resident and Fellow, Rheumatology at Duke University. Dr. Kingsmore
received his M.B. and his Ch.B. from Queen's University, Belfast, United
Kingdom.

Richard H. Booth, C.P.A., C.L.U., Ch.F.C. is Executive Vice President,
Corporate Strategic Development of Phoenix Home Life Mutual Insurance Company,
a position he has held since October 1994. He also currently serves as a
director of Phoenix Duff & Phelps Corporation, HSB Group, Inc., Aberdeen Asset
Management, PLC and Mechanics Savings Bank. From August 1994 to September
1994, Mr. Booth served as a consultant for Phoenix Home Life Mutual Insurance
Company. From February 1991 to June 1994, he served as President, Chief
Operating Officer and as a director of The Travelers Corporation, a
diversified financial services company. Mr. Booth received his B.S. and his
M.S.P.A. from the University of Hartford.

Vincent T. DeVita, Jr., M.D. has served as a Director of the Company since
September 1995. Currently, he serves as a director of Imclone Systems, Inc.
and is Director of the Yale University Comprehensive Cancer Center, a position
he has held since July 1993. From September 1988 to July 1993, Dr. DeVita
served as Physician-in-Chief of the Memorial Sloane-Kettering Cancer Center.
From July 1980 to August 1988, he served as Director of the National Cancer
Institute. Dr. DeVita received his B.S. from the College of William and Mary
and his M.D. from the George Washington University School of Medicine.

Robert E. Patricelli, J.D. is the President and Chief Executive Officer of
Patient Centered Health Care, Inc., a physicians' group practice management
company, a position he has held since August 1997. He also currently serves as
a director of Northeast Utilities, Inc. and Hartford Life, Inc. From May 1987
to August 1997, he served as Chairman, President and Chief Executive Officer
of Value Health, Inc. Mr. Patricelli received his B.A. from Wesleyan
University and his J.D. from Harvard Law School.

James L. Vincent has been Chairman of the Board of Directors of Biogen since
October 1985. From October 1985 until February 1997, Mr. Vincent served as
Chief Executive Officer of Biogen. He also served as Chief Operating Officer
and President of Biogen from April 1988 until February 1994. Prior to that he
served as Group Vice President of Allied Corporation (now Allied-Signal, Inc.)
and as President of Allied Health and Scientific Products Company from 1982 to
1985. He also served as Executive Vice President, Chief Operating Officer and
as a director of Abbott Laboratories, Inc., a pharmaceutical company. Mr.
Vincent received his B.S. from Duke University and his M.B.A. from Wharton
Graduate Business School, University of Pennsylvania.

COMMITTEES OF THE BOARD OF DIRECTORS

The Board of Directors established a Compensation Committee and an Audit
Committee in October 1997. The Audit Committee oversees the engagement of the
Company's independent accountants, reviews the annual financial statements and
the scope of annual audits and considers matters relating to accounting policy
and internal controls. The Compensation Committee reviews, approves and makes
recommendations to the Board of Directors concerning the Company's
compensation policies, practices and procedures for its executive officers.
The Compensation Committee also administers the Company's 1997 Employee,
Director and Consultant Stock Plan (the "1997 Stock Plan") and the 1993 Stock
Option and Incentive Award Plan (the "1993 Stock Plan"). See "--Stock Option
Plans."

51
<PAGE>

SCIENTIFIC ADVISORY BOARD

In 1995, the Company established a Scientific Advisory Board to assist the
Company in its research and development activities. The Scientific Advisory
Board is comprised of several distinguished scientists from outside the Company
who have significant accomplishments in areas of science and technology that
are important to the Company's future. The following individuals are the
current members of the Scientific Advisory Board:

MEDICAL/MOLECULAR BIOLOGY

Richard P. Lifton, M.D., Ph.D. serves as Chairman of the Company's Scientific
Advisory Board. Dr. Lifton is Professor of Medicine, Genetics, Molecular
Biophysics and Biochemistry at the Yale University School of Medicine where he
also serves as Director of the Programs in Molecular Genetics and
Cardiovascular Genetics. He also serves as Director of the Yale University
Specialized Center of Research in Hypertension and as investigator of the
Howard Hughes Medical Institute. Dr. Lifton received his B.A. from Dartmouth
College and his M.D. and Ph.D. from Stanford University.

Jose Costa, M.D. is Director of Anatomical Pathology and Vice-Chairman of
Pathology at the Yale University School of Medicine, Deputy Director of the
Yale University Comprehensive Cancer Center and Chief of Yale University's
Program for Critical Technologies in Breast Oncology. Dr. Costa received his
B.A. from Lycee Francais College International, Barcelona, Spain and his M.D.
from the University of Barcelona Medical School.

Pietro De Camilli, M.D. is Professor and former Director of Medical Studies
in the Department of Cell Biology at the Yale University School of Medicine
where he also serves as a member of the Executive Committee of the Yale
University Diabetes Endocrinology Research Center. He is an investigator of the
Howard Hughes Medical Institute and is a member of the National Advisory
Committee of the Pew Scholars Program in the BioMedical Sciences. Dr. De
Camilli received his M.D. from the University of Milano, Italy and carried out
postdoctoral studies at the Yale University School of Medicine.

BIOINFORMATICS

Daniel Seligson, Ph.D. has held various senior management positions in the
Technology and Manufacturing Group at Intel Corporation and currently serves at
Intel as Manager of 300mm Process Equipment Development. Dr. Seligson received
his B.S. from the Massachusetts Institute of Technology and his Ph.D. from the
University of California, Berkeley.

Lincoln D. Stein, M.D., Ph.D. has served as Director of Information Systems
of the Company since September 1997. From December 1995 to July 1997, Dr. Stein
was Director of Informatics Core at the Massachusetts Institute of Technology
Whitehead Institute. Dr. Stein received his B.A. from The Johns Hopkins
University and his M.D. and Ph.D. from Harvard Medical School.

TECHNOLOGY AND AUTOMATION

Harold G. Craighead, Ph.D. is Professor of Applied and Engineering Physics at
Cornell University. From January 1988 to June 1995, he served as Director of
the Cornell University Nanofabrication Facility. Dr. Craighead received his
B.S. from the University of Maryland and his Ph.D. from Cornell University.

Lynn W. Jelinski, Ph.D. is Director of both the Office of Economic
Development and the Center for Advanced Technology in Biotechnology as well as
a Professor of Engineering at Cornell University. Dr. Jelinski received her
B.S. from Duke University and her Ph.D. from the University of Hawaii.

Other than Dr. Stein, each of the Scientific Advisory Board members is
employed by an employer other than the Company or is self-employed and may have
commitments to, or consulting or advisory contracts with, other entities that
may conflict or compete with his or her obligations to the Company. Generally,
members of the Scientific Advisory Board are not expected to devote a
substantial portion of their time to Company matters.

52
<PAGE>

COMPENSATION OF DIRECTORS AND SCIENTIFIC ADVISORS

Non-employee directors are reimbursed for travel costs and other out-of-
pocket expenses incurred in attending each directors' meeting and committee
meeting. Non-employee directors receive no directors' fees but are eligible to
receive automatic grants of non-qualified stock options under the 1997 Stock
Plan. Each non-employee director, upon first being elected or appointed to the
Board of Directors, will receive an option to purchase 20,000 shares of Common
Stock, which will vest one-third immediately and one-third each on the first
and second anniversaries of the grant date. Any non-employee director who
joined the Board of Directors prior to the adoption of the 1997 Stock Plan
will receive an option to purchase 5,000 shares of Common Stock, which will
also vest one-third immediately and one-third each on the first and second
anniversaries of the grant date. Upon joining the Board of Directors in
September 1995, Dr. DeVita was granted an option to purchase 15,000 shares of
Common Stock under the 1993 Stock Plan. Additionally, the 1997 Stock Plan
provides for an annual grant of an immediately exercisable option to purchase
5,000 shares of Common Stock to each non-employee director following each
annual meeting of stockholders commencing with the 1998 annual meeting
(provided such non-employee director was not first elected at any such annual
meeting). All automatic option grants to non-employee directors will have a
term of ten years and an exercise price equal to the fair market value of the
Common Stock on the date of grant. Pursuant to the foregoing provisions of the
1997 Stock Plan, Dr. DeVita and Messrs. Booth, Patricelli and Vincent have
been granted options to purchase 5,000, 20,000, 20,000, and 20,000 shares of
Common Stock, respectively, at the initial public offering price. See "--Stock
Option Plans."

Each member of the Scientific Advisory Board is paid a stipend of $1,000 per
day, plus expenses for each day of service. In addition, members have received
options to purchase shares of the Common Stock. These options were granted at
various exercise prices and are exercisable at various dates through May 2007.
Members of the Scientific Advisory Board may receive additional option grants
from time to time.

In May 1997, the Company entered into a Scientific Advisory Board Agreement
with Richard P. Lifton, M.D. Ph.D. (the "SAB Agreement"). The SAB Agreement
provides for Dr. Lifton to be retained as chairman of the Company's Scientific
Advisory Board and as a consultant to the Company in the field of genomics.
Dr. Lifton will not be required to spend more than 24 days each year providing
services pursuant to the SAB Agreement. The initial term of the SAB Agreement
is for a period of three years and can be extended for
one-year periods. Either party may, however, terminate the SAB Agreement, with
or without cause, by giving at least thirty days prior written notice to the
other party.

During the term of the SAB Agreement, and for a period of six months
following the termination of the SAB Agreement, Dr. Lifton will not directly
or indirectly be a founder of, serve as a member of the scientific board of,
or act as an officer or employee of, or, without written permission of the
Company, consult for any entity that provides biotechnology services or
products or otherwise assists an entity or person in developing, producing,
marketing or selling any biotechnology product or service. Dr. Lifton, may,
however, continue to perform services and research on behalf of the Howard
Hughes Medical Institute or Yale University School of Medicine. If the Company
terminates the SAB Agreement without cause, the foregoing restrictions do not
apply.

Pursuant to the SAB Agreement, Dr. Lifton will receive a consulting fee of
$1,000 for each day of services provided to the Company, as well as
reimbursement for all reasonable and necessary expenses incurred in connection
with his consulting services. Dr. Lifton has also received a stock option to
purchase 86,250 shares of Common Stock at an exercise price of $4.10 per
share.

53
<PAGE>

EXECUTIVE COMPENSATION

Summary Compensation. The following table presents certain information
concerning compensation paid or accrued for services rendered to the Company
in all capacities during the year ended December 31, 1996, for the chief
executive officer and the other most highly compensated executive officers of
the Company earning greater than $100,000 in the year ended December 31, 1996
(the "Named Executive Officer").

SUMMARY COMPENSATION TABLE

<TABLE>
<CAPTION>
ANNUAL COMPENSATION
------------------------------
OTHER ANNUAL
NAME AND PRINCIPAL POSITION SALARY BONUS COMPENSATION
- --------------------------- -------- ----- ------------
<S> <C> <C> <C>
Jonathan M. Rothberg, Ph.D. ..................... $125,000(1) $-- $--
Chief Executive Officer
</TABLE>
- --------
(1) From the Company's inception through September 30, 1996, Dr. Rothberg
indefinitely deferred the payment of his salary on an interest-free basis.
Accordingly, $93,750 of Dr. Rothberg's salary for the year ended December
31, 1996 has been deferred and $308,125 of Dr. Rothberg's salary has been
deferred in the aggregate.

Option Grants. There were no options granted by the Company during the year
ended December 31, 1996 to the Named Executive Officer.

Option Exercises and Year-End Option Values. The Named Executive Officer did
not exercise any options during 1996 and did not hold any stock options at
December 31, 1996.

EMPLOYMENT ARRANGEMENTS

The Company has entered into letter agreements (collectively, the
"Employment Letters") with the following executive officers: Dr. Went, Mr.
Wurzer, Dr. Fuller and Dr. Kingsmore in February 1997, July 1997, August 1997,
and August 1997, respectively. The Employment Letters do not specify a term of
employment. Pursuant to the Employment Letters, Drs. Went and Kingsmore and
Mr. Wurzer receive base salaries of $125,000 and Dr. Fuller receives a base
salary of $115,000. Each Employment Letter also provides for a bonus, which
the Board of Directors may, in its discretion, award from time to time. The
Company has agreed that, upon the closing of this Offering, the Board of
Directors will review Dr. Went's, Mr. Wurzer's, Dr. Fuller's and Dr.
Kingsmore's compensation and provide an enhanced compensation package to each
employee.

COMPENSATION COMMITTEE INTERLOCKS AND INSIDER PARTICIPATION

and , both non-employee directors, constitute the Company's
Compensation Committee. No executive officer of the Company will serve as a
member of the board of directors or compensation committee of any entity that
has one or more executive officers serving as a member of the Company's Board
of Directors or Compensation Committee.

STOCK OPTION PLANS

1997 Stock Plan. The Company's 1997 Stock Plan was approved by the Company's
Board of Directors and stockholders in October 1997. The 1997 Stock Plan
provides for the issuance of stock options and stock grants ("Stock Rights")
to employees, directors and consultants of the Company. A total of 1,500,000
shares of Common Stock have been reserved for issuance under the 1997 Stock
Plan. Options to purchase 65,000 shares of Common Stock have been granted
under the 1997 Stock Plan. The 1997 Stock Plan is administered by the
Compensation Committee of the Board of Directors. The Compensation Committee
has the authority to administer the provisions of the 1997 Stock Plan and to
determine the persons to whom Stock Rights will be granted, the number of
shares to be covered by each Stock Right and the terms and conditions upon
which a Stock Right may be granted.

54
<PAGE>

Stock grants under the 1997 Stock Plan will be subject to such terms and
conditions as the Compensation Committee deems to be appropriate and in the
best interest of the Company. These terms may include conditions relating to
the right of the Company to reacquire the shares subject to the Stock grant,
including the time and events upon which such rights shall accrue, and the
purchase price of the shares.

Options granted under the 1997 Stock Plan may be either (i) options intended
to qualify as "incentive stock options" under Section 422 of the Internal
Revenue Code of 1986, as amended (the "Code"), or (ii) non-qualified stock
options. The exercise price of options granted under the 1997 Stock Plan will
be determined by the Compensation Committee, provided that, in the case of
incentive stock options, the price will not be less than 100% of the fair
market value of the Common Stock on the date of grant, or not less than 110%
of the fair market value of the Common Stock on the date of grant if the
optionee holds 10% or more of the voting stock of the Company. The 1997 Stock
Plan also provides for the automatic grant of non-qualified options to non-
employee directors of the Company. See "--Compensation of Directors and
Scientific Advisors." An incentive stock option granted under the 1997 Stock
Plan may be exercised after the termination of the optionholder's employment
with the Company (other than by reason of death, disability or termination for
"cause" as defined in the 1997 Stock Plan), to the extent exercisable on the
date of termination, at any time prior to the earlier of the option's
specified expiration date or 90 days after such termination. The Compensation
Committee may specify the termination or cancellation provisions applicable to
a non-qualified stock option. In the event of the optionholder's death or
disability, both incentive stock options and non-qualified stock options
generally may be exercised, to the extent exercisable on the date of death or
disability, by the optionholder or the optionholder's survivors at any time
prior to the earlier of the option's specified expiration date or one year
from the date of death or disability. Generally, in the event of the
optionholder's termination for cause, all outstanding and unexercised options
are forfeited.

If the Company is to be consolidated with or acquired by another entity in a
merger, sale of all or substantially all of the Company's assets or otherwise
(an "Acquisition"), the Compensation Committee or the board of directors of
any entity assuming the obligations of the Company under the Plan shall, as to
outstanding options under the plan, either (i) make appropriate provision for
the continuation of such options by substituting, on an equitable basis, for
the shares then subject to such options, the consideration payable with
respect to the outstanding shares of Common Stock in connection with an
Acquisition or securities of the successor or acquiring entity; or (ii) upon
written notice to the optionholders, provide that all options must be
exercised (either to the extent then exercisable or, at the discretion of the
Compensation Committee, all options being made fully exercisable for purposes
of such transaction) within a specified number of days of the date of such
notice, at the end of which period the options shall terminate; or (iii)
terminate all options in exchange for a cash payment equal to the excess of
the fair market value of the shares subject to each such option (either to the
extent then exercisable or, at the discretion of the Compensation Committee,
all options being made fully exercisable for purposes of such transaction)
over the exercise price thereof.

1993 Stock Plan. The Company's 1993 Stock Plan was approved by the Company's
Board of Directors and stockholders in December 1993 and subsequently amended
by the Board of Directors in May 1997. The 1993 Stock Plan provides for the
issuance of stock options and stock awards to employees and consultants of the
Company and members of the Company's Board of Directors and Scientific
Advisory Board. Of the 1,500,000 shares of Common Stock which were reserved
for issuance under the 1993 Stock Plan, options to purchase 1,028,884 shares
have been granted and are outstanding at September 30, 1997. The Company does
not intend to grant any additional options or awards under the 1993 Stock
Plan.

Upon termination of service to the Company (other than by reason of death,
disability or termination for "cause" as defined in the 1993 Stock Plan) an
option granted under the 1993 Stock Plan is generally exercisable, to the
extent exercisable on the date of termination, for up to three months
following termination. In the event of the optionholder's death or disability,
options generally may be exercised, to the extent exercisable on the date of
death or disability, by the optionholder or the optionholder's survivors for
up to one year from the date of death or disability. In the event of the
optionholder's termination for cause, all outstanding and unexercised options
are forfeited.

55
<PAGE>

If the Company is to be consolidated with or merged into another entity
(such that the Company is not the surviving entity), or upon a sale of all or
substantially all of the Company's assets or otherwise (a "Change in
Control"), the Compensation Committee or the board of directors of any entity
assuming the obligations of the Company under the plan shall, as to
outstanding options, either (i) make appropriate provision for the
continuation of such options by substituting, on an equitable basis, the
shares then subject to such options for the consideration payable with respect
to the outstanding shares of Common Stock in connection with a Change in
Control or securities of the successor or acquiring entity; or (ii) upon
written notice to the optionholders, provide that all options must be
exercised (to the extent then exercisable) within a specified number of days
of the date of such notice, at the end of which period the options shall
terminate; or (iii) terminate all options in exchange for a cash payment equal
to the excess of the fair market value of the shares subject to each such
option (to the extent then exercisable) over the exercise price thereof.

Additional Options. In addition to the options granted under the 1993 Stock
Plan, the Company has granted options to purchase an aggregate of 570,000
shares of Common Stock pursuant to individual agreements with Company
employees and consultants. These options incorporate the provisions of the
1993 Stock Plan to the extent such provisions are not inconsistent with the
terms of those options.

LIMITATION OF DIRECTORS' LIABILITY AND INDEMNIFICATION

The DGCL authorizes corporations to limit or eliminate the personal
liability of directors to corporations and their stockholders for monetary
damages for breach of directors' fiduciary duty of care. The Restated
Certificate limits the liability of directors of the Company to the Company or
its stockholders to the fullest extent permitted by Delaware law. See
"Description of Capital Stock--Delaware Law and Certain Charter and Bylaw
Provisions."

The Restated Certificate provides mandatory indemnification rights to any
officer or director of the Company who, by reason of the fact that he or she
is an officer or director of the Company, is involved in a legal proceeding of
any nature. Such indemnification rights include reimbursement for expenses
incurred by such officer or director in advance of the final disposition of
such proceeding in accordance with the applicable provisions of the DGCL.

There is no pending litigation or proceeding involving a director, officer,
employee or agent of the Company in which indemnification by the Company will
be required or permitted. The Company is not aware of any threatened
litigation or proceeding that may result in a claim for such indemnification.

56
<PAGE>

CERTAIN TRANSACTIONS

Since January 1, 1994, there has not been nor is there currently proposed,
any transaction or series of similar transactions to which the Company was or
is to be a party in which the amount involved exceeded or exceeds $60,000 and
in which any director, executive officer, holder of more than 5% of the Common
Stock of the Company or any member of the immediate family of any of the
foregoing persons had or will have a direct or indirect material interest
other than the transactions described below.

In 1993, seven members of Dr. Rothberg's family, including Henry M. Rothberg
and Lillian R. Rothberg, who are Dr. Rothberg's parents and five percent
beneficial stockholders of the Company, and Michael J. Rothberg who is Dr.
Rothberg's brother and a five percent beneficial stockholder of the Company,
loaned $898,000 to the Company. On December 30, 1993, the notes evidencing
these loans were canceled in exchange for 898,000 shares of Common Stock and
two-year warrants to purchase 1,122,500 shares of Common Stock at an exercise
price of $1.00 per share. In 1995, the Company modified these warrants to
extend their terms from two years to seven years.

In March 1997, the Company raised gross proceeds of approximately $1,750,000
by completing a private placement of 175,000 shares of Series B Preferred
Stock with five investors at a price of $10.00 per share. In connection with
this private placement, the Company issued five-year warrants to purchase
358,361 shares of Common Stock at an exercise price of $5.86 per share. Henry
and Lillian Rothberg purchased 60,000 shares of such Series B Preferred Stock
and were issued warrants to purchase 122,866 shares of Common Stock. Hemroc II
Trust, a trust of which Michael J. Rothberg is a co-trustee, purchased 10,000
shares of Series B Preferred Stock and was issued warrants to purchase 20,478
shares of Common Stock. Gianpiero Molinari, the brother-in-law of Dr. Rothberg
and Michael J. Rothberg and the son-in-law of Henry and Lillian Rothberg,
purchased 5,000 shares of the Series B Preferred Stock and was issued warrants
to purchase 10,239 shares of Common Stock.

In March 1997, the Company raised gross proceeds of $11,787,202 by
completing a private placement of 2,011,468 shares of Series C Convertible
Preferred Stock (the "Series C Preferred Stock") with eleven investors at a
price of $5.86 per share. In connection with this private placement, the
Company also issued three-year warrants to purchase 366,894 shares of Common
Stock at an exercise price of $9.00 per share to two investors who purchased
1,706,485 and 127,986 shares of Series C Preferred Stock, respectively. Henry
and Lillian Rothberg purchased 34,130 shares of the Series C Preferred Stock.
Quantum Industrial Partners LDC, a five percent beneficial stockholder of the
Company, purchased 1,706,485 shares of the Series C Preferred Stock and was
issued warrants to purchase 341,297 shares of Common Stock.

In May 1997, Pioneer became a five percent beneficial stockholder of the
Company, through the purchase of 1,000,000 shares of Series D Convertible
Preferred Stock (the "Series D Preferred Stock") at a price of $7.50 per
share. The Company and Pioneer also entered into a Collaborative Research and
License Agreement related to the discovery and development of genes associated
with plant growth and development. See "Business--Research Collaborations" for
a description of this Agreement.

Upon the closing of the Offering, all of the Company's 175,000 outstanding
shares of Series B Preferred Stock will be redeemed by the Company. In
addition, upon the closing of the Offering, as part of the Automatic
Conversion, all of the Series C Preferred Stock and Series D Preferred Stock
will convert into Common Stock on a one for one basis. The holders of the
Series C Preferred Stock and the Series D Preferred Stock have been granted
registration rights. See "Description of Capital Stock--Registration Rights"
for a description of these rights.

In June 1997, the Company raised gross proceeds of approximately $1,000,000
by completing a private placement of 100,000 shares of Series E Convertible
Preferred Stock to Biogen at a price of $10.00 per share. In October 1997, the
Company and Biogen entered into the Biogen Agreement. Pursuant to the Biogen
Agreement, Biogen agreed to purchase the Biogen Shares and to provide a $10
million loan facility to the Company. See "--Business--Research
Collaborations" for a description of the Biogen Agreement. James L. Vincent, a
Director of the Company, currently serves as Chairman of the Board of Biogen.

57
<PAGE>

From September 1993 to July 1997, Michael J. Rothberg arranged a number of
capital leases and purchases of equipment and supplies on behalf of the
Company. The Company believes that these capital leases and purchases were on
terms at least as favorable as would have been available from a third party.
As compensation for these services, the Company granted stock options to
Michael J. Rothberg as follows: in November 1994, an immediately exercisable
stock option to purchase 15,000 shares of Common Stock at a price of $2.23 per
share; and in March 1996, a stock option to purchase 35,800 shares of Common
Stock at a price of $3.00 per share, which vests over a six-year period from
the date of grant. Both options expire ten years from the date of grant.

58
<PAGE>

PRINCIPAL STOCKHOLDERS

The following table sets forth certain information known to the Company
regarding the beneficial ownership of Common Stock as of October 1, 1997 and
as adjusted to reflect the sale of the shares offered hereby, by (i) each
person known to the Company to be the beneficial owner of more than 5% of its
outstanding shares of Common Stock, (ii) each director of the Company, (iii)
each executive officer named in the Summary Compensation Table and (iv) all
directors and executive officers of the Company as a group. Except as
otherwise indicated, the persons or entities listed below have sole voting and
investment power with respect to all shares of Common Stock owned by them.

<TABLE>
<CAPTION>
PERCENTAGE OF SHARES
BENEFICIALLY OWNED(1)(2)
------------------------
NUMBER OF SHARES BEFORE AFTER
BENEFICIAL OWNER BENEFICIALLY OWNED THE OFFERING THE OFFERING
---------------- ------------------ ------------ ------------
<S> <C> <C> <C>
Jonathan M. Rothberg, Ph.D.
(3)....................... 3,592,000 40.5% %
c/o CuraGen Corporation
555 Long Wharf Drive, 11th
Floor
New Haven, CT 06511
Quantum Industrial Partners
LDC (4)................... 2,047,782 22.2% %
Kaya Flamboyan
Willemstad, Curacao
Netherlands Antilles
Pioneer Hi-Bred
International, Inc........ 1,000,000 11.3% %
700 Capital Square
400 Locust Street
Des Moines, IA 50309
Henry M. Rothberg (5)...... 944,496 10.3% %
c/o Law Offices of Marshal
D. Gibson, P.C.
152 Temple Street
New Haven, CT 06510
Lillian R. Rothberg (6).... 944,496 10.3% %
c/o Law Offices of Marshal
D. Gibson, P.C.
152 Temple Street
New Haven, CT 06510
Michael J. Rothberg (7).... 544,388 6.0% %
c/o Law Offices of Marshal
D. Gibson, P.C.
152 Temple Street
New Haven, CT 06510
Gregory T. Went, Ph.D.
(8)....................... 189,500 2.1% %
Vincent T. DeVita, Jr.,
M.D. (9).................. 16,666 * %
Richard H. Booth, C.P.A.,
C.L.U., Ch.F.C. (10)...... 28,731 * %
Robert E. Patricelli (11).. 6,666 * %
James L. Vincent (12)...... 6,666 * %
All directors and executive
officers as a group (10
persons) (13)............. 3,908,730 42.6% %
</TABLE>
- --------
*Less than 1%.

59
<PAGE>

(1) Shares of Common Stock that an individual or group has the right to
acquire within 60 days of October 1, 1997 pursuant to the exercise of
options or warrants are deemed to be outstanding for the purposes of
computing the percentage ownership of such individual or group, but are
not deemed to be outstanding for the purpose of computing the percentage
ownership of any other person shown in the table.
(2) Percentage of ownership is based on 8,871,987 shares of Common Stock
outstanding on October 1, 1997.
(3) Includes 500,000 shares of Common Stock held by a limited partnership of
which Dr. Rothberg is the sole general partner.

(4) Includes 341,297 shares of Common Stock subject to currently exercisable
warrants. Each of Mr. George Soros and Mr. Stanley Druckenmiller, as a
result of various contractual arrangements, may be deemed to be the
beneficial owner of shares of Common Stock held for the account of
Quantum Industrial Partners LDC.
(5) Includes (i) 61,433 shares of Common Stock subject to currently
exercisable warrants, (ii) 350,000 shares of Common Stock and 187,500
shares of Common Stock subject to currently exercisable warrants held
jointly with his wife, Lillian R. Rothberg, and (iii) 142,065 shares of
Common Stock and 61,433 shares of Common Stock subject to currently
exercisable warrants held by his wife, Lillian R. Rothberg. Mr. Rothberg
disclaims beneficial ownership of the shares of Common Stock held by or
which may be acquired by his wife.
(6) Includes (i) 61,433 shares of Common Stock subject to currently
exercisable warrants, (ii) 350,000 shares of Common Stock and 187,500
shares of Common Stock subject to currently exercisable warrants held
jointly with her husband, Henry M. Rothberg, and (iii) 142,065 shares of
Common Stock and 61,433 shares of Common Stock subject to currently
exercisable warrants held by her husband, Henry M. Rothberg. Mrs.
Rothberg disclaims beneficial ownership of the shares of Common Stock
held by or which may be acquired by her husband.

(7) Includes (i) 108,750 shares of Common Stock subject to currently
exercisable warrants, (ii) 22,160 shares of Common Stock subject to
currently exercisable options, (iii) 6,000 shares of Common Stock held by
his wife, Judith Rothberg and (iv) 100,000 shares of Common Stock and
145,478 shares of Common Stock subject to currently exercisable warrants
all held by Hemroc Trust II of which Michael J. Rothberg is a co-trustee
with his sister, Celia Rothberg Meadow. Mr. Rothberg disclaims beneficial
ownership of the shares of Common Stock held by his wife.
(8) Consists of 189,500 shares of Common Stock subject to currently
exercisable options of which 10,500 shares are held by trusts for the
benefit of Dr. Went's wife and children. Dr. Went's wife is a co-trustee
of the trusts, and Dr. Went disclaims beneficial ownership of such 10,500
shares. Does not include an additional 220,500 shares subject to options
which are not currently exercisable.

(9) Consists of 16,666 shares of Common Stock subject to currently
exercisable options.

(10) Includes 5,000 shares of Common Stock subject to currently exercisable
warrants and 6,666 shares of Common Stock subject to currently
exercisable options.

(11) Consists of 6,666 shares of Common Stock subject to currently exercisable
options.

(12) Consists of 6,666 shares of Common Stock subject to currently exercisable
options.

(13) Includes 10,000 shares of Common Stock subject to currently exercisable
options held by Peter A. Fuller, 20,000 shares of Common Stock subject to
currently exercisable options held by Stephen F. Kingsmore, 18,500 shares
of Common Stock subject to currently exercisable options held by
Elizabeth A. Whayland, and 20,000 shares of Common Stock subject to
currently exercisable options held by David M. Wurzer. See also footnotes
3 and 8 through 12 above.

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<PAGE>

DESCRIPTION OF CAPITAL STOCK

The Company's authorized capital stock consists of 50,000,000 shares of
Common Stock, par value of $.01 per share ("Common Stock"), and 3,000,000
shares of preferred stock, par value of $.01 per share ("Preferred Stock").
Upon completion of the Offering, there will be shares of Common Stock and
no shares of Preferred Stock outstanding. As of November 1, 1997, there were
8,871,987 shares of Common Stock outstanding, held of record by 31
stockholders. In addition, as of November 1, 1997, there were outstanding
options to purchase 1,663,884 shares of Common Stock and warrants to purchase
1,583,866 shares of Common Stock.

COMMON STOCK

The holders of Common Stock are entitled one vote for each share held of
record on all matters submitted to a vote of stockholders. Subject to the
rights and preferences of the holders of any outstanding Preferred Stock, the
holders of Common Stock are entitled to receive ratably such dividends as are
declared by the Board of Directors out of funds legally available therefor.
See "Dividend Policy." In the event of a liquidation, dissolution or winding
up of the Company, holders of Common Stock have the right to a ratable portion
of assets remaining after the payment of all debts and other liabilities,
subject to the liquidation preferences of the holders of any outstanding
Preferred Stock. Holders of Common Stock have neither preemptive rights nor
rights to convert their Common Stock into any other securities and are not
subject to future calls or assessments by the Company. There are no redemption
or sinking fund provisions applicable to the Common Stock. All outstanding
shares of Common Stock are, and the shares offered hereby upon issuance and
sale will be, fully paid and non-assessable. The rights, preferences and
privileges of the holders of Common Stock are subject to, and may be adversely
affected by, the rights of the holders of shares of Preferred Stock that the
Company may designate and issue in the future.

Upon the closing of the Offering, certain redemption rights relating to
394,031 shares of Redeemable Common Stock will terminate. See Note 6 of Notes
to Financial Statements for a description of the Redeemable Common Stock.

PREFERRED STOCK

Upon the closing of the Offering, all of the outstanding shares of the
Company's Series A Convertible Preferred Stock (the "Series A Preferred
Stock"), Series C Convertible Preferred Stock (the "Series C Preferred
Stock"), Series D Convertible Preferred Stock (the "Series D Preferred Stock")
and Series E Convertible Preferred Stock (the "Series E Preferred Stock") will
be converted into 3,418,635 shares of Common Stock pursuant to the Automatic
Conversion. In addition, all of the outstanding shares of Series B Preferred
Stock will be redeemed. The Preferred Stock so converted and redeemed will be
retired and may not be reissued. See Notes 5 and 6 of Notes to Financial
Statements for a description of the Preferred Stock. The Board of Directors is
authorized, subject to certain limitations prescribed by Delaware law, without
further action by the stockholders, to issue shares of Preferred Stock in one
or more series and to fix the rights, preferences, privileges and restrictions
thereof, including dividend rights, conversion rights, voting rights, terms of
redemption, liquidation preferences, sinking fund terms and the number of
shares constituting any series or the designation of such series. The Company
believes that the power to issue Preferred Stock will provide flexibility in
connection with possible corporate transactions. The issuance of Preferred
Stock, however, could adversely affect the voting power of holders of Common
Stock and restrict their rights to receive payments upon liquidation. It could
also have the effect of delaying, deferring or preventing a change in control
of the Company. The Company has no present plans to issue any shares of
Preferred Stock.

REGISTRATION RIGHTS

Following this Offering, the holders of 3,610,510 shares of Common Stock,
including 3,318,635 shares of Common Stock issuable upon conversion of the
Series A Preferred Stock, Series C Preferred Stock and Series D

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<PAGE>

Preferred Stock, and holders of warrants to purchase a total of 366,894 shares
of Common Stock will have certain rights to cause the Company to register
those shares under the Securities Act at any time after the first anniversary
of the closing date of this Offering (except that 291,875 shares of Common
Stock can be registered immediately after the closing of this Offering).
Thereafter, the Company may be required to effect up to two registrations
requested by the former holders of the Series A Preferred Stock, two
registrations requested by the persons who formerly held the Series C
Preferred Stock and who hold the warrants to purchase 366,894 shares of Common
Stock, two registrations requested by the former holder of the Series D
Preferred Stock and one registration requested by the holder of 291,875 shares
of Common Stock. In addition, following this Offering, the foregoing holders
and Biogen (as a holder of the Biogen Shares and the former holder of 100,000
shares of Common Stock issuable upon conversion of the Series E Preferred
Stock will have certain rights to cause the Company to register their shares
on Form S-3 under the Securities Act at any time after the first anniversary
of the closing date of this Offering. There is no limit to the number of Form
S-3 registrations that the Company may be required to effect. Biogen will also
have the right to cause the Company to register on Form S-3 any shares issued
to it pursuant to the conversion of the loan facility provided by Biogen to
the Company. Stockholders not part of the initial registration demand are
entitled to notice of such registration and are entitled to include shares of
Common Stock therein. These registration rights are subject to certain
conditions and limitations, including (i) the right, under certain
circumstances, of the underwriters of an offering to limit the number of
shares included in such registration and (ii) the right of the Company to
delay the filing of a registration statement for not more than 180 days after
receiving the registration demand.

In addition, if the Company proposes to register any of its equity
securities under the Securities Act, whether or not for sale for its own
account, other than in connection with a Company employee benefit plan, the
foregoing holders of 3,710,510 shares of Common Stock and warrants to purchase
366,894 shares of Common Stock, along with the holder of warrants to purchase
21,111 shares of Common Stock, are entitled to notice of such registration and
are entitled to include their Common Stock therein. These rights are subject
to certain conditions and limitations, including the right of the underwriters
of an offering to limit the number of shares included in such registration
under certain circumstances and the right of the Company to delay or withdraw
any such registration.

All expenses incurred in connection with such registrations (other than
underwriters' discounts and commissions and stock transfer fees or expenses)
and the fees and expenses of a single counsel to the selling stockholders will
be borne by the Company. The right of any holder to demand or be included in
any registration terminates on the date on which such holder may sell all
shares of Common Stock held by such holder under Rule 144 of the Securities
Act (except that the demand rights with respect to the 291,875 shares of
Common Stock held by one holder will only terminate when such shares are sold
to the public).

DELAWARE LAW AND CERTAIN CHARTER AND BYLAW PROVISIONS

Upon the consummation of the Offering made hereby, the Company will be
subject to the provisions of Section 203 of the DGCL, an anti-takeover law. In
general, Section 203 prohibits a publicly-held Delaware corporation from
engaging in a "business combination" with an "interested stockholder" for a
period of three years after the date of the transaction in which the person
became an interested stockholder, unless the business combination is, or the
transaction in which the person became an interested stockholder was, approved
in a prescribed manner or another prescribed exception applies. For purposes
of Section 203, a "business combination" is defined broadly to include a
merger, asset sale or other transaction resulting in a financial benefit to
the interested stockholder, and subject to certain exceptions, an "interested
stockholder" is a person who, together with affiliates and associates, owns
(or within three years prior, did own) 15% or more of the corporation's voting
stock.

The Board of Directors of the Company is divided into three classes as
nearly equal in number as possible. Each year the stockholders will elect the
members of one of the three classes to a three year term of office. Messrs.
Patricelli and Vincent serve in the class whose term expires in 1998; Drs.
Went and DeVita serve in the class whose term expires in 1999; and Dr.
Rothberg and Mr. Booth serve in the class whose term expires in 2000. All
directors elected to the Company's classified Board of Directors will serve
until the election and qualification of their successors or their earlier
resignation or removal. The Board of Directors is authorized to

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<PAGE>

create new directorships and to fill such positions so created and is
permitted to specify the class to which such new position is assigned, and the
person filling such position would serve for the term applicable to that
class. The Board of Directors (or its remaining members, even though less than
a quorum) is also empowered to fill vacancies on the Board of Directors
occurring for any reason for the remainder of the term of the class of
Directors in which the vacancy occurred. Members of the Board of Directors may
only be removed for cause. These provisions are likely to increase the time
required for stockholders to change the composition of the Board of Directors.
For example, in general, at least two annual meetings will be necessary for
stockholders to effect a change in a majority of the members of the Board of
Directors.

The Company's Amended and Restated Bylaws (the "Restated Bylaws"), provide
that, for nominations to the Board of Directors or for other business to be
properly brought by a stockholder before a meeting of stockholders, the
stockholder must first have given timely notice thereof in writing to the
Secretary of the Company. To be timely, a stockholder's notice generally must
be delivered not less than sixty days nor more than ninety days prior to the
annual meeting. If the meeting is not an annual meeting, the notice must
generally be delivered not more than ninety days prior to the special meeting
and not later than the later of sixty days prior to the special meeting or ten
days following the day on which public announcement of the meeting is first
made by the Company. Only such business shall be conducted at a special
meeting of stockholders as is brought before the meeting pursuant to the
Company's notice of meeting. The notice by a stockholder must contain, among
other things, certain information about the stockholder delivering the notice
and, as applicable, background information about the nominee or a description
of the proposed business to be brought before the meeting.

The Restated Certificate also requires that any action required or permitted
to be taken by stockholders of the Company must be effected at a duly called
annual or special meeting of stockholders and may not be effected by a consent
in writing. Special meetings may be called only by the Board of Directors of
the Company pursuant to a resolution adopted by a majority of the total number
of directors authorized.

The DGCL provides generally that the affirmative vote of a majority of the
shares entitled to vote on any matter is required to amend a corporation's
certificate of incorporation or bylaws, unless the corporation's certificate
of incorporation or bylaws, as the case may be, requires a greater percentage.
The Restated Certificate requires the affirmative vote of the holders of at
least 70% of the outstanding voting stock of the Company to amend or repeal
any of the provisions discussed in this section entitled "Delaware Law and
Certain Charter and Bylaw Provisions" or to reduce the number of authorized
shares of Common Stock and Preferred Stock. Such 70% vote is also required for
any amendment to or repeal of the Restated Bylaws by the stockholders. The
Restated Bylaws may also be amended or repealed by a majority vote of the
Board of Directors. Such 70% stockholder vote would be in addition to any
separate class vote that might in the future be required pursuant to the terms
of any Preferred Stock that might then be outstanding.

The provisions of the Restated Certificate and Restated Bylaws discussed
above could make more difficult or discourage a proxy contest or other change
in the management of the Company or the acquisition or attempted acquisition
of control by a holder of a substantial block of the Company's stock. It is
possible that such provisions could make it more difficult to accomplish, or
could deter, transactions which stockholders may otherwise consider to be in
their best interests.

As permitted by the DGCL, the Restated Certificate provides that Directors
of the Company shall not be personally liable to the Company or its
stockholders for monetary damages for breach of their fiduciary duties as
Directors, except for liability (i) for any breach of their duty of loyalty to
the Company and its stockholders, (ii) for acts or omissions not in good faith
or which involve intentional misconduct or a knowing violation of law, (iii)
for unlawful payments of dividends or unlawful stock repurchases or
redemptions, as provided in Section 174 or successor provisions of the DGCL or
(iv) for any transaction from which the Director derives an improper personal
benefit.

The Restated Certificate and Restated Bylaws provide that the Company shall
indemnify its Directors and officers to the fullest extent permitted by
Delaware law (except in some circumstances, with respect to suits

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initiated by the Director or officer) and advance expenses to such Directors
or officers to defend any action for which rights of indemnification are
provided. In addition, the Restated Certificate and Restated Bylaws also
permit the Company to grant such rights to its employees and agents. The
Restated Bylaws also provide that the Company may enter into indemnification
agreements with its Directors and officers and purchase insurance on behalf of
any person whom it is required or permitted to indemnify. The Company believes
that these provisions will assist the Company in attracting and retaining
qualified individuals to serve as Directors, officers and employees.

TRANSFER AGENT AND REGISTRAR

The transfer agent and registrar for the Common Stock will be American Stock
Transfer & Trust Company. The transfer agent's telephone number is (212) 936-
5100.

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<PAGE>

SHARES ELIGIBLE FOR FUTURE SALE

Prior to the Offering there has been no market for the Common Stock of the
Company. The Company can make no prediction as to the effect, if any, that
sales of shares or the availability of shares for sale will have on the market
price prevailing from time to time. Nevertheless, sales of significant amounts
of the Common Stock in the public market, or the perception that such sales
may occur, could adversely affect prevailing market prices. See "Risk
Factors--Shares Eligible for Future Sale."

Upon completion of the Offering, the Company expects to have shares of
Common Stock outstanding (excluding 1,663,884 and 1,583,866 shares reserved
for issuance upon the exercise of outstanding stock options and warrants,
respectively) ( shares of Common Stock outstanding if the Underwriters'
over-allotment option is exercised in full). Of these shares, the shares
offered hereby will be freely tradable without restrictions or further
registration under the Securities Act, except for any shares purchased by
"affiliates" of the Company, as that term is defined in Rule 144 under the
Securities Act, which will be subject to the resale limitations imposed by
Rule 144, as described below.

All of the remaining 8,871,987 shares of Common Stock outstanding will be
"restricted securities" within the meaning of Rule 144 and may not be resold
in the absence of registration under the Securities Act, or pursuant to
exemptions from such registration including, among others, the exemption
provided by Rule 144 under the Securities Act. Of the restricted securities,
561,731 shares are eligible for sale in the public market immediately after
the Offering pursuant to Rule 144(k) under the Securities Act. A total of
4,867,167 additional restricted securities will be eligible for sale in the
public market in accordance with Rule 144 under the Securities Act beginning
90 days after the date of this Prospectus. Taking into consideration the
effect of the lock-up agreements described below and the provisions of Rules
144 and 144(k), restricted shares will be eligible for sale in the public
market immediately after the Offering, restricted shares (excluding
and shares issuable upon the exercise of outstanding stock options and
warrants, respectively) will be eligible for sale beginning 90 days after the
date of this Prospectus, and the remaining restricted shares will be eligible
for sale upon the expiration of the lock-up agreements 180 days after the date
of this Prospectus, subject to the provisions of Rule 144 under the Securities
Act.

In general, under Rule 144 as currently in effect, beginning 90 days after
the date of this Prospectus, a person (or persons whose shares are required to
be aggregated) whose restricted securities have been outstanding for at least
one year, including a person who may be deemed an "affiliate" of the Company,
may only sell a number of shares within any three-month period which does not
exceed the greater of (i) one percent of the then outstanding shares of the
Company's Common Stock (approximately shares after the Offering) or (ii)
the average weekly trading volume in the Company's Common Stock in the four
calendar weeks immediately preceding such sale. Sales under Rule 144 are also
subject to certain requirements as to the manner of sale, notice and the
availability of current public information about the Company. A person who is
not an affiliate of the issuer, has not been an affiliate within three months
prior to the sale and has owned the restricted securities for at least two
years is entitled to sell such shares under Rule 144(k) without regard to any
of the limitations described above.

Beginning 90 days after the date of this Prospectus, certain shares issued
or issuable upon the exercise of options granted by the Company prior to the
date of this Prospectus will also be eligible for sale in the public market
pursuant to Rule 701 under the Securities Act. In general, Rule 701 permits
resales of shares issued pursuant to certain compensatory benefit plans and
contracts, commencing 90 days after the issuer becomes subject to the
reporting requirements of the Securities Exchange Act of 1934, as amended, in
reliance upon Rule 144, but without compliance with certain restrictions of
Rule 144, including the holding period requirements. As of November 1, 1997,
the Company has granted options covering 1,663,884 shares of Common Stock
which have not been exercised and which become exercisable at various times in
the future. Any shares of Common Stock issued upon the exercise of these
options will be eligible for sale pursuant to Rule 701.

The executive officers and directors and certain other existing stockholders
of the Company, who beneficially own in the aggregate shares of Common
Stock and options to purchase shares of

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Common Stock, have agreed that they will not, without the prior written
consent of Morgan Stanley & Co. Incorporated (i) offer, pledge, sell, contract
to sell, sell any option or contract to purchase, purchase any option or
contract to sell, grant any option, right or warrant to purchase, lend or
otherwise transfer or dispose of, directly or indirectly, any shares of Common
Stock or any securities convertible into or exercisable or exchangeable for
Common Stock or (ii) enter into any swap or other arrangement that transfers
to another, in whole or in part, any of the economic consequences of ownership
of the Common Stock, whether any such transaction described in clause (i) or
(ii) above is to be settled by delivery of Common Stock or such other
securities, in cash or otherwise, for a period of 180 days after the date of
the Prospectus.

Upon completion of this Offering, the holders of the Biogen Shares, of
3,710,000 shares of Common Stock and warrants to purchase 388,005 shares of
Common Stock are entitled to certain rights with respect to the registration
of such shares under the Securities Act. See "Description of Capital Stock--
Registration Rights." Registration of such shares under the Securities Act
would result in such shares becoming freely tradeable without restriction
under the Securities Act (except for shares purchased by affiliates)
immediately upon the effectiveness of such registration. All of the Company's
executive officers and directors and certain other existing stockholders who
beneficially own in the aggregate shares of Common Stock and options to
purchase shares of Common Stock have agreed that, without the prior
written consent of Morgan Stanley & Co. Incorporated, they will not, for a
period of 180 days after the date of the Prospectus, make any demand for or
exercise any right with respect to, the registration of any shares of Common
Stock or any security exercisable for Common Stock.

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<PAGE>

UNDERWRITERS

Under the terms and subject to the conditions in the Underwriting Agreement
dated the date hereof (the "Underwriting Agreement"), the Underwriters named
below (the "Underwriters"), for whom Morgan Stanley & Co. Incorporated, Lehman
Brothers Inc. and Bear, Stearns & Co. Inc. are serving as Representatives (the
"Representatives"), have severally agreed to purchase, and the Company has
agreed to sell to the Underwriters, severally, the respective number of shares
of Common Stock set forth opposite the names of such Underwriters below:

<TABLE>
<CAPTION>
NUMBER
NAME OF SHARES
---- ---------
<S> <C>
Morgan Stanley & Co. Incorporated...............................
Lehman Brothers Inc. ...........................................
Bear, Stearns & Co. Inc.........................................
---
Total.........................................................
===
</TABLE>

The Underwriting Agreement provides that the obligations of the several
Underwriters to pay for and accept delivery of the shares of Common Stock
offered hereby are subject to the approval of certain legal matters by their
counsel and to certain other conditions. The Underwriters are obligated to
take and pay for all the shares of Common Stock offered hereby (other than
those covered by the overallotment option described below) if any such shares
are taken.

The Underwriters initially propose to offer part of the shares of Common
Stock directly to the public at the public offering price set forth on the
cover page hereof and part to certain dealers at a price which represents a
concession not in excess of $ a share under the public offering price. Any
Underwriter may allow, and such dealers may reallow, a concession not in
excess of $ a share to other Underwriters or to certain other dealers.
After the initial offering of the shares of Common Stock, the offering price
and other selling terms may from time to time be varied by the Underwriters.

The Company has granted the Underwriters an option, exercisable for 30 days
from the date of the Prospectus, to purchase up to additional shares of
Common Stock at the public offering price set forth on the cover page hereof,
less underwriting discounts and commissions. The Underwriters may exercise
such option to purchase solely for the purpose of covering overallotments, if
any, made in connection with the offering of the shares of Common Stock
offered hereby. To the extent such option is exercised, each Underwriter will
become obligated, subject to certain conditions, to purchase approximately the
same percentage of such additional shares as the number set forth next to such
Underwriter's name in the preceding table bears to the total number of shares
of Common Stock offered by the Underwriters hereby.

See "Shares Eligible for Future Sale" for a description of certain
arrangements by which all of the Company's executive officers and directors
and certain other existing stockholders, who beneficially own in the aggregate
shares of Common Stock and options to purchase shares of Common Stock,
have agreed not to sell or otherwise dispose of Common Stock or convertible
securities of the Company for up to 180 days after the date of this Prospectus
without the prior written consent of Morgan Stanley & Co. Incorporated. The
Company has agreed in the Underwriting Agreement that it will not, directly or
indirectly, without the prior written consent of Morgan Stanley & Co.
Incorporated, contract to sell, sell any option or contract to purchase,
purchase any option or contract to sell, grant any option, right or warrant to
purchase, lend or otherwise transfer or dispose of any shares of Common Stock
or any securities convertible into or exchangeable for Common Stock, for a
period of 180 days after the date of this Prospectus, except under certain
circumstances.

In March 1997, Frederick Frank, Vice Chairman of Lehman Brothers, purchased
100,000 shares of Series B Preferred Stock for a purchase price of $10.00 per
share, or an aggregate of $1,000,000. Upon the closing of the Offering, all of
Mr. Frank's 100,000 shares of Series B Preferred Stock will be redeemed by the
Company. In addition, Mr. Frank received a warrant to purchase 204,778 shares
of Common Stock at $5.86 per share.

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At the request of the Company, the Underwriters have reserved for sale at
the initial public offering price up to shares offered hereby for
officers, directors, employees and certain other persons associated with the
Company. The number of shares available for sale to the general public will be
reduced to the extent such persons purchase such reserved shares. Any reserved
shares not so purchased will be offered by the Underwriters to the general
public on the same basis as the other shares offered hereby.

The Representatives have informed the Company that the Underwriters do not
intend to confirm sales in excess of five percent of the total number of
shares of Common Stock offered hereby to accounts over which they exercise
discretionary authority.

The Company and the Underwriters have agreed to indemnify each other against
certain liabilities, including liabilities under the Securities Act.

Application has been made to list the Common Stock for quotation on the
Nasdaq National Market under the symbol "CRGN."

In order to facilitate the offering of the Common Stock, the Underwriters
may engage in transactions that stabilize, maintain or otherwise affect the
price of the Common Stock. Specifically, the Underwriters may over-allot in
connection with the offering, creating a short position in the Common Stock
for their own account. In addition, to cover overallotments or to stabilize
the price of the Common Stock, the Underwriters may bid for, and purchase,
shares of Common Stock in the open market. Finally, the underwriting syndicate
may reclaim selling concessions allowed to an underwriter or a dealer for
distributing the Common Stock in the offering, if the syndicate repurchases
previously distributed Common Stock in transactions to cover syndicate short
positions, in stabilization transactions or otherwise. Any of these activities
may stabilize or maintain the market price of the Common Stock above
independent market levels. The Underwriters are not required to engage in
these activities, and may cease any of these activities at any time.

PRICE OF THE OFFERING

Prior to the Offering, there has been no public market for the Common Stock.
The initial public offering price for the Common Stock will be determined by
negotiations between the Company and the Representatives of the Underwriters.
Among the factors considered in determining the initial public offering price
will be the future prospects of the Company and its industry in general; net
revenue, earnings and certain other financial and operating information of the
Company in recent periods; and certain ratios, market prices of securities and
certain financial operating information of companies engaged in activities
similar to those of the Company. The estimated initial public offering price
range set forth on the cover page of this Prospectus is subject to change as a
result of market conditions or other factors.

LEGAL MATTERS

The validity of the Common Stock offered hereby will be passed upon for the
Company by Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., One Financial
Center, Boston, Massachusetts 02111 and for the Underwriters by Ropes & Gray,
One International Place, Boston, Massachusetts 02110. Members of Mintz, Levin,
Cohn, Ferris, Glovsky and Popeo, P.C. own an aggregate of 20,486 shares of
Common Stock and warrants to purchase 15,000 shares of Common Stock.

EXPERTS

The financial statements of CuraGen Corporation included in this Prospectus
have been audited by Deloitte & Touche LLP, independent auditors, as stated in
their report appearing herein. These financial statements have been included
herein in reliance upon the report of said firm given upon their authority as
experts in accounting and auditing.

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The statements in this Prospectus under the captions "Risk Factors--Patents
and Proprietary Rights; Third-Party Rights" and "Business--Intellectual
Property" relating to United States patent matters have been passed upon by
Pennie & Edmonds LLP, 1155 Avenue of the Americas, New York, New York 10036,
patent counsel to the Company. Members of Pennie & Edmonds LLP own an
aggregate of 42,673 shares of Common Stock.

ADDITIONAL INFORMATION

The Company has filed with the Securities and Exchange Commission (the
"Commission") a Registration Statement on Form S-1 under the Securities Act,
with respect to the Common Stock offered hereby. As permitted by the rules and
regulations of the Commission, this Prospectus, which is part of the
Registration Statement, omits certain information, exhibits, schedules and
undertakings set forth in the Registration Statement. For further information
pertaining to the Company and the Common Stock, reference is made to such
Registration Statement and the exhibits and schedules thereto. Statements
contained in this Prospectus as to the contents or provisions of any documents
referred to herein are not necessarily complete, and in each instance where a
copy of the document has been filed as an exhibit to the Registration
Statement, reference is made to the exhibit so filed. The Registration
Statement may be inspected without charge at the office of the Commission at
450 Fifth Street, N.W., Washington, D.C. 20549. Copies of the Registration
Statement may be obtained from the Commission at prescribed rates from the
Public Reference Section of the Commission at such address, and at the
Commission's regional offices located at 7 World Trade Center, 13th Floor, New
York, New York 10048, and at Citicorp Center, 500 West Madison Street, Suite
1400, Chicago, Illinois 60661. In addition, registration statements and
certain other filings made with the Commission through its Electronic Data
Gathering, Analysis and Retrieval ("EDGAR") system are publicly available
through the Commission's site on the Internet's World Wide Web, located at
http://www.sec.gov. The Registration Statement, including all exhibits thereto
and amendments thereof, has been filed with the Commission through EDGAR.

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GLOSSARY

The four chemical building blocks, represented
by the letters A, C, G and T, that compose DNA.
Base

Bioinformatics Computer software to assist in the acquisition
and analysis of information relating to genes,
proteins, biological pathways and drugs.

The physical structures in cells containing
large stretches of DNA (hundreds of millions of
Chromosome bases) and the information for thousands of
genes.

DNA The molecule that encodes genetic information
through the sequence of four constituent bases.

DNA Sequence The precise order of bases for a DNA fragment,
a gene, a chromosome or an entire genome.

Fluorescent Label
A molecule attached to a gene fragment that
emits light when stimulated by a laser. The
emitted light is detected to measure the
quantity of labeled gene fragments.

Gel Electrophoresis A laboratory process using a gel matrix and an
electric field to determine the size (in number
of bases) of a DNA molecule.

Gene The fundamental unit of heredity. A gene is a
specific sequence of bases (usually thousands
to tens of thousands of bases) located in a
specific location on a particular chromosome.
Genes are transcribed to produce multiple
molecules of mRNA which are then translated to
produce multiple copies of a specific protein.

Gene Expression
The process used by a cell to determine which
proteins to produce. The number of copies of a
particular protein produced by a cell is
determined primarily by the number of copies of
the mRNA which encodes it.

Gene Expression Analysis The process of correlating the expression
levels of individual genes (in terms of the
number of copies of mRNA present for a gene)
with cellular behavior as a cause or result of
disease, in response to drug treatment, or over
time.

Gene Fragment
A physical piece of a gene (in a test tube or
electrophoresis gel) containing on the order of
50 to 500 bases.

Gene Mapping Determining the position of a gene (or gene
fragment) on a chromosome.

All the bases in all the genes on all the
Genome chromosomes of a species. The human genome
contains over 3 billion bases.

Genomics
The comprehensive study of all genes and their
function in biological pathways.

70
<PAGE>

Hybridization
Determining the sequence of bases in a gene
fragment by measuring its ability to pair with
trial complementary gene fragments.

mRNA A messenger molecule that serves as the
intermediate between the stretch of DNA that
contains a gene and the final protein that the
gene encodes.

Mutation A change (usually deleterious, but in some
cases protective) in the DNA of a gene.
Mutations can be inherited.

Pathways Networks of protein interactions used to carry
out biological functions including metabolism
and signal transduction.

Pharmacogenomics The study of genes and biological pathways to
predict the efficacy and safety of drug
candidates, review the performance and safety
of marketed drugs and identify appropriate
patient populations.

Protein
A molecule composed of amino acids arranged in
a sequence determined by a gene. The types and
numbers of proteins produced by a cell are
determined by the expression levels of
individual genes. Proteins are required for the
structure, function and regulation of the
body's cells, tissues, and organs. Each protein
has a unique function and can act in biological
pathways.

Quantitative Expression
Analysis CuraGen's technology that measures the
expression levels of the different mRNA
molecules present in a cell.

Sequencing The process of determining the identity and
precise order of all the bases in a piece (or
fragment) of DNA.

Signal Transduction
One of the processes through which cells
communicate. In a typical signal transduction
pathway, a signal in the form of a protein is
secreted from one cell and binds to a cell-
surface receptor on another cell. The signal is
transduced by downstream pathways in the second
cell to affect its gene expression and the
activities of its biological pathways.

Subsequence A small number of bases (4 to 8) of fixed
sequence used to tag longer stretches of DNA
that constitute a gene. ATCGATC is an example
of a subsequence of 7 bases.

Subsequence Pair

A pair of subsequences that are used to tag
genes. The existence of both subsequences
within a gene, together with the distance in
bases between the pair, serves in GeneCalling
like an area code plus a phone number to
identify a gene uniquely.

71
<PAGE>

CURAGEN CORPORATION

INDEX TO FINANCIAL STATEMENTS

<TABLE>
<CAPTION>
PAGE
----
<S> <C>
Independent Auditors' Report.............................................. F-2
Balance Sheets, December 31, 1995 and 1996 and September 30, 1997
(unaudited).............................................................. F-3
Statements of Operations for the Years Ended December 31, 1994, 1995 and
1996
and for the Nine Months Ended September 30, 1996 and 1997 (unaudited).... F-4
Statements of Changes in Stockholders' Equity (Deficiency) for the Years
Ended
December 31, 1994, 1995 and 1996 and for the Nine Months Ended September
30, 1997 (unaudited)..................................................... F-5
Statements of Cash Flows for the Years Ended December 31, 1994, 1995 and
1996
and for the Nine Months Ended September 30, 1996 and 1997 (unaudited).... F-6
Notes to Financial Statements............................................. F-7
</TABLE>

F-1
<PAGE>

INDEPENDENT AUDITORS' REPORT

To the Board of Directors of
CuraGen Corporation
New Haven, Connecticut

The accompanying financial statements retroactively reflect the conversion
of all outstanding shares of Series A, C, D and E Preferred Stock (Convertible
Preferred Stock) to Common Stock on a one for one basis. The below opinion is
in the form which will be signed by Deloitte and Touche LLP upon consummation
of a waiver by the Convertible Preferred stockholders eliminating: i) the
closing of a firm commitment underwritten public offering of the Company's
common stock subject to the offering price being at least $12.00 per share and
ii) net proceeds raised of at least $10,000,000 as conditions to conversion,
as described in Note 6 to the financial statements, and no other events shall
have occurred that would effect the accompanying financial statements and
notes thereto.

"We have audited the accompanying balance sheets of CuraGen Corporation (the
"Company") as of December 31, 1995 and 1996, and the related statements of
operations, changes in stockholders' equity (deficiency) and cash flows for
each of the three years in the period ended December 31, 1996. These financial
statements are the responsibility of the Company's management. Our
responsibility is to express an opinion on these financial statements based on
our audits.

We conducted our audits in accordance with generally accepted auditing
standards. Those standards require that we plan and perform the audit to
obtain reasonable assurance about whether the financial statements are free of
material misstatement. An audit includes examining, on a test basis, evidence
supporting the amounts and disclosures in the financial statements. An audit
also includes assessing the accounting principles used and significant
estimates made by management, as well as evaluating the overall financial
statement presentation. We believe that our audits provide a reasonable basis
for our opinion.

In our opinion, the financial statements referred to above present fairly,
in all material respects, the financial position of the Company at December
31, 1995 and 1996, and the results of its operations and its cash flows for
each of the three years in the period ended December 31, 1996, in conformity
with generally accepted accounting principles.

The Company was in the development stage at December 31, 1995; during the
year ended December 31, 1996, the Company completed its development
activities, with the signing of its first collaborative research agreement,
and commenced its planned principal operations."

DELOITTE & TOUCHE LLP
Hartford, Connecticut
September 12, 1997

F-2
<PAGE>

CURAGEN CORPORATION

BALANCE SHEETS

<TABLE>
<CAPTION>
DECEMBER 31,
------------------------ SEPTEMBER 30,
1995 1996 1997
----------- ----------- -------------
(UNAUDITED)
<S> <C> <C> <C>
ASSETS
Current assets:
Cash and cash equivalents....................... $ 9,129 $ 3,298,642 $ 20,781,115
Grants receivable............................... 205,456 466,089 544,478
Accounts receivable............................. -- 200,000 --
Stock subscriptions receivable.................. 100,000 100,000 --
Other current assets............................ 15,086 13,031 3,800
Prepaid expenses................................ 12,483 22,951 314,408
----------- ----------- ------------
Total current assets.......................... 342,154 4,100,713 21,643,801
----------- ----------- ------------
Property and equipment, net...................... 635,172 1,471,496 4,959,731
----------- ----------- ------------
Other assets:
Notes receivable--related parties............... -- -- 100,000
Deferred real estate commissions, net........... -- -- 62,953
Deferred financing costs, net................... 14,526 11,670 --
Organization costs, net......................... 4,000 2,000 500
Deposits........................................ 10,964 67,512 177,461
----------- ----------- ------------
Total other assets............................ 29,490 81,182 340,914
----------- ----------- ------------
Total assets................................ $ 1,006,816 $ 5,653,391 $ 26,944,446
=========== =========== ============
LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIENCY)
Current liabilities:
Accounts payable................................ $ 40,540 $ 351,997 $ 778,662
Accrued payroll--related party.................. 214,375 308,125 308,125
Accrued expenses................................ 300,293 574,630 297,210
Deferred revenue................................ 265,079 -- 670,000
Current portion of obligations under capital
leases......................................... 129,636 391,923 1,112,617
Deferred rent................................... 17,246 -- --
----------- ----------- ------------
Total current liabilities..................... 967,169 1,626,675 3,166,614
----------- ----------- ------------
Long-term liabilities:
Deferred rent................................... -- -- 173,869
Note payable.................................... 487,242 509,425 --
Interest payable................................ 145,183 221,014 21,000
Obligations under capital leases, net of current
portion........................................ 265,266 752,162 3,203,191
----------- ----------- ------------
Total long-term liabilities................... 897,691 1,482,601 3,398,060
----------- ----------- ------------
Commitments and contingencies
Redeemable common stock.......................... 914,063 1,142,579 5,319,419
----------- ----------- ------------
Stockholders' equity (deficiency):
Preferred stock:
Series A Preferred.............................. -- 1,800,000 --
Series B Preferred.............................. -- 1,390,772 1,442,090
Common stock; $.01 par value, issued and
outstanding shares 4,919,575 at December 31,
1995, 5,019,575 at December 31, 1996, and
8,477,956 at September 30, 1997 (unaudited).... 49,196 50,196 84,779
Additional paid-in capital...................... 645,237 1,023,267 20,509,028
Accumulated deficit............................. (2,466,540) (2,862,699) (6,975,544)
----------- ----------- ------------
Total stockholders' equity (deficiency)....... (1,772,107) 1,401,536 15,060,353
----------- ----------- ------------
Total liabilities and stockholders' equity
(deficiency)............................... $ 1,006,816 $ 5,653,391 $ 26,944,446
=========== =========== ============
</TABLE>

See notes to financial statements.

F-3
<PAGE>

CURAGEN CORPORATION

STATEMENTS OF OPERATIONS

<TABLE>
<CAPTION>
NINE MONTHS ENDED
YEARS ENDED DECEMBER 31, SEPTEMBER 30,
---------------------------------- -----------------------
1994 1995 1996 1996 1997
---------- ---------- ---------- ---------- -----------
(UNAUDITED)
<S> <C> <C> <C> <C> <C>
Revenue:
Grant revenue.......... $ 257,536 $1,581,175 $4,047,947 $2,901,322 $2,558,167
Collaboration revenue.. -- -- 375,000 200,000 1,613,583
---------- ---------- ---------- ---------- -----------
Total revenue.......... 257,536 1,581,175 4,422,947 3,101,322 4,171,750
---------- ---------- ---------- ---------- -----------
Operating expenses:
Research and
development........... 647,640 1,466,375 3,516,035 2,192,740 6,431,139
General and
administrative........ 525,671 961,815 1,140,325 666,803 2,071,435
---------- ---------- ---------- ---------- -----------
Total operating
expenses.............. 1,173,311 2,428,190 4,656,360 2,859,543 8,502,574
---------- ---------- ---------- ---------- -----------
Income (loss) from
operations............. (915,775) (847,015) (233,413) 241,779 (4,330,824)
---------- ---------- ---------- ---------- -----------
Other income (expenses):
Interest income........ 20,544 12,306 20,848 2,587 525,021
Interest expense....... (60,798) (106,035) (183,594) (121,175) (307,042)
---------- ---------- ---------- ---------- -----------
Total other income
(expenses)............ (40,254) (93,729) (162,746) (118,588) 217,979
---------- ---------- ---------- ---------- -----------
Net income (loss)....... (956,029) (940,744) (396,159) 123,191 (4,112,845)
Preferred dividends..... -- -- (17,106) -- (51,318)
---------- ---------- ---------- ---------- -----------
Net income (loss)
attributable to common
stockholders........... $ (956,029) $ (940,744) $ (413,265) $ 123,191 ($4,164,163)
========== ========== ========== ========== ===========
Net income (loss) per
share attributable to
common stockholders.... $ (0.18) $ (0.17) $ (0.07) $ 0.02 $ (0.50)
========== ========== ========== ========== ===========
Weighted average number
of shares of common
stock outstanding...... 5,458,381 5,692,211 5,874,198 5,865,522 8,334,036
========== ========== ========== ========== ===========
Pro forma net loss per
share attributable to
common stockholders.... $ (0.07) $ (0.50)
========== ===========
Pro forma weighted
average number of
shares of common stock
outstanding............ 5,876,723 8,334,036
========== ===========
</TABLE>

See notes to financial statements.

F-4
<PAGE>

CURAGEN CORPORATION

STATEMENTS OF CHANGES IN STOCKHOLDERS' EQUITY (DEFICIENCY)

YEARS ENDED DECEMBER 31, 1994, 1995, AND 1996 AND THE NINE MONTHS ENDED
SEPTEMBER 30, 1997

<TABLE>
<CAPTION>
COMMON
NUMBER STOCK NUMBER ADDITIONAL
OF ($.01 PAR OF PREFERRED PAID-IN ACCUMULATED
SHARES VALUE) SHARES STOCK CAPITAL DEFICIT TOTAL
--------- --------- ---------- ------------ ----------- ----------- -----------
<S> <C> <C> <C> <C> <C> <C> <C>
JANUARY 1, 1994......... 4,590,000 $45,900 -- -- $ 1,052,100 $ (569,767) $ 528,233
Exercise of common stock
warrants............... 210,000 2,100 -- -- 207,900 -- 210,000
Adjustment of redeemable
common stock........... -- -- -- -- (575,973) -- (575,973)
Net loss................ -- -- -- -- -- (956,)029) (956,029)
--------- ------- ---------- ------------ ----------- ----------- -----------
DECEMBER 31, 1994....... 4,800,000 48,000 -- -- 684,027 (1,525,796) (793,769)
Issuance of common
stock.................. 19,575 196 -- -- 45,023 -- 45,219
Exercise of common stock
warrants............... 100,000 1,000 -- -- 99,000 -- 100,000
Adjustment of redeemable
common stock........... -- -- -- -- (182,813) -- (182,813)
Net loss................ -- -- -- -- -- (940,744) (940,744)
--------- ------- ---------- ------------ ----------- ----------- -----------
DECEMBER 31, 1995....... 4,919,575 49,196 -- -- 645,237 (2,466,540) (1,772,107)
Exercise of common stock
warrants............... 100,000 1,000 -- -- 151,000 -- 152,000
Issuance of preferred
stock-- Series A....... -- -- 307,167 $ 1,800,000 -- -- 1,800,000
Issuance of preferred
stock with warrants--
Series B............... -- -- 175,000 1,373,666 376,334 -- 1,750,000
Issuance of options to
non-employees.......... -- -- -- -- 96,318 -- 96,318
Preferred stock
dividends.............. -- -- -- 17,106 (17,106) -- --
Adjustment of redeemable
common stock........... -- -- -- -- (228,516) -- (228,516)
Net loss................ -- -- -- -- -- (396,159) (396,159)
--------- ------- ---------- ------------ ----------- ----------- -----------
DECEMBER 31, 1996....... 5,019,575 50,196 482,167 3,190,772 1,023,267 (2,862,699) 1,401,536
Unaudited:
Issuance of common
stock................. 39,746 397 -- -- 162,561 -- 162,958
Issuance of preferred
stock with warrants--
Series C.............. -- -- 2,011,468 11,787,202 -- -- 11,787,202
Issuance of preferred
stock-- Series D...... -- -- 1,000,000 7,500,000 -- -- 7,500,000
Issuance of preferred
stock-- Series E...... -- -- 100,000 1,000,001 -- -- 1,000,001
Issuance of options ... -- -- -- -- 616,374 -- 616,374
Issuance of warrants--
capital lease
obligations........... -- -- -- -- 59,520 -- 59,520
Preferred stock
dividends............. -- -- -- 51,318 (51,318) -- --
Adjustment of
redeemable common
stock................. -- -- -- -- (3,354,393) -- (3,354,393)
Adjustment to reflect
automatic conversion
of preferred stock.... 3,418,635 34,186 (3,418,635) (22,087,203) 22,053,017 -- --
Net loss............... -- -- -- -- -- (4,112,845) (4,112,845)
--------- ------- ---------- ------------ ----------- ----------- -----------
SEPTEMBER 30, 1997
(UNAUDITED)............ 8,477,956 $84,779 175,000 $ 1,442,090 $20,509,028 $(6,975,544) $15,060,353
========= ======= ========== ============ =========== =========== ===========
</TABLE>

See notes to financial statements.

F-5

<PAGE>

CURAGEN CORPORATION

STATEMENTS OF CASH FLOWS

<TABLE>
<CAPTION>
NINE MONTHS ENDED
YEARS ENDED DECEMBER 31, SEPTEMBER 30,
-------------------------------- -----------------------
1994 1995 1996 1996 1997
--------- --------- ---------- ---------- -----------
(UNAUDITED)
<S> <C> <C> <C> <C> <C>
CASH FLOWS FROM
OPERATING ACTIVITIES:
Net income (loss)..... $(956,029) $(940,744) $ (396,159) $ 123,191 $(4,112,845)
Adjustments to
reconcile net income
(loss) to net cash
(used in) provided by
operating activities:
Depreciation and
amortization......... 127,632 223,626 366,283 274,712 822,692
Non-monetary
compensation......... -- -- 96,318 94,288 616,374
Changes in assets and
liabilities:
Grants receivable.... -- (205,456) (260,633) (387,302) (78,389)
Accounts receivable.. -- -- (200,000) (200,000) 200,000
Other current
assets.............. -- (15,086) 2,055 14,086 9,231
Prepaid expenses..... 100 (8,448) (10,468) 1,224 (70,324)
Payment of deferred
real estate
commissions......... -- -- -- -- (68,949)
Deposits............. 99 (6,082) (56,548) (43,895) (109,949)
Accounts payable..... (9,679) 24,727 311,457 94,933 426,665
Accrued payroll--
related party....... 75,000 105,000 93,750 93,750 --
Accrued expenses..... 2,156 300,293 274,337 154,829 (114,462)
Deferred revenue..... -- 265,079 (265,079) (265,079) 670,000
Deferred rent........ 35,497 (37,204) (17,246) 17,246 173,869
Interest payable..... 51,917 72,266 75,831 51,848 22,433
--------- --------- ---------- ---------- -----------
Net cash (used in)
provided by
operating
activities......... (673,307) (222,029) 13,898 23,831 (1,613,654)
--------- --------- ---------- ---------- -----------
CASH FLOWS FROM
INVESTING ACTIVITIES:
Acquisitions of
property and
equipment............ (77,148) (170,471) (248,033) (79,643) (1,415,390)
Loans to related
parties.............. -- -- -- -- (100,000)
--------- --------- ---------- ---------- -----------
Net cash used in
investing
activities......... (77,148) (170,471) (248,033) (79,643) (1,515,390)
--------- --------- ---------- ---------- -----------
CASH FLOWS FROM
FINANCING ACTIVITIES:
Payment of deferred
financing costs...... (20,000) -- -- -- --
Payments on capital
lease obligations.... (21,113) (85,261) (178,352) (113,175) (535,760)
Proceeds from issuance
of notes/loan
payable.............. 600,000 -- 175,000 175,000 --
Payment of loan
payable.............. -- -- (175,000) -- --
Proceeds from issuance
of common stock...... 100,000 210,000 252,000 152,000 --
Proceeds from issuance
of preferred stock... -- -- 3,450,000 1,500,000 20,387,203
Proceeds from sale-
leaseback of fixed
assets............... -- -- -- -- 981,207
Payments of stock
issuance costs....... -- -- -- -- (221,133)
--------- --------- ---------- ---------- -----------
Net cash provided by
financing
activities......... 658,887 124,739 3,523,648 1,713,825 20,611,517
--------- --------- ---------- ---------- -----------
Net (decrease) increase
in cash and cash
equivalents........... (91,568) (267,761) 3,289,513 1,658,013 17,482,473
Cash and cash
equivalents, beginning
of year............... 368,458 276,890 9,129 9,129 3,298,642
--------- --------- ---------- ---------- -----------
Cash and cash
equivalents, end of
period................ $ 276,890 $ 9,129 $3,298,642 $1,667,142 $20,781,115
========= ========= ========== ========== ===========
SUPPLEMENTAL CASH FLOW
INFORMATION:
Interest paid......... $ 8,881 $ 33,770 $ 107,763 $ 69,326 $ 284,609
NONCASH FINANCING
TRANSACTIONS:
Reduction of note and
related interest
payable upon exercise
of common stock
warrants............. $ -- $ -- $ -- $ -- $ 822,447
Reduction of accrued
expenses upon
issuance of common
stock................ -- 45,219 -- -- 162,958
Obligations under
capital leases....... 64,180 385,314 979,096 459,116 3,767,003
Common stock
subscription
receivable........... 210,000 100,000 -- -- --
Preferred stock
subscription
receivable........... -- -- 100,000 250,000 --
Adjustment of
redeemable common
stock................ 575,973 182,813 228,516 58,685 4,176,840
</TABLE>

See notes to financial statements.

F-6

<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS

1. ORGANIZATION AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES

Organization--CuraGen Corporation ("CuraGen" or the "Company") is a
biotechnology company focusing on the application of genomics to systematic
discovery of genes, biological pathways and drug candidates in order to
accelerate the discovery and development of the next generation of
therapeutic, diagnostic and agricultural products. The Company was
incorporated in November 1991 and, until March 1993 (inception), was engaged
principally in organizational activities, grant and patent preparation and
obtaining financing. In March 1993, the Company began construction of
approximately 8,000 square feet of custom laboratory and office space in a
leased facility in Branford, Connecticut, and opened its laboratories in July
1993. In March 1997, the Company expanded its custom laboratory and office
space into a 26,000 square foot leased facility in New Haven, Connecticut (see
Note 3).

Interim Financial Statements--The unaudited financial statements as of
September 30, 1997 and for the nine months ended September 30, 1996 and 1997
and related note information have been prepared on a basis consistent with the
audited financial statements, and in the opinion of management, include all
adjustments (consisting of only normal recurring adjustments) necessary for a
fair presentation of the results of the interim periods. The results for the
nine months ended September 30, 1997 are not necessarily indicative of the
results to be expected for the entire year.

Revenue Recognition--The Company has entered into collaborative research
agreements which provide for the partial or complete funding of specified
projects in exchange for access to and certain rights in the resultant data
discovered under the related project. Revenue is recognized based upon work
performed or upon the attainment of certain benchmarks specified in the
related agreements (see Note 5). Grant revenue is recognized as related costs
qualifying under the terms of the grants are incurred. Grant revenue is
derived solely from federal and Connecticut agencies (see Note 8). Deferred
revenue arising from payments received from grants and collaborative
agreements is recognized as income when earned.

Cash and Cash Equivalents--The Company considers investments readily
convertible to cash and amounts with a maturity of three months or less at the
date of purchase to be cash equivalents.

Property and Equipment--Property and equipment are recorded at cost.
Equipment under capital leases is recorded at the lower of the net present
value of the minimum lease payments required over the term of the lease or the
fair value of the assets at the inception of the lease. Additions, renewals
and betterments that significantly extend the life of an asset are
capitalized. Minor replacements, maintenance and repairs are charged to
operations as incurred. Equipment is depreciated over the estimated useful
lives of the related assets, ranging from three to seven years, using the
straight-line method. Equipment under capital leases is amortized over the
shorter of the estimated useful life or the terms of the lease, using the
straight-line method. Leasehold improvements are amortized over the term of
the lease, using the straight-line method. When assets are retired or
otherwise disposed of, the assets and related accumulated depreciation or
amortization are eliminated from the accounts and any resulting gain or loss
is reflected in income. For income tax purposes, depreciation is computed
using various accelerated methods and, in some cases, different useful lives
than those used for financial reporting purposes.

Deferred Real Estate Commissions--Deferred real estate commissions were paid
in January 1997 in connection with the signing of the operating lease in New
Haven, Connecticut (see Note 3). These costs are

F-7
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

amortized over the remaining life of the lease as of the date of occupancy,
sixty-nine months, using the straight-line method. Accumulated amortization
aggregated $5,996 as of September 30, 1997 (unaudited).

Deferred Financing Costs--Deferred financing costs are amortized over the
life of the loan, eighty-four months, using the straight-line method.
Accumulated amortization aggregated $5,474, $8,330 and $0 as of December 31,
1995 and 1996 and September 30, 1997 (unaudited), respectively. Related
amortization expense was $2,618 for 1994 and $2,856 for 1995 and 1996.

In April 1997, the Company's note payable was converted into common stock
(see Notes 4 and 6) and as a result the related deferred financing costs were
written off. Amortization expense for the nine months ended September 30, 1996
and 1997 (unaudited) was $2,142 and $11,670, respectively.

Organization Costs--Organization costs are amortized over sixty months,
using the straight-line method. Accumulated amortization was $6,000, $8,000
and $9,500 as of December 31, 1995 and 1996 and September 30, 1997
(unaudited), respectively. Related amortization expense was $2,000 for 1994,
1995 and 1996 and $1,500 for the nine months ended September 30, 1996 and 1997
(unaudited).

Patent Application Costs--Costs incurred in filing for patents are charged
to operations, until such time as it is determined that the filing will be
successful. When it becomes evident with reasonable certainty that an
application will be successful, the costs incurred in filing for patents will
begin to be capitalized. Capitalized costs related to successful patent
applications will be amortized over a period not to exceed twenty years or the
remaining life of the patent, whichever is shorter, using the straight-line
method. As of December 31, 1994, 1995 and 1996 and September 30, 1997
(unaudited), since all patent applications remain in process and no patents
have been issued, all patent application costs have been charged to
operations.

Research and Development Costs--Research and development costs are charged
to operations as incurred.

Stock-Based Compensation--In October 1995, the Financial Accounting
Standards Board issued Statement of Financial Accounting Standards No. 123
"Accounting for Stock-Based Compensation" ("SFAS 123"), which was effective
for the Company beginning January 1, 1996. SFAS 123 requires expanded
disclosures of stock-based compensation arrangements with employees and non-
employees and encourages (but does not require) compensation cost to be
measured based on the fair value of the equity instruments awarded to
employees. Companies are permitted to continue to apply Accounting Principles
Board ("APB") No. 25, which recognizes compensation cost based on the
intrinsic value of the equity instruments awarded. The Company will continue
to apply APB No. 25 to its stock-based compensation awards to employees. For
equity instruments awarded to non-employees, the Company records the
transactions based upon the consideration received for such awards or the fair
value of the equity instruments issued, whichever is more reliably measurable.
The Company recorded stock-based compensation expense attributable to non-
employees totaling $96,318, $94,288 and $277,247 for the year ended December
31, 1996 and the nine months ended September 30, 1996 and 1997 (unaudited),
respectively. In addition, the Company recorded stock-based compensation
expense for options issued to employees of $339,127 for the nine months ended
September 30, 1997 (unaudited).

Income Taxes--Income taxes are provided for as required under Statement of
Financial Accounting Standards No. 109, "Accounting for Income Taxes" ("SFAS
109"). This Statement requires the use of the asset and liability method in
determining the tax effect on future years of the "temporary differences"
between the tax basis of assets and liabilities and their financial reporting
amounts.

Fair Value of Financial Instruments--Statement of Financial Accounting
Standards No. 107, "Disclosures about Fair Value of Financial Instruments"
("SFAS 107"), requires the disclosure of fair value information for certain
assets and liabilities, whether or not recorded in the balance sheets, for
which it is practicable to estimate

F-8
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

that value. The Company has the following financial instruments: cash,
receivables, accounts payable and accrued expenses, and certain long-term
liabilities including a note payable. Additionally, the Company has redeemable
common stock (see Note 6). The Company considers the carrying amount of these
items, excluding the note payable and the redeemable common stock, to
approximate fair value. In addition, it was not practicable to estimate the
fair value of the note payable due to a lack of availability of similar
instruments for comparative purposes.

Net Loss Per Share Attributable to Common Stockholders--Net loss per share
attributable to common stockholders is based on the weighted average number of
shares outstanding for each of the periods presented using the treasury stock
method. Pursuant to the rules of the Securities and Exchange Commission, all
options and warrants granted at prices less than the initial public offering
price during the twelve months preceding the offering date have been included
as common stock equivalents in the calculation of weighted average shares
outstanding for all periods presented.

Statement of Financial Accounting Standards No. 128, "Earnings Per Share"
("SFAS 128"), was issued in February 1997, and is effective for periods ending
after December 15, 1997. Earlier application is not permitted. SFAS 128
simplifies the standards for computing earnings per share ("EPS") and makes
them comparable to international standards for computing EPS. When effective,
this statement will replace the presentation of primary EPS with the
presentation of basic EPS and will require a dual presentation of basic EPS
and diluted EPS on the face of the Statements of Operations. For the Company,
basic and diluted EPS under SFAS 128 would have equaled the reported EPS for
the years ended December 31, 1994, 1995 and 1996 and for the nine month
periods ended September 30, 1996 and 1997 (unaudited).

Pro Forma Net Loss Per Share Attributable to Common Stockholders--At
December 31, 1996 and September 30, 1997 (unaudited), pro forma net loss per
share attributable to common stockholders and the pro forma weighted average
number of shares of common stock outstanding have been presented in the
statement of operations assuming the Series A, Series C, Series D and Series E
Preferred Stock (see Note 6) was converted to common stock upon issuance.

Conversion of Preferred Stock--The accompanying financial statements
retroactively reflect the conversion of all outstanding shares of Series A, C,
D and E Preferred Stock (Convertible Preferred Stock) to Common Stock on a one
for one basis. The above conversion has been presented as it is the Company's
intention to obtain a waiver by the Convertible Preferred stockholders
eliminating: i) the closing of a firm commitment underwritten public offering
of the Company's common stock subject to the offering price being at least
$12.00 per share and ii) net proceeds raised of at least $10,000,000 as
conditions to conversion, as described in Note 6 to the financial statements.

Recently Enacted Pronouncements--Statements of Financial Accounting
Standards No. 130, "Reporting Comprehensive Income" ("SFAS 130"), and No. 131,
"Disclosures About Segments of an Enterprise and Related Information" ("SFAS
131"), were issued in June 1997.

SFAS 130 establishes standards for reporting and display of comprehensive
income and its components in a full set of general purpose financial
statements. It requires that all items that are required to be recognized
under accounting standards as components of comprehensive income be reported
in a financial statement that is displayed with the same prominence as the
other financial statements. Comprehensive income is defined as "the change in
equity of a business enterprise during a period from transactions and other
events and circumstances from non-owner sources." It includes all changes in
equity during a period, except those resulting from investments by owners and
distributions to owners. This statement is effective for fiscal years
beginning after December 15, 1997.

SFAS 131 establishes the way that public business enterprises report
information about operating segments in annual financial statements and
requires that those enterprises report selected information about operating
segments in interim financial reports issued to stockholders. It also
establishes standards for related disclosures about products and services,
geographic areas and major customers. This statement is effective for
financial statements for periods beginning after December 15, 1997.

F-9
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

As the Company does not have changes in equity other than from investments
by owners and distributions to owners and operates in a single segment the
implementation of both of these standards is not expected to have a material
effect on the Company.

Use of Estimates--The preparation of financial statements in conformity with
generally accepted accounting principles requires management to make estimates
and assumptions that affect the reported amounts of assets and liabilities and
disclosure of contingent assets and liabilities at the date of the financial
statements and the reported amounts of revenues and expenses during the
reporting period. Actual results could differ from those estimates.

2. PROPERTY AND EQUIPMENT

Property and equipment consisted of the following:

<TABLE>
<CAPTION>
DECEMBER 31,
------------------- SEPTEMBER 30,
1995 1996 1997
-------- ---------- -------------
(UNAUDITED)
<S> <C> <C> <C>
Laboratory equipment..................... $169,589 $ 351,251 $ 505,649
Leased equipment......................... 505,246 1,432,780 5,199,783
Leasehold improvements................... 169,706 205,998 305,788
Office equipment......................... 141,423 171,501 351,497
-------- ---------- ----------
Total property and equipment........... 985,964 2,161,530 6,362,717
Less accumulated depreciation and
amortization............................ 350,792 690,034 1,402,986
-------- ---------- ----------
Total property and equipment, net...... $635,172 $1,471,496 $4,959,731
======== ========== ==========
</TABLE>

3. LEASES

Capital Leases

In April 1997, the Company signed a lease-financing commitment to receive
$4,000,000 to purchase equipment and expand its facilities. The lease
commitment, which expires on March 15, 1998, provides for a payment term of 48
months per individual lease schedule. In addition, the commitment provides for
the issuance to the lessor of two warrants (the "First Warrant" and the
"Second Warrant") to purchase shares of the Company's common stock. The First
Warrant was issued in April 1997 and entitles the lessor to purchase 11,111
shares of common stock at an exercise price of $9.00 per share. The Second
Warrant was issued when the Company's aggregate equipment cost under the
agreement exceeded $2,000,000. The aggregate exercise price for the shares
represented by the Second Warrant is $100,000, and the per share exercise
price is $10.00 per share. The value ascribed to the warrants was $59,521
(unaudited).

The Company has also entered into other capital lease agreements to finance
the purchase of equipment. Leased equipment under all such agreements
consisted of the following:

<TABLE>
<CAPTION>
DECEMBER 31,
------------------- SEPTEMBER 30,
1995 1996 1997
-------- ---------- -------------
(UNAUDITED)
<S> <C> <C> <C>
Leased equipment........................... $505,246 $1,432,780 $5,199,783
Less accumulated amortization.............. 116,827 338,879 945,355
-------- ---------- ----------
Leased equipment, net...................... $388,419 $1,093,901 $4,254,428
======== ========== ==========
</TABLE>

F-10
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

The Company financed assets with costs of $64,180, $385,314, and $979,096
for the years ended December 31, 1994, 1995, and 1996, respectively, and
$459,116 and $3,767,003 for the nine months ended September 30, 1996 and 1997
(unaudited). These arrangements have terms of three to five years with
interest rates ranging primarily from 8% to 22%. At the end of the respective
lease terms, the Company has the right to either return the equipment to the
lessor or purchase the equipment at between $1 and 10% of the fair market
value of the equipment.

The future minimum lease payments under capital lease obligations were as
follows:

<TABLE>
<CAPTION>
DECEMBER 31, SEPTEMBER 30,
1996 1997
------------ -------------
(UNAUDITED)
<S> <C> <C>
Within 1 year................................... $ 547,296 $1,613,398
Within 1 to 2 years............................. 502,137 1,451,646
Within 2 to 3 years............................. 245,971 1,155,424
Within 3 to 4 years............................. 96,933 1,292,562
Within 4 to 5 years............................. 53,946 83,369
---------- ----------
Total minimum lease payments.................... 1,446,283 5,596,399
Less amounts representing interest.............. 302,198 1,221,070
---------- ----------
Present value of future minimum lease payments.. 1,144,085 4,375,329
Less current portion of obligations............. 391,923 1,112,617
---------- ----------
Obligations under capital leases, net of current
portion........................................ $ 752,162 $3,262,712
========== ==========
</TABLE>

Operating Leases

On December 27, 1996, the Company entered into a six-year lease agreement
for 26,000 square feet to house its principal administrative and research
facilities at 555 Long Wharf Drive, New Haven, Connecticut. The lease allows
for two five-year extensions and an option to lease an additional 26,000
square feet.

The future minimum rental payments for the operating lease are as follows as
of December 31, 1996:

<TABLE>
<CAPTION>
YEAR
----
<S> <C>
1997.............................................................. $ 131,330
1998.............................................................. 469,505
1999.............................................................. 538,453
2000.............................................................. 538,453
2001.............................................................. 538,453
2002.............................................................. 538,453
----------
Total........................................................... $2,754,647
==========
</TABLE>

The Company also leases its research facilities in Branford, Connecticut,
under a lease agreement expiring in May 1998. During 1996, the Company
exercised an option to extend the term of the operating lease for one
additional two-year term expiring in May 1998. In addition, the Company has an
option to extend the term of the operating lease for one subsequent one-year
term. The future minimum rental payments for this operating lease as of
December 31, 1996 are $100,914 and $42,048 due in fiscal years 1997 and 1998,
respectively. Total rent expense under all operating leases for 1994, 1995 and
1996 was approximately $35,500, $44,000 and

F-11
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

$77,200, respectively. In addition, rent expense for the nine months ended
September 30, 1996 and 1997 (unaudited) totaled $51,974 and $328,048,
respectively. There were no significant operating leases entered into during
the nine months ended September 30, 1997 (unaudited).

4. NOTE PAYABLE

In February 1994, the Company borrowed $600,000 (the "CII Note") from
Connecticut Innovations, Incorporated ("CII"), a Connecticut state agency. The
CII Note bears interest at the rate of 10% per annum, and is secured by
certain technology and intellectual property of the Company. The principal
balance is payable on January 10, 2001. In connection with the CII Note, the
Company issued 102,156 shares of common stock to CII (the "CII Stock") and a
stock subscription warrant (the "CII Warrant") to purchase 291,875 shares of
common stock at an aggregate price equal to CII's Note's original principal
balance ($600,000) plus unpaid interest. Both the CII Stock and the CII
Warrants were valued at $155,277 and were recorded as original issue discount.
Such discount was being amortized over eighty-four months, the term of the
loan. The discount was fully amortized upon repayment of the note as discussed
below. In April 1997, the CII Warrant was exercised and CII received 291,875
shares of common stock of the Company for consideration of $822,447, which
represented full payment of the CII Note totaling $600,000 and unpaid interest
of $222,447.

5. COLLABORATIONS

Genentech, Inc.

In June 1996, the Company entered into a Pilot Research Services and
Evaluation Agreement with Genentech, Inc. pursuant to which the Company
performed certain research services for a $200,000 fee. The pilot
collaboration was superseded by the Evaluation Agreement, signed December 27,
1996, pursuant to which the Company is performing additional research services
during 1997 for a minimum research fee. In connection with the execution of
this agreement Genentech made an equity investment of $1,800,000 in the form
of 307,167 shares of Series A Convertible Preferred Stock (see Note 6). The
Company has recorded revenue of $500,250, which represents 12% of total
revenue, under the Evaluation Agreement for the nine months ended September
30, 1997 (unaudited). In addition, the entire accounts receivable balance at
December 31, 1996 was due from Genentech.

Pioneer Hi-Bred International, Inc.

Effective June 1, 1997, the Company entered into a Collaborative Research
and License Agreement with Pioneer Hi-Bred whereby the Company is to perform
research which will be funded by Pioneer Hi-Bred. In conjunction with the
execution of this agreement Pioneer Hi-Bred made an equity investment of
$7,500,000 in the form of 1,000,000 shares of Series D Convertible Preferred
Stock (see Note 6). In addition, Pioneer Hi-Bred will pay the Company a
minimum research fee per year over the term of the agreement which expires in
five years. This fee is based upon an established number of CuraGen employees
whom will be devoted to the Pioneer Hi-Bred research. Under certain
circumstances, as defined in the agreement, Pioneer Hi-Bred can elect to
terminate the agreement upon payment of certain termination fees to the
Company, as early as November 1998. For the nine months ended September 30,
1997 (unaudited), the Company has recorded revenue of $833,333, which
represents 20% of total revenue, related to this agreement. In addition,
$625,000 (unaudited) has been received from Pioneer Hi-Bred for which the
related services have not been performed and, therefore, such amount is
recorded as deferred revenue at September 30, 1997.

6. STOCKHOLDERS' EQUITY (DEFICIENCY)

Authorized Capital Stock and Stock Split

In December 1993, the Board of Directors of the Company (i) increased the
authorized shares of common stock of the Company to 20,000,000 shares, (ii)
authorized a class of 3,000,000 shares of serial preferred stock,

F-12
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

and (iii) approved a 34,820 for 1 common stock split. In June 1997, the Board
of Directors of the Company, upon stockholder approval, increased the
authorized shares of common stock of the Company to 25,000,000 and increased
the authorized number of shares of serial preferred stock to 7,500,000.

At December 31, 1996, the Company had reserved 1,329,375 shares of common
stock for issuance pursuant to the 1993 Warrants, the Incentive Warrant and
the CII Warrant and 1,500,000 shares of common stock for issuance pursuant to
the Stock Option and Incentive Award Plan discussed below. At September 30,
1997 (unaudited), the Company has reserved 1,583,666 shares of common stock
pursuant to outstanding warrants and 1,500,000 shares of common stock for
issuance pursuant to the Stock Option and Incentive Award Plan.

Common Stock and Warrants to Purchase Common Stock

During 1993, eight persons advanced an aggregate of $1,008,000 (the "1993
Debt") to the Company to fund certain start-up expenses incurred by, and to
provide certain working capital for, the Company. On December 30, 1993, the
Company converted the 1993 Debt into 1,008,000 shares of common stock, and
issued warrants (the "1993 Warrants") to such persons to purchase an aggregate
of 1,122,500 shares of common stock, at an exercise price of $1.00 per share.
The 1993 Warrants expire on various dates through December 1, 2000. In
December 1994, four 1993 Warrants to purchase an aggregate of 210,000 shares
of common stock were exercised for consideration of $210,000. In December
1995, two 1993 Warrants to purchase an aggregate of 100,000 shares of common
stock were exercised for $100,000. The proceeds were received in January 1996.

In December 1993, the Company entered into an agreement, concluded in March
1994, with a scientific advisor to issue for consideration of $100,000 (i)
100,000 shares of common stock, and (ii) a warrant (the "Investor Warrant") to
purchase 125,000 shares of common stock, at an exercise price of $1.52 per
share. In March 1996, the Investor Warrant to purchase 100,000 shares of
common stock was exercised for consideration of $152,000. The remainder of the
Investor Warrant expired in March 1996.

During February 1994, in connection with the CII Note (see Note 4), the
Company issued 102,156 shares of common stock to CII (the "CII Stock") and a
stock subscription warrant (the "CII Warrant") to purchase 291,875 shares of
common stock at an aggregate price equal to the CII Note's original principal
balance ($600,000) plus any unpaid interest. Both the CII Stock and CII
Warrants were valued at $155,277. In April 1997, the CII Warrant was exercised
and CII received 291,875 shares of common stock of the Company for
consideration of $822,447, which represented full payment of the CII note
totaling $600,000 and unpaid interest of $222,447. The Company has the right
to purchase (the "Call Right") the CII Stock and the CII Warrant from CII (i)
after June 30, 1996, for the greater of (a) the fair market value of the CII
Stock and the CII Warrant or (b) $600,000 plus a compounded annual rate of
return of 30%, if certain levels of capital are raised, or (ii) after February
10, 1999, for the greater of (a) the fair market value of the CII Stock and
the CII Warrant, or (b) $600,000, plus a compounded annual rate of return from
the date of the note of 25%. Further, CII has the right to sell (the "Put
Right") the CII Stock and the CII Warrant to the Company (i) at any time until
February 10, 2004, in the event that the Company failed to maintain a
Connecticut presence, for the greater of (a) the fair market or book value of
the CII Stock and the CII Warrant, or (b) $600,000, plus a compounded annual
rate of return from the date of the note of 40%, or (ii) at any time in the
event that the Company violates certain covenants or a default occurs under
the CII documents, or at any time after February 10, 1999, for the greater of
(a) the fair market value of the CII Stock and the CII Warrant or (b)
$600,000, plus a compounded annual rate of return from the date of the note of
25%. Given the redemption features in place, the Company has classified the
stock as redeemable common stock in the balance sheet. The carrying value of
the redeemable common stock has been adjusted through charges to additional
paid-in capital to amounts approximating the redemption value pursuant to the
Put Right.

In March 1997, the Company also issued shares of 17,073 and 22,673 for a
total value of $70,000 and $92,958, respectively, for the settlement of
outstanding accrued expense balances with two separate entities.

F-13
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

Stock Options

In December 1993, the Company adopted a Stock Option and Incentive Award
Plan (the "Option Plan"), which enables the Company to grant non-qualified and
incentive stock options to purchase up to 1,500,000 shares of common stock to
officers, directors, advisors, employees, and affiliates of the Company. At
December 31, 1996, under the Option Plan, the Company had 541,550 options
outstanding and an additional 958,450 available for grant. At September 30,
1997 (unaudited), the Company had 1,028,884 options outstanding under the
Option Plan and an additional 471,116 available for grant. In addition to the
stock options granted under the Option Plan, the Company has granted 456,000
and 570,000 non-qualified stock options at December 31, 1996 and September 30,
1997 (unaudited), respectively, which are not part of a specific plan. No
stock options have been exercised.

A summary of all stock option activity during the years ended December 31,
1994, 1995 and 1996 and the nine months ended September 30, 1997 (unaudited)
is as follows:

<TABLE>
<CAPTION>
WEIGHTED
NUMBER AVERAGE
OF SHARES EXERCISE PRICE
--------- --------------
<S> <C> <C>
Outstanding January 1, 1994........................ 223,000 $1.00
Granted.......................................... 107,500 1.68
Canceled or lapsed............................... (9,000) 1.52
---------
Outstanding December 31, 1994...................... 321,500 1.21
Granted.......................................... 452,000 2.00
Canceled or lapsed............................... (32,500) 1.00
---------
Outstanding December 31, 1995...................... 741,000 1.70
Granted.......................................... 269,550 3.16
Canceled or lapsed............................... (13,000) 3.00
---------
Outstanding December 31, 1996...................... 997,550 2.08
Granted (unaudited).............................. 632,583 6.33
Canceled or lapsed (unaudited)................... (31,249) 3.29
---------
Outstanding September 30, 1997 (unaudited)......... 1,598,884 3.75
=========
Exercisable December 31, 1994...................... 193,083 1.19
=========
Exercisable December 31, 1995...................... 282,450 1.30
=========
Exercisable December 31, 1996...................... 408,832 1.58
=========
Exercisable September 30, 1997 (unaudited)......... 698,711 2.36
=========
</TABLE>

F-14
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

The following table summarizes information about stock options at December
31, 1996:

<TABLE>
<CAPTION>
WEIGHTED
NUMBER OF AVERAGE WEIGHTED
RANGE OF OPTIONS CONTRACTUAL AVERAGE
EXERCISE PRICES OUTSTANDING LIFE EXERCISE PRICE
--------------- ----------- -------------- --------------
<S> <C> <C> <C>
$1.00--$2.50 736,000 8 years $1.70
3.00--4.10 261,550 9.5 years 3.16
-------
997,550 8.5 years 2.08
=======
<CAPTION>
WEIGHTED
AVERAGE
NUMBER OF EXERCISE PRICE
RANGE OF OPTIONS OF OPTIONS
EXERCISE PRICES EXERCISABLE EXERCISABLE
--------------- ----------- --------------
<S> <C> <C> <C>
$1.00--$2.50 406,166 $1.58
3.00--4.10 2,666 3.00
-------
408,832 1.58
=======
</TABLE>

Had compensation cost for the Company's stock option plans been determined
in accordance with the minimum value method for non-public companies as
prescribed under SFAS 123, the Company's net loss attributable to common
stockholders and net loss per share attributable to common stockholders would
have approximated the pro forma amounts shown below for each of the years
ended December 31, 1995 and 1996 and nine months ended September 30, 1997
(unaudited):

<TABLE>
<CAPTION>
DECEMBER 31, SEPTEMBER 30,
------------------------------------- ---------------------
1995 1996 1997
------------------ ------------------ ---------------------
AS AS AS
REPORTED PRO FORMA REPORTED PRO FORMA REPORTED PRO FORMA
-------- --------- -------- --------- ---------- ----------
(UNAUDITED)
<S> <C> <C> <C> <C> <C> <C>
Net loss attributable to
common stockholders.... $940,744 $974,239 $413,265 $492,540 $4,164,163 $4,481,458
Net loss per share
attributable to common
stockholders........... $ 0.17 $ 0.17 $ 0.07 $ 0.08 $ 0.50 $ 0.54
</TABLE>

The assumptions utilized by the Company in deriving the pro forma amounts
are as follows: 1) 0% dividend yield, 2) .1% expected volatility, 3) risk-free
interest rate of approximately 6%, and 4) expected life of the options of 10
years. The weighted average grant date fair value of options granted during
the years ended December 31, 1995 and 1996 and the nine months ended September
30, 1997 (unaudited) was approximately $0.58 per share, $0.81 per share, and
$6.00 per share, respectively.

Preferred Stock

The Company received aggregate consideration of $1,750,000 from five persons
as subscriptions for the purchase of 175,000 shares of Series B Redeemable
Preferred Stock. In September 1996, October 1996 and January 1997, the Company
received proceeds of $1,600,000, $50,000 and $100,000, respectively. The
Series B Preferred Stock is non-convertible and accrues dividends at the prime
rate. Dividends are payable when declared by the board of directors. Dividends
in arrears at December 31, 1996 and September 30, 1997 (unaudited) were
$36,094 and $145,469, respectively. At any time the Company may redeem the
Series B Preferred Stock for an aggregate purchase price of $1,750,000 plus
accrued dividends and dividends in arrears.

F-15
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

If the Company enters into certain qualified equity financings subsequent to
the Series B issuance, as defined in the agreement, the Company will be
required, if requested by all of the holders of the Series B Preferred Stock,
to redeem such shares at an aggregate redemption price of $1,750,000 plus
accrued dividends and dividends in arrears. Such terms have not been met at
September 30, 1997 (unaudited). In addition, holders of the Series B Preferred
Stock received 5 year warrants to purchase an aggregate of 358,361 shares of
Common Stock at $5.86 per share, which warrants expire on March 27, 2002. Such
warrants were valued at $376,334. The value of such warrants is being accreted
over the warrant period and such accretion is classified as preferred
dividends. For the year ended December 31, 1996 and nine months ended
September 30, 1997 (unaudited) such accretion amounted to $17,106 and $51,318,
respectively. At September 30, 1997 (unaudited) the Series B Preferred Stock
has a liquidation preference of $1,895,469.

In December 1996, in connection with the Genentech Evaluation Agreement (see
Note 5), Genentech, Inc. purchased 307,167 shares of Series A Preferred Stock
for $1,800,000, or $5.86 per share. At any time the holders of such stock may
convert their shares to common stock on a 1 for 1 basis. The Series A
Preferred Stock is automatically convertible to common stock on a 1 for 1
basis upon the closing of a firm commitment underwritten public offering of
the Company's common stock subject to the offering price being at least $12.00
per share and net proceeds raised of at least $10,000,000. The Series A
Preferred Stock has a liquidation preference of $1,800,000.

In March 1997, the Company issued 2,011,468 shares of convertible Series C
Preferred Stock for an aggregate purchase price of $11,787,202. At any time
the holders of such stock may convert their shares to common stock on a 1 for
1 basis. The Series C Preferred Stock is automatically convertible to common
stock on a 1 for 1 basis upon the closing of a firm commitment underwritten
public offering of the Company's common stock subject to the offering price
being at least $12.00 per share and net proceeds raised of at least
$10,000,000. In addition, three year warrants were issued to certain
purchasers of the Series C Preferred Stock to purchase an aggregate of 366,894
shares of Common Stock at an exercise price of $9.00 per share. Such warrants
were valued at $0 upon issuance. The Series C Preferred Stock has a
liquidation preference of $11,787,202.

In May 1997, as a result of the Pioneer Hi-Bred Agreement (see Note 5), the
Company issued 1,000,000 shares of Series D Convertible Preferred Stock, for
an aggregate purchase price of $7,500,000 (unaudited). At any time the holders
of such stock may convert their shares to common stock on a 1 for 1 basis. The
Series D Preferred Stock is automatically convertible to common stock on a 1
for 1 basis upon the closing of a firm commitment underwritten public offering
of the Company's common stock subject to the offering price being at least
$12.00 per share and net proceeds raised of at least $10,000,000. The Series D
Preferred Stock has a liquidation preference of $7,500,000 (unaudited).

In June 1997, the Company issued 100,000 shares of Series E Convertible
Preferred Stock for an aggregate purchase price of $1,000,001 (unaudited). At
any time the holders of such stock may convert their shares to common stock on
a 1 for 1 basis. The Series E Preferred Stock is automatically convertible to
common stock on a 1 for 1 basis upon the closing of a firm commitment
underwritten public offering of the Company's common stock subject to the
offering price being at least $12.00 per share and net proceeds raised of at
least $10,000,000. The Series E Preferred Stock has a liquidation preference
of $1,000,001 (unaudited).

F-16
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

7. INCOME TAXES

The net deferred tax assets consisted of:

<TABLE>
<CAPTION>
DECEMBER 31,
------------------------ SEPTEMBER 30,
1995 1996 1997
----------- ----------- -------------
(UNAUDITED)
<S> <C> <C> <C>
Total deferred tax assets............ $ 1,229,000 $ 1,689,000 $ 3,820,000
Valuation allowance.................. (1,229,000) (1,689,000) (3,820,000)
----------- ----------- -----------
Total.............................. $ -- $ -- $ --
=========== =========== ===========
</TABLE>

The deferred tax assets are primarily a result of the federal and
Connecticut net operating loss carryforwards and timing differences relating
to accrued payroll and depreciation and amortization. As the Company has no
prior earnings history, a valuation allowance has been established due to the
Company's uncertainty in its ability to benefit from the federal and
Connecticut net operating loss carryforwards. The change in the valuation
allowance was $375,000, $623,000, $460,000, and $2,131,000 for the years ended
December 31, 1994, 1995 and 1996 and the nine months ended September 30, 1997
(unaudited), respectively.

At December 31, 1996 and September 30, 1997 (unaudited), the Company has
federal and Connecticut net operating loss carryforwards for income tax
purposes of approximately $2,299,000 and $ 5,786,000, respectively. Federal
and Connecticut net operating loss carryforwards expire beginning in 2008 and
1998, respectively. The Company also has federal and Connecticut research and
development tax credit carryforwards of approximately $191,000 and $387,000,
respectively at December 31, 1996 and $456,000 and $837,000, respectively at
September 30, 1997 (unaudited).

8. GRANTS

The Company has received federal grants for specific purposes that are
subject to review and audit by the grantor agencies. Such audits could lead to
requests for reimbursement by the grantor agency for any expenditures
disallowed under the terms of the grant. Additionally, any noncompliance with
the terms of the grant could lead to loss of current or future awards.

During 1995, the Company received two grants from CII in the amounts of
$450,000 and $237,500. Under certain circumstances, such as if the Company
were to cease to have a Connecticut presence, the Company could be required to
repay up to 200% of these amounts.

In March 1997, the Company was awarded by the Advanced Technology Program
("ATP") of the U.S. Department of Commerce's National Institute of Standards
and Technology a grant in the amount of $2,000,000, payable over a period of
two years, through March 1999. This is the Company's third such grant from the
ATP.

9. RELATED PARTIES

The Chief Executive Officer of the Company has elected to defer payment of a
portion of his salary to future periods on an interest free basis. This amount
has been recorded as accrued payroll--related party as of December 31, 1995
and 1996, and September 30, 1997 (unaudited).

In March 1997, the Company loaned one of its officers $50,000 (unaudited).
The term of the note receivable--related party is 4 years and the note bears
interest at 8% per annum. The note will automatically be forgiven upon
consummation of an initial public offering if certain net proceed amounts are
received by the Company, as defined in the agreement.

F-17
<PAGE>

CURAGEN CORPORATION

NOTES TO FINANCIAL STATEMENTS--(CONTINUED)

In September 1997, the Company agreed to loan one of its officers $50,000
(unaudited) with a term of 17 months bearing interest at 8% per annum. If this
officer remains an employee through the maturity date, the loan will be
extended contingent upon continued employment. This note will be forgiven if
such officer remains an employee through September 2001.

10. SUBSEQUENT EVENTS

In October 1997, the Company entered into an agreement with CII whereby,
among other things, the Call Right and Put Right with respect to the CII
Stock, as defined in Note 6, will be terminated when the Company's Form S-1
Registration Statement becomes effective.

In October 1997, CuraGen and Biogen entered into a research collaboration
and database subscription arrangement to discover novel genes and
therapeutics. Under the terms of the agreement, Biogen agreed to invest $5
million (unaudited) in CuraGen to purchase common stock of the Company at the
initial public offering price and to provide a $10 million (unaudited) loan
facility. At any time during the term of the agreement, the loan is
convertible at CuraGen's option into Common Stock at the prevailing market
price. Biogen will additionally provide payments over five years to support a
research collaboration to generate project-specific GeneCalling and
PathCalling databases from Biogen-specified disease systems and to gain non-
exclusive access to CuraGen's GeneCalling and PathCalling subscription
databases. Payments could reach $18.5 million if the research collaboration
and database subscription arrangement both continue for the full five-year
term. Biogen has an option to acquire exclusive licenses to certain
discoveries arising from the collaboration.

* * * * * *

F-18
<PAGE>

[ADD COMPANY'S LOGO FOR OUTSIDE BACK COVER PAGE]

<PAGE>

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

ITEM 13. OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION

The following table sets forth all expenses, other than underwriting
discounts and commissions, payable by the Company in connection with the sale
of the Common Stock being registered. All amounts are estimated except the
registration fee.

<TABLE>
<S> <C>
Commission Registration Fee........................................ $
NASD filing fee....................................................
Nasdaq National Market listing fee.................................
Printing and engraving expenses....................................
Legal fees and expenses............................................
Accounting fees and expenses.......................................
Blue sky fees and expenses (including legal fees)..................
Transfer agent and registrar fees and expenses.....................
Miscellaneous......................................................
-----
TOTAL............................................................ $
=====
</TABLE>

ITEM 14. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

The amendment and restatement of the Company's Certificate of Incorporation
(the "Restated Certificate") provides that the Company shall indemnify to the
fullest extent authorized by the Delaware General Corporation Law ("DGCL"),
each person who is involved in any litigation or other proceeding because such
person is or was a director or officer of the Company or is or was serving as
an officer or director of another entity at the request of the Company,
against all expense, loss or liability reasonably incurred or suffered in
connection therewith. The Restated Certificate provides that the right to
indemnification includes the right to be paid expenses incurred in defending
any proceeding in advance of its final disposition; provided, however, that
such advance payment will only be made upon delivery to the Company of an
undertaking, by or on behalf of the director or officer, to repay all amounts
so advanced if it is ultimately determined that such director is not entitled
to indemnification. If the Company does not pay a proper claim for
indemnification in full within 60 days after a written claim for such
indemnification is received by the Company, the Restated Certificate and
Restated Bylaws authorize the claimant to bring an action against the Company
and prescribe what constitutes a defense to such action.

Section 145 of the DGCL permits a corporation to indemnify any director or
officer of the corporation against expenses (including attorney's fees),
judgments, fines and amounts paid in settlement actually and reasonably
incurred in connection with any action, suit or proceeding brought by reason
of the fact that such person is or was a director or officer of the
corporation, if such person acted in good faith and in a manner that he or she
reasonably believed to be in, or not opposed to, the best interests of the
corporation, and, with respect to any criminal action or proceeding, if he or
she had no reason to believe his or her conduct was unlawful. In a derivative
action, (i.e., one brought by or on behalf of the corporation),
indemnification may be made only for expenses, actually and reasonably
incurred by any director or officer in connection with the defense or
settlement of such an action or suit, if such person acted in good faith and
in a manner that he reasonably believed to be in, or not opposed to, the best
interests of the corporation, except that no indemnification shall be made if
such person shall have been adjudged to be liable to the corporation, unless
and only to the extent that the court in which the action or suit was brought
shall determine that the defendant is fairly and reasonably entitled to
indemnity for such expenses despite such adjudication of liability.

Pursuant to Section 102(b)(7) of the DGCL, Article Tenth of the Restated
Certificate eliminates the liability of a director or the corporation or its
stockholders for monetary damages for such breach of fiduciary duty as a
director, except for liabilities arising (i) from any breach of the director's
duty of loyalty to the corporation or its stockholders, (ii) from acts or
omissions not in good faith or which involve intentional misconduct or a
knowing

II-1
<PAGE>

violation of law, (iii) under Section 174 of the DGCL, or (iv) from any
transaction from which the director derived an improper personal benefit.

The Company has obtained primary and excess insurance policies insuring the
directors and officers of the Company against certain liabilities that they
may incur in their capacity as directors and officers. Under such policies,
the insurers, on behalf of the Company, may also pay amounts for which the
Company has granted indemnification to the directors or officers.

Additionally, reference is made to the Underwriting Agreement filed as
Exhibit 1.1 hereto, which provides for indemnification by the Underwriters of
the Company, its directors and officers who sign the Registration Statement
and persons who control the Company, under certain circumstances.

ITEM 15. RECENT SALES OF UNREGISTERED SECURITIES.

In the three years preceding the filing of this Registration Statement, the
Company has sold the following securities that were not registered under the
Securities Act.

(a) Issuances of Capital Stock.

On February 14, 1995, the Company sold an aggregate of 210,000 shares of its
Common Stock to five investors at $1.00 per share in exchange for payments of
an aggregate of $210,000 by such investors upon the exercise of warrants to
purchase Common Stock.

On May 9, 1995, the Company issued an aggregate of 19,575 shares of its
Common Stock to two investors in exchange for financial advisory services
rendered by such investors to the Company having a value of $45,218.75.

On December 29, 1995, the Company sold an aggregate of 100,000 shares of its
Common Stock to two investors at $1.00 per share in exchange for payments of
an aggregate of $100,000 by such investors upon the exercise of warrants to
purchase Common Stock.

On March 30, 1996, the Company sold 100,000 shares of its Common Stock to
one investor at $1.52 per share in exchange for payment of $152,000 by such
investor upon the exercise of a warrant to purchase Common Stock.

On December 27, 1996, the Company sold 307,167 shares of its Series A
Convertible Preferred Stock at a purchase price of $5.86 per share to
Genentech, Inc. in a private placement for $1,800,000.

In March 1997, the Company issued 17,073 and 22,673 shares of its Common
Stock to Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. and Pennie &
Edmonds LLP, respectively, at $4.10 per share in exchange for legal services
rendered on behalf of the Company and having an aggregate value of
$162,958.60.

On March 27, 1997, the Company sold an aggregate of 175,000 shares of its
Series B Redeemable Preferred Stock at a purchase price of $10.00 per share to
five investors in a private placement for $1,750,000 in cash. In connection
with this private placement, the Company issued five-year warrants to purchase
358,361 shares of Common Stock at an exercise price of $5.86 per share.

On March 27, 1997, the Company sold an aggregate of 2,011,468 shares of its
Series C Convertible Preferred Stock at a purchase price of $5.86 per share to
eleven investors in a private placement for $11,787,202.48. In connection with
this private placement, the Company also issued three-year warrants to
purchase 366,894 shares of Common Stock at an exercise price of $9.00 per
share to two investors who each purchased 1,706,485 and 127,986 shares of
Series C Convertible Preferred Stock, respectively.

On April 10, 1997, the Company sold 291,875 shares of its Common Stock to
Connecticut Innovations Incorporated in exchange for the cancellation of a
$600,000 principal amount promissory note (plus accrued interest thereon) upon
the exercise of a warrant to purchase Common Stock.

II-2
<PAGE>

On May 16, 1997, the Company sold 1,000,000 shares of its Series D
Convertible Preferred Stock at a purchase price of $7.50 per share to Pioneer
Hi-Bred International, Inc. in a private placement for $7,500,000.

On June 25, 1997, the Company sold 100,000 shares of its Series E
Convertible Preferred Stock at a purchase price of $10.00 per share to Biogen,
Inc. in a private placement for $1,000,000.

In October 1997, the Company agreed to sell $5,000,000 of its Common Stock
to Biogen, Inc. in a private placement concurrent with this Offering at a
price per share equal to the price per share at which the Common Stock is sold
in this Offering.

(b) Certain Grants and Exercises of Stock Options.

Pursuant to the 1993 Stock Option and Incentive Award Plan (the "1993 Stock
Plan"), the Company has granted options to purchase an aggregate of 1,028,884
shares of Common Stock, of which options to purchase an aggregate of 343,961
shares of Common Stock are exercisable at a weighted average exercise price of
$3.43 per share. As of November 1, 1997, no options pursuant to the foregoing
have been exercised.

Pursuant to the 1997 Employee, Director and Consultant Stock Plan (the "1997
Stock Plan"), the Company has granted options to purchase an aggregate of
65,000 shares of Common Stock at a price per share equal to the initial public
offering price, of which options to purchase an aggregate of 21,331 shares of
Common Stock are exercisable. As of November 1, 1997, no options pursuant to
the foregoing have been exercised.

In addition to the options granted under the 1993 Stock Plan and the 1997
Stock Plan, the Company has issued options to purchase an aggregate of 570,000
shares of Common Stock pursuant to individual agreements with Company
employees and consultants, of which options to purchase an aggregate of
345,750 shares of Common Stock are exercisable at a weighted average exercise
price of $1.31 per share. As of November 1, 1997, no options pursuant to the
foregoing have been exercised.

No underwriters were involved in the foregoing offers and sales of
securities. Such offers and sales were made in reliance upon an exemption from
the registration provisions of the Securities Act set forth in Section 4(2)
thereof relative to sales by an issuer not involving any public offering or
the rules and regulations thereunder, or, in the case of options to purchase
Common Stock, Rule 701 under the Securities Act. All of the foregoing
securities are deemed restricted securities for purposes of the Securities
Act.

ITEM 16. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES.

(a) Exhibits

<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION
------- -----------
<C> <S>
*1.1 Form of Underwriting Agreement
@3.1 Amended and Restated Certificate of Incorporation of the Registrant
*3.2 Form of Amended and Restated Certificate of Incorporation of the
Registrant
@3.3 Amended and Restated Bylaws of the Registrant
*3.4 Form of Amended and Restated Bylaws of the Registrant
4.1 Article Fourth of the Amended and Restated Certificate of
Incorporation of the Registrant (see Exhibit 3.1)
*4.2 Form of Common Stock Certificate
*5.1 Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. with
respect to the legality of the securities being registered
@10.1 Lease Agreement (New Haven), dated December 23, 1996, between the
Registrant and Fusco Harbour Associates, LLC
</TABLE>

II-3
<PAGE>

<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION
------- -----------
<C> <S>
@10.2 Standard Form of Office Lease, as amended (Branford), dated February
11, 1993 and April 26, 1996, between the Registrant and Branford
Office Venture
@10.3 Sid Martin Biotechnology Development Institute Incubator License
Agreement, dated July 15, 1997, between the Registrant and the
University of Florida Research Foundation, Inc.
*10.4 1997 Employee, Director and Consultant Stock Plan
@10.5 1993 Stock Option and Incentive Award Plan
@10.6 Amendment to 1993 Stock Option and Incentive Plan, dated May 12, 1997
@10.7 Employment Letter, dated February 20, 1997, between the Registrant and
Gregory T. Went, Ph.D.
@10.8 Employment Letter, dated July 18, 1997, between the Registrant and
David M. Wurzer
@10.9 Employment Letter, dated August 21, 1997, between the Registrant and
Peter A. Fuller, Ph.D.
@10.10 Employment Letter, dated August 22, 1997, between the Registrant and
Stephen F. Kingsmore, M.B., Ch.B.
@+10.11 Option and Exclusive License Agreement, dated October 4, 1996, between
the Registrant and Wisconsin Alumni Research Foundation
@+10.12 Standard Non-Exclusive License Agreement--Brumley, dated July 1, 1996,
between the Registrant and Wisconsin Alumni Research Foundation
@+10.13 Collaborative Research and License Agreement, dated May 16, 1997,
between the Registrant and Pioneer Hi-Bred International, Inc.
+10.14 Research and Option Agreement, dated October 1, 1997, between the
Registrant and Biogen, Inc.
+10.15 Notice of Grant Award and Grant Application to Department of Health
and Human Services for Automated Sequencing System for Human Genome
Project, dated March 25, 1995
10.16 ATP Agreement for Integrated Microfabricated DNA Analysis Device for
Diagnosis of Complex Genetic Disorders, dated February , 1995
10.17 ATP Agreement for Molecular Recognition Technology for Precise Design
of Protein-Specific Drugs, dated March 2, 1995
10.18 ATP Agreement for Programmable Nanoscale Engines for Molecular
Separation, dated May 6, 1997
11.1 Schedule of Computation of Net Loss Per Share
@21.1 Subsidiaries of the Registrant
23.1 Consent of Deloitte & Touche LLP
23.2 Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
(included in Exhibit 5.1)
23.3 Consent of Pennie & Edmonds LLP
@24.1 Power of Attorney of Messrs. Went, Wurzer and DeVita
#24.2 Power of Attorney of Messrs. Booth, Patricelli and Vincent
27.1 Financial Data Schedule
</TABLE>
- --------

@ Previously filed.
* To be filed by amendment.
+ Confidential treatment requested as to certain portions, which portions are
omitted and filed separately with the Commission.
# As filed in Part II of this Registration Statement

(b) Financial Statement Schedules

All schedules are omitted because they are not required, are not applicable
or the information is included in the financial statements or notes thereto.

II-4
<PAGE>

ITEM 17. UNDERTAKINGS.

The undersigned registrant hereby undertakes to provide to the Underwriters
at the closing specified in the Underwriting Agreement, certificates in such
denominations and registered in such names as required by the Underwriters to
permit prompt delivery to each purchaser.

Insofar as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers and controlling persons of the
Registrant pursuant to the foregoing provisions, or otherwise, the Registrant
has been advised that in the opinion of the Securities and Exchange Commission
such indemnification is against public policy as expressed in the Securities
Act and is, therefore, unenforceable. In the event that a claim for
indemnification against such liabilities (other than the payment by the
Registrant of expenses incurred or paid by a director, officer or controlling
person of the Registrant in the successful defense of any action, suit or
proceeding), is asserted by such director, officer or controlling person in
connection with the securities being registered, the Registrant will, unless in
the opinion of its counsel the matter has been settled by controlling
precedent, submit to a court of appropriate jurisdiction the question whether
such indemnification by it is against public policy as expressed in the
Securities Act and will be governed by the final adjudication of such issue.

The undersigned registrant hereby undertakes that:

(1) For purposes of determining any liability under the Securities Act,
the information omitted from the form of prospectus filed as part of this
registration statement in reliance upon Rule 430A and contained in a form
of prospectus filed by the registrant pursuant to Rule 424(b)(1) or (4) or
497(h) under the Securities Act shall be deemed to be part of this
registration statement as of the time it was declared effective.

(2) For the purposes of determining any liability under the Securities
Act, each post-effective amendment that contains a form of prospectus shall
be deemed to be a new registration statement relating to the securities
offered therein, and the offering of such securities at that time shall be
deemed to be the initial bona fide offering thereof.

The undersigned registrant hereby undertakes to provide to the Underwriters
at the Closing specified in the Underwriting Agreement, certificates in such
denominations and registered in such names as required by the Underwriters to
permit prompt delivery to each purchaser.

II-5
<PAGE>

SIGNATURES

PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, AS AMENDED, THE
REGISTRANT HAS DULY CAUSED THIS AMENDMENT NO. 1 TO THE REGISTRATION STATEMENT
TO BE SIGNED ON ITS BEHALF BY THE UNDERSIGNED, THEREUNTO DULY AUTHORIZED, IN
THE CITY OF BOSTON, MASSACHUSETTS ON THIS 6TH DAY OF NOVEMBER, 1997.

CuraGen Corporation (Registrant)

/s/ Jonathan M. Rothberg
By: _________________________________
JONATHAN M. ROTHBERGCHIEF
EXECUTIVE OFFICER, PRESIDENT
ANDCHAIRMAN OF THE BOARD

PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, AS AMENDED, THIS
AMENDMENT NO. 1 TO THE REGISTRATION STATEMENT HAS BEEN SIGNED BELOW BY THE
FOLLOWING PERSONS IN THE CAPACITIES AND ON THE DATES INDICATED.

SIGNATURE TITLE DATE

/s/ Jonathan M. Rothberg Chief Executive
- ------------------------------------- Officer, President November 6,
JONATHAN M. ROTHBERG and Chairman of the 1997
Board (principal
executive officer)

Executive Vice
* President and a November 6,
- ------------------------------------- Director 1997
GREGORY T. WENT

Executive Vice
* President, November 6,
- ------------------------------------- Treasurer and Chief 1997
DAVID M. WURZER Financial Officer
(principal
financial and
accounting officer)

Director
* November 6,
- ------------------------------------- 1997
VINCENT T. DEVITA, M.D.

/s/ Richard H. Booth** Director November 6,
- ------------------------------------- 1997
RICHARD H. BOOTH

/s/ Robert E. Patricelli** Director November 6,
- ------------------------------------- 1997
ROBERT E. PATRICELLI

/s/ James L. Vincent** Director November 6,
- ------------------------------------- 1997
JAMES L. VINCENT

II-6
<PAGE>

*By executing his name hereto, Jonathan M. Rothberg is signing this document
on behalf of the persons indicated above pursuant to powers of attorney duly
executed by such persons and filed with the Securities and Exchange
Commission.

By: /s/ Jonathan M. Rothberg
----------------------------------
JONATHAN M. ROTHBERG
(ATTORNEY-IN-FACT)

**Each of Messrs. Booth, Patricelli and Vincent constitutes and appoints
Jonathan M. Rothberg and Gregory T. Went, and each of them (with full power to
each of them to act alone), his true and lawful attorneys-in-fact and agents,
with full power of substitution and resubstitution in each of them for him and
in his name, place and stead, and in any and all capacities, to sign any and
all amendments (including post-effective amendments) to this Registration
Statement (or any other Registration Statement for the same offering that is
to be effective upon filing pursuant to Rule 462(b) under the Securities Act
of 1933, as amended), and to file the same, with all exhibits thereto and
other documents in connection therewith, with the Securities and Exchange
Commission, granting unto said attorneys-in-fact and agents, and each of them,
full power and authority to do and perform each and every act and thing
requisite or necessary to be done in and about premises, as full to all
intents and purposes as he might or could do in person, hereby ratifying and
confirming all that said attorneys-in-fact and agents or any of them or their
or his substitute or substitutes may lawfully do or cause to be done by virtue
hereof.

II-7
<PAGE>

EXHIBIT INDEX

<TABLE>
<CAPTION>
EXHIBIT NO. DESCRIPTION
----------- -----------
<C> <S>
*1.1 Form of Underwriting Agreement
@3.1 Amended and Restated Certificate of Incorporation of the
Registrant
*3.2 Form of Amended and Restated Certificate of Incorporation of the
Registrant
@3.3 Amended and Restated Bylaws of the Registrant
*3.4 Form of Amended and Restated Bylaws of the Registrant
4.1 Article Fourth of the Amended and Restated Certificate of
Incorporation of the Registrant (see Exhibit 3.1)
*4.2 Form of Common Stock Certificate
*5.1 Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
with respect to the legality of the securities being registered
@10.1 Lease Agreement (New Haven), dated December 23, 1996, between the
Registrant and Fusco Harbour Associates, LLC
@10.2 Standard Form of Office Lease, as amended (Branford), dated
February 11, 1993 and April 26, 1996, between the Registrant and
Branford Office Venture
@10.3 Sid Martin Biotechnology Development Institute Incubator License
Agreement, dated July 15, 1997, between the Registrant and the
University of Florida Research Foundation, Inc.
*10.4 1997 Employee, Director and Consultant Stock Plan
@10.5 1993 Stock Option and Incentive Award Plan
@10.6 Amendment to 1993 Stock Option and Incentive Plan, dated May 12,
1997
@10.7 Employment Letter, dated February 20, 1997, between the Registrant
and Gregory T. Went, Ph.D.
@10.8 Employment Letter, dated July 18, 1997, between the Registrant and
David M. Wurzer
@10.9 Employment Letter, dated August 21, 1997, between the Registrant
and Peter A. Fuller, Ph.D.
@10.10 Employment Letter, dated August 22, 1997, between the Registrant
and Stephen F. Kingsmore, M.B., Ch.B.
@+10.11 Option and Exclusive License Agreement, dated October 4, 1996,
between the Registrant and Wisconsin Alumni Research Foundation
@+10.12 Standard Non-Exclusive License Agreement--Brumley, dated July 1,
1996, between the Registrant and Wisconsin Alumni Research
Foundation
@+10.13 Collaborative Research and License Agreement, dated May 16, 1997,
between the Registrant and Pioneer Hi-Bred International, Inc.
+10.14 Research and Option Agreement, dated October 1, 1997, between the
Registrant and Biogen, Inc.
+10.15 Notice of Grant Award and Grant Application to Department of
Health and Human Services for Automated Sequencing System for
Human Genome Project, dated March 25, 1995
10.16 ATP Agreement for Integrated Microfabricated DNA Analysis Device
for Diagnosis of Complex Genetic Disorders, dated February , 1995
10.17 ATP Agreement for Molecular Recognition Technology for Precise
Design of Protein-Specific Drugs, dated March 2, 1995
10.18 ATP Agreement for Programmable Nanoscale Engines for Molecular
Separation, dated May 6, 1997
11.1 Schedule of Computation of Net Loss Per Share
@21.1 Subsidiaries of the Registrant
23.1 Consent of Deloitte & Touche LLP
23.2 Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
(included in Exhibit 5.1)
23.3 Consent of Pennie & Edmonds LLP
@24.1 Power of Attorney of Messrs. Went, Wurzer and DeVita
#24.2 Power of Attorney of Messrs. Booth, Patricelli and Vincent
27.1 Financial Data Schedule
</TABLE>
- --------

<PAGE>

Exhibit 10.14

CuraGen Corporation has omitted from this Exhibit 10.14 portions of the
Agreement for which CuraGen Corporation has requested confidential treatment
from the Securities and Exchange commission. The portions of the Agreement for
which confidential treatment has been requested are marked with X's in brackets
and such confidential portions have been filed separately with the Securities
and Exchange Commission.

RESEARCH AND OPTION AGREEMENT

This Research and Option Agreement ("Agreement") is made effective as of
October 1, 1997 (the "Effective Date") by and between BIOGEN, INC., a
Massachusetts corporation having its principal business office at 14 Cambridge
Center, Cambridge, MA 02142 ("BIOGEN"), and CURAGEN CORPORATION, a Delaware
corporation with its principal place of business at 555 Long Wharf Drive, 11th
Floor, New Haven, Connecticut 06511 ("CURAGEN"). BIOGEN and CURAGEN are each
hereafter referred to individually as a "Party" and together as the "Parties".

WHEREAS, BIOGEN desires to have access to CURAGEN's functional genomics
technologies (including GeneScape(R), QEA/GeneCalling, MIM/PathCalling and all
additional services provided by CURAGEN) and to have CURAGEN apply such
technologies to certain BIOGEN Proprietary Material in order to expedite the
discovery of information which may lead to the development of novel
pharmaceutical products;

WHEREAS, BIOGEN and CURAGEN wish to initiate the performance of certain
research by CURAGEN;

WHEREAS, BIOGEN wishes to obtain an option to evaluate and license the
inventions obtained or made by CURAGEN in the performance of the research
pursuant to this Agreement, as well as an option to evaluate and license certain
other inventions of CURAGEN;

WHEREAS, BIOGEN will agree to make an equity investment in CURAGEN Common
Stock itself, or through one of its Affiliates, in the amount of Five Million
Dollars ($5,000,000), such investment to be made contemporaneously with the
initial public offering of CURAGEN Common Stock;
<PAGE>

WHEREAS, BIOGEN will itself, or through one of its Affiliates, also agree
to loan CURAGEN up to Ten Million Dollars ($10,000,000) on the terms and
conditions as set forth herein; and

WHEREAS, BIOGEN and CURAGEN therefore agree to undertake the foregoing, all
under the terms and conditions set forth in this Agreement.

NOW, THEREFORE, in consideration of the mutual covenants contained
herein, and for other good and valuable consideration, the receipt and adequacy
of which are hereby acknowledged, the Parties hereby agree as follows:

1. DEFINITIONS

Whenever used in the Agreement with an initial capital letter, the terms
defined in this Section 1 shall have the meanings specified.

1.1 "Affiliate" shall mean any corporation, firm, limited liability
company, partnership or other entity which directly or indirectly controls or is
controlled by or is under common control with a Party to this Agreement.
"Control" means ownership, directly or through one or more Affiliates, of fifty
percent (50%) or more of the shares of stock entitled to vote for the election
of directors, in the case of a corporation, or fifty percent (50%) or more of
the equity interests in the case of any other type of legal entity, status as a
general partner in any partnership, or any other arrangement whereby a Party
controls or has the right to control the Board of Directors or equivalent
governing body of a corporation or other entity.

1.2 [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

1.3 [XXXXXXXXXXXXXXXXX] shall have the meaning set forth in Section 2.6.

1.4 "BIOGEN Proprietary Material" shall mean samples provided by BIOGEN to
CURAGEN for the purposes of performing the Research Program and shall also be
deemed to include the nucleic acids and other substances actually contained in
such samples.

1.5 "Clone" shall mean a segment of DNA representing a whole or partial
gene whose sequence or utility is determined from the use of one or more Data
Sets.

[Confidential Treatment Requested]

<PAGE>

1.6 "CURAGEN Background Inventions" shall mean all patent rights and
know-how of CURAGEN, other than those relating primarily to Inventions, which
CURAGEN has the right to license as of the Effective Date or at any time during
the Term hereof, and which would be infringed by the activities of BIOGEN
permitted by this Agreement or by the development, manufacture, use, sale or
importation of a Licensed Product; provided, however, that CURAGEN Background
Inventions shall expressly exclude (i) any patent rights or know-how
specifically relating to Clones or genes not licensed by BIOGEN pursuant to an
executed License Agreement and (ii) any patent rights or know-how arising from
any CURAGEN collaboration with a third party, except to the extent permitted
thereby.

1.7 "CURAGEN Data" shall mean all information obtained by CURAGEN from the
processing of specified CURAGEN samples, including QC data, expression data,
sequence data and any other information obtained or generated by CURAGEN in the
performance of a discrete CURAGEN Project outside the performance of the
Research Program.

1.8 "CURAGEN Data Set" shall mean all CURAGEN Data resulting from a
discrete CURAGEN Project.

1.9 "CURAGEN Project" shall mean a particular project undertaken by
CURAGEN outside the Research Program to process and analyze a specified set of
samples which do not contain BIOGEN Proprietary Material, and as to which
CURAGEN is free to grant rights to BIOGEN hereunder.

1.10 "CURAGEN Project Invention" shall mean any discovery, invention,
know-how or trade secret conceived or made by employees of CURAGEN in the
performance of a CURAGEN Project that results in CURAGEN Data that becomes part
of an Exclusive Data Set, that is based on, incorporates or makes material use
of the corresponding CURAGEN Data.

1.11 "CURAGEN Proprietary Material" shall mean all substances made by
CURAGEN in the performance of the Research Program other than mRNA pools
extracted from BIOGEN Proprietary Material . CURAGEN Proprietary Material shall
also mean all substances made by CURAGEN in the performance of CURAGEN Projects,
including mRNA pools. CURAGEN Proprietary Materials shall include, without
limitation, QEA fragments and materials derived or constructed from QEA
fragments, including, without limitation, fragment and full length cDNA clones.

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1.12 "Data Set," which may be either a Project Data Set or a CURAGEN Data
Set, shall mean all Project Data resulting from a discrete Research Project or
all CURAGEN Data resulting from a discrete CURAGEN Project, respectively.

1.13 "Discovery Project" shall have the meaning set forth in Section 1.29.

1.14 [XXXXXXXXXXXXXXX] shall have the meaning set forth in Section 7.5.

1.15 "Exclusive Data Set" shall mean any Project Data Set during the
corresponding Exclusive Evaluation Period as provided in Section 2.4 or any
CURAGEN Data Set during the corresponding Exclusive Evaluation Period as
provided in Section 2.5.2.

1.16 "Exclusive Evaluation Period" shall have the meaning set forth in
Section 2.4 or 2.5.2.

1.17 "FTE" shall mean the equivalent of a full year of effort on a full
time basis of a researcher possessing skills and experience necessary to carry
out applicable tasks under the Research Program.

1.18 "Invention" shall mean either a CURAGEN Project Invention or a
Research Project Invention.

1.19 [XXXXXXXXXXXXXX] shall have the meaning set forth in Section 2.1.3.

1.20 "License Agreement" shall mean a license agreement in the form of
Appendix C hereto executed by the Parties upon exercise of any Option pursuant
to Section 7.

1.21 "Optioned Clone" shall have the meaning set forth in Section 7.1.

1.22 "Option Period" shall have the meaning set forth in Section 7.3.

1.23 "Patent Rights" means the rights and interests in and to issued
patents and pending patent applications in any country, including, but not
limited to, all provisional applications, substitutions, continuations,
continuations-in-part, divisions, and renewals, all letters patent granted
thereon, and all reissues, reexaminations and extensions thereof, whether owned
solely or jointly by a Party or licensed in by a Party, with the right to
sublicense, now or in the future, wherein at least one claim of such patent
right is to an Invention.

1.24 "Previously Committed Clone" shall mean any Clone (a) which is subject
to a license or an option previously granted by CURAGEN to any third party, (b)
which a third party has requested CURAGEN to full-length clone, or (c) of which
a third party has commenced full-length cloning and notified CURAGEN thereof.

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1.25 "Project Data" shall mean all information obtained by CURAGEN from
the processing of BIOGEN Proprietary Material in a particular Research Project,
including QC data, expression data, sequence data and any other information
obtained or generated by CURAGEN in the performance of each Research Project in
the Research Program.

1.26 "Project Data Set" shall mean all Project Data resulting from a
discrete Research Project.

1.27 "Research Committee" or "RC" shall have the meaning set forth in
Section 2.2.1.

1.28 "Research Plan" shall mean the written description of the research to
be performed by CURAGEN under this Agreement, as further described in Section
2.1.3. The Research Plan may specify one or more independent Research Projects.

1.29 "Research Project" shall mean (i) a particular project to process and
analyze a specified set of samples in the Research Program, one of the primary
purposes of which is the discovery of novel genes or novel utilities of genes (a
"Discovery Project") or (ii) any other project mutually agreed to by the
Parties. Each individual Research Project shall involve the analysis of no more
than [XX] samples unless otherwise agreed by the Parties.

1.30 "Research Project Invention" shall mean any discovery, invention,
know-how or trade secret conceived or made by employees of CURAGEN or BIOGEN or
jointly by employees of both, (a) in the performance of a Research Project
hereunder, or (b) in the course of evaluating or utilizing any Data Set, in each
case that is based on, incorporates or makes material inventive use of the
corresponding Project Data or CURAGEN Data.

1.31 "Research Program" shall mean the research program to be performed
by CURAGEN under this Agreement as described in the Research Plan and amendments
thereto.

1.32 "Research Term" shall have the meaning set forth in Section 2.3.1.

1.33 "Term" shall have the meaning set forth in Section 8.1.

1.34 "Territory" shall mean the world.

2. RESEARCH PROGRAM

2.1 Implementation of Research Program.
----------------------------------

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2.1.1 Basic Provisions of Program.
---------------------------

(a) The objective of the Research Program will be for CURAGEN to generate
and deliver to BIOGEN Project Data Sets by performing Research Projects
utilizing BIOGEN Proprietary Material. CURAGEN shall use commercially reasonable
efforts to perform such tasks as are set forth in the Research Plan, including
use of its functional genomics technologies (including GeneScape(R),
QEA/GeneCalling, MIM/PathCalling and all additional services provided by
CURAGEN) and the provision of such facilities and materials (other than BIOGEN
Proprietary Material), equipment and consultants as it deems necessary to the
achievement of such Research Plan and shall deliver each Project Data Set to
BIOGEN using the GeneScape(R) database and software. In carrying out the
Research Program, CURAGEN shall devote an average of at least [XXXXXXXX] FTEs
per year to the Research Program over its five year duration (the "Staffing
Level") unless BIOGEN and CURAGEN have agreed on a change in the Staffing Level
as provided in (b) below.

(b) BIOGEN may request an increase in the Staffing Level of up to [XXX
XXX] additional FTEs per year to be devoted to the Research Program, subject to
the agreement of CURAGEN. CURAGEN will use commercially reasonable efforts to
increase the staffing level if mutually agreed as promptly as practical. Once
the Staffing Level is increased, it may not be decreased during the following
[XXXXXXXXX] period without the consent of CURAGEN, which consent shall not be
unreasonably withheld.

(c) BIOGEN shall have the right, at BIOGEN's expense, to have an
independent certified public accountant review CURAGEN's accounting records for
the purpose of verifying the allocation of the required number of FTE's to the
Research Program.

2.1.2 Collaborative Efforts and Reports.
---------------------------------

(a) The Parties agree that the successful execution of the Research
Program will require the collaborative use of both Parties' areas of expertise.
The Parties shall keep the RC fully informed about the status of the portions of
the Research Program they respectively perform. In particular, without
limitation, each Party shall furnish to the RC quarterly written reports within
thirty (30) days after the end of each quarterly period, describing the progress
of its activities in reasonable detail, including (x) a summary of Project Data
from ongoing Research Projects, (y) a summary of uses of Project Data and (z) a
description of Project Data Sets from

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completed Research Projects. At any time, upon the reasonable request of BIOGEN,
CURAGEN will provide an update of the status of Research Projects to BIOGEN.

(b) Scientists at CURAGEN and BIOGEN shall cooperate in the performance of
the Research Program and, subject to any confidentiality obligations to third
parties, shall exchange information and materials (including BIOGEN Proprietary
Material) as necessary to carry out the Research Program, subject to the
provisions of Section 4. Each Party will attempt to accommodate any reasonable
request of the other Party to send or receive personnel for purposes of
collaborating or exchanging information under the Research Program. Such visits
and/or access will have defined purposes and be scheduled in advance. The
requesting Party will bear the reasonable travel and lodging costs of any such
personnel.

(c) CURAGEN will give written notice to BIOGEN and the RC upon completion
of the Project Data Set from each Research Project. "Completion" of a Project
Data Set shall occur upon generation of all QEA/GeneCalling data or
MIM/PathCalling data from a Research Project as contemplated by the Research
Plan.

(d) CURAGEN shall set up and maintain, throughout the Research Term, a
secure partition of its GeneScape(R) database and software for the exclusive use
of BIOGEN and CURAGEN for the purpose of identifying genes from Exclusive Data
Sets, and shall provide online E-mail and telephone help during normal business
hours in the use thereof to BIOGEN. CURAGEN and BIOGEN shall jointly set up and
maintain a secure connection to said partition of the GeneScape(R) database and
software in order to give BIOGEN on-line access thereto. Through such
connection, BIOGEN shall have the right to utilize all features and functions of
the GeneScape(R) database and software (including, without limitation,
GeneTools(TM)) in connection with the Research Program.

(e) BIOGEN will also receive access to CURAGEN's QEA/GeneCalling and
MIM/PathCalling subscription databases and to GeneTools(TM) pursuant to one or
more subscription agreements to be executed by the Parties, with terms
substantially as described in Appendix D hereto. Such subscriptions [XXXXXXXX
----------
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXX]

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[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] until the
expiration of the Research Term. Such subscription agreements may be terminated
by BIOGEN at any time, without affecting the Research Program, either in their
entirety or with respect to any database at BIOGEN's sole discretion upon three
(3) months prior written notice. BIOGEN shall have no rights to use the
GeneScape(R) database and software except as expressly set forth herein or in an
executed database subscription agreement.

2.1.3 Research Plans.
--------------

The Research Plan for the [XXXXXXXXXXXXXXXXX] of the Research Program shall
be agreed upon by the Parties within [XXXXXXXXXXXXXX] of the Effective Date and
shall include the initial Research Projects and plans to implement the
installation of access to the GeneScape(R) database and software for BIOGEN. The
initial Research Projects shall include a project on [XXXXXXXXXXXXXX
XXXXXXXXXXXXXX] and a project on [XXXXXXXXXX] as further described in Section
2.6. Every [XXXXXXXXXXXXXX] during the Research Term [XXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXX] the Research Plan shall be updated by BIOGEN in
consultation with CURAGEN to cover the next twelve months and shall be approved
by the RC no later than thirty (30) days before the end of each semi-annual
period. The Research Plan shall set forth specific Research Projects for the
period covered by the Research Plan. The RC will consider adjustments in the
Research Plan at any time upon the request of BIOGEN or CURAGEN. Notwithstanding
the foregoing, no project shall become a Research Project without the express
consent of both BIOGEN and CURAGEN; provided, however, that CURAGEN shall
consent to any reasonable proposed Discovery Project which is not substantially
similar to a project that is ongoing, planned, the subject of negotiation with a
third party or subject to a prior commitment to a third party, and which would
not violate a prior restriction under an agreement with a third party. The
Parties shall negotiate in good faith the terms to apply generally to any
Research Project that is not a Discovery Project, other than the [XXXXXXXXXX
XXXXXXXX] which is covered by Section 2.6.

2.1.4 Exclusivity.
-----------

(a) CURAGEN agrees that, during the conduct of a Research Project and
for the duration of any subsequent Exclusive Evaluation Period, CURAGEN shall
not undertake to perform a substantially similar research project with any third
party.

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(b) CURAGEN agrees that during any Exclusive Evaluation Period, CURAGEN
will not grant access to any Exclusive Data Set to any other party and that
during any Option Period, CURAGEN shall not grant to any third party rights to
any Optioned Clone. In addition, CURAGEN shall not, during any Exclusive
Evaluation Period, grant a third party any exclusive rights to license a Clone
contained in the corresponding Exclusive Data Set (i) which BIOGEN has requested
CURAGEN to full-length clone or (ii) for which BIOGEN has commenced full-length
cloning and notified CURAGEN thereof. Notwithstanding the provisions of Article
4 and except as provided in Section 2.6 hereof, upon the expiration of any
Exclusive Evaluation Period for any Exclusive Data Set, CURAGEN shall have the
right, at its sole option, to make such Data Set and reasonable descriptions of
the data contained therein available to third parties or to put the Data Set and
such descriptions in the subscription portion of the GeneScape(R) database.
Nothing contained in this Agreement shall in any way restrict CURAGEN's right to
perform research or collaborate with third parties and to grant to third parties
the right to exploit the results of any such research or collaborations without
restriction other than as set forth above or as expressly provided in an
executed License Agreement. CURAGEN agrees that CURAGEN will not use and/or
replicate any BIOGEN Proprietary Material for any purpose other than as provided
herein.

(c) CURAGEN acknowledges that BIOGEN may, in the course of reviewing
Data Sets, obtain general information not specifically relating to any Clone or
to the utility thereof. BIOGEN shall be permitted to use any such general
information that is non-proprietary to CURAGEN in the course of conducting its
internal research programs, or as otherwise permitted herein, but for no other
purpose.

(d) BIOGEN agrees that, until any such information is in the public
domain, other than as a result of a disclosure by BIOGEN in violation of this
Agreement, an executed subscription agreement or an executed License Agreement,
BIOGEN will only utilize Project Data, CURAGEN Data, CURAGEN Proprietary
Material, Inventions or Patent Rights as expressly provided herein, in an
executed License Agreement or in an executed subscription agreement.

2.1.5 Research License. CURAGEN hereby grants to BIOGEN a non-exclusive
----------------
license under CURAGEN Background Inventions and CURAGEN's interest in any
Inventions solely

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<PAGE>

during the Term hereof and to the extent necessary to allow BIOGEN to perform
its obligations under the Research Program and to exercise the rights granted
herein.

2.1.6 Software License. Any access granted to the GeneScape(R) database
----------------
and software hereunder, or any components thereof, is granted according to the
following terms:

The GeneScape(R) database, software and display screeens are protected by
copyright, patent, trade secret and other intellectual property laws. CURAGEN
hereby grants to BIOGEN and its employees a non-exclusive non-transferrable
license to access the GeneScape(R) database and software solely for the purposes
of and during the Term of this Agreement. BIOGEN shall access Project Data Sets
and CURAGEN Data Sets only through the GeneScape(R) database and software
provided by CURAGEN. BIOGEN shall not copy the GeneScape(R) database, software
or display screens except as occurs during the normal course of CURAGEN-provided
access. In particular, BIOGEN will not retain such normal copies for a time not
reasonably related to CURAGEN-provided access. BIOGEN shall not reverse
engineer, decompile, or disassemble the GeneScape(R) software or display
screens. The GeneScape(R) database and software embody trade secrets of CURAGEN
that are considered Confidential Information of CURAGEN and subject to the
provisions of Article 6 hereof.

2.2 Research Committee.
------------------

2.2.1 Establishment and Functions of RC.
---------------------------------

(a) CURAGEN and BIOGEN shall establish a "Research Committee" (the
"RC"). The RC will be responsible for the planning and monitoring of the
Research Program. In particular, the activities of the RC shall include
reviewing progress in the Research Program and recommending necessary
adjustments to the Research Program, including any Research Project
substitutions deemed desirable based on results and on BIOGEN's commercial
interest, as the research and development progresses.

(b) In planning and monitoring the Research Program, the RC shall assign
tasks and responsibilities taking into account each Party's respective specific
capabilities and expertise in order in particular to avoid duplication and
enhance efficiency and synergies.

2.2.2 RC Membership.
-------------

CURAGEN and BIOGEN each shall appoint, in their sole discretion, three
members to the RC, which shall include a Co-Chair to be designated by BIOGEN and
a Co-Chair to be

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designated by CURAGEN. Substitutes or alternates for the Co-Chairs or other RC
members may be appointed at any time by notice in writing to the other Party.
The Parties may mutually agree to change the size of the RC as long as there
shall be an equal number of representatives of each Party on the RC. The initial
Co-Chairs and other RC members shall be designated by the Parties upon execution
of this Agreement. CURAGEN shall appoint a Project Coordinator, who shall be
reasonably satisfactory to BIOGEN, to serve as the principal liaison with BIOGEN
for the Research Program. Such Project Coordinator will be one of CURAGEN's
members of the RC.

2.2.3 Meetings.
--------

The RC shall meet at least quarterly, with such meetings to be held,
alternately, in New Haven, Connecticut, and Cambridge, Massachusetts unless the
Parties agree otherwise. Any additional meetings shall be held at places and on
dates selected by the Co-Chairs of the RC. In addition, the RC may act without a
formal meeting by a written memorandum signed by the Co-Chairs of the RC.
Whenever any action by the RC is called for hereunder during a time period in
which the RC is not scheduled to meet, the Co-Chairs of the RC shall cause the
RC to take the action in the requested time period by calling a special meeting
or by action without a meeting. Subject to the obligations set forth in Section
4, representatives of each Party or of its Affiliates, in addition to the
members of the RC, may attend RC meetings at the invitation of either Party with
the prior approval of the other Party, which shall not be unreasonably withheld.

2.2.4 Minutes.
-------

The RC shall keep accurate minutes of its deliberations which record all
proposed decisions and all actions recommended or taken. Drafts of the minutes
shall be delivered to the Co-Chairs of the RC within twenty (20) days after the
meeting. The Party hosting the meeting shall be responsible for the preparation
and circulation of the draft minutes. Draft minutes shall be edited by the
Co-Chairs and shall be issued in final form only with their approval and
agreement as evidenced by their signatures on the minutes.

2.2.5 Quorum; Voting; Decisions.
-------------------------

At each RC meeting, at least two (2) member(s) appointed by each Party
present in person or by telephone shall constitute a quorum and decisions shall
be made by majority vote. Each RC member shall have one vote on all matters
before the RC, provided that the member or members of each Party present at an
RC meeting shall have the authority to cast the votes of any

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of such Party's members on the RC who are absent from the meeting.
Notwithstanding the foregoing, the objective of the Parties to this Agreement is
that decisions of the RC shall be made by consensus. However, except as
otherwise set forth herein, in the event that the RC is unable to resolve any
matter before it as set forth above, such matter shall be resolved in good faith
by BIOGEN. Notwithstanding the foregoing, no project shall become a Research
Project without the express consent of both BIOGEN and CURAGEN; provided,
however, that CURAGEN shall consent to any reasonable proposed Discovery Project
which is not substantially similar to a project that is ongoing, planned, the
subject of negotiation with a third party or subject to a prior commitment to a
third party, and which would not violate a prior restriction under an agreement
with a third party.

2.2.6 Expenses.
--------

CURAGEN and BIOGEN shall each bear all expenses of their respective RC
members related to their participation on the RC and attendance at RC meetings.

2.3 Research and Development Term.
-----------------------------

2.3.1 Term of the R&D Program.
-----------------------

The Research Program shall expire five (5) years after the Effective Date
unless extended as provided below or unless earlier terminated by either Party
pursuant to the provisions in Section 2.3.3 and/or Article 8 (the "Research
Term").

2.3.2 Extension of the Research Phase of the R&D Program.
--------------------------------------------------

The Research Term may be extended upon [XXXXXXXXXX] prior written notice
by mutual agreement of the Parties on terms to be agreed upon between the
Parties.

2.3.3 Early Termination of the R&D Program.
------------------------------------

(a) BIOGEN may terminate the Research Program at its sole discretion upon
six (6) months prior written notice to CURAGEN, which notice may be given at any
time after the second anniversary of the Effective Date. Notwithstanding any
other provision of this Agreement, any such early termination of the Research
Program shall automatically terminate any ongoing Exclusive Evaluation Period or
Option Period, but shall not affect any License Agreement executed between the
Parties prior to such early termination or any Option that has been exercised
prior to such early termination.

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(b) Any termination of the Research Program under Section 2.3.3(a) shall
be without prejudice to the rights of either Party against the other, then
accruing or otherwise accrued under this Agreement and upon any such
termination, all remaining BIOGEN Proprietary Material provided to CURAGEN under
this Agreement shall be returned to BIOGEN or destroyed and all remaining
CURAGEN Proprietary Material provided to BIOGEN under this Agreement shall be
returned to CURAGEN or destroyed, except for any CURAGEN Proprietary Material
licensed pursuant to an executed License Agreement.

2.4 Project Data Evaluations.
------------------------

2.4.1 Exclusive Access. From the time at which a Research Project is begun
----------------
and continuing through a [xxxxxxx] period which shall commence on the first day
of the [XXXXXXXXXXXX] following the [XXXXXXXXXXXX] in which delivery of a
notice of a complete Project Data Set is made pursuant to Section 2.1.2(c) (the
"Exclusive Evaluation Period"), CURAGEN: (a) shall not use such Project Data Set
and related CURAGEN Proprietary Material resulting from such Research Project
for any purpose other than conducting the Research Program hereunder and (b)
shall keep such Project Data Set and related Inventions and CURAGEN Proprietary
Material confidential and will not disclose or transfer the Project Data Set, or
related Inventions and CURAGEN Proprietary Material, to third parties by
publication or otherwise, without the prior written consent of BIOGEN.

2.4.2 Extensions. BIOGEN may elect to extend the Exclusive Evaluation
----------
Period for any Project Data Set for up to [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX] from the end of the initial, unextended Exclusive Evaluation Period by
giving written notice to CURAGEN and making a payment of [XXXXXXXXXXXXXXXXX
XXXXXXXXXXXX] to CURAGEN prior to expiration of the then current Exclusive
Evaluation Period for such Project Data Set. An Exclusive Evaluation Period will
be automatically extended for [XXXXXXXXXXXXXX] for up to [XXXXXXXXXX] in order
to allow the completion of any reasonable requests for confirmation of data made
by BIOGEN during the primary [XXXXXXXXXXXX] of such Exclusive Evaluation
Period.

2.4.3 Non-exclusive Access. Except with respect to any information which
--------------------
becomes part of the public domain other than as a result of a disclosure by
BIOGEN in violation of this Agreement, an executed subscription agreement or an
executed License Agreement, following the expiration of the Exclusive Evaluation
Period for a Project Data Set, BIOGEN shall continue

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to have non-exclusive access to such Project Data Set solely through the
GeneScape(R) database and solely for the purpose of identifying Clones of
interest to BIOGEN in such Data Set, or to the extent expressly permitted in
Section 2.1.4(c), in an executed License Agreement or in an executed
subscription agreement.

2.4.4. Data Annotations. Upon the expiration of the Exclusive Evaluation
----------------
Period for each Project Data Set, CURAGEN shall furnish to BIOGEN reasonable
descriptions of the Project Data Set to be included in the GeneScape(R) database
with the Project Data Set. BIOGEN shall have a period of [XXXXXXXXXXXXXX] to
review such descriptions and advise CURAGEN of reasonable objections. CURAGEN
shall not include in the GeneScape(R) database any descriptions, or portions
thereof, to which BIOGEN reasonably objects.

2.5 CURAGEN Projects.
----------------

2.5.1 Access. BIOGEN shall have the option, for such period or periods as
------
CURAGEN may specify, to obtain exclusive access to specified proprietary CURAGEN
Data Sets and related CURAGEN Project Inventions which are offered by CURAGEN in
its sole discretion to BIOGEN for review. Such option shall be exercisable as
set forth in Section 2.5.2 below.

2.5.2 Exclusive Evaluation Option. Subject to any rights which CURAGEN may
---------------------------
grant or have granted to third parties, BIOGEN may request at any time during
the time period specified by CURAGEN that it receive exclusive access (as
described in Section 2.5.1) to any CURAGEN Data Set offered to BIOGEN pursuant
to Section 2.5.1. Such exclusive access to such CURAGEN Data Set shall be
granted to BIOGEN for an Exclusive Evaluation Period of [XXXXXXXXXX] commencing
upon CURAGEN's receipt of written notice from BIOGEN and payment of an exclusive
evaluation fee of [XXXXX] unless BIOGEN is notified by CURAGEN at any time
prior to CURAGEN's receipt of BIOGEN's written notice that exclusive access to
such CURAGEN Data Set is no longer available as a result of CURAGEN's agreements
with third parties existing at the time of the request.

2.5.3 Extensions. BIOGEN may elect to extend the Exclusive Evaluation
----------
Period for any CURAGEN Data Set for up to [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX] from the end of the initial unextended Exclusive Evaluation Period by
giving written notice to CURAGEN and making a second payment [XXXXXXXXXX
XXXXXXXXX] to CURAGEN prior to expiration of the then current
Exclusive Evaluation Period for such CURAGEN Data Set. An

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Exclusive Evaluation Period will be automatically extended for [XXXXXXXXXXXX]
for up to [XXXXXXXXXXXX] in order to allow the completion of any reasonable
requests for confirmation of data made by BIOGEN during the primary [XXXXXXXXXX]
period of such Exclusive Evaluation Period. Following the expiration of the
Exclusive Evaluation Period for a CURAGEN Data Set, BIOGEN shall have no access
to or right to use such CURAGEN Data Set, other than as expressly permitted in
Section 2.1.4(c), in an executed License Agreement or in an executed
subscription agreement.

2.6 [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXX]

3. FINANCIAL TERMS

3.1 Equity Investment. BIOGEN agrees itself, or through one of its
-----------------
Affiliates, to make an equity investment in CURAGEN in the amount of Five
Million Dollars ($5,000,000), such investment to be made in a transaction exempt
from registration under the Securities Act of 1933 contemporaneously with the
closing of the initial public offering of CURAGEN Common Stock at the public
offering price and pursuant to a mutually agreeable stock purchase agreement
containing reasonable and customary terms for the purchase of stock in such
circumstances and a

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registration rights agreement providing for the filing of a registration
statement covering the resale of the purchased shares to be filed by CURAGEN
within twenty (20) days of the first anniversary of the effective date of the
registration statement pertaining such initial public offering. In the event
that CURAGEN has not closed an initial public offering within [XXXXXXXXXX
XXXXXX] from the Effective Date, BIOGEN shall be released from its obligation
pursuant to this Section 3.1.

3.2 Loan Commitment. As partial consideration for rights granted
---------------
hereunder, BIOGEN hereby commits to the following:

(a) BIOGEN shall itself, or through one of its Affiliates, subject to the
terms set forth below, make funds available to CURAGEN for general corporate
purposes in the form of a loan or loans to CURAGEN in an amount not to exceed
Ten Million Dollars ($10,000,000.00) (the "Loan"). Unless this Agreement has
been terminated for any reason, CURAGEN may, in such amounts and at such times
as CURAGEN, in it sole discretion, may determine, upon [XXXXXXXXXXXXXX] written
notice draw down the balance of the Loan over a period of five (5) Loan Years
(as defined below) following the Effective Date. For the purposes of this
section, a "Loan Year" commences on the Effective Date or an anniversary thereof
and terminates twelve months later. BIOGEN shall not be obligated to advance
more than Five Million Dollars ($5,000,000) in the first Loan Year or to advance
any funds under the Loan at any time during which (i) CURAGEN is in default
under any Note (defined below); or (ii) any proceeding, voluntary or
involuntary, in bankruptcy or insolvency, is pending against CURAGEN, or a
receiver is operating CURAGEN with or without the consent of CURAGEN. BIOGEN's
obligation to advance any funds under the Loan shall terminate upon the earlier
to occur of (i) the last day of the fifth Loan Year or (ii) termination or
expiration of the Research Program and the Research Term.

(b) On the Effective Date, CURAGEN shall execute and deliver to BIOGEN an
unsecured note, substantially in the form set forth in Appendix B attached
----------
hereto and made a part hereof (the "Note"), evidencing the Loan. The schedule
attached to the Note shall be revised each time any amount is drawn down under
the Loan and each time any amount is repaid. Once any principal amount has been
repaid, BIOGEN shall not be obligated to advance such amount to CURAGEN during
the remainder of the term of the Loan. The Note shall be subordinated to [XXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX]

[Confidential Treatment Requested]

<PAGE>

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX and may
be prepaid by CURAGEN at any time without premium or penalty on a date specified
by CURAGEN, in cash or at CURAGEN's option, in CURAGEN Common Stock valued at
its then Fair Market Value (as defined in Section 3.2(e) below).

(c) The Note shall bear interest on the outstanding principal amount
thereof at a rate per annum equal to [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXX] Such interest shall accrue and be paid semi-annually commencing on the
six-month anniversary of the date first following any advance under the Loan and
continuing every six months thereafter until the Note is paid in full, unless
otherwise specified in this Section 3.2. Interest payments shall be made in cash
or at CURAGEN's option, in CURAGEN Common Stock valued at its then Fair Market
Value (as defined in Section 3.2(e) below). The applicable rate of interest for
the Note shall be adjusted semi-annually according to the [XXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] on each
six-month anniversary date of the Effective Date.

(d) Within [XXXXXXXXXXXXXX] of the expiration of the fifth Loan Year,
repayment in full of the principal amount and accrued interest, under the Note
shall be made in cash or, at CURAGEN's option, in CURAGEN Common Stock valued at
its then Fair Market Value (as defined in Section 3.2(e) below). Notwithstanding
the foregoing, if this Agreement is terminated by BIOGEN pursuant to Section
8.2(a), or if the Research Program is terminated pursuant to Section 2.3.3,
CURAGEN shall repay the principal and accrued interest owed under the Note
within [XXXXXXXXXXXXX] of the date the Agreement or the Research Program, as
the case may be, is terminated; provided, however, that any such repayment may
be made in cash or stock as set forth above, at CURAGEN's sole discretion.

(e) For purposes of subsection (c) of this Section 3.2, [XXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXX] For purposes of subsections (b), (c), (d) and (f) of this Section
3.2, "Fair Market Value" of CURAGEN Common Stock shall mean: [XXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXX]

17
<PAGE>

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXX Delivery of any shares of Common Stock shall take place
no later than five (5) days after the repayment date and shall be subject to
execution by the Parties of an agreement containing customary representations
and provisions to comply with Federal and State securities laws, as mutually
agreed between the Parties. Additionally, if CURAGEN Common Stock is not
publicly traded at the time of any such repayment, BIOGEN shall receive
registration rights with respect to any such shares on the same terms and
conditions as set forth in the Registration Rights Agreement between CURAGEN and
Biotech Manufacturing Limited dated June 25, 1997.

(f) In the event that CURAGEN makes any repayment hereunder in CURAGEN
Common Stock and CURAGEN is eligible to file a registration statement on Form
S-3 (or successor short form) at the time of repayment, then within [XXXXXX] of
the repayment date, CURAGEN shall file a registration statement on Form S-3
covering the resale by BIOGEN of any shares so delivered to BIOGEN; provided,
however, that with respect to any repayment in CURAGEN Common Stock made under
subsection (c) hereof, to the extent not already included in any other
registration, CURAGEN shall [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] file a
registration statement on Form S-3 covering the resale by BIOGEN of any such
shares so delivered to BIOGEN. Notwithstanding anything herein to the contrary,
BIOGEN may require that CURAGEN repay the amounts borrowed under the Note in
cash and stock to the extent necessary to ensure that receipt of CURAGEN's
shares will not cause BIOGEN's holdings in CURAGEN to equal [XXXXXXXX] or more
of CURAGEN's total Common Stock outstanding after the issuance of such shares to
BIOGEN.

3.3 Research Funding.
----------------

[Confidential Treatment Requested]

<PAGE>

During the Research Term, BIOGEN will pay CURAGEN non-refundable research
payments of [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] per year plus
the sum of [XXXXXX] per year per FTE in the Staffing Level above [XX]FTEs. Such
payments will be made quarterly in advance, commencing on the Effective Date,
and on or before the first day of each calendar quarter thereafter, with the
first and last payments prorated in the event that the Effective Date or the
expiration or termination date is not the first day or last day of a calendar
quarter, respectively. In the event that the Staffing Level is to change in any
calendar quarter, such payment shall be pro-rated accordingly, if necessary,
based on the above-specified level of funding per FTE. The first research
payment shall be made simultaneously with the execution of this Agreement and
shall include all amounts necessary to make BIOGEN current in research payments
due since the Effective Date. BIOGEN will fund its own activities under the
Research Program.

4. TREATMENT OF CONFIDENTIAL INFORMATION

4.1 Confidential Information. During the course of the Research Program,
------------------------
or in discussions concerning Exclusive Data Sets, each Party may disclose to the
other proprietary technical and business information, including but not limited
to information contained in Data Sets (which information shall be deemed
Confidential Information of CURAGEN), (collectively, "Confidential
Information"). For a period of [XXXXXXXXXXX] after the receipt of any such
Confidential Information, except as expressly permitted hereunder, the receiving
Party shall keep confidential all such Confidential Information of the other
Party and will not disclose such Confidential Information of the other Party to
third parties by publication or otherwise. Each Party shall take reasonable
steps to ensure that all of its employees, consultants and RC members shall
protect and use Confidential Information of the other Party only in accordance
with the terms hereof. Each Party further agrees not to use Confidential
Information of the other Party for any purpose other than conducting or
evaluating research hereunder, evaluating and analyzing Data Sets or exercising
any rights granted to it or reserved by it hereunder, in an executed License
Agreement or executed subscription agreement, or as otherwise expressly
permitted hereunder. Notwithstanding the foregoing, it is understood and

[Confidential Treatment Requested]

<PAGE>

agreed that the receiving Party's obligations of confidentiality and nonuse
herein shall not apply to any information which:

(a) is, at the time of disclosure by the disclosing Party hereunder,
or thereafter becomes, a part of the public domain or publicly known
or available through no fault or negligence of the receiving Party or
any of its Affiliates; or

(b) was otherwise in the receiving Party's lawful possession prior to
disclosure by the disclosing Party, as demonstrated by the receiving
Party's written records; or

(c) is lawfully disclosed to the receiving Party or any of its
Affiliates on a non-confidential basis by a third party who is not in
violation of an obligation of confidentiality to the disclosing Party
relative to such information.

4.2 Publications. It is expected that each Party may wish to publish the
------------
results of its research under this Agreement. In order to safeguard intellectual
property rights, the Party wishing to publish or otherwise publicly disclose the
results of its research hereunder shall first submit a draft of the proposed
manuscripts to the Research Committee for review, comment and consideration of
appropriate patent action at least [XXXXXXXXXX] prior to any submission for
publication or other public disclosure. Within [XXXXXXXXXXXX] of receipt of
the prepublication materials, the Research Committee will advise the Party
seeking publication as to whether a patent application will be prepared and
filed or whether trade secret protection should be pursued and, if so, the
Research Committee will, in cooperation with both Parties, determine the
appropriate timing and content of any such publications.

4.3 Press Release and Regulatory Filings. The Parties shall mutually
------------------------------------
agree on a press release announcing the execution of this Agreement and on any
confidential treatment request to be filed with the Securities and Exchange
Commission with respect to this Agreement. Once any written statement is
approved for disclosure by both Parties, either Party may make subsequent public
disclosures of the contents of such statement without the further approval of
the other Party.

[Confidential Treatment Requested]

<PAGE>

5. INTELLECTUAL PROPERTY RIGHTS

5.1 BIOGEN Proprietary Material. mRNA pools extracted by CURAGEN from a
---------------------------
BIOGEN Proprietary Material in the performance of the Research Program shall
remain BIOGEN Proprietary Material. All other substances made by CURAGEN in the
performance of the Research Program shall be CURAGEN Proprietary Material.
BIOGEN Proprietary Material shall remain the property of BIOGEN and CURAGEN
shall use such BIOGEN Proprietary Material only for the purpose of conducting
the Research Program hereunder and shall not transfer BIOGEN Proprietary
Material to any other person or entity.

5.2 CURAGEN Proprietary Material. Substances made by BIOGEN from CURAGEN
----------------------------
Proprietary Material shall remain CURAGEN Proprietary Material. CURAGEN
Proprietary Material shall remain the property of CURAGEN and BIOGEN shall use
such CURAGEN Proprietary Material only for purposes relating to performance of
the Research Program, evaluation of the Project Data, the exercise of the option
provided in Section 7.1, or pursuant to the terms of an executed License
Agreement. BIOGEN shall not transfer CURAGEN Proprietary Material to any other
person or entity except in connection with rights granted to BIOGEN pursuant to
an executed License Agreement.

5.3 Inventions. Each Party shall promptly disclose to the other Party all
----------
Inventions. Except as set forth in Sections 5.1 and 5.2, (i) all Research
Project Inventions, and Patent Rights thereon, shall be owned jointly by CURAGEN
and BIOGEN; and (ii) all CURAGEN Project Inventions, and Patent Rights thereon,
shall be owned by CURAGEN. The rights and interests of CURAGEN and BIOGEN in
Inventions shall be subject to the provisions of Article 7.

6. PROVISIONS CONCERNING THE FILING, PROSECUTION AND
MAINTENANCE OF PATENT RIGHTS

6.1 Applicability. The provisions of this Section 6 shall be applicable
-------------
to all Inventions and Patent Rights unless and until (i) they become subject to
a License Agreement, whereupon the License Agreement will govern the rights of
the Parties with respect to the subject matter thereof, or (ii) the relevant
Research Project is completed and the relevant Exclusive

21
<PAGE>

Evaluation Period expires and the relevant Option Period, if any, expires,
whereupon this Section 6 shall cease to apply.

6.2 Patent Filing.
-------------
(a) CURAGEN shall have the first right (but not the obligation) to
prepare, file, prosecute, obtain and maintain patent applications and patents on
Inventions, at its sole expense. BIOGEN agrees to provide reasonable assistance
and cooperation to CURAGEN to facilitate such filing, prosecution and
maintenance. CURAGEN agrees that any such preparation, filing, prosecution and
maintenance shall be conducted diligently and that BIOGEN shall be kept fully
informed of the progress thereof and provided with copies of all material
documents pertaining thereto until the end of the Exclusive Evaluation Period,
and for any Invention which becomes subject to an Option, until the end of the
Option Period. BIOGEN shall, whenever possible, be given the opportunity to
review and comment in advance on any patent filings or other correspondence with
the patent office during such periods and CURAGEN shall consider incorporating
any comments provided by BIOGEN in good faith.

(b) CURAGEN may elect not to exercise its first right to prepare, file,
prosecute, obtain and maintain patent applications and patents on Inventions as
described in Section 6.2(a) above at any time for any such patent applications
and patents by giving written notice thereof to BIOGEN. Such notice shall
specifically identify the patent application(s) and/or patent(s) for which
CURAGEN wishes to relinquish such first right. Following the receipt of such
notice, BIOGEN shall have the right to prepare, file, prosecute, obtain and
maintain the patent application(s) and patent(s) identified in the notice, at
its sole expense, on behalf of the owner of the Invention, subject to the rights
granted herein, until the end of the Exclusive Evaluation Period, and for any
Invention which becomes subject to an Option, until the end of the Option
Period.

(c) The Parties shall mutually agree before permitting any patent
application or patent within Patent Rights to lapse as well as before
authorizing any amendment to any patent application or patent within Patent
Rights that would irrevocably limit the lawful scope of the Patent Rights, until
the end of the Exclusive Evaluation Period, and for any Invention which becomes
subject to an option, until the end of the Option Period.

22
<PAGE>

(d) No Party shall have any obligation under this Agreement to pay any
fees or costs: (i) for bringing a lawsuit or other action to enforce any of the
Patent Rights against an actual or suspected infringement or (ii) for any other
Party to obtain for its own benefit independent business or legal advice
concerning any of the Patent Rights.

6.3 Notice of Infringement. If either Party learns of any infringement or
----------------------
threatened infringement by a third party of the patents within Patent Rights,
such Party shall promptly notify the other Party and shall provide such other
Party with available evidence of such infringement.

6.4 Infringement. CURAGEN shall have all rights, at its own expense, to
------------
bring suit (or other appropriate legal action) against any actual or suspected
infringement of the Patent Rights.

6.5 Cooperation. BIOGEN shall execute all papers and perform such other
-----------
acts as may be reasonably required to maintain any infringement suit brought in
accordance with Section 6.4 above (including giving legal consent for bringing
such suit, and agreeing to be named as a plaintiff or otherwise joined in such
suit). BIOGEN shall be reimbursed by CURAGEN for any out of pocket expenses
incurred in connection with the foregoing. BIOGEN, at its option and expense,
may be represented in such suit by counsel of its choice.

7. OPTION TO BIOGEN

7.1 Option Grant.
------------

7.1.1 Option. Subject to rights third parties have obtained by virtue of
------
access to other CURAGEN Data Sets, data sets resulting from agreements between
CURAGEN and third parties, or the subscription portion of the GeneScape(R)
database prior to BIOGEN's election, CURAGEN hereby grants to BIOGEN the right
to elect an exclusive option (the "Option") to license all Inventions and other
CURAGEN patents or patent applications as described in Section 2.3 of the
License Agreement relating to any Clone whose sequence or utility is determined
in whole or in part from the use of an Exclusive Data Set which is not a
Previously Committed Clone. Such Option shall give BIOGEN the right to obtain,
at BIOGEN's sole discretion, either (a) subject to the rights reserved by
CURAGEN in Section 7.1.3, an exclusive license to the Clone specified in
BIOGEN's notice of exercise (the "Optioned Clone") and to all Patent Rights

23
<PAGE>

and Inventions to the extent that they relate to such Optioned Clone including
but not limited to Patent Rights claiming whole or partial sequences or utility,
to develop, make, have made, use, have used, sell, offer for sale, have sold,
import and have imported products (i) incorporating or derived from such
Optioned Clone, or (ii) discovered or developed using such Optioned Clone, in
the Territory, for any and all human uses, under the terms and conditions set
forth in the License Agreement; (b) a non-exclusive license to the Optioned
Clone and to all Patent Rights and Inventions to the extent that they relate to
such Optioned Clone, solely for use of the Optioned Clone as a target to develop
small molecule products; or (c) subject to the rights reserved by CURAGEN in
Section 7.1.3, an exclusive license to all Patent Rights and Inventions claiming
utility of a known Optioned Clone, as further described in the License
Agreement. Such Option shall be exercisable at any time during the Option Period
specified in Section 7.3.

7.1.2 Option Election.
---------------
Such Option shall be elected by BIOGEN by giving written notice to CURAGEN
within the Exclusive Evaluation Period for such Exclusive Data Set, which shall
specify in detail the Optioned Clone to be included within the terms of any such
Option and which shall be accompanied by the payment of any Option Fee as
specified in Section 7.2. Each Optioned Clone, and the term of the corresponding
Option Period, shall be listed on Appendix A hereto from time to time.
Notwithstanding the foregoing, for Project Data Sets, BIOGEN may request such an
Option after expiration of the Exclusive Evaluation Period, which Option shall
be granted by CURAGEN upon payment of the Option Fee specified in Section 7.2,
unless prohibited by agreements with third parties.

7.1.3 Reservation of Rights. Notwithstanding the foregoing, in any
---------------------
exclusive license granted pursuant to the exercise of an Option, CURAGEN shall
retain for itself the right to use the Optioned Clone or the protein derived
therefrom as part of a general library of nucleic acids, which library is used
for research purposes.

7.2 Option Fee. An Option Fee of [XXXXXX] per Optioned Clone shall be due
----------
upon the election of an Option with respect to any Clone from any Exclusive Data
Set; [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX]

[Confidential Treatment Requested]

<PAGE>

7.3 Option Period. Each Option shall remain in effect for a period of
-------------
[XXXXXXXXXXXX] from receipt by CURAGEN of BIOGEN's written notice of its
election of such Option and payment of any required Option Fee (the "Option
Period"); provided, however, that any Option Period may be extended for [XXX
XXXXXXXXXXXXXXXXXXXXXXXX] period upon payment by BIOGEN of [XXXXXXXXXXXXXX]
per Optioned Clone.

7.4 Option Exercise. During each Option Period, upon notice to CURAGEN
---------------
and upon payment of the corresponding license fee, BIOGEN shall have the right
to receive a license to the Optioned Clone under the terms and conditions set
forth in an executed License Agreement. The license fee for a license described
in Section 7.1.1, clause (a) shall be [XXXXXX] and the license fee for a license
described in Section 7.1.1, clause (b) or (c), shall be [XXXXXX]
Notwithstanding the foregoing, [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]The License Agreement shall be executed in
substantially the form attached hereto upon exercise of the first Option, unless
previously executed pursuant to Section 7.5, and shall be amended from time to
time in accordance with the terms hereof and thereof as additional Options are
exercised.

7.5 [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

7.6 Reversion of Rights. CURAGEN shall retain all rights to all Project
-------------------
Data, CURAGEN Data, CURAGEN Proprietary Material, Inventions and Patent Rights
not expressly granted to BIOGEN hereunder. Upon expiration of any Exclusive
Evaluation Period,

[Confidential Treatment Requested]

<PAGE>

CURAGEN shall recover and retain all of CURAGEN's rights to the corresponding
Exclusive Data Set and related Inventions and Patent Rights thereon other than
such rights as BIOGEN may have as provided in Sections 2.1.4, 2.1.5, 2.4.3 and
2.6 or with respect to Optioned Clones. In the event that upon the expiration of
any Option Period the corresponding Option has not been exercised by BIOGEN, all
of CURAGEN's rights in the corresponding Optioned Clone and related Inventions
and Patent Rights thereon shall revert to CURAGEN. Notwithstanding the
foregoing, nothing contained in this Section 7.6 shall be deemed to limit any
rights of BIOGEN expressly provided in an executed License Agreement or an
executed subscription agreement. In addition, BIOGEN shall (a) upon the
expiration of each Exclusive Evaluation Period, without any further action on
its part, be deemed to have granted to CURAGEN an exclusive (except for uses by
BIOGEN permitted in Section 2.4.3), royalty-free license for all purposes under
BIOGEN's rights in Inventions or Patent Rights claiming (i) any Clones other
than [XXXXXXXXXXX] whose sequence or utility is determined in whole or in part
from the use of the corresponding Exclusive Data Set and which are not the
subject of any Option or License Agreement, or (ii) any uses of such Clones, and
(b) upon the expiration of each Option Period, without any further action on its
part, be deemed to have granted to CURAGEN a license as set forth in (a) above
with respect to each Optioned Clone for which an Option has not been exercised.
Prior to any disposition of rights as set forth above or in an executed License
Agreement, BIOGEN shall not assign, encumber or otherwise limit its ownership
interest in any Invention or Patent Right.

7.7 No Other Rights. BIOGEN shall receive no rights to Data Sets or
---------------
Clones under CURAGEN Patent Rights or Inventions except as expressly set forth
herein or in an executed License Agreement.

8. TERM AND TERMINATION

8.1 Term. Unless earlier terminated as provided in this Section 8, the
----
term of this Agreement shall be for five (5) years following the Effective Date
plus the length of any available Exclusive Evaluation Periods and any permitted
extensions thereof and the length of

[Confidential Treatment Requested]

<PAGE>

any Options and any permitted extensions thereof, or until the date on which
BIOGEN no longer has access to Project Data Sets, whichever is later (the
"Term").

8.2 Termination.
-----------
(a) This Agreement and the options granted herein may be terminated by
either Party upon any breach by the other Party of any material obligation or
condition, effective thirty (30) days after giving written notice to the
breaching Party of such termination in the case of a payment breach and sixty
(60) days after giving written notice to the breaching Party of such termination
in the case of any other breach, which notice shall describe such breach in
reasonable detail. The foregoing notwithstanding, if the default or breach is
cured or shown to be non-existent within the aforesaid thirty (30) or sixty (60)
day period, the notice shall be deemed automatically withdrawn and of no effect.

(b) If either Party files for protection under bankruptcy laws, makes an
assignment for the benefit of creditors, appoints or suffers appointment of a
receiver or trustee over its property, files a petition under any bankruptcy or
insolvency act or has any such petition filed against it which is not discharged
within sixty (60) days of the filing thereof, then the other Party may terminate
this Agreement by notice to such Party.

8.3 Remedies. If either Party shall fail to perform or observe or
--------
otherwise breaches any of its material obligations under this Agreement, in
addition to any right to terminate this Agreement, the non-defaulting Party may
elect to obtain other relief and remedies available under law.

8.4 Surviving Provisions. Notwithstanding any provision herein to the
--------------------
contrary, the rights and obligations set forth in Sections 2.1.4, 2.1.6 and
2.3.3(b), Articles 4, 5, and 6, Sections 7.6 and 8.4, and Article 9 hereof, as
well as any rights and obligations otherwise accrued, shall survive the
expiration or termination of the Term of this Agreement.

9. MISCELLANEOUS

9.1 CURAGEN Representations and Covenants. CURAGEN represents and
warrants that: (a) the execution and delivery of this Agreement and the
performance of the transactions contemplated hereby have been duly authorized by
all appropriate CURAGEN

27
<PAGE>

corporate action; (b) CURAGEN is under no obligation which is inconsistent with
this Agreement, (c) CURAGEN is not aware of any patent held by any third party
which would prevent CURAGEN's use of its technology in the performance of the
Research Program, and (d) CURAGEN has the full right and legal capacity to grant
the rights to BIOGEN pursuant to Article 7 without violating the rights of any
third party. CURAGEN covenants that (a) CURAGEN will obtain from its employees
and consultants rights of assignment with respect to all Inventions and (b)
CURAGEN will not enter into any agreement with any third party that is
inconsistent with the terms of this Agreement. Nothing in this Agreement shall
be interpreted as obligating either Party to commercialize technology made
hereunder or to perform any additional work beyond that set forth in the
Research Plan.

9.2 BIOGEN Representations. BIOGEN represents and warrants that: (a) the
----------------------
execution and delivery of this Agreement and the performance of the transactions
contemplated hereby have been duly authorized by all appropriate BIOGEN
corporate action; (b) BIOGEN is under no obligation which is inconsistent with
this Agreement, and (c) BIOGEN has the full right and legal capacity to grant
the rights to CURAGEN pursuant to Article 7 without violating the rights of any
third party. Nothing in this Agreement shall be interpreted as obligating either
Party to commercialize technology made hereunder or to perform any additional
work beyond that set forth in the Research Plan.

9.3 No Warranties.
-------------
(a) Nothing in this Agreement is or shall be construed as:

(i) a warranty or representation by CURAGEN as to the
validity or scope of any application or patent within the
Patent Rights;

(ii) a warranty or representation that anything made,
used, sold or otherwise disposed of under any license granted
pursuant to this Agreement is or will be free from infringement
of patents, copyrights, and other rights of third parties,
except as expressly set forth in Section 9.1.

28
<PAGE>

INFRINGEMENT OF ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER RIGHTS, OR ANY OTHER
EXPRESS OR IMPLIED WARRANTIES.

9.4 Liability. NOTWITHSTANDING ANYTHING ELSE IN THIS AGREEMENT OR
---------
OTHERWISE, NEITHER PARTY WILL BE LIABLE WITH RESPECT TO ANY SUBJECT MATTER OF
THIS AGREEMENT UNDER ANY CONTRACT, NEGLIGENCE, STRICT LIABILITY OR OTHER LEGAL
OR EQUITABLE THEORY FOR (I) ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE
DAMAGES OR LOST PROFITS OR (II) COST OF PROCUREMENT OF SUBSTITUTE GOODS,
TECHNOLOGY OR SERVICES

9.5 Notices. Any notices, requests, deliveries, approvals or consents
-------
required or permitted to be given under this Agreement to BIOGEN or CURAGEN
shall be in writing and shall be personally delivered or sent by telecopy (with
written confirmation to follow via United States first class mail), overnight
courier providing evidence of receipt or certified mail, return receipt
requested, postage prepaid, in each case to the respective address specified
below (or to such address as may be specified in writing to the other Party
hereto):

CURAGEN: 555 Long Wharf, 11th Floor
New Haven, CT 06511
Attn: Executive Vice President
Telecopy: (203) 401-3333

BIOGEN: 14 Cambridge Center
Cambridge, MA 02142
Attn: Director, Marketing and Business Development
Telecopy: (617) 679-2804

with copies to: Vice President - General Counsel
Telecopy: (617) 679-2838

Such notices shall be deemed to have been sufficiently given on: (a) the
date sent if delivered in person or transmitted by telecopy, (b) the next
business day after dispatch in the case of overnight courier or (c) five (5)
business days after deposit in the U.S. mail in the case of certified mail.

9.6 Governing Law. This Agreement will be construed, interpreted and
-------------
applied in accordance with the laws of the State of Connecticut (excluding its
body of law controlling conflicts of law).

29
<PAGE>

9.7 Limitations. Except as set forth elsewhere in this Agreement, neither
-----------
Party grants to the other Party any right or license to any of its intellectual
property.

9.8 Entire Agreement. This is the entire Agreement between the Parties
----------------
with respect to the subject matter hereof and supersedes all prior agreements
between the Parties with respect to the subject matter hereof. No modification
shall be effective unless in writing with specific reference to this Agreement
and signed by the Parties.

9.9 Waiver. The terms or conditions of this Agreement may be waived only
------
by a written instrument executed by the Party waiving compliance. The failure of
either Party at any time or times to require performance of any provision hereof
shall in no manner affect its rights at a later time to enforce the same. No
waiver by either Party of any condition or term shall be deemed as a continuing
waiver of such condition or term or of another condition or term.

9.10 Headings. Section and subsection headings are inserted for
--------
convenience of reference only and do not form part of this Agreement.

9.11 Assignment. This Agreement may not be assigned by either Party
----------
without the consent of the other, except that each Party may, without such
consent, assign this Agreement and the rights, obligations and interests of such
Party, in whole or in part, to any of its Affiliates, to any purchaser of all or
substantially all of its assets in the line of business to which this Agreement
pertains or to any successor corporation resulting from any merger or
consolidation of such Party with or into such corporations.

9.12 Force Majeure. Neither Party shall be liable for failure of or delay
-------------
in performing obligations set forth in this Agreement, and neither shall be
deemed in breach of its obligations, if such failure or delay is due to natural
disasters or any causes beyond the reasonable control of such Party. In event of
such force majeure, the Party affected thereby shall use reasonable efforts to
cure or overcome the same and resume performance of its obligations hereunder.

9.13 Construction. The Parties hereto acknowledge and agree that: (i) each
------------
Party and its counsel reviewed and negotiated the terms and provisions of this
Agreement and have contributed to its revision; (ii) the rule of construction to
the effect that any ambiguities are resolved against the drafting Party shall
not be employed in the interpretation of this Agreement; and (iii) the terms and
provisions of this Agreement shall be construed fairly as to all Parties

30
<PAGE>

hereto and not in a favor of or against any Party, regardless of which Party was
generally responsible for the preparation of this Agreement.

9.14 Severability. If any provision(s) of this Agreement are or become
------------
invalid, are ruled illegal by any court of competent jurisdiction or are deemed
unenforceable under then current applicable law from time to time in effect
during the Term hereof, it is the intention of the Parties that the remainder of
this Agreement shall not be affected thereby provided that a Party's rights
under this Agreement are not materially affected. The Parties hereto covenant
and agree to renegotiate any such term, covenant or application thereof in good
faith in order to provide a reasonably acceptable alternative to the term,
covenant or condition of this Agreement or the application thereof that is
invalid, illegal or unenforceable, it being the intent of the Parties that the
basic purposes of this Agreement are to be effectuated.

9.15 Status. Nothing in this Agreement is intended or shall be deemed to
------
constitute a partner, agency, employer-employee, or joint venture relationship
between the Parties.

9.16 Indemnification.
---------------

(a) BIOGEN shall indemnify, defend and hold harmless CURAGEN, its
Affiliates and their respective directors, officers, employees, and agents and
their respective successors, heirs and assigns (the "CURAGEN Indemnitees"),
against any liability, damage, loss or expense (including reasonable attorneys'
fees and expenses of litigation) incurred by or imposed upon the CURAGEN
Indemnitees, or any of them, in connection with any claims, suits, actions,
demands or judgments of third parties, including without limitation personal
injury matters (except to the extent such claims, suits, actions, demands or
judgments result from a material breach of this Agreement, or the negligence or
willful misconduct on the part of CURAGEN or are the subject matter of CURAGEN's
indemnification of BIOGEN as set forth in Section 9.16(b)) arising out of or
relating to any actions of BIOGEN under this Agreement including, without
limitation, the supply of samples for use in the Research Program.

31
<PAGE>

judgments result from a material breach of this Agreement, or the negligence or
willful misconduct on the part of BIOGEN) arising out of the performance of the
Research Program by CURAGEN, except to the extent such claims, suits, actions,
demands or judgments are based on the use of the samples or information provided
to CURAGEN by BIOGEN under this Agreement.

REMAINDER OF PAGE INTENTIONALLY LEFT BLANK

32
<PAGE>

IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed
by their duly authorized representative in two (2) originals.

BIOGEN, INC. CURAGEN CORPORATION

By: By:
/s/ James R. Tobin /s/ Gregory Went
--------------------------------- -----------------------------------
Title: President and CEO Title: Executive Vice President
------------------------------ --------------------------------

33
<PAGE>

APPENDIX A

Optioned Clones

34
<PAGE>

APPENDIX B

Note

35
<PAGE>

PROMISSORY NOTE

Up to $10,000,000.00 __________, 1997

FOR VALUE RECEIVED, the undersigned, CURAGEN CORPORATION (the "Borrower"),
having an address of 555 Long Wharf Drive, 11th Floor, New Haven, Connecticut
06511, hereby promises to pay to BIOGEN, INC., having an address at 14 Cambridge
Center, Cambridge, MA 02142 (the "Lender"), the principal sum of

TEN MILLION DOLLARS ($10,000,000)

or such lesser sum which may from time to time be advanced pursuant to the terms
of the section of the Research and Option Agreement dated October 1, 1997
between the Borrower and the Lender (the "Agreement") entitled "Section 3.2-Loan
Commitment". Capitalized terms used herein and not defined herein have the
meanings assigned to them in the Agreement.

Payments
--------

(a) The Borrower shall pay the accrued interest and principal balance of
this Note, which represents the Loan, in full within [XXXXXXXXXXXX] of the
last day of the Fifth Loan Year, or within [XXXXXXXXX] after any earlier
termination of the Research Program or the Agreement, whichever shall first
occur.

(b) This Note may be prepaid by Borrower at any time without premium or
penalty.

(c) Payments pursuant to paragraph (a) or (b) shall be paid in cash or, at
the option of Borrower, in CuraGen Common Stock, valued at its then Fair Market
Value, as set forth in the Agreement.

Interest
--------

(a) Interest shall accrue on the outstanding principal balance hereunder at
a rate per annum equal to [XXXXXXXXXXXXXXXXXXXXXXXXXXX] shall be determined and
adjusted in accordance with Section 3.2(c) and 3.2(e) of the Agreement. Interest
shall accrue and be paid semi-annually commencing on the six-month anniversary
date of the first advance under the Loan and continuing every six months
thereafter until all amounts due hereunder have been paid in full.

(b) Payments pursuant to paragraph (a) shall be made in cash or, at the
option of Borrower, in CuraGen Common Stock, valued at its then Fair Market
Value, as set forth in the Agreement.

[Confidential Treatment Requested]

<PAGE>

Recording of Advances and Repayments
------------------------------------

The advances described in the Agreement and made by the Lender to the
Borrower, and all repayments made on the account of principal thereof, shall be
recorded by the Lender on the Schedule attached hereto which is a part of this
Note; provided, however, that the failure of the Lender so to record on this
Note (or any error in recording on this Note) shall not affect the Borrower's
obligations hereunder.

Subordination
-------------

This Note shall be Subordinated to [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

General
-------

The Borrower hereby waives presentment, demand, protest or notice of
any kind in connection with this Note. No failure on the part of the Lender in
exercising any right or remedy hereunder, and no single, partial or delayed
exercise by the Lender of any right or remedy shall preclude the full and timely
exercise by the Lender at any time of any right or remedy of the Lender
hereunder without notice. No course of dealing or other conduct, no oral
agreement or representation made by the Lender or usage of trade shall operate
as a waiver of any right or remedy of the Lender. This Note and the Agreement
contain the entire agreement between the parties with respect to the subject
matter hereof, and supersedes every course of dealing, other conduct, oral
agreement or representation previously made by the Lender. In the event that any
court of competent jurisdiction shall determine that any provision, or portion
thereof, contained in this Note shall be unenforceable in any respect, then such
provision shall be deemed limited to the extent that such court deems it
enforceable, and the remaining provisions of this Note shall nevertheless remain
in full force and effect.

None of the terms or provisions of this Note may be excluded, modified, or
amended except by a written instrument duly executed on behalf of both the
Borrower and the Lender expressly referring hereto and setting forth the
provision so excluded, modified or amended. No waiver or forbearance of any of
the rights and remedies of the Lender hereunder shall be effective unless made
specifically in a writing signed by the Lender, and any such waiver or
forbearance shall be effective only in the specific instance and for the
specific purpose for which given.

This Note is the "Note" referred to in the Agreement and is entitled to all
of the rights and benefits referred to therein.

This note is delivered to the Lender at its principal office in
Cambridge, Massachusetts, shall be governed by, and construed and enforced in
accordance with, the laws of the state of

- 2 -

[Confidential Treatment Requested]

<PAGE>

Connecticut, without regard to its principles of conflicts of laws and shall
take effect as a sealed instrument.

IN WITNESS WHEREOF, the Borrower has caused this Note to be executed as an
instrument under seal by its duly authorized officer as of the date first above
written.

Witness: CURAGEN CORPORATION

by:
- ------------------------- -------------------------------
(Signature)

----------------------------
(Print or type name)
its:
----------------------------
(Title or Capacity)

- 3 -
<PAGE>

Schedule to Promissory Note
dated October ___, 1997
from CURAGEN CORPORATION
to BIOGEN, INC.
in the amount of up to $10,000,000

Biogen CuraGen
Date Amount Drawn Amount Repaid Acknowledgement Acknowledgement
- ---- ------ ----- ------ ------ --------------- ---------------
<S> <C> <C> <C> <C>

</TABLE>

- 4 -
<PAGE>

APPENDIX C

Form of License Agreement

40
<PAGE>

LICENSE AGREEMENT

This License Agreement ("Agreement") is made effective as of _________,
_____ (the "Effective Date") by and between BIOGEN, INC., a Massachusetts
corporation having its principal business office at 14 Cambridge Center,
Cambridge, MA 02142 ("BIOGEN"), and CURAGEN CORPORATION, a Delaware corporation
with its principal place of business at 555 Long Wharf Drive, 11th Floor, New
Haven, Connecticut 06511 ("CURAGEN"). BIOGEN and CURAGEN are each hereafter
referred to individually as a "Party" and together as the "Parties".

WHEREAS, BIOGEN wishes to obtain a license to certain inventions made by
CURAGEN as provided in the Research and Option Agreement between the Parties
hereto dated as of _______, 1997 (the "Research Agreement");

WHEREAS, CURAGEN has agreed to provide such license under the terms and
conditions set forth herein.

NOW, THEREFORE, in consideration of the mutual covenants contained herein,
and for other good and valuable consideration, the receipt and adequacy of which
are hereby acknowledged, the Parties hereby agree as follows:

1. DEFINITIONS

Whenever used in the Agreement with an initial capital letter, the terms
defined in this Section 1 shall have the meanings specified.

1
<PAGE>

or any other arrangement whereby a Party controls or has the right to control
the Board of Directors or equivalent governing body of a corporation or other
entity.

1.2 "Clone" shall mean a segment of DNA representing a whole or partial
gene whose sequence or utility is determined from the use of one or more Data
Sets.

1.3 "CURAGEN Background Inventions" shall mean all patent rights and
know-how of CURAGEN, other than those relating primarily to Inventions, which
CURAGEN has the right to license as of the Effective Date or at any time during
the term hereof and which would be infringed by the development, manufacture,
use, sale or importation of a Licensed Product; provided, however, that CURAGEN
Background Inventions shall expressly exclude any patent rights or know-how
specifically relating to Clones or genes not licensed by BIOGEN pursuant to this
Agreement and any patent rights or know-how arising from any CURAGEN
collaboration with a third party, except to the extent permitted thereby.

1.4 "CURAGEN Data" shall mean, with respect to a Licensed Clone, all
information pertaining to such Licensed Clone obtained by CURAGEN from the
processing of specified CURAGEN samples, including QC data, expression data,
sequence data and any other information obtained or generated by CURAGEN in the
performance of the CURAGEN Project relating to such Licensed Clone.

1.5 "CURAGEN Data Set" shall mean all CURAGEN Data resulting from a
discrete CURAGEN Project.

1.6 "CURAGEN Project" shall mean a particular project undertaken by CURAGEN
outside the Research Program to process and analyze a specified set of samples
which do not contain BIOGEN Proprietary Material, and as to which CURAGEN is
free to grant rights to BIOGEN hereunder.

1.7 "CURAGEN Project Invention" shall mean any discovery, invention,
know-how or trade secret conceived or made by employees of CURAGEN (i) in the
performance of a CURAGEN Project that results in CURAGEN Data that becomes part
of an Exclusive Data Set,

2
<PAGE>

that is based on, incorporates or makes material use of the corresponding
CURAGEN Data or (ii) relating to a Lead.

1.8 "CURAGEN Proprietary Material" shall mean, with respect to a Licensed
Clone, all substances made by CURAGEN in the performance of the Research Project
relating to such Licensed Clone other than mRNA pools extracted from BIOGEN
Proprietary Material. CURAGEN Proprietary Material shall also mean, with respect
to a Licensed Clone, all substances made by CURAGEN in the performance of the
CURAGEN Project relating to such Licensed Clone, including mRNA pools. CURAGEN
Proprietary Materials shall include, without limitation, QEA fragments and
materials derived or constructed from QEA fragments, including, without
limitation, fragment and full length cDNA clones.

1.9 "Data Set," which may be either a Project Data Set or a CURAGEN Data
Set, with respect to a Licensed Clone, shall mean all Project Data resulting
from the discrete Research Project relating to the Licensed Clone or all CURAGEN
Data resulting from the discrete CURAGEN Project relating to the Licensed Clone,
respectively.

1.10 [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

1.11 "Exclusive Data Set" shall mean any Project Data Set during the
corresponding Exclusive Evaluation Period as provided in Section 2.4 of the
Research Agreement or any CURAGEN Data Set during the corresponding Exclusive
Evaluation Period as provided in Section 2.5.2 of the Research Agreement.

1.12 "Exclusive Evaluation Period" shall have the meaning set forth in
Section 2.4 or 2.5.2 of the Research Agreement.

1.13 "Extended License" shall have the meaning set forth in Section 2.3.

1.14 "Invention," as to each Licensed Clone, shall mean any CURAGEN Project
Invention or Research Project Invention that is based on, incorporates or makes
material use of the Project Data or CURAGEN Data corresponding to the Licensed
Clone.

[Confidential Treatment Requested]

<PAGE>

1.15 [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXX]

1.16 "Lead" shall mean a lead compound discovered or developed by CURAGEN
outside of the Research Program using a Licensed Clone or the protein expressed
thereby as a target, which lead compound is accepted by BIOGEN for use pursuant
to the terms of this Agreement.

1.17 "Licensed Clone" shall have the meaning set forth in Section 2.1.

1.18 "Licensed Product," as to each Licensed Clone, shall have the meaning
set forth in the relevant subsection of Section 2.1.

1.19 "Net Sales" shall mean [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX.

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXX]

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXX]

1.20 "Optioned Clone" shall have the meaning set forth in Section 7.1 of
the Research Agreement.

1.21 "Patent Rights," as to each Licensed Clone, mean the rights and
interests in and to issued patents and pending patent applications in any
country, including, but not limited to, all provisional applications,
substitutions, continuations, continuations-in-part, divisions, and renewals,
all letters patent granted thereon, and all reissues, reexaminations and
extensions thereof, whether owned solely or jointly by a Party or licensed in by
a Party, with the right to sublicense, now or in the future, wherein at least
one claim of such patent right is to an Invention. "CURAGEN Patent Rights" shall
mean Patent Rights owned solely or jointly by CURAGEN or licensed in by CURAGEN.

1.22 "Project Data" shall mean all information obtained by CURAGEN from the
processing of BIOGEN Proprietary Material in a particular Research Project,
including QC data,

[Confidential Treatment Requested]

<PAGE>

expression data, sequence data and any other information obtained or generated
by CURAGEN in the performance of the Research Project relating to such Licensed
Clone.

1.23 "Project Data Set" shall mean all Project Data resulting from a
discrete Research Project.

1.24 "Research Program" shall mean the Research Program to be performed by
CURAGEN under the Research Agreement.

1.25 "Research Project" shall mean a particular project to process and
analyze a specified set of samples in the Research Program.

1.26 "Research Project Invention" shall mean any discovery, invention,
know-how or trade secret conceived or made by employees of CURAGEN or BIOGEN or
jointly by employees of both, (a) in the performance of a Research Project
hereunder, or (b) in the course of evaluating any Exclusive Data Set, in each
case that is based on, incorporates or makes material inventive use of the
corresponding Project Data or CURAGEN Data.

1.27 "Sublicensee" shall mean any non-Affiliate third party expressly
sublicensed by BIOGEN under the license granted to BIOGEN hereunder, to make,
have made, use, have used, offer to sell, sell, have sold, import or have
imported any Licensed Product.

1.28 "Territory" shall mean the world.

1.29 "Valid Claim(s)" shall mean an unexpired claim of (i) any issued
patent within Patent Rights which has not been finally declared invalid or
unenforceable by a patent office or by a court or other body of competent
jurisdiction in any unappealed or unappealable decision and which has not been
lost through an interference or opposition proceeding or (ii) any pending patent
application within Patent Rights which has not been finally rejected by a patent
office of competent jurisdiction in any unappealed or unappealable decision and
which has not been pending for more than seven (7) years.

6
<PAGE>

2. LICENSE GRANT

2.1. License Grant. Upon exercise of an Option pursuant to Section 7.4 of
-------------
the Research Agreement for any Optioned Clone, BIOGEN shall elect one of the
following license types and the Parties shall indicate such election on Schedule
I attached hereto and shall complete the information on Schedule I for such
Optioned Clone and sign such Schedule I. Such Optioned Clone shall thereafter be
deemed a Licensed Clone. Additionally, upon written request of BIOGEN made
pursuant to Section 7.5 of the Research Agreement for any [XXXXXXXXXXX], BIOGEN
shall elect one of the following license types and the Parties shall indicate
such election on Schedule I attached hereto and shall complete the information
on Schedule I for such [XXXXXXXXXXXXXX] and sign such Schedule I. Such [XXXXXXX
XXXXX] shall thereafter be deemed a Licensed Clone.

(a) For each Licensed Clone listed on Schedule I for which a Section 2.1(a)
exclusive license is elected subject to the rights reserved to CURAGEN in
Section 2.5 below, CURAGEN hereby grants to BIOGEN an exclusive license (even as
to CURAGEN) in the Territory, to develop, make, have made, use, have used, sell,
have sold, offer for sale, import and have imported products (i) incorporating
or derived from such Licensed Clone or the protein expressed thereby, (ii)
discovered or developed using any such Licensed Clone or the protein expressed
thereby as a target or (iii) discovered or developed using a Lead which was
itself discovered or developed using such Licensed Clone or the protein
expressed thereby as a target ("Licensed Products"), for any and all human uses,
under (x) all Patent Rights, Inventions, and CURAGEN Proprietary Material
pertaining to such Licensed Clone or the uses thereof, including but not limited
to Patent Rights claiming whole or partial sequences or utility and (y) all
Patent Rights and know-how of CURAGEN which CURAGEN has the right to license to
BIOGEN relating to Leads discovered or developed using the Licensed Clone or the
protein expressed thereby as a target. Such license shall be perpetual unless
terminated as set forth herein.

(b) For each Licensed Clone listed on Schedule I for which a Section 2.1(b)
exclusive license is elected and which was "known" by third parties prior to the
exercise of the corresponding Option as determined pursuant to subsection (d)
below, subject to the rights reserved to CURAGEN in Section 2.5 below, CURAGEN
hereby grants to BIOGEN an

[Confidential Treatment Requested]

<PAGE>

exclusive license (even as to CURAGEN) in the Territory, to develop, make, have
made, use, have used, sell, have sold, offer for sale, import and have imported
products (i) incorporating or derived from such Licensed Clone or the protein
expressed thereby, (ii) discovered or developed using any such Licensed Clone or
the protein expressed thereby as a target or (iii) discovered or developed using
a Lead which was itself discovered or developed using such Licensed Clone or the
protein expressed thereby as a target ("Licensed Products"), for any and all
human uses, under (x) all Patent Rights, Inventions, and CURAGEN Proprietary
Material pertaining to such Licensed Clone or the uses thereof, including but
not limited to Patent Rights claiming whole or partial sequences or utility and
(y) all Patent Rights and know-how of CURAGEN which CURAGEN has the right to
license to BIOGEN relating to Leads discovered or developed using the Licensed
Clone or the protein expressed thereby as a target. Such license shall be
perpetual unless terminated as set forth herein.

(c) For each Licensed Clone listed on Schedule I for which a Section 2.1(c)
non-exclusive license is elected, CURAGEN hereby grants to BIOGEN a
non-exclusive license in the Territory to use such Licensed Clone or the protein
expressed thereby as a target for discovering or developing small molecule drugs
and to develop, make, have made, use, have used, sell, have sold, offer for
sale, import and have imported any small molecule discovered or developed by
BIOGEN using such Licensed Clone or the protein expressed thereby as a target
("Licensed Products"), for any and all human uses, under all Patent Rights,
Inventions, and CURAGEN Proprietary Materials pertaining to such Licensed Clone
or the uses thereof, including but not limited to Patent Rights claiming whole
or partial sequences or utility. Such license shall be perpetual unless
terminated as set forth herein.

(d) The Parties shall mutually agree in good faith on whether any Licensed
Clone is "known" by third parties prior to the exercise of an Option, based
primarily on the availability of the whole or substantially whole coding domains
identical to such Licensed Clone in publicly available literature or databases.
Licensed Clones which are "known" only as a result of either a previous Research
Project or a CURAGEN Project from which BIOGEN received access to an Exclusive
Data Set from which the Licensed Clone was optioned, and are not "known" to
third

8
<PAGE>

parties other than through any disclosure of research results related to such
Research Project or CURAGEN Project, shall not be deemed "known" for the
purposes hereof.

(e) A Licensed Product will be deemed to be discovered or developed using a
Licensed Clone or the protein expressed thereby as a target if the Licensed
Clone or the whole or partial sequence thereof or the protein expressed thereby
is utilized in any material way in the discovery, development, modification or
testing of the Licensed Product, or of analogs thereof or of molecules used in
the discovery, development or modification thereof.

2.2 Non-exclusive License. CURAGEN hereby grants to BIOGEN a non-exclusive
---------------------
license, coterminus with each license grant in Section 2.1, under CURAGEN
Background Inventions solely to the extent necessary to allow BIOGEN to practice
the license granted in Section 2.1 and for no other purpose.

2.3 Extended License. In the event that (a) CURAGEN is the owner of any
----------------
patent or patent application resulting from any activities other than the
Research Program that claims (i) any Licensed Clone, (ii) the protein expressed
by such Licensed Clone, (iii) any product discovered or developed using any such
Licensed Clone or the protein expressed thereby as a target, or (iv) a human
gene functionally equivalent to such Licensed Clone [XXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] and (b) CURAGEN is not utilizing
the invention or inventions claimed in such patent or application in a research
or development project then being actively planned or conducted by CURAGEN
(alone or in collaboration with any third party), and (c) CURAGEN has the right
to grant a license thereunder to BIOGEN, then any license granted to BIOGEN
under Section 2.1(a) or (b) shall include a license to such patent or patent
applications (an "Extended License").

2.4 Due Diligence. BIOGEN shall use commercially reasonable efforts, at
-------------
least equivalent to those efforts which BIOGEN uses with respect to its own
products, to develop, test, obtain regulatory approval of, market and sell
Licensed Products with respect to each Licensed Clone; provided, however, that
BIOGEN shall not be required hereby to be actively developing [XXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] at any
one time. Failure to use

[Confidential Treatment Requested]

<PAGE>

diligent efforts as set forth herein for a given Licensed Clone shall give
CURAGEN the right, but not the obligation, to terminate BIOGEN's license
hereunder with respect to such Licensed Clone.

2.5 Reservation of Rights. Notwithstanding anything in this Agreement to
---------------------
the contrary, CURAGEN hereby retains for itself the right to use each Licensed
Clone and the proteins derived therefrom for as part of a general library of
nucleic acids, which library is used for research purposes.

2.6 Sublicenses. BIOGEN shall have the right to grant sublicenses to all or
-----------
any portion of its rights under any license granted herein to any Affiliate or
Sublicensee, provided, however, that BIOGEN shall remain obligated to ensure
payment of royalty and milestone obligations as set forth in Article 3.

3. CONSIDERATION

3.1 License Fees. Upon exercise of an Option pursuant to Section 7.1.2 of
------------
the Research Agreement for any Optioned Clone, BIOGEN shall pay to CURAGEN the
license fee specified in the Research Agreement which shall be as set forth
below:
<TABLE>
<CAPTION>

License Type $ (thousands)
------------ -------------
<S> <C>
Exclusive license under Section 2.1(a) [XXX]
Exclusive license under Section 2.1(b) [XXX]
Non-exclusive license under Section 2.1(c) [XXX]
</TABLE>

No license fees shall be due with respect to [XXXXXXXXXXXX] licensed during the
Exclusive Evaluation Period of the [XXXX] [XXXXXX]. Additionally, [XXXXXXXX]
fees shall be due with respect to the [XXXXXXXXX] Optioned Clones which are
licensed hereunder.

3.2 Milestone Payments for Therapeutic or Prophylactic Products.
-----------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

3.2.1 Milestone Payments under Exclusive License. BIOGEN shall make the
------------------------------------------
following milestone payments to CURAGEN for each therapeutic or prophylactic
Licensed Product under an exclusive license under Section 2.1(a) or Section
2.1(b):

(a) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days following
the date BIOGEN or an Affiliate or Sublicensee files the first
Investigational New Drug application (or foreign equivalent) with the
FDA (or equivalent foreign regulatory agency) for the Licensed
Product ("IND");

(b) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days following
the date BIOGEN or an Affiliate or Sublicensee commences the first
Phase III or Phase II/III clinical trial in any country for the
Licensed Product;

(c) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days following
the date BIOGEN or an Affiliate or Sublicensee submits the first
Biologics License Application, Product License Application, New Drug
Application or other application for approval to sell the Licensed
Product to the FDA (or equivalent foreign regulatory agency) for the
Licensed Product;

(d) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days following
the date BIOGEN or an Affiliate or Sublicensee receives FDA (or
equivalent foreign regulatory agency) approval of the Licensed
Product for commercial sale; and

(e) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within
forty-five (45) days following the end of the first calendar year in
which annual gross sales of such Licensed Product exceed [XXXXX
XXXXXXXX] provided that such event has occurred prior to the end of
the fifth full calendar year following first commercial sale in the
United States or Europe of such Licensed Product.

3.2.2 Milestone Payments under Non-exclusive License. BIOGEN shall make the
----------------------------------------------
following milestone payments to CURAGEN for each therapeutic or prophylactic
Licensed Product covered by a non-exclusive license under Section 2.1(c):

[Confidential Treatment Requested]

<PAGE>

(a) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10)
days following the date BIOGEN or an Affiliate or Sublicensee files
the first Investigational New Drug application (or foreign
equivalent) with the FDA (or equivalent foreign regulatory agency)
for the Licensed Product ("IND");

(b) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days
following the date BIOGEN or an Affiliate or Sublicensee commences
the first Phase III or Phase II/III clinical trial in any country for
the Licensed Product;

(c) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10)
days following the date BIOGEN or an Affiliate or Sublicensee submits
the first Biologics License Application, Product License Application,
NDA or other application for approval to sell the Licensed Product to
the FDA (or equivalent foreign regulatory agency) for the Licensed
Product;

(d) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days following
the date BIOGEN or an Affiliate or Sublicensee receives FDA (or
equivalent foreign regulatory agency) approval of the Licensed
Product for commercial sale; and

(e) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10) days following
the end of the first calendar year in which annual gross sales of
such Licensed Product exceed [XXXXXXXXXXX] provided that such event
has occurred prior to the end of the fifth full calendar year
following first commercial sale in the United States or Europe of
such Licensed Product.

3.2.3 [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
[XXXXXXXXXXXXXXX]

3.3 Milestone Payments for Diagnostic Products. BIOGEN shall make the
------------------------------------------
following milestone payment to CURAGEN for each diagnostic Licensed Product
under an exclusive license under Section 2.1(a) or Section 2.1(b):

[Confidential Treatment Requested]

<PAGE>

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] within ten (10)
days following the date BIOGEN or an Affiliate or Sublicensee
receives FDA (or equivalent foreign regulatory agency)
approval of the Licensed Product for commercial sale.

Notwithstanding the foregoing, the milestone payment set forth above shall
not be due with respect to any Licensed Product with a substantially similar
purpose and format to one for which such milestone has already been paid to
CURAGEN.

3.4 Royalties on Licensed Products from Research Project Inventions.
---------------------------------------------------------------
BIOGEN shall pay to CURAGEN a royalty on Net Sales of Licensed Products if the
sequence and/or utility of the relevant Licensed Clone is a Research Project
Invention or if the Licensed Product results from a Research Project Invention
or a Lead using a Licensed Clone which is a Research Project Invention as
follows:

(a) If the Licensed Product is: (1) a recombinant protein form of a
naturally occurring protein or a modified form or fragment thereof ("Protein
Product"), (2) a product involving insertion of nucleic acid into a human host
in order to induce cells in such host to express the protein encoded by such
nucleic acid for therapeutic benefit, or a product involving ex vivo insertion
of nucleic acid into human cells where such cells are then reimplanted into a
human to express the protein encoded by such nucleic acid for therapeutic
benefit ("Gene Therapy Product"), (3) a product designed to activate the
expression of an endogenous gene ("Gene Activation Product"), (4) a product
which is an oligonucleotide which binds to mRNA in vivo to inhibit or block
-------
protein production ("Anti-sense/ribozyme Product"), or (5) an antibody to the
protein encoded by a Licensed Clone ("Antibody Product"), the royalty rate on
Net Sales of such Licensed Product shall be as follows:

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXX]

(b) If the Licensed Product is a small molecule discovered or developed
using a Licensed Clone or the protein expressed thereby as a target, which
target is non-exclusively licensed by BIOGEN pursuant to the provisions of
Section 2.1(c), the royalty rate on Net Sales of such Licensed Product shall be:

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

such Licensed Product shall be negotiated in good faith by the Parties prior to
the commencement of pre-clinical regulatory testing of such Licensed Product;
provided, however, that in no event shall the negotiated royalty rates be less
than those set forth in Section 3.4(b) above.

(d) If the Licensed Product is derived from, or is a chemical, structural
or functional analog of, a Lead identified by CURAGEN and provided to BIOGEN
pursuant to an exclusive license granted pursuant to the provisions of Section
2.1 (a) or (b), the royalty rate on Net Sales of such Licensed Product shall be:

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

(e) If the Licensed Product is a diagnostic product or any product other
than one whose royalty rate is set forth in Section 3.4(a), (b), (c) or (d)
above, then the royalty rate on Net Sales of such Licensed Product shall be:

2% if covered by a Valid Claim of a CURAGEN Patent Right;

[Confidential Treatment Requested]

<PAGE>

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXX]

Notwithstanding the foregoing, in no event shall BIOGEN be obligated
pursuant to this subsection (e) to pay to CURAGEN more than [XXXXXXXXXXXXXXXXX]
of the running royalties received by BIOGEN or its Affiliates from a Sublicensee
with respect to any such Licensed Product.

(f) Royalties due to CURAGEN pursuant to subsections (a), (b), (c), (d)
or (e) above for a given Licensed Product [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] may be reduced by (i) [XXXXXXXXXXXXXXXXX] of
any royalties paid to third parties by BIOGEN on net sales of such Licensed
Product under licenses that are required [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] and
(ii) [XXXXXXXXXXXXX] of any royalties in excess of a total of [XXXXXXXXXX
XXXX] paid to third parties by BIOGEN on net sales of such Licensed Product
under licenses [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]. Royalties due
to CURAGEN pursuant to subsections (a), (b), (c), (d) or (e) above for a given
Licensed Product [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] of any royalties paid to third parties by
BIOGEN on net sales of such Licensed Product under licenses [XXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]. [XXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

3.5 Royalties on Licensed Products from CURAGEN Project Inventions.
--------------------------------------------------------------
BIOGEN shall pay to CURAGEN a royalty on Net Sales of Licensed Products if (i)
the sequence and/or utility of the relevant Licensed Clone is a CURAGEN Project
Invention or if the Licensed Product results from a CURAGEN Project Invention or
a Lead developed using a Licensed Clone which is a CURAGEN Project Invention, or
(ii) the manufacture, use or sale of the Licensed Product is covered by an
Extended License, as follows:

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX]

[Confidential Treatment Requested]

<PAGE>

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXX]

(c) If the Licensed Product is a small molecule discovered or developed
using a Licensed Clone or the protein expressed thereby as a target (and is not
derived from, or a chemical, structural or functional analog of, a Lead), which
target is exclusively licensed by BIOGEN pursuant to the provisions of Sections
2.1(a) or (b), the royalty rate on Net Sales of such Licensed Product shall be
negotiated in good faith by the Parties prior to the commencement of
pre-clinical regulatory testing of such Licensed Product; provided, however,
that in no event shall the negotiated royalty rates be less than those set forth
in Section 3.5(b) above.

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXX]

[Confidential Treatment Requested]

<PAGE>

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXX

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

(e) If the Licensed Product is a diagnostic product or any product other
than one whose royalty rate is set forth in Section 3.5(a), (b), (c) or (d)
above, then the royalty rate on Net Sales of such Licensed Product shall be:

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

(e) above for a given Licensed Product [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] of any royalties paid
to third parties by BIOGEN on net sales of such Licensed Product under licenses
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX]

3.6 One Royalty. Only one royalty, calculated at the highest applicable
-----------
royalty rate hereunder, shall be payable to CURAGEN hereunder for each sale of a
Licensed Product.

3.7 Payment Terms.
-------------
(a) Royalty payments shall be made to CURAGEN in United States Dollars
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXX] Each royalty payment shall be accompanied by a
report summarizing the total Net Sales for each Licensed Product [XXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXX]

(b) All royalties shall be payable in full in the United States in United
States Dollars, regardless of the countries in which sales are made. For the
purpose of computing Net Sales for Licensed Products sold in a currency other
than United States dollars, such currency shall be converted into United States
dollars at the exchange rate for buying U.S. dollars set forth in The Wall
--------
Street Journal for the last business day of the calendar quarter.
- --------------

3.8 Royalty Term. BIOGEN shall pay royalties with respect to each
------------
Licensed Product on a country by country basis until [XXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] Following such
period, BIOGEN shall have a fully paid-up, irrevocable license in such country
under the relevant Patent Rights and Inventions and CURAGEN Background
Inventions, to make, have made, use,

[Confidential Treatment Requested]

<PAGE>

have used, sell, have sold, offer for sale, import and have imported such
Licensed Product in such country.

3.9 Overdue Royalties. Royalties not paid within the time period set
-----------------
forth in this Article 3 shall bear interest at a rate of [XXXXXXXXXXXXXXXXXX
XXXXXXX] from the due date until paid in full.

3.10 Records Retention. Audits. BIOGEN, its Affiliates and Sublicensees
-------------------------
shall keep for three (3) years from the date of each payment of royalties
complete and accurate records of sales by BIOGEN and its Affiliates and
Sublicensees of each Licensed Product in sufficient detail to allow the accruing
royalties to be determined accurately. CURAGEN shall have the right for a period
of three (3) years after receiving any report or statement with respect to
royalties due and payable to appoint an independent certified public accountant
reasonably acceptable to BIOGEN to inspect the relevant records of BIOGEN and
its Affiliates and Sublicensees to verify such report or statement. BIOGEN and
its Affiliates and Sublicensees shall each make its records available for
inspection by such independent certified public accountant during regular
business hours at such place or places where such records are customarily kept,
upon reasonable notice from CURAGEN, solely to verify the accuracy of the
reports and payments. Such inspection right shall not be exercised more than
once in any calendar year nor more than once with respect to sales of any
Licensed Product in any given payment period. CURAGEN agrees to hold in strict
confidence all information concerning royalty payments and reports, and all
information learned in the course of any audit or inspection, except to the
extent necessary for CURAGEN to reveal such information in order to enforce its
rights under this Agreement or if disclosure is required by law, regulation or
judicial order. The results of each inspection, if any, shall be binding on both
Parties. CURAGEN shall pay for such inspections, except that in the event there
is any upward adjustment in aggregate royalties payable for any year shown by
such inspection of more than [XXXXXXXXXXXXXX] of the amount paid, BIOGEN shall
pay for such inspection.

3.11 Tax Withholding. CURAGEN agrees that any tax burden levied by any
---------------
countries foreign to the United States covered by this Agreement on receipt by
CURAGEN of royalties from BIOGEN under this Agreement shall be borne by CURAGEN.
In the event that

[Confidential Treatment Requested]

<PAGE>

such tax is required to be withheld by BIOGEN, its Affiliates, licensees or
Sublicensees, it shall deliver to CURAGEN a statement including the amount of
tax withheld and justification therefor, and such other information as may be
necessary for United States foreign tax credit purposes.

4. TREATMENT OF CONFIDENTIAL INFORMATION

4.1 Confidential Information. During the term of this Agreement, each
------------------------
Party may disclose to the other proprietary technical and business information
(collectively, "Confidential Information"). For a period of [XXXXXXXXXX] after
the receipt of any such Confidential Information, the receiving Party shall keep
confidential all such Confidential Information of the other Party and will not
disclose such Confidential Information of the other Party to third parties by
publication or otherwise. Each Party further agrees not to use Confidential
Information of the other Party for any purpose other than exercising any rights
granted to it or reserved by it hereunder. Notwithstanding the foregoing, it is
understood and agreed that the receiving Party's obligations of confidentiality
and nonuse herein shall not apply to any information which:

(a) is, at the time of disclosure by the disclosing Party
hereunder, or thereafter becomes, a part of the public domain or
publicly known or available through no fault or negligence of the
receiving Party or any of its Affiliates; or

(b) was otherwise in the receiving Party's lawful possession prior
to disclosure by the disclosing Party, as demonstrated by the
receiving Party's written records; or

4.2 Press Release and Regulatory Filings. The Parties shall mutually
------------------------------------
agree on a press release announcing the execution of this Agreement and on any
confidential treatment request to be filed with the Securities and Exchange
Commission with respect to this Agreement.

[Confidential Treatment Requested]

<PAGE>

Once any written statement is approved for disclosure by both Parties, either
Party may make subsequent public disclosures of the contents of such statement
without the further approval of the other Party.

5. PROVISIONS CONCERNING THE FILING, PROSECUTION AND
MAINTENANCE OF PATENT RIGHTS

5.1 Patent Filing. During the term of this Agreement, with respect to any
-------------
Patent Rights or Inventions licensed hereunder:

(a) Upon inclusion of a Licensed Clone or Lead under the terms of this
Agreement, CURAGEN and BIOGEN shall meet to discuss the feasibility of filing
requests for divisional patent applications in order to create Patent Rights
relating solely to Licensed Clones or Leads which are exclusively licensed
hereunder and not to other Clones or Inventions. CURAGEN shall cause such
actions to be taken if the Parties reasonably agree that such actions are
feasible and desirable.

(b) BIOGEN shall have the right to prepare, file, prosecute, obtain and
maintain, at its expense, all Patent Rights relating solely to Licensed Clones
or Leads which are exclusively licensed hereunder. CURAGEN agrees to provide
reasonable assistance and cooperation to BIOGEN to facilitate such filing,
prosecution and maintenance. BIOGEN agrees that any such preparation, filing,
prosecution and maintenance shall be conducted with reasonable diligence and
that CURAGEN shall be kept fully informed of the progress thereof and provided
with copies of all material documents pertaining thereto. CURAGEN shall,
whenever possible, be given the opportunity to review and comment in advance on
any patent filings or other correspondence with the patent office during such
periods and BIOGEN shall consider incorporating any comments provided by CURAGEN
in good faith.

(c) Except as provided in (b) above, CURAGEN shall have the first right
(but not the obligation) to prepare, file, prosecute, obtain and maintain patent
applications and patents on Inventions relating to the Licensed Clones or Leads
which are licensed hereunder at its sole expense. BIOGEN agrees to provide
reasonable assistance and cooperation to CURAGEN to

23
<PAGE>

facilitate such filing, prosecution and maintenance. CURAGEN agrees that any
such preparation, filing, prosecution and maintenance shall be conducted with
reasonable diligence and that BIOGEN shall be kept fully informed of the
progress thereof and provided with copies of all material documents pertaining
thereto during the term of this agreement. BIOGEN shall, whenever possible, be
given the opportunity to review and comment in advance on any patent filings or
other correspondence with the patent office during such periods and CURAGEN
shall consider incorporating any comments provided by BIOGEN in good faith.

(d) CURAGEN may elect not to exercise its first right to prepare, file,
prosecute, obtain and maintain patent applications and patents on Inventions as
described in Section 5.1(c) above at any time for any such patent applications
and patents by giving written notice thereof to BIOGEN. Such notice shall
specifically identify the patent application(s) and/or patent(s) for which
CURAGEN wishes to relinquish such first right. Following the receipt of such
notice, BIOGEN shall have the right to prepare, file, prosecute, obtain and
maintain the patent application(s) and patent(s) identified in the notice, at
its sole expense, on behalf of the owner of the Invention, subject to the rights
granted herein, during the term of this Agreement.

(e) The Parties shall mutually agree before permitting any patent
application or patent within Patent Rights exclusively licensed hereunder to
lapse as well as before authorizing any amendment to any patent application or
patent within such Patent Rights that would irrevocably limit the lawful scope
of the Patent Rights.

(f) BIOGEN may elect not to exercise its right to prepare, file, prosecute,
obtain and maintain patent applications and patents on Inventions or Leads as
described in Section 5.1(b) above at any time for any such Patent Rights by
giving written notice thereof to CURAGEN. Such notice shall specifically
identify the patent application(s) and/or patent(s) for which BIOGEN wishes to
relinquish such right. Following the receipt of such notice, CURAGEN shall have
the right to prepare, file, prosecute, obtain and maintain the patent
application(s) and patent(s) identified in the notice, at its sole expense, and
CURAGEN shall thereafter be deemed the sole owner of any such application or
patent, and any such patents and patent applications shall be removed from
operation of this Agreement.

(g) No Party shall have any obligation under this Agreement to pay any fees
or costs: (i) for bringing a lawsuit or other action to enforce any of the
Patent Rights against an actual or

24
<PAGE>

suspected infringement or (ii) for any other Party to obtain for its own benefit
independent business or legal advice concerning any of the Patent Rights.

5.2 Notice of Infringement. If, during the term of this Agreement or the
----------------------
term of any license hereunder, either Party learns of any infringement or
threatened infringement by a third party of the patents within Patent Rights,
such Party shall promptly notify the other Party and shall provide such other
Party with available evidence of such infringement.

5.3 Infringement. BIOGEN shall have the first right (but not the
------------
obligation), at its own expense, to bring suit (or other appropriate legal
action) against any actual or suspected infringement of the Patent Rights
licensed hereunder provided that BIOGEN has an exclusive license to the
infringed claim(s) of any such Patent Right pursuant to Article 2. If BIOGEN
does not take such action within one hundred twenty (120) days after written
notice from CURAGEN of the infringement, CURAGEN shall have the right (but not
the obligation), at its own expense, to bring suit against such infringement.
Any amount recovered, whether by judgment or settlement, shall first be applied
to reimburse the costs and expenses (including attorneys' fees) of the Party
bringing suit, then to the costs and expenses (including attorneys' fees), if
any, of the other Party. Any amounts remaining shall be allocated [XXXXXXXXXXX
XXXXXX] to the Party bringing suit and [XXXXXXXXXX] to the other Party or
shall be allocated one-half to each Party if the suit is brought jointly.

5.4 Cooperation. Each Party shall, at the expense of the other Party,
-----------
execute all papers and perform such other acts as may be reasonably required to
maintain any infringement suit brought in accordance with Section 5.3 above
(including giving legal consent for bringing such suit, and agreeing to be named
as a plaintiff or otherwise joined in such suit), and at its option and expense,
may be represented in such suit by counsel of its choice.

6. TERM AND TERMINATION

6.1. Termination Provisions.
----------------------
(a) This Agreement and the licenses granted herein may be terminated by
CURAGEN upon any breach by BIOGEN of any material obligation or condition,
effective thirty (30) days

[Confidential Treatment Requested]

<PAGE>

after giving written notice to BIOGEN of such termination in the case of a
payment breach and sixty (60) days after giving written notice to BIOGEN of such
termination in the case of any other breach, which notice shall describe such
breach in reasonable detail; provided, however, that a breach of Section 2.4
shall only give rise to the termination rights specified therein. The foregoing
notwithstanding, if the default or breach is cured or shown to be non-existent
within the aforesaid thirty (30) or sixty (60) day period, the notice shall be
deemed automatically withdrawn and of no effect.

6.2 Effect of Termination.
---------------------

(a) Upon termination of this Agreement under Section 6.1, all relevant
licenses and sublicenses granted by CURAGEN to BIOGEN hereunder shall terminate
automatically and BIOGEN shall promptly transfer to CURAGEN all related Licensed
Clones, Leads, Data Sets and CURAGEN Proprietary Material in its possession
without retaining any copies thereof, as well as any full-length sequence data
relating to such Licensed Clone(s) and a summary of any safety information
generated by or at the direction of BIOGEN with respect to products derived from
such Licensed Clone(s) or Leads. In addition, upon any termination pursuant to
Section 6.1(a), BIOGEN shall be deemed without any further action to have
granted to CURAGEN an exclusive, worldwide, royalty-free license (including the
right to grant sublicenses), under BIOGEN's ownership interest in any Inventions
and Patent Rights covering or related to the relevant Licensed Clone(s) or Leads
to develop, have developed, make, have made, use, have used, offer for sale,
sell, have sold, import and have imported any and all products in all fields.

(b) Documentation. At the request of CURAGEN, BIOGEN shall execute and
-------------
deliver such bills of sale, assignments and licenses and other documents, if
any, as may be

26
<PAGE>

necessary to fully vest in CURAGEN all right, title and interest to which it is
entitled as aforesaid pursuant to this Section 6.2.

(c) Payment Obligations. BIOGEN shall have no obligation to make any
milestone or royalty payment to CURAGEN that has not accrued prior to the
effective date of such termination, but shall remain liable for all obligations
accruing prior to termination.

6.3 Termination by BIOGEN. BIOGEN may terminate this Agreement, and the
---------------------
rights and obligations hereunder, or may remove any Licensed Clone and the
licenses related thereto from operation of this Agreement, in its sole
discretion at any time by giving written notice thereof to CURAGEN. Such
termination shall be effective [XXXXXXXXXXXXXXXX] following the date such notice
is received by CURAGEN and shall have all consequences as set forth in Section
6.2 above, but only with respect to the specified Licensed Clone(s), as if this
Agreement had been terminated pursuant to Section 6.1(a).

6.4 Remedies. If either Party shall fail to perform or observe or otherwise
--------
breaches any of its material obligations under this Agreement, in addition to
any right to terminate this Agreement, the non-defaulting Party may elect to
obtain other relief and remedies available under law.

6.5 Surviving Provisions. Notwithstanding any provision herein to the
--------------------
contrary, the rights and obligations set forth in Article 4, Sections 6.2 and
6.4, and Article 7 hereof, as well as any rights or obligations otherwise
accrued, shall survive the expiration or termination of the term of this
Agreement.

7. MISCELLANEOUS

7.1 CURAGEN Representations. CURAGEN represents and warrants that: (a) the
-----------------------
execution and delivery of this Agreement and the performance of the transactions
contemplated hereby have been duly authorized by all appropriate CURAGEN
corporate action; (b) CURAGEN is under no obligation which is inconsistent with
this Agreement; and (c) CURAGEN has the full right and legal capacity to grant
the rights to BIOGEN pursuant to Article 2 above without violating the rights of
any third party.

[Confidential Treatment Requested]

<PAGE>

7.2 BIOGEN Representations. BIOGEN represents and warrants that: (a) the
----------------------
execution and delivery of this Agreement and the performance of the transactions
contemplated hereby have been duly authorized by all appropriate BIOGEN
corporate action; and (b) BIOGEN is under no obligation which is inconsistent
with this Agreement.

7.3 No Warranties.
-------------
(a) Nothing in this Agreement is or shall be construed as:

(i) a warranty or representation by CURAGEN as to the validity or
scope of any application or patent within the Patent Rights;

(ii) a warranty or representation that anything made, used, sold or
otherwise disposed of under any license granted in this Agreement is
or will be free from infringement of patents, copyrights, and other
rights of third parties.

(b) Except as expressly set forth in this Agreement, NEITHER PARTY MAKES
ANY REPRESENTATIONS OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR
IMPLIED. THERE ARE NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE, THAT ANY LICENSED PRODUCT WILL BE SUCCESSFULLY
DEVELOPED OR MARKETED, OR THAT THE DEVELOPMENT, MANUFACTURE, SALE, IMPORTATION
OR USE OF THE LICENSED PRODUCT(S) WILL NOT INFRINGE ANY PATENT, COPYRIGHT,
TRADEMARK, OR OTHER RIGHTS, OR ANY OTHER EXPRESS OR IMPLIED WARRANTIES.

7.4 Liability. NOTWITHSTANDING ANYTHING ELSE IN THIS AGREEMENT OR
---------
OTHERWISE, NEITHER PARTY WILL BE LIABLE WITH RESPECT TO ANY SUBJECT MATTER OF
THIS AGREEMENT UNDER ANY CONTRACT, NEGLIGENCE, STRICT LIABILITY OR OTHER LEGAL
OR EQUITABLE THEORY FOR (I) ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE
DAMAGES OR LOST

28
<PAGE>

PROFITS OR (II) COST OF PROCUREMENT OF SUBSTITUTE GOODS, TECHNOLOGY OR SERVICES

7.5 Notices. Any notices, requests, deliveries, approvals or consents
-------
required or permitted to be given under this Agreement to BIOGEN or CURAGEN
shall be in writing and shall be personally delivered or sent by telecopy (with
written confirmation to follow via United States first class mail), overnight
courier providing evidence of receipt or certified mail, return receipt
requested, postage prepaid, in each case to the respective address specified
below (or to such address as may be specified in writing to the other Party
hereto):

CURAGEN: 555 Long Wharf, 11th Floor
New Haven, CT 06511
Attn: Executive Vice President
Telecopy: (203) 401-3333

BIOGEN: 14 Cambridge Center
Cambridge, MA 02142
Attn: Director, Marketing and Business Development
Telecopy: (617) 679-2804

with copies to: Vice President - General Counsel
Telecopy: (617) 679-2838

7.6 Governing Law. This Agreement will be construed, interpreted and
-------------
applied in accordance with the laws of the State of Connecticut (excluding its
body of law controlling conflicts of law).

7.7 Limitations. Except as set forth elsewhere in this Agreement, neither
-----------
Party grants to the other Party any right or license to any of its intellectual
property.

29
<PAGE>

7.8 Entire Agreement. This is the entire Agreement between the Parties with
----------------
respect to the subject matter herein. No modification shall be effective unless
in writing and signed by the Parties.

7.9 Waiver. The terms or conditions of this Agreement may be waived only by
------
a written instrument executed by the Party waiving compliance. The failure of
either Party at any time or times to require performance of any provision hereof
shall in no manner affect its rights at a later time to enforce the same. No
waiver by either Party of any condition or term shall be deemed as a continuing
waiver of such condition or term or of another condition or term.

7.10 Headings. Section and subsection headings are inserted for convenience
--------
of reference only and do not form part of this Agreement.

7.11 Assignment. This Agreement may not be assigned by either Party without
----------
the consent of the other, except that each Party may, without such consent,
assign this Agreement and the rights, obligations and interests of such Party,
in whole or in part, to any of its Affiliates, to any purchaser of all or
substantially all of its assets in the line of business to which this Agreement
pertains or to any successor corporation resulting from any merger or
consolidation of such Party with or into such corporations.

7.12 Force Majeure. Neither Party shall be liable for failure of or delay
-------------
in performing obligations set forth in this Agreement, and neither shall be
deemed in breach of its obligations, if such failure or delay is due to natural
disasters or any causes beyond the reasonable control of such Party. In event of
such force majeure, the Party affected thereby shall use reasonable efforts to
cure or overcome the same and resume performance of its obligations hereunder.

7.13 Construction. The Parties hereto acknowledge and agree that: (i) each
------------
Party and its counsel reviewed and negotiated the terms and provisions of this
Agreement and have contributed to its revision; (ii) the rule of construction to
the effect that any ambiguities are resolved against the drafting Party shall
not be employed in the interpretation of this Agreement; and (iii) the terms and
provisions of this Agreement shall be construed fairly as to all Parties

30
<PAGE>

hereto and not in a favor of or against any Party, regardless of which Party was
generally responsible for the preparation of this Agreement.

7.14 Severability. If any provision(s) of this Agreement are or become
------------
invalid, are ruled illegal by any court of competent jurisdiction or are deemed
unenforceable under then current applicable law from time to time in effect
during the term hereof, it is the intention of the Parties that the remainder of
this Agreement shall not be affected thereby provided that a Party's rights
under this Agreement are not materially affected. The Parties hereto covenant
and agree to renegotiate any such term, covenant or application thereof in good
faith in order to provide a reasonably acceptable alternative to the term,
covenant or condition of this Agreement or the application thereof that is
invalid, illegal or unenforceable, it being the intent of the Parties that the
basic purposes of this Agreement are to be effectuated.

7.15 Status. Nothing in this Agreement is intended or shall be deemed to
------
constitute a partner, agency, employer-employee, or joint venture relationship
between the Parties.

7.16 Indemnification.
---------------

(a) BIOGEN shall indemnify, defend and hold harmless CURAGEN, its
Affiliates and their respective directors, officers, employees, and agents and
their respective successors, heirs and assigns (the "CURAGEN Indemnitees"),
against any liability, damage, loss or expense (including reasonable attorneys'
fees and expenses of litigation) incurred by or imposed upon the CURAGEN
Indemnitees, or any of them, in connection with any claims, suits, actions,
demands or judgments of third parties, including without limitation personal
injury and product liability matters (except to the extent that such claims,
suits, actions, demands or judgments result from a material breach of this
Agreement, or the negligence or willful misconduct on the part of CURAGEN or are
the subject matter of CURAGEN'S indemnification of BIOGEN as set forth in
Section 7.16(b)) arising out of or relating to any actions of BIOGEN or any
Affiliate, licensee, sublicensee, distributor or agent of BIOGEN in the
development, testing, production, manufacture, promotion, import, sale or use by
any person of any Licensed Product manufactured or sold by BIOGEN or by an
Affiliate, licensee, sublicensee, distributor or agent of BIOGEN.

31
<PAGE>

(b) CURAGEN shall indemnify, defend and hold harmless BIOGEN, its
Affiliates and their respective directors, officers, employees, and agents and
their respective successors, heirs and assigns (the "BIOGEN Indemnitees"),
against any liability, damage, loss or expense (including reasonable attorneys'
fees and expenses of litigation) incurred by or imposed upon the BIOGEN
Indemnitees, or any of them, in connection with any claims, suits, actions,
demands or judgments of third parties, including without limitation personal
injury matters (except to the extent that such claims, suits, actions, demands
or judgments result from a material breach of this Agreement, or the negligence
or willful misconduct on the part of BIOGEN) arising directly out of the use by
BIOGEN or CURAGEN of CURAGEN'S technology under the Research Agreement, except
to the extent such claims, suits, actions, demands or judgments are based on the
use of the samples or information provided to CURAGEN by BIOGEN under the
Research Agreement.

32
<PAGE>

IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed
by their duly authorized representative in two (2) originals.

BIOGEN, INC. CURAGEN CORPORATION

By: By:
------------------------------ ------------------------------

Title: Title:
----------------------------- -----------------------------

33
<PAGE>

SCHEDULE I
(To be completed for each Licensed Clone)

Licensed Clone:
- ---------------

Type of License:
- ----------------

Project Data Set
- ----------------
or
- --
CURAGEN Data Set
- ----------------
Pertaining to Licensed Clone:
- -----------------------------

CURAGEN Proprietary
- -------------------
Material Pertaining to
- ----------------------
Licensed Clone:
- ---------------

CURAGEN Patent Rights
- ---------------------
Pertaining to Licensed Clone:
- -----------------------------

Rights under
- ------------
Extended License:
- -----------------

Signed this day of
------ -------------, -----
CURAGEN CORPORATION

By:
--------------------------------------
Name:
Title:

BIOGEN, INC.

By:
--------------------------------------
Name:
Title:

34
<PAGE>

APPENDIX D
----------

Terms of Subscription Agreements

QEA/Gene Calling
- ----------------

Subscriber will receive secure access to CuraGen's QEA/GeneCalling subscription
database through the GeneScape( data base and software. Access will be provided
for up to [XXX] users on equipment to be provided by Subscriber.

CURAGEN will support and maintain the software provided for such access and will
use commercially reasonable efforts to update and maintain the database and to
keep it reasonably available for use.

Options and Licenses to clones identified using the database shall be provided
on terms substantially similar to those contained in this Agreement and the
License Agreement.

MIM/Path Calling
- ----------------

Subscriber will receive access to the MIM/PathCalling database through the
GeneScape(R) data base and software. Access will be provided for up to [XXX]
users on equipment to be provided by Subscriber.

CURAGEN will support and maintain the software provided for such access and will
use commercially reasonable efforts to update and maintain the database and to
keep it reasonably available for use.

Options and Licenses to clones identified using the database shall be provided
on terms substantially similar to those contained in this Agreement and the
License Agreement.

GeneTools
- ---------

Pursuant to any subscription agreement as described above Subscriber will also
receive secure access to the GeneTools database through the GeneScape(R)
software. Access will be provided for up to [XXX] users on equipment to be
provided by Subscriber.

[Confidential Treatment Requested]

<PAGE>

Exhibit 10.15

CuraGen Corporation has omitted from this Exhibit 10.15 portions of the
Agreement for which CuraGen Corporation has requested confidential treatment
from the Securities and Exchange Commission. The portions of the Agreement for
which confidential treatment has been requested are marked with X's in brackets
and such confidential portions have been filed separately with the Securities
and Exchange Commission.

1. SUPERCEDES AWARD NOTICE dated ____________________

Restrictions previously imposed remain in effect unless specifically rescinded

- --------------------------------------------------------------------------------
4. PLANT NO 5. ADMINISTRATIVE CODES
5 RO1 HGO1491-02 X7JP

Formerly:
- --------------------------------------------------------------------------------
6. PROJECT PERIOD Mo., Day, Yr. Mo., Day, Yr.
05/01/96 04/30/99

From Through
- --------------------------------------------------------------------------------
7. BUDGET PERIOD Mo., Day, Yr. Mo., Day, Yr.
05/01/97 04/30/98
From Through
- --------------------------------------------------------------------------------

NATIONAL INSTITUTES OF HEALTH
NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NOTICE OF GRANT AWARD
AUTHORIZATION (Legislation Regulation)

42 USC 241 42 CFR 52
RESEARCH
- --------------------------------------------------------------------------------
8. TITLE OF PROJECT (Limit to 56 spaces)

AUTOMATED SEQUENCING SYSTEM FOR THE HUMAN GENOME PROJECT SRC (3)
- --------------------------------------------------------------------------------
9. GRANTEE NAME AND ADDRESS

a. CURAGEN CORPORATION
322 E MAIN ST
b. BRANFORD, CT 06405

d.
- --------------------------------------------------------------------------------
10. DIRECTOR OF PROJECT (PROGRAM DIRECTOR/PRINCIPAL INVESTIGATOR)
(LAST NAME FIRST AND ADDRESS)

WENT, GREGORY PHD
CURAGEN CORPORATION
LONG WHARF MARITIME CENTER
555 LONG WHARF DRIVE 11TH FL
NEW HAVEN, CONNECTICUT 06511

- --------------------------------------------------------------------------------
11. APPROVED BUDGET (Excludes PHS Direct Assurance)
- --------------------------------------------------------------------------------
1 PHS Grant Funds Only
-----
[_] Total project costs including grant funds and all other I
Financial participation -----

(Select one and place NUMERAL in box.)
- --------------------------------------------------------------------------------
a. Salaries and Wages . . . . $ [XXXXXX]

b. Fringe Benefits . . . . . $ [XXXXXX]

c. Total Personnel Costs . . . $ [XXXXXX]

d. Consultant Costs . . . . . . . . . . [XXXXXX]

e. Equipment. . . . . . . . . . . . . . [XXXXXX]

f. Supplies . . . . . . . . . . . . . . [XXXXXX]

g. Travel . . . . . . . . . . . . . . . [XXXXXX]

h. Patient Care -- Inpatient. . . . . . [XXXXXX]

i. -- Outpatient . . . . . [XXXXXX]

j. Alterations and Renovations. . . . . [XXXXXX]

k. Other. . . . . . . . . . . . . . . . [XXXXXX]

l. Consortium/Contractual Costs . . . . [XXXXXX]

m. Trainee Related Expenses . . . . . .

n. Trainee Stipends . . . . . . . . . . [XXXXXX]

o. Trainee Tuition and Fees . . . . . . [XXXXXX]

p. Trainee Travel . . . . . . . . . . . [XXXXXX]

-----------
q. TOTAL DIRECT COSTS $ [XXXXXX]
- --------------------------------------------------------------------------------
r. INDIRECT COSTS Date ? of S&W TADC $ [XXXXXX]
- --------------------------------------------------------------------------------
s. TOTAL APPROVED BUDGET $ [XXXXXX]
- --------------------------------------------------------------------------------
t. SAIR Fee $ [XXXXXX]
- --------------------------------------------------------------------------------
u. Federal Share. . . . . . . . . . . $ [XXXXXX]

v. Non-Federal Share. . . . . . . . . $
- --------------------------------------------------------------------------------
12. AWARD COMPUTATION FOR FINANCIAL ASSISTANCE
- --------------------------------------------------------------------------------
a. Amount of PHS Financial Assistance (from Item 11.v.). . . . $ [XXXXXX]

b. Less Unobligated Balance From Prior Budget Periods. . . . . $ [XXXXXX]

c. Less Cumulative Prior Award(s) This Budget Period . . . . . $ [XXXXXX]

-------------
d. AMOUNT OF FINANCIAL ASSISTANCE THIS ACTION. . . . . . . . . $ [XXXXXX]
- --------------------------------------------------------------------------------
13. RECOMMENDED FUTURE SUPPORT (SUBJECT TO THE AVAILABILITY OF FUNDS AND
SATISFACTORY PROGRESS OF THE PROJECT-
- --------------------------------------------------------------------------------
YEAR TOTAL DIRECT COSTS/STIPENDS YEAR TOTAL DIRECT COSTS/STIPENDS
- --------------------------------------------------------------------------------
a. 03 [XXXXXX] d.

b. e.

c. f.
- --------------------------------------------------------------------------------
14. APPROVED DIRECT ASSISTANCE BUDGET (IN LIEU OF CASH)

a. Amount of PHS Direct Assistance . . . . . . . . . . . $

b. Less Unobligated Balance From Prior Budget Periods. . $

c. Less Cumulative Prior Award(s) This Budget Period . . $

-------------------
d. AMOUNT OF DIRECT ASSISTANCE THIS ACTION . . . . . . . $
- --------------------------------------------------------------------------------
15. PROGRAM INCOME SUBJECT TO 45 CFR PART 74, SUBPART F. OR 45 CFR 92.25.
SHALL BE USED IN ACCORD WITH ONE OF THE FOLLOWING ALTERNATIVES:
(Select One and Place LETTER in box.)

a. DEDUCTION

b. ADDITIONAL COSTS
-----
c. MATCHING A
-----
d. OTHER RESEARCH (Add Deduct Option)

e. OTHER (See REMARKS)
- --------------------------------------------------------------------------------
16. THIS AWARD IS BASED ON AN APPLICATION SUBMITTED TO AND AS APPROVED BY THE
PHS ON THE ABOVE TITLED PROJECT AND IS SUBJECT TO THE TERMS AND CONDITIONS
INCORPORATED EITHER DIRECTLY OR BY REFERENCE IN THE FOLLOWING:

a. The grant program legislation cited above.

b. The grant program regulation cited above.

c. This award notice including terms and conditions, if any, noted below
under REMARKS.

d. PHS Grants Policy Statement including addenda in effect as of the
beginning date of the budget period.

e. 45 CFR Part 74 or 45 CFR Part 92 at applicable.

In the event there are conflicting or otherwise inconsistent policies
applicable to the grant, the above order of precedence shall prevail.
Acceptance of the grant terms and conditions is acknowledged by the grantee
when funds are drawn or otherwise obtained from the grant payment system.
- --------------------------------------------------------------------------------
REMARKS: (Other Terms and Conditions Attached - [X] Yes [_] No)

GRANT SPECIALIST: LINDA HALL 301-402-0733
PROGRAM OFFICIAL: DR. J. PETERSON 301-496-7531

* Indirect costs were calculated as indicated in Term and Condition #11.
** RECOMMENDED FUTURE SUPPORT REFLECTS TOTAL COSTS.

THIS GRANT IS EXCLUDED FROM STREAMLINED NONCOMPETING AWARD PROCEDURES (SNAP).
THIS GRANT IS INCLUDED UNDER EXPANDED AUTHORITIES.
- --------------------------------------------------------------------------------
PHS GRANTS MANAGEMENT OFFICER: (Signature)

/s/ Jean M. Cahill
- --------------------------------------------------------------------------------
(Name/Typed/Print)

JEAN M. CAHILL
- --------------------------------------------------------------------------------
(Title)

GRANTS MANAGEMENT OFFICER
- --------------------------------------------------------------------------------
17. OBJ. CLASS 18. CRS - EIN 19. LIST NO.
41 4E 1061331400A1
- --------------------------------------------------------------------------------
FY CAN DOCUMENT NO. ADMINISTRATIVE CODE
20.a. b. c.

21.a. 97 8427201 b. R1HG01491A c.

22.a. 970423 1710 b. c.
- --------------------------------------------------------------------------------
AMT ACTION FIN ASST. AMT ACTION DIR ASST.
d. e.

d. e.

d. e.
- --------------------------------------------------------------------------------
PHS 5152-5 (Rev. 7/94) (Note: See reverse for payment information.) 13G

NOTICE OF GRANT AWARD

Page 2
5 R01 HG01491-02
WENT, GREGORY T., PH.D.

1. The terms and conditions include the requirements of the Omnibus
Consolidated FY 1997 Appropriations Act (P. L. 104-208) as explained in the NIH
Guide for Grants and Contracts, Volume 26, Number 4, February 7, 1997.

2. The grantee institution may not provide any funds from this award to any
institution with which it has a research subcontract/consortium agreement until
the grantee has ensured that the third party institution has complied with all
applicable certifications and assurances as specified in the PHS Grants Policy
Statement. The grantee is responsible for retaining documentation to this
effect.

3. Applicant organization must comply with the Public Health Service (PHS)
policy relating to distribution of unique research resources produced with PHS
funding (NIH Guide for Grants and Contracts, Vol. 25, no. 23, July 12, 1996).
Grantee should also comply with the NIH-DOE guidelines for access to mapping and
sequencing data and materials resources, adopted by the NIH-DOE joint
subcommittee on December 7, 1992.

4. Allowable costs of activities conducted by for-profit organizations will be
determined by applying the costs principles of Contracts with Commercial
Organizations set forth in 48 CFR 31.2. However, independent research and
development costs (including the indirect costs allocable to them) are
unallowable.

5. Normally, the awardee organization retains the principal worldwide patent
rights to any invention developed with United States government support. Under
Title 37 Code of Federal Regulations Part 401, the Government receives a
royalty-free license for its use, reserves the right to require the patent
holder to license others in certain circumstances, and requires that anyone
exclusively licensed to sell the invention in the

NOTICE OF GRANT AWARD

Page 3
5 R01 HG01491-02
WENT, GREGORY T., PH.D.

United States must normally manufacture it substantially in the United States.
To the extent authorized by Title 35 United States Code Section 205, the
Government will not make public any information disclosing a
Government-supported invention for a 4-year period to allow the awardee
organization a reasonable time to file a patent application, nor will the
Government release any information that is part of that application.

6. Two months after disclosure, any invention developed under this award should
be reported to the Office for Policy on Extramural Research Administration
(OPERA), 6701 Rockledge Drive, MSC 7750, Bethesda, MD 20892-7750, Attn: Sue
Ohata. Phone (301) 435-0678, for disposition of patent rights in accordance with
45 CFR, Parts 6 and 8. Disposition rights on inventions made by small businesses
are subject to Chapter 18 of Title 35 U.S. Code.

7. Prior approval to implement budgetary and programmatic changes, where
required by PHS Policy, must be obtained in writing from the Grants Management
contact shown on this Notice of Grant Award.

8. The indirect cost portion of the commitments is calculated using the current
negotiated indirect cost (IC) rates, as follows:

03 Year
<TABLE>

<S> <C>
Direct Costs: $ [XXXXXX]
IC Calculation:
$ [XXXXXX] (fringe)
$ [XXXXXX]
Total indirect costs: [XXXXXX]
Total costs: $ [XXXXXX]
</TABLE>

9. Effective with the August 25, 1994 issuance of 45 CFR Part 74, certain
expanded authorities were extended to all research grants and cooperative
agreements. Under this grant award, the carryover authority is not authorized.

NOTICE OF GRANT AWARD
(Additional Remarks)

Page 5

If you need assistance from National Center for Human Genome Research during the
course of this grant, please contact the grants management and program staff
whole telephone numbers are shown on the Notice of Grant Award. These
individuals work closely with one another through all phases of each project to
facilitate the award and the administration of the grant. Their functions are
defined as follows:

GRANTS MANAGEMENT CONTACT: The Grants Management Specialist, whose name and
telephone number are indicated in the "Remarks" section of the Notice of Grant
Award, is responsible for all business management matters associated with the
review, negotiation, award, and administration of grants. The Grants Management
Specialist serves as the focal point for receiving and responding to all
questions and correspondence related correspondence giving or denying any prior
approval required by Public Health Service policy or special Terms of Award,
transfer of the grant to another institution, a change in the period of support,
or any actions which commit, or may result in committing the NCHGR to a change
in the amount of funding.

PROGRAM CONTACT: The Health Scientist Administrator, or program official, whose
name and telephone number also are indicated in the "Remarks" section of the
Notice of Grant Award, is responsible for all scientific and technical matters
dealing with the administration of the grant. The Health Scientist Administrator
reviews and monitors scientific progress of the project and provides advice and
assistance relative to all technical problems to ensure that the scientific
objectives of the research program can be pursued effectively and successfully.
All questions or correspondence dealing with research progress, changes in
research direction, unique scientific opportunities, or any other scientific
need should be addressed to the Health Scientist Administrator.

PRIOR APPROVAL: Requests which require the prior approval of the NCHGR must be
submitted in writing to the Grants Management Officer. All requests should
reference the complete grant number, e.g., 1 R01 HG12345-01, and must be signed
by the authorized official of the business office of the grantee institution and
by the principal investigator.

<TABLE>
<S> <C>
- ------------------------------------------------------------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES LEAVE BLANK FOR PHS USE ONLY.
-------------------------------------------------------------------------
PUBLIC HEALTH SERVICE Type Activity Number
-------------------------------------------------------------------------
GRANT APPLICATION Review Group Formerly
-------------------------------------------------------------------------
Follow Instruction carefully. Type in the Council/Board (Month, Year) Date Received
unshaded areas only. Type density must be
10 cpi
- ------------------------------------------------------------------------------------------------------------------------
1. TITLE OF PROJECT (Do not exceed 55 typewritten spaces.)
Automated Sequencing System for the Human Genome Project
- ------------------------------------------------------------------------------------------------------------------------
2a. RESPONSE TO SPECIFIC REQUEST FOR APPLICATIONS OR PROGRAM ANNOUNCEMENT [_] NO [X] YES (if "YES", state number)
Number HG-95-004 Title: Improved Electrophoretic DNA Sequencing Technologies
- ------------------------------------------------------------------------------------------------------------------------
2b. TYPE OF GRANT PROGRAM R01 3. PRINCIPAL INVESTIGATOR/PROGRAM DIRECTOR
- ------------------------------------------------------------------------------------------------------------------------
3a. NAME (Last, first, middle) 3b. DEGREE(S) 3c. SOCIAL SECURITY NO.
Went, Gregory T. B.S. Ph.D. ###-##-####
- ------------------------------------------------------------------------------------------------------------------------
3d. POSITION TITLE 3e. MAILING ADDRESS (Street, city, state, zip code)
VICE PRESIDENT
- --------------------------------------------------
3f. DEPARTMENT, SERVICE, LABORATORY, OR EQUIVALENT
CuraGen Corporation 322 East Main Street
- -------------------------------------------------- Branford, CT 06405
3g. MAJOR SUBDIVISION
None
- -------------------------------------------------
3h. TELEPHONE AND FAX (Area code, number and extension
TEL: (203) 481-1104 ext. 31
FAX: (203) 481-1106 --------------------------------------------------------------------
BITNET/INTERNET ADDRESS [email protected]
- ------------------------------------------------------------------------------------------------------------------------
4. HUMAN SUBJECTS IRB 5. VERTEBRATE ANIMALS if "YES" 5b. Animal Welfare
If "Yes" approval 4b. Assurance of IACUE approval date assurance no.
- ----- 4a. ---- exemption no. or date compliance no. ----- 5a. -----
X NO YES X NO YES
- ------------------------------------------------------------------------------------------------------------------------
6. DATES OF ENTIRE PROPOSED PROJECT 7. COSTS REQUESTED FOR INITIAL 8. COSTS REQUESTED FOR ENTIRE
PERIOD BUDGET PERIOD PROPOSED PROJECT PERIOD

From(MMDDYY) Through(MMDDYY) 7a. Direct Costs($) 7b. Total Costs($) 8a. Direct Costs($) 8b. Total Costs
04/01/96 03/31/99 $ [XXXXXX] $ [XXXXXX] $ [XXXXXX] $ [XXXXXX]
- ------------------------------------------------------------------------------------------------------------------------
9. PERFORMANCE SITES (Organizations and addresses) 10. INVENTIONS AND PATENTS (Competing continuation application only)

---- ---- If ---- previously ---- not previously
CuraGen Corporation Cornell University NO YES "YES" reported reported
322 East Main Street College of Engineering ---------------------------------------------------------------
Branford, CT 06405 Clare Hall 11. NAME OF APPLICANT ORGANIZATION
Ithaca, NY 14853-2501
CuraGen Corporation
ADDRESS 322 East Main Street
Suane BioSciences, Inc. The Whitehead Institute for Branford, CT 06405
3916 Trust Way Biomedical Research
Hayworth, CA 94545 Nine Cambridge Center
Cambridge, MA 02142-1479
- ------------------------------------------------------------------------------------------------------------------------
12. TYPE OF ORGANIZATION 13. ENTITY IDENTIFICATION NUMBER Congressional District
[_] Public specify [_] Federal [_] State [_] Local 06-1331400 #3
---------------------------------------------------------------
[_] Private nonprofit 14. BIOMEDICAL RESEARCH SUPPORT GRANT CREDIT
[X] For profit (General) [_] (Small Buiness) Code: Identification:
- ------------------------------------------------------------------------------------------------------------------------
15. NAME OF ADMINISTRATIVE OFFICIAL TO BE NOTIFIED IF 16. NAME OF OFFICIAL SIGNING FOR APPLICANT ORGANIZATION
AWARD IS MADE
Gregory T. Went, Ph.D. Gregory T. Went, Ph.D.
TELEPHONE (203) 481-1104, Ext 31 TELEPHONE (203) 481-1104, Ext 31
FAX (203) 481-1106 FAX (203) 481-1106
TITLE Vice President TITLE Vice President
ADDRESS CuraGen Corporation ADDRESS CuraGen Corporation
322 East Main Street 322 East Main Street
Branford, CT 06405 Branford, CT 06405

BITNET/INTERNET ADDRESS [email protected] BITNET/INTERNET ADDRESS [email protected]
- ------------------------------------------------------------------------------------------------------------------------
17. PRINCIPAL INVESTIGATOR/PROGRAM DIRECTOR SIGNATURE OF PERSON NAMED IN 3a. DATE
ASSURANCE: I agree to accept responsibility (In ink. "Per" signature
for the scientific conduct of the project not acceptable.)
and to provide and to provide the required /s/ Gregory Went 8/25/95
progress reports if a grant is awarded as a
result of this application. Will ful provision
of false information is a criminal offense
(U.S. Code, Title 18, Section 1001). I am aware
that any false, fictitious or fraudulent
statement may, in addition to other remedies
available to the Government, subject me to
civil penalties under the Program Fraud
Civil Remedies Act of 1986 (45 CFR 79).
- ------------------------------------------------------------------------------------------------------------------------
18. CERTIFICATION AND ACCEPTANCE: I certify that the SIGNATURE OF PERSON NAMED IN 15. DATE
statements herein are true and complete to the (In ink. "Per" signature
best of my knowledge, and accept the obligation to not acceptable.)
comply with Public Health Services terms and /s/ Gregory Went 8/25/95
conditions if a grant is awarded as the result of
this application. A willfully false certification
is a criminal offense (U.S. Code, Title 18, Section
1001). I am aware that any false, fictitious, or
fraudulent statement may, in addition to other
remedies available to the Government, subject me
to civil penalties under the Program Fraud Civil
Remedies Act of 1986 (45 CFR 79).
- ------------------------------------------------------------------------------------------------------------------------
</TABLE>

[Confidential Treatment Requested]

<PAGE>

BB
Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

DESCRIPTION: State the application's broad, long-term objectives and specific
aims, making reference to the health relatedness of the project. Describe
concisely the research design and methods for achieving these goals. Avoid
summaries of past accomplishments and the use of the first person. This abstract
is meant to serve as a succinct and accurate description of the proposed work
when separated from the application. DO NOT EXCEED THE SPACE PROVIDED.
- --------------------------------------------------------------------------------
The genetic information encoded in the human genome specifies all life processes
from conception to death, and contains within it the origin of over 3500 known
genetic diseases. It is necessary to substantially reduce the cost and
dramatically raise the speed of producing accurate DNA sequences in order to
determine the sequence of the 3 billion basepairs of DNA that compose the human
genome. This proposal describes a three-year project to develop, integrate and
distribute into parallel sequencing projects a fluorescent sequencing instrument
and software system capable of meeting these logistical and cost demands. This
approach allows for the identification and removal of the major bottlenecks
encountered in producing a fully automated system, without duplication of
mapping, sample processing or informatics efforts ongoing at other HGP
facilities. Current bottlenecks arise primarily from inefficiencies in workflow
and data analysis. Specifically, we will develop and integrate into existing
centers the following: 8-dye bi-directional sequencing methods; solid phase
loading of an advanced electrophoresis instrument; high-throughput and low cost
ready-to-run disposable microeplicated separation sub-systems; sensitive
detection optics; and advanced base-calling software. These advances will enable
the completion of fully automated systems including all the steps necessary to
proceed from a physical map to a finished sequence with a quantifiable measure
of confidence. Full process automation coupled with automated data analysis and
reduced materials cost will enable a 60-fold increase in throughput with the
required 10-fold decrease in cost relative to systems based on currently
available technology. This project is coordinated by CuraGen Corporation and
builds on the automation, data analysis, sequencing instrumentation, and
fabrication experience of collaborators at Soane BioSciences, MIT and Cornell.
The final product of our efforts will be tested and ready for wide-spread
distribution for use in sequencing the human genome.
- --------------------------------------------------------------------------------
PERSONNEL ENGAGED ON PROJECT, INCLUDING CONSULTANTS/COLLABORATORS. Use
continuation pages as needed for ?????? required information in the format shown
below on all individuals participating in the project.
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>

<S> <C> <C> <C>
Name Gregory T. Went Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ----------------
Position Title Vice President D.O.B. 7/1/63 Role on Project Prin. Investig.
---------------------------------------------------- ----------------- -----------------
Organization CuraGen Corporation Department
------------------------------------------------------------------------------ -----------------
Name Jonathatn M. Rothberg Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ----------------
Position Title Chief Executeve Officer D.O.B. 4/28/62 Role on Project Scientist
---------------------------------------------------- ----------------- -----------------
Organization CuraGen Corporation Department
------------------------------------------------------------------------------ -----------------
Name Michael P. McKenna Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ----------------
Position Title Senior Research Scientist D.O.B. 3/3/62 Role on Project Scientist
---------------------------------------------------- ----------------- -----------------
Organization CuraGen Corporation Department
------------------------------------------------------------------------------ -----------------
Name Gregory T. Mulhern Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ----------------
Position Title Senior Research Scientist D.O.B. 8/11/67 Role on Project Scientist
---------------------------------------------------- ----------------- -----------------
Organization CuraGen Corporation Department
------------------------------------------------------------------------------ -----------------
Name Darin R. Latimer Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ----------------- -----------------
Position Title Senior Research Engineer D.O.B. 6/1/63 Role on Project Engineer
---------------------------------------------------- ----------------- -----------------
Organization CuraGen Corporation Department
------------------------------------------------------------------------------ -----------------
Name John W. Simpson Degree(s) M.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ----------------
Position Title Senior Research Engineer D.O.B. 3/6/65 Role on Project Engineer
---------------------------------------------------- ----------------- -----------------
Organization CuraGen Corporation Department
------------------------------------------------------------------------------ --------------------
</TABLE>

2
<PAGE>

BB
Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
<TABLE>
<S> <C> <C>
Name Aleksandar Milosavljevic Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Director of Bioinformatics D.O.B. 04/12/61 Role on Project Scientist
---------------------------------------------------- ---------------- ------------------

Organization CuraGen Corporation Department
----------------------------------------------------------------------------- ------------------

Name Joseph C. Kaufman Degree(s) B.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Director of Software Development D.O.B. 3/25/59 Role on Project Scientist
---------------------------------------------------- ---------------- ------------------

Organization CuraGen Corporation Department
----------------------------------------------------------------------------- ------------------

Name Gordon S. Freckleton Degree(s) B.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Technician D.O.B. 12/03/66 Role on Project
---------------------------------------------------- ---------------- ------------------

Organization CuraGen Corporation Department
----------------------------------------------------------------------------- ------------------

Name To Be Hired Degree(s) Social Security #
------------------------------------------------------------ ------------- ------------------

Position Title Fabrication D.O.B. Role on Project
---------------------------------------------------- ---------------- ------------------

Organization CuraGen Corporation Department
----------------------------------------------------------------------------- ------------------

Name To Be Hired Degree(s) Social Security #
------------------------------------------------------------ ------------- ------------------

Position Title Programmer D.O.B. Role on Project
---------------------------------------------------- ---------------- ------------------

Organization CuraGen Corporation Department
----------------------------------------------------------------------------- ------------------

Name Harold Craighead Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Professor D.O.B. 9/21/52 Role on Project
---------------------------------------------------- ---------------- ------------------

Organization Cornell University Department
----------------------------------------------------------------------------- ------------------

Name Warren Wright Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Research Associate D.O.B. 12/11/50 Role on Project Research Assoc.
---------------------------------------------------- ---------------- ------------------

Organization Cornell University Department
----------------------------------------------------------------------------- ------------------

Name To Be Hired Degree(s) Social Security #
------------------------------------------------------------ ------------- ------------------

Position Title Graduate Student D.O.B. Role on Project
---------------------------------------------------- ---------------- ------------------

Organization Cornell University Department
----------------------------------------------------------------------------- ------------------

Name Herbert H. Hooper Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Vice President of Research D.O.B. 09/01/63 Role on Project Prin. Investig.
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciences, Inc. Department
----------------------------------------------------------------------------- ------------------

Name David S. Soane Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Chairman, Scientific Advisory Board D.O.B. 08/22/51 Role on Project Scientist
---------------------------------------------------- ---------------- ------------------

Organization Soane Technologies, Inc. Department
----------------------------------------------------------------------------- ------------------

Name Goretty Alonso Amigo Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Senior Scientist D.O.B. 10/01/56 Role on Project Scientist
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciencies, Inc. Department
----------------------------------------------------------------------------- ------------------

Name Alexander P. Sassi Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Senior Research Engineer D.O.B. 04/25/67 Role on Project Engineer
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciences, Inc. Department
----------------------------------------------------------------------------- ------------------

Name Daniel Hion Degree(s) B.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Research Biochemist D.O.B. 03/02/70 Role on Project Biochemist
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciences, Inc. Department
---------------------------------------------------- ------------- ------------------

Name Shi Lin Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Postdoctoral D.O.B. 08/24/62 Role on Project Scientist
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciencies, Inc. Department
----------------------------------------------------------------------------- ------------------

Name Jules Moolenaar Degree(s) B.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Designer/Machinist D.O.B. 04/30/33 Role on Project Machinist
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciences, Inc. Department
----------------------------------------------------------------------------- ------------------

Name To Be Determined Degree(s) Social Security #
------------------------------------------------------------ ------------- ------------------

Position Title Polymer Engineer D.O.B. Role on Project
---------------------------------------------------- ---------------- ------------------

Organization Soane BioSciences, Inc. Department
----------------------------------------------------------------------------- ------------------

Name Trevor L. Hawkins Degree(s) Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Research Scientist D.O.B. 03-07-60 Role on Project Prin. Investig.
---------------------------------------------------- ---------------- ------------------

Organization The Whitehead Institute Department
----------------------------------------------------------------------------- ------------------

Name Lincoln D. Stein Degree(s) M.D.,Ph.D. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Director of Informatics Core D.O.B. 01/13/60 Role on Project Scientist
---------------------------------------------------- ---------------- ------------------

Organization The Whitehead Institute of Biomedical Research, MIT Department
----------------------------------------------------------------------------- ------------------

Name David Goon Degree(s) B.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Technical Assistant D.O.B. 12/13/71 Role on Project Technican
---------------------------------------------------- ---------------- ------------------

Organization The Whitehead Institute of Biomedical Research, MIT Department
----------------------------------------------------------------------------- ------------------

Name William Lee Degree(s) B.S. Social Security ####-##-####
------------------------------------------------------------ ------------- ------------------

Position Title Research Specialist D.O.B. 12/23/74 Role on Project Research
---------------------------------------------------- ---------------- ------------------

Organization The Whitehead Institute of Biomedical Research, MIT Department
----------------------------------------------------------------------------- ------------------
</TABLE>

3
<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
---------------
- -------------------------------------------------------------------------------

RESEARCH GRANT
TABLE OF CONTENTS

PAGE NUMBERS
------------
<S> <C>
Face Page................................................................................. 1
Description and Personnel................................................................. 2-3
Table of Contents......................................................................... 4
Detailed Budget for Initial Budget Period................................................. 5
Budget for Entire Proposed Project Period................................................. 6-9
Budgets Pertaining to Consortium/Contractual Arrangements................................. 10-21
Biographical Sketch-Principal Investigator/Program Director (Not to exceed two pages)..... 22-23
Other Biographical Sketches (Not to exceed two pages for each)............................ 24-49
Other Support............................................................................. 50-74
Resources and Environment................................................................. 75-78

Research Plan

Introduction to Revised Application (Not to exceed three pages).......................... _______
Introduction to Supplemental Application (Not to exceed one page)......................... _______
1. Specific Aims.................................................................... 79-80
2. Background and Significance...................................................... 80-84
3. Progress Report/Preliminary Studies (Not to exceed 25 pages*).................... 85-92
4. Research Design and Methods...................................................... 92-103
5. Human Subjects................................................................... _______
6. Vertebrate Animals............................................................... _______
7. Consultants/Collaborators........................................................ 104-107
8. Consortium/Contractual Arrangements.............................................. 108-111
9. Literature Cited (Not to exceed six pages)....................................... 112-114
Checklist................................................................................. 115-116
*Type density and size must conform to limits provided in Specific Instructions on page 10.
</TABLE>
Appendix (Five collated sets. No page numbering necessary for Appendix)
Number of publications and manuscripts accepted or submitted for
publication (Not to exceed 10):
Other items (list):
[X] Check if Appendix is
Included

Appendix 1: Color Copies of Figures
Appendix 2: Detailed Cost Analysis

4
<PAGE>

DD Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
- ------------------------------------------------------------------------------------------------------------------------------
DETAILED BUDGET FOR INITIAL BUDGET PERIOD FROM FROM THROUGH
DIRECT COSTS ONLY (CuraGen Corporation) 04/01/96 03/31/97
- ------------------------------------------------------------------------------------------------------------------------------
PERSONNEL (Applicant Organization Only) DOLLAR AMOUNT REQUESTED (omit cents)
- ------------------------------------------ INST. -----------------------------------------------
ROLE ON TYPE APPT. % EFFORT BASE SALARY FRINGE
NAME PROJECT (months) ON PROJ. SALARY REQUESTED BENEFITS TOTALS
- ------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C> <C> <C>
- ------------------------------------------------------------------------------------------------------------------------------
Principal
Gregory T. Went Investigator 12 [XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Jonathan M. Rothberg CSO/CEO 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Senior
Michael P. McKenna Scientist 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Senior
Gregory T. Mulhern Scientist 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Senior
Darin R. Latimer Engineer 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Senior
John W. Simpson Engineer 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Director of
Aleksandar Milosavljevic Bioinformatics 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Director of
Joseph C. Kaufman Software Dev 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Gordon S. Freckleton Technician 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
To be hired Fabrication 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
To be hired Programmer 12 XXX XXXXXXXX XXXXXXXX XXXXXXXX XXXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
- -------------------------------------------------------------------------------===============================================
SUBTOTALS----------------------------------------- [XXXXXXXX XXXXXXXX XXXXXXXX]
- -------------------------------------------------------------------------------===============================================
<CAPTION>
<S> <C> <C> <C> <C>
CONSULTANT COSTS
[XX]
- ------------------------------------------------------------------------------------------------------------------------------
[XXXXXXXXXXXXXXXXXX]
[XXXXXXXX] [XXXXXX] Optical components [XXXXXX]
[XXXXXXXX] [XXXXXX] Software [XXXXXX]
Lab equipment [XXXXXX] Support hardware [XXXXXX]
Power supplies [XXXXXX] [XXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
SUPPLIES (Itemize by category)
Substrates for fabrication [XXXXXX] Plastic disposables [XXXXXX]
Other fabrication materials/reagents [XXXXXX] Test reagents/chemicals [XXXXXX]
Gel box materials [XXXXXX] Fluorescent labelling [XXXXXX]
DNA sequence supplies [XXXXXX] [XXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
TRAVEL
Sixteen trips per year to conferences and MIT [XXXXXX]
Two trips per year for P.I. for semi-annual project management [XXXXXX] [XXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
PATIENT CARE COSTS INPATIENT [XXXXXX]
---------------------------------------------------------------------------------------------------
OUTPATIENT [XXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
ALTERATIONS AND RENOVATIONS (Itemize by category)
[XXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
OTHER EXPENSES (Itemize by category)
Machining/Engineering [XXXXXXXXXXXXXXXXXXXXX] [XXXXXX]
Fabrication - NNF [XXXXXXXXXXXXXXXXXXXXX] [XXXXXX]
Publication Costs [XXXXXX] [XXXXXX]
- -------------------------------------------------------------------------------------------------------------=================
SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD [XXXXXX]
- -------------------------------------------------------------------------------------------------------------=================
CONSORTIUM/CONTRACTUAL COSTS
DIRECT COSTS [XXXXXX]
---------------------------------------------------------- TOTAL---- [XXXXXX]
INDIRECT COSTS [XXXXXX]
- -------------------------------------------------------------------------------------------------------------=================
TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page)---- [XXXXXX]
==============================================================================================================================
</TABLE>

[Confidential Treatment Requested]
<PAGE>

Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
<TABLE>
<CAPTION>

- ------------------------------------------------------------------------------------------------------------------
BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD
DIRECT COSTS ONLY (CuraGen Corporation)

- ------------------------------------------------------------------------------------------------------------------
BUDGET CATEGORY INITIAL BUDGET ADDITIONAL YEARS OF SUPPORT REQUESTED
PERIOD --------------------------------------------------------------
TOTALS (from page 4) 2nd 3rd 4th 5th
- ------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
PERSONNEL:
Salary & fringe benefits
Applicant organization only [XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
CONSULTANT COSTS XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
EQUIPMENT XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
SUPPLIES XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
TRAVEL XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
PATIENT INPATIENT XXXXXXXX XXXXXXXX XXXXXXXX
CARE ------------------------------------------------------------------------------------------------------
COSTS OUTPATIENT XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
ALTERATIONS AND
RENOVATIONS XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
OTHER EXPENSES XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
CONSORTIUM/
CONTRACTUAL COSTS XXXXXXXX XXXXXXXX XXXXXXXX
- ------------------------------------------------------------------------------------------------------------------
TOTAL DIRECT COSTS XXXXXXXX XXXXXXXX XXXXXXXX]
- ------------------------------------------------------------------------------------------------------------------
TOTAL DIRECT COSTS FOR ENTIRE PROPOSED PROJECT PERIOD (Item 8a)- [XXXXXXXX]
- ------------------------------------------------------------------------------------------------------------------
JUSTIFICATION (Use continuation pages if necessary):
</TABLE>

From Budget for Initial Period: Describe the specific functions of the
personnel, collaborators, and consultants and identify individuals with
appointments that are less than full time for a specific period of the year,
including VA appointments.

For All Years: Explain and justify purchase of major equipment, unusual supplies
requests, patient care costs, alterations and renovations, tuition remission,
and donor/volunteer costs.

From Budget for Entire Period: Identify with an asterisk (*) on this page and
justify any significant increase or decrease in any category over the initial
budget period. Describe any change in effort of personnel.

For Competing Continuation Applications: Justify any significant increases or
decreases in any category over the current level of support.

See Attached Budget Justifications Pages

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - CuraGen Corporation

PERSONNEL

Management
- ----------
Dr. Gregory T. Went is the principal investigator and will be responsible for
overall project management, scientific direction, and coordination among
collaborating sites. Dr. Went is a cofounder of CuraGen with Dr. Jonathan
Rothberg and has been responsible for research and corporate development. He
currently manages a staff of 24 internally at CuraGen (16 Ph.Ds), as well as 3
subcontracts with leading University researchers. He oversaw the development of
CuraGen's DNA analysis device employed herein. He will devote 20% of his time to
this project.

Dr. Jonathan M. Rothberg is the CEO of CuraGen. Dr. Rothberg's Ph.D. is in
Molecular Biology and he is the Chief Scientific Officer responsible for
CuraGen's molecular biology efforts. He will devote 10% of his time to the
project to insure that novel molecular methods are integrated into the genome
sequencing efforts at MIT. Dr. Rothberg will also oversee all contractual
matters related to this collaboration.

Other personnel will be deployed as described below.

Electrophoresis System
- ----------------------
Dr. Gregory T. Mulhern will lead the prototyping and development of channel
structures and coordinate activities in Dr. Harold Craighead's group. Dr.
Mulhern is a graduate of Berkeley (Howe and Soane groups) and is an expert in
macro aspects of micromachined components. He spent 1 year working at Soane
Technologies during his thesis and that experience will aid project coordination
with Soane BioSciences. Dr. Mulhern is experienced both in replication
technologies and MEMs. Under Dr. Mulhern's direction will be Dr. Darin R.
Latimer who is responsible for all engineering/machining of electrophoresis
components and Mr. John W. Simpson, who is the originator of CuraGen optical,
electrophoresis and base calling technology. A fabrication engineer working
directly with Dr. Mulhern at contract fabrication centers (NNF) will be hired.

Methods development
- -------------------
Dr. Michael P. McKenna is a molecular biologist carrying out the development of
novel fluorescent protocols for DNA sequencing. Dr. McKenna is experienced in
molecular methods, fluorescence and instrument machining. In addition, Dr.
McKenna is well versed in fluorescent dye strategies, coupling chemistries, and
protocol development. Dr. McKenna will be assisted by a full time technician,
Gordon S. Freckleton. Dr. McKenna will act as a visiting scientist at MIT to
insure close collaboration between methods development and sample preparation.

Informatics
- -----------
Mr. Joseph C. Kaufman and Dr. Aleksandar Milosavljevic will lead the refinement
and integration of CuraGen's base calling software into genomic assembly
routines. Mr. Kaufman was the lead programmer on the MacVector product from
Kodak and has extensive experience with commercial software development and
maintenance. Dr. Milosavljevic who is an expert in pattern analysis will
coordinate the algorithm development and evaluation. Mr. Kaufman's and Dr.
Milosavljevic's efforts reduce to 25% and 10% in years 2 and 3. They will be
assisted by a BS/MS computer scientist.

In Years 2 & 3, the salaries have been increased by 5 percent for inflation.

Fringe benefits have been calculated as 14 percent of salary.
<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - CuraGen Corporation
Page 2

EQUIPMENT

Lab Equipment Electronics for measuring electrical outputs will be required to
test the developing electrophoresis station. An oscilloscope with probes,
capacitance meters, spectrophotometer (for dye QC) are included. Funding remains
available for years 2 and 3.

Power Supplies For electrophoresis experiments, we requests funds for two high
voltage, high power, power supplies. Funding remains available for years
2 and 3.

Software Maintenance of existing graphics and CAD packages. Funding remains
available for years 2 and 3.

Support Hardware Request for hardware for assembly and testing of electrophores
is station. Funding remains available for years 2 and 3.

SUPPLIES

Substrates for fabrication Wafers (Glass and silicon), 500@ $ 55/piece. Expenses
increase 100% in years 2 and 3 as the efforts gear up.

Other fabrication materials/reagents Etchants, coatings. Expenses increase 100%
in years 2 and 3 as the efforts gear up.

Gel Box materials [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXX]

DNA Sequence supplies [XXXXXXXXXXXXXXXXXXXXXXXX]

Plastic disposables and Test Reagents/chemicals. For general use.

Fluorescent labelling For coupling novel dyes to primers.

TRAVEL

A total of 2 trips to Soane BioSciences @ $1000/each are budgeted for the PI.
Most travel will be to CuraGen, where we have set up a visiting office for Soane
BioSciences. We believe that this level of interaction with our collaborators is
essential. 16 trips (1 week each) are requested to fund travel/expenses
associated with our MIT collaboration. CuraGen has a visiting scientist position
that rotates at MIT.

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - CuraGen Corporation
Page 2

OTHER EXPENSES

Machining/Engineering [XXXXXXXXXXXXXXXXXXX] CuraGen works closely with a number
of design and machining firms in the New Haven area. This number is based on our
historical experience and is adjusted to reflect significant efforts at
delivering a robust and maintenance free system.

Fabrication - NNF [XXXXXXXXXXXXXXXXXXXX] Expense associated with time on
instruments at major fabrication centers, including Cornell's NNF. CuraGen is a
routine user of this facility. Budget increases to 1500 hours in year 2 and
reduces to 1000 hours in year 3.

Publication Costs are estimated at $2,000 per year, as we expect to report on
advances in several technology areas, including separation media, surface design
of plastics for use in DNA electrophoresis, and microreplication methods.

INDIRECT COSTS
Indirect costs are budgeted [XXXXXXX] of direct costs, excluding equipment.

[Confidential Treatment Requested]

<PAGE>

DD Principal investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
- ------------------------------------------------------------------------------------------------------------------------------
DETAILED BUDGET FOR INITIAL BUDGET PERIOD FROM THROUGH
DIRECT COSTS ONLY (Cornell University) 04/01/96 03/31/97
- ------------------------------------------------------------------------------------------------------------------------------
PERSONNEL (Applicant Organization Only) DOLLAR AMOUNT REQUESTED (omit cents)
- ------------------------------------------ INST. -----------------------------------------------
ROLE ON TYPE APPT. % EFFORT BASE SALARY FRINGE
NAME PROJECT (months) ON PROJ. SALARY REQUESTED BENEFITS TOTALS
- ------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C> <C> <C>
Principal 12 [XXXX XXXXXX XXXXXX XXXXXX XXXXXXX
Dr. Harold G. Craighead Investigator 12 XXXX XXXXXX XXXXXX XXXXXX XXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Research
Dr. Warren Wright Associate 12 XXXX XXXXXX XXXXXX XXXXXX XXXXXXX
- ------------------------------------------------------------------------------------------------------------------------------
Research 9 XXXX XXXXXX XXXXXX XXXXXX XXXXXXX
Graduate Student Assistant 3 XXXX XXXXXX XXXXXX XXXXXX XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------

- ------------------------------------------------------------------------------------------------------------------------------

- -------------------------------------------------------------------------------===============================================
SUBTOTALS----------------------------------------- [XXXXXXXX XXXXXXXXX XXXXXXXXX]
- -------------------------------------------------------------------------------===============================================
<CAPTION>
<S> <C>
CONSULTANT COSTS
[XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
EQUIPMENT (Itemize)
Micropositioning Equip; Photomultiplier tubes, housing and power supply; AR Laser;
Filters & gratings; Optical table; Custom optics arrays [XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
SUPPLIES (Itemize by category)
Substrates, deposition materials, stockroom, machine shop, chemicals and
misc optical components [XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
TRAVEL

See Budget Justifications Pages [XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
PATIENT CARE COSTS INPATIENT [XXXXXXX]
-----------------------------------------------------------------------------------------------------
OUTPATIENT [XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
ALTERATIONS AND RENOVATIONS (Itemize by category)
[XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
OTHER EXPENSES (Itemize by category)
Publications [XXXXXXX]
Communications (Xerox, Fax, Postage, Phone Tolls) [XXXXXXX]
NNF Charges (Photolithography, Electron Beam Lithography, Etching, Other Fab) [XXXXXXX]
MSC Charges (AFM, SEM, Computer, Thin Film Deposition, etc.) [XXXXXXX] [XXXXXXX]
- ------------------------------------------------------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD [XXXXXXX]
- ---------------------------------------------------------------------------------------------------------------===============
CONSORTIUM/CONTRACTUAL COSTS
DIRECT COSTS TOTAL ------------ [XXXXXXX]
-----------------------------------------------------------
INDIRECT COSTS [XXXXXXX] [XXXXXXX]
- ---------------------------------------------------------------------------------------------------------------===============
TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page) ------------ [XXXXXXX]
==============================================================================================================================
</TABLE>

[Confidential Treatment Requested]

<PAGE>

EE Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
- --------------------------------------------------------------------------------------------------------
BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD
DIRECT COSTS ONLY (Cornell University)
- --------------------------------------------------------------------------------------------------------
INITIAL BUDGET ADDITIONAL YEARS OF SUPPORT REQUESTED
BUDGET CATEGORY PERIOD -----------------------------------------------------------
TOTALS (from page 4) 2nd 3rd 4th 5th
- --------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
PERSONNEL:
Salary & fringe benefits
Applicant organization only [XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
CONSULTANT COSTS XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
EQUIPMENT XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
SUPPLIES XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
TRAVEL XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
PATIENT INPATIENT XXXXXXXX XXXXXXXXX XXXXXXXXX
CARE -------------------------------------------------------------------------------------------
COSTS OUTPATIENT XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
ALTERATIONS AND
RENOVATIONS XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
OTHER EXPENSES XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
CONSORTIUM/
CONTRACTUAL COSTS XXXXXXXX XXXXXXXXX XXXXXXXXX
- --------------------------------------------------------------------------------------------------------
TOTAL DIRECT COSTS XXXXXXXX XXXXXXXXX XXXXXXXXX]
- ------------------------------------------------------------------------------------------==============

TOTAL DIRECT COSTS FOR ENTIRE PROPOSED PROJECT PERIOD (Item 8a)- [XXXXXXX]

- ------------------------------------------------------------------------------------------==============
</TABLE>

JUSTIFICATION (Use continuation pages if necessary):

From budget for Initial Period: Describe the specific functions of the
personnel, collaborators, and consultants and identify individuals with
appointments that are less than full time for a specific period of the year,
including VA appointments.

For All Years: Explain and justify purchase of major equipment, unusual
supplies requests, patient care costs, alterations and renovations, tuition
remission, and donor/volunteer costs.

For Competing Continuation Applications: Justify any significant increases or
decreases in any category over the current level of support.

See Attached Budget Justifications Pages

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - Cornell University

PERSONNEL

The personnel working on this aspect of the project will be Professor Harold
Craighead who will oversee and manage the effort at Cornell. He will be
responsible for overall system design and establishing testing paradigms. Dr.
Warren Wright is a research associate currently at Cornell who has worked with
the group of Professor Craighead on the fabrication and optical [XXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

In Years 2 & 3, the faculty and research associate salaries have been increased
by 4 percent. Graduate student tuition is determined by the University and
increases at a rate of approximately 4%. In academic year 1997-1998, Cornell
will be restructuring its tuition charges which will result in a substantial
reduction in charges for graduate students.

EQUIPMENT

The capital equipment in Year 1 will be used to construct and test the prototype
optical system. [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

<TABLE>
<S> <C>
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXX]
</TABLE>

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - Cornell University
Page 2

In Year 2 we will look at optimizing the signal to noise and therefore
throughput of the system and require equipment for analyzing multiple channels
of optical data. Additional optical array components will be required.

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXX]
</TABLE>

In the third year we will be fabricating and testing in-house made components.

SUPPLIES

Substrates, deposition materials, chemicals and misc. optical components. A
major part of this is basic optical components for testing of optical substrates
for our fabricated and custom coated components. In Years 2 & 3, the supplies
costs have been increased by 4 percent for inflation.

TRAVEL

Travel is for three person-trips to scientific conferences and two trips to
CuraGen Corporation each year. In Years 2 & 3, the travel costs have been
increased by 5 percent for inflation.

OTHER EXPENSES

These include local shop, stockroom and lab fees associated with micro-optics
fabrication and testing as well as communication and publication costs
associated with graduate research. In Years 2 & 3, the expenses have been
increased by 4 percent for inflation.

[Confidential Treatment Requested]

<PAGE>

DD Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
DETAILED BUDGET FOR INITIAL BUDGET PERIOD FROM THROUGH
DIRECT COSTS ONLY (Soane BioSciences, Inc.) 04/01/96 03/31/97
- -------------------------------------------------------------------------------------------------------------------
PERSONNEL (Applicant Organization Only) % DOLLAR AMOUNT REQUESTED (omit cents)
- ----------------------------------------- TYPE EFFORT INST. ----------------------------------------------
ROLE ON APPT. ON BASE SALARY FRINGE
NAME PROJECT (months) PROJ. SALARY REQUESTED BENEFITS TOTALS
- -------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C> <C> <C>
Principal
Herbert H. Hooper Investigator 12 [XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
David S. Soane Scientist 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
Goretty Alonso Amigo Scientist 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
Molecular
Alexander P. Sassi Biologist 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
Daniel Hion Scientist 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
Polymer
Shi Lin Chemist 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
Designer
Jules Moolenaar Machinist 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX
- -------------------------------------------------------------------------------------------------------------------
Polymer
To be determined Engineer 12 XXX XXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX]
- --------------------------------------------------------------------===============================================
SUBTOTALS----------------------------- [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
- --------------------------------------------------------------------===============================================
<CAPTION>
<S> <C> <C>
CONSULTANT COSTS
[XXXXXXXXX]
- -------------------------------------------------------------------------------------------------------------------
EQUIPMENT (Itemize)
Thin Slab Sequencer [XXXXXXXX]
UV/VIS Spectrophotometer [XXXXXXXX]
Flouorescent Spectrophotometer [XXXXXXXX]
Fabrication of curing &
spin-coating stations [XXXXXXXX] [XXXXXXX]
- -------------------------------------------------------------------------------------------------------------------
SUPPLIES (Itemize by category)
Sequencing Kits, Template, Dyes [XXXXXX]
Monomers, Polymers, Solvents, Buffers [XXXXXX]
Miscellaneous Chemicals & Supplies [XXXXXX] [XXXXXX]
- -------------------------------------------------------------------------------------------------------------------
TRAVEL
Travel to CuraGen Corporation and Key Conferences [XXXXXXX]
- -------------------------------------------------------------------------------------------------------------------
PATIENT CARE COSTS INPATIENT [XXXXXXX]
----------------------------------------------------------------------------------------
OUTPATIENT [XXXXXXX]
- -------------------------------------------------------------------------------------------------------------------
ALTERATIONS AND RENOVATIONS (Itemize by category)
[XXXXXXX]
- -------------------------------------------------------------------------------------------------------------------
OTHER EXPENSES (Itemize by category)
Publication Costs [XXXXXXX]
- -------------------------------------------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD [XXXXXXX]
- -------------------------------------------------------------------------------------------------------============
CONSORTIUM/CONTRACTUAL COSTS
DIRECT COSTS TOTAL---- [XXXXXXX]
-----------------------------------------------------
INDIRECT COSTS [XXXXXXXXXX XXXXXXXXXXX]
- -------------------------------------------------------------------------------------------------------============
TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page)---- [XXXXXX]
- -------------------------------------------------------------------------------------------------------============
</TABLE>

[Confidential Treatment Requested]

<PAGE>

EE Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------

<TABLE>
<CAPTION>
- -----------------------------------------------------------------------------------------------------------
BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD
DIRECT COSTS ONLY (Soane BioSciences, Inc.)

- -----------------------------------------------------------------------------------------------------------
BUDGET CATEGORY INITIAL BUDGET PERIOD ADDITIONAL YEARS OF SUPPORT REQUESTED
----------------------------------------------------------
TOTALS (from page 4) 2nd 3rd 4th 5th
- -----------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
PERSONNEL:
Salary & fringe benefits
Applicant organization only [XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
CONSULTANT COSTS XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
EQUIPMENT XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
SUPPLIES XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
TRAVEL XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
PATIENT INPATIENT XXXXXXXX XXXXXXXXX XXXXXXXX
CARE ----------------------------------------------------------------------------------------------
COSTS OUTPATIENT XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
ALTERATIONS AND
RENOVATIONS XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
OTHER EXPENSES XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
CONSORTIUM/
CONTRACTUAL COSTS XXXXXXXX XXXXXXXXX XXXXXXXX
- -----------------------------------------------------------------------------------------------------------
TOTAL DIRECT COSTS XXXXXXXX XXXXXXXXX XXXXXXXX]
- -----------------------------------------------------------------------------------------------------------
TOTAL DIRECT COSTS FOR ENTIRE PROPOSED PROJECT PERIOD (Item 8a)- [XXXXXXXXXX]
- -----------------------------------------------------------------------------------------------------------
JUSTIFICATION (Use continuation pages if necessary):
</TABLE>

For All Years: Explain and justify purchase of major equipment, unusual supplies
requests, patient care costs, alterations and renovations, tuition remission,
and donor/volunteer costs.

For Competing Continuation Applications: Justify any significant increases or
decreases in any category over the current level of support.

See Attached Budget Justifications Pages

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - Soane BioSciences, Inc.

PERSONNEL

Dr. Hooper will be responsible for project management at Soane BioSciences,
Inc., as well as scientific direction, and coordination with the collaborating
sites. Dr. Soane will provide scientific guidance in the areas of
electrophoresis media, polymer formulation, replication and microfabrication.
Other personnel will be deployed as described below.

Media development
- -----------------
Dr. Alex Sassi will lead the media development effort. He is an expert in
hydrogels, including temperature-responsive gels, with considerable
electrophoresis experience. He will be responsible for overall experimental
design, and will directly conduct experiments on gel phase behavior, stability,
and polymerization of media in the microreplicated systems. Danny Hion will
prepare DNA samples and perform sequencing runs to evaluate gel performance,
activities with which he has significant experience. Dr. Steve Lin will be
responsible for monomer synthesis and for synthesizing novel polymer structures,
such as the graft polymers required for the dynamic porosity gels. Dr. Lin is an
expert in monomer and polymer synthesis. It is expected that Dr. Lin will spend
about 50% of his time on media development, and the other half of his time on
Microreplication development.

Microreplication development
- ----------------------------
Dr. Goretty Alonso will lead the Microreplication effort at SBio, which will
consist of developing base-substrate bonding methods, substrate prototyping via
replication, polymer formulation, and channel surface design and testing. Dr.
Alonso is an accomplished polymer scientist with extensive experience in
polymerization methods, formulation, surface modification and capillary
electrophoresis. Dr. Alonso also has extensive experience in hydrogels from
previous research on contact lenses, and she will consult on the gel development
efforts. Dr. Steve Lin will spend 50% time on this project, assisting Dr. Alonso
in the formulation and surface modification efforts. A polymer engineer will be
hired for design and construction of UV curing and spin coating stations, along
with testing of replication processes. Jules Moolenaar, an experienced
mechanical designer and machinist, will assist the polymer engineer during
design and construction of curing and spin-coating stations, performing
requisite machining tasks. Mr. Moolenaar will also machine plastic plates for
testing in the thin slab system, and perform miscellaneous design/machining
tasks.

In Years 2 & 3, the salaries have been increased by 4 percent for inflation.

Fringe benefits have been calculated as 14 percent of salary.

EQUIPMENT

A prototype of CuraGen's thin slab sequencer is budgeted at [XXXXXX], which will
enable efficient evaluation of media separation properties and testing of
plastic substrates. A UV/VIS (Perkin Elmer model Lambda 11 or equivalent) and a
fluorescence spectrophotometer (PE LX50B or equivalent) are budgeted for
characterizing the optical properties of plastic substrate formulations. We have
budgeted the purchase of components for constructing UV curing and spin-coating
stations, including UV lamp, power supply, motor and mechanical parts. The UV
curing station will be used for replication experiments, and for UV
polymerization of media within the microreplicated systems.

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - Soane BioSciences, Inc.
Page 2

SUPPLIES

Sequencing reagents will be needed to evaluate gel performance, and [XXXXXXXXXX
XXXXXXXXXXXXXXXXX] We budgeted [XXXXXXX] for the purchase of monomers, polymers,
solvents and buffers required in both gel development and microreplication
development. Miscellaneous supplies include machine tools, contract analytical
services (e.g., for specialized surface characterization), replacement parts or
necessary accessories for equipment used in this project, etc.

TRAVEL

A total of 7 trips to CuraGen [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXX]

OTHER EXPENSES

Publication costs are estimated at $2,000 per year, as we expect to report on
advances in several technology areas, including separation media, surface design
of plastics for use in DNA electrophoresis, and microreplication methods.

INDIRECT COSTS

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

DD Principal Investigator/Program Director (Last, first, middle)
Went, Gregory, T.
-----------------
- --------------------------------------------------------------------------------

<TABLE>
<CAPTION>
- ---------------------------------------------------------------------------------------------------------------------------
DETAILED BUDGET FOR INITIAL BUDGET PERIOD FROM THROUGH
DIRECT COSTS ONLY (The Whitehead Institute) 04/01/96 03/31/97
- ---------------------------------------------------------------------------------------------------------------------------
PERSONNEL (Applicant Organization Only) DOLLAR AMOUNT REQUESTED (omit cents)
- --------------------------------------- -----------------------------------------
TYPE
ROLE ON APPT. % EFFORT INST BASE SALARY FRINGE
NAME PROJECT (months) ON PROJ. SALARY REQUESTED BENEFITS TOTALS
- ---------------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C> <C>
Trevor L. Hawkins Principal Investigator 12 [XX] [XXXXXX] [XXXXXX] [XXXXXXX] [XXXXXXX]
- ---------------------------------------------------------------------------------------------------------------------------
Lincoln D. Stein Research Scientist 12 [XX] [XXXXXX] [XXXXXX] [XXXXXXX] [XXXXXXX]
- ---------------------------------------------------------------------------------------------------------------------------
David Goon Technical Assistant 12 [XX] [XXXXXX] [XXXXXX] [XXXXXXX] [XXXXXXX]
- ---------------------------------------------------------------------------------------------------------------------------
William Lee Research Specialist 12 [XX] [XXXXXX] [XXXXXX] [XXXXXXX] [XXXXXXX]
- ---------------------------------------------------------------------------------------------------------------------------

- ---------------------------------------------------------------------------------------------------------------------------

SUBTOTALS---------[XXXXXXX] [XXXXXXXX] [XXXXXXXXX]
- ---------------------------------------------------------------------------------------------------------------------------
<CAPTION>
<S> <C> <C>
CONSULTANT COSTS
[XXXXX]
- -------------------------------------------------------------------------------
EQUIPMENT (Itemize)
Prototype 9mm spacing coated pins for solid-phase additions
(3 @ $5,000/each)) [XXXXXX]

SUPPLIES (Itemize by category)
Magnetic particles, custom synthesis [XXXXXX]
Sequencing reagents (5,000 @ $1/each) [XXXXXX]
Magnets, donuts, dots, bars, custom [XXXXXX]
Plastic plates, tips, etc. [XXXXXX] [XXXXXX]
- --------------------------------------------------------------------------------
TRAVEL

[XXXXXX]
- --------------------------------------------------------------------------------
PATIENT CARE COSTS INPATIENT [XXXXXX]
-------------------------------------------------------
OUTPATIENT [XXXXXX]
- --------------------------------------------------------------------------------
ALTERATIONS AND RENOVATIONS (Itemize by category)
[XXXXXX]
- --------------------------------------------------------------------------------
OTHER EXPENSES (Itemize by category)
Phone $1,000
Photocopying $200
Mail $500
Publication costs $500 [XXXXXX]
- --------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD [XXXXXX]
- --------------------------------------------------------------------------------
CONSORTIUM/CONTRACTUAL COSTS
DIRECT COSTS TOTAL---- [XXXXXX]
- -----------------------------------------------
INDIRECT COSTS [XXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page)---- [XXXXXX]
- --------------------------------------------------------------------------------
</TABLE>

[Confidential Treatment Requested]

<PAGE>

EE Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD
DIRECT COSTS ONLY (The Whitehead Institute)

- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>

BUDGET CATEGORY INITIAL BUDGET ADDITIONAL YEARS OF SUPPORT REQUESTED
PERIOD ------------------------------------------------------------
TOTALS (from page 4) 2nd 3rd 4th 5th
- ---------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C> <C>
PERSONNEL:
Salary & fringe benefits
Applicant organization only [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
CONSULTANT COSTS [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
EQUIPMENT [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
SUPPLIES [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
TRAVEL [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
PATIENT INPATIENT [XXXXXX] [XXXXXX] [XXXXXX]
CARE -------------------------------------------------------------------------------------------
COSTS OUTPATIENT [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
ALTERATIONS AND
RENOVATIONS [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
OTHER EXPENSES [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
SUBTOTAL DIRECT COSTS [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
CONSORTIUM/
CONTRACTUAL COSTS [XXXXXX] [XXXXXX] [XXXXXX]
- ---------------------------------------------------------------------------------------------------------
TOTAL DIRECT COSTS [XXXXXX] [XXXXXX] [XXXXXX]
- -------------------------------------------------------------------------------------------==============
TOTAL DIRECT COSTS FOR ENTIRE PROPOSED PROJECT PERIOD (Item 8a)-- [XXXXXXX]
- -------------------------------------------------------------------------------------------==============
</TABLE>
JUSTIFICATION (Use continuation pages if necessary):

For All Years: Explain and justify purchase of major equipment, unusual
supplies requests, patient care costs, alterations and renovations, tuition
remission, and donor/volunteer costs.

For Competing Continuation Applications: Justify any significant increases or
decreases in any category over the current level of support.

See Attached Budget Justifications Pages

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
---------------
- -------------------------------------------------------------------------------

BUDGET JUSTIFICATIONS - The Whitehead Institute

PERSONNEL

Year 1
Trevor L. Hawkins (Research Scientist and group head of the Center's DNA
sequencing and automation group) [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX]

Lincoln Stein (Research Scientist) is Director of Informatics at the Whitehead
Institute/MIT Center for Genome Research. [XXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX]

David Goon (Technical Assistant) will be committed to the project [XXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

William Lee (Research Specialist) will be committed to this project [XXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

Year 2
As above, with the exception of the reduction of David Goon and William Lee to
[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXX]

Year 3
As Year 2. In Year 3, the salaries have been increased by 4 percent for
inflation.

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

[Confidential Treatment Requested]

<PAGE>

BUDGET JUSTIFICATIONS - The Whitehead Institute
Page 2

EQUIPMENT

Year 1
Qty Item Unit Price Total Price
<S> <C> <C> <C>

3 Prototype 9mm spacing coated pins for
solid-phase additions $5,000 $15,000
<CAPTION>
Our plan for the solid-phase loading is to use a reusable 12 channel
9mm spacing pin set. This allows us to move from any standard 96, 192 or 384
well plate to the gel electrophoresis system without modification. We expect to
make three basic types of pins, one for SPRI, one for Biotin-streptavidin and
one for digoxigenin-anti-digoxigenin.

Year 2
<S> <C> <C> <C>
Qty Item Unit Price Total Price
1 9mm spacing pins for solid or liquid-phase
additions $10,000 $10,000

</TABLE>

The exact design of the 9mm tool head will be the subject of our work
in year 1. At this point we would redesign and improve our best approach from
year 1 to enable us to use the system in year 2. The increased cost of this tool
head reflects the fact that in year 1 we built prototype units.

We will use existing robotic systems for development, to show our strong
commitment to the project.

SUPPLIES

In Years 2 & 3, the supplies costs have been increased by 4 percent for
inflation.

OTHER EXPENSES

In Years 2 & 3, the other expenses will be adjusted 4 percent for inflation.
<PAGE>

FF Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
BIOGRAPHICAL SKETCH
Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Gregory T. Went Vice President

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- -------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Carnegie-Mellon University, Pittsburgh, PA B.S. 1985 Chemical Engineering
University of California, Berkeley, Berkeley, CA Ph.D. 1991 Chemical Engineering
Cornell University, Ithaca, NY PostDoc 1993 Chemical Physics
- -------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------

1993-1994 Director of Structural Biology
CuraGen Corporation, Branford, CT

1994-Present Vice President
CuraGen Corporation, Branford, CT

Honors and Awards:
- -----------------

Olin Summer Research Program, 1984
University Honors, 1985

Bibliography:
- ------------

1. "Microfabricated Device for High-Resolution Multiplex DNA Analysis",
G.T.Went, and J.W.Simpson, to be submitted.

2. "Imaging Spectrograph for DNA Analysis",J.W. Simpson, and G.T. Went,
Analytical Chemistry (1995), to be submitted.

3. "Algorithm for DNA Sequence Determination", J.W.Simpson, R.N. Wright, and
G.T. Went, in preparation (1995).

4. "Standard Absorption Isotherms for Nitrogen and Methane on Graphite:
Improved Resolution at Low Pressure", C.L. Rhykerd, G.T. Went, T.M. Duncan
and K.E. Gubbins, submitted for publication, Langmuir (June 1995)

5. "Oxidation of Reduced Platinum Clusters in Pt-NaY Catalysts", B.F. Chmelka,
G.T. Went, R.Csenscits, A.T. Bell, E.E. Petersen, and C.J. Radke, accepted
for publication, Journal of Catalysis (1994).

6. "A Physico-Chemical Study of the Aging of Zeolite Synthesis Gels", D.M.
Ginter, G.T. Went, C.J. Radke, and A.T. Bell, Zeolites 12 (1992) 733.

- --------------------------------------------------------------------------------
<PAGE>

7. "Laser Raman Spectroscopy of NH3 and ND3 adsorbed on TiO2 (Anatase)", G.T.
Went, A.T. Bell, Catalysis Letters 11, 111 (1992).

8. "Quantitative Structural Analysis of Dispersed Vanadia Species in TiO2
(Anatase)- Supported V2O5", G.T. Went, L. Leu, S. Lombardo, A.T. Bell,
Journal of Catalysis 134, 479 (1992).

Invited Presentations (16 total):
- --------------------------------

"Engineering Novel Pharmaceuticals," Invited Lecture, Department of Chemical
Engineering, University of California, Santa Barbara, CA, May 18, 1995.

"Microfabricated Device for DNA Fragment Analysis," Invited Lecture, BioChips
Conference, Washington DC, May 10, 1995.

"Modular Platform for DNA Fragment Analysis," Invited Lecture, DNA Sequencing,
Mapping and Bioinformatics Conference, San Francisco, CA, July, 1994.

"Kinetic, Thermodynamic and Spectroscopic Studies of Surface Phenomena", Invited
Lecture, Department of Chemical Engineering, Purdue University, Purdue, IL,
November, 1992.

Patents:
- -------

"Apparatus and Method for the Generation, Separation, Detection, and Recognition
of Biopolymer Fragments", J.W. Simpson, J.M. Rothberg, and G.T. Went, U.S.
and Foreign Patent Pending.

"Consensus Configurational Bias Monte Carlo Method and System for Pharmacophore
Structure Determination", M.W. Deem, J.M. Rothberg, and G.T. Went, U.S. and
Foreign Patent Pending.

<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Jonathan M. Rothberg Chief Executive Officer

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- ------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Carnegie-Mellon University, Pittsburgh, PA B.S. 1985 Chemical Engineering
Yale University, New Haven, CT Ph.D. 1991 Molecular Biology
Yale University, New Haven, CT PostDoc 1993 Molecular Biology
- ------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------

1988-Present Member of the Board of Directors
Laticrete International, Inc., Bethany, CT

1991-Present Chairman of the Board of Directors
CuraGen Corporation, Branford, CT

1993-Present Chief Executive Officer
CuraGen Corporation, Branford, CT

Honors and Awards:
- -----------------

National Research Service Award, NIH, 1985-1989
John Spangler Nicholas Prize for the Outstanding Doctoral candidate in
Experimental Zoology, 1991

Bibliography:
- ------------

1. "Modularity of the Slit Protein", J. M. Rothberg, and S. Artavanis-
Tsakonas, S., J. Mol. Biol. 227, 367-370 (1992).

2. "Gene Patents", J.M. Rothberg, Nature 356, 738 (1992).

3. "slit: an Extracellular Protein Necessary for the Development of Midline
Glia and Axon Pathways of the Central Nervous System contains both EGF and
Flank-LRR-Flank Domains", J.M. Rothberg, Ph.D. Thesis, Yale University
(1991).

4. "slit: an Extracellular Protein Necessary for Development of Midline Glia
and Commissural Axon Pathways Contains both EGF and LRR Domains", J.M.
Rothberg, J.R. Jacobs, C.S. Goodman, and S. Artavanis-Tsakonas, Genes &
Development 4, 2169-2187 (1990).

5. "slit: An EGF-Homologous Locus of D. melanogaster Involved in the
Development of the Embryonic Central Nervous System", J.M. Rothberg, D. A.
Hartley, Z. Walther, and S. Artavanis-Tsakonas, Cell 55, 1047-1059 (1988).

<PAGE>

Patents:
- -------

"Apparatus and Method for the Generation, Separation, Detection, and Recognition
of Biopolymer Fragments", J.W. Simpson, J.M. Rothberg, and G.T. Went, U.S.
and Foreign Patent Pending.

"Consensus Configurational Bias Monte Carlo Method and System for Pharmacophore
Structure Determination", M.W. Deem, J.M. Rothberg, and G.T. Went, U.S. and
Foreign Patent Pending.

"Purified slit Protein and Sequence Elements thereof", J.M. Rothberg, and S.
Artavanis-Tsakonas, US Patent Pending, (1990).

<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Michael P. McKenna Senior Research Scientist

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- ------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Carnegie-Mellon University, Pittsburgh, PA B.S. 1984 Molecular Biology
Yale University, New Haven, CT Ph.D. 1993 Biology
- ------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------

1984-1986 Research Associate
Max-Planck-Institute-fur-Entwicklungsbiogiogie, Tubingen, Germany

1992-1994 Graduate Scholar
Miles Biotechnology, West Haven, CT

1994-Present Senior Research Scientist
CuraGen Corporation, Branford, CT

Bibliography:
- ------------
1. "A Single Amino Acid Distinguishes the Interaction of Two Rhinovirus
Stereotypes with Their Receptor, ICAM-1," M.P. McKenna and J. Greve, in
preparation (1994).

2. "Putative Drosophila pheromone-Binding Proteins Expressed in a Subregion of
the Olfactory System," M.P. McKenna, D.S. Heknat-Scafe, P. Gaines, and J.
Carlson, J. Biol. Chem. in press, (1994).

3. "A Simple Chemosensory Response in Drosophila and the Isolation of Acj
Mutants in Which it is Affected," M.P. McKenna, M.P. Monte, S.L. Helfand,
C. Woodard, and J. Carlson, Proc. Nat. Acad. Sci. 86, 8118-8122 (1989).

4. "Growth Cone Behavior on Gradients of Substratum Bound Laminin," M.P.
McKenna, and J. A. Raper, Dev. Biology 130, 232-236 (1988).

5. "A Transient Rise in Cytosolic Calcium Follows Stimulation of Quiescent
Cell with Growth Factors and is Inhabitable with Phorbal Myristate
Acetate," P.L. McNeil, M.P. McKenna, and D. L. Taylor, J. Cell Biology 101,
372-379 (1985).

- --------------------------------------------------------------------------------
<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Gregory T. Mulhern Senior Research Scientist

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- -------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Carnegie-Mellon University, Pittsburgh, PA B.S. 1989 Chemical Engineering
University of California, Berkeley, Berkeley, CA Ph.D. 1995 Chemical Engineering
- -------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------
1988 Research Engineer
Air Products and Chemicals, Allentown, PA

1989 Research Assistant
Carnegie Mellon University, Pittsburgh, PA

1994-1995 Project Engineer
Soane Technologies, Inc., Hayward, CA

1995-Present Senior Research Scientist
CuraGen Corporation, Branford, CT

Honors and Awards:
- -----------------

American Institute of Chemical Engineers Chapter Award for Scholastic
Achievement, 1987
Andrew Carnegie Society Award Finalist, 1989
American Institute of Chemists Foundation Award, 1989

- --------------------------------------------------------------------------------
<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Darin R. Latimer Senior Research Engineer

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- -------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
University of Saskatchewan, Saskatchewan, Canada B.S. 1986 Chemistry
University of Saskatchewan, Saskatchewan, Canada M.Sc. 1989 Chemistry
University of Arizona, Tuscon, AZ Ph.D. 1994 Chemistry
Cornell University, Ithaca, NY PostDoc 1995 Chemistry
- -------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------

1983-1985 Assistant
Global Thermoelectric Generator Systems, Ltd, Alberta, Canada

1995-Present Senior Research Engineer
CuraGen Corporation, Branford, CT

Bibliography:
- ------------

1. "The Preparation and Crystal Structure of Tetrakis (phenylmethoxy methane",
D.R. Latimer, J.A. Weil, J.W. Quail, and W.T. Robinson, Can. J. Chem., 67,
143 (1989).

2. "The ~B - ~X Laser-Induced Fluroescence Excitation Spectrum of Jet-Cooled
Cl2CS: Origin Location and Partial Vibronic Analysis", M. Ludwiczak, D.R.
Latimer, and R.P. Steer, J. Mol. Spectrosc., 147, 414 (1991).

3. "Ion-molecule Reaction Studies Below 10 K: The State Specific Reactions of
Ar+ (2PJ) with H2, D2 and HD", M. A. Smith, M. Hawley, D.R. Latimer, and N.
A. Melosh, Acta Physica Universitatis Comenianae, XXXIV 3 (1994).

4. "Direct Observation of HSF6+ and the Bracketing of the SF6 Proton Affinityt
5 K", D. R. Latimer and M. A. Smith, J. Chem. Phys., 101, 3410 (1994).

5. "Electronic Energy Transfer Kinetics of Xe+ (2P1/2) at Very Low
Temperature", D. A. Latimer, and M.A.Smith, J. Chem. Phys., 101, 3852
(1994).

6. "Gas-Phase Reactions Relevant for Plasma Deposition of Diamond:
Dissociative Charge Transfer of Ar+ ions with CH4 in the Energy Range From
10-4 from 2 e V", P. Tosi, D. Cappelletti, O. Dmitriev, S. Giordani, D.
Bassi, D. R. Latimer, and M. A. Smith, manuscript in preparation.

- --------------------------------------------------------------------------------
<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
John W. Simpson Senior Research Engineer

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- -------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
California Institute of Technology, Pasadena, CA B.S. 1987 Mathematics
California Polytechnic State University, San Luis M.S. 1991 Mechanical Eng.
Obispo, CA
- -------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------
1988-1989 Assistant in Research and Instruction
Princeton University, Princeton, NJ

1992 Research Associate
California Polytechnic State University, San Luis Obispo, CA

1994-Present Senior Research Engineer
CuraGen Corporation, Branford, CT

Honors and Awards:
- -----------------
Caltech Prize Scholarship, 1985
Herbert J. Ryser Memorial Scholarship, 1986
Mobil Fellowship and First Year Merit Prize, 1987

Bibliography:
- ------------

1. "Microfabricated Device for High-Resolution Multiplex DNA Analysis",
G.T.Went, and J.W.Simpson, to be submitted.

2. "Imaging Spectrograph for DNA Sequencing", J. W.Simpson and G. T. Went,
manuscript in preparation, Analytical Chemistry (1995).

3. "Algorithm for DNA Sequence Determination," J.W. Simpson, R.N. Wright, and
G.T. Went, in preparation (1995).

Patents:
- -------

"Apparatus and Method for the Generation, Separation, Detection, and Recognition
of Biopolymer Fragments", J.W. Simpson, J.M. Rothberg, and G.T. Went, U.S.
and Foreign Patent Pending.

<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Aleksandar Milosavljevic Director of Bioinformatics

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- --------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Belgrade University, Belgrade, Yugoslavia B.S. 1984 Electrical Engineering
Santa Clara University, Santa Clara, CA M.Sc. 1986 Computer Science
University of California, Santa Cruz, Santa Cruz, CA Ph.D 1990 Computer and
Informational Sciences
- --------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------

1984-1985 Research Assistant and Lecturer
Santa Clara University, Santa Clara, CA

1986-1990 Research and Teaching Assistant
University of California, Santa Cruz, Santa Cruz, CA

1990-1991 Adjunct Lecturer
Santa Clara University, Santa Clara, CA

1990-1992 Computer Scientist
Linus Pauling Institute of Science and Medicine, Palo Alto, CA

1992-1995 Assistant Scientist
Argonne National Laboratory, Argonne, IL

1995-Present Director of Bioinformatics
CuraGen Corporation, Branford, CT

Bibliography:
- ------------

1. "Learning in the Presence of Background Knowledge", A. Milosavljevic,
Technical Report UCSC-CRL-87-27, (1987).

2. "A Model of Learning Based on the Principle of Cognitive Economy", A.
Milosavljevic, Technical Report UCSC-CRL-88-33, (1988).

3. "Informed Parsimonious Inference of Prototypical Genetic Sequences", A.
Milosavljevic, D. Haussler, and J. Jurka, Proceedings of the Second
Workshop on Computational Learning Theory, (1989).

4. "Categorization of Macromolecular Sequences by Minimal Length Encoding", A.
Milosavljevic, Ph.D. Thesis (1990).

<PAGE>

5. "Reconstruction and Analysis of Human Alu Genes", A. Milosavljevic, Journal
of Molecular Evolution, 32, 105-121 (1991).

6. "Enhanced Malignant Transformation Induced by Expression of a Distinct
Protein Domain of Ribonucleotide Reductase Large Subunit from Herpes
Simplex Virus Type 2", M., Ali, D. McWeeney, A. Milosavljevic, J. Jurka,
and R. Jariwalla, Proc. Natl. Acad. Sci., 88, 8257-8261 (1991).

7. "Prototypic Sequences for Human Repetitive DNA", J. Jurka, J. Walichiewicz,
and A. Milosavljevic, J. Mol. Evol., 35, 286-291 (1992).

8. "Discovery by Minimal Length Encoding: A Case Study in Molecular
Evolution", A. Milosavljevic and J. Jurka, Machine Learning Journal,
Special Issue on Machine Discovery, 12, nos. 1, 2, 3 (1993).

9. "Discovering Simple DNA Sequences by the Algorithmic Significance Method",
A. Milosavljevic, and J. Jurka, Computer Applications in Biosciences, 9,
no. 4 (1994).

10. "Identification and Characterization of New Human Medium Reiteration
Frequency Repeats", J. Jurka, D.J. Kaplan, C.H. Duncan, J. Walichiewicz, A.
Milosavljevic, G. Murali, and J.F. Solus, Nucleic Acids Research, 21, no.
5, 1273-1279 (1993).

11. "Discovering Sequence Similarity by the Algorithmic Significance Method",
A. Milosavljevic, Proceedings of the First International Conference on
Intelligent Systems for Molecular Biology, (1993).

12. "Clone Clustering by Hybridization", A. Milosavljevic, Z. Strezoska, M.
Zeremski, D. Grujuc, T. Paunesku, and R. Crkvenjakov, Genomics, in press.

13. "Repeat Analysis", A. Milosavljevic, Chapter 13, Section IV, Handbook of
Genome Analysis, in press.

- --------------------------------------------------------------------------------
<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.

- --------------------------------------------------------------------------------
NAME POSITION TITLE
Joseph C. Kaufman Director of Software Development

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.)
- --------------------------------------------------------------------------------
<TABLE>
<CAPTION>
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- -------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
California State University, Long Beach, CA B.S. 1983 Chemical
- -------------------------------------------------------------------------------------------------------------
</TABLE>
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- -----------------------

1980-1984 Research Associate
Specialty Labs Inc., Los Angeles, CA

1984-1986 Research Associate
Beckman Research Institute of the City of Hope, Duarte, CA

1986-1991 Scientist/Systems Chemist
Beckman Instruments, Inc., Brea, CA

1991-1995 Senior Software Engineer
Eastman Kodak, New Haven, CT

1994-1995 Software Consultant
Neurogen Corporation, Branford, CT

1995-Present Director of Software Development
CuraGen Corporation, Branford, CT

Honors and Awards:
- -----------------

Gold Nugget Award, Associated Students Honors for Service, CSLUB, 1983
Chemistry Alumni Award, CSLUB, 1983
Distinguished Service Award, Department of Chemistry, CSLUB, 1983
Distinguished Service Award, School of Natural Science, CSLUB, 1983

Bibliography:
- ------------

1. "Evaluation of the recovery between samples presented in primary tubes and
those presented in cups on the Beckman Synchron CX(R)7", B.Davis, and J.C.
Kaufman, Clin.Chem. 37, 872 (1991).

2. "Differential detection of viral DNA and RNA in situ cells infected with
human cytomegalovirus", J.R. McCarrey, J. C. Kaufman, M. A. Churchill, and
J.A. Zaia, Journal of Virological Methods 25, 301-314 (1989).

3. "Evaluation of Cold-Stable Rate-Jaffe creatinine reagent for the use on the
Beckman Synchron CX4/5", J. C. Kaufman et. al, Clin.Chem, 33 951 (1987).

- --------------------------------------------------------------------------------
<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person.
- --------------------------------------------------------------------------------
NAME POSITION TITLE

Harold G. Craighead Professor of Applied and Engineering Physics

- --------------------------------------------------------------------------------
RESEARCH AND/OR PROFESSIONAL EXPERIENCE. Concluding with present position, list,
in chronological order, previous employment, experience and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership or any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

After completing his thesis in experimental physics at the end of 1979,
Dr. Craighead joined Bell Laboratories as a Member of Technical Staff in the
Device Physics Research Department. Research included studies of high-resolution
semiconductor fabrication processes including electron beam lithography with
high energy finely focused electron beams. This work resulted, at the time, in
the creation of the smallest wires and etched structures on GaAs. He did some
of the deepest UV lithography studies with excimer lasers.
At the breakup of AT&T, Dr. Craighead transferred to the newly created
Bell Communications Research and became a research manager in the Solid State
Science and Technology Laboratory. He formed and headed the group responsible
for advanced lithography and device fabrication and ultra-small experimental
device studies. His personal research centered on advanced semiconductor
processing and the properties of ultra-small structures. He explored ion etching
processes in compound semiconductors, with in several cases the first published
accounts of reactive ion etching processes in several material systems. Studies
of ion induced damage and enhanced compositional disordering were exploited to
create quantum wire and dot structures in GaAs/AlGaAs systems. He has worked
extensively on optical materials, device and system studies.
In 1989 Dr. Craighead joined the faculty of Cornell University as a
Professor in the School of Applied and Engineering Physics. From 1989 until 1995
he was Director of the National Nanofabrication Facility at Cornell University.
He is involved in collaborative projects on new molecular species for
microfabrication and cell growth and a developing project on the use of
microfabrication in biology.

Publications (last three years)

"Anisotropic reactive ion etching of InP in methane/hydrogen based plasmas",
J. W. McNabb, H. G. Temkin, and R. A. Logan, J. Vac, Sci. Technol, B. 9,
-
3535 (1991).

"Anisotropic reactive ion etching of InP in methane/hydrogen based plasmas",
J. McNabb, H. G. Craighead, and H. Temkin, in Integrated Photonics Research,
1991, Technical Digest Series, (Optical Society of America, Washington, DC
1991), pp26-27.

"High resolution reactive ion etching of SiGe Alloys", J. G. Couillard, H. G.
Craighead, J. Vac, Sci. Technol, B. 11, 717 (1993).
--

"Lateral patterning of nanostructures", H. G. Craighead in Physics of
Nanostructure, A. Long, editor (1992) (NATO summer school).

"Ballistic electron emission microscopy investigation of SiGe nanostructures
fabricated using high resolution electron beam lithography and reactive ion
etching", A. Davies, J. G. Couillard, and H. G. Craighead, Appl. Phys. Lett. 61,
--
1040 (1992).

<PAGE>

Principal Investigator/Program Director (Last, first, middle): Went, Gregory T.
- --------------------------------------------------------------------------------

"Ballistic electron emission microscopy investigation of SiGe nanostructures
fabricated using reactive ion etching", J. G. Couillard, A. Davies, and H. G.
Craighead, J. Vac. Sci. Technol B, 10, 3112 (1992).
--

"A method of fabrication submicrometer gold wires on optical fibers", L. M.
Schiavone, H. G. Craighead, and S. DiVita, Thin Silid Films, 208, 156 (1992).
---

"A self assembled monolayer electron beam resist on GaAs", R. C. Tiberio, H. G.
Craighead, M. Lercel, T. Lau, C. W. Sheen and D. L. Allara, Appl. Phys. Lett,
62, 476, (1993).
- --

"Proton implantation intermixing of GaAs/AlGaAs quantum wells", G. F. Redinbo,
H. G. Craighead and J. M. Hong, J. Appl. Physics 74, 3099, (1993).
--

"A simple surface emitting LED array for free-space optical interconnects",
H. F. Bare, F. Haas, D. A. Honey, D. Mikolas, H. G. Craighead, G. Pugh and
R. Soave Photonics Technol. Lett, 5, 172 (1993).
-

"Fabrication of aspheric high numerical aperture reflective diffractive optic
elements using electron beam lithography", D. Mikolas, R. Bojko, H. G.
Craighead, F. Haas, D. A. Honey and H. F. Bare, J. Vac. Sci. Technol. B, 12, 20
--
(1994).

"Photolithography of Porous Silicon", J. G. Couillard and H. G. Craighead, J.
Vac. Sci. Technol. B. 12, 161 (1994).
--

"Focused ion beam interactions with a shallow two-dimensional electron gas",
Y. A. Soh, G. L. Snider, M. J. Skvarla, and H. G. Craighead, J. Vac. Sci.
Technol. B, 11, 2629 (1993).
--

"Self assembled monolayer electron beam resists on GaAs and SiO2", M. Lercel, R.
C. Tiberio, H. G. Craighead, C. W. Sheen, A. N. Parikh, and D. L. Allara, J.
Vac. Sci. Technol. B, 11, 2823 (1993).
--

"Ballistic-electron-emission microscopy characteristics of reverse-biased
Schottky diodes", A. Davies and H. G. Craighead, Appl. Phys. Lett, 64, 2833
--
(1994).

"Fabrication of a multilevel structure for nanophysics in two-dimensional
electron gases", Y-A. Soh. G. L. Snider, M. J. Rooks, H. G. Craighead and
J. Parpia, J. Vac. Sci. Technol. B, 12, 1372 (1994).
--

"Binary optics for optical interconnects", S. M. Shank and H. G. Craighead, (to
appear in Proc. SPIE 2216 (1994))
----

"Scanning tunneling microscopy based lithography of octadecanethiol on Au and
GaAs", M. J. Lercel G. F. Redinbo, H. G. Craighead, C. W. Sheen and D. L.
Allara, Appl. Phys. Lett 65, 974 (1994).
--

"Diffractive phase elements based on two-dimensional artifical dielectrics",
F. T. Chen and H. G. Craighead, Optics Letters 20 No. 2, 121 (1995)
--

- --------------------------------------------------------------------------------

<PAGE>

Trevor Hawkins Research Scientist

- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding with present position, list in
chronological order previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the project. Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership on any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. DO NOT
EXCEED TWO PAGES.

Professional Experience:
- ------------------------
1989-1990 Research and Teaching Assistant, Center for Medical Research,
University of Sussex, United Kingdom.
1990-1992 Research Scientist, Medical Research Council, Cambridge, United
Kingdom.
1992-1993 Staff Scientist, Medical Research Council, Cambridge, United
Kingdom.
1993 Senior Scientist, Promega Corporation, Madison Wisconsin.
1993-present Research Scientist, Whitehead Institute/MIT Center for Genomic
Research.

Publications:
- -------------
Hawkins, T.L., and Sulston, J.E.(1990). Automated fluorescent primer walking.
Technique-A journal of methods in cell and molecular biology. 2.6. 307-310.
Hawkins, T.L., and Sulston, J.E.(1991). The resolution of compressions in
automated fluorescent sequencing. Nucl. Acids. Res. 19.10.2784.
Sulston, J., and Hawkins, T.L., et al (1992). The C.elegans genome sequencing
project: A beginning. Nature 356:37-41.
Waterson, R. and Hawkins, T.L. et al (1992). A survey of expressed genes in
Caenorhabditis elegans. Nature genetics 1:114-123.
Hawkins, T.L., Du, Z., Halloran, N.D., and Wilson, R.K.(1992). Fluorescence
chemistries for automated primer-directed DNA sequencing. Electrophoresis
13:552-559.
Hawkins, T.L. (1992). M13 single-stranded purification using a biotinylated
probe and streptavidin coated magnetic beads. DNA sequence- J.DNA Sequencing
and Mapping. 3:65-69.
Hawkins, T.L. The use of magnetic particles in molecular biology. In Automated
DNA sequencing and analysis techniques, Ed. Craig Venter, J.
Ainscough, R., and Hawkins, T.L. et al. (1993). Sequencing the genome. WBG
93.340-343.

Berks, M., and Hawkins, T.L. et al (1993). WBG 123.22-25.

Watson, A., Smaldon, N., Lucke, R., and Hawkins, T.L. (1993). The Caenorhabdiris
elegans project: first steps in automation. Nature. 362:569-570.
Wilson, R., Hawkins, T., et al. (1994). 2.2Mb of contiguous nucleotide sequence
from chromosome III of C. elegans. Nature 368:32-38.
Hawkins, T.L. (1994). In automated DNA sequence analysis. Ed. Craig Ventor,
Academic Press.

Hawkins, T.L., O'Connor-Morin, T., Roy A., and Santillan, C. (1994). DNA
purification and isolation using a solid-phase, Nucl. Acids, Res. In press
Hawkins, T.L., O'Connor-Morin, T., Ingalls, K., Levinson, D., DeAngelis, M.,
Santillan, C., and Evans, C. (1994). Solid-phase molecular biology. Biomedical
products. December issue. Ed Steve Ernst.

<PAGE>

FF Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
Page 2

Hawkins, T.L., Banerjee S.R., Brodowski, C., Days, F., Levinson, D., and
Ingalls, K. (1995) Thermal Cycle DNA Sequence set up using a modified
lab workstation. In press.
Whitfield, L.S., Goodfellow, P.N., Sulston, J., and Hawkins, T.L., 41 Kilobases
of Analyzed Sequence from the pseudoautosomal and Sex-determining
regions of the short arm of Human Y chromosome. Submitted.
Santillan, C., Roy, A., and Hawkins, T.L., Isolation of DNA from agarose gel
using a solid-phase. Submitted.

DeAngelis, M., and Hawkins, T.L., Solid-Phase Reverse immobilzation for the
isolation of PCR products. Submitted.
Ingalls, K., Levinson, D., and Hawkins, T.L., Solid-Phase Reversible
immobilization for the isolation of cosmid DNA suitable for library
construction. Submitted.

- --------------------------------------------------------------------------------

<PAGE>

Herbert H. Hooper Vice President, Research

North Carolina State University B.S. 1985 Chem. Eng.

University of California, Berkeley Ph.D. 1990 Chem. Eng.

- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE. Concluding with present position, list, in
chronological order, previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the project. Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership on any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. If
the list of publications in the last three years exceeds two pages, select the
most pertinent publications. DO NOT EXCEED TWO PAGES.

Experience:
- -----------

1985-1990 Graduate Research Assistant, University of California, Berkeley
1990 Postdoctoral Research Fellow, University of California, Berkeley
1990-1993 Senior Research Engineer, Air Products and Chemicals, Inc.,
Allentown, PA
1993-present Vice President, Research, Soane BioSciences, Inc.

Awards:
- -------
Principal Investigator on NIH SBIR awards and Advanced Technology Program award.

Publications:
- -------------
Sassi, A.P., S. Beltran, H.H. Hooper, H.W. Blanch and J.M. Prausnitz, Monte
Carlo Simulations of Hydrophobic Weak Polyelectrolytes; Titration Properties
and pH-Induced Structural Transitions. J. Chem. Phys., 97(11), 8767(1992).
Baker, J.P., H.H. Hooper, H.W. Blanch and J.M. Prausnitz, Swelling Equilibria
for Weakly-Ionizable, Temperature-Sensitive Hydrogels, Macromolecules, 24,
549(1991).
Hooper, H.H., S. Beltran, A.P. Sassi, H.W. Blanch and J.M. Prausnitz, Monte
Carlo Simulations of Hydrophobic Polyelectrolytes: Evidence for a Structural
Transition in Response to Increasing Chain Ionization, J. Chem. Phys., 93(4),
2715(1990).
Hooper, H.H., H.W. Blanch and J.M. Prausnitz, Configurational Properties of
Partially Ionized Polyelectrolytes from Monte Carlo Simulation,
Macromolecules, (1990).
Beltran, S., H.H. Hooper, H.W. Blanch and J.M. Prausnitz, Swelling Equilibria
for Ionized Temperature Sensitive Gels in Water and Aqueous Salt Solutions, J.
Chem. Phys., 92(3), 2061(1990).
Hooper, H.H., H.W. Blanch, J.M. Prausnitz, Molecular Thermodynamics of Aqueous
Polymers and Gels, in Absorbent Polymer Technology, Elsevier Publishers
(1990).
Hooper, H.H., Swelling Equilibria for Positively Ionized Polyacrylamide
Hydrogels, Macromolecules, 23, 1096(1990).
Prange, M.M., H.H. Hooper and J.M. Prausnitz, Thermodynamics of Aqueous Systems
Containing Hydrophilic Polymers or Gels, AICHE J., 35(5), 803(1989).
Michel, S., H.H. Hooper and J.M. Prausnitz, Mutual Solubilities of Water and
Hydrocarbons from an Equation of State, Fluid Phase Equil., 45, 173(1989).

<PAGE>

Hooper, H.H., S. Michel and J.M. Prausnitz. Correlation of Liquid-Liquid
Equilibria for Some Water/Organic-Liquid Systems in the Region 20-250C. Ind.
Eng. Chem. Res., 27(11), 2182(1988).
Hooper, H.H., S. Michel and J.M. Prausnitz. High-Temperature Mutual
Solubilities for some Binary and Ternary Aqueous Mixtures Containing
Aromatic and Chlorinated Hydrocarbons, J. Chem. Eng. Data. 33(4), 502
(1988).

Patents:
--------
H.H. Hooper, S. Pacetti, D.S. Soane and Y.C. Bae. Separation Media for
Electrophoresis, patent pending.

- --------------------------------------------------------------------------------
<PAGE>

David S. Soane Chairman, Scientific Advisory Board

National Taiwan University B.S. 1973 Chemistry
University of California, Berkeley M.S. 1977 Chemical Eng.
University of California, Berkeley Ph.D. 1978 Chemical Eng.

- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE. Concluding with present position, list, in
chronological order, previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the proper Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership or any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. If
the list of publications in the last three years exceeds two pages, select the
most pertinent publications. DO NOT EXCEED TWO PAGES.

Experience
- ----------

1978-1979 Postdoctoral Research Associate, Department of Chemical
Engineering, UC Berkeley
1979-1983 Assistant Professor, Department of Chemical Engineering, UC
Berkeley
1983-1987 Associate Professor, Department of Chemical Engineering, UC
Berkeley
1984-present Associate Faculty Scientist, Center for Advanced Materials,
Lawrence Berkeley Lab
1985-1986 Sabbatical Leave at IBM, Almaden Research Laboratory and Kyoto
University, Japan
1986-1989 Vice Chairman, Department of Chemical Engineering, UC Berkley
1987-1994 Professor, Department of Chemical Engineering, UC Berkeley
1994-present Adjunct Professor, Department of Chemical Engineering, UC
Berkeley
1991-present Founder and Chairman, Soane Technologies, Inc.
1993-present Chairman, Scientific Advisory Board, Soane BioSciences, Inc.

Honors:
- ------
Earl C. Anthony Fellowship, 1976
Camille and Henry Dreyfus Teach-Scholar Award, 1984

Society Activities:
- ------------------
Editorial Advisory Board, Journal of Applied Polymer Science, 1983-1989
Editorial Advisory Board, Journal of Biomaterials, 1985-present
Membership and Examination Committees, Polymer Division, American Chemical
Society, 1982-present
Board of Directors, Golden Gate Chapter, Society of Plastics Engineers,
1982-present
Executive Committee, Northern California Section, American Institute of
Chemical Engineers, 1983-1984

Selected Publications (total greater than 170):
- ----------------------------------------------
Barron, A.E., H.W. Blanch and D.S. Soane. A Transient Entanglement Coupling
Mechanism for DNA Separation by Capillary Electrophoresis in Ultra-Dilute
Polymer Solutions.
Electrophoresis. 15.597 (1994).

- --------------------------------------------------------------------------------

<PAGE>

Yonkoski, R.K., A Mathematical Model for Planarization of Microelectronic
Topographies. J. Electochem. Soc., 141,585 (1994)
Monk, D.J., D.S. Soane and R.T. Howe, Hydrofluoric Acid Etching of Silicon
Dioxide Sacrificial Layers, 2. Modeling, J. Electochem. Soc., 141, 270
(1994).
Monk, D.J., D.S. Soane and R.T. Howe, Hydrofluoric Acid Etching of Silicon
Dioxide Sacrificial Layers, 1. Experimental Observations, J. Electrochem,
Soc., 141. 264 (1993).
Barron, A.E.D.S. Soane and H.W. Blanch, Capillary Electrophoresis of DNA in
Uncrosslinked Polymer Solutions, J. Chrom., 652.3 (1993).
Bae, Y.C., and D.S. Soane, Polymeric Separation Media for Electrophoresis;
Crosslinked Systems or Entangled Solutions, J. Chrom. A., 652 (1), 17
(1993).
Monk, D.J., D.S. Soane and R.T. Howe, A Review of the Chemical Reaction
Mechanism and Kinetics for Hydrofluoric Acid Etching of Silicon Dioxide for
Surface Micromachining Applications, Thin Solid Films, 231,1 (1993).
Monk, D.J. Soane and R.T. Howe, LPCVD Silicon Dioxide Sacrificial Layer Etching
for Surface Micromachining, Proc. Mac. Res. Soc. 264,303 (1992).
Hino, T., P.D. Grossman and D.S. Soane, Dynamic Light Scattering Studies of HEC
Solutions used as Sieving Media for Electrophoretic Separations, J. Chrom.,
608,79 (1992).
Grossman, P.D., and D.S. Soane, Capillary Electrophoresis of DNA in Entangled
Polymer Solutions, J. Chrom., 559,257 (1991).
Grossman, P.D., and D.S. Soane, Experimental and Theoretical Studies of DNA
Separations by Capillary Electrophoresis in Entangled Polymer Solutions,
Biopolymers, 31,1221 (1991).

Selected Presentations:
- -----------------------
Soane, D.S., Advances in Gel Matrices for DNA Electrophoresis, presented at The
Human Genome Project: Commercial Implications, San Francisco, CA. March,
1995.
Soane, D.S., Replaceable Crosslinked Gels for DNA Analysis by Capillary
Electrophoresis, presented at Third International Symposium on Capillary
Electrophoresis, York, UK, August, 1994.

Books:
- ------
Soane, D.S. ed. Polymers for Biotechnology; Macromolecular Separation and
Identification. Prentice Hall, New York, 1992.
Soane, D.S. and Z. Martynenko, Polymers in Microelectronics; Fundamentals and
Applications, Elsevier, New York and Amsterdam, 1989.

Selected Patents (total greater than 15);
- -----------------------------------------
Soane, D.S. and Y.C. Bae, Separation Media for Electrophoresis, WO 94/10561.
Soane, D.S., Mosaic Microcolumns, Slabs and Separation Media for Electrophoresis
and Chromatography, US Patent 5,135,627 (1992).
Soane, D.S. and Z.M. Soane, Method and Device for Moving Molecules by the
Applications of a Plurality of Electrical Fields, US Patent 5.126.022
(1992).
Soane, D.S. Controlled Casting of a Shrinkable Material, US Patent 5.110.514
(1992).
Soane, D.S., Gel Casting Method and Apparatus, US Patent 5.061.336 (1991).
Soane, D.S., Casting of Gradient Geis, US Patent 5.135.627 (1991).

<PAGE>

Goretty Alonso Amigo Senior Scientist

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.
- --------------------------------------------------------------------------------
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- --------------------------------------------------------------------------------
University of Valladolid, Spain BS 1978 Chemistry
University of Detroit, Michigan MSEC 1983 Science & Chem.
University of Detroit, Michigan Ph.D. 1988 Macromolecular
Ch.
- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE. Concluding with present position, list, in
chronological order, previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the project Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership on any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. If
the list of publications in the last three years exceeds two pages, select the
most pertinent publications. DO NOT EXCEED TWO PAGES.

Experience:
- -----------
1979-1981 Science Teacher, ICEDE Professional School, Burgos, Spain
1981-1984 Research Assistant, Polymer Technologies Inc., University of
Detroit, Detroit, MI
1984-1988 Graduate Research Assistant, University of Detroit, Detroit, MI
1989-1991 Materials Scientist, Polymer R&D, Pilkington Barnes Hind,
Sunnyvale, CA
1991-1993 Manager, Analytical Chemistry R&D, Pilkington Barnes Hind,
Sunnyvale, CA
1994 Adjunct Professor, San Jose State University, San Jose, CA
1993-1995 Manager, Polymer R&D, Pilkington Barnes Hind, Sunnyvale, CA
1995-present Senior Scientist, Soane BioSciences, Inc.

Publications:
- -------------

M.G. Alonso-Amigo and S. Schlick, ESR of Cu/2+/ in Nafion Ionomers,
Polymer Preprints (American Chemical Society, Polymer Division
Preprints, 27,337(1986).

M.G. Alonso-Amigo and S. Schlick, Detection of Isolated and Paired
Cu/2+/ Ions in Nafion Membranes by ESR Spectroscopy, Journal of Physical
Chemistry, 90, 6353 (1986).

D. Becker, J. Yanez, M.D. Sevilla, M.G. Alonso-Amigo and S. Schlick, An
Electron Spin Resonance Investigation of the Motion of Lipid Peroxyl
Radicals, Journal of Physical Chemistry. 91, 492, (1987).

M.G. Alonso-Amigo and S. Schlick, Study of Mobile and Rgid Peroxy
Radicals in Polypropylene, Macromolecules, 20, 795, (1987).

M.G. Alonso-Amigo and S. Schlick, Binding of Paramagnetic Ions in
Ionomers, Cu/2+/ and Ti/3/- in Nafion Membranes, Journal of Chemical
Society, Faraday Transactions I. 83, 3575 (1987).

M.G. Alonso-Amigo and S. Schlick, Detection of Isolated, Paired and
Clustered Ti/3+/ in Nafion by ESR Spectroscopy, Polymer Preprints
(American Chemical Society, Polymer Division Preprints), 28(2), 363,
(1987).

S. Schlick, R.D. Harvey, M.G. Alonso-Amigo and D. Klempner, Study of
Phase Separation in LPNs Using Nitroxide Spin Labels, Macromolecules,
22, 822 (1989).

M.G. Alonso-Amigo and S. Schlick, Determination of the Distance Between
Paramagnetic Centers from ESR Spectra at L. S and X Bands, Cu/2+/ in
Nafion Ionomers. Macromolecules, 22 2638 (1989).

- --------------------------------------------------------------------------------

<PAGE>

FF Principal Investigator Program Director (Last, first, middle):
Went Gregory T.
---------------
- --------------------------------------------------------------------------------
Biographical Sketch
Goretty A. Amigo
Page 2

M.G. Alonso-Amigo and S. Schlick, Local Environment and Clustering of
Cations in Ionomers. ESR of Cu/2/+ in Nafion Swollen by Water,
Methanol,Dimethylformamide and Tetrahydrofuran. Macromolecules, 22, 2634
(1989).

S. Schlick, M.G. Alonso-Amigo and S.S. Eaton, Structure of Cu/2/+_Cu/2/
Dimers in Nafion Swollen by Water, Methanol, DMF and THF. ESR Results and
Theoretical Simulations. Journel of Physical Chemistry, 93, 7906 (1989)

S. Schlick and M.G. Alonso-Amigo, Co-Cation Enhanced Electron Transfer in
Nafion Neutralized by Ti/3/+. Study of O\\2\\ Formation by ESR. Polymer
Preprints (American Chemical Society), 30 (1), 440 (1989).

M.G. Alonso-Amigo and S. Schlick, O\\2\\ Formation in Nafion by Electron
Transfer from Ti/3/+. The Effect of Al/3/+ as Cocation, Journal of Physical
Chemistry, 93, 7526 (1989).

Shulamith Schlick, M.G. Alonso-Amigo and Janusz Bednareck, Multifrequency
Electron Spin Resonance and Electron Nuclear Double Resonance Studies of
Metal Carions in Perfluorinated Ionomers, Colloids and Surfaces A:
Physicochemical and Engineering Aspects. 72, 1 (1993).

<PAGE>

Alexander P. Sassi Senior Research Engineer

University of Washington, Seattle BSChE 1988 Chemical Eng.

University of California, Berkeley Ph.D. 1994 Chemical Eng.

- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE. Concluding with present position, list, in
chronological order, previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the project Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership on any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. If the
list of publications in the last three years exceeds two pages, select the most
pertinent publications. DO NOT EXCEED TWO PAGES.

Experience:
- -----------
1988 Engineer Intern, Exxon Production Research, Houston, TX
1988-1995 Graduate Research Assistant, University of California, Berkeley
1994 Visiting Researcher, Eisai Co., Ltd., Tsukuba, Japan
1995-present Senior Research Engineer, Soane BioSciences, Inc.

Awards:
- -------
Principal Investigator on NIH SBIR Phase I grant, Constant-Field Electrophoresis
of Large DNA.

Publications:
- -------------

Sassi, A.P., H.W. Blanch, and J.M. Prausnitz, Phase Equilibria for Aqueous
Protein/Polyelectrolyte Gel Systems, submitted to AIChE Journal.
Sassi, A.P., D. Freed, H.W. Blanch, and J.M. Prausnitz, Partitioning of
Hexavalent Chromium in Temperature-Sensitive, Polyelectrolyte Hydrogels,
submitted to Polymer Gels and Networks.
Sassi, A.P., A. Shaw, S. Han, H.W. Blanch, and J.M. Prausnitz, Partitioning of
Proteins and Small Biomolecules in Temperature-and pH-Sensitive Hydrogels,
accepted by Polymer (1995).
Sassi, A.P. S.H. Lee, Y. Park, H.W. Blanch, and J.M. Prausnitz, Sorption of
Lysozyme by HEMA Copolymer Hydrogels, accepted by Journal of Applied Polymer
Science (1995).
Sassi, A.P., H.W. Blanch, and J.M. Prausnitz, Characterization of Size-Exclusion
Effects in Highly Swollen Hydrogels: Correlation and Prediction, accepted by
Journal of Applied Polymer Science (1995).
Sassi, A.P., H.W. Blanch, and J.M. Prausnitz, Feasibility Studies for
Separations Processes Using Environmentally Sensitive Hydrogels, Lawrence
Berkeley Laboratory, LBL Report #36405 (1994).
Sassi, A.P., J.L.F. Abascal, H.W. Blanch, and J.M. Prausnitz, Monte Carlo
Simulations of a Hydrophobic Weak Polyelectrolyte. Charge Distribution as a
Function of Conformation. J. Chem. Phys. 99(5), 4231 (1993).

<PAGE>

Sassi, A.P., S. Beltran, H.H. Hooper, H.W. Blanch, J.M. Prausnitz and R.A.
Siegel Monte Carlo Simulations of Hydrophobic Weak Polyelectrolytes:
Titration Properties and pH-Induced Structural Transitions for Polymers
Containing Weak Electrolytes, J. Chem. Pys., 97 (11), 8767 (1992).

Sassi, A.P., H.W. Blanch, and J.M. Prausnitz, Crosslinked Gels as Water
Absorbents in Separations, chapter 8 in Polymer Applications for
------------------------
Biotechnology, D.S. Soane, ed. Englewood Cliffs: Prentice Hall (1992)
-------------

Hooper, H.H. S. Beltran. A.P. Sassi, H.W. Blanch and J.M. Prausnitz, Monte Carlo
Simulations of Hydrophobic Polyelectrolytes: Evidence for a Structural
Transition In Response to Increasing Chain Ionization, J. Chem. Phys.,
93 (4), 2715 (1990).

<PAGE>

Danny Hion Research Biochemist

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training.
- --------------------------------------------------------------------------------
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- --------------------------------------------------------------------------------
University of California, Berkeley BA 1992 Molecular
Biology
Genetics
- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE. Concluding with present position, list, in
chronological order, previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the project Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership on any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. If the
list of publications in the last three years exceeds two pages, select the most
pertinent publications. DO NOT EXCEED TWO PAGES.

Experience:
- -----------
1993-present Research Biochemist, Soane BioSciences, Inc.
Experienced in DNA sequencing sample prep and electrophoresis
(Slab and Capillary).

<PAGE>

Give the following information for the key personnel and consultants and
collaborators. Begin with the principal investigator/program director.
Photocopy this page for each person
- --------------------------------------------------------------------------------
NAME POSITION TITLE

Shi Lin Postdoctoral Scientist

- --------------------------------------------------------------------------------
EDUCATION (Begin with baccalaureate or other initial professional education,
such as nursing, and include postdoctoral training
- --------------------------------------------------------------------------------
YEAR
INSTITUTION AND LOCATION DEGREE CONFERRED FIELD OF STUDY
- --------------------------------------------------------------------------------
South China University of Technology BS 1982 Chem. Eng.
South China University of Technology MS 1985 Chem. Eng.
SUNY College of Env. Sci. & Forestry Ph.D. 1994 Polym. Chem
Syracuse
- --------------------------------------------------------------------------------
RESEARCH AND PROFESSIONAL EXPERIENCE. Concluding with present position, list, in
chronological order, previous employment, experience and honors. Key personnel
include the principal investigator and any other individuals who participate in
the scientific development or execution of the project. Key personnel typically
will include all individuals with doctoral or other professional degrees, but in
some projects will include individuals at the masters or baccalaureate level
provided they contribute in a substantive way to the scientific development or
execution of the project. Include present membership on any Federal Government
public advisory committee. List, in chronological order, the titles, all
authors, and complete references to all publications during the past three years
and to representative earlier publications pertinent to this application. If the
list of publications in the last three years exceeds two pages, select the most
pertinent publications. DO NOT EXCEED TWO PAGES.

Experience:
- -----------
1982 Research Associate, Guangdong Provincial Research Institute of
Man-Made Fiber, China
1982-1985 Graduate Assistant, South China University of Technology
1985-1986 Faculty of Chemical Engineering, South China University of
Technology
1987-1994 Research Project Assistant, SUNY College of Environmental Science
and Forestry, Syracuse
1995-present Postdoctoral Scientist, Soane BioSciences, Inc.

Publications:
- -------------
Shi Lin and Israel Cabasso, Synthesis and Characterization of
Carbamoylphosphonate Monomer and It's Copolymer with Styrene, II, submitted
to J. Polym. Sci. Polym. Chem. Ed.
Shi Lin and Israel Cabasso, Synthesis and Properties of
Poly{5-oxy[2-(2',2'-diethoxyphosphonoethyl)-1.3-dioxane]methyl siloxane}, to
be published
Shi Lin and Israel Cabasso, Synthesis and Characterization of
Poly{[(diethylphosphonobenzyl) a. b-ethyl] methyl siloxane} and Its Salt
Complexes, to be published
Su Maoyao, Gao Guang and Lin Shi, A Study on the Effects of Pretreatment by
Chemical Activation on the Fine Structure and Reactivity of Cellulose Fiber,
J. South China University of Technology, 17(1), 94, (1984)
Yang ZhiLi, Wu GuoMin, Mei ChienFong, Gao Guang, Lin Shi, Liu HaiMin and Zou
JingHong, Study on the Manufacture of Rayon Fiber from a PF/DMSO Solvent
System, Cellulose Chem. Technol., 21.493 (1987)

Patents:
- --------
I. Cabasso and S. Lin, Water Soluble Phosphorylated Polysiloxanes. US patent
pending.
I. Cabasso and S. Lin, Hydrogels and Salt Complexes form Novel Phosphorylated
Siloxane. US patent pending.

- --------------------------------------------------------------------------------
<PAGE>

William Lee Research Specialist

Massachusetts Institute of Technology B.S. 1995 Mechanical Eng.

- --------------------------------------------------------------------------------
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list
in chronological order previous employment, experience, and honors. Key
personnel include the principal investigator and any other individuals who
participate in the scientific development or execution of the project. Key
personnel typically will include all individuals with doctoral or other
professional degrees, but in some projects will include individuals at the
masters or baccalaureate level provided they contribute in a substantive way to
the scientific development or execution of the project. Include present
membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all
publications during the past three years and to representative earlier
publications pertinent to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- ------------------------

1992-1995 Artificial Muscle Group. Artificial Intelligence Laboratory,
MIT
(1995) Second Phase Gel Model
(1994) pH Imaging System
(1994) Linear Gel Based Actuaor Test Bed
(1994) Small Scale Test Bed and Gel Fluid Model
(1993) Tabletop Cylindrical Gel Based Actuator Test Bed
(1992) Investigation of Mechanical Properties of PAN Fiber Gels
1995-present Research Specialist. Whitehead Institute for Biomedical
Research/MIT Center for Genome Research

Publications:
- -------------
None.

<PAGE>

Lincoln Stein Research Scientist

- --------------------------------------------------------------------------------
RESEARCH AND/OR PROFESSIONAL EXPERIENCE: Concluding with present position, list,
in chronological order, previous employment, experience and honors, the
principal investigator and any other individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project. Include present membership on any Federal Government public
advisory committee. List, in chronological order, the titles, all authors,
during the past three years and to representative earlier publications pertinent
to this application. DO NOT EXCEED TWO PAGES.

Professional Experience:
- ------------------------
1980-1982 Graduate Student Laboratory of George Scangos, John Hopkins
University Dept. of Biology; eukaryotic transcription promoters
using DNA-mediated gene transfer
1983 Graduate Student Laboratory of Richard Mulligan, M.I.T. Center
for Cancer Research; extendin of retrovirus vectors
1986 Microbiology laboratory instructor, New England Baptist Hospital
School of Nursing
1986-1988 Lecturer for veterinary parasitology and infectious disease
courses at Tufts University Veterinary
1984-1989 Graduate Student Laboratory of John David Harvard School of
Public Health; cloning of deve?? regulated genes from
Schistosoma mansoni
1990 Instructor for Harvard Medical School courses in infectious
diseases and gastrointestinal pathop???
1992-1994 Assistant Director, Informatics Core, Whitehead Institute/MIT
Center for Genome Research.
1990-present Instructor, Harvard Medical School, Department of Pathology.
Brigham and Women's Hospital
1994-present Director, Informatics Core, Whitehead Institute/MIT Center for
Genome Research.

Honors and Awards:
- ------------------

1978 National Merit Scholarship, Johns Hopkins University
1979 Phi Beta Kappa, Johns Hopkins University
1984 Medical Scientist Training Program Scholarship, Harvard Medical
School
Publications:
- -------------

Copeland, N.G., D.J. Gilbert, N.A. Jenkins, J.H. Nadeau, J.T. Eppig, L.J.
Maltais, J.C. Miller, W.F. Dietrich, S.E. Lincoln, A. Weaver, D.C. Joyce, M.
Merchant, M. Wessel, H. Katz, L.D. Stein, M.P. Reeve, R.D. Dredge, A. Marquis,
N. Goodman, and E.S. Lander(1993) Genome Maps IV Science 262:67-82
--------------
Copeland, N.G., N.A. Jenkins, D.J. Gilbert, J.T. Eppig, L.J. Maltais, J.C.
Miller, W.F. Dietrich, A. Weaver, R.G. Steen, L.D. Stein, J.H. Nadeau, and
E.S. Lander(1993) A genetic linkage map of the mouse: C applications and
future prospects. Science 262:57-66.
-------
Dietrich, W.F., J.C. Miller, R.G. Steen, M. Merchant, D. Damron, R. Nahf, D.C.
Joyce, R.D. Dredge, A. Weaver, L.D. Stein, N. Goodman, D.C. Page, and E.S.
Lander(1994). A genetic map of the mouse with 4,006 simple length
polymorphisms. Nature Genetics, 7:220-245.
------ --------
Genest, D., Stein, L., Cibas, E., Sheets, E., Zitz. J., Crum, C.(1993) A Binary
(Bethesday) System for Class Cancer Precursors: Criteria, Reproducibility and
Viral Correlates. Human Path, 24:730-736.
----------
Goodman, N., Rozen S., Stein, L.(1993). Requirements for a Deductive Query
Language in the MapBase Ge???? Database. Workshop on Programming with Logic
----------------------------------
Databases, Vancouver, BC. Oct. 30, 1993.
---------
Goodman, N., Rozen S., Stein, L.(1994). Constructing a domain-specific DBMS
using a persistent object systems International Workshop on Persistent Object
-------------------------------------------
Systems, In press.
-------

<PAGE>

FF Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
Page 2
Miller, J., W. Dietrich, R. Steen, D. Joyce, M. Merchant, M. Wessel, D. Damron,
R. Nahi, L. Stein, R. Dredg M. Daly, M.P. Reeve, N. Goodman, C.J. Lord,
C.T. Montague, J.B. Prins. J. Todd, and E.s. Lande SSLP/Microsatellite
genetic linkage map of the mouse. In: Genetic Variants and Strains of the
------- -------- --- ------- -- ---
Laboratory Edition. M.F. Lyon, and A.G. searle, eds., Oxford University
---------- -------
Press.
Shoemaker, C. Ramachandran, H. Landa, H. dos Reis, M. Stin, L. (1992),
Alternative splicing of the Six gene encoding a homologue of epidermal
growth factor receptor. Mol Biochem Parasitol 53:17-32.
---------------------
Skelly, P.J., Stein, L.D. Shoemaker, C. (1993). Expression of Schistosoma
mansoni genes involved in ____ oxidative glucose metabolism during the
cercaria to adult transformation. Mol Biochem Parasitol. 60:93
STEIN, L. SNYDR-MICHAL, J., AND GREENES, R. (1991) Realistic Viewing and
Manipulation of Radiographic ____ Computer--a User Interface for
Educational Applications. Journal of Digital Imaging 4:3 169-176.
Stein, L., Ham. D., and David J. (1990), A cloned ATP:Guanidino Kinase in the
Trematode Schistosoma ___ Duplicated Structure, J. Biol. Chem. 265:6582-
--------------
6588.
Stein, L., David, J. (1987), Isolation of a tandemly repeated cDNA from S.
mansoni which contains four long reading frames. Federation Proc., April
----------------
1987.
Stein L., David, J. (1986). Cloning of a developmentally regulated tegument
antigen of Schistosoma mansoni: 20:253-264
Stein, L., Dessein. A., David. J. (1985). Cloning of two Schistosome Antigens
Recognized by Human _______. Proc. April. 1985.
----
Stein. L., Dessein. A., Harn. D., Miller. J., Bina. J., David. J. (1984).
Immunoprecipitation of Schistosome _____ Translation Products using Human
Antisera. Federation Proc., April. 1984.
---------------
Stein. L., Marquis> A., Dredge. E., Reeve. M.P., Daly. M., Rozen. S., Goodman.
N. (1994). Splicing UNIX Mapping Laboratory. USENIX Summer Technical
Conference. pp. 221-229. 1994.
Samuelson. J., and Stein. L. (1989). Schistosoma mansoni: increasing saline
concentration signals cercariae to schistosomula. Exp. Parasitol. 69:23-29.
--------------
Stein. L., Rozen. S., and Goodman. N. (1995). Managing laboratory Workflow With
LabBase. In Proceedings of the 1994 Conference on Computers in Medicine
(CompMed94). World Scientific Publishing Company.
Stein. L. (1995). How to Set Up and Maintain a World Wide Web Site: the Guide
for Information Providers. Addison-Wesley Publishing. Reading. MA.

Software Development

Explorer (1987) a medical hypertext teaching system developed in the laboratory
of Robert Greenes at Harvard ______
RWS (1987) an ultrasound image analysis package used by the Framingham Heart
Study to asses carotid _______ disease.
CWS (1990) an ultrasound image acquisition and analysis package based loosely on
RWS and used by the ______ Cardiovascular Health and the IRAS studies.
Quote Init (1988) a desktop publishing utility for producing typographically
correct quotes.
QT Batch Compressor (1991) an image compression utility for the Macintosh.
MapBase. and LabBase (1992.1994) two object-oriented genome databases for UNIX
platforms.
RHMAPPER (1994) a package for creating radiation hybrid maps for genome mapping.
CGI.pm (1995) An interface between the World Wide Web and the Perl programming
language.

- --------------------------------------------------------------------------------
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

FOLLOW INSTRUCTIONS CAREFULLY. Incomplete, inaccurate, or ambiguous information
about OTHER SUPPORT could lead to significant delays in the review and/or
possible funding of the application. If there are changes in the information
after submission, notify the scientific review administrator or the initial
review group before the review; if changes occur after the review, notify the
appropriate institute.

Other support is defined as all funds or resources, whenever Federal,
non-Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. Key personnel
are defined as all individuals who participate in the scientific development or
execution of the project. Key personnel typically will include all individuals
with doctoral or other professional degrees, but in some projects will include
individuals at the masters or baccalaureate level provided they contribute in a
substantive way to the scientific development or execution of the project.

Name Gregory T. Went. Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST 70NANB5H1036 P.I. Gregory T. Went
---------------------- -----------------------

Title Integrated Microfabricated DNA Analysis Device for Diagnosis of Complex
-------------------------------------------------------------------------
Genetic Disorder
----------------

b. Your role on project Principal Investigator [XXXXXXXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project This project proposes to develop a device to
----------------------------------------------------
extend the use of DNA analysis from the characterization of simple inborn
- --------------------------------------------------------------------------------
genetic disorders to the efficient diagnosis and treatment of complex illnesses
- --------------------------------------------------------------------------------
like cardiovascular disease and cancer.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap This present application contains
-----------------------------------
optical components similar to those described herein.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

Adjustments will be made to the aims of the NIST project during 1997 if an award
- --------------------------------------------------------------------------------
is received.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. Key
personnel are defined as all individuals who participate in the scientific
development or execution of the project. Key personnel typically will include
all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Gregory T. Went, Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST 70NANB5H1066 P.I. Jonathon M. Rothberg
---------------------- -----------------------

Title Molecular Recognition Technology for Precise Design of Protein-Specific
-------------------------------------------------------------------------
Drugs
-----

b. Your role on project Business Administrator [XXXXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project This project, through state-of-the-art molecular
----------------------------------------------------
biology, structural physics, and computation methods, proposes to understand how
- --------------------------------------------------------------------------------
small highly constrained mimics of protein modules bind to a target protein.
- --------------------------------------------------------------------------------
This technological discovery uncovers rules governing protein recognition which
- --------------------------------------------------------------------------------
can be applied to guide the development of drugs to combat major uncured
- --------------------------------------------------------------------------------
diseases.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap No Scientific or budgetary
-----------------------------------
overlap
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

Dr. Went's effort will be reduced to [XXX] if the current project is funded.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. Key personnel
are defined as all individuals who participate in the scientific development or
execution of the project. Key personnel typically will include all individuals
with doctoral or other professional degrees, but in some projects will include
individuals at the masters or baccalaureate level provided they contribute in a
substantive way to the scientific development or execution of the project.

Name Gregory T. Went, Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH SBIR 2 R44 HGOO960-02 P.I. Gregory T. Went
---------------------------- -----------------

Title Modular UltraHigh ThroughPut DNA Sequencing
-------------------------------------------------------------------------

b. Your role on project Principal Investigator [XXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project This project proposes to develop a working
----------------------------------------------------
prototype incorporating a microfabricated separation module and loading
- --------------------------------------------------------------------------------
interface.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap This project serves as the basis
-----------------------------------
to the microchannel structures needed for the current proposal.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

No Adjustments will be necessary
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Jonathon M. Rothberg, Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST 70NANB5H1036 P.I. Gregory T. Went
---------------------- -----------------------

Title Integrated Microfabricated DNA Analysis Device for Diagnosis of Complex
-------------------------------------------------------------------------
Genetic Disorder
----------------

b. Your role on project Business Administrator [XXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Jonathon M. Rothberg, Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST 70NANB5H1066 P.I. Jonathon M. Rothberg
---------------------- -----------------------

Title Molecular Recognition Technology for Precise Design of Protein-Specific
-------------------------------------------------------------------------
Drugs
-------------------------------------------------------------------------

b. Your role on project Principal Investigator [XXXXXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap No Scientific or budgetary
-----------------------------------
overlap
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

Dr. Rothberg's effort will be reduced to [XXX] if the current project is funded.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal,
non-Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. Key personnel
are defined as all individuals who participate in the scientific development or
execution of the project. Key personnel typically will include all individuals
with doctoral or other professional degrees, but in some projects will include
individuals at the masters or baccalaureate level provided they contribute in a
substantive way to the scientific development or execution of the project.

Name Jonathon M. Rothberg, Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH SBIR 2 R44 HG00960-02 P.I. Gregory T. Went
---------------------------- -----------------

Title Modular UltraHigh Throughput DNA Sequencing
-------------------------------------------------------------------------

b. Your role on project Investigator [XXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap This project serves as the basis
-----------------------------------
to the michrochannel structures needed for the current proposal.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

No Adjustments will be necessary
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------
55

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal,
non-Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. Key personnel
are defined as all individuals who participate in the scientific development or
execution of the project. Key personnel typically will include all individuals
with doctoral or other professional degrees, but in some projects will include
individuals at the masters or baccalaureate level provided they contribute in a
substantive way to the scientific development or execution of the project.

Name Michael P. McKenna, Ph.D Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST 70NANB5H1036 P.I. Gregory T. Went
---------------------- -----------------------

Title Integrated Microfabricated DNA Analysis Device for Diagnosis of Complex
-------------------------------------------------------------------------
Genetic Disorder
-------------------------------------------------------------------------

b. Your role on project Senior Research Scientist [XXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

Adjustments will be made to the aims of the NIST during 1997 if an award is
- --------------------------------------------------------------------------------
received.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------
56

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name John W. Simpson Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST 70NANB5H1036 P.I. Gregory T. Went
---------------------- -----------------------

b. Your role on project Senior Research Engineer [XXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name John W. Simpson Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIST SBIR 2 R44 HG00960-02 P.I. Gregory T. Went
---------------------------- -----------------

Title Modular UltraHigh Throughput DNA Sequencing
-------------------------------------------------------------------------

b. Your role on project Senior Engineer [XXXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

No Adjustments will be necessary
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------
58

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Harold G. Craighead Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. ARPA/AF - F49620-93-C-0061 P.I. Craighead
---------------------------- ----------------

Title Micro-Column Arrays for Nanolithography
-------------------------------------------------------------------------

b. Your role on project % Effort
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project Develop a miniaturized electron beam source and
----------------------------------------------------
optical column
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------
59

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
================================================================================
OTHER SUPPORT
(Use continuation pages if necessary)

FOLLOW INSTRUCTIONS CAREFULLY. Incomplete, inaccurate, or ambiguous information
about OTHER SUPPORT could lead to significant delays in the review and/or
possible funding of the application. If there are changes in the information
after submission, notify the scientific review administrator of the initial
review group before the review; if changes occur after the review, notify the
appropriate insurance.

Other support is defined as all funds or resources, whether Federal,
non-Federal, or institutional, available to the principal investigator/program
(director and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. Key
personnel are defined as all individuals who participate in the scientific
development or execution of the project. Key personnel typically will include
all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Reporting requirements are: for each of the key personnel, describe (1) all
currently active support and (2) all applications and proposals pending review
or award, whether related to the application or not. If the support is part of
a larger project, identify the principal investigator/program director and
provide the data for the relevant subproject(s). If an individual has no active
or pending support, check "None." Use continuation pages as needed to provide
the required information in the format as shown below.

Name Harold G. Craighead Active X Pending None
-------------------------------- ------ ------ ------

a. Source and identifying no. ARPA/ONR - NOOO14-93-1-1080 P.I. Craighead
-------------------------------- -------------

Title Molecular Approaches to Device Nanofabrication
---------------------------------------------------------------------------

b. Your role on project PI % Effort
---------- -------------------- ---------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project Investigate the properties and use of
----------------------------------------------------
self-assembled organic monolayers as resists for nanofabrication
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

================================================================================

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Harold G. Craighead Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. DoD/Rome Labs - F30602-93-C-0061
--------------------------------------------------

P.I. Craighead
----------------------------------------------------------------------------

Title Advancement of Free-Space Optical Interconnects
-------------------------------------------------------------------------

b. Your role on project PI [XXXXXXXXXXXXXXXXX] Summer
-------- -------- --------- ---------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project Fabricate and test an optical interconnect for
----------------------------------------------------
electronic circuits based on microfabricated diffractive optics.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap Uses advanced microfabrication
-----------------------------------
technologies
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Harold G. Craighead Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. MSC/NSF - DMR-9121654 P.I. Craighead
--------------------------- -------------------

Title Electron Scattering in Mesoscopic Systems
-------------------------------------------------------------------------

b. Your role on project PI % Effort
---------- -------------- -------------------

c. Dates and costs of entire project
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project Explore electron scattering in small electronic
----------------------------------------------------
devices
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Harold G. Craighead Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. Cornell Center for Advanced Tech
--------------------------------------------------

P.I. Craighead
----------------------------------------------------------------------------

Title Nanofabrication of Artificial Insect Eggs for use in Biological Control
-------------------------------------------------------------------------
of Parasites
-------------------------------------------------------------------------

b. Your role on project PI % Effort
----------- ------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year
---------------------------------------------

e. Specific aims of project This study involves creating micro-structures
----------------------------------------------------
on the surface of artificial insect eggs to encourage egg laying by beneficial
- --------------------------------------------------------------------------------
insect parasites. The goal is to mass rear beneficial parasites in artificial
- --------------------------------------------------------------------------------
eggs.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
-----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Reporting requirements are: for each of the key personnel, describe (1) all
currently active support and (2) all applications and proposals pending review
or award whether related to this application or not. If the support is part of a
larger project, identify the principal investigator/program director and provide
the data for the relevant subproject(s). If an individual has no active or
pending support, check "None." Use continuation pages as needed to provide the
required information in the format as shown below. Information may be combined
as long as the format remains the same. For example, all key personnel who have
no other support may be listed on a single page. DO NOT SEND in a separate page
for each person listed for whom "None" is checked.

Name Harold G. Craighead Active Pending X None
----------------------------------- ------ ------- --------

a. Source and identifying no. NY State Health Dept/NIH P.I. William Shain
---- --- ----------------

Title Brain Prostheses: Tissue Compatibility and Integration
------ ---------------

b. Your role on project PI of Subcontract from Cornell % Effort
--- ------ --------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year
---------------------------------------------

e. Specific aims of project Develop surface coatings and treatments for the
----------------------------------------------------
selective attachment of neurons to electrodes
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Harold G. Craighead Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. CuraGen Corp. P.I. Craighead
---------------------- -----------------------

Title Nanofabrication of Devices for Genetic Analysis
-------------------------------------------------------------------------

b. Your role on project PI % Effort
---------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year
---------------------------------------------

e. Specific aims of project This project is to find efficient ways of
----------------------------------------------------
microfabricating multiple parallel lanes for conventional gel electrophoresis.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap Gel channels made under this
-----------------------------------
project can be used with the proposed optics.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- -------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported.Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Harold G. Craighead Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. DOD/MPO P.I. Craighead
---------------------- -----------------------

Title Electron Beam Programming
-------------------------------------------------------------------------

b. Your role on project PI % Effort
---------- ----------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year
---------------------------------------------

e. Specific aims of project Electron beam programming of MOS transistor
----------------------------------------------------
memories
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- -------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported.Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Herbert H. Hooper Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH HG01289-01 P.I. H. Hooper
---------------------- -----------------------

Title Replaceable Gels for Microchannel DNA Electrophoresis
-------------------------------------------------------------------------

b. Your role on project PI [XXXXXXXXXXX]
-------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year same
---------------------------------------------

e. Specific aims of project Develop replaceable matrices for DNA sequencing
----------------------------------------------------
and typing by capillary electrophoresis with low viscosity during loading and
- --------------------------------------------------------------------------------
unloading.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None. Related area but different
-----------------------------------
approach and technology.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Herbert H. Hooper Active X Pending None
----------------------------------- ------ ------- --------

H. Hooper (Soane)
a. Source and identifying no. NIST 70NANB5H1036 P.I. G. Went (CuraGen)
---------------------- -----------------------

Title Integrated Microfabricated DNA Analysis Device
-------------------------------------------------------------------------

b. Your role on project PI at Soane [XXXXXXXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
---------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

e. Specific aims of project Develop replaceable gels for microfabricated
----------------------------------------------------
device that flow at room temperature and gel upon heating.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whenever Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Herbert H. Hooper Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH HGO1338-01 P.I. A.P. Sassi
---------------------- -----------------------

Title Constant - Field Electrophoresis of Large DNA
-------------------------------------------------------------------------

b. Your role on project Scientist [XXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
---------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

e. Specific aims of project Develop gels for separates large (greater than
----------------------------------------------------
50kbp) DNA fragments without pulsed fields.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whether Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts, fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name David Soane Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH HGO1338-01 P.I. A.P. Sassi
---------------------- -----------------------

Title Constant - Field Electrophoresis of Large DNA
-------------------------------------------------------------------------

b. Your role on project Scientist [XXXXXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
---------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

e. Specific aims of project Develop gels for separating large (greater than
----------------------------------------------------
50kbp) DNA fragments without pulsed fields
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None
-----------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None
- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whenever Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name David Soane Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH HG01289-01 P.I. H. Hooper
---------------------- -----------------------

Title Replaceable Gels for Microchannel DNA Electrophoresis
-------------------------------------------------------------------------

b. Your role on project Scientist [XXXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

d. Dates and costs of current year [XXXX]
---------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Other support is defined as all funds or resources, whenever Federal, non-
Federal, or institutional, available to the principal investigator/program
director (and other key personnel named in the application) in direct support of
their research endeavors through research or training grants, cooperative
agreements, contracts fellowships, gifts, prizes, and other means. However, in
the case of prizes and gifts, only those that support the specific project must
be reported. Key personnel are defined as all individuals who participate in the
scientific development or execution of the project. Key personnel typically will
include all individuals with doctoral or other professional degrees, but in some
projects will include individuals at the masters or baccalaureate level provided
they contribute in a substantive way to the scientific development or execution
of the project.

Name Alexander P. Sassi Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. NIH HG01338-01 P.I. A.P. Sassi
---------------------- -----------------------

Title Constant - Field Electrophoresis of Large DNA
-------------------------------------------------------------------------

b. Your role on project Scientist [XXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project (For renewals, include only the most
recent competitive award. List direct and indirect costs separately.)

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX] [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
---------------------------------------------
XXXXXXXXXXXXXXXXXXXXX]
- --------------------------------------------------------------------------------

e. Specific aims of project Develop gels for separating large (greater than
----------------------------------------------------
50kbp) DNA fragments without pulsed fields.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap None. Project ends before subject
-----------------------------------
grant will begin.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

None.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

OTHER SUPPORT
(Use continuation pages if necessary)

Name Trevor Hawkins Active X Pending None
----------------------------------- ------ ------- --------

a. Source and identifying no. Department of Energy DE-FGO2-95ER62099
--------------------------------------------------

P.I. Trevor L. Hawkins
-----------------------

Title DNA Sample Munipulation and Automation
-------------------------------------------------------------------------

b. Your role on project Principal Investigator [XXXXXXXXX]
---------------------------- -------------------

c. Dates and costs of entire project [XXXXXXXXXXXXXXXXXXXXXXXXXXX]
-------------------------------------------

d. Dates and costs of current year [XXXXXXXXXXXXXXXXXXXXXXXXXXX]
---------------------------------------------

e. Specific aims of project The Aims of this Project are:
----------------------------------------------------
1) Produce sub-clone libraries from a variety of templates and automate
- --------------------------------------------------------------------------------
library construction process.
- --------------------------------------------------------------------------------
2) Sequence large numbers of DNA templates for analysis on sequencers and
- --------------------------------------------------------------------------------
capillary systems.
- --------------------------------------------------------------------------------
3) Evaluate capillary array for DNA sequence while integrating and automating
- --------------------------------------------------------------------------------
the procedures from MAP clone to get ready samples.
- --------------------------------------------------------------------------------

f. Describe scientific and budgetary overlap No Scientific or budgetary
-----------------------------------
overlap
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

g. Describe adjustments you will make if the present application is funded
(budget, % effort, aims, etc.)

No adjustment is necessary.
- --------------------------------------------------------------------------------

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

GG Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

Name Trevor L. Hawkins Active Pending X None
--------------------------------- --------- ----- -------

a. Source and identifying no. NIH RFA HG95-001 with Intelligent Automation
---------------------------------------------------
P.I. Steve Gordon
---------------------------------

Title Improved Electrophoretic DNA Sequencing Technology
---------------------------------------------------------------------------

b. Your role on project: Co-Investigator [XXXXXXXXXXX]
--------------------------------- ---------------

c. Dates and costs of entire project: Dates and Costs Currently Under Review
-------------------------------------------

d. Date and costs of current year: Dates and Costs Currently Under Review
----------------------------------------------

e. Specific aims of project: The Aims of this Project are: Studies using gel
----------------------------------------------------
electrophoresis systems that could yield reductions in scale and increased
- --------------------------------------------------------------------------------
throughput of DNA sequencing.
- --------------------------------------------------------------------------------

f. Describe scientific and buggetary overlap: Effort will be reduced if there is
-----------------------------------
overlap.
- --------------------------------------------------------------------------------

f. Describe adjustments you will make if the present application is funded
(budget % effort, aims, etc.)

Effort will be reduced if RFA HG 95-004 is funded.
- --------------------------------------------------------------------------------

OTHER SUPPORT CONTINUED:

NAME ACTIVE PENDING
- -----------------------------------------------------
<S> <C> <C>
Lincoln Stein None None
William Lee None None

</TABLE>

- --------------------------------------------------------------------------------

[Confidential Treatment Requested]
<PAGE>

HH Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

RESOURCES AND ENVIRONMENT
(CuraGen Corporation)
- --------------------------------------------------------------------------------

FACILITIES. Mark the facilities to be used at each performance site listed in
item 9. Face Page, and briefly indicate their capabilities, relative
capabilities, relative proximity, and extent of availability to the project. Use
"Other" to describe the facilities at any other performance sites listed in item
9 on the Face Page and at sites for field studies. Use continuation pages if
necessary. Include an explanation of any consortium/contractual arrangements
with other organizations.

[X] Laboratory: CuraGen has 8000 sq. ft. of state-of-the-art molecular and
structural biology laboratory and office space at its research headquarters in
Branford. A recent buildout of 3000 square feet of space was completed for
structural biology and computation laboratories. This space also houses the
Company's 1000 sequence/day DNA analysis facility and 3500 square feet of
molecular biology facilities, which includes standard equipment. By 1996, the
Company plans to occupy over 15,000 sq. ft. of lab and office space.

[_] Clinical:

[_] Animal:

[X] Computer: Four workstation class SGI computers are available for CuraGen's
software development. Twenty Macintoshes and PowerPC's are also onsite. Large
scale sequence databases, such as GenBank, are available on-site, as are
literature search databases such as CAS on-line. Entrez and MedLine.

[X] Office: Ample (2500 sq. Ft.) office space (with a library in our new
expansion) is available for CuraGen's 25 employees.

[X] Other ( ): CuraGen collaborates closely with all three coinvestigators as a
part of ongoing projects. In addition, CuraGen has a visiting scientist position
at MIT/The Whitehead Institute with office and computer access.

- --------------------------------------------------------------------------------
MAJOR EQUIPMENT List the most important equipment items already available for
this project, noting the location and pertinent capabilities or each

CuraGen has developed under NIH and NIST funding a high throughput DNA analysis
instrument, placing in its core facility. These systems are driven by TECAN and
Beckman robot stations with integrated thermal cycling (384 well). Our molecular
biology facilities are modern and well equipped with freezers, incubators, PCR,
HPLC, electroporation, electrophoresis, centrifuges, plate readers, microscopes
and hoods.

- --------------------------------------------------------------------------------
ADDITIONAL INFORMATION: Provide any other information describing the environment
for the project. Identify support services such as consultant, secretarial,
machine shop, and electronics shop, and the extent to which they will be
available to the project.

Secretarial, administrative support, and accounting are all provided onsite, as
are reporting and regulatory support.

- --------------------------------------------------------------------------------

<PAGE>

HH Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

RESOURCES AND ENVIRONMENT

(Cornell University)
- --------------------------------------------------------------------------------

FACILITIES Mark the facilities to be used at each performance site listed in
item 9. Face Page, and briefly indicate their capabilities, pertinent
capabilities, relative proximity, and extent of availability to the project. Use
"Other" to describe the facilities at any other performance sites listed in item
9 on the Face Page and at sites for field studies. Use continuation pages if
necessary. Include an explanation of any consortium/contractual arrangements
with other organizations.

[X] Laboratory: Harold Craighead's laboratory has the capabilities to evaluate
and test optical components and systems. Cornell University has extensive
facilities and equipment for optical device fabrication research, prototyping
and testing. The National Nanofabrication Facility (NNF) provides resources and
technical expertise to researchers in microstructure science. Extensive
experience also exists in fine feature patterning of semiconductors and optical
materials. Unique capabilities exist for integration of electron beam
lithography and ion etching for novel thin film fabrication. The NNF is located
in the Knight Laboratory, specifically designed and construed for nanostructures
research, on the Cornell University campus. The cleanroom facilities comprise
7,500 sq. ft. of approximately Class 500 area, including Class 10 local
processing benches within that area. Particular care was given during
construction to vibration and electromagnetic isolation of the advanced
lithography facilities. The Materials Science Center at Cornell provides
computational facilities and extensive electron microscopy and thin film
capabilities.

[_] Clinical:

[_] Animal:

[_] Computer:

[_] Office:

[_] Other( ):

- --------------------------------------------------------------------------------
ADDITIONAL INFORMATION Provide any other information describing the environment
for the project. Identify support services such as consultant, secretarial,
machine shop, and electronics shop, and the extent to when they will be
available to the project.

<PAGE>

HH Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------

RESOURCES AND ENVIRONMENT

(Soane Biosciences Inc.)
- --------------------------------------------------------------------------------

FACILITIES. Mark the facilities to be used at each performance site listed in
Item 9, Face Page, and briefly indicate their capabilities, pertinent
capabilities relative proximity, and extent of availability to the project. Use
"Other" to describe the facilities at any other performance sites listed in Item
9 on the Face Page and at sites for field studies. Use continuation pages if
necessary. Include an explanation of any consortium/contractual arrangements
with other organizations.

[X] Laboratory: Soane BioSciences (SBio) was formed as a division of Soane
Technologies (STI) in 1993, and was spun-off as an independent, venture-capital
backed company in 1995 to develop and commercialize advanced electrophoresis
media and devices. SBio currently has 12 employees and is located in a 6,000 sq.
ft. facility in Hayward, California, about 70% of which is lab space. Adjoining
SBio is STI's 6,000 sq. ft. facility, providing additional equipment and
resources freely available to SBio.

SBio's labs are well-suited for organic and polymer synthesis, with a total of 6
chemical fume hoods and extensive synthesis equipment. SBio also has extensive
equipment for performing material characterization, electrophoresis and
molecular biology experiments. SBio's labs and offices are equipped with a
total of 12 PC's (pentium and 486 model), networked with Novell software.

[_] Clinical:

[_] Animal:

[_] Computer:

[_] Office:

[_] Other( ):

Bioanalytical and Molecular Biology Equipment
SBio has a Pharmacia A.L.F. DNA sequencer, a Beckman P/ACE 2100 capillary
electrophoresis system with UV detection (a laser-induced fluorescence detector
is on order); vertical and horizontal electrophoresis units, including a manual
DNA sequencer, with power supplies and visualization equipment; equipment for
preparation of DNA sequencing samples including thermocycler, microcentrifuge,
and centrifugal evaporator; along with other miscellaneous items including a
Millipore Milli-Q Plus ultra-pure water system, freezers, refrigerators,
glassware, etc.

Monomer and Polymer Synthesis and Characterization Equipment
SBio has extensive polymer and organic synthesis equipment including reaction
kettles, homogenizer, temperature controllers, rotary evaporators, vacuum ovens,
centrifuge, filtration equipment, freeze dryer, UV curing lamps and other
miscellaneous items (balances, pH/conductivity meter, etc.) For analysis and
characterization, SBio has a Hewlett-Packard 1090 HPLC with both diode array and
refractive index detection. Brookfield viscometer with temperature control,
Nikon visible microscope with CCD camera, differential scanning calorimeter, and
a refractometer.

Machine Shop
SBio has access to STI's machine shop with state-of-the-art equipment including
CNC mill, which will be used for this project.

<PAGE>

HH Principal Investment/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
RESOURCES AND ENVIRONMENT
(The Whitehead Institute)
- --------------------------------------------------------------------------------

FACILITIES: Mark the facilities to be used at each performance site listed in
Item 9. Face Page, and briefly indicate their capacities, pertinent
capabilities, relative proximity, and extent of availability to the project. Use
"Other" to describe the facilities at any other performance site listed in Item
9 on the Face Page and a: sites for field studies. Use continuation pages if
necessary. Include an explpanation of any consortium/contractual arrangements
with other organizations.

[X] Laboratory: There is 16,500 square feet of laboratory space divided between
the 4th and 5th floors of The Whitehead Institute/MIT Genome Center. These
include bench space, shared rooms for radioisotope handling, consistent
temperature (4 degrees C and 37 degrees C), darkrooms, and heavy equipmemt
rooms.

[_] Clinical:

[_] Animal:

[X] Computer: The Center currently has a network of UNIX workstations (7 DEC
workstations, 7 SUN workstations, and 4 new DEC Alphas) and Macintosh personal
computers connected through Ethernet. Outside connections provide full access to
computer services at The Whitehead Institute (e.g. MedLine) as well as to other
sources of information available at MIT and over the world-wide Internet. Also
available is a PC set-up for automatic visual entry of dot blot data with CCD
Camera and a Montage film recorder.

[X] Office: There is approximately 5500 square feet of office space on the 5th
floor of the Genone Center. Available to me are Ricoh photocopy machines, Cannon
FAX machines, IBM typewriters, secretarial support, file cabinets and storage
space.

[_] Other ():

- --------------------------------------------------------------------------------
MAJOR EQUIPMENT. List the most important equipment items already available for
this project, noting the location and pertinent capabilities of each.

There are low and medium speed centrifuges, preparative ultracentrifuges,
scintillation counters, incubators for bacteria, liquid nitrogen freezers,
laminar flow hoods, microscopes, electrophoresis and sequencing facilities and
PCR machines available.

- --------------------------------------------------------------------------------
ADDITIONAL INFORMATION. Provide any other information describing the environment
for the project. Identify support services such as consultant, secretarial,
machine shop, and electronics shop, and the extent to which they will be
available to the project.

We have available to us the resources of The Whitehead Institute, including an
electron microscopy laboratory, a florescence photomicroscope, an histology
laboratory, polynucleotide and polypeptide synthesis facilities, a P3
laboratory, a library and computer facility. Chemical storage, media preparation
and a glassware washing facility are located on the 4th floor of the Genome
Center. Also available to us is access to the resources of the MIT Biology
Department.

<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
1. Specific Aims

In this proposal, we describe a three-year project to develop, integrate and
distribute into the Human Genome Program (HGP) pilot sequencing projects a
fluorescent sequencing instrument and software system capable of meeting the
logistic and cost demands of sequencing the entire human genome. This project
consists of taking a system level approach to developing methods,
instrumentation and software designed from the start to work within, and be
proven in, the framework of genome laboratories. These aims will be met by
building upon the high-throughput system (version 1.0) developed under NIH
funding at CuraGen. This program will produce two sequential improvements:

. version 1.1, for pilot scale sequencing [XXXXXXXXXXXXXXXXXXXXXX]

. version 2.0, for full scale genome sequencing [XXXXXXXXXXXXXXXXX
XXXXXX]

Project Overview

MIT Whitehead Genome Center
-----------------------------------
Automation Workflow Informatics
-----------------------------------------------------
Sample Prep Finishing
Autoloading Assembly
---------------------------------------------------
SBio NNF
Media Optics
---------------------------
Electrophoresis BaseCalling
system
Replicated Substrates
-----------------------------------
---------------------------------------------------

The project duration is designed to parallel that of planned HGP pilot studies,
allow for the use of the systems in these studies, and produce a finished system
ready for distribution to sites selected to carry out full scale human genome
sequencing efforts. The project is designed to effect the research tasks
necessary both to achieve the requisite technical objectives as well as to
create the track record necessary to make this the system of choice for wide
scale genome sequencing.

As indicated by the diagram above, CuraGen, Soane BioSciences (SBio), and their
academic collaborators at MIT/Whitehead and the Cornell National Nanofabrication
Facility (NNF) are taking a modular phased approach built upon existing and
proven technology. The evolving CuraGen/SBio DNA analysis system has been
developed and "road tested" in a production sequencing environment at CuraGen.
Since July 1995, it has been in place at the Whitehead Institute. This project
builds on the NIH and DOE funded efforts at each of the four groups. The P.I.
Dr. Went will coordinate, integrate and focus the actives of the individual
groups and rely on his interdisciplinary team at CuraGen for instrument,
software and system development. The experiences of Drs. Trevor Hawkins and
Lincoln Stein at Whitehead in automation, workflow and informatics is brought to
bear to insure dove-tailing of the instrument development into existing
infrastructure. The expertise of Drs. Herb Hooper, David Soane and the Soane
BioScience team in advanced media and replication enables the development of
advanced reusable and disposable separation systems. Leadership in the field of
microfabrication, with an emphasis on microfabricated optics, is provided by Dr.
Harold Craighead at the Cornell NNF.

[Confidential Treatment Requested]
<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------

We begin with the system in routine operation at CuraGen and make the following
specific improvements to produce advanced generations: version 1.1 (by October
1997) and version 2.0 (by April 1999).

Component (Performance Site) Specific Aim
<S> <C>
Sample preparation(MIT, CuraGen) Develop and automate solid phase loading and
purification methods to remove the bottleneck at
the interface between existing robotic sample
preparation and loading of fluorescent
electrophoretic systems and to reduce the overall
reagent costs (v. 1.1).

Develop novel bi-directional sequencing protocols
(v. 1.1, 2.0).

Electrophoresis system (CuraGen, SBio) Produce a low cost, robust electrophoresis system
with a disposable, ready-to-run microchannel
(microreplicated) separation sub-assembly (v. 2.0).

Media (SBio) Develop advanced separation media for multiple runs per
gel (v. 1.1).

Develop dynamic porosity media to extend read lengths
(v. 1.1, 2.0).

Develop media for disposable, microreplicated gel
assemblies (v. 2.0).

Detection (Cornell): Implement a binary detection system for use with the
microreplicated separation system (v. 2.0).

Informatics (CuraGen, MIT) Tie electrophoresis instruments into laboratory work-flow
(v. 1.1).
Produce sequencing data with explicit confidence levels
for each base call (v. 1.1).
Enable 8-dye protocols (v. 1.1, 2.0).
Enable automated assembly and statistically qualified
finishing of sequences (v. 2.0).

</TABLE>

2. Background and Significance

The human genome comprises three billion base pairs of DNA. In order to sequence
the entire genome, a phased approach has been implemented by the NIH and DOE.
The first requirement is the production of a conceptual array of large
contiguous DNA sequences (large insert clones) spanning the 23 chromosomes.
These "physical maps" must accurately represent the human genome and be in a
form amenable to DNA sequencing. To make these physical maps amenable to
sequencing, the individual large-insert clones will be further sub-divided into
templates (either physically by subcloning or by primer walking) for direct DNA
sequencing. Once the precise sequence of these templates is determined (by
Sanger sequencing and fluorescent detection) they will be "assembled" into
accurate ("finished" sequence) virtual representations of the original
large-insert clones. The sequences of these large-insert clones are then
assembled to form the full finished sequence of the human genome.

2.1 HGP: Technical Challenges

The challenge, constrained by economics and time, is to produce a finished
genome sequence at a cost of under $0.10 per base at a rate of 600 Mb per year,
in order to complete the genome for under $300 million dollars in a five-year
period. Physical maps of the genome are now estimated to contribute less than 1
penny per base to the finished sequence cost (Lander et al., 1995) and to be
nearly complete in time for the start of large scale sequencing of the human
genome. This leaves $0.09 per base to go from the physical map to assembled and
finished sequence. The most successful high-throughput DNA sequencing centers in
the world are currently
<PAGE>

Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
producing C. elegans sequence from physical maps at $0.50 per finished base at a
rate of 10 Mb/year (Sulston et al., 1992; Wilson et al., 1994 ). The rate and
cost of sequencing complete bacterial genomes and yeast chromosomes is
comparable. To meet the HGP goals, it is necessary to increase the rate of
production of finished sequence 60-fold while decreasing the cost 5-fold over
these current projects.

The logistical concerns of genome-scale DNA sequencing are essentially those
derived from the need to increase throughput and reduce cost. This can only be
done by improved technology integration and automation. Historically, the
introduction of fluorescent four color sequencing into the life science research
market enabled the sequencing of individual clones, small contiguous regions,
and, when pushed to the limits of the original technology, the sequencing of the
first complete bacterial genome (Fleischmann et al., 1995). An early 4-dye
commercial instrument produced by Applied Biosystems, Inc., the ABI 373, and its
subsequent replacement, the 377, were not designed with the logistics of large
scale genomic sequencing in mind. Specifically, these instruments were not
designed to efficiently integrate into a "factory environment" consisting
primarily of robotic sample handling automated within an informatics framework.

Producing finished sequence at 600 Mb per year or 2 Mb per day requires the
production of upwards of 40,000 template and sequencing ladders a day (based on
500 bp reads/sample and 10 fold redundancy). Pilot programs are currently aimed
at achieving 1/10th of this rate. The workflow, upstream robotics and
informatics that are being planned and currently developed for pilot studies
(Lander et al., 1995), if properly assisted by a new generation of sequencing
technology such as the v. 1.1 system proposed here, would be capable of
processing 4,000 samples per day. With the advent of the v. 2.0 system, these
pilot programs could be scaled to meet the expected 40,000 sample per day
throughput required for a large scale sequencing effort. In order not in any way
--------------
to duplicate the upstream workflow and robotics efforts, we concentrate in this
- -------------------------------------------------------
proposal on developing advanced sequencing instrumentation and systems to
dove-tail into the upstream capabilities. This represents an approach in which
increases in lane density, electrophoresis speed, and sensitivity of a
fluorescent sequencing instrument are integrated into existing front-end
robotics to yield the requisite targeted "system level" throughput increases and
concomitant cost reductions.

2.2 HGP: Cost Analysis

Cost analysis studies are regularly used to determine which problems to work on
from a return on investment standpoint, and which components of a problem are
sensitive to cost reductions. Recent examinations of the Human Genome Project
(HGP) have led to a separation of the project into two phases. During the first
phase, scheduled to last three years, additional technology will be developed
and pilot studies will be conducted to provide a solid basis for determining how
best to carry out the full scale project during the subsequent five year second
phase.

Technology improvements are often driven by the need for better cost
performance. In the computer industry this has lead to a doubling of potential
with a concomitant halving of cost every 18 months. This has become known as
Moore's law, in recognition of its major proponent, Gordon Moore of Intel
Corporation. With this in mind we have investigated the impact that advances in
the major technology components would have (primarily) on the sequencing portion
of the HGP. Ultimately, the impact of the HGP will be judged by the number of
genetic disorders that can be more effectively diagnosed and treated, which will
require many-fold genomic sequencing.

Physical mapping and sub-cloning efforts, which are planned prerequisites of
large scale sequencing are expected to contribute from $.01 to $.03 to the cost
per base of finished sequence. (Throughout this discussion we have adapted the
NCHGR convention of using the finished base as the unit of measure to allow a
comparison of the impact of technological advances on cost.) Pilot projects are
better suited to address these costs and we therefore concentrate our efforts
here on improved sub-clone sequencing and assembly to produce a finished
sequence.

A sequencing cost analysis (Table 2.1; see Appendix 2 for a breakdown of the
analysis and supporting assumptions) highlights the major contributions to the
final cost, which can be reduced by improvements in the following technology
areas: sample preparation and loading, electrophoresis systems, separation
media, detection and informatics. Specifically, the two largest contributions to
the finished cost per base are (1) materials for template preparation and
sequencing reactions and (2) labor costs associated with sequence assembly. The
aggregate sensitivity and bi-directional sequencing improvements described
herein have the potential to reduce this cost 3-fold, while the addition of
confidence information in base calling, and accurate lane tracking provided by
micro-channels would enable the automation of the assembly and lane-finding
processes, and another 3-fold decrease in cost. This analysis further indicates
that the expected improvements in automation being developed in pilot studies
are sufficient to meet the overall goals, and do not need to be undertaken here.
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In addition to financial issues, these calculations provide additional
information on other resource and labor issues that may contribute to logistical
problems. These specifically include the demand existing technology presents for
pouring and handling over 1000 gels a day and the space and power requirements
to house over 250 sequencing instruments. From this information, it is clear
that disposable, ready-to-run gels will tremendously decrease the logistical and
financial burdens of gel-pouring.

These improvements taken together can yield a cost saving based on using
commercially available systems of over $800 million. Using the expected
investment of approximately $80 million for the first phase of the human genome
project (over the next 3 years), this 10-fold return on investment would yield
in the ensuing 5 years a 50% compounded return on investment. This analysis
clearly indicates the importance of the pilot programs and an emphasis on
technology development for the success of the humane genome project. This
project aims to address those critical components highlighted above, and to
deliver a system to cost-effectively sequence the genome.

Table 2.1 Cost analysis for sequencing the human genome.
<TABLE>
<CAPTION>
Advanced Commercial [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
------------------- ----------- ----------- -----------
<S> <C> <C> <C> <C>
Project cost summary:
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Total Fixed costs $54,594,000 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Total Material Costs $273,600,000 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Total Labor Costs $329,550,000 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
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Total project cost $657,744,000 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]

Cost per finished base:
Fixed cost/finished base $0.018 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Material cost/finished base $0.0912 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Gel related labor cost/finished base $0.0139 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Sample labor cost/finished base $0.0160 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Sequence assemble labor cost/finished base $0.0800 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
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Total sequencing cost/finished base $0.2192 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]

Totals with 70% Indirect cost on labor and materials:
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Total project cost $1,025,355,000 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Total sequencing cost/finished base $0.3418 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Physical mapping and sub-cloning $0.0333 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
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Total cost/finished base $0.3751 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]

Summary of Resource needs:
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Gels to set up per day 1,108 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Total Seq Units needed to meet quota 277 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Number of people necessary 1,373 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
Estimated Sq. ft 186,265 [XXXXXXXXX] [XXXXXXXXX] [XXXXXXXXX]
</TABLE>

2.3 Component Technologies

The process of sequencing the genome leads to the production of small (less
than 2 Kb) fragments of DNA from large-insert clones (BACs, YACs, P1s). Sanger
sequencing ladder products can be generated from these fragments by a number of
robotic means, with final product residing in the wells of a microtiter dish (96
or 384 well). This process is executed now at major genome facilities. At this
point, a second stage of systems for performing electrophoresis, fluorescent
sequencing, and sequence assembly take over. This project replaces the second
stage, enables new Sanger protocols, and carries through to use the host site
informatic system to deposit automatically the finished sequence into a
database.

2.3.1 Sample Preparation/Loading

The output of most Sanger protocols is a mixture of input DNA, fluorescent DNA
ladders, and unreacted fluorescent primers or nucleotides. In order to prepare
the sample for electrophoresis, it must be purified. The

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use of solid phase techniques for this purification step has increased
dramatically over the last few years as more biochemical methods are adapted for
use with magnetic particles (Uhlen, 1989; Hultman et al., 1989; Hultman et al.,
1991; Hawkins, 1994). The advantages of using magnetic particles are based upon
the ease with which DNA can be manipulated once immobilized on the magnetic
particles. In theory, the need for centrifugation stages could be removed from
molecular biology if DNA fragments were fixed either temporarily or permanently
to the magnetic solid phase. However, the use of a solid-phase has not yet been
successfully applied to the automated loading, a process that could benefit from
the simplicity and throughput increases associated with the coupling of the
transport and purification advantages of solid-phase systems.

2.3.2 Gel Electrophoresis

There are several important features of a gel electrophoresis system: (1) the
interfaces for gel and sample loading, (2) throughput, i.e., the number of
samples (and bases) that can be processed per unit time, (3) read length, (4)
sample volume required, and (5) the back-end interface for fragment detection.
Traditionally, electrophoresis has been carried out between two plates of glass
(or plastic) separated by a spacer, with a polymeric medium to sieve the DNA.
Commercial state-of-the art is now the ABI 377 at 36 sample/450 bases/2.5 hrs.,
providing 6.5 Kb/hour of raw sequence. Performance has been improved using thin
slab gels, capillary arrays, and microchannel devices.

Thin slab gels. One of the primary factors in determining electrophoresis time
- --------------
is the ability to apply high voltages, generating significant heat, without
significant temperature gradients. Smith and coworkers (Brumley and Smith, 1991)
pioneered (less than) 100 (um)m gel widths and established that 10 bp/min can
be attained at 200 V/cm. Vertical and horizontal thin gels have been used, but
the horizontal approach has significant advantages from the standpoint of
automating sample loading. CuraGen has adapted the horizontal thin gel approach
with traditional gel and sample loading to produce a routine and automatable
device (see Section 3).

Capillary array electrophoresis. Introduced to DNA sequencing by Mathies and
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coworkers (Huang et al., 1992a,b), CAE combines the high-speed separation
attainable in individual capillaries with the throughput provided by
multiplexing. Several groups are actively developing capillary array systems
(Takahashi et al., 1994; Ueno and Yeung, 1994; Barker, 1995), including at least
three commercial entities. In addition to throughput, CAE offers the potential
for automated gel and sample loading, which is now being realized with the
recent advances in replaceable matrices. Lower viscosity matrices are still
needed, as are more stable wall coatings. Electrokinetic injection is
inefficient with respect to sample utilization, requiring a concentrated DNA
sample of which only a fraction is injected. The detection region of capillary
arrays is ultimately determined by the capillary outer diameters, an inherent
limitation for high lane densities.

Microchannel gel devices. Miniaturized separation lanes and devices can be
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fabricated in planar substrates using micromachining techniques. Terry et al.
(1979) microfabricated a gas chromatograph in silicon sixteen years ago,
providing the basis for a commercial, portable GC manufactured by Microsensor
Technologies Inc. Microfabricated electrophoresis devices were proposed by
several groups around 1990 (Kovacs et al., 1989; Pace, 1990; Manz et al., 1991;
Harrison et al., 1992a). Several reports have demonstrated sample injection
schemes, high speed electrophoretic separations of dyes and labeled amino acids,
and pre- and post-column reactions (Harrison et al., 1992b; Jacobson et al.,
1994a-c). Recently, rapid, high-resolution separations of dsDNA (Wooley and
Mathies, 1994), oligonucleotides (Effenhauser et al., 1994) and DNA sequencing
ladders (Balch et al., 1994; Went, 1995) have been reported. The revolutionary
vision is to create fully-integrated chip-sized devices with on-board sample
preparation, followed by automated injection, separation and detection. While
this goal appears fundamentally achievable, it presents significant technical
risk in the 3-5 year time frame. The more evolutionary approach is to
microfabricate the separation device, and utilize continually improving robotic
methods for sample preparation and loading. We have taken the second approach,
utilizing the modular design of CuraGen's horizontal thin gel system (Section
3). This device can be integrated with microfabricated front-ends as they become
available.

2.3.3 Electrophoretic Separation Media

The separation matrix is a critical element of the separation platform in DNA
sequencing. The use of crosslinked polyacrylamide in slab gel sequencing has
changed little since its introduction in the late 1950's . The disadvantages of
in-situ acrylamide polymerization are well-known, including monomer toxicity,
labor intensity, and reproducibility issues. These effects become logistically
untenable at the 40,000 lane (1000+ gel) per day level. Pre-cast gels, popular
in a number of electrophoresis applications, have not been introduced for DNA
sequencing. In contrast to slab gels, there has been significant innovation in
media for capillary electrophoresis, centered around the use of uncrosslinked
polymer solutions as replaceable matrices. Since the early reports by Zhu et al.
(1989) and Chin and Colburn (1989), a number of groups have demonstrated that a
wide variety of uncrosslinked polymer solutions can be used for separating dsDNA
fragments (e.g., Heiger et al., 1990;
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Grossman and Soane, 1991; Pulyaeva et al., 1992). These dsDNA matrices typically
have low viscosities and can be routinely filled and replaced at low pressures.

The development of replaceable matrices for DNA sequencing has been more
difficult, as higher concentration, higher viscosity solutions are required. In
1993, Karger and coworkers (Ruiz -Martinez et al., 1993) reported the use of a
6% uncrosslinked polyacrylamide (PAA), which provided single base resolution to
350-400 bases. Since then, additional reports on the use of uncrosslinked PAA
(Grossman, 1994) and other polymers (Johnson et al., 1995; Yeung et al., 1995)
as replaceable matrices for DNA sequencing have appeared. These matrices are
still relatively viscous, typically requiring several hundred psi and several
minutes for loading into standard (e.g., 75-100 (mu)m ID) capillaries. Matrix
loading in microfabricated lanes is likely to be more difficult, and existing
reports on sequencing in microfabricated devices have employed in-situ
polymerized gels (Balch et al., 1994; Went, 1995), similar to the early work in
capillaries.

2.3.4 Fluorescent Detection

Fluorescent detection of 4-dye Sanger fragments from a single lane was pioneered
by Smith and coworkers (Smith, 1986) and is currently available only from
Applied Biosystems. In its early and current embodiment, a scanning
laser/detection unit rasters across a slab gel simultaneously exciting a
detecting fluorescence from four select dye labels. Filters, initially employed
on a rotating wheel, have been replaced with a more efficient reflective
grating, allowing for the detection of 1.5 (upsilon)l of a standard Sanger
ladder.

Scanning. As capillary arrays are employed, scanning systems have been improved
- --------
to contain confocal illumination and detection (Mathies and Huang, 1992) to
reduce scattering off the glass. These systems are very efficient and have been
commercialized for non-sequencing use. Their use for imaging slab systems is
also growing (Brumely, 1994). Sample volumes that are actually required for
robust detection are less than 100 nl (Smith, 1993), 15-fold more sensitive than
the ABI system.

2.3.5 Informatics: Image Processing, Base Calling and Sequence Assembly

Determination of DNA sequence from fluorescent images involves the following
steps: lane finding and identification, background elimination, spectral matrix
conversion, base calling, and analysis/editing . At the 36 sample per day level,
this process involves a significant amount of human intervention for lane
calling and sequence editing. At 40,000/day, the system must permit automated
transfer throughout with under 1% manual intervention. Existing automated lane
finding software is capable of calling only 90% of sequencing gels without human
intervention (Stein, pers. comm.). Tibbetts and coworkers (Golden, et al., 1993;
Tibbetts, 1993) have applied neural networks to the base calling problem, with
significant improvements over traditional methods. Giddings (1993) has also
worked on this problem using expert modules which judge peaks to evaluate the
confidence of base calls.

Unlike all other stages of the process, assembly and finishing have
traditionally required considerable human attention including hours of attention
at a computer screen and custom-designed experiments to resolve uncertainties.
More than 60% of the costs of large scale sequencing projects may go to assembly
and finishing, due to their low efficiencies. There have been considerable
advances in sequence assembly. Specifically, PHRAP (Phil Green, pers. comm.) and
FAK (Gene Myers, pers. comm.) represent substantial improvements over previous
tools and essentially solve the issues of assembly with few repeats, yet still
have serious difficulties with many mammalian sequences.

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In this section, we review development at each of our four groups which provides
the foundation for this project. These preliminary results are organized by
component technology rather than group, consistent with our systems approach.
The starting point of this project is CuraGen's current version 1.0 DNA analysis
system, shown in Figure 3.1. As an end user requiring high throughput,
integrated DNA analysis systems, CuraGen has developed

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a horizontal thin gel electrophoresis system with a proprietary imaging
spectrograph adapted to DNA sequencing, ready for integration into automated
systems. The optical schematic shown in Figure 3.1 highlights the principle
hardware components of CuraGen's DNA analysis system. This device has been in
operation at CuraGen since early 1993 for a variety of applications, including
sequencing (see Figure 3.1 and A.0 in the Appendix for representative M13
results). The system has several advantages:

. It is a high speed modular device that is adaptable and
upgradeable. Current speeds are 700 bph (bases per hour) with read
lengths of 450bp typical, as shown in Figure A.0. In general, we
load 1/15th of a standard ABI sample. The system is running at 36
lanes per gel at 14 Kb of raw sequence/hr.

. Full spectrum detection under software control allows any dyes to
be used (see Figure 3.3). We have demonstrated the feasibility of
five colors being used simultaneously (four for sequencing, the
fifth for reverse sequence or fingerprint information).

. It includes trainable image analysis and base calling software. In
collaboration with Dan Seligson of Intel, CuraGen has developed a
modular set of algorithms for preprocessing and base calling. The
advantages of the software are full UNIX compatibility, a database
access tool set (with easy i/o) and high processing speed (less
than 5 secs/lane on an Intel P90).

The ability to integrate this device into automated systems, both in terms of
front end sample handling and back end image processing and base calling, makes
this system a cost effective alternative to the ABI.

3.1 Sample Preparation (MIT, CuraGen)

3.1.1 Automated Protocols for Large Scale Genome Sequencing (MIT)

Work at MIT/Whitehead has culminated in a second-generation automation system
for purification of templates and production of sequencing ladders. The current
"Sequatron" system has a throughput of 80 microtiter plates per 24 hours,
starting with grown M13 supernatants for DNA isolation or plates of PCR products
and ending with completed pooled sequencing reactions ready for denaturing and
loading on a gel.

3.1.2 Solid phase technology /Automated Loading/Concentrating (MIT, CuraGen)

We have developed a simplified system for the manipulation and isolation of DNA
using solid phase purification that does not rely on streptavidin-biotin,
digoxigenin-antidigoxigenin or sequence-specific interactions. We refer to this
as Solid-Phase Reversible Immobilization (SPRI, Hawkins et al., 1994). The
method provides a solid-phase purification procedure that can be used for DNA
extraction, purification and concentration. These methods have been introduced
into routine use in the Whitehead DNA Sequencing Core.

[GRAPHIC APPEARS HERE]

Figure 3.2 Trace file obtained from direct SPRI loading experiment performed
at MIT on a CuraGen device. Sequence of M13 obtained using standard
ABI kit. Trace shows bases 100 - 200 taken over a 7 minute stretch.
Applied voltage was 5 KV over 25 cm, 200 V/cm.

The isolation of extension products using solid phase support has had
limited use, mostly due its lack of applicability to cycle sequencing, the
elevated cost of magnetic particles and the lack of demand for replacements to
ethanol precipitations. A key advantage of the SPRI procedure is that the
isolation step functions as a concentrating step and can be directly
incorporated into an automated loading step. We found that SPRI can both
concentrate dye-primer reactions as well as clean-up dye terminator reactions
prior to electrophoresis. This removes the need for ethanol precipitation or
spin columns. Of great importance, the primers do not have to be derivatized
---
with haptens such as biotin or digoxigenin to be subsequently isolated using
SPRI, and hence it is applicable to amplification based sequencing techniques,
now the methods of choice in the genome community. Direct loading with SPRI
beads into formamide wells (see Figure 3.2) allows the precise control of the
loading and motivates the design of an automated system.
<PAGE>

One principal advantage of the CuraGen DNA Sequencer is the ability to image
many distinct dyes simultaneously. Methods for producing sequencing ladders from
both directions have been tested, and to date we have shown that 5- dye
sequencing can be achieved with the fifth color being used to obtain a T track
from the opposite end of the sequencing template (Figure 3.3). Strategies
employing more then 4 dyes have utility in fingerprinting, assembly and
finishing. Combined with Figure 3.4, this clearly establishes (1) the
feasibility of 5-dye protocols for alignment (using far distant red-dyes) and
(2) the potential to sequence in both directions using 8 dyes. With this proof
of principle and our current advances in fluorescent detection, we are in a
position to develop full bi-directional sequencing strategies.

[GRAPHIC APPEARS HERE]

Figure 3.3 Bi-directional sequencing. The trace shown in 3.3a is a
sequence off the forward primer of a sequamark template, while
trace 3.3c is the same template sequenced from the reverse primer.
The center trace 3.3b is the result of a sequencing run from a
single tube in which two different primers, FAM-forward and
JOE-reverse, were placed with the ddT mix. The resulting product
terminates in both directions with two different dye labels. A
color copy of this figure is included in the Appendix.

[LINE GRAPH APPEARS HERE]

Figure 3.4 Spectral emission measured from spatial cross section taken
from electrophoresing dye-labeled primers. All 8 have been tested
and the individual dyes are easily resolved. A 5-dye set can be
chosen and we are currently evaluating 8 dye possibilities. A color
copy of this figure is included in the Appendix.

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3.2 Gel Electrophoresis (CuraGen)

We have developed a flexible thermal regulation box (air, water, and passive)
for the use and testing of a variety of thin slab and microfabricated channel
devices (see Figure 3.1). It requires under 10 minutes of assembly time and
yields bubble-free, high quality 50 (mu)m gels over 95% of the time.
Representative capabilities are shown in Figure A.0, 3.2 and 3.3, in which raw
data (i.e., matrix converted without any filtering) clearly indicates the
ability to load, electrophorese and detect from these gels.

3.1.1 Routine Thin Gel Capabilities.

CuraGen has logged over 7000 lanes on its thin slab system and currently has 4
systems in place. During the month of August 1995, MIT carried out over 500
lanes with comparable results.

Multiplicity (36). Figure A.0, 3.2 and 3.4 taken from 36 lane runs using
sharkstooth combs. Manual lane identification easily picks separate lanes.

Length of Read (500). Figure A.0 shows a sequence of M13 at 450+ bp.

Speed (1 hr). The results shown in Figure 3.2 from a SPRI experiment
run at MIT clearly show that at 5kV, we can obtain base pair resolution to
400 bases at 17 cm from the loading region at a rate of 15 bp/min.

3.2.2 Microchannel Substrates

Figure 3.5 shows a trace taken from a 96-channel glass substrate used to test
microchannel electrophoresis in which 10 nl of input Sanger ladder was loaded.
Although the quality is less than a comparable run on a thin slab, the sequence
was correctly called. Improvements to the loading (larger volumes) and imaging
capabilities are being developed under a NIH Phase II SBIR.

[GRAPHIC APPEARS HERE]

Figure 3.5 Processed sequencing data obtained from sequencing an M13 template
in two different configuration: (a) top, short thin slab with laser
10 cm from loading region; (b) bottom, glass microchannels with
laser 10 cm from loading region. Color copies of this figure are
included in the Appendix.

3.2.3 Polymeric Substrates

Mass production of polymeric substrates via molding or casting will be
significantly less expensive than etching glass, will not produce acid waste,
and will therefore enable our strategy of providing ready-to-use, disposable
microchannel substrates. Moreover, there are a great number of methods for
fabricating plastics and a variety of transparent materials to employ. The
personnel at SBio have investigated the polymerization and optical
characteristics of a variety of plastic materials. We have a long track record
of replicating the surface and bulk features of molds in plastic with high
precision, as will be required for microreplication of lanes in plastic. In
addition, our experience with mass producing such substrates in a commercial
setting will enable the eventual production of the proposed microreplicated
separation subsystems.

3.3 Advanced Separation Media (SBio)

SBio is developing improvements in replaceable gels for DNA sequencing by
capillary electrophoresis (CE), as reviewed below. These preliminary results
demonstrate SBio's expertise in gel media, and a technology base that serve as a
foundation for this project.

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1st generation replaceable matrices. SBio is developing non-crosslinked,
replaceable matrices for CE based on N-substituted acrylamide polymers, which
are known to provide an order-of-magnitude increase in hydrolytic stability
relative to polyacrylamide (Righetti et al., 1993). Hydrolysis of the amide
bonds in polyacrylamide (PAA), which is accelerated at high pH and urea levels,
will limit the shelf life of replaceable matrices based on uncrosslinked PAA. We
have developed copolymer formulations of N-substituted acrylamides that provide
resolution comparable to PAA matrices (Figure 3.6), while simultaneously
providing enhanced stability and shelf life. We have also developed
reproducible, scaleable synthesis and purification processes for these matrices.
We are currently optimizing matrix formulations to reduce viscosity and
electrophoretic run time. The matrix used in Figure 3.6 was loaded into the 65
cm long, 75 (mu)m ID capillary in less than 3 minutes under an applied pressure
of 400psi. We believe that incremental reductions in loading pressure and time
can be realized through optimization of MW and MW distributions.

[GRAPHIC OMITTED]

Figure 3.6 Capillary electrophoresis separation of T-terminated extension
products from M13mp18 template on SBio replaceable matrix.
Experimental conditions: capillary length: 65.0 cm (40.0
effective), DNA injection: 12.0 kV - 15 seconds, run voltage: 12.0
kV. M13 sequence prepared via cycle sequencing using labeled primer
and imaged by laser-induced fluorescent detection.

2nd generation replaceable matrices. SBio is developing a novel proprietary
class of replaceable matrices which undergo phase transitions in response to
temperature (Soane and Bae, 1994; Soane, 1994 and 1995), offering the potential
for dramatic reductions in loading viscosity. In these "reversible gels", the
matrix polymer is highly soluble on one side of the transition, and much less
soluble (or insoluble) on the other side. We have demonstrated that this phase
transition property can be utilized to drive a viscosity transition (Figure
3.7), and have used this transition to demonstrate matrix loading in capillaries
under very low pressures, including simple vacuum injection. We have also
developed polymer compositions which provide excellent electrophoretic
properties in addition to this viscosity transition behavior. One family of
compositions is based on a subset of the N-substituted acrylamides which are
temperature-sensitive. Other, non-acrylamide compositions are also being
developed, along with matrices which have a low viscosity at room temperature
and gel upon heating. These 2nd generation matrices hold the promise for
dramatically improving the process of matrix loading and unloading, which will
be especially important if replaceable matrices are to be used in very small
channel microfabricated devices.
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Figure 3.7 Temperature induced phase transition in crosslinked microgel system
(A) and uncrosslinked polymer solution (B), resulting in a
reversible viscosity transition in both cases. The exemplary
viscosity curve (C) is for a microgel system with a transition
around 30C. By modifying the polymer composition, matrices can be
designed with viscosity transitions at temperatures ranging from
room temperature to 95 C.

3.4 Fluorescent Detection (CuraGen, Cornell)

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3.4.2 Microfabricated Optics (Cornell NNF, CuraGen)

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Figure 3.8 AFM area scan of a continuously blazed grating using focused
ion-beam milling (Shank et al., 1994)

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Figure 3.9 Diagram of a vertical optical interconnect showing the location of
the individual components (Bare et al., 1994)

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3.5 Informatics (CuraGen,MIT)

Critical issues in high-throughput genomic sequencing include sample
tracking, work-flow management, image analysis, base calling (speed and
confidence), assembly and finishing.

3.5.1 Image Analysis and Base Calling (CuraGen)

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Figure 3.10 Base calling algorithm and output. [XXXXXXXXXXXXXXXXXXXXXXXXXXXX
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Principal Investigator/Program Director (Last, first, middle):
Went, Gregory T.
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CuraGen has developed a modular set of algorithms for preprocessing and base
calling. The software has several advantages:

. it is trainable to new chemistries, dyes or dye coding strategies,

. it reports quantifiable confidence values on each base called, and

. it is based upon a UNIX development platform and easily integrated in
LabBase and other informatics systems.

There are three main modules: a signal preprocessing module, a pattern
recognition module (i.e., base calling for DNA sequencing), and a proofreading
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3.5.2 Assembly and Finishing (MIT)

Major assembly and finishing packages, including PHRAP and FAK, are in use in
our laboratories. We have written our own software, including MAPPER, which
assembles map contigs based on existing assembly tools with forward and reverse
constraints, and FINISHER, which uses the information from the map contigs to
select further experiments. Using these programs we have evaluated sequencing
strategies on simulated and real data. The ability to quantify the confidence of
individual base calls will set the precedent for allowing this entire process to
be conducted in an automated way, and to maintain the integrity of the data.

3.5.3 Work flow

Over the past two years, the MIT Genome Center's Informatics Core has gained
extensive experience in database and sample-tracking issues, and developed three
major systems: LabBase, Workflow Manager, and BuilderIO. Our laboratory
informatics system has been developed to allow FINISHER to download instructions
to robotic workstations. With the direct incorporation of the sequencing
instrumentation into workflow we will be able to place the instrument into an
automated environment and take advantage of the advanced base calling software.

4. Research Design and Methods

The research program outlined herein builds upon the combined experience of the
collaborators to develop technologies to accelerate the completion of the human
genome sequence as well as to enable more routine genome sequencing. As outlined
before, the HGP has evolved to the point where its completion is tractable. This
project plans to hasten that timeline in stages:

1) Version 1.1, a thin slab gel platform addressing the cost and throughput
needs of a 4000 sample/day pilot facility;

2) Version 2.0, a microchannel platform solving the gel and informatics
logistics of a 40,000 sample/day operation, capable of sequencing multiple
genomes and extending high throughput sequencing to other markets in the future.

The project is divided into the five components discussed shown below. Although
primary responsibility for the execution of each sub-task rests with the
collaborating investigators, all advances will be tested in CuraGen's evolving
DNA analysis system. Moreover, each of the project teams will have
instrumentation in place to accelerate the design and testing of individual
components.

A component breakdown with primary responsibilities and delivery dates is shown
below in Table 4.2.

4.0 A Modular Phased Approach

<TABLE>
<CAPTION>
Component Site Deliverable Date
<S> <C> <C> <C>

4.1 Sample Preparation MIT/Whitehead v. 1.1 Manual device 4/1/97
</TABLE>

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CuraGen v. 1.1 5-dye protocol 10/1/96
(Gregory Went) v. 1.1, 2.0 8-dye protocol 4/1/97
4.2 Electrophoresis System CuraGen/Cornell v. 1.1 Electrophoresis station 4/1/97
(Harold Craighead) v. 2.0 Microreplication 10/1/97
prototype

Soane BioSciences v. 2.0 Materials 10/1/97
(Herbert Hooper and v. 2.0 Surface design 10/1/97
David Soane) v. 2.0 Processing 4/1/98

4.3 Separation Media Soane BioSciences v 1.1 Reusable gels 4/1/97
v 1.1, 2.0 Dynamic porosity 10/1/97
v. 2.0 Disposable media 10/1/98

4.4 Binary optics Cornell v. 2.0 Collection optics 4/1/99
4.5 Informatics CuraGen v. 1.1 5-dye base calling 10/1/96
v. 1.1, 2.0 8-dye base calling 10/1/97
MIT/Whitehead v. 1.1, 2.0 Assembly/ 4/1/97
(Lincoln Stein) finishing with confidence
v. 1.1 5-dye assembly 4/1/97
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4.1 Sample Preparation and Loading (MIT, CuraGen)

4.1.1 Manual and Robotic Solid-Phase Sample Concentration and Gel Loading

In preparation for pilot projects, fully automated systems that process DNA
subclones into dye-labeled sequencing ladders have been developed with
throughput capacities of greater than 4,000 samples per day. Our system starts
with the sequencing products (Sanger ladders) presented in 96 or 384 well
bar-coded plates. This approach has three major benefits: (1) it reduces
redundancy with other efforts; (2) it allows new systems to dovetail into
planned pilot studies; and, (3) it reduces the upstream burden by decreasing the
number and the concentration requirements of the sequencing reactions. In
preparation for pilot sequencing, MIT has developed the Sequatron. This device
is currently being tested and used at the MIT Genome Center. We will enhance the
system with the ability to concentrate samples and load CuraGen's DNA sequencing
gels, allowing the integrated system to generate base called sequences directly
from DNA subclones. This enables increased throughput through the continuous
operation of DNA sequencers at lower variable costs.

We will utilize our combined expertise in solid-phase methods, including SPRI
(Hawkins et al., 1994a), biotin-streptavidin (Hawkins, 1994) with photocleavable
biotin derivatives (Olejnik et al., 1995), and digoxigenin-antidigoxigenin
(Hawkins et al., 1994b), to concentrate and purify the final sequencing ladders
produced by sequencing reaction as part of automated gel loading. During the
first year, we will focus on SPRI technology, a highly effective
biochemical/biophysical technique. SPRI uses inexpensive carboxyl-coated
magnetic particles that compose the base material for most magnetic particle
manufacture. The sequencing products are absorbed onto the surface of the
magnetic beads, which are then transferred to the gel using magnetic pins. As an
alternative to magnetic particles, we will also develop a manifold of 12
9mm-spaced pins coated to absorb reaction products directly, allowing washing
and finally elution of products into wells for electrophoresis. This will enable
us to transfer samples from standard 96, 192, or 384-well microtiter plates (9mm
well spacing) into a sequencing gel. Integration of this manifold onto the arm
of a robotic system will allow the full automation of this process.

In conjunction with using coated pins, we will also attempt to use graphite tips
(as used by Tecan and Packard to allow capacitance sensing) to absorb reaction
products and load the gels for electroelution. In addition to automation and
reproducibility improvements, autoloading from a solid substrate enables us to
take advantage of the 15-fold sensitive advantage of the CuraGen device. This
advantage reduces the enzyme utilization requirements at least 10-fold and
translates to a large savings in sample preparation costs.

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1. Year 1. Modify and improve our solid-phase approaches to enable us to coat 12
channel pins to perform SPRI, biotin-streptavidin capture or
digoxigenin-antidigoxigenin capture and fragment selection.

2. Year 1. Develop a 12 pin loading device to carry out parallel loading from 96
and 384 well plates directly into the wells of the electrophoresis system.

3. Year 1,2. Develop 12 channel pin tools to be fixed to the head of a CRS
articulated robot, as used in our Sequatron system. Set up the robotic system to
enable reproducible loading into wells less than 0.1mm apart. The use of a CRS
articulated arm will give us the necessary flexibility.

4. Year 1,2. Integrate the automated sample concentration and gel loading into
the Sequatron system to provide a fully integrated and automated system.

5. Year 3. Resolve problems of final integration into Sequatron system. Modify
Sequatron software to include collection software of CuraGen electrophoresis
instrumentation.

4.1.2 8-Dye Bi-directional Sequencing

Advances in detection and software allow two reactions, one in each direction,
to be produced from a single template (see Figure 3.2). Initially the reverse
read will be for only one base (5-dye sequencing) for fingerprinting, sizing, or
to enhance assembly strategies. Later evolution to a full 8-dye system will
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1. Year 1. Establish alternative dye sets for 5-dye and 8-dye sequencing. We
will evaluate the properties (shifting, signal/noise) of a number of publicly
available dyes to expand our current set of 8. Dye-transfer (tested and soon to
be available) dyes (Yu et al., 1995) will also be investigated.

2. Year 1. Build on CuraGen's 2-dye, bi-directional success to develop a kit for
full 5-dye sequencing. The 5th dye will be chosen such that a full 5 basis
matrix transform is robust. This is rather straightforward in a two-laser system
(i.e., no spectral overlap between the standard 4 and the 5th dye).

3. Year 1,2. Reduce enzyme costs by using highly efficient loading protocols.
Sensitivity improvements will minimize the concentration of enzyme needed.
Reaction and cycling conditions will be modified to optimize the results.
Properties of other dyes, including incorporation and detectability, will be
investigated.

4. Year 2. Develop and implement full bi-directional sequencing. This primarily
involves protocol application and software confirmation that the 8-dye transform
matrix works. Again, given the 2-laser, 2-region capabilities we have in version
1.0, this is completely feasible with current state of technology.

4.2 Electrophoresis System (CuraGen, SBio, Cornell)

4.2.0 System Design - Reusable (v. 1.1) to Disposable (v. 2.0) Separation
System

The 2+ years of production experience with the thin gel system at CuraGen,
combined with MIT's experience in the logistics of executing thousands of
electrophoresis runs/day, suggested to us separating the electrophoresis plates
and media from an electrophoresis station residing in an optical detection
compartment. Such a decoupling can reduce the optical "downtime" between runs to
minutes, thereby maximizing the throughput of the system. We propose to achieve
this efficient operation through a modular design:

1. an electrophoresis station integrating loading and electrophoresis
electronics with high speed thermal regulation;

2. female end connectors that contain the buffer, loading and optical
illumination accessories; and

3. gel plate devices (both thin slab and microchannel) that are either
disposable or remotely filled/cleaned.

These developments are readily tested on CuraGen's version 1.0 platform.

4.2.1 Electrophoresis Station/Accessories

CuraGen's version 1.0 thin slab device is a component that enables high voltage
electrophoresis with a variety of cooling (air, water, passive) and laser
illumination strategies. To reduce turnaround times (currently 20 minutes) and
to enable temperature sensitive gels and disposable gel devices, we will produce
a platform that accommodates a plate between two end-caps. A principle feature
is the decoupling of the electrophoresis system from the thermal regulation in a
safe, well-interlocked system, allowing direct and flexible testing of

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Principal Investigator/Program Director (Last, first, middle):
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microreplicated systems. Buffer caps have been designed that seal to the
radiused surface of the glass or plastic electrophoresis plates. For
non-disposable glass substrates, a separate pouring station is constructed to
enable rapid end-capping, pouring, and polymerization. Once prepared, the gel
plates are placed onto the electrophoresis station. Electrical contact is made
through the end-caps to the station, and final voltage contact is established
when the station lid is shut. Should longer lengths or better thermal control be
required, this system will be adaptable to different shapes and cooling
strategies. Our yearly plans are as follows:

Year 1. Evaluate materials and designs for the end-caps. Key considerations
include sealing to radiused glass/plastic gel plates, tensioning to the loading
combs, and proper tensioning of the plates. Prototypes will be machined from
delrin with non-conducting O-rings providing the sealing. We expect to address
first the sealing/loading characteristics, maintaining as much similarity to
working systems at CuraGen and MIT.

Year 2. Issues associated with producing large numbers of these systems,
including casting/molding, will be addressed in Years 2 and 3. Materials for
microreplicated gels substrates will be evaluated to insure their utility.

[GRAPHIC APPEARS HERE]

Figure 4.1 Electrophoresis system in version 2.0.

4.2.2 Microreplication Development

Our objective is to develop disposable microchannel substrates that can be
pre-filled with gel and supplied ready-to-use at low cost (less than $20/gel).
To accomplish this, we will investigate the production of lanes in plastic,
which has several advantages over a glass substrate: (1) lower production costs;
(2) reduced disposal and handling problems related to wet etch chemicals; (3)
facile bonding of base and cover substrates to form closed channels; and (4)
positionally-defined channel surface properties. These advantages are magnified
by the large consumption of plates, 500 to 1000 per day, in a high throughput
lab.

It is important to note that this effort is backed by experience with slab gels
(CuraGen), plastics and replication (Soane Technologies, Soane BioSciences), and
microfabricated electrophoresis channels (CuraGen with Cornell NNF). Rather than
a device on a glass microscope slide scale, our intent is to carry out
electrophoresis over suitable distances (10 cm - 30 cm) in a microchannel array
that takes advantage of proven loading and detection methodologies. In short, we
aim to replace the thin-gel plates we use now (10 cm and 14 cm width by 10 cm
and 30 cm length) with micro channel plates of the same size, increasing the
channel density to allow 64 (v. 1.1), 96 (v. 2.0), and ultimately 384 lanes.

Microreplication development will involve 6 component efforts: (a) establish
design features; (b) develop prototyping methods to test system designs and
plastic formulations; (c) investigate electrode deposition; (d) develop polymer
formulations exhibiting the required bulk properties; (e) develop channel
surface modifications to enable high-resolution separations; and (f) demonstrate
a microreplication production process. These six efforts, involving
contributions from CuraGen, Cornell and Soane, are reviewed below.
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Principal Investigator/Program Director (Last, first, middle):
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4.2.2.a Design Considerations
- -----------------------------

The design considerations focus on developing a standard geometry for
interfacing the sample handling system, either combs or reactors, with the
sample imaging system (existing and proposed microfabricated optics discussed
below). Open lanes at the entrance converge in the imaging region in order to
present the correct size scale to each module. This strategy does not introduce
serpentine patterns that may broaden electrophoresis bands. We have already
fabricated masks to make converging lanes and will continue to investigate other
lane geometries, such as a fan of straight lanes at different angles. The
underlying principle is to have a size scale near the loading end that is
consistent with available solid phase and micromachined sample loading methods
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4.2.2.b Substrate Prototyping
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Prototyping methods are being established now and during the first year to lay a
foundation for testing different system designs (lane geometries, electrode
locations), polymer formulations, and surface modifications. We have identified
three methods for the prototyping of lanes. Most can be configured to
accommodate the long substrates required for electrophoresis.

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4.2.2.d Formulation Development
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We will develop polymer formulations that are amenable to the processing
techniques outlined above, and which provide optical, mechanical, thermal and
surface characteristics to enable high-resolution separations and high-
sensitivity detection. We note that plastics are commonly used as an alternative
to glass in slab and tube gel electrophoresis, particularly for pre-cast gels
where cost is a concern. Plastic has also demonstrated utility in capillary
electrophoresis (e.g., Lukas and Jorgenson, 1985; Nielen, 1993; Liu et al.,
1993). The dominant use of fused silica in CE is due to the commercial
availability of high-quality fused silica capillaries, the higher thermal
conductivity and higher UV transparency of fused silica compared to plastic, and
the established means for modifying silica surfaces in CE separations. However,
none of these are inherent limitations in our system, and manufacturability is
actually a significant advantage of plastic in our approach.

Our focus will be on curable (UV, heat) and injection moldable materials, which
will be amenable to prototyping methods 2 and 3, and ultimately to production
methods (Section 4.2.2.f). Acrylics and aliphatic urethane acrylates will be
investigated first for their excellent optical properties and formulation
latitude. In general, they are highly transparent above 250nm and exhibit low
background fluorescence. Further, we have considerable experience in formulating
and processing these classes of polymers for optical applications. Any specific
formulations under consideration will be examined for transparency and
fluorescence before being used. Raw material purity is critical to eliminating
fluorescence, and we will implement established purification methods developed
by Soane Technologies. Mechanical rigidity can be imparted through crosslinking
or providing a rigid support (e.g., glass) under the microreplicated substrate.
The glass-plastic composite approach can also be used to improve thermal
dissipation if required, wherein the plastic layer need only be thicker than the
channel depths. Surface properties are considered separately in the next
section. Regarding potential scattering of the excitation beam, we view this as
a system issue and have designed channel geometries where the laser does not
pass through the channel walls.

4.2.2.e Surface Modification
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Principal Investigator/Program Director (Last, first, middle):
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Surface chemistry and topology are critical in narrow bore separations, and
unmodified fused silica capillaries have traditionally required modification to
suppress electroosmotic flow in DNA sequencing applications. The two common
approaches are: (1) covalently linking the separation matrix to the capillary
wall, and (2) covalently or physically coating the capillary wall with a
hydrophilic polymer to suppress the surface charges and adsorption. Both in-situ
polymerized gels and replaceable matrices can be used with coated capillaries.
Like fused silica, most native polymer surfaces also exhibit a surface charge in
electrolyte solutions (Schutzner and Kenndler, 1992), and we will need to employ
one of the two basic strategies noted above. The silane coupling chemistry used
with fused silica is not applicable to organic polymer surfaces. However, there
are numerous methods for derivatizing polymer surfaces, and we have identified
three approaches to be investigated here as discussed below.

1. Surface Activation: Free radicals created at the polymer surface and present
- ---------------------
during acrylamide polymerization will result in covalent attachment between the
polyacrylamide and the surface. Liu et al. (1994) demonstrated a
hydroperoxidation preactivation method for covalently coating polypropylene
capillaries with polyacrylamide. This hydroperoxidation method should be
applicable to a wide variety of polymer surfaces, and will be used here. We can
also use electron discharges (RF, microwave, corona) in inert gas plasma to
activate the channel surfaces (Yasuda et al., 1987).

2. Coupling agents: This approach, analogous to silane coupling with silica,
- ------------------
involves a hetero bifunctional reagent, wherein one functional group reacts with
the polymer surface, and the other functional group (a vinyl or an acryl group)
later reacts with a growing polyacrylamide chain (e.g., urethane acrylates could
be used with surface hydroxyl groups). The first step is to ensure functional
groups are present at the polymer surface. We will design UV-curable
formulations containing latent functional groups that orient preferentially at
the surface (e.g., amine, carboxylic acid, hydroxyl groups). Other approaches to
incorporate surface functionality include using oxygen plasmas, and
photopolymerization of vinyl polymers (e.g. hydroxyethyl methacrylate) onto the
substrate surfaces (Wright, 1978). A wide range of hetero-bifunctional reagents
can then be used to react with these surface groups, and provide a reactive
group for incorporation into a polyacrylamide chain.

3. Surface Interpenetrating networks (SIPN's): This third approach is practiced
- ---------------------------------------------
by the contact lens industry (Thakrar and Gandhi, 1995). The polymer substrate
is first contacted with a liquid monomer (e.g., dimethyl acrylamide) which
penetrates the substrate surface without causing dimensional deformation. Next,
the gel-forming monomer solution (e.g., acrylamide) is injected into the channel
and polymerized. The first, surface-penetrating monomer will polymerize in the
presence of the free radicals, interpenetrating with the polymer substrate and
the gel matrix, forming a SIPN.

The above three methods provide us with a means for addressing a wide variety of
polymer substrates as we move through prototyping to production. The surface
activation method will be developed and applied for substrates fabricated by
direct patterning. The coupling agent approach will be developed in concert with
UV curable polymer formulations used for in-situ curing and replication.
Finally, we will explore surface activation, coupling agents and the SIPN
approach for applicability to molded thermoplastics. As described above, both
surface linkage of the gel matrix and coating of the channel surface are
feasible strategies, and either can be pursued using the three surface
modification methods. We will initially form polyacrylamide coatings on the
channels to enable quantitative evaluation of the surface treatment. This will
be done by measuring the EOF before and after surface coating. This enables
comparison of different polymer formulations and surface treatment methods. Upon
determining that a polymer composition and surface modification method are
acceptable, either surface coating followed by gel formation, or direct gel
formation with surface attachment can be used for evaluating separation
performance. While reference is made to polyacrylamide in this section, methods
applicable to polyacrylamide will be equally applicable to our advanced media
(Section 4.3).

4.2.2.f Development of Production Technology
- ---------------------------------------------
Casting or molding from a master substrate (microreplication) is expected to be
the most economical and robust production approach. The prototyping studies will
provide initial process parameters for replication using the optimized
formulation. A major technical difference between production and prototyping
will be the molds employed. For production, electroformed metal molds will be
preferred for ruggedness and economics. One method of producing electroformed
molds for micro scale parts is the well-known LIGA process depicted in Figure
4.3 (Becker et al., 1986). In this process, a thick (~100 (mu)m)
polymethylmethacrylate (PMMA) film is exposed to X-rays through an X-ray mask
which defines the lane geometries. The exposed areas are chemically altered and
can be selectively dissolved to form trenches. Nickel is electroplated into
these trenches to form a metal mold and the mold is released by dissolving the
remaining PMMA. This technology is well-established, but can prove costly due to
the need for access to a synchrotron for X-ray exposure and the expense of
fabricating
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Principal Investigator/Program Director (Last, first, middle):
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X-ray masks. Typically, LIGA is used to produce thick structures with fine
resolution (less than 1 (mu)m). In our application, this fine resolution is not
required and therefore we can use an alternate technology to manufacture metal
molds more cheaply. A photopatternable polyimide can be used in place of the
PMMA employed in the LIGA process. This allows us to use standard UV light
photolithographic tools and masks to form trenches for nickel electroplating.
This greatly reduces costs and a resolution of 10 microns can be easily achieved
in 100 micron thick structures.

[GRAPHIC APPEARS HERE]

Figure 4.3 Schematic representation of the LIGA processing for replicating
channel features.

As indicated earlier, microreplication can be accomplished by injection molding
or casting. The decision on replication method will be made in the third year
based on knowledge gained during the project, specifically on the processing
requirements of the optimized formulation and the replication accuracy
attainable with molding vs. casting. The objective in year three will be to
demonstrate on a small scale the production of high-quality microreplicated
systems from electroformed metal molds using the optimized polymer formulation.

4.3 Separation Media (SBio)

4.3.1 Reusable Media - v. 1.1

A reusable matrix will be developed to improve the efficiency of the Phase I
system in a production environment. Reuse of polyacrylamide has been
investigated in capillary and slab gel formats (Swerdlow et al., 1992 and 1994;
Ansorge et al., 1992). Three primary factors are reported to limit gel reuse:
(1) hydrolysis of amide bonds in polyacrylamide, (2) ion depletion at the
gel-liquid interface, and (3) difficult removal of DNA templates and large
fragments from the gel. As discussed in Section 3.3, SBio has developed
non-crosslinked matrices based on N-substituted acrylamides which provide high
resolution and greatly enhanced hydrolytic stability. We will develop
crosslinked gel formulations based on these hydrolytically-stable compositions
for use in the v. 1.1 system. We will also investigate the use of buffer
additives (Swerdlow et al., 1994) to match the environment of the gel and
running buffer, limiting the formation of a liquid junction potential. Rather
than monomers, uncrosslinked polymer solutions will be used as additives,
thereby limiting user exposure to toxic chemicals. Formamide and mixed
formamide/urea buffers will be investigated if standard 7M urea gels demonstrate
unacceptable deformation in the loading region (Swerdlow et al., 1994).
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Principal Investigator/Program Director (Last, first, middle):
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----------------
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[GRAPHIC APPEARS HERE]

Figure 4.4 A schematic diagram of the "collapsible" gel pore concept. The
framework of the polymer network will be formed by crosslinked,
hydrophilic, non-temperature-sensitive polymers (shown as thick
lines). Grafted onto the backbones of the crosslinked polymers will
be long, temperature-sensitive side-chains (thin lines). At one
temperature (A), the side-chains are more soluble and assume
extended conformations, "fingering" across the gel pore to form a
physically entangled network for the separation of DNA sequencing
fragments. When the temperature is changed (B), the side-chain
solubility is dramatically reduced, resulting in side-chain
collapse and dilation of the gel pores. The phase transition
temperature and the direction of the transition (low-to-high or
high-to-low temperature) can be controlled through the chemical
composition of the side-chains.

The above efforts should enable several runs per gel for samples not containing
template or large fragments. When these larger fragments are present, they may
remain in the gel or migrate out very slowly. We will investigate a "collapsible
pore" concept for dynamically opening the gel pores after a run to flush out
rapidly templates and large fragments. This scheme, depicted in Figure 4.4,
involves temperature-responsive side chains grafted onto a large-pore framework
of a non-temperature sensitive polymer. SBio has initial candidate compositions
for both the polymer framework and side chains from previous work, both of which
are hydrolytically stable. This research will involve synthesizing the graft
structures and testing different framework pore sizes and side chain molecular
weights. A variety of methods for polymerizing graft structures are known
(Dreyfuss and Quirk, 1987) and should be directly applicable here. A variation
of this strategy which does not require grafting is to synthesize the framework
polymer in an uncrosslinked solution of the temperature-responsive polymer. In
this approach, the temperature-sensitive polymer will be physically entrapped
within the framework structure, and will exhibit a transition from expanded to
collapsed structures (Section 3.3). Temperature-responsive polymers can be
designed to collapse due to either heating or cooling, providing additional
design flexibility.

4.3.2 Dynamic Porosity Media

The importance of long reads in genome sequencing is well established. In manual
sequencing, where the entire gel is imaged after a run, gradient gels have been
used to extend read length (States et al., 1991). However, the factors limiting
resolution and read length in manual and automated sequencing are different. As
reported by Slater and Drouin (1992), read length in a manual sequencer is
limited by the interband spacing of the large fragments, a problem which
directly lends itself to the gradient gel approach. In contrast, the read length
in automated slab sequencers is reported to be diffusion (band width) limited,
indicating that a static spatial gradient would not improve read length in
automated sequencers. Instead, longer gels and lower voltage drops have been
used to extend read lengths in automated sequencers (Luckey and Smith, 1993).

Theoretical and experimental evidence (Harke et al., 1992) indicates that the
resolution for a given DNA fragment length is optimized at a single gel
composition (other factors constant), and that this optimal gel concentration
decreases with increasing fragment length. Based on this evidence, we propose a
new strategy for increasing read length in automated sequencers. This strategy,
if successful, will be implemented in our v. 1.1 and v. 2.0 systems. We will
employ a temporal concentration gradient, reducing the effective gel
concentration during the run. The collapsible pore concept provides a basis for
developing dynamic porosity gels. We will design
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polymer side chains which convert from extended to collapsed conformation
gradually over a 10-20 degree range, creating a dynamic concentration gradient
in the pores via thermal control. Variations of this strategy include combining
different side chain compositions that have sharp transitions spanning a 10-20
degree range, and combining temperature-sensitive and non temperature-sensitive
side chains. We will investigate these different approaches and determine which
provides the optimal increase in read length. As in section 4.3.1, an alternate
approach to the grafted side chains will be temperature-sensitive uncrosslinked
polymer physically entrapped in a crosslinked framework. Dynamic porosity can,
of course, be coupled with other methods for increasing read length (e.g.,
longer gels) if necessary.

4.3.3 Media for Disposable Separation System - v. 2.0

We will develop media compositions and polymerization methods enabling the
microreplicated subsystem to be manufactured with self-contained media and
supplied ready-to-use. In production, the media will be polymerized in the
channels, followed by sealing the microreplicated system in a foil with excess
buffer (similar to how pre-cast protein gels are currently packaged).
Alternatively, the media can be supplied dehydrated in the channels, and then
rehydrated with buffer at the point of use. The gel-filled microreplicated
subsystem will need a shelf life of 6 months or greater. The matrix polymer
stability should not be a problem, as we can use the hydrolytically stable
polymers discussed in Section 4.3.1 if required. Urea is known to be unstable in
solution, however urea sequencing buffer is sold commercially with a reported
shelf life of over 6 months when refrigerated. We will determine whether urea
can if fact meet the shelf life requirements, or whether alternate denaturants
(Smith et al., 1990) need to be investigated. If these approaches are
unsuccessful, we can dehydrate the matrix in the channels for shipment. A
re-sealable cover/base design will be preferred in this approach for rehydration
kinetics, and should be feasible through the formulation of the cover material
(e.g., use of an elastomeric polymer layer enabling sealing through
compression). Polymerization of crosslinked gels in capillary size channels can
result in shrinkage-induced defects, particularly when the gel is linked to the
channel walls. SBio's patented process (Soane, 1991) with proven ability to
prepare defect-free, gel-filled capillaries can be employed here. This method
compensates for polymerization-induced shrinkage by a sequential curing
technique similar to that described for substrate replication. This process can
be readily applied to all of the channels simultaneously using a single UV scan
from one end to the other of the sealed microreplicated system. The above
methods should also allow for incorporation of dynamic porosity compositions for
situations where longer read lengths are desired.

4.4 Advanced Detection: Replicated Optics (Cornell NNF, CuraGen)

We are proposing to fabricate and test a microfabricated optical system for
excitation and detection of fluorescence from channels. This optical system is
designed to dovetail into the microreplicated gel systems. The system employs
arrays of micro[XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
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4.4.1. Side Illumination Spectral Detection.

Building on CuraGen's grating spectrograph, we will extend the techniques of
micro-optics to make a 10-fold reduction in the size and cost of the v. 1.0
imaging system. The 0.5 numerical aperture described above implies a large
collection angle. This is desirable for collecting the maximum amount of light
and results in a very short depth of focus. This will result in the compact
system we desire and will allow a dense array of optical elements and efficient
light collection. High quality lens arrays are commercially available in this
range of parameters, e.g. Gelsil Inc., which uses the Corning technology for
high quality molded silica optics. In the final phase of the work after
optimizing the design and testing prototype systems, our efforts will be
directed toward reducing the number of optical elements by combining
functionalities. For example, the wavelength dispersion and spatial focusing of
the fluorescent radiation can be combined in one unit by forming a grating on
the surface of the lens array. While our schematic shows discrete optical
elements, we will work to combine these into a maximally integrated unit for
increased simplicity in and operation.

[Confidential Treatment Requested]
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[XXXXXXXXXXXXXXXXXXX]

Figure 4.4 Schematic of microfabricated optical elements that accomplish the
same function as CuraGen's existing device at a 10-fold higher
throughput. For side laser illumination, the confocal laser and
dichroic can be omitted.

4.4.2. Confocal Illumination and Detection.

The fluorescence collection system we have outlined will work with a variety of
laser illumination methods. Depending on the outcome of the channel prototyping,
we may chose to explore the possibilities of confocal illumination. The
outstanding feature, compared to the conventional scanning confocal fluorescence
method, is that we do not need to slew mechanically the optics across the
capillary array. The result is a more robust design. We can also employ rigid
alignment methods, impossible in a scanned system, required for the short depth
of focus of the high numerical aperture lens system.

4.4.3. Laser illumination

It is intended to investigate the use of both pulsed and continuous wave laser
source excitation with the objective of ascertaining the minimum limits of
fluorophore concentration for the reliable identification of fluorophore tags.
Of particular importance is the level of unwanted background light generated by
Rayleigh and Raman scattering in the gel and surrounding media, specular
reflection of the laser beam into the collection optics and any fluorescent
emission produced in the glass components of the system by the laser. We will
investigate the tradeoffs involved with continuous wave excitation (with and
without scanning) and pulsed laser excitation with

[Confidential Treatment Requested]
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respect to signal-to-noise ratio and observation time and ascertain minimum
fluorophore detection limits under these conditions.

4.4.4. Production.

Once the lane and optical features have been resolved, we will complete
development by characterizing methods for producing these in large quantities.
In particular, we will explore replication means similar to those being
evaluated for the formation of channel features. Principle difficulties will be
to develop robust means for replicating sub-micron features. However, previous
research in fabricating micro-optics has show that such resolution is
achievable.

4.5 Informatics (CuraGen,MIT)

4.5.1 Image Analysis and Base Calling

The preprocessing module will be modified to allow the use of more than 4 dyes
with the base calling software. For the 5-dye system, this can be accomplished
simply by adding a spectrally distinct 5th dye and using a 5x5 matrix for the
transformation from "wavelength space" to "dye space." The conversion produces 5
independent signal channels, which can be used in any base-coding scheme. For
example, 4 channels can be used to identify bases in one DNA strand, while the
5th channel identifies a single base in the reverse strand as an aid in sequence
alignment. For the 8-dye system, one option is as follows. Two lasers are used
to excite two spectrally distinct sets of four dyes each, each in two
independent wavelength regions. Thus the same 4x4 matrix operations used in
conventional preprocessing can be applied independently to the sets of four
dyes. The combined wavelength transform is then a block-diagonal 8x8 matrix with
two 4x4 blocks. We will investigate the possibility of using an analogous matrix
transform to deconvolute the signal from many dyes directly, even if there is
some spectral overlap between dyes.

The base calling module will be redesigned to produce a statistical measure of
the likelihood that a particular signal was generated by each of the four
nucleotides. This probability function can be obtained, for instance, by
comparing the measured signal to the expected signal, or "cluster center," for
each of the four bases (see Figure 3.11). For instance, one can define a metric
which measures the distance between the experimental signal and each of the four
cluster centers. If one of these distances is much smaller than the other three,
then the identity of the base is clear. We will be conducting ongoing research
to investigate the optimal form for the distance metric, including such factors
as the length of the DNA sequence and the identities of nearby bases. We will
also investigate different algorithms for converting distances from cluster
centers into base call probabilities. The best form will be investigated in
conjunction with our ongoing research into the best method of "training," i.e.
the optimum approach to allocating and locating base call prototypes within each
cluster.

4.5.2 Assembly and Finishing

While various definitions of finished sequence have been proposed, they are
usually based on a specific level of accuracy (e.g. 1 error in 1000 bases). The
direct incorporation of the complete information on a base call will allow for
full information to be taken into account during assembly, as opposed to an
arbitrary single call. For an assembled sequence, this translates to a
quantifiable confidence level that can be experimentally correlated with an
error rate. Integration of the base call information with the assembled sequence
will allow the contiguous sequence to be scanned and the quantitative confidence
in the finished sequence to be displayed.

A suitable function of the distances to base call clusters described above and
shown in Figure 3.10 can be used in multiple alignments to greatly increase the
confidence in finished sequence. The goal is demonstrated with a simple example,
showing only two bases. If a base is sequenced three times as A, A, and T, it is
difficult to determine a consensus with confidence. However if the same base is
sequenced as (A=0.95,T=0.05), (A=0.98,T=0.02), and (T=0.59,A=0.41), then it is
reasonable to declare with confidence that A is the correct call. In practice,
we will use the information available to create statistical measures of the
likelihood that each base call is correct, and then will use these to generate
mismatch penalty tables to be used in existing multiple alignment tools.
Furthermore, we will investigate other options for more direct conflict
resolution in multiple alignments. These will use the full information available
from the base calling software.

Our approach will lead to an integration of the base calling software directly
into the assembly and finishing process. This tie-in will allow for sequence
assembly and finishing to take place in a statistically valid and fully
automated fashion.
<PAGE>

Automated Sequencing System for the Human Genome Project
RFA: HG-95-004

<TABLE>
<CAPTION>
Collaborators Principal Investigators
------------- -----------------------
<S> <C>

Cornell University Dr. Harold G. Craighead

Soane BioSciences, Inc. Dr. Herbert H. Hooper

The Whitehead Institute for Biomedical Research Dr. Trevor L. Hawkins, Ph.D.
</TABLE>

(See attached confirming letters)

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Principal Investigator/Program Director (Last, first, middle):
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8. Consortium/Contractual Arrangements

Automated Sequencing System for the Human Genome Project

RFA: HG-95-004

CuraGen Corporation, Cornell University, Soane BioSciences, Inc. & The Whitehead
Institute for Biomedical Research hereby state that there are currently in place
the necessary programmatic, fiscal and administrative arrangements to ensure
that all necessary legal, financial and administrative matters are dealt with in
the appropriate manner.

In addition, CuraGen Corporation hereby confirms (see attached letters received
from each of the respective consortia) that all of the required programmatic and
administrative personnel of all consorita involved are aware of the NIH
consortium grant policy and are prepared to establish the necessary
interorganization agreements that will ensure compliance with all Federal
regulations and policies.

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Principal Investigator/Program Director (Last, first, middle):
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----------------
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Appendix

PI: Gregory T. Went

Project Title: Automated Sequencing System for the Human Genome Project

Appendix 1 - Color Figures

Appendix 2- Detailed Cost Analysis

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d. Department and Suspension [X] No [_] Yes (Attach explanation)

e. Drug-Free Workplace (Applicable only to new or revised applications being
submitted to the PHS for the first proposed project. Type 1)

[X] Yes [_] No (Attach explanation)

f. Lobbying

With Federal appropriated funds [X] No

With other than Federal appropriated funds [X] No [_] Yes
(If "Yes." see page 29 and
attach Standard Form LLL
"Disclosure of Lobbying
Activities" to the application
behind the second page of the
Checklist)

g. Delinquent Federal Debt [X] No [_] Yes (Attach explanation)

h. Misconduct in Science (Form PHS 6315) [X] Fired [_] Not Fired
If filed, date of initial Assurance or Latest Annual Report 2/21/95
-----------------
<TABLE>

<S> <C> <C> <C>
i. Civil Rights j. Handicapped Individuals K. Sex Discrimination l. Age Discrimination
Form HHS 441 Form HHS 641 Form HHS 639-A Form HHS 680

[X] Filed [X] Filed [X] Filed [X] Filed

[_] Not Filed [_] Not Filed [_] Not Filed [_] Not Filed

</TABLE>

- --------------------------------------------------------------------------------
<PAGE>

- --------------------------------------------------------------------------------
CHECKLIST (Continued)
- --------------------------------------------------------------------------------
2. PROGRAM INCOME (See instructions, page ??)

All applicants must indicate (Yes or No) whether program income is anticipated
during the ???????) for which grant support is requested.
[X] No [ ] Yes If "Yes." use the format below to reflect the amount and
source(s) of anticipatedprogram income.
<TABLE>
<CAPTION>
- --------------------------------------------------------------------------------
?????? ????? Anticipated Amount Source(s)
- --------------------------------------------------------------------------------
<S> <C> <C>

- --------------------------------------------------------------------------------
</TABLE>
3. INDIRECT COSTS

Indicate the applicant organization's most recent indirect cost rate established
with the appropriate DHHS Regional Office, or, in the case of for profit
organizations, the rate established with the appropriate PHS Agency Cost
Advisory Office. If the applicant organization is in the process of initially
developing or renegotiating a rate, or has established a rate with another
Federal agency, it should immediately upon notification that an award will be
made develop a tentative indirect cost rate proposal. This is to be based on its
most recently completed fiscal year in accordance with the principles set forth
in the pertinent DHHS Guide for Establishing Indirect Cost Rates and submitted
to the appropriate DHHS Regional Office or PHS Agency Cost Advisory Office.
Indirect costs will not be paid on foreign grants, construction grants, grants
to Federal organizations, and grants to individuals and usually not on
conference grants. Follow any additional instructions provided for Research
Career Development Awards. Institutional National Research Service Awards, and
the specialized grant applications listed on page 6.

[_] DHHS Agreement dated:______________ [_] No Indirect Cases Requested.

[_] DHHS Agreement being negotiated with _______________ Regional Office.

[X] No DHHS Agreement cut rate being negotiated with * Date April 24, 1995
CALCULATION*
(The entire grant application, including the Checklist will be ???????? and
provided to peer reviewers as CONFIDENTIAL ???????????. ???????? ??? following
information on interest costs if OPTIONAL for ??????? organizations.)

a. Initial budget period:
Amount of base [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

b. Entire proposed project:
Amount of base [XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX]

(1) Add to total direct costs from form page 4 and enter new total on FACE
Page. Item 7?.
(2) Add to total direct costs from form page 5 and enter new total on FACE
Page. Item 8?.

*Check appropriate box(es):

[_] Salary and wages case [X] Modified total direct costs base

[_] Other base (Explain below)

[_] Off-site, other special rate, or more than one rate involved (Explain below)

Explanation (Attach separate sheet, if necessary.):

* National Institute of Standards and Technologies
Atlanta, GA

[Confidential Treatment Requested]
<PAGE>

KK Principal Investigator/Program Director (Last, first, middle)
Went, Gregory T.
----------------
- --------------------------------------------------------------------------------
Attach this form to the signed original of the
application after the CHECKLIST. Do not duplicate.

PERSONAL DATA ON
PRINCIPAL INVESTIGATOR/PROGRAM DIRECTOR
- --------------------------------------------------------------------------------

The Public Health Service has a continuing commitment to monitoring the
operation of its review and aware processes to detect--and deal
appropriately with--any instances of real or apparent inequities with
respect to age, sex, race or ethnicity of the proposed principal
investigator/program director.

To provide the PHS with the information it needs for this important task,
complete the form below and attach it to the signed original of the
application after the Checklist. Do not attach copies of this form to the
duplicated copies of the application.

Upon receipt and assignment of the application by the PHS, this form will
be separated from the application. This form will not be duplicated, and it
will not be a part of the review process. Data will be confidential and
will be maintained in Privacy Act record system 09-25-0036. "Grants:IMPAC
(Grant/Contract information)." All analysis conducted on the data will
report aggregate statistical findings only and will not identify
individuals.

If you decline to provide this information, it will no way affect
consideration of your application.

Your cooperation will be appreciated.

================================================================================
DATE OF BIRTH (month/day/year) SEX

July 1, 1963 [_] Female [X] Male

- --------------------------------------------------------------------------------
PLACE AND/OR ETHNIC ORIGIN (check one)

Note: The category that most closely reflects the individual's recognition in
the community should be used for purposes of recording mixed racial and/or
ethnic origins.

[_] American Indian or Alaskan Native. A person having origins in any of the
original peoples of North America and who maintains a cultural
identification through tribal affiliation or community recognition.

[_] Asian or Pacific Islander. A person having origins in any of the original
peoples of the Far East. Southeast Asia, the indian subcontinent, or the
Pacific islands. This area includes, for example, China, India, Japan,
Korea, the Philippine Islands, and Samoa.

[_] Black, not of Hispanic origin. A person having origins in any of the black
racial groups of Africa.

[_] Hispanic. A person of Mexican, Puerto Rican, Cuban. Central or South
American, or other Spanish culture or origin, regardless of race.

[X] White, not of Hispanic origin. A person having origins in any of the
original peoples of Europe, North Africa, or the Middle East.

[_] Check here if you do not wish to provide some or all of the above
information.

<PAGE>

Exhibit 10.16
-------------
<TABLE>

- ---------------------------------------------------------------------------- ----------------------------------------
<S> <C> <C> <C>
FORM CD-450 U.S. DEPARTMENT OF COMMERCE
(REV. 10-93) [_] GRANT [X]
DAO 203-26 COOPERATIVE
FINANCIAL ASSISTANCE AWARD AGREEMENT
--------------------------------------
ACCOUNTING CODE
**SEE BELOW
- ---------------------------------------------------------------------------- ----------------------------------------
RECIPIENT NAME AWARD NUMBER

CuraGen Corporation 7ONANB5H1036
- ---------------------------------------------------------------------------- ----------------------------------------
STREET ADDRESS FEDERAL SHARE OF COST

322 East Main Street $ 2,266,924.00
- ---------------------------------------------------------------------------- ----------------------------------------
CITY, STATE, ZIP CODE RECIPIENT SHARE OF COST

Branford, CT 06405 $ 2,749,144.000
- ---------------------------------------------------------------------------- ----------------------------------------
AWARD PERIOD TOTAL ESTIMATED COST

February 1, 1995 through January 31, 1998 $ 5,016,068.00
- ---------------------------------------------------------------------------- ----------------------------------------
DEPARTMENT OF COMMERCE OPERATING UNIT
NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY, GRANTS OFFICE
BUILDING 301, ROOM B129, GAITHERSBURG, MARYLAND 20899-0001
- ---------------------------------------------------------------------------------------------------------------------
AUTHORITY
Authorized by Section 5131 of P. L. 100-418, codified at 15 USC 278n as modified by P.L. 102-242,
the Final Rule 15 CFR Part 295, and Program Announcement ATP 94-05.
- ---------------------------------------------------------------------------------------------------------------------
PROJECT TITLE
Integrated Microfabricated DNA Analysis Device for Diagnosis of Complex Genetic Disorders.

- ---------------------------------------------------------------------------------------------------------------------

</TABLE>

This Award approved by the Grants Officer is Issued in triplicate and
constitutes an obligation of Federal funding. By signing the three documents,
the Recipient agrees to comply with the Award provisions checked below and
attached. Upon acceptance by the Recipient, two signed Award documents shall be
returned to the Grants Officer and the third document shall be retained by the
Recipient. If not signed and returned by the Recipient within 15 days of
receipt, the Grants Officer may declare this Award null and void.

[X] Department of Commerce Financial Assistance Standard Terms and Conditions

[X] Special Award Conditions

[X] Line Item Budget

[X] OMB Circular A-21, Cost Principles for Educational Institutions

[_] OMB Circular A-87, Cost Principles for State and Local Governments

[X] OMB Circular A-110, Grants and Agreements with Institutions of Higher
Education, Hospitals, and Other Nonprofit Organizations Uniform
Administrative Requirements

[X] OMB Circular A-122, Cost Principles for Nonprofit Organizations

[_] 15 CFR Part 24, Uniform Administrative Requirements for Grants and
Cooperative Agreements to State and Local Governments

[_] 15 CFR Part 29a, Audit Requirements for State and Local Governments

[_] 15 CFR Part 29b, Audit Requirements for Institutions of Higher Education
and Nonprofit Organizations

[X] 48 CFR Part 31, Contract Cost Principles and Procedures

[X] Other(s): General Terms and Conditions Advanced Technology Program - Joint
Venture

<TABLE>

- ---------------------------------------------------------------------------------------------------------------------
**ACCOUNTING CODE: CC: 5/150-9346 Ob. C1. 4110 Req. No. 5-150-5041 $639,017.00
- ---------------------------------------------------------------------------------------------------------------------
<S> <C> <C>
B-AE93-N-C-F-N-A-09-07240 EIN:06-1331400 150/SAbramowitzz
- ---------------------------------------------------------------------------- ----------------------------- ----------
SIGNATURE OF DEPARTMENT OF COMMERCE GRANTS OFFICER TITLE DATE
/s/ Sharon D. Green Grants Officer 7/5/94
- ---------------------------------------------------------------------------- ----------------------------- ----------
TYPED NAME AND SIGNATURE OF AUTHORIZED RECIPIENT OFFICIAL TITLE DATE
/s/ Gregory T. Went Vice President 7/5/94

- ---------------------------------------------------------------------------- ----------------------------- ----------

</TABLE>
<PAGE>

SPECIAL AWARD CONDITIONS
ADVANCED TECHNOLOGY PROGRAM - JOINT VENTURE
COOPERATIVE AGREEMENT NO. 70NANB5H1066

1. RECIPIENT CONTACT

The Recipient Contact's name, title, address, and telephone number are:

(Technical) Gregory T. Went (203) 481-1104
(Administrative) Gregory T. Went (203) 481-1104
CuraGen Corporation
322 East Main Street
Branford, CT 06405

2. JOINT VENTURE MEMBERS

The organizations named below have been approved as joint venture members to
conduct research described herein. Any changes or new members must be approved
in writing by the Grants Officer:

CuraGen Corporation, Branford, CT
American Cynamid, Pearl River, NY

3. GRANTS OFFICER

The Grants Officer's name, address, and telephone number are:

Sharon D. Green
National Institute of Standards and Technology
Bldg. 301, Room B129
Gaithersburg, MD 20899-0001
(301) 975-6328

4. GRANTS SPECIALIST

The Grants Specialist's name, address, and telephone number are:

Shamin Shaikh
National Institute of Standards and Technology
Bldg. 301, Room B129
Gaithersburg, MD 20899-0001
(301) 975-6428

5. PROJECT MANAGEMENT

a. The Technical Project Manager's name, address, and telephone number are:

Stanley Abramowitz
National Institute of Standards and Technology
Bldg. 101, Room A417
Gaithersburg, MD 20899-0001
(301) 975-2587

b. The Business Project Manager's name, address, and telephone number are

Florina Hoofer
National Institute of Standards and Technology
Bldg.. 101, Room A321
Gaithersburg, MD 20899-001
(301) 975-6049

6. PROJECT DESCRIPTION

The Recipient shall conduct research and provide technical and business reports
under the Tools for DNA Diagnostic program. This project purposes to develop a
device to extend the use of DNA analysis from the characterization of simple
inborn genetic disorders to the efficient diagnosis and treatment of complex
illnesses like cardiovascular disease and cancer.

All research shall be conducted in accordance with the Recipient's proposal
dated July 5, 1994 and revised budget dated 1/10/95 (Attachment A).

7. COST SHARE

The cost sharing ratio applicable to the first year period of this award is
45.27% the Recipient's contribution and 45.73% NIST's contribution. Recipients
must meet or exceed the cost share ratio on a quarterly financial reporting
basis.

8. TRAVEL

Reimbursement for travel costs shall not exceed the established company rates.
However, regardless of company policy, less than first class accommodations must
be used when available and, for foreign travel, U.S. flag carriers must be used
for departure from and entry into the U.S. and for any other portion of the trip
for which U.S. carriers are available.

Any travel charged against the amount authorized must be directly related to the
work described herein.

9. FUNDING LIMITATIONS

The scope of work and budget incorporated into this award covers a three year
----------
period for a total amount of $2,266,924.00 in Federal funds. However, Federal
-------------
funding available at this time is limited to $579,469.00 for the first year
-----------
period. Receipt of any additional funding up to the level projected under this
award is contingent upon the availability of funds from Congress, satisfactory
performance, and will be at the sole discretion of the Agency. The Recipient may
not obligate, incur any expenditures, nor engage in any commitments which
involve any amount in excess of the Federal amount presently available. No legal
liability will exist or result on the part of the Federal Government for payment
of any portion of the remaining funds which have not been made available under
the award. The notice of availability or non-availability of additional funding
for the second and third year(s) will be made in writing only by the Grants
---------------- ------------------
Officer. This written notification shall be made prior to or no later than 30
- -------
days after the expiration of each year's activities.

10. COMMERCIALIZATION STRATEGY

The Recipient will be required to submit the following business planning
deliverables at each annual review: a detailed business and technology
commercialization plan complete with major milestones and critical decision
points. Most important, a Gantt chart should be prepared for the first annual
review; an analysis of the Recipient's primary and secondary target markets for
the major application area of the technology (including a rationale for choosing
those markets, a brief description of their key characteristics, and an overview
of the firm's likely competitors in those markets). Finally, a summary of how
the firm will leverage it's technical success in the ATP project into a
sustainable competitive advantage in the marketplace vis-a-vis its competitors
will be presented to the ATP program managers at each annual review.

11. COST ESCALATION LIMIT

The ATP practice limits the annual escalation to 3.5% applicable to the future
years.

12. VERTEBRATE ANIMALS

If this project involves the use of vertebrate animals, the Recipient is
required to comply, as applicable, with the Animal Welfare Act as amended, and
implementing regulations (7 USC 2131 et seq., 9 CFR parts 1, 2 and 3), and other
Federal Statutes and regulations relating to animals.

If vertebrate animals are involved, the Principal Investigator shall submit to
the ATP Program Manager:
<PAGE>

(1) A completed Extramural Animal Study Proposal Form (NIST-1258), with signed
approvals by the Institutional Animal Care and Use Committee (IACUC).

(2) Copies of other governmental approvals for Recipient's animal care and use
procedures and showing the current status of Recipient's assurance by the Public
Health Service/National Institutes of Health (PHS/NIH), and copies of animal
care facility accreditation.

(3) Certification that the Principal Investigator and other personnel involved
in the care and use of the animals are trained as required by NIST and the
PHS/NIH Guide for the Care and Use of Laboratory Animals.
- --------------------------------------------------------

The Recipient must inform ATP Program Manager in writing of any proposed
deviation from procedures involving animals described in Form NIST-1258, any
change in personnel and their training, and change in the status of their
PHS/NIH assurance or other government inspecting bodies; and the results of any
inspections of their animal care facilities that take place during the course of
the award.

13. HUMAN SUBJECTS

If this project involves human subjects, the Department of Commerce regulations
(15 CFR Part 27) require that applicant organizations establish and maintain
appropriate policies and procedures for the protection of human subjects. These
regulations are available from the NIST Grants Office.

14. AUDITS

General Terms and Conditions, Advanced Technology Program - Joint Venture
Applicant, No. 27, "Audits", is revised to read as follows:

27. AUDITS

The Recipient shall provide sufficient funds in the project budget to
have a project audit performed, including audits of all Joint Venture
members. For 2 and 3 year awards, an audit is required within ninety
(90) days after the first year and at the end of the project.

The cost of the project audit may be charged as a direct cost provided that
costs of audits are not included in the Recipient's indirect cost rate.

15. AWARD PAYMENTS

Condition No. 8.b. under General Terms and Conditions entitled "Payments" has
been revised to allow the Recipient to be reimbursed on a monthly basis as
requested by the Recipient. All other conditions remain the same and in effect.

8. Payments:
- -------------

b. Standard Form SF-269 "Financial Status Report" and Standard Form
SF-270, "request for Advance or Reimbursement", shall be submitted in
triplicate (an original and two copies) to the Grants Officer:

- The SF-269, "Financial Status Report", shall be submitted within
thirty (30) days for calendar quarters ending March 31, June 20, and
December 31, and within fifteen (15) days for the calendar quarter
ending September 30:

- The SF-270, "Request for Advance or Reimbursement", may be submitted
for reimbursement on a monthly basis.

<PAGE>

Exhibit 10.17
-------------

- ------------------------------------------------ -------------------------------
FORM CD-450 U.S. DEPARTMENT OF COMMERCE
(REV. 10-93) [_] GRANT [X] COOPERATIVE
DAO 203-26 AGREEMENT
------------------------------
ACCOUNTING CODE
FINANCIAL ASSISTANCE AWARD **SEE BELOW
- ------------------------------------------------ -------------------------------
RECIPIENT NAME AWARD NUMBER
CuraGen Corporation 70NANB5H1066

- ------------------------------------------------ -------------------------------
STREET ADDRESS FEDERAL SHARE OF COST
322 East Main Street 2,378,814.00

- ------------------------------------------------ -------------------------------
CITY, STATE, ZIP CODE RECIPIENT SHARE OF COST
Branford, CT 06405 2,905,122.00

- ------------------------------------------------ -------------------------------
AWARD PERIOD TOTAL ESTIMATED COST
March 1, 1995 through February 28, 1998 5,283,937.00

- ------------------------------------------------ -------------------------------
DEPARTMENT OF COMMERCE OPERATING UNIT
National Institute of Standards and Technology, Grants Office
Building 301, Room B129, Gaithersburg, Maryland 20899-0001

- --------------------------------------------------------------------------------
AUTHORITY
Authorized by Section 5131 of P.L. 100-418, codified at 15 USC 278n as modified
by P.L. 102-245, the Final Rule 15 CFR Part 295 and Program Announcement ATP
94-01

- --------------------------------------------------------------------------------
PROJECT TITLE
Molecular Recognition Technology for Precise Design of Protein-Specific Drugs

- --------------------------------------------------------------------------------
This Award approved by the Grants Officer is Issued in triplicate and
constitutes an obligation of Federal funding. By signing the three documents,
the Recipient agrees to comply with the Award provisions checked below and
attached. Upon acceptance by the Recipient, two signed Award documents shall be
returned to the Grants Officer and the third document shall be retained by the
Recipient. If not signed and returned by the Recipient within 15 days of
receipt, the Grants Officer may declare this Award null and void.

[X] Department of Commerce Financial Assistance Standard Terms and Conditions

[X] Special Award Conditions

[_] Line Item Budget

[_] OMB Circular A-21, Cost Principles for Educational Institutions

[X] OMB Circular A-87, Cost Principles for State and Local Governments

[X] OMB Circular A-110, Grants and Agreements with Institutions of Higher
Education, Hospitals, and Other Nonprofit Organizations Uniform
Administrative Requirements

[_] OMB Circular A-122, Cost Principles for Nonprofit Organizations

[X] 15 CFR Part 24, Uniform Administrative Requirements for Grants and
Cooperative Agreements to State and Local Governments

[X] 15 CFR Part 29a, Audit Requirements for State and Local Governments

[X] 15 CFR Part 29b, Audit Requirements for Institutions of Higher Education
and Nonprofit Organizations

[X] 48 CFR Part 31, Contact Cost Principles and Procedures

[X] Other(s):

- --------------------------------------------------------------------------------
**ACCOUNTING CODE: CC: 5/150-9346 Ob. C1. 4110 Req. No. 5-150-5041
$579,469.00
- ------------------------------------------------ -------------------------------
SIGNATURE OF DEPARTMENT OF COMMERCE TITLE DATE
GRANTS OFFICER
/s/ Sharon D. Green Grants Officer 2/28/95

- ------------------------------------------------ -------------------------------
TYPED NAME AND SIGNATURE OF AUTHORIZED TITLE DATE
RECIPIENT OFFICIAL
/s/ Gregory T. Went Vice President 3/2/95

- --------------------------------------------------------------------------------
<PAGE>

SPECIAL AWARD CONDITIONS
ADVANCED TECHNOLOGY PROGRAM - JOINT VENTURE
COOPERATIVE AGREEMENT NO. 70NANB5H1066

1. RECIPIENT JOINT VENTURE ADMINISTRATOR CONTACT

The Recipient Joint Venture Administrator Contact's name, title, address, and
telephone number are:

(Technical) Johnathan M. Rothberg (203) 481-1104 ext. 22
(Administrative) Gregory T. Went (203) 481-1104 ext. 31
322 East Main Street
Branford, CT 06405

2. JOINT VENTURE MEMBERS

The organizations named below have been approved as joint venture members to
conduct research described herein. Any changes or new members must be approved
in writing by the Grants Officer:

CuraGen Corporation, Branford, CT
American Cynamid, Pearl River, NY

3. GRANTS OFFICER

The Grants Officer's name, address, and telephone number are:

Sharon D. Green
National Institute of Standards and Technology
Bldg. 301, Room B129
Gaithersburg, MD 20899-0001
(301) 975-6328

4. GRANTS SPECIALIST

The Grants Specialist's name, address, and telephone number are:

George A. Tucker
National Institute of Standards and Technology
Bldg. 301, Room B129
Gaithersburg, MD 20899-0001
(301) 975-6072

5. PROJECT MANAGEMENT

a. The Technical Project Manager's name, address, and telephone number are:

David King
National Institute of Standards and Technology
Bldg. 101, Room A430
Gaithersburg, MD 20899-0001
(301) 975-2369

b. The Business Project Manager's name, address, and telephone number are

Florina Hoofer
National Institute of Standards and Technology
Bldg.. 101, Room A303
Gaithersburg, MD 20899-001
(301) 975-6049

6. PROJECT DESCRIPTION

The Recipient shall conduct research and provide technical and business reports
on the state-of-the-art molecular biology, structural physics, and computation
methods to understand how small highly constrained mimics of protein modules
bind to a target protein. This technological discovery uncovers rules governing
protein recognition which can be applied to guide the development of drugs to
combat major uncured diseases.

All research shall be conducted in accordance with the Recipient's proposal
dated June 22, 1994 and revised budget dated February 10, 1995.

7. FUNDING LIMITATIONS

The scope of work and budget incorporated into this award covers a three year
period for a total amount of $2,378,814.00 in Federal funds. However, Federal
funding available at this time is limited to $639,017.00 for the first year
period. Receipt of any additional funding up to the level projected under this
award is contingent upon the availability of funds from Congress, satisfactory
performance, and will be at the sole discretion of the Agency. The Recipient may
not obligate, incur any expenditures, nor engage in any commitments which
involve any amount in excess of the Federal amount presently available. No legal
liability will exist or result on the part of the Federal Government for payment
of any portion of the remaining funds which have not been made available under
the award. The notice of availability or non-availability of additional funding
for the second and third years will be made in writing only by the Grants
Officer. This written notification shall be made prior to or no later than 30
days after the expiration of each year's activities.

Anticipated Future Funding:

March 1, 1996 through February 28, 1997; $848,362, Second Year.

March 1, 1997 through February 28, 1998; $891,435, Third year.

8. COST SHARE

The cost sharing ratio applicable to this award is 55% the Recipient's
contribution and 45% NIST's contribution. Recipient's must meet or exceed the
cost share ratio on a quarterly financial reporting basis.

9. TRAVEL

Any travel charged against the amount authorized must be directly related to the
work described herein.

10. COMMERCIALIZATION STRATEGY

11. AUDITS

General Terms and Conditions, Advanced Technology Program-Single Recipient, No.
24, "AUDITS," is revised to read as follows:

The Recipient shall provide sufficient funds in the project budget to have a
project audit performed. For two and three year awards, an audit is required
within ninety (90) days after the first year and at the end of the project.

The cost of the project audit may be charged as a direct cost provided that
costs of audits are not included in the Recipient's indirect cost rate.

<PAGE>

Exhibit 10.18
-------------

<TABLE>

- ------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C>
FROM CD-451 U.S. DEPARTMENT OF COMMERCE [_] GRANT [X] COOPERATIVE
(REV.10-93) AGREEMENT
DAO 203-26 ------------------------------------------
AMENDMENT TO FINANCIAL ASSISTANCE AWARD ACCOUNTING CODE
**SEE BELOW
- ------------------------------------------------------------------------------------------------------------------------------
RECIPIENT NAME AWARD NUMBER
CURAGEN CORPORATION 70NANB7H3004
- ------------------------------------------------------------------------------------------------------------------------------
STREET ADDRESS AMENDMENT NUMBER
LONG WHARF MARITIME CENTER, 555 LONG WHARF DRIVE, 11TH FLOOR 01
- ------------------------------------------------------------------------------------------------------------------------------
CITY, STATE, ZIP CODE EFFECTIVE DATE
NEW HAVEN, CT 06511 April 28, 1997
- ------------------------------------------------------------------------------------------------------------------------------
EXTENDED WORK COMPLETION TO
N/A
- ------------------------------------------------------------------------------------------------------------------------------
DEPARTMENT OF COMMERCE OPERATING UNIT
NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY, GRANTS OFFICE
BUILDING 301, ROOM B129, GAITHERSBURG, MARYLAND 20899-0001
- ------------------------------------------------------------------------------------------------------------------------------
<CAPTION>
<S> <C> <C> <C> <C>
COSTS ARE REVISED AS PREVIOUS ESTIMATED ADD DEDUCT TOTAL ESTIMATED COST
FOLLOWS: COSTS
- ------------------------------------------------------------------------------------------------------------------------------
FEDERAL SHARE OF COST $2,000,000 $-0- $-0- $2,000,000
- ------------------------------------------------------------------------------------------------------------------------------
RECIPIENT SHARE OF COST $-0- $-0- $-0- $-0-
- ------------------------------------------------------------------------------------------------------------------------------
TOTAL ESTIMATED COST $2,000,000 $-0- $-0- $2,000,000
- ------------------------------------------------------------------------------------------------------------------------------
</TABLE>

REASON(S) FOR AMENDMENT

Project Title: Programmable Nonoscale Engines for Molecular Separation

This amendment is issued to change the Special Award Conditions as shown on the
attached page. Reference CuraGen Corporation's letter dated April 10, 1997.

ALL OTHER TERMS AND CONDITIONS REMAIN THE SAME.

- --------------------------------------------------------------------------------
This Amendment approved by the Grants Officer is issued in triplicate and
constitutes an obligation of Federal funding. By signing the three documents,
the Recipient agrees to comply with the Amendment provisions checked below and
attached, as well as previous provisions incorporated into the Award. Upon
acceptance by the Recipient, two signed Amendment documents shall be returned to
the Grants Officer and the third document shall be retained by the Recipient. If
not signed and returned by the Recipient within 15 days of receipt, the Grants
Officer may declare this Amendment null and void.

[X] Special Award Conditions

[_] Line Item Budget

[_] Other(s):
------------------------------------------------------------------

- --------------------------------------------------------------------------------
**ACCOUNTING CODE: 7-470-1347 Obj. Cl. 4110 Reg. No. 7-470-2104 $-0-
- --------------------------------------------------------------------------------
B-AE93-N-C-F-N-A-09 07240 EIN: 06-1331400 470/S Abramowitz
- --------------------------------------------------------------------------------
<TABLE>

- ------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C>
SIGNATURE OF DEPARTMENT OF COMMERCE GRANT OFFICER TITLE DATE

/s/ Shamim Shaikh Grants Officer 4/28/97
- ------------------------------------------------------------------------------------------------------------------------------
TYPED NAME AND SIGNATURE OF AUTHORIZED RECIPIENT OFFICIAL TITLE DATE

/s/ Elizabeth A. Whayland Director of Fund Mgmt. 5/6/97
- ------------------------------------------------------------------------------------------------------------------------------
</TABLE>
<PAGE>

SPECIAL AWARD CONDITIONS
ADVANCED TECHNOLOGY PROGRAM - SINGLE RECIPIENT
COOPERATIVE AGREEMENT NO. 70NANB7H3004, Amendment #01

The following Special Award Conditions placed in the original award document
have been amended and are earmarked as such in "bold" print as follows:

1. RECIPIENT CONTACT

The recipient Contact's name, address, and telephone number are:

(Technical) Joel S. Bader, Ph.d.
Telephone: (203)401-3330, Ext. 236

CuraGen Corporation
Long Wharf Maritime Center
555 Long Wharf Drive, 11th Floor
New Haven, CT 06511

(Administrative) Elizabeth A. Whayland, C.P.A.
Telephone: (203)401-3330, Ext. 224
Fax: (203)401-3333

Curagen Corporation
Long Wharf Maritime Center
555 Long Wharf Drive, 11th Floor
New Haven, CT 06511

2. GRANTS OFFICER

The Grants Officer's name and address are:

Shamim Shaikh
National Institute of Standards and Technology
Bldg. 301, Room B129
Gaithersburg, MD 20899-0001

3. GRANTS SPECIALIST

The Grants Specialist's name, address, and telephone number are:

Shirley Shoemaker
National Institute of Standards and Technology
Bldg. 301, Room B129
Gaithersburg, MD 20899-0001
(301)975-6428
<PAGE>

<TABLE>

- ------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C>
FROM CD-450 U.S. DEPARTMENT OF COMMERCE [_] GRANT [X] COOPERATIVE
(REV.10-93) AGREEMENT
DAO 203-26 ------------------------------------------
FINANCIAL ASSISTANCE AWARD ACCOUNTING CODE
**SEE BELOW
- ------------------------------------------------------------------------------------------------------------------------------
RECIPIENT NAME AWARD NUMBER
CURAGEN CORPORATION 70NANB7H3004
- ------------------------------------------------------------------------------------------------------------------------------
STREET ADDRESS FEDERAL SHARE OF COST
LONG WHARF MARITIME CENTER, 555 LONG WHARF DRIVE, 11TH FLOOR 2,000,000
- ------------------------------------------------------------------------------------------------------------------------------
CITY, STATE, ZIP CODE RECIPIENT SHARE OF COST
NEW HAVEN, CT 06511 -0-
- ------------------------------------------------------------------------------------------------------------------------------
AWARD PERIOD TOTAL ESTIMATED COST
April 1, 1997 - March 31, 1999 2,000,000
- ------------------------------------------------------------------------------------------------------------------------------
DEPARTMENT OF COMMERCE OPERATING UNIT
NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY, GRANTS OFFICE
BUILDING 301, ROOM B129, GAITHERSBURG, MARYLAND 20899-0001

- ------------------------------------------------------------------------------------------------------------------------------
AUTHORITY
Authorized by Section 5131 of P.L. 100-418, codified at 15 USC 278n as modified by P.L. 102-245 the Final Rule 15 CFR Part
295, and Program Announcement 96-01.
- ------------------------------------------------------------------------------------------------------------------------------
PROJECT TITLE
Programmable Nanoscale Engines for Molecular Separation
- ------------------------------------------------------------------------------------------------------------------------------
</TABLE>

This Award approved by the Grants Officer is issued in triplicate and
constitutes an obligation of Federal funding. By signing the three documents,
the Recipient agrees to comply with the Award provisions checked below and
attached. Upon acceptance by the Recipient, two signed Award documents shall be
returned to the Grants Officer and the third document shall be retained by the
Recipient. If not signed and returned by the Recipient within 15 days of
receipt, the Grants Officer may declare this Award null and void.

[X] Department of Commerce Financial Assistance Standard Terms and Conditions
[X] Special Award Conditions
[X] Line Item Budget
[_] OMB Circular A-21, Cost Principles for Educational Institutions
[_] OMB Circular A-87, Cost Principles for State and Local Governments
[X] OMB Circular A-110, Grants and Agreements with Institutions of Higher
Education, Hospitals, and Other Nonprofit Organizations Uniform
Administrative Requirements
[_] OMB Circular A-122, Cost Principles of Nonprofit Organizations
[_] 15 CFR Part 24, Uniform Administrative Requirements for Grants and
Cooperative Agreements to State and Local Governments
[_] 15 CFR Part 29a, Audit Requirements for State and Local Governments
[_] 15 CFR Part 29b, Audit Requirements for Institutions of Higher Education
and Nonprofit Organizations
[X] 48 CFR Part 31, Contract Cost Principles and Procedures
[X] Other(s): General Terms and Conditions-Advanced Technology Program-Single
-----------------------------------------------------------------
Recipient - 3/97 Program Specific Audit Guidelines for Advanced Technology
- --------------------------------------------------------------------------------
Program-Single Recipient - 11/96
- --------------------------------------------------------------------------------
<TABLE>

<S> <C> <C>
- ------------------------------------------------------------------------------------------------------------------------------
**ACCOUNTING CODE: CC: 7-470-1347 Obj. Class 4110 Req. No. 7470-2104 $1,000,000
- ------------------------------------------------------------------------------------------------------------------------------
B-AE93-N-C-F-N-A-09 07240 EIN: 06-1331400 470/S Abramowitz
- ------------------------------------------------------------------------------------------------------------------------------
SIGNATURE OF DEPARTMENT OF COMMERCE GRANT OFFICER TITLE DATE

SPECIAL AWARD CONDITIONS
ADVANCED TECHNOLOGY PROGRAM - SINGLE RECIPIENT
CuraGen, Corporation
COOPERATIVE AGREEMENT NO. 70NANB7H3004

1. RECIPIENT CONTACT

The Recipient Contact's name, address, and telephone number are:

(Technical) Joel S. Bader, Ph.d.
(203)481-1104 Ext. 236
CuraGen, Corporation
Long Wharf Maritime Center
555 Long Wharf Drive, 11th Floor
New Haven, Connecticut 06511

(Administrative) Elizabeth A. Whayland, CPA
(203)481-1104 Ext. 224
CuraGen, Corporation
322 East Main Street
Branford, Connecticut 06405

2. GRANTS OFFICER

The Grants Officer's name and address are:

Shamim A. Shaikh
National Institute of Standards and Technology
Bldg. 301, Room B147
Gaithersburg, MD 20899-0001

3. GRANTS SPECIALIST

Shirley Shoemaker
National Institute of Standards and Technology
Bldg. 301, Room B147
Gaithersburg, MD 20899-0001
(301)975-6428

4. PROJECT MANAGEMENT

a. The Technical Project Manager's name, address, and telephone number are:

Stanley Abramowitz
National Institute of Standards and Technology
Bldg. 101, Room A627
Gaithersburg, MD 20899-0001
(301)975-2587

b. The Business Project Manager's name, address, and telephone number are:

David King
National Institute of Standards and Technology
Bldg. 101, Room A633
Gaithersburg, MD 20899-0001
(301)975-2369

The structure of the ATP Project Management Team is subject to change.

5. PROJECT DESCRIPTION

All research shall be conducted in accordance with the Recipient's proposal
dated September 17, 1996.

6. FUNDING LIMITATIONS

The scope of work and budget incorporated into this award covers a two-year
--------
period (referred to as the "project period") for a total amount of $2,000,000 in
----------
Federal funds. However, Federal funding available at this time is limited to
$1,000,000 for the first year period (referred to as the "budget period").
- ----------
Receipt of any additional funding up to the level projected under this award is
contingent upon the availability of funds from Congress, satisfactory
performance, and will be at the sole discretion of the Agency. The Recipient may
not obligate, incur any expenditures, nor engage in any commitments which
involve any amount in excess of the Federal amount presently available. No legal
liability will exist or result on the part of the Federal Government for payment
of any portion of the remaining funds which have not been made available under
the award. Should additional funds not be made available, expenses incurred
related to closeout activities must be funded from the amount included on this
award. The notice of availability or non-availability of additional funding for
the Second and Final year(s) will be made in writing only by the Grants Officer.
------ ----- --------------------------
This written notification shall be made prior to or no later than 30 days after
the expiration of each year's activities.

Proposed Future Funding:

Year Funds Budget Period
Yr 2 $1,000,000 04-01-98 - 03-31-99
<PAGE>

7. VERTEBRATE ANIMALS

If this project involves the use of vertebrate animals, the Recipient is
required to comply, as applicable, with the Animal Welfare Act as amended, and
implementing regulations (7 USC 2131 et seq., 9 CFR parts 1, 2, and 3), and
other Federal Statutes and regulations relating to animals.

If vertebrate animals are involved, the Principal Investigator shall submit to
the ATP Program Manager:

(1) A completed Extramural Animal Study Proposal Form (NIST-1258), with singed
approvals by the International Animal Care and Use Committee (IACUC).

The Recipient must inform the ATP Program Manager in writing of any proposed
deviation from procedures involving animals described Form NIST-1258, any change
in personnel and their training, and change in the status of their PHS/NIH
assurance or other government inspecting bodies; and the results of any
inspections of their animal care facilities that take place during the course of
the award.

8. HUMAN SUBJECTS

If this project involves human subjects, the Department of Commerce Regulations,
15 CFR Part 27, require that recipients whose research involves human subjects
maintain appropriate policies and procedures for the protection of human
subjects. These regulations are available from the NIST Grants Office upon
request.

No research involving human subjects is permitted under this award until NIST
has reviewed and approved those activities.

9. CONTINGENCY

Recipient must conduct a separations demonstration in the middle of the second
year. The demonstration should show the experimental ability using the proposed
technology to separate two DNA samples having at least 100 oligoners that differ
by three bases. Continuation of research efforts and funding is contingent upon
the satisfactory demonstration of the above requirement and approval by the
ATP/NIST Program Manager and NIST Grants Officer.
<PAGE>

- ---------------------------------------------------------------------------------------------------------------------------------
ESTIMATED MULTI-YEAR BUDGET-SINGLE COMPA_____
- ---------------------------------------------------------------------------------------------------------------------------------
YEAR ONE YEAR TWO YEAR THREE YEAR FOUR
- ---------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C>
1. OBJECT CLASS CATEGORY
- ---------------------------------------------------------------------------------------------------------------------------------
A. Technical Personnel Salaries/Wages $544,000 $544,000 $1,088,000
- ---------------------------------------------------------------------------------------------------------------------------------
B. Technical Personnel Fringe Benefits 79,097 79,097 158,194
- ---------------------------------------------------------------------------------------------------------------------------------
C. Administrative Support Salaries/Wages 74,000 74,000 148,000
- ---------------------------------------------------------------------------------------------------------------------------------
D. Administrative Support Fringe Benefits 10,760 10,760 21,520
- ---------------------------------------------------------------------------------------------------------------------------------
E. Travel 18,000 18,000 36,000
- ---------------------------------------------------------------------------------------------------------------------------------
F. Equipment 75,143 75,143 150,266
- ---------------------------------------------------------------------------------------------------------------------------------
G. Materials/Supplies 134,000 134,000 268,000
- ---------------------------------------------------------------------------------------------------------------------------------
H. Subcontracts 60,000 60,000 120,000
- ---------------------------------------------------------------------------------------------------------------------------------
I. Other 5,000 5,000 10,000
- ---------------------------------------------------------------------------------------------------------------------------------
J. Total Direct Costs (Line A thru I) 1,000,000 1,000,000 2,000,000
- ---------------------------------------------------------------------------------------------------------------------------------
K. Total Direct Costs Requested From ATP 1,000,000 1,000,000 2,000,000
- ---------------------------------------------------------------------------------------------------------------------------------
L. Total Direct Costs Shared by Proposer 0 0 0
- ---------------------------------------------------------------------------------------------------------------------------------
M. Total Indirect Costs Absorbed by Proposer 715,410 715,410 1,430,820
- ---------------------------------------------------------------------------------------------------------------------------------
N. Total Costs (Lines K, L, and M) 1,1715,410 1,715,410 3,430,820
- ---------------------------------------------------------------------------------------------------------------------------------

- ---------------------------------------------------------------------------------------------------------------------------------
2. SOURCES OF FUNDS
- ---------------------------------------------------------------------------------------------------------------------------------
A. ATP (Same as Line K) $1,000,000 $1,000,000 $2,000,000
- ---------------------------------------------------------------------------------------------------------------------------------
B. Company Funds 715,410 715,410 1,430,820
- ---------------------------------------------------------------------------------------------------------------------------------
C.
- ---------------------------------------------------------------------------------------------------------------------------------
D.
- ---------------------------------------------------------------------------------------------------------------------------------
E.
- ---------------------------------------------------------------------------------------------------------------------------------
F.
- ---------------------------------------------------------------------------------------------------------------------------------
G. Total Sources of Funds (Same as Line N) $1,715,410 $1,715,410 $3,430,820
- ---------------------------------------------------------------------------------------------------------------------------------

- ---------------------------------------------------------------------------------------------------------------------------------
3. TASKS
- ---------------------------------------------------------------------------------------------------------------------------------
A. Separation Device $961,913 $965,913 $1,923,626
- ---------------------------------------------------------------------------------------------------------------------------------
B. Real-Time ImageEnhancement 320,637 320,637 641,274
- ---------------------------------------------------------------------------------------------------------------------------------
C. Biological Separations 432,860 432,860 865,720
- ---------------------------------------------------------------------------------------------------------------------------------
D.
- ---------------------------------------------------------------------------------------------------------------------------------
E.
- ---------------------------------------------------------------------------------------------------------------------------------
F.
- ---------------------------------------------------------------------------------------------------------------------------------
G. Total Costs of All Tasks (Same as Line N) $1,715,410 $1,715,410 $3,430,820
- ---------------------------------------------------------------------------------------------------------------------------------
</TABLE>

<PAGE>

EXHIBIT 11.1

SCHEDULE OF COMPUTATION OF NET INCOME (LOSS) PER SHARE

<TABLE>
<CAPTION>
YEAR ENDED DECEMBER 31, NINE MONTHS ENDED SEPTEMBER 30,
---------------------------------- --------------------------------
1994 1995 1996 1996 1997
---------- ---------- ---------- --------------- ----------------
<S> <C> <C> <C> <C> <C>
Net Income (Loss)
Attributable to
Common Stockholders... $ (956,029) $ (940,744) $ (413,265) $ 123,191 $ (4,164,163)
========== ========== ========== =============== ================
Weighted Average Number
of Shares Outstanding
During the Period..... 4,681,256 4,915,086 5,097,073 5,088,397 5,334,562
Add:
Common Stock
Equivalent Shares
Represented by Stock
Options Granted
Related to stock
Plans(1)............ 777,125 777,125 777,125 777,125 777,125
Assumed Conversion of
Series A, C, D & E
Preferred Shares to
Common Shares(2)...... -- -- -- -- 2,222,349
---------- ---------- ---------- --------------- ----------------
5,458,381 5,692,211 5,874,198 5,865,522 8,334,036
========== ========== ========== =============== ================
Net Loss Per Share
Attributable to
Common Stockholders... $ (0.18) $ (0.17) $ (0.07) $ 0.02 $ (0.50)
========== ========== ========== =============== ================
</TABLE>
- --------
(1) Pursuant to the rules of the Securities and Exchange Commission, all
options and warrants granted at prices less than the initial public
offering price during the twelve months preceding the offering date have
been included as common stock equivalents in the calculation of weighted
shares outstanding for all periods presented.

(2) In connection with the initial public offering Series A, C, D and E
Preferred Shares will automatically convert to common stock on a one for
one basis. The additive shares reflect such conversion had the conversion
occurred during the nine months ended September 30, 1997.

<PAGE>

EXHIBIT 23.1
INDEPENDENT AUDITORS' CONSENT

The accompanying financial statements retroactively reflect the conversion
of all outstanding shares of Series A, C, D and E Preferred Stock (Convertible
Preferred Stock) to Common Stock on a one for one basis. The below consent is
in the form which will be signed by Deloitte and Touche LLP upon consummation
of a waiver by the Convertible Preferred stockholders eliminating: i) the
closing of a firm commitment underwritten public offering of the Company's
common stock subject to the offering price being at least $12.00 per share and
ii) net proceeds raised of at least $10,000,000 as conditions to conversion,
as described in Note 6 to the financial statements, and no other events shall
have occurred that would effect the accompanying financial statements and
notes thereto.

"We consent to the use in this Amendment No. 1 to the Registration Statement
of CuraGen Corporation on Form S-1 of our report dated September 12, 1997,
appearing in the Prospectus, which is part of this Registration Statement. We
also consent to the reference to us under the headings "Experts" and "Selected
Financial Data" in such Prospectus."

DELOITTE & TOUCHE LLP

Hartford, Connecticut

November 6, 1997

<PAGE>

EXHIBIT 23.3

CONSENT OF PENNIE & EDMONDS LLP

We consent to the reference to our firm under the caption "Experts" in the
Registration Statement on Form S-1 and related Prospectus of CuraGen
Corporation.

/s/ Pennie & Edmonds llp
PENNIE & EDMONDS LLP

New York, New York

November 6, 1997

<PAGE>

<ARTICLE> 5
<LEGEND>
THIS SCHEDULE CONTAINS SUMMARY FINANCIAL INFORMATION EXTRACTED FROM THE CURAGEN
CORPORATION SEPTEMBER 30, 1997 FINANCIAL STATEMENTS AND IS QUALIFIED IN ITS
ENTIRETY BY REFERENCE TO SUCH FINANCIAL STATEMENTS.
</LEGEND>

<S> <C>
<PERIOD-TYPE> 9-MOS
<FISCAL-YEAR-END> SEP-30-1997
<PERIOD-START> JAN-01-1997
<PERIOD-END> SEP-30-1997
<CASH> 20,781,115
<SECURITIES> 0
<RECEIVABLES> 544,478
<ALLOWANCES> 0
<INVENTORY> 0
<CURRENT-ASSETS> 21,643,801
<PP&E> 6,362,717
<DEPRECIATION> (1,402,986)
<TOTAL-ASSETS> 26,944,446
<CURRENT-LIABILITIES> 3,166,614
<BONDS> 0
0
1,442,090
<COMMON> 84,779
<OTHER-SE> 13,533,484
<TOTAL-LIABILITY-AND-EQUITY> 26,944,446
<SALES> 0
<TOTAL-REVENUES> 4,171,750
<CGS> 0
<TOTAL-COSTS> 0
<OTHER-EXPENSES> 6,431,139
<LOSS-PROVISION> 0
<INTEREST-EXPENSE> 307,042
<INCOME-PRETAX> (4,112,845)
<INCOME-TAX> 0
<INCOME-CONTINUING> (4,112,845)
<DISCONTINUED> 0
<EXTRAORDINARY> 0
<CHANGES> 0
<NET-INCOME> (4,112,845)
<EPS-PRIMARY> (.50)
<EPS-DILUTED> (.50)

</TABLE>