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SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported) November 15, 1994
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CENTOCOR, INC.
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(Exact name of registrant as specified in its charter)
Pennsylvania 0-11103 23-2117202
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(State or other juris- (Commission file (IRS Employer
diction of incorporation) number) Identification No.)
200 Great Valley Parkway, Malvern, Pennsylvania 19355
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(Address of principal executive offices) (Zip Code)
Registrant's telephone number, including area code (215) 651-6000
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Not applicable
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(Former name or former address, if changed since last report)
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Item 5. Other Events.
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On November 15, 1994, the Registrant entered into a certain First
Supplemental Agreement and a certain Wellcome Clinical Development Agreement
(collectively, the "Agreements") with The Wellcome Foundation Limited
("Wellcome") pursuant to which the Registrant and Wellcome amended certain
aspects of the alliance agreements entered into by the Registrant and Wellcome
in 1993. Under the Agreements, Wellcome's territorial rights to Panorex, the
Registrant's 17-1A monoclonal antibody-based cancer therapeutic product, have
been extended to include Japan, Taiwan, Korea and China (the "Extended
Territory"). In addition, Wellcome will undertake the clinical and regulatory
development of Panorex in the Extended Territory.
Under the Agreements, Wellcome paid $3.5 million to the Registrant in
exchange for one hundred forty thousand (140,000) newly issued shares of the
Registrant's common stock. Upon entering into the Agreements, Wellcome paid $4.5
million to the Registrant. In addition, Wellcome is obligated to pay additional
amounts to the Registrant in 1995, and may make certain other milestone payments
to the Registrant upon the achievement of regulatory approvals in the Extended
Territory, the total of such amounts aggregating up to $7 million.
Item 7. Financial Statements and Exhibits.
---------------------------------
Exhibits:
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10(a) First Supplemental Agreement dated November 15, 1994 by and
among the Registrant, Centocor B.V., ("CBV"), Wellcome and
Burroughs Wellcome Co. ("BW"). (The Registrant has requested
confidential treatment for portions of this Agreement, which
have been filed separately with the Securities and Exchange
Commission).
10(b) Wellcome Clinical Development Agreement dated November 15,
1994 among the Registrant, CBV, Wellcome and BW. (The
Registrant has requested confidential treatment for portions
of this Agreement, which have been filed separately with the
Securities and Exchange Commission).
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SIGNATURES
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Pursuant to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
CENTOCOR, INC.
Registrant
Dated: December 29, 1994 By:/s/ George D. Hobbs
----------------------------------
George D. Hobbs, Vice President,
Corporate Counsel and Secretary
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Exhibit 10(a)
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN
PORTIONS OF THIS AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED
FROM THIS COPY OF THE AGREEMENT AT THE PLACES INDICATED BY DOUBLE
ASTERISKS (**) AND HAVE BEEN FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION.
THE WELLCOME FOUNDATION LIMITED
and
BURROUGHS WELLCOME CO.
and
CENTOCOR, INC.
and
CENTOCOR B.V.
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FIRST SUPPLEMENTAL AGREEMENT
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THE WELLCOME FOUNDATION LIMITED
Legal Department
Unicorn House
P O Box 129
160 Euston Road
London NW1 2BP
England
Dated: November 15, 1994
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FIRST SUPPLEMENTAL AGREEMENT
THIS FIRST SUPPLEMENTAL AGREEMENT (the "Supplemental
------------
Agreement"), is dated as of the 15th day of November, 1994 by and
- ---------
among THE WELLCOME FOUNDATION LIMITED, a United Kingdom corporation
of Unicorn House, P.O. Box 129, 160 Euston Road, London NW1 2BP,
England ("WFL"), BURROUGHS WELLCOME CO., a North Carolina
---
corporation of 3030 Cornwallis Road, Research Triangle Park, North
Carolina 27709, USA (individually, "BW" and, collectively with WFL,
--
unless the context requires otherwise, "WELLCOME"), CENTOCOR, INC.,
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a Pennsylvania corporation of 200 Great Valley Parkway, Malvern,
Pennsylvania 19355, USA ("CENTOCOR"), and CENTOCOR B.V., a
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Netherlands corporation of Einsteinweg 101, P.O. Box 251, 2300 AG
Leiden, the Netherlands ("CBV").
---
W I T N E S S E T H:
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WHEREAS, the parties hereto are parties to the Anti-
Cancer Alliance Agreement dated as of November 5, 1993 (the
"Alliance Agreement") and the other Alliance Documents (as defined
------------------
in Appendix A to certain of the Alliance Documents, other than the
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Alliance Agreement ("Appendix A"));
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WHEREAS, Section 4 of the Supply Agreement (as defined in
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Appendix A) contemplates that CENTOCOR and CBV will grant WFL and
- ----------
BW, and their Affiliates (as defined in Appendix A), certain rights
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with respect to the 17-1A Product (as defined in Appendix A) in the
----------
Ajinomoto Territory (as defined in Appendix A) upon the occurrence
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of certain events;
WHEREAS, CENTOCOR and CBV have taken all steps necessary
and appropriate to terminate duly and properly the rights of
Ajinomoto (as defined in Appendix A) with respect to the Ajinomoto
----------
Territory;
WHEREAS, the parties desire to amend the Alliance
Documents in order to grant to WFL and its Affiliates, the
exclusive right to develop, use, promote, sell, market and
distribute the 17-1A Product in the Ajinomoto Territory;
WHEREAS, the parties also desire to amend the Alliance
Documents to provide for WFL and its Affiliates, (i) to take
principal responsibility for all future clinical development of the
17-1A Product in connection with sales in the Territory (as defined
prior to effectiveness of this Supplemental Agreement) and (ii) to
jointly undertake with Centocor principal responsibility for all
future regulatory development of the 17-1A Product in connection
with sales in the Territory (as defined prior to effectiveness of
this Supplemental Agreement);
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WHEREAS, the parties also desire to amend the Alliance
Documents to require WFL and its Affiliates, under certain
circumstances to purchase additional shares of CENTOCOR common
stock;
WHEREAS, the parties desire to amend the Supply
Agreement, the Development Agreement, the License Agreement, the
Relicense and the Novation as is necessary in order to effectuate
(i) the grant to WFL and its Affiliates, of the exclusive right to
use, promote, sell, market and distribute the 17-1A Product in the
Ajinomoto Territory and (ii) the vesting in WELLCOME and its
Affiliates with principal responsibility for all future clinical
and regulatory development of the 17-1A Product in connection with
sales in the Ajinomoto Territory;
NOW THEREFORE, in consideration of the premises and the
mutual covenants and agreements herein contained, and for other
good and valuable consideration, the receipt and sufficiency of
which is hereby acknowledged, the parties hereto, intending to be
legally bound hereby, do hereby agree as follows:
1. Effective Date. This Supplemental Agreement shall
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be effective as of the date hereof (the "Effective Date").
--------------
2. Definitions.
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a. Capitalized terms not otherwise defined herein
shall have the meanings set forth in Appendix A, as herein amended.
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b. Appendix A is amended to include the following
----------
definitions:
"Development Data" means all information (including,
----------------
without limitation, case report forms, data bases, analyses and
reports, whether written or in other media or machine readable
form, from investigators, contract research organizations or
otherwise), all preclinical, toxicological, pharmacological,
pharmacokinetics and any other data (other than Manufacturing
Technology) necessary, relevant, appropriate or useful in
performing the Target Program or Post Target Program or preparing
regulatory submissions.
"Extended Territory" means Japan, the Republic of Korea,
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the People's Republic of China and Taiwan.
"External Costs" means any and all out-of-pocket payments
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made to Third Parties by WELLCOME and its Affiliates relating to or
connected with the activities of Third Parties with respect to the
design, implementation or execution of the Target Program pursuant
to the Wellcome Clinical Development Agreement, including without
limitation any amounts disbursed for materials, supplies, travel
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and subsistence, regulatory filing fees, contract research
organizations, grants and independent contractors.
"Fully Burdened Cost" of the Clinical Trial Material or
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the Placebo Material means the (**)
"Japan" means the country of Japan and its territories.
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"Supplemental Agreement" means the First Supplemental
----------------------
Agreement dated as of November 15, 1994 among, WFL, BW, CENTOCOR,
and CBV.
"Wellcome Clinical Development Agreement" means the
---------------------------------------
Wellcome Clinical Development Agreement among WFL, BW, CENTOCOR and
CBV, dated as of November 15, 1994 and attached as Exhibit 1 to the
---------
Supplemental Agreement, as the same may be amended or modified.
c. Appendix A is amended to include the following
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definitions, each of which shall have the meaning set forth in the
Wellcome Clinical Development Agreement: "Centocor Participants",
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"Centocor Qualified Person", "First Indication", "IND", "Maximum
------------------------- ---------------- --- -------
Payment", "Payment Amount", "Placebo Material", "Project Leader",
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and "Project Team".
------------
d. Appendix A is further amended to revise certain
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of the definitions contained therein as set forth in this Section
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2.d:
- ---
(1) "Alliance Documents" is amended to add the
------------------
following language at the end of the definition: "and the
Supplemental Agreement and the Wellcome Clinical Development
Agreement".
(2) "Conducted Clinical Trials" for purposes
-------------------------
of the Development Agreement, shall continue to have the meaning in
effect immediately prior to the Effective Date and, for all other
purposes, is amended to mean, in its entirety, those Clinical
Trials conducted by or on behalf of CENTOCOR and described in
Schedule 16.2.4 to the Wellcome Clinical Development Agreement.
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(3) "Manufacturing Technology" is amended by
------------------------
deleting the words "Manufacturing Technology Option" and inserting,
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in their place, the words "Supplemental Agreement" and by deleting
all of the words after the word "thereto".
(4) "Oversight Committee" is amended to be
-------------------
referred to as the "Marketing Oversight Committee" and means the
-----------------------------
oversight committee formed pursuant to Section 31.2 of the Supply
------------
Agreement and relating to the supply, distribution and marketing of
the Salable 17-1A Product.
(5) "Permitted Distributor" is amended in its
---------------------
entirety to mean "CENTOCOR or such other party that is distributing
the 17-1A Product in a country in the Territory pursuant to the
authority granted in Section 3.3 of the Supply Agreement."
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(6) "Post Target Program" for purposes of the
-------------------
Development Agreement, shall continue to have the meaning in effect
immediately prior to the Effective Date and, for all other
purposes, is amended to mean, in its entirety, as more fully set
forth in Section 9 of the Wellcome Clinical Development Agreement,
---------
a clinical and regulatory development program for a country with
respect to the 17-1A Product, subsequent to obtaining Regulatory
Approval of the Targeted Indications in such country.
(7) "Product Committee" is amended in its
-----------------
entirety to mean the product committee formed pursuant to Section
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31.1 of the Supply Agreement and relating to the supply,
- ----
distribution and marketing of the Salable 17-1A Product.
(8) "Target Program" for purposes of the
--------------
Development Agreement, shall continue to have the meaning in effect
immediately prior to the Effective Date and, for all other
purposes, is amended to mean, in its entirety, as more fully set
forth in Section 5 of the Wellcome Clinical Development Agreement,
---------
a clinical and regulatory development program for the 17-1A
Product, which program shall conclude with respect to a country
upon obtaining Regulatory Approval of the Targeted Indications in
such country, except as provided in the Supply Agreement.
(9) "Targeted Indications" for purposes of the
--------------------
Development Agreement, shall continue to have the meaning in effect
immediately prior to the Effective Date and, for all other
purposes, is amended to delete the words "the Product Committee"
from the last two lines of such definition and insert, in their
place, the word "WELLCOME".
(10) "Territory" is amended, with respect to
---------
each Alliance Document other than the Novation, by deleting all of
the language appearing therein after the word "world."
(11) Each of the definitions of "Alliance
--------
Agreement", "Supply Agreement", "Development Agreement", "Cancer
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Products Agreement", "Novation", "License", "Relicense", "Escrow
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Agreement", "Wellcome House Mark Agreement", "Trademark Agreement",
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"Stock Purchase Agreement", "Registration Rights Agreement" and
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"Hybridoma Letter" is hereby amended to add to the end of each such
----------------
definition the words "as the same may be amended or modified".
3. Stock Purchase Agreement. The Stock Purchase
------------------------
Agreement is hereby amended to include a new Article 2A to read as
follows:
ARTICLE 2A
Purchase and Sale of Additional Shares
--------------------------------------
2A.1 Purchase and Sale of Additional Shares. At
--------------------------------------
the closing referred to in Section 2A.2 hereof (the
------------
"Second Closing"), CENTOCOR shall issue, sell and deliver
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to WELLCOME 140,000 shares of Common Stock, which number
of shares of Common Stock shall be adjusted appropriately
to reflect any securities which may be issued from time
to time, as a result of stock splits, stock dividends,
recapitalizations, reorganizations or similar events, the
record date for which occurs between September 30, 1994
and the Second Closing Date (as defined below), inclusive
(the "Additional Shares"), and WELLCOME shall subscribe
-----------------
for and purchase the Additional Shares from CENTOCOR, all
upon the terms and subject to the conditions set forth
herein. At the Second Closing, CENTOCOR will deliver to
WELLCOME duly authorized and executed certificates
evidencing the Additional Shares, all of which will have
been registered in the name of WELLCOME (the "Additional
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Share Certificates"), and WELLCOME will deliver to
------------------
CENTOCOR the sum of Three Million Five Hundred Thousand
United States Dollars (US $3,500,000) (the "Additional
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Purchase Price") by certified or official bank check
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payable to the order of CENTOCOR or by wire transfer to
CENTOCOR'S bank account at (**) , or such
other account of CENTOCOR as to which WELLCOME shall have
been so notified at least 48 hours in advance of the
Second Closing Date.
2A.2 The Second Closing. The Second Closing shall
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take place at the offices of Pepper, Hamilton & Scheetz,
3000 Two Logan Square, Eighteenth and Arch Streets,
Philadelphia, Pennsylvania 19103-2799, or such other
place as the parties shall mutually agree, on a date to
be selected by WELLCOME (who shall so notify CENTOCOR in
writing of the selected date at least two Business Days
in advance of such date), but in no event after November
15, 1994 (the "Second Closing Date"). The Second Closing
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shall be effective as of the close of business on the
Second Closing Date. At the Second Closing, CENTOCOR
shall deliver, or cause to be delivered, to WELLCOME the
Additional Share Certificates referred to in Section 2A.1
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hereof against receipt from WELLCOME of the Additional
Purchase Price to be delivered in accordance with Section 2A.1
------------
hereof.
2A.3 Condition Precedent. WELLCOME'S obligation to
-------------------
purchase the Additional Shares shall be conditioned on
the Alliance Documents remaining in full force and effect
on the Second Closing Date, there having been no Default
by CENTOCOR or CBV thereunder prior to the Second Closing
Date, and WELLCOME receiving on or before the Second
Closing Date, with respect to the Additional Shares, the
opinion of Duane, Morris & Hecksher (or other outside
counsel reasonably acceptable to WELLCOME) in
substantially the form delivered to WELLCOME on the
Closing Date.
2A.4 Interpretation. For the purposes of Sections
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3 through 7 of this Agreement (inclusive), the term
-----------
"Shares" shall be construed to include the Additional
Shares; the term "Share Certificates" shall be construed
to include the Additional Share Certificates; and the
term "Closing" shall be construed to include the Second
Closing.
4. Registration Rights Agreement. The term Common
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Stock, as used in the Registration Rights Agreement, shall be
construed to include the Additional Shares as defined in Section 3
---------
hereof.
5. Wellcome Clinical Development Agreement. WFL, BW,
---------------------------------------
CENTOCOR and CBV shall duly execute and deliver the Wellcome
Clinical Development Agreement which automatically shall become
effective as of the Effective Date.
6. Supply Agreement.
----------------
a. The parties agree that this Supplemental
Agreement will be deemed to satisfy the obligations imposed on
CENTOCOR by Section 4 of the Supply Agreement.
---------
b. Section 26.1.1 of the Supply Agreement is
--------------
hereby amended to refer to the Wellcome Clinical Development
Agreement instead of the Development Agreement.
c. Section 26.1.4 of the Supply Agreement is
--------------
hereby amended to refer to the Wellcome Clinical Development
Agreement instead of the Development Agreement.
d. A new Section 31 shall be added to the Supply
----------
Agreement which shall read, in its entirety, as follows:
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31.1. As soon as possible after the date of
the Supplemental Agreement, WELLCOME and CENTOCOR shall
establish a Product Committee consisting of not more than
six (6) representatives of each of WELLCOME and CENTOCOR
having expertise in the supply, distribution and
marketing issues to be presented to the Product Committee
pursuant to this Agreement. Each of WELLCOME and
CENTOCOR shall name and may replace its representatives
on the Product Committee, provided that each of the
replacement representatives shall be of an appropriate
level for the tasks and responsibilities to be fulfilled.
The Product Committee shall meet, at the request of
either WELLCOME or CENTOCOR, at mutually agreeable times
and locations (or by teleconference) in order to
discharge the supply, distribution and marketing
functions to be presented to the Product Committee
pursuant this Agreement, it being understood that the
Product Committee shall have no jurisdiction or any
decision making authority with respect to the clinical
or, except as set forth in Section 32 hereof, regulatory
----------
development of the 17-1A Product. Any decision of the
Product Committee shall be made only by the unanimous
consent of WELLCOME and CENTOCOR. Each of WELLCOME and
CENTOCOR shall bear the expenses of their respective
representatives on the Product Committee.
31.2. As soon as possible after the date of
the Supplemental Agreement, WELLCOME and CENTOCOR shall
establish a Marketing Oversight Committee consisting of
two (2) senior executives of each of WELLCOME and
CENTOCOR. Each of WELLCOME and CENTOCOR shall name and
may replace its representatives on the Marketing
Oversight Committee, provided that each of the
replacement representatives shall be a senior executive
of the appointing party. The Marketing Oversight
Committee shall meet, at the request of either WELLCOME
or CENTOCOR, at mutually agreeable times and locations
(or by teleconference) in order to review the status of
the marketing of the Salable 17-1A Product and to resolve
any questions referred to it by the Product Committee
relating to the supply, distribution or marketing of the
Salable 17-1A Product. Any decision of the Marketing
Oversight Committee shall be made only by the unanimous
consent of its members. A member of the Marketing
Oversight Committee may give a proxy to the other member
of the Marketing Oversight Committee appointed by the
same party which appointed such member giving the proxy.
Each of WELLCOME and CENTOCOR shall bear the expenses of
their respective representatives on the Marketing
Oversight Committee.
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e. A new Section 32 shall be added to the Supply
----------
Agreement which shall read, in its entirety, as follows:
32.1. The Product Committee shall determine
the priority among countries within the Territory with
respect to the seeking of Regulatory Approval for
Targeted Indications.
32.2. In setting the priority among countries
in which Regulatory Approval for Targeted Indications
will be sought, the Product Committee will include
Germany as its highest priority and will also include the
United States and Japan among the higher priority
countries and will seek CPMP approval at the earliest
possible time. The Product Committee will give the
following countries priority with the goal that
Regulatory Approval for Targeted Indications be obtained
therein not later than two (2) years after the later of
Regulatory Approval for Targeted Indications by the FDA
or all approvals for commercial sale for Targeted
Indications by the CPMP: France, Italy, Spain, the
United Kingdom, Canada, Australia, South Africa, Austria,
Belgium, Denmark, Finland, Greece, Ireland, Luxembourg,
the Netherlands, Norway, Portugal, Sweden and
Switzerland. The Product Committee will designate
priorities, if any, for such other countries as it may
determine from time to time.
7. License Agreement and Relicense.
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a. Clause (a) of Section 9.1.2 of the License
-------------
Agreement is hereby amended to read, in its entirety, as follows:
(a) the Wellcome Clinical Development Agreement
pursuant to Sections 8.2.2 or 8.4 thereof, and
---------------------
b. Section 9.1.4 of the License Agreement is
-------------
hereby amended to read, in its entirety, as follows:
CENTOCOR terminates the Wellcome Clinical
Development Agreement other than pursuant to
Section 8.4 thereof.
-----------
c. Clause (a) of Section 2 of the Relicense is
---------
hereby deleted in its entirety and the numbering of clauses (b) and
(c) are hereby amended to read "(a)" and "(b)", respectively.
d. Clause (a) of Section 3.3.2 of the Relicense is
-------------
hereby amended to read, in its entirety, as follows:
(a) the Wellcome Clinical Development Agreement
pursuant to Sections 8.2.2 or 8.4 thereof, and
---------------------
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e. Section 3.3.4 of the Relicense is hereby
-------------
amended to read, in its entirety, as follows:
CENTOCOR terminates the Wellcome Clinical
Development Agreement other than pursuant to
Section 8.4 thereof.
-----------
8. Trademark Agreement.
-------------------
a. Clause (a) of Section 7.1.2 of the Trademark
-------------
Agreement is hereby amended to read, in its entirety, as follows:
(a) the Wellcome Clinical Development Agreement
pursuant to Sections 8.2.2 or 8.4 thereof, and
---------------------
b. Section 7.1.4 of the Trademark Agreement is
-------------
hereby amended to read, in its entirety, as follows:
CENTOCOR terminates the Wellcome Clinical
Development Agreement other than pursuant to
Section 8.4 thereof.
-----------
9. Novation. Section 6.1.1 of the Novation is hereby
-------- -------------
amended to refer to the Wellcome Clinical Development Agreement
instead of the Development Agreement.
10. Payment Terms. WFL, in addition to the amounts
-------------
accruing under the other Alliance Documents and Section 3 hereof,
---------
agrees to pay CENTOCOR for CENTOCOR'S prior research and
development which is of future benefit to WELLCOME a maximum of
(**)
in non-refundable up-front, periodic and milestone payments as
follows:
(**)
9
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(**)
11. Representations and Warranties.
------------------------------
a. By CENTOCOR and CBV. As a material inducement
-------------------
to WFL and BW to enter into this Supplemental Agreement and the
Wellcome Clinical Development Agreement, and to consummate the
transactions contemplated hereby and thereby, CENTOCOR and CBV
hereby, jointly and severally, represent and warrant to WFL and BW
as follows, which representations and warranties shall survive the
execution and delivery of this Supplemental Agreement and the
Wellcome Clinical Development Agreement:
(1) Organization and Good Standing. Each of
------------------------------
CENTOCOR and CBV is a corporation duly organized and validly
existing under the laws of the jurisdiction of its incorporation
with the requisite power and authority (corporate or otherwise) to
carry on its business as presently being conducted and as proposed
to be conducted pursuant to the Alliance Documents (as herein
amended), and to own and operate its properties and assets.
(2) Corporate Power and Authority;
------------------------------
Enforceability. Each of CENTOCOR and CBV has the requisite power
- --------------
and authority (corporate and otherwise) to execute, deliver and
perform this Supplemental Agreement and the Wellcome Clinical
Development Agreement, and to consummate the transactions
contemplated hereby and thereby. The execution, delivery and
performance by each of CENTOCOR and CBV of this Supplemental
Agreement and the Wellcome Clinical Development Agreement, and the
consummation by each of them of the transactions contemplated
hereby and thereby, have been duly authorized by all necessary
action (corporate or otherwise) on its part. Each of the
Supplemental Agreement and the Wellcome Clinical Development
Agreement constitutes a legal, valid and binding obligation of each
of CENTOCOR and CBV, enforceable in accordance with its terms.
(3) Validity of Contemplated Transactions.
-------------------------------------
The execution, delivery and performance by each of CENTOCOR and CBV
of this Supplemental Agreement and the Wellcome Clinical
Development Agreement, and the consummation by each of CENTOCOR and
CBV of the transactions contemplated hereby and thereby, do not (a)
violate or contravene any provision of CENTOCOR'S or CBV'S charter
or bylaws; (b) violate, breach, be in conflict with, constitute a
Default under, cause the acceleration of any payments pursuant to,
or otherwise impair the good standing, validity, or effectiveness
of any agreement, contract, indenture, lease, license, or mortgage
to which CENTOCOR or CBV is a party or by which CENTOCOR or CBV is
bound; (c) violate any provision of any Law, Permit or Court Order
applicable to CENTOCOR or CBV or (d) require any Permit or Required
Consent of any Person (including, without limitation any
10
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Governmental Entity) to be obtained by CENTOCOR or CBV which has
not been obtained.
(4) Litigation; Compliance with Laws. There
--------------------------------
is no Litigation pending or, to CENTOCOR'S or CBV'S knowledge,
threatened against or related to CENTOCOR or CBV, nor any failure
to comply with, violation of or any Default under, any Law, Permit,
or Court Order applicable to CENTOCOR or CBV, in each case which
might have a material adverse effect on the ability of CENTOCOR or
CBV to execute, deliver and perform this Supplemental Agreement or
the Wellcome Clinical Development Agreement, or on the ability of
CENTOCOR or CBV to consummate the transactions contemplated hereby
or thereby.
(5) Alliance Documents. Except as set forth
------------------
on Schedule 2 hereto, all of the representations and warranties of
----------
CENTOCOR and CBV contained in the Alliance Documents are true and
correct as if they were made again on the date hereof. All of the
Alliance Documents (as amended by this Supplemental Agreement),
other than the Manufacturing Technology Option, are in full force
and effect as of the date hereof and there has been no Default by
CENTOCOR or CBV thereunder.
(6) Ajinomoto. CENTOCOR and CBV have duly and
---------
properly taken all actions and have executed all documents which
are necessary legally to terminate in full all of Ajinomoto's
rights to develop, use, market, promote, sell and distribute the
17-1A Product in the Extended Territory, and Ajinomoto does not
have any current or future right to obtain from CENTOCOR or to have
reinstated any rights to develop, use, market, promote, sell or
distribute the 17-1A Product in the Extended Territory whether
resulting from the failure on the part of CENTOCOR to perform its
obligations under that certain October 31, 1994 letter agreement
between CENTOCOR and Ajinomoto, or otherwise.
(7) Additional Shares. The shares of common
-----------------
stock of CENTOCOR issued to WFL and paid for pursuant to Section 3
hereof, (a) when aggregated with the shares of common stock of
CENTOCOR previously issued to WFL by CENTOCOR, represent less than
five percent (5%) of the currently outstanding shares of common
stock of CENTOCOR, (b) will have been validly issued, fully paid
and non-assessable, (c) will be free and clear of any Liens (as
defined in the Stock Purchase Agreement), other than Liens imposed
by the Securities Act (as defined in the Stock Purchase Agreement),
and (d) will have been issued without violation of any preemptive
or other right to purchase securities of CENTOCOR. Neither
CENTOCOR nor any Person acting on behalf of CENTOCOR has offered or
will offer the shares of common stock of CENTOCOR to be issued to
WFL pursuant to Section 3 hereof, or any part thereof, or any
similar securities of issue and sale to, or has solicited or will
solicit any offer to acquire any of the same from, any Person so as
to bring the issuance and sale of the shares of common stock of
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CENTOCOR to be issued to WFL pursuant to Section 3 hereof, within
the provisions of the registration and prospectus delivery
requirements of the Securities Act.
b. Representations and Warranties of WFL and BW.
--------------------------------------------
As a material inducement to CENTOCOR and CBV to enter into this
Supplemental Agreement and the Wellcome Clinical Development
Agreement, and to consummate the transactions contemplated hereby
and thereby, WFL and BW hereby, jointly and severally, represent
and warrant to CENTOCOR and CBV as follows, which representations
and warranties shall survive the execution and delivery of this
Supplemental Agreement and the Wellcome Clinical Development
Agreement:
(1) Organization and Good Standing. Each of
------------------------------
WFL and BW is a corporation duly organized and validly existing
under the Laws of its respective jurisdiction of incorporation with
the requisite power and authority (corporate or otherwise) to carry
on its business as presently being conducted and as proposed to be
conducted pursuant to the Alliance Documents (as herein amended),
and to own and operate its properties and assets.
(2) Corporate Power and Authority;
------------------------------
Enforceability. Each of WFL and BW has the requisite power and
- --------------
authority (corporate and otherwise) to execute, deliver and perform
this Supplemental Agreement and the Wellcome Clinical Development
Agreement, and to consummate the transactions contemplated hereby
and thereby. The execution, delivery and performance by WFL and BW
of this Supplemental Agreement and the Wellcome Clinical
Development Agreement, and the consummation by WFL and BW of the
transactions contemplated hereby and thereby, have been duly
authorized by all necessary action (corporate or otherwise) on the
part of WFL and BW. Each of the Supplemental Agreement and the
Wellcome Clinical Development Agreement constitutes a legal, valid
and binding obligation of WFL and BW, enforceable in accordance
with its terms.
(3) Validity of Contemplated Transactions.
-------------------------------------
The execution, delivery and performance by each of WFL and BW of
this Supplemental Agreement and the Wellcome Clinical Development
Agreement, and the consummation by each of WFL and BW of the
transactions contemplated hereby and thereby, do not (a) violate or
contravene any provision of WFL'S or BW'S charter or bylaws; (b)
violate, breach, be in conflict with, constitute a Default under,
cause the acceleration of any payments pursuant to, or otherwise
impair the good standing, validity, or effectiveness of any
agreement, contract, indenture, lease, license, or mortgage to
which WFL or BW is a party or by which WFL or BW is bound; (c)
violate any provision of any Law, Permit or Court Order applicable
to WFL or BW; or (d) require any Permit or Required Consent of any
Person (including, without limitation, any Governmental Entity) to
be obtained by WFL and BW which has not been obtained.
12
<PAGE>
(4) Litigation; Compliance with Laws. There
--------------------------------
is no Litigation pending or, to WFL's or BW's knowledge, threatened
against or related to WFL or BW, nor any failure to comply with,
violation of or any Default under, any Law, Permit or Court Order
applicable to WFL or BW, in each case which might have a material
adverse effect on the ability of WFL or BW to execute, deliver and
perform this Supplemental Agreement or the Wellcome Clinical
Development Agreement, or on the ability of WFL or BW to consummate
the transactions contemplated hereby or thereby.
(5) Alliance Documents. All of the
------------------
representations and warranties of WFL and BW contained in the
Alliance Documents are true and correct as if they were made again
on the date hereof. All of the Alliance Documents (as amended by
this Supplemental Agreement), other than the Manufacturing
Technology Option, are in full force and effect as of the date
hereof and there has been no Default by WFL or BW thereunder.
12. Termination. Upon the occurrence of a Termination
-----------
Event (as defined in the Wellcome Clinical Development Agreement),
WELLCOME shall have the right to terminate this Supplemental
Agreement as to the executory obligations of any party hereto which
remain to be performed as of the time of such termination, it being
understood that any such termination shall not result in the
termination of any of the amendments to the Alliance Documents set
forth herein. Any such termination shall be effective on a date
specified in a written notice to CENTOCOR, which date shall be not
later than ninety (90) days following the date of such written
notice, such notice to contain a statement setting forth the
existence of the applicable Termination Event and the facts giving
rise to such Termination Event.
13. Miscellaneous.
-------------
a. Entire Agreement. This Supplemental Agreement,
----------------
the Wellcome Clinical Development Agreement and the other Alliance
Documents constitute the entire understanding of the parties with
respect to the subject matter contained herein and supersede any
prior understandings and agreements among them respecting such
subject matter; provided, however, the confidentiality agreement
-------- -------
between WFL and CENTOCOR dated September 14, 1993 shall in all
cases remain in full force and effect in accordance with its terms.
b. Amendments. This Supplemental Agreement may be
----------
amended and supplemented only by a written instrument duly executed
by each of the parties.
c. Headings. The headings in this Supplemental
--------
Agreement are for convenience of reference only and shall not
affect its interpretation.
13
<PAGE>
d. Gender; Number. Words of gender may be read as
--------------
masculine, feminine, or neuter, as required by context. Words of
number may be read as singular or plural, as required by context.
e. Appendices; Exhibits; and Schedules. All
-----------------------------------
appendices, exhibits and schedules referred to herein, if any, form
an integral part of this Supplemental Agreement and are
incorporated into this Supplemental Agreement by such reference.
f. Severability. If any provision of this
------------
Supplemental Agreement or the application thereof to any Person or
circumstance is held illegal, invalid, or unenforceable, such
illegality, invalidity, or unenforceability shall not affect any
other provision hereof. This Supplemental Agreement shall, in such
circumstances, be deemed modified to the extent necessary to render
enforceable the provisions hereof to the fullest extent permitted
by Law.
g. Remedies. Each of CENTOCOR and CBV on the one
--------
hand, and WFL and BW on the other, stipulates that the remedies at
law of the other in the event of any Default or threatened Default
in the performance of or compliance with any of the terms of this
Supplemental Agreement are not and will not be adequate and that,
to the fullest extent permitted by Law, such terms may be
specifically enforced by a decree for specific performance of any
agreement contained herein or by an injunction against any
violation of any terms hereof or otherwise.
h. Joint and Several Liability. CENTOCOR and CBV
---------------------------
shall be jointly and severally responsible and liable for all of
their respective obligations to WFL or BW arising under this
Supplemental Agreement. WFL and BW shall be jointly and severally
liable for all of their respective obligations to CENTOCOR or CBV
arising under this Supplemental Agreement.
i. Notices. All notices and other communications
-------
hereunder shall be in writing and shall be given to the Person
either personally or by sending a copy thereof by first class
United States express mail, postage prepaid and return-receipt
requested, or by a nationally-recognized courier service
guaranteeing next-day delivery, charges prepaid, or by telecopier
(with the original sent by either of the foregoing manners), to
such Person's address (or to such Person's telecopier number). All
notices shall be deemed to have been given to the Person entitled
thereto when received.
14
<PAGE>
If to WFL, to:
THE WELLCOME FOUNDATION LIMITED
Unicorn House, P.O. Box 129
160 Euston Road
London NW1 2BP, England
Attention: Company Secretary
Telecopy No.: 011-44-71-388-5462
With a copy to:
BURROUGHS WELLCOME CO.
3030 Cornwallis Road
Research Triangle Park, NC 27709
USA
Attention: Company Secretary
Telecopy No.: (919) 315-0478
If to BW, to:
BURROUGHS WELLCOME CO.
3030 Cornwallis Road
Research Triangle Park, NC 27709
USA
Attention: Company Secretary
Telecopy No.: (919) 315-0478
If to CENTOCOR or CBV, to:
CENTOCOR, INC.
200 Great Valley Parkway
Malvern, Pennsylvania 19355-1307
USA
Attention: Corporate Secretary
Telecopy No.: (215) 651-6100
Notice of any change in any such address shall also be given in the
manner set forth above. Whenever the giving of notice is required,
the giving of such notice may be waived by the Person entitled to
receive such notice.
j. Waiver. No provision of this Supplemental
------
Agreement may be waived except by a written instrument signed by
the party hereto sought to be bound. No failure or delay by any
party hereto in exercising any right or remedy hereunder or under
applicable Law will operate as a waiver thereof, and a waiver of a
particular right or remedy on one occasion will not be deemed a
waiver of any other right or remedy, or a waiver on any subsequent
occasion (it being understood that specific time frames for notice
or actions to be taken shall be binding on the parties).
15
<PAGE>
k. Assignment. No party hereto may assign its
----------
rights or delegate any of its obligations hereunder without the
prior written consent of the other parties, except that, without
such consent, (a) WFL may assign to any Affiliate of WFL all or any
part of its rights and obligations hereunder so long as WFL
unconditionally guarantees the obligations of such assignee; (b)
WFL and BW may assign all of their rights and delegate all of their
duties under this Supplemental Agreement to the transferee of all
or substantially all of the line of business of which this
Supplemental Agreement forms a part or by way of merger or
consolidation with another company; and (c) CENTOCOR and CBV may
assign all of their rights and delegate all of their duties to a
transferee of all or substantially all their assets or by way of
merger or consolidation with another company. Without limiting the
foregoing, all rights and obligations with respect to the subject
matter of this Supplemental Agreement as to the United States shall
inure to the benefit of and be performed by BW, subject to such
further assignments as may be permitted by this Section 13.k. If
------------
any party shall assign its rights and delegate its duties pursuant
to clauses (b) or (c) of this Section 13.k, the Person to whom such
------------------ ------------
rights are assigned and duties are delegated shall assume all of
the obligations of the applicable party under this Supplemental
Agreement. The guarantee by WFL referenced in clause (a) of this
----------
Section 13.k is a guaranty of payment and performance, and not of
- ------------
collection; and in case of a default by an assignee to which rights
have been assigned or obligations delegated pursuant to such clause
------
(a), CENTOCOR and CBV shall have the right to proceed first against
- ---
WFL without the necessity to proceed against or join such assignee.
l. Successors and Assigns. This Supplemental
----------------------
Agreement shall bind, inure to the benefit of, and be enforceable
by the successors and permitted assigns of the parties hereto.
m. Governing Law. This Supplemental Agreement
-------------
shall be construed and enforced in accordance with the Laws of the
Commonwealth of Pennsylvania without regard to principles of
conflicts of law applicable in such jurisdiction.
n. No Benefit to Others. The representations,
--------------------
warranties, covenants and agreements contained in this Supplemental
Agreement are for the sole benefit of the parties hereto and their
successors and permitted assigns, and they shall not be construed
as conferring, and are not intended to confer, any rights on any
other Person.
o. Independent Contractors. It is expressly
-----------------------
understood and agreed that the CENTOCOR Group and the WELLCOME
Group are independent contractors; neither the CENTOCOR Group or
any of its members, nor the WELLCOME Group or any of its members,
shall be deemed the agent of the other group or of any of its
members for any purpose whatsoever, and neither the CENTOCOR Group
or any of its members, nor the WELLCOME Group or any of its
16
<PAGE>
members, shall have authority to enter into any contract or
agreement, assume any obligation or make any warranty or
representation for or on behalf of the other group or any of its
members. Nothing in this Supplemental Agreement shall be deemed to
create or constitute a partnership or the relationship of employer
and employee between the WELLCOME Group or any of its members on
the one hand and the CENTOCOR Group or any of its members on the
other.
p. Counterparts. This Supplemental Agreement and
------------
any amendment or supplement hereto may be executed in any number of
counterparts and any party hereto may execute any such counterpart,
each of which when executed and delivered shall be deemed to be an
original and all of which counterparts taken together shall
constitute but one and the same instrument. The execution of this
Supplemental Agreement and any such amendment or supplement by any
party hereto will not become effective until counterparts hereof
have been executed by all the parties hereto.
q. Further Assurances. At the request of any
------------------
party hereto, the other parties hereto shall execute and deliver
from time to time such further instruments and shall provide
reasonable cooperation in such proceedings or actions as shall be
necessary or reasonably appropriate to effectuate the purposes of
this Supplemental Agreement including, without limitation,
registering or recording the rights granted hereunder; provided,
--------
however, if any party hereto desires to notify this Supplemental
- -------
Agreement under Article 85(3) of the Treaty of Rome establishing
the European Economic Community, such party shall give the other
parties at least ninety (90) days' prior written notice of such
notification and if during such period a party shall reasonably
object to such notification, the objecting party need not cooperate
in such notification and such notification shall not be
implemented. Except as otherwise provided in the Alliance
17
<PAGE>
Documents, the executions, deliveries and cooperation of each party
under this Section 13.q shall be without further consideration and
------------
at such party's expense.
IN WITNESS WHEREOF, the parties hereto have caused
this Supplemental Agreement to be executed as of the day and year
first above written by their duly authorized representatives.
For and on behalf of
THE WELLCOME FOUNDATION LIMITED
By: /s/ Dawn E. Knight
------------------
Name: Dawn E. Knight
--------------
Title: Assistant Company Secretary
---------------------------
BURROUGHS WELLCOME CO.
By: /s/ Richard S. Kent, M.D.
-------------------------
Name: Richard S. Kent, M.D.
---------------------
Title: Vice President, Research,
Development and Medical
-----------------------
CENTOCOR, INC.
By: /s/ David P. Holveck
--------------------
Name: David P. Holveck
----------------
Title: President and Chief Executive
Officer
------------------------------
CENTOCOR B.V.
By: /s/ David P. Holveck
--------------------
Name: David P. Holveck
----------------
Title: Managing Director
-----------------
18
<PAGE>
SCHEDULE 1
(**)
<PAGE>
SCHEDULE 2 TO
FIRST SUPPLEMENTAL AGREEMENT
----------------------------
I. Schedule 1.12 of the Stock Purchase Agreement is to read in
-------------
its entirety, as of September 30, 1994, as follows:
Derivative Securities
---------------------
Shares Issuable Upon Exercise of Warrants Outstanding at
September 30, 1994:
<TABLE>
<CAPTION>
Shares Exercise Exercise Original Year
Issuable Price/Share Period Financing Issued
- -------- ----------- -------- --------- ------
<S> <C> <C> <C> <C>
1,475,548 $19.33 Through 2/28/95 CPIII 1988
880,966 $16.655 Through 2/28/95 CPIII 1987
494,156 $13.33 Through 2/28/96 CPIII 1988
5,437,600 $11.25 Through 12/31/94 Tocor, Inc. 1989
127,041 $64.50 Through 12/31/96 Tocor II, Inc. 1992
127,041 $49.75 1/1/96 Through Tocor II, Inc. 1992
12/31/97
=============
8,542,352
</TABLE>
Shares Issuable Upon Exercise of
Options Outstanding at September 30, 1994 5,250,855
Shares Reserved for Issuance at
September 30, 1994 in Connection With
Stock Option Plans 7,317,366
Shares Issuable Upon Vesting of
Restricted Stock Awards Outstanding
at September 30, 1994 246,619
Shares Reserved For Issuance at
September 30, 1994 in Connection
With Restricted Stock Award Plan 965,321
Shares Reserved For Issuance at
September 30, 1994 in Connection
With the Company's Convertible
Subordinated Notes Due February 1, 2001 3,842,883
Shares Reserved For Issuance at
September 30, 1994 in Connection
With the Company's Convertible
Subordinated Debentures Due 2001 2,049,181
<PAGE>
II. Centocor's representations in Section 6.5 of the Stock
-----------
Purchase Agreement are amended to effect the following:
(a) The number of shares of Centocor Common Stock at
November 1, 1994 was 51,249,782; and
(b) On December 16, 1994 Centocor issued 2,000,000 shares
for Common Stock to The Wellcome Foundation Limited
pursuant to the terms of the Stock Purchase
Agreement.
III. The representations in Sections 21.2.7 and 21.2.8 of the
--------------------------
Supply Agreement are updated to reflect the following:
(a) All policies listed in the July 1993 Schedule expired
on December 1, 1993 and have been replaced by
comparable policies with equivalent coverages, terms
and conditions.
(b) The limits of Centocor's directors and officers
coverage has been increased to (**) . The
limits of Centocor's product liability coverage
remains (**) .
<PAGE>
Exhibit 10(b)
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY DOUBLE ASTERISKS (**) AND HAVE BEEN FILED SEPARATELY
WITH THE SECURITIES AND EXCHANGE COMMISSION.
THE WELLCOME FOUNDATION LIMITED
and
BURROUGHS WELLCOME CO.
and
CENTOCOR, INC.
and
CENTOCOR B.V.
- --------------------------------------------------------------------------------
WELLCOME CLINICAL DEVELOPMENT AGREEMENT
- --------------------------------------------------------------------------------
THE WELLCOME FOUNDATION LIMITED
Legal Department
Unicorn House
P O Box 129
160 Euston Road
London NW1 2BP
England
Dated: November 15, 1994
<PAGE>
TABLE OF CONTENTS
Page
1. DEFINITIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. RELATIONSHIP TO DEVELOPMENT AGREEMENT . . . . . . . . . . . . . . . 2
3. STANDARDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
4. RESERVED. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
5. THE TARGET PROGRAM. . . . . . . . . . . . . . . . . . . . . . . . . 3
6. CLINICAL TRIAL MATERIAL . . . . . . . . . . . . . . . . . . . . . . 8
7. CONSIDERATION . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
8. TERMINATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
9. POST TARGET DEVELOPMENT . . . . . . . . . . . . . . . . . . . . . . 17
10. APPROVALS TO SELL 17-1A PRODUCT . . . . . . . . . . . . . . . . . . 17
11. PUBLIC STATEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . 17
12. ADVERSE REACTIONS . . . . . . . . . . . . . . . . . . . . . . . . . 18
13. CONFIDENTIALITY . . . . . . . . . . . . . . . . . . . . . . . . . . 18
14. OTHER ANTIBODIES. . . . . . . . . . . . . . . . . . . . . . . . . . 19
15. JOINT AND SEVERAL LIABILITY . . . . . . . . . . . . . . . . . . . . 20
16. REPRESENTATIONS AND WARRANTIES. . . . . . . . . . . . . . . . . . . 21
17. INDEMNIFICATION WITH RESPECT TO TARGET PROGRAM AND POST
TARGET PROGRAM. . . . . . . . . . . . . . . . . . . . . . . . . . . 23
18. MISCELLANEOUS . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
<PAGE>
WELLCOME CLINICAL DEVELOPMENT AGREEMENT
---------------------------------------
THIS WELLCOME CLINICAL DEVELOPMENT AGREEMENT (the
"Agreement") is dated as of the 15th day of November, 1994 by and
---------
among THE WELLCOME FOUNDATION LIMITED, a United Kingdom corporation
of Unicorn House, P.O. Box 129, 160 Euston Road, London NW1 2BP,
England ("WFL"), BURROUGHS WELLCOME CO., a North Carolina
---
corporation of 3030 Cornwallis Road, Research Triangle Park, North
Carolina 27709 (individually, "BW" and, collectively with WFL,
--
"WELLCOME"), CENTOCOR, INC., a Pennsylvania corporation of 200
Great Valley Parkway, Malvern, Pennsylvania 19355, USA ("CNTO"),
----
and CENTOCOR B.V., a Netherlands corporation of Einsteinweg 101,
PO Box 251, 2300 AG Leiden, the Netherlands (individually, "CBV"
---
and, collectively with CNTO, "CENTOCOR").
--------
WITNESSETH:
WHEREAS, the parties hereto are parties to the Anti-
Cancer Alliance Agreement dated as of November 5, 1993 (the
"Alliance Agreement") and the other Alliance Documents (as defined
------------------
in Appendix A to certain of the Alliance Documents ("Appendix A"));
---------- ----------
WHEREAS, CENTOCOR, pursuant to the Alliance Documents has
heretofore borne principal responsibility for conducting Clinical
Trials (as defined in Appendix A) with respect to 17-1A Product (as
----------
defined in Appendix A) in the Territory; and
----------
WHEREAS, the parties desire to alter their relationship
in order to provide for WFL and its Affiliates, (i) to take
principal responsibility for all future clinical development of the
17-1A Product in connection with sales in the Territory (including
the Extended Territory) and all future regulatory development of
the 17-1A Product in connection with sales in the Extended
Territory, and (ii) to jointly undertake with CNTO and its
Affiliates principal responsibility for all future regulatory
development of the 17-1A Product in connection with sales in the
Territory other than the Extended Territory;
NOW THEREFORE, in consideration of the premises and the
mutual covenants and agreements herein contained, and for such
other good and valuable consideration, the receipt and sufficiency
of which is hereby acknowledged, the parties hereto, intending to
be legally bound hereby, agree as follows:
1. DEFINITIONS
-----------
The terms defined in Appendix A, when used in this
----------
Agreement, shall have the meanings set forth in Appendix A as
----------
<PAGE>
amended by the Supplemental Agreement, unless the context requires
otherwise.
2. RELATIONSHIP TO DEVELOPMENT AGREEMENT
-------------------------------------
This Agreement shall govern all activities undertaken by the
parties hereto after the date of this Agreement with respect to the
subject matter hereof, and the Development Agreement shall have no
effect with respect to those activities. Further, (a) (i) Section
-------
10 of the Supplemental Agreement shall govern any and all
- --
consideration payable by WELLCOME to CENTOCOR for CENTOCOR'S
collaboration in connection with the Target Program in the Extended
Territory, (ii) Section 7 of this Agreement shall govern any and
---------
all consideration payable by WELLCOME to CENTOCOR for CENTOCOR'S
collaboration in connection with the Target Program in the
remainder of the Territory and, without limiting the effect of
Subsections (a)(i) or (a)(ii) of this Section 2, WELLCOME shall
- ----------------------------- ---------
have no obligation whatsoever to make payments to any party under
Section 8 of the Development Agreement; (b) CENTOCOR'S obligations
- ---------
under the Development Agreement for the future clinical and
regulatory development of the 17-1A Product are superseded in their
entirety by the terms of this Agreement; and (c) Sections 2, 3, 4
----------------
and 5 of the Development Agreement are superseded in their entirety
- -----
by the terms of this Agreement. Except as provided above, however,
the Development Agreement (including, without limitation, Sections
--------
15, 18 and 19 thereof and the terms defined therein) remains in
- -------------
full force and effect with respect to the obligations of the
parties thereto prior to the date of this Agreement.
3. STANDARDS
---------
Each party agrees to carry out as expeditiously as possible
its respective duties and obligations with respect to the supply of
Clinical Trial Material, the Target Program and the Post Target
Program in accordance with good manufacturing and clinical research
practices, as applicable, all applicable Laws (including but not
limited to each party's respective obligations arising out of its
Investigational New Drug Application concerning the 17-1A Product
and equivalent regulatory submissions (in each case an "IND")),
---
WELLCOME'S and CENTOCOR'S internal standards, as the case may be,
and the requirements for Regulatory Approval in each country in the
Territory for which Regulatory Approval is sought. No
representation or warranty is made by any party hereto that any
Regulatory Approval with respect to the 17-1A Product will be
obtained in any country in the Territory.
2
<PAGE>
4. (RESERVED)
--------
5. THE TARGET PROGRAM
------------------
5.1. WELLCOME'S Responsibilities.
---------------------------
5.1.1. With respect to each country in the Territory
for which Regulatory Approval for the 17-1A Product will be sought
after the date of this Agreement, WELLCOME shall have full control
over, and principal responsibility for, the strategy, design,
conduct and execution of the Target Program under WELLCOME'S IND.
Without limiting the foregoing, and notwithstanding anything in the
other Alliance Documents to the contrary, WELLCOME shall be
responsible for choosing and contracting with contract research
organizations and investigators. Except as expressly provided by
this Agreement, WELLCOME'S activities pursuant to this Section 5.1
-----------
shall be at its sole risk and expense.
5.1.2. If any Clinical Trials or other studies
(including, without limitation, toxicologic studies) are required
to maintain a Regulatory Approval in the Territory for a Targeted
Indication or are a condition to a Regulatory Approval in the
Territory for a Targeted Indication, the satisfactory completion of
such Clinical Trials or other studies shall be deemed a part of the
Target Program.
5.1.3. WELLCOME will establish a project team (the
"Project Team") to be led by a project leader (the "Project
------------ -------
Leader") and staffed by employees with experience in, among other
- ------
things, designing and conducting oncology clinical trials, and
preparing applications for regulatory approvals. WELLCOME will
invite CENTOCOR to appoint two (2) CENTOCOR working level personnel
(or such other number of Centocor personnel as the parties may
mutually agree from time to time) who are reasonably acceptable to
WELLCOME (the "Centocor Participants") to act as participants in
---------------------
the WELLCOME Project Team in accordance with Section 5.2.4 hereof
-------------
as well as several of the smaller working parties formed from
Project Team members. The CENTOCOR Participants will have such
responsibilities as the Project Leader may assign from time to
time.
5.1.4. The Project Leader will provide the Marketing
Oversight Committee with semiannual reports which reports shall
detail the progress of the clinical and regulatory development
effort under this Agreement.
5.2. CENTOCOR'S Responsibilities.
---------------------------
5.2.1. CENTOCOR, promptly upon the execution of this
Agreement and to the extent permitted by applicable Law, shall
provide to WELLCOME all Development Data (including, without
limitation, all Development Data relating to or arising from the
Clinical Trials performed in Germany and any country in the
3
<PAGE>
Extended Territory) received or held at the date of this Agreement
by CENTOCOR or any current or past CENTOCOR licensee (including,
without limitation, Ajinomoto), any contract research organization
or any investigator with respect to 17-1A Product. In addition,
CENTOCOR shall promptly provide (and continue to provide) to
WELLCOME all additional Development Data received or held by
CENTOCOR during the term of this Agreement.
5.2.2. In addition to the Development Data specified
by Section 5.2.1 hereof, CENTOCOR shall make all commercially
-------------
reasonable efforts to secure for WELLCOME (**) .
5.2.3. CENTOCOR shall also take such steps
(including without limitation granting WELLCOME access to the drug
master file(s) and CENTOCOR'S IND for the 17-1A Product) and
provide such information as may be necessary or appropriate to
permit WELLCOME to cross reference an IND or similar submission
with the FDA and any other Regulatory Authority or Regulatory
Adjunct; provided, however, nothing in this Section 5.2.3 shall
-------- ------- -------------
require CENTOCOR to divulge to WELLCOME any of CENTOCOR'S
Manufacturing Technology to which WELLCOME is not otherwise
entitled pursuant to the Alliance Documents. WELLCOME acknowledges
that access to such drug master file(s) and CENTOCOR'S IND, for the
purposes of this Section 5.2.3, represents the right and ability to
-------------
incorporate by reference such drug master file(s) and IND in whole
or in part into WELLCOME'S submissions to the FDA or any other
Regulatory Authority or Regulatory Adjunct.
5.2.4. CENTOCOR shall participate in the Project
Team as specified by this Section 5.2.4.
-------------
5.2.4.1. As soon as possible after the execution
of this Agreement, CENTOCOR shall appoint to the Project Team the
Centocor Participants, which Centocor Participants shall have
skills, experience and authority from CENTOCOR appropriate to carry
out the duties assigned to them from time to time by the Project
Leader. In the event a Centocor Participant becomes unavailable to
serve on the Project Team, or if WELLCOME reasonably becomes
dissatisfied with the performance of one or more of the Centocor
Participants, WELLCOME'S sole remedy shall be to require CENTOCOR
promptly to replace such Centocor Participant(s) with other
representative(s) possessing the requisite skills, experience and
authority.
5.2.4.2. CENTOCOR shall use best efforts to
ensure that the Centocor Participants cooperate in the work of the
Project Team, execute and comply with such confidentiality
agreements as WELLCOME shall reasonably request, are available to
attend the meetings conducted from time to time by the Project
Team, and that such Centocor Participants diligently and promptly
4
<PAGE>
carry out the tasks and responsibilities assigned from time to time
to them by the Project Leader. CENTOCOR shall bear all costs and
expenses associated with the participation by the Centocor
Participants in the Project Team.
5.2.5. Subject to the limitations set forth in this
Section 5.2.5, CENTOCOR agrees to pay WELLCOME an amount (the
- -------------
"Payment Amount") equal to (**) of the External
--------------
Costs for any given calendar year up to the Maximum Payment (as
defined below). WELLCOME, within thirty (30) days after the end of
each calendar quarter, shall submit to CENTOCOR an invoice for
(**) of the External Costs incurred in respect of such
quarter and, to the extent not previously invoiced, any prior
quarter after the date hereof. The invoice shall be accompanied by
a report describing the nature and amount of the External Costs
reflected in such invoice. CENTOCOR agrees within sixty (60) days
of receiving each invoice to pay the same to WELLCOME or its
Affiliates by wire transfer in immediately available United States
funds pursuant to the instructions WELLCOME provides to CENTOCOR
from time to time. For purposes of making the payments required to
be made in Dollars hereunder, currencies shall be converted on the
basis established by Section 7.4.3 of the Supply Agreement. The
-------------
"Maximum Payment," for the purposes of this Section 5.2.5, shall be
--------------- -------------
defined as follows:
5.2.5.1. In respect of External Costs incurred
in calendar year 1995, the Maximum Payment shall be (**) ; and
5.2.5.2. In respect of calendar year 1996 and
subsequent calendar years, the Maximum Payment shall be
(**) plus the amount, if any, by which the
Payment Amount actually paid to WELLCOME for the preceding calendar
year was less than the Maximum Payment for such calendar year.
Notwithstanding the foregoing, CENTOCOR'S obligation to pay
WELLCOME for such External Costs shall not exceed a total of
(**) and with respect to any payments accruing
hereunder in excess of (**) , WELLCOME shall be
entitled, if at all, to obtain such payments only (at WELLCOME'S
option) as (a) a set-off against the milestone payment that may
become due and owing under Section 7.1.3 hereof (for submission to
-------------
the FDA of a PLA Submission for the 17-1A Product for the First
Indication), or (b) a refund by CENTOCOR of consideration WELLCOME
has previously paid to CENTOCOR pursuant to Section 7.1.3 hereof,
-------------
or (c) a combination of the foregoing.
5.2.6. CENTOCOR shall have the right upon prior
notice to WELLCOME, not more than once in each WELLCOME fiscal year
nor more than once in respect of any WELLCOME fiscal year, through
5
<PAGE>
an independent public accountant selected by CENTOCOR and
acceptable to WELLCOME, which acceptance shall not unreasonably be
refused, to have access during normal business hours to those
records of WELLCOME as may reasonably be necessary to verify the
accuracy of WELLCOME'S calculation of External Costs. If such
independent public accountant's report shows any overcharges by
WELLCOME for External Costs, within thirty (30) days after
WELLCOME'S receipt of such report, WELLCOME shall remit or shall
cause its Affiliate to remit to CENTOCOR (a) the amount of such
overcharges and (b) if such overcharges exceed five percent (5%) of
the total External Costs invoiced for the fiscal year then being
reviewed, the reasonable and necessary fees and expenses of such
independent accountant performing the audit. Otherwise such fees
and expenses associated with the audit shall be borne by CENTOCOR.
CENTOCOR agrees that all information obtained by the independent
public accountant in the course of conducting any audit pursuant to
this Section 5.2.6 is strictly confidential to WELLCOME, and
-------------
CENTOCOR hereby undertakes and agrees that it shall cause its
accountant to retain all such information in the strictest of
confidence.
5.3. Regulatory Approvals. The parties shall cooperate in
--------------------
seeking, obtaining and maintaining Regulatory Approvals for the 17-
1A Product as follows:
5.3.1. To the extent Regulatory Approval is sought
in a country in the Extended Territory, WFL or its Affiliates shall
be primarily responsible for preparing submissions to Regulatory
Authorities and Regulatory Adjuncts in each such country, and shall
be the License Holder in each such country. In addition, WELLCOME
shall be fully responsible for obtaining any and all necessary
licenses, authorizations, registrations, permits and approvals to
act as a contract filler of the 17-1A Product at the Greenville
Facility.
5.3.2. Except to the extent expressly contemplated
by Sections 5.3.1 and 10 hereof or as the parties may otherwise
---------------------
agree from time to time with respect to one or more countries in
the Territory, CNTO, in its own name or in the name of an
Affiliate, shall apply for and hold all licenses and other
Regulatory Approvals necessary to permit the marketing,
distribution and sale in the Territory of the 17-1A Product for the
Targeted Indications. CENTOCOR shall promptly apply for and
diligently pursue such Regulatory Approval for each country in the
Territory as the Project Team shall request.
5.3.3. With respect to the PLA Submission and
Establishment License Application in the United States, CENTOCOR
shall apply (a) with respect to 17-1A Product that is produced as
Final 17-1A Product in the Leiden Facility and (b) with respect to
17-1A Product that is fully purified in the Leiden Facility, is
transported as Pre Formulated Bulk Antibody to the Greenville
Facility and is then prepared by WELLCOME as Final 17-1A Product.
6
<PAGE>
5.3.4. Each submission by any party hereto to any
Regulatory Authority or Regulatory Adjunct in the Territory (other
than the Extended Territory) with respect to the 17-1A Product
shall be jointly prepared by the parties hereto in the manner and
on the time schedule reasonably established from time to time by
the Project Team. WELLCOME shall prepare and defend the clinical
portions of any and all submissions to Regulatory Authorities or
Regulatory Adjuncts, and CENTOCOR shall prepare and defend the
manufacturing portions of any and all submissions to Regulatory
Authorities or Regulatory Adjuncts. Each party hereto, in
consultation with the other parties hereto, shall be primarily
responsible for arranging and conducting any and all meetings
initiated by the parties hereto with Regulatory Authorities or
Regulatory Adjuncts with respect to the clinical and regulatory
development of the 17-1A Product conducted under its own IND and
Regulatory Approvals. With respect to other meetings with
Regulatory Authorities or Regulatory Adjuncts, each party hereto
shall provide the other parties hereto with reasonable prior notice
and an opportunity to attend all such meetings concerning the 17-1A
Product.
5.3.5. CENTOCOR shall provide to WELLCOME regular
progress reports on the Regulatory Approvals for the 17-1A Product
at such reasonable intervals as WELLCOME shall request, and shall
promptly upon receipt thereof provide WELLCOME with copies of all
correspondence to and from all Regulatory Authorities and
Regulatory Adjuncts pertaining to the 17-1A Product and promptly
report to WELLCOME all other discussions with Regulatory
Authorities and Regulatory Adjuncts that may be material to the
prospects, timing or scope of the approval, licensing, marketing or
sale of the 17-1A Product.
5.3.6. To the extent CENTOCOR reasonably believes
necessary to comply with its obligations under Law, CENTOCOR shall
have the right but not the obligation to observe all aspects of the
Clinical Trials, including, but not limited to, the activities of
contract research organizations and investigators. Such
observation shall be conducted on reasonable prior notice to
WELLCOME and shall be conducted in such a manner as not to disrupt
or interfere with the work of the contract research organizations
and investigators. Any communications between CENTOCOR and
investigators or the contract research organizations shall make
clear that CENTOCOR is an observer only and any and all
instructions are to be made by WELLCOME. If WELLCOME so elects,
its representatives may accompany CENTOCOR'S representatives during
such observations. The observations by CENTOCOR pursuant to this
Section 5.3.6 may include audits of the Clinical Trials with
- -------------
respect to good clinical research practices, WELLCOME'S and
CENTOCOR'S internal standards and the requirements of applicable
Regulatory Authorities. WELLCOME, to the extent necessary to
permit CENTOCOR to conduct the observations contemplated by this
Section 5.3.6, shall authorize and direct all of its applicable
- -------------
employees, contract research organizations and investigators to
7
<PAGE>
furnish to CENTOCOR, to the extent permitted by applicable Law,
information with respect to Clinical Trials as CENTOCOR may from
time to time request.
5.3.7. CENTOCOR shall file in a timely, efficient
and orderly manner all submissions to Regulatory Authorities and
Regulatory Adjuncts in connection with the Post Target Program as
WELLCOME shall reasonably request from time to time. WELLCOME
shall reimburse CENTOCOR for any application fees paid by CENTOCOR
in connection with any such submissions.
6. CLINICAL TRIAL MATERIAL.
-----------------------
6.1. General.
-------
6.1.1. CENTOCOR shall provide, and WELLCOME shall
pay for, Clinical Trial Material for the Target Program in
unlabeled 100 mg vials packed in a manner suitable for shipping.
6.1.2. With respect to Clinical Trial Material for
the Target Program to be conducted in the Extended Territory, the
price for such Clinical Trial Material shall be equal to CENTOCOR'S
Fully Burdened Cost for the same.
6.1.3. With respect to Clinical Trial Material for
the Target Program to be conducted in the remainder of the
Territory, the price for such Clinical Trial Material shall be
(**) for the same, except that the total cost to
WELLCOME for Clinical Trial Material for use with the first
(**) patients to receive 17-1A Product in Clinical Trials
conducted by or for WELLCOME (other than for the Post Target
Program) shall not exceed (**) . Notwithstanding the
foregoing, the parties hereto agree that amounts paid by WELLCOME
for Clinical Trial Material shall not be counted toward the
(**) limit imposed by the preceding sentence if and to the
extent such Clinical Trial Material replaces Clinical Trial
Material that (a) (i) CENTOCOR delivered to WELLCOME in accordance
with a firm order made by WELLCOME in accordance with Section 6.2
-----------
hereof with at least (**) shelf life remaining, and (ii)
---
WELLCOME failed to use in Clinical Trials before its shelf life
expired, or (b) was lost, spilled or otherwise rendered unusable in
quantities that are unreasonably high in light of the type and
nature of the Target Program by any Person other than CENTOCOR or
its representative. WELLCOME shall have the right upon prior
notice to CENTOCOR, not more than once in each CENTOCOR fiscal year
nor more than once in respect of any CENTOCOR fiscal year, through
an independent public accountant selected by WELLCOME and
acceptable to CENTOCOR, which acceptance shall not unreasonably be
refused, to have access during normal business hours to those
records of CENTOCOR as may reasonably be necessary to verify the
accuracy of CENTOCOR'S calculation of its Fully Burdened Cost of
Clinical Trial Material. If such independent public accountant's
8
<PAGE>
report shows any overcharges for Clinical Trial Material, within
thirty (30) days after CENTOCOR'S receipt of such report, CENTOCOR
shall remit or shall cause its Affiliate to remit to WELLCOME (x)
the amount of such overcharges and (y) if such overcharges exceed
five percent (5%) of the total price of Clinical Trial Material
charged for the fiscal year then being reviewed, the reasonable and
necessary fees and expenses of such independent accountant
performing the audit. Otherwise such fees and expenses associated
with the audit shall be borne by WELLCOME. WELLCOME agrees that
all information obtained by the independent public accountant in
the course of conducting any audit pursuant to this Section 6.1.3
-------------
is strictly confidential to CENTOCOR, and WELLCOME hereby
undertakes and agrees that it shall cause its accountant to retain
all such information in the strictest of confidence.
6.2. Firm Orders.
-----------
6.2.1. From time to time during the term of this
Agreement, WELLCOME may submit firm orders to CENTOCOR for Clinical
Trial Material at least (**)
prior to the date requested in such order
for delivery of the Clinical Trial Material. On CENTOCOR'S
reasonable request made not more than once per calendar quarter,
WELLCOME shall use commercially reasonable efforts to provide
to CENTOCOR a rolling twelve (12) month forecast of its
requirements for Clinical Trial Material, which forecast shall be
nonbinding and have no legal effect.
6.2.2. CENTOCOR shall fill each firm order submitted
by WELLCOME to CENTOCOR pursuant to Section 6.2.1 hereof for
-------------
Clinical Trial Material on (or, if agreed by the parties hereto,
within ten (10) days before) the delivery date specified in such
firm order. Upon delivery to WELLCOME, all Clinical Trial Material
shall have at least (**) of shelf life remaining. At
CENTOCOR'S request, WELLCOME will accept Clinical Trial Material
with a shelf life less than (**) , but in the event
such Clinical Trial Material is not used due to the limited shelf
life remaining, CENTOCOR will refund the payment made by WELLCOME
to CENTOCOR for such Clinical Trial Material. Without limiting the
foregoing and in accordance with Section 16.2.5 hereof, CENTOCOR
--------------
shall make available to WELLCOME for use in the Clinical Trials (or
as determined by WELLCOME under the Supply Agreement) all 17-1A
Product currently held by CENTOCOR in inventory, all 17-1A Product
completed from the materials currently in process at any CENTOCOR
facility, and such future production of 17-1A Product as may be
required to fill WELLCOME'S firm orders for Clinical Trial
Material.
6.2.3. CNTO and CBV shall use commercially
reasonable efforts to fill any WELLCOME firm orders for Clinical
Trial Material made less than the (**)
9
<PAGE>
before the requested delivery date (as applicable) specified in
Section 6.2.1 hereof.
- -------------
6.2.4. Notwithstanding the order times specified in
Section 6.2.1 hereof, WELLCOME hereby submits, and CENTOCOR hereby
- -------------
agrees to fill and deliver to WELLCOME the following firm orders
for Clinical Trial Material on (or, if agreed by the parties,
within ten (10) days before) the following dates:
(**)
CENTOCOR represents and warrants that, if WELLCOME submits firm
orders in accordance with Section 6.2.1 hereof for subsequent
-------------
delivery of Clinical Trial Material in quantities less than or
equal to the following, CENTOCOR shall fill and deliver such firm
orders on (or, if agreed by the parties hereto, within ten (10)
days before) the following dates:
(**)
CENTOCOR further represents and warrants that it shall fill in a
timely manner firm orders submitted from time to time by WELLCOME
in accordance with Section 6.1.1 for delivery during any month
-------------
commencing on or after (**) of quantities consisting of
one (1) or two (2) (**) lots.
6.2.5. In addition to the foregoing, CENTOCOR agrees
at WELLCOME'S option and promptly upon WELLCOME'S request to
deliver as Clinical Trial Material up to (**) .
6.2.6. If there is a shortfall or anticipated
shortage of Clinical Trial Material and/or any delay in shipment or
delivery occasioned by CENTOCOR or its Affiliates, CENTOCOR hereby
undertakes and agrees immediately to notify WELLCOME and its
Affiliates as to the reason for the shortage of supply and to
provide an indication of the duration of the delay. CENTOCOR shall
use best efforts to make up all shortfalls in delivery of Clinical
Trial Material in accordance with WELLCOME'S instructions as
promptly as possible.
6.3. Delivery Terms; Inspection upon Delivery and Non-
-------------------------------------------------
Conforming Clinical Trial Material.
- ----------------------------------
6.3.1. CENTOCOR shall arrange for shipment of
Clinical Trial Material (**) with a carrier selected and paid for
by WELLCOME. Title to, and risk of loss of, the Clinical Trial
Material shall pass to WELLCOME upon receipt of the Clinical Trial
Material by (**) .
10
<PAGE>
6.3.2. Each shipment of Clinical Trial Material, in
addition to the quantities ordered, shall include such samples as
may be reasonably necessary for testing for quality assurance and
verification. WELLCOME may, but is not obligated to, as soon as
reasonably practicable, but in any event not later than fifteen
(15) Business Days following receipt, inspect samples of all
shipments of the Clinical Trial Material, once received at the
destination specified in WELLCOME'S firm order to determine whether
or not such shipments conform with the 17-1A Product Specification.
6.3.3. In the event that any sample of a shipment of
Clinical Trial Material is delivered to WELLCOME by CENTOCOR
hereunder and shall fail to conform with the 17-1A Product
Specification, WELLCOME shall notify CENTOCOR within ten (10) days
of WELLCOME'S confirming such nonconformity and shall specify the
manner in which the shipment fails to meet the 17-1A Product
Specification.
6.3.4. If WELLCOME gives notice as contemplated by
Section 6.3.3 hereof, CENTOCOR at its own cost and expense shall
- -------------
promptly supply WELLCOME with replacement Clinical Trial Material.
CENTOCOR shall deliver to WELLCOME such replacement Clinical Trial
Material as soon as commercially practicable after receiving notice
under Section 6.3.3 hereof.
-------------
6.3.5. Notwithstanding any other provision hereof,
Clinical Trial Material excluded from the (**) limit
pursuant to Section 6.1.3 hereof shall be supplied by CENTOCOR at
-------------
a price equal to CENTOCOR'S Fully Burdened Cost plus (**) of
such cost.
6.4. Quality Assurance and Quality Control of Clinical Trial
-------------------------------------------------------
Material.
- --------
6.4.1. CENTOCOR shall provide WELLCOME at regular
intervals for the term of this Agreement with all necessary
material safety data and information concerning the safe handling
and storage of Clinical Trial Material known to CENTOCOR and
warrants that at delivery such data and information will be
accurate and up-to-date.
6.4.2. In addition to its own routine quality
control and other tests required by applicable Regulatory
Authorities, CENTOCOR shall conduct, at WELLCOME'S expense, such
quality control and other tests for the Clinical Trial Material as
required from time to time by written notice from WELLCOME to
CENTOCOR.
6.4.3. CENTOCOR shall, at its expense, supply to
WELLCOME the protocol of assay for all the tests performed on
batches of Clinical Trial Material made, together with samples from
each batch and each lot of Clinical Trial Material. WELLCOME, at
its own expense, shall have the right to assay samples and to
11
<PAGE>
perform such biological tests as WELLCOME deems necessary on
samples from any batch or lot of Clinical Trial Material produced
for WELLCOME hereunder.
6.4.4. For each batch or lot of Clinical Trial
Material produced for WELLCOME hereunder, CENTOCOR shall furnish to
WELLCOME on or before the date of each shipment, along with any
testing samples that may be requested by WELLCOME for assay and
microbiological testing purposes, a certificate that the batch or
lot of Clinical Trial Material of which the submitted samples are
representative, was manufactured, tested and delivered in full
compliance with all applicable Laws and a copy of CENTOCOR'S
certificate of analysis that all Clinical Trial Material included
in such shipment complies in all respects with the 17-1A Product
Specification, showing release of each such batch or lot. CENTOCOR
shall be responsible for the completion of all tests necessary to
release Clinical Trial Material for use in each country in the
Territory for which Regulatory Approval is being sought. Where
requested by WELLCOME, CENTOCOR shall provide the services of a
"qualified person" (a "Centocor Qualified Person") within the
-------------------------
meaning of the 2nd Council Directive of 20th May 1975 on the
approximation of provisions laid down by law, regulation or
administrative action relating to proprietary medicinal products
75/319/EEC and appropriate local legislation enacting such
Directive or the equivalent person under other applicable Law in
connection with such release.
6.4.5. CENTOCOR shall conduct all necessary
Stability Studies to validate the lead times for shipment, the
shelf life of inventory and the specifications for shipping,
storing and handling of Clinical Trial Material.
6.4.6. To the extent reasonably requested by
WELLCOME from time to time to comply with regulatory requirements
or for quality assurance purposes, CENTOCOR shall promptly provide
to WELLCOME (a) a full protocol of test results concerning the
Clinical Trial Material delivered to WELLCOME, and (b) a
certification signed by a Centocor Qualified Person that (i) all
manufacturing processes are in accordance with the documented
processes as submitted to the relevant Regulatory Authorities or
Regulatory Adjuncts, and (ii) all manufacturing facilities,
systems, equipment and validations are in full compliance with the
relevant regulatory requirements for every batch of Clinical Trial
Material delivered to WELLCOME.
6.4.7. In accordance with CENTOCOR'S normal safety
and security procedures in force from time to time and with
reasonable advance notice, WELLCOME shall have the right to send
authorized representatives to facilities where Clinical Trial
Material is manufactured during each production run of Clinical
Trial Material to audit any manufacturing, formulation and testing
operations as WELLCOME deems reasonably appropriate to confirm that
production of each batch of Clinical Trial Material is in
12
<PAGE>
compliance with the CGMP Regulations, and at any other time upon
reasonable advance notice to CENTOCOR. Any such audit shall not
include any information that constitutes Manufacturing Technology
to which WELLCOME is not otherwise entitled under the Alliance
Documents. WELLCOME shall have the right to send authorized
representatives to facilities where Clinical Trial Material is
stored to inspect the stock and confirm the method and adequacy of
storage. Upon request of WELLCOME, CENTOCOR agrees to notify
WELLCOME of the next production run of Clinical Trial Material.
CENTOCOR agrees to cooperate with WELLCOME'S authorized
representatives conducting such audits. WELLCOME shall from time
to time identify the persons and timetable for such inspections.
6.4.8. If WELLCOME is required by a Regulatory
Authority or Regulatory Adjunct in any country of the Territory to
have inspected or approved the site of manufacturing Clinical Trial
Material, CENTOCOR will permit officials of the applicable
Regulatory Authorities or appropriate Regulatory Adjunct to inspect
the Leiden Facility or such other CENTOCOR facility where Clinical
Trial Material is manufactured and will take all such action as
such Regulatory Authorities or Regulatory Adjunct may require.
6.5. CNTO'S and CBV'S Obligations as Manufacturer.
--------------------------------------------
6.5.1. CNTO and CBV shall at all times comply with,
and shall manufacture the Clinical Trial Material in accordance
with, CGMP Regulations and in compliance with all applicable Laws,
including Environmental Laws.
6.5.2. CNTO and CBV shall acquire all the necessary
plant, equipment, facilities and sufficiently and appropriately
qualified personnel to enable them to produce and package the
Clinical Trial Material in accordance with the 17-1A Product
Specification, and in accordance with any and all relevant local
regulations where appropriate.
6.5.3. CNTO and CBV undertake that the Leiden
Facility and its manufacturing environment where CNTO and CBV will
manufacture the Clinical Trial Material and all the procedures used
in manufacturing and processing, shall be in accordance with CGMP
Regulations and shall enable CNTO and CBV to maintain in good
standing all applicable Permits.
6.5.4. CNTO and CBV shall provide suitable storage
facilities for the Clinical Trial Material.
6.5.5. CNTO and CBV shall maintain ongoing Stability
Studies throughout the duration of this Agreement using Centocor
Methodology and shall provide WELLCOME with regular samples,
specimens and full reports of the results of the Stability Studies
so as to ensure that the Clinical Trial Material manufactured by
CNTO and CBV is in accordance with the 17-1A Product Specification.
13
<PAGE>
6.5.6. Capacity. CNTO and CBV will at all relevant
--------
times own or lawfully control facilities and Intellectual Property,
and have employees with expertise necessary or appropriate to
produce the Clinical Trial Material in quantities sufficient to
fulfill its obligations under this Agreement.
6.6. Placebo Material. The parties agree that they will
----------------
cooperate in producing or having produced the Placebo Material
required for the Clinical Trials. "Placebo Material," for the
----------------
purposes of this Section 6.6, shall mean materials suitable in
-----------
color, clarity, viscosity and otherwise for use as a placebo in
Clinical Trials of the 17-1A Product.
7. CONSIDERATION
-------------
7.1. In consideration for the intellectual property rights
and other benefits accruing to WELLCOME under this Agreement and
the other Alliance Documents, WELLCOME will make payments to
CENTOCOR as set forth in this Section 7.1. The term "First
----------- -----
Indication" for a given country shall, for the purposes of this
- ----------
Section 7, mean the Targeted Indications or such other indication
- ---------
for which Regulatory Approval for the 17-1A Product is first
received.
7.1.1. (**) upon receipt of
Regulatory Approval of the 17-1A Product for the First Indication
in each of Germany, France, Italy, Spain and the United Kingdom,
being an aggregate maximum under this Section 7.1.1 of (**);
-------------
7.1.2. (**) upon receipt of
Regulatory Approval of the 17-1A Product for the First Indication
in each of the following countries: Austria, Belgium, Denmark,
Finland, Greece, Ireland, Luxembourg, the Netherlands, Norway,
Portugal, Sweden and Switzerland; provided, however, the aggregate
-------- -------
maximum of payments under this Section 7.1.2 shall not exceed
-------------
(**);
7.1.3. Subject to the provisions of Section 5.2.5.2
---------------
hereof, (**) upon submission to the FDA of a PLA
Submission for the 17-1A Product for the First Indication, which
PLA Submission is accepted for review by the FDA; and
7.1.4. (**) upon Regulatory Approval
for the United States of the 17-1A Product for the First
Indication.
7.2. With respect to the consideration under Section 7.1.1
-------------
hereof for Regulatory Approval of the 17-1A Product in Germany, it
shall be a condition of such payment that the Chief Financial
Officer of CNTO and of CBV or such other executive officer of CNTO
and CBV as is reasonably acceptable to WELLCOME shall have
14
<PAGE>
delivered a certificate to WELLCOME certifying that the Regulatory
Approval for the Targeted Indications in Germany has been obtained
and remains in full force and effect. With respect to the
Regulatory Approval under Section 7.1 hereof for Germany and any
-----------
other country, it shall be a condition of each payment due
hereunder that (a) the Regulatory Approvals for the First
Indication in each other country for which a payment under this
Section 7 has previously been made have not been rescinded,
- ---------
suspended or materially limited, which rescission, suspension or
limitation has not been terminated (unless such rescission,
suspension or limitation results from WELLCOME'S negligence); and
(b) the Chief Financial Officer of CNTO and of CBV or such other
executive officer of CNTO and CBV as is reasonably acceptable to
WELLCOME shall have delivered a certificate to WELLCOME certifying
that CNTO and CBV agree that they continue to be bound by the terms
of and will fully perform this Agreement and the Supply Agreement
and have no right to terminate this Agreement and the Supply
Agreement or their performances thereunder except in accordance
with the terms of this Agreement and the Supply Agreement, as
applicable.
7.3. Each payment to CENTOCOR hereunder shall be made in
immediately available United States funds wired to CENTOCOR at such
location in the United States as CENTOCOR may designate in writing
not later than three (3) Business Days prior to the time such
payment is due.
7.4. If any Regulatory Approval for a First Indication for
which a payment has been made under this Section 7 is rescinded by
---------
the applicable Regulatory Authority within (**) of
the date such Regulatory Approval is issued (unless such rescission
results from WELLCOME'S negligence), CENTOCOR shall promptly pay to
WELLCOME an amount equal to (**) of the payment made
by WELLCOME to CENTOCOR with respect to such Regulatory Approval.
If subsequent to such rescission and during the term of this
Agreement such Regulatory Approval is again issued, WELLCOME shall
pay to CENTOCOR the amount so paid by CENTOCOR to WELLCOME.
7.5. Notwithstanding the foregoing, if a Termination Event
as defined in Section 8 hereof shall have occurred and be
---------
continuing, the obligation of WELLCOME to pay under this Section 7
---------
shall be suspended and upon an exercise of the right to terminate
pursuant to Section 8.3 hereof, the obligation to make any such
-----------
suspended payment or any payment under this Section 7 subsequent to
---------
such termination shall terminate.
8. TERMINATION
-----------
8.1. This Agreement shall terminate upon the termination of
the Supply Agreement.
15
<PAGE>
8.2. The following events or circumstances shall constitute
"Termination Events":
------------------
8.2.1. An Event of Termination as defined in the
Supply Agreement shall have occurred.
8.2.2. Any representation or warranty of CNTO or CBV
contained herein or given in connection with this Agreement shall
be untrue or incorrect in any respect material to this Agreement as
a whole.
8.3. If a Termination Event shall have occurred and be
continuing, WELLCOME shall have the option to terminate its
obligations under this Agreement with respect to suspended payments
and any payments not yet due hereunder by giving written notice to
CENTOCOR not later than the date ninety (90) days following the
date on which CENTOCOR gives written notice to WELLCOME of the
existence of the applicable Termination Event, such notice
containing a statement of the facts giving rise to such Termination
Event. WELLCOME'S remedies under this Agreement shall be
cumulative. If CENTOCOR shall terminate its performance under this
Agreement or the Supply Agreement other than by reason of a
material default under, or voluntary termination of, this Agreement
or the Supply Agreement by WELLCOME, WELLCOME shall continue to
have exclusive rights to the Clinical Information, Development Data
and all clinical data arising out of any Clinical Trials to be
conducted by WELLCOME hereunder, and any rights hereunder of
CENTOCOR to such Clinical Information, Development Data and
clinical data arising out of the Clinical Trials to be conducted by
WELLCOME hereunder, shall terminate.
8.4. Except as otherwise provided in this Section 8, if
---------
there shall be a material breach by a party hereto, the other party
(CNTO and CBV being deemed one party for purposes of this Section 8.4
-----------
and WFL and BW being deemed one party for purposes of this
Section 8.4) shall give written notice to the breaching party to
- -----------
cure. Upon receipt of such notice, such breaching party shall have
ninety (90) days to respond by curing such default or by delivering
to the other party a certificate that such breach is not capable of
being cured within such ninety (90) days and that the breaching
party is working diligently to cure such breach. If the breaching
party does not so respond or fails so to work diligently, then the
other party may terminate this Agreement.
8.5. Notwithstanding any other provision of this
Section 8.5, the parties shall cooperate following termination of
- -----------
this Agreement to complete any Clinical Trial and perform any
activity as WELLCOME shall reasonably determine is required by Law
or applicable ethical consideration.
16
<PAGE>
9. POST TARGET DEVELOPMENT
-----------------------
9.1. Upon completion of the Target Program with respect to
a country in the Territory, WELLCOME at its sole option shall have
the right but not the obligation to have conducted at its expense
the Post Target Program with respect to such country.
9.2. The Post Target Program shall be conducted at
WELLCOME'S sole expense, risk and responsibility, subject to the
express indemnities provided by CENTOCOR to WELLCOME.
9.3. CENTOCOR shall provide, and WELLCOME shall pay
(**) for, Clinical Trial Material for the Post Target
Program on the same terms and conditions as are specified in
Section 6 hereof other than the provisions of Section 6.1.3 hereof.
- --------- -------------
9.4. The Post Target Program may include Clinical Trials
and other studies to expand the market for and remove restrictions
on the use of the 17-1A Product, but shall not include Clinical
Trials or other studies necessary to maintain Regulatory Approval
for the Targeted Indications to the extent the foregoing fall
within the definition of the Target Program.
10. APPROVALS TO SELL 17-1A PRODUCT
-------------------------------
WELLCOME shall be responsible, at its sole cost and expense,
for obtaining and maintaining any licenses, registrations, permits
and approvals necessary for WELLCOME as distributor to sell 17-1A
Product in the Territory; provided, however, nothing in this
-------- -------
Section 10 shall limit the obligations of CENTOCOR under Section
- ---------- -------
5.3 hereof to obtain any and all necessary or appropriate licenses,
- ---
registrations, permits and approvals for the manufacture, sale by
manufacturer or use of the 17-1A Product, it being understood that
the licenses, registrations, permits and approvals contemplated by
this Section 10 are solely those required by local law for the
----------
distributor of a finished product the use of which for the
applicable indications is fully approved and licensed. WELLCOME
shall use its commercially reasonable efforts to obtain and
maintain all such licenses, registrations, permits and approvals
contemplated by this Section 10 in those countries in which
----------
Regulatory Approval is obtained and in which sale is contemplated
by the Country Marketing Plans.
11. PUBLIC STATEMENTS
-----------------
11.1. No party hereto, nor its representatives or employees,
shall make any disclosure, including any news release or other
public statement, whether to the press, stockholders, or otherwise,
disclosing the terms of this Agreement or of any amendment hereto,
without the prior written approval of the other parties, which
approval shall not be unreasonably withheld or delayed, providing
that nothing in this Section 11 shall be deemed to prevent any
----------
17
<PAGE>
party hereto from making such disclosures or statements which, in
the opinion of counsel, are legally required. In the event such
disclosure or statement is required, the disclosing party shall
give prior notice to the other party of the proposed disclosure or
statement and the reason therefor. CENTOCOR acknowledges that it
shall file a Current Report on Form 8-K under the Exchange Act
reporting the transactions contemplated by the this Agreement and
the Supplemental Agreement, including exhibits thereto, subject to
appropriate requests for confidential treatment.
11.2. Notwithstanding Section 11.1 hereof, nothing herein
------------
shall prohibit the publication by principal investigators of
scientific papers with respect to their research to the extent
permitted by their clinical trial agreements, provided that to the
extent permitted by such agreements, each party hereto shall have
the opportunity to review and comment upon such papers prior to
publication and shall have reasonable advance notice of the time of
such publication.
12. ADVERSE REACTIONS
-----------------
During the term of this Agreement each party hereto shall
immediately report to the other parties hereto any information
coming into the first party's possession concerning Adverse
Reactions arising out of any Clinical Trials or any other studies
(including without limitation toxicologic studies) and each party
hereto shall take all steps required by applicable Law with respect
to such Adverse Reactions.
13. CONFIDENTIALITY
---------------
13.1. "Proprietary Information" for the purposes of this
-----------------------
Section 13 means all inventions, discoveries, improvements and
- ----------
methods, business plans, marketing techniques and plans,
manufacturing and other plant designs, locations of operations and
any other information affecting the business operations of the
Disclosing Party and which is identified by the Disclosing Party at
the time of disclosure as being confidential or proprietary.
13.2. Except as expressly provided herein otherwise, each
Receiving Party shall, during the term of this Agreement including
any renewals hereof, and for a period of five (5) years following
expiration or the termination hereof, but in any event not for less
than a period of ten (10) years from the date hereof, maintain the
confidentiality of all Proprietary Information disclosed by the
Disclosing Party hereunder and shall neither use the same except as
expressly authorized by this Agreement or any other Alliance
Document, nor disclose the same to any Third Party without the
prior written consent of the Disclosing Party. Nothing in this
Section 13, however, shall be construed to require any party hereto
- ----------
to maintain the confidentiality and non-use of any information or
material that (a) at the time of disclosure, is already in the
public domain; (b) after disclosure, enters the public domain
18
<PAGE>
otherwise than by an act or omission of the Receiving Party in
violation of the terms of this Agreement; (c) prior to disclosure
under this Agreement was already in the possession of the Receiving
Party or its Affiliates, provided that such information or material
was not obtained, directly or indirectly, from the Disclosing Party
under this Agreement or under any other obligation of
confidentiality from the Receiving Party to the Disclosing Party;
(d) becomes known to the Receiving Party from a Third Party,
provided that such information or material was not obtained,
directly or indirectly, from the other party on a confidential
basis; (e) is required in the reasonable judgment of the Receiving
Party to be disclosed to a Governmental Entity in furtherance of
this Agreement or the Alliance Agreement or pursuant to any Law,
Permit, or Court Order; or (f) results from research or development
by the Receiving Party or its Affiliate independent of disclosures
from the Disclosing Party. Disclosures made prior to the date of
this Agreement pursuant to that certain Confidentiality Agreement
between CNTO and WFL dated September 14, 1993 shall be governed by
such Confidentiality Agreement and to the extent not inconsistent
therewith this Section 13; other disclosures prior to the date of
----------
this Agreement of Proprietary Information shall be governed by the
terms of this Section 13.
----------
13.3. Nothing in this Section 13 shall prevent any party
----------
hereto from disclosing its own information relating to its
business, financial affairs, products, research development,
marketing and other commercial activities to any Affiliate. In
addition, notwithstanding the restrictions in this Section 13 on
----------
confidentiality and use, any party hereto may disclose Proprietary
Information which is disclosed to it hereunder to any of its
Affiliates which agrees to be bound by the terms of this Section 13.
----------
13.4. Nothing in this Section 13 shall prevent or restrict
----------
WELLCOME and its Affiliates from using and/or disclosing
Proprietary Information received from CENTOCOR or CBV where such
use and/or disclosure is reasonably regarded by WELLCOME or its
Affiliates as necessary to enable WELLCOME to carry out its
obligations under the Target Program or the Post Target Program,
provided that WELLCOME and its Affiliates shall take all reasonable
steps to ensure that disclosure of any such Proprietary Information
is as limited as possible and disclosed on a confidential basis.
14. OTHER ANTIBODIES
----------------
14.1. During the term of this Agreement and the Supply
Agreement, CENTOCOR shall not develop, conduct clinical trials or
seek regulatory approval or license out rights to any Third Party
with respect to, marketing, selling or distributing any Derivative
17-1A Antibody or any product derived therefrom or from the 17-1A
Antibody except with, and pursuant to an agreement with, WELLCOME.
19
<PAGE>
14.2. If WELLCOME determines that it is not scientifically
or commercially feasible to continue the Target Program with the
17-1A Product, or a Termination Event occurs, WELLCOME may, but is
under no obligation to, substitute under this Agreement for the 17-
1A Product another product that is or contains a Derivative 17-1A
Antibody.
15. JOINT AND SEVERAL LIABILITY
---------------------------
15.1. Each obligation and liability of CENTOCOR under this
Agreement shall be an independent, joint and several obligation of
CNTO and CBV. Each of CNTO and CBV shall be fully liable for
performance under this Agreement notwithstanding (a) the voluntary
or involuntary liquidation, dissolution, sale or other disposition
of all, or substantially all of the assets, marshalling of assets
and liabilities, receivership, insolvency, bankruptcy, assignment
for the benefit of creditors, reorganization, arrangement,
composition with creditors or readjustment of, or other similar
proceedings affecting CBV or CNTO or any contest of the validity of
this Agreement in any such proceeding; or (b) any Law or Court
Order now or hereafter in effect in any jurisdiction which might in
any manner affect any of such terms or provisions or any of the
rights of WFL or BW with respect thereto or which might cause or
permit CBV or CNTO to invoke any defense to, or any alteration in
the time, amount or manner of performance of any or all of their
respective obligations under this Agreement except to the extent
such Law or Court Order renders such obligations unlawful or to the
extent such Court Order constitutes a remedy for a breach by WFL or
BW. The invalidity or unenforceability of this Agreement as to
either of CNTO or CBV shall not render this Agreement invalid or
unenforceable as to the other. The invalidity or unenforceability
of this Agreement in any jurisdiction shall not in itself render
this Agreement unenforceable in another jurisdiction. If any
obligation hereunder of either CBV or CNTO is not performed by such
party punctually, the other of CBV or CNTO, as applicable, will,
without demand being made by WELLCOME, immediately perform such
obligation.
15.2. To the extent that BW has an obligation hereunder,
either expressly or by assignment by WFL, WFL hereby guarantees the
full payment and performance of such obligation. Each of WFL and
BW shall be fully liable for performance of their obligations under
this Agreement notwithstanding (a) the voluntary or involuntary
liquidation, dissolution, sale or other disposition of all, or
substantially all of the assets, marshalling of assets and
liabilities, receivership, insolvency, bankruptcy, assignment for
the benefit of creditors, reorganization, arrangement, composition
with creditors or readjustment of, or other similar proceedings
affecting BW or WFL or any contest of the validity of this
Agreement in any such proceeding; or (b) any Law or Court Order now
or hereafter in effect in any jurisdiction which might in any
manner affect any of such terms or provisions or any of the rights
of CENTOCOR with respect thereto or which might cause or permit BW
20
<PAGE>
or WFL to invoke any defense to, or any alteration in the time,
amount or manner of performance of any or all of their respective
obligations under this Agreement, except to the extent such Law or
Court Order renders such obligations unlawful or to the extent such
Court Order constitutes a remedy for a breach by CNTO or CBV. The
invalidity or unenforceability of this Agreement as to either of
WFL or BW shall not render the respective obligations of the other
under this Agreement invalid or unenforceable. The invalidity or
unenforceability of this Agreement in any jurisdiction shall not in
itself render this Agreement unenforceable in another jurisdiction.
If any obligation hereunder of BW is not performed by it
punctually, WFL will, without demand being made by CENTOCOR,
immediately perform such obligation.
16. REPRESENTATIONS AND WARRANTIES
------------------------------
16.1. All Parties. WFL and BW hereby represent and warrant
-----------
jointly and severally as to each of WFL and BW; and CNTO and CBV
hereby jointly and severally represent and warrant as to each of
CNTO and CBV:
16.1.1. Organization, Standing and Qualification. It
----------------------------------------
is a corporation duly organized, validly existing, and in good
standing under the laws of its jurisdiction of incorporation.
16.1.2. Power and Authority; Enforceability. It has
-----------------------------------
the requisite power and authority (corporate and otherwise) to
execute, deliver and perform this Agreement and to consummate the
transactions contemplated hereby. The execution, delivery and
performance by it of this Agreement and the consummation by it of
the transactions contemplated hereby have been duly authorized by
all necessary action (corporate and otherwise) on its part. This
Agreement constitutes its legal, valid and binding obligation
enforceable in accordance with its terms.
16.1.3. Validity of Contemplated Transactions. The
-------------------------------------
execution, delivery and performance by it of this Agreement and the
consummation by it of the transactions contemplated hereby do not
(a) violate or contravene any provision of its charter or bylaws;
(b) violate, breach, conflict with, constitute a Default under,
cause the acceleration of any payments pursuant to, or otherwise
impair the good standing, validity, or effectiveness of any
agreement, contract, indenture, lease, license, or mortgage to
which it is a party or by which it or any of its properties or
assets are bound; (c) subject any of its properties or assets to
any Lien or to any indenture, mortgage, contract, commitment, or
agreement (other than this Agreement) to which it is a party or by
which it or any of its properties or assets are bound; (d) violate
any provision of any Law, Permit or Court Order applicable to it or
any of its properties or assets; or (e) other than filings which
have already been made, require any Permit or Required Consent of
any Governmental Entity to be obtained by it.
21
<PAGE>
16.1.4. Litigation; Compliance with Laws. There is
--------------------------------
no Litigation pending or, to its knowledge, threatened against or
related to it, nor any failure to comply with, violation of or any
Default under, any Law, Permit or Court Order applicable to it, in
each case which might have a material adverse effect on the ability
of it to execute, deliver and perform this Agreement or on the
ability of it to consummate the transactions contemplated hereby.
16.2. By CNTO and CBV. CNTO and CBV represent and warrant
---------------
that with respect to each of them:
16.2.1. Intellectual Property. To the best of CNTO'S
---------------------
knowledge, CNTO and CBV own, possess or lawfully use pursuant to
legal, valid, binding and enforceable agreements all Intellectual
Property necessary or appropriate in connection with the
development, production, testing and sale by them of the 17-1A
Product. The inception, development and reduction to practice of
any of the Intellectual Property in connection with the
development, production, testing and sale by them of the 17-1A
Product has not constituted or involved the misappropriation by
CENTOCOR or its Affiliates or, to the best of its knowledge, by
Third Parties, of trade secrets or other rights of any other Person
(including, without limitation, any Governmental Entity). In
connection with the development, production, testing and sale
(including sale for resale) by them of the 17-1A Product, neither
CENTOCOR nor any of its Affiliates (and in connection with their
resale of the 17-1A Product, neither WELLCOME nor any of its
Affiliates), to the best of CENTOCOR'S knowledge, is or may be
infringing on or otherwise acting adversely to the rights of any
Person under or in respect of any of the Intellectual Property of
such Person. To the best of CNTO'S and CBV'S knowledge, no Person
is or may be infringing on or otherwise acting adversely to the
rights of CENTOCOR or any of its Affiliates under or in respect of
any of the Intellectual Property which is used in connection with
the development, production, testing and sale by them of the 17-1A
Product.
16.2.2. Wistar License. CENTOCOR is party to the
--------------
Wistar License, which is valid, binding and enforceable, and,
pursuant to such license, is the exclusive licensee of the Wistar
Rights, has not sublicensed the Wistar Rights to any Person
excluding Ajinomoto pursuant to the Ajinomoto Agreement, and no
Person other than CENTOCOR is entitled, either currently or during
the term of the Supply Agreement, to license the Wistar Rights.
CENTOCOR holds such Wistar Rights free and clear of all Liens,
claims and other encumbrances, covenants, conditions, or
restrictions. There are no licenses, options, rights of first
refusal, conditional sales agreements or other arrangements,
whether oral or written, which affect any portion of or all such
Wistar Rights.
22
<PAGE>
16.2.3. Cell Line. The cell line from which CNTO and
---------
CBV obtain the 17-1A Antibody is the Centocor Hybridoma. To the
extent that such cell line differs from the Wistar Hybridoma, CNTO
and CBV own all right, title and interest in such cell line, free
and clear of all Liens, claims and other encumbrances, conditions,
covenants or restrictions.
16.2.4. Conducted Clinical Trials. The Conducted
-------------------------
Clinical Trials were conducted solely and exclusively by the
Persons identified on Schedule 16.2.4 hereto, and CENTOCOR owns all
---------------
data, information, and results of the Conducted Clinical Trials
free and clear of all Liens, claims and other encumbrances,
conditions, covenants or restrictions except applicable patient
confidentiality rights. There are no licenses, options, rights of
first refusal, conditional sales agreements or other arrangements,
whether oral or written, which affect any portion of or all the
data, information, and results of the Conducted Clinical Trials, or
that would limit the ability of the parties to incorporate any of
the foregoing in submissions by the parties hereto to Regulatory
Authorities and Regulatory Adjuncts as contemplated by this
Agreement.
16.2.5. Capacity. CNTO and CBV own or lawfully
--------
control facilities and Intellectual Property, and have employees
with expertise, necessary or appropriate to produce the 17-1A
Product pursuant to Regulatory Approvals in quantities sufficient
to fulfill their obligations under this Agreement and the Supply
Agreement without, to the best of CNTO'S and CBV'S knowledge,
infringing the rights of any Third Party.
16.2.6. Veracity of Statements. No representation or
----------------------
warranty by it contained in this Agreement or in any certificate,
schedule or other document or instrument furnished to it pursuant
hereto, contains or will contain any untrue statement of a material
fact or omits or will omit to state a material fact necessary to
make it not misleading.
16.3. The representations and warranties contained herein
shall survive execution and delivery of this Agreement.
17. INDEMNIFICATION WITH RESPECT TO TARGET PROGRAM AND POST
-------------------------------------------------------
TARGET PROGRAM.
- --------------
17.1. By CNTO and CBV. Subject to compliance by the
---------------
applicable Indemnitee as defined below with its obligations set
forth in Sections 17.4 and 17.5 hereof, CNTO and CBV shall defend,
----------------------
indemnify and hold WFL, BW and their respective Affiliates and the
respective directors, officers, employees and agents of WFL, BW and
their respective Affiliates, harmless from and against any and all
Losses arising out of, relating to or resulting from acts and
omission after the date of this Agreement with respect to the
Target Program and Post Target Program to the extent such Losses
arise out of the negligence, willful misconduct or a breach of a
23
<PAGE>
representation or warranty of CNTO, CBV or any of their respective
Affiliates in connection with the Target Program or Post Target
Program.
17.2. By WFL and BW. Subject to compliance by the
-------------
applicable Indemnitee as defined below with its obligations set
forth in Sections 17.4 and 17.5 hereof, WFL and BW shall defend,
----------------------
indemnify and hold CNTO, CBV and their respective Affiliates and
the respective directors, officers, employees and agents of CNTO,
CBV and the their respective Affiliates, harmless from and against
any and all Losses arising out of, relating to or resulting from
acts and omissions after the date of this Agreement with respect to
the Target Program and Post Target Program, except to the extent
such Losses arise out of the negligence, willful misconduct or
breach of a representation or warranty by CNTO, CBV or any of their
respective Affiliates in connection with the Target Program or Post
Target Program.
17.3. "Indemnitor" means CNTO and CBV with respect to
----------
Section 17.1 hereof and WFL and BW with respect to Section 17.2
- ------------ ------------
hereof. "Indemnitee" means any of WFL, BW and their respective
----------
Affiliates and the respective directors, officers, employees and
agents of WFL, BW and their respective Affiliates with respect to
Section 17.1 hereof and any of CNTO, CBV and their respective
- ------------
Affiliates and the respective directors, officers, employees and
agents of CNTO, CBV and their respective Affiliates with respect to
Section 17.2 hereof.
- ------------
17.4. Notice. Promptly after receipt by an Indemnitee of
------
written notice of the commencement of any suit, audit, demand,
judgment, action, investigation or proceeding relating to a Loss (a
"Third Party Action") or promptly after an Indemnitee incurs a Loss
------------------
or has knowledge of the existence of a Loss, such Indemnitee will,
if a claim with respect thereto is to be made against the
Indemnitor due to the Indemnitor's obligation to provide
indemnification hereunder, give the Indemnitor written notice of
such Loss or the commencement of such Third Party Action; provided,
--------
however, the failure to provide such notice within a reasonable
- -------
period of time shall not relieve the Indemnitor of any of its
obligations hereunder except to the extent it is prejudiced by such
failure.
17.5. Defense. The Indemnitor shall control the defense and
-------
settlement of a Third Party Action, except that the applicable
Indemnitee may assume such defense provided that the obligation of
the Indemnitor to pay the attorneys' fees of such Indemnitee shall
cease upon such election. If the Indemnitor defends such action,
it shall not enter into any resolution or other compromise of such
action unless it (a) pays in cash or posts an adequate bond for the
payment of the amount of such resolution or other compromise and
obtains a complete release of the Indemnitee, or (b) obtains the
prior written consent of the Indemnitee, which shall not be
unreasonably withheld or delayed. If the Indemnitee defends such
24
<PAGE>
action, such Indemnitee shall not enter into any resolution or
other compromise of such action unless such Indemnitee obtains the
consent of the Indemnitor, which shall not be unreasonably withheld
or delayed. The party defending the action shall keep the other
parties informed on an ongoing basis of the status of such Third
Party Action and shall deliver to such other parties copies of all
documents relating to the Third Party Action as the other party may
reasonably request. The party assuming such defense shall receive
from the others all necessary and reasonable cooperation in the
defense of a Third Party Action including, but not limited to, the
services of employees of such other parties who are familiar with
the events or circumstances out of which any such Third Party
Action may have arisen.
17.6. The indemnifications contained in this Section 17
----------
shall survive termination of this Agreement.
18. MISCELLANEOUS
-------------
18.1. Entire Agreement. This Agreement and the other
----------------
Alliance Documents constitute the entire understanding of the
parties with respect to the subject matter contained herein and
supersede any prior understandings and agreements among them
respecting such subject matter; provided, however, the
-------- -------
confidentiality agreement between WFL and CNTO dated September 14,
1993 shall in all cases remain in full force and effect in
accordance with its terms.
18.2. Amendments. This Agreement may be amended and
----------
supplemented only by a written instrument duly executed by each of
the parties.
18.3. Headings. The headings in this Agreement are for
--------
convenience of reference only and shall not affect its
interpretation.
18.4. Gender; Number. Words of gender may be read as
--------------
masculine, feminine, or neuter, as required by context. Words of
number may be read as singular or plural, as required by context.
18.5. Appendices; Exhibits; and Schedules. All appendices,
-----------------------------------
exhibits and schedules referred to herein form an integral part of
this Agreement and are incorporated into this Agreement by such
reference.
18.6. Severability. If any provision of this Agreement or
------------
the application thereof to any Person or circumstance is held
illegal, invalid, or unenforceable, such illegality, invalidity, or
unenforceability shall not affect any other provision hereof. This
Agreement shall, in such circumstances, be deemed modified to the
extent necessary to render enforceable the provisions hereof to the
fullest extent permitted by Law.
25
<PAGE>
18.7. Remedies. Each of CNTO and CBV on the one hand, and
--------
WFL and BW on the other, stipulates that the remedies at Law of the
other in the event of any default or threatened default in the
performance of or compliance with any of the terms of this
Agreement are not and will not be adequate and that, to the fullest
extent permitted by Law, such terms may be specifically enforced by
a decree for specific performance of any agreement contained herein
or by an injunction against any violation of any terms hereof or
otherwise.
18.8. Notices. All notices and other communications
-------
hereunder shall be in writing and shall be given to the Person
either personally or by sending a copy thereof by first class
United States express mail, postage prepaid and return-receipt
requested, or by a nationally-recognized courier service
guaranteeing next-day delivery, charges prepaid, or by telecopier
(with the original sent by either of the foregoing manners), to
such Person's address (or to such Person's telecopier number). All
notices shall be deemed to have been given to the person entitled
thereto when received.
If to WFL or BW, to:
THE WELLCOME FOUNDATION LIMITED
Unicorn House, P.O. Box 129
160 Euston Road
London NW1 2BP, England
Attention: Company Secretary
Telecopy No.: 011-44-71-388-5462
and
BURROUGHS WELLCOME CO.
3030 Cornwallis Road
Research Triangle Park, NC 27709
USA
Attention: Company Secretary
Telecopy No.: (919) 315-0478
If to CNTO or CBV, to:
CENTOCOR, INC.
200 Great Valley Parkway
Malvern, Pennsylvania 19355-1307
USA
Attention: Corporate Secretary
Telecopy No.: (215) 651-6100
26
<PAGE>
with a copy to:
Duane, Morris & Heckscher
One Liberty Place
Philadelphia, PA 19103
Attention: David C. Toner, Esquire
Telecopy No.: (215) 979-1020
Notice of any change in any such address shall also be given in the
manner set forth above. Whenever the giving of notice is required,
the giving of such notice may be waived by the Person entitled to
receive such notice.
18.9. Waiver. No provision of this Agreement may be waived
------
except by a written instrument signed by the party hereto sought to
be bound. No failure or delay by any party hereto in exercising
any right or remedy hereunder or under applicable Law will operate
as a waiver thereof, and a waiver of a particular right or remedy
on one occasion will not be deemed a waiver of any other right or
remedy, or a waiver on any subsequent occasion (it being understood
that specific time frames for notice or actions to be taken shall
be binding on the parties).
18.10. Assignment. No party hereto may assign its rights or
----------
delegate any of its obligations hereunder without the prior written
consent of the other parties hereto, except that, without such
consent, (a) WFL may assign all or any part of its rights and
obligations hereunder to an Affiliate of WELLCOME, including but
not limited to BW and Nippon Wellcome K.K., so long as WFL
unconditionally guarantees the obligations of such Affiliate; (b)
WFL and BW may assign all of their rights and delegate all of their
duties under this Agreement to the transferee of all or
substantially all of the line of business of which this Agreement
forms a part or by way of merger or consolidation with another
company; and (c) CNTO and CBV may assign all of their rights and
delegate all of their duties to a transferee of all or
substantially all their assets or by way of merger or consolidation
with another company. Without limiting the foregoing, all rights
and obligations with respect to the subject matter of this
Agreement as to the United States (including the payment of the
amounts contemplated by Sections 7.1.3 and 7.1.4 hereof) shall
------------------------
inure to the benefit of and be performed by BW, subject to such
further assignments as may be permitted by this Section 18.10. If
-------------
any party hereto shall assign its rights and delegate its duties
pursuant to clauses (b) or (c) of this Section 18.10, the Person to
------------------ -------------
whom such rights are assigned and duties are delegated shall assume
all of the obligations of the applicable party under this
Agreement. The guarantee by WFL referenced in clause (a) of this
----------
Section 18.10 is a guaranty of payment and performance, and not of
- -------------
collection; and in case of a default by an Affiliate of WFL to
which rights have been assigned or obligations delegated pursuant
to such clause (a), CNTO and CBV shall have the right to proceed
----------
27
<PAGE>
first against WFL without the necessity to proceed against or join
such Affiliate.
18.11. Successors and Assigns. This Agreement shall bind,
----------------------
inure to the benefit of, and be enforceable by the successors and
permitted assigns of the parties hereto.
18.12. Governing Law. This Agreement shall be construed and
-------------
enforced in accordance with the Laws of the Commonwealth of
Pennsylvania without regard to principles of conflicts of law
applicable in such jurisdiction.
18.13. No Benefit to Others. The representations,
--------------------
warranties, covenants and agreements contained in this Agreement
are for the sole benefit of the parties hereto and their successors
and permitted assigns, and they shall not be construed as
conferring, and are not intended to confer, any rights on any other
Person.
18.14. Independent Contractors. It is expressly understood
-----------------------
and agreed that the CENTOCOR Group and the WELLCOME Group are
independent contractors; neither the CENTOCOR Group or any of its
members, nor the WELLCOME Group or any of its members, shall be
deemed the agent of the other group or of any of such group's
members for any purpose whatsoever, and neither the CENTOCOR Group
or any of its members, nor the WELLCOME Group or any of its
members, shall have authority to enter into any contract or
agreement, assume any obligation or make any warranty or
representation for or on behalf of the other group or any of its
members. Nothing in this Agreement shall be deemed to create or
constitute a partnership or the relationship of employer and
employee between the WELLCOME Group or any of its members on the
one hand and the CENTOCOR Group or any of its members on the other.
18.15. Further Assurances. At the request of any party
------------------
hereto, the other parties hereto shall execute and deliver from
time to time such further instruments and shall provide reasonable
cooperation in such proceedings or actions as shall be necessary or
reasonably appropriate to effectuate the purposes of this Agreement
including, without limitation, (a) registering or recording the
rights granted hereunder in appropriate offices of particular
Governmental Entities, and (b) completing the drug master file(s)
for the 17-1A Product and obtaining and maintaining the parties'
respective Investigational New Drug Applications and other
Regulatory Approvals contemplated by this Agreement and fulfilling
the parties' obligations under the applicable Law by reason of
their respective INDs; provided, however, if any party hereto
-------- -------
desires to notify this Agreement under Article 85(3) of the Treaty
of Rome establishing the European Economic Community, such party
shall give the other parties ninety (90) days' prior written notice
of such notification and if during such period a party shall
reasonably object to such notification, the objecting party need
not cooperate in such notification and such notification shall not
28
<PAGE>
be implemented. Except as otherwise provided in the Alliance
Documents, the executions, deliveries and cooperation of each party
under this Section 18.15 shall be without further consideration and
-------------
at such party's expense.
29
<PAGE>
18.16. Counterparts. This Agreement and any amendment or
------------
supplement hereto may be executed in any number of counterparts and
any party hereto may execute any such counterpart, each of which
when executed and delivered shall be deemed to be an original and
all of which counterparts taken together shall constitute but one
and the same instrument. The execution of this Agreement and any
such amendment or supplement by any party hereto will not become
effective until counterparts hereof have been executed by all the
parties hereto.
18.17. Savings Clause. Any restriction or information
--------------
provision (as each of these terms or expressions are defined in the
RTPA) contained in this Agreement or in any arrangement of
which this Agreement forms part by virtue of which this Agreement
or any such arrangement is registrable under the RTPA shall not
take effect in the United Kingdom until the day after the day on
which full particulars of this Agreement (and of any such
arrangement) shall have been duly furnished to the Office of Fair
Trading under Section 24 of the RTPA.
----------
IN WITNESS WHEREOF, the parties hereto have caused this
Agreement to be executed as of the day and year first above written
by their duly authorized representatives.
For and on behalf of
THE WELLCOME FOUNDATION LIMITED
Signed: /s/ Dawn E. Knight
------------------
Name: Dawn E. Knight
--------------
Title: Assistant Company Secretary
---------------------------
BURROUGHS WELLCOME CO.
Signed: /s/ Richard S. Kent, M.D.
-------------------------
Name: Richard S. Kent, M.D.
---------------------
Title: Vice President, Research,
Development and Medical
-----------------------
[EXECUTIONS CONTINUED]
30
<PAGE>
CENTOCOR, INC.
Signed: /s/ David P. Holveck
-----------------------
Name: David P. Holveck
-------------------
Title: President and Chief Executive
Officer
-------------------------------
CENTOCOR B.V.
Signed: /s/ David P. Holveck
-----------------------
Name: David P. Holveck
------------------
Title: Managing Director
-------------------
31
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APPENDIX A
----------
GLOSSARY OF TERMS
-----------------
[See Appendix A to the Supply Agreement
(as amended by the Supplemental Agreement)]
32
<PAGE>
SCHEDULE 16.2.4
CONDUCTED CLINICAL TRIALS
(**)
