<PAGE> 1
AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON JANUARY 28, 1997
REGISTRATION NO. 333-17661
- --------------------------------------------------------------------------------
- --------------------------------------------------------------------------------
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
------------------------
AMENDMENT NO. 4 TO
FORM S-1
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
------------------------
COULTER PHARMACEUTICAL, INC.
(EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)
<TABLE>
<S> <C> <C>
DELAWARE 2834 94-3219075
(STATE OR OTHER JURISDICTION OF (PRIMARY STANDARD INDUSTRIAL (I.R.S. EMPLOYER
INCORPORATION OR ORGANIZATION) CLASSIFICATION CODE NUMBER) IDENTIFICATION NUMBER)
</TABLE>
------------------------
550 CALIFORNIA AVENUE, SUITE 200
PALO ALTO, CALIFORNIA 94306-1440
(415) 842-7300
(ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER,
INCLUDING AREA CODE, OF REGISTRANT'S PRINCIPAL EXECUTIVE OFFICES)
------------------------
MICHAEL F. BIGHAM
PRESIDENT AND CHIEF EXECUTIVE OFFICER
COULTER PHARMACEUTICAL, INC.
550 CALIFORNIA AVENUE, SUITE 200
PALO ALTO, CALIFORNIA 94306-1440
(415) 842-7300
(NAME, ADDRESS AND TELEPHONE NUMBER OF AGENT FOR SERVICE)
------------------------
COPIES TO:
<TABLE>
<S> <C>
JAMES C. KITCH, ESQ. ALAN K. AUSTIN, ESQ.
JOHN A. DADO, ESQ. ELIZABETH R. FLINT, ESQ.
COOLEY GODWARD LLP WILSON SONSINI GOODRICH & ROSATI
FIVE PALO ALTO SQUARE PROFESSIONAL CORPORATION
3000 EL CAMINO REAL 650 PAGE MILL ROAD
PALO ALTO, CALIFORNIA 94306 PALO ALTO, CALIFORNIA 94304
</TABLE>
------------------------
APPROXIMATE DATE OF PROPOSED SALE TO THE PUBLIC: As soon as practicable
after the effective date of this Registration Statement.
------------------------
If any of the Securities being registered on this Form are to be offered on
a delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, check the following box. [ ]
If this Form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, please check the following box
and list the Securities Act registration statement number of the earlier
effective registration statement for the same offering. [ ]
If this Form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. [ ]
If delivery of the Prospectus is expected to be made pursuant to Rule 434,
please check the following box. [ ]
------------------------
THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR
DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT SHALL
FILE A FURTHER AMENDMENT THAT SPECIFICALLY STATES THAT THIS REGISTRATION
STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH SECTION 8(A) OF
THE SECURITIES ACT OF 1933 OR UNTIL THE REGISTRATION STATEMENT SHALL BECOME
EFFECTIVE ON SUCH DATE AS THE COMMISSION, ACTING PURSUANT TO SAID SECTION 8(A),
MAY DETERMINE.
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<PAGE> 2
PART II
INFORMATION NOT REQUIRED IN PROSPECTUS
ITEM 13. OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION.
The following table sets forth all expenses, other than the underwriting
discounts and commissions, payable by the Registrant in connection with the sale
of the Common Stock being registered. All the amounts shown are estimates except
for the registration fee, the NASD filing fee and the Nasdaq National Market
application fee.
<TABLE>
<S> <C>
SEC Registration fee...................................................... $ 12,197
NASD filing fee........................................................... 4,525
Nasdaq National Market application fee.................................... 42,589
Blue sky qualification fee and expenses................................... 1,000
Printing and engraving expenses........................................... 140,000
Legal fees and expenses................................................... 300,000
Accounting fees and expenses.............................................. 150,000
Transfer agent and registrar fees......................................... 4,500
Miscellaneous fees........................................................ 10,189
----------
Total........................................................... $665,000
==========
</TABLE>
ITEM 14. INDEMNIFICATION OF OFFICERS AND DIRECTORS.
Under Section 145 of the Delaware General Corporation Law, the Registrant
has broad powers to indemnify its directors and officers against liabilities
they may incur in such capacities, including liabilities under the Securities
Act of 1933, as amended (the "Securities Act"). The Registrant's Bylaws also
provide that the Registrant will indemnify its directors and executive officers
and may indemnify its other officers, employees and other agents to the fullest
extent not prohibited by Delaware law.
The Registrant's Certificate of Incorporation provides for the elimination
of liability for monetary damages for breach of the directors' fiduciary duty of
care to the Registrant and its stockholders. These provisions do not eliminate
the directors' duty of care and, in appropriate circumstances, equitable
remedies such as injunctive or other forms of non-monetary relief will remain
available under Delaware law. In addition, each director will continue to be
subject to liability for breach of the director's duty of loyalty to the
Registrant, for acts or omissions not in good faith or involving intentional
misconduct, for knowing violations of law, for any transaction from which the
director derived an improper personal benefit, and for payment of dividends or
approval of stock repurchases or redemptions that are unlawful under Delaware
law. The provision does not affect a director's responsibilities under any other
laws, such as the federal securities laws or state or federal environmental
laws.
The Registrant has entered into agreements with its directors and executive
officers that require the Registrant to indemnify such persons against expenses,
judgments, fines, settlements and other amounts actually and reasonably incurred
(including expenses of a derivative action) in connection with any proceeding,
whether actual or threatened, to which any such person may be made a party by
reason of the fact that such person is or was a director or officer of the
Registrant or any of its affiliated enterprises, provided such person acted in
good faith and in a manner such person reasonably believed to be in or not
opposed to the best interests of the Registrant and, with respect to any
criminal proceeding, had no reasonable cause to believe his or her conduct was
unlawful. The indemnification agreements also set forth certain procedures that
will apply in the event of a claim for indemnification thereunder.
II-1
<PAGE> 3
The Underwriting Agreement filed as Exhibit 1.1 to this Registration
Statement provides for indemnification by the Underwriters of the Registrant and
its officers and directors for certain liabilities arising under the Securities
Act or otherwise.
The Registrant intends to purchase a general liability insurance policy
which covers certain liabilities of directors and officers of the Registrant
arising out of claims based on acts or omissions in their capacity as directors
or officers.
ITEM 15. RECENT SALES OF UNREGISTERED SECURITIES.
Since its inception in February 1995, the Registrant has sold and issued
the following unregistered securities:
(1) In February 1995, the Registrant sold and issued an aggregate of
7,500,000 shares of Series A Preferred Stock to two accredited investors
for cash in the aggregate amount of $2,500,000 and the assignment of
certain intellectual property rights.
(2) In August 1995, the Registrant sold and issued an aggregate of
2,333,333 shares of Series B Preferred Stock to six accredited investors
for cash in the aggregate amount of $3,500,000.
(3) In March 1996, the Registrant sold and issued 1,200,000 shares of
Common Stock to one accredited investor in exchange for a promissory note
in the amount of $180,000.
(4) In April 1996, the Registrant sold and issued an aggregate of
9,964,607 shares of Series C Preferred Stock and Warrants to purchase
1,496,182 shares of Common Stock to a group of accredited investors for
$22,420,363.74.
(5) From March 1995 to December 6, 1996, the Registrant granted
incentive stock options and nonstatutory stock options to employees,
directors and consultants covering an aggregate of 2,362,803 shares of the
Registrant's Common Stock, at a weighted average exercise price of $.36 per
share. As of December 6, 1996, the Registrant has sold 112,038 shares of
its Common Stock to employees, directors and consultants pursuant to
exercise of stock options.
(6) In December 1996, the Registrant issued a warrant to purchase
74,000 shares of Common Stock to one accredited investor in connection with
an equipment lease financing.
The share amounts set forth above do not take into account the
one-for-three reverse stock split that will be effected prior to the closing of
this offering.
The sale and issuance of securities in the transactions described in
paragraphs (1), (2), (4) and (6) above were deemed to be exempt from
registration under the Securities Act by virtue of Section 4(2) adopted
thereunder. The purchasers in each case represented their intention to acquire
the securities for investment only and not with a view to distribution thereof.
Appropriate legends are affixed to the stock certificates or warrants issued in
such transactions. All recipients either received adequate information about the
Registrant or had access, through employment or other relationships, to such
information.
The sale and issuance of securities in the transactions described in
paragraph (3) and (5) above were deemed to be exempt from registration under the
Securities Act by virtue of Rule 701 promulgated thereunder, in that they were
issued either pursuant to written compensatory benefit plans or pursuant to a
written contract relating to compensation, as provided by Rule 701.
II-2
<PAGE> 4
ITEM 16. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES.
(a) EXHIBITS.
<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION OF DOCUMENT
- ------- ---------------------------------------------------------------------------------
<C> <S>
1.1** Form of Underwriting Agreement.
3.1** Amended and Restated Certificate of Incorporation of the Registrant.
3.2** Form of Amendment to Certificate of Incorporation to be filed prior to the
offering.
3.3** Form of Amended and Restated Certificate of Incorporation of the Registrant to be
filed upon the closing of the offering.
3.4** Bylaws of the Registrant.
3.5** Bylaws of the Registrant to be effective upon the closing of the offering.
4.1 Reference is made to Exhibits 3.1 through 3.5.
4.2** Specimen stock certificate.
4.3** Amended and Restated Investors' Rights Agreement, dated April 18, 1996, between
the Registrant and certain investors.
4.4** Warrant Agreement to purchase Common Stock, dated December 6, 1996, between the
Registrant and Lease Management Services, Inc.
5.1** Opinion of Cooley Godward LLP.
10.1** Form of Indemnity Agreement to be entered into between the Registrant and its
officers and directors.
10.2** 1996 Equity Incentive Stock Option Plan.
10.3** Form of Equity Incentive Stock Option.
10.4** Form of Nonstatutory Stock Option.
10.5** 1996 Employee Stock Purchase Plan.
10.6** Assignment Agreement, dated February 24, 1995, between the Registrant, Coulter
Corporation and certain investors.
10.7 + Manufacturing Agreement, dated August 20, 1996, between Lonza Biologics PLC and
the Registrant.
10.8** Equipment Lease Financing Agreement, dated December 6, 1996, between the
Registrant and Lease Management Services, Inc.
10.9 +** First Amendment to Manufacturing Agreement, dated November 21, 1996, by and
between Lonza Biologics PLC and the Registrant.
10.10+** Development Agreement, dated November 15, 1995, by and between Nordion
International, Inc. and the Registrant.
10.11+** Patent License Agreement, dated March 15, 1996, by and between the Region
Wallone, the Universite Catholoique de Louvain and Coulter Pharma Belgium, SA.
11.1** Statement regarding computation of loss per share.
21.1** Subsidiaries of the Registrant.
23.1 Consent of Ernst & Young LLP. Reference is made to page II-7.
23.2** Consent of Cooley Godward LLP. Reference is made to Exhibit 5.1.
24.1 Power of Attorney. Reference is made to page II-5.
27.1** Financial Data Schedule.
</TABLE>
- ------------------------------
** Previously filed.
+ Portions omitted pursuant to a request of confidentiality filed separately
with the Commission.
(b) FINANCIAL STATEMENT SCHEDULES.
All other schedules are omitted because they are not required, they are not
applicable or the information is already included in the financial statements or
notes thereto.
II-3
<PAGE> 5
ITEM 17. UNDERTAKINGS.
The undersigned Registrant hereby undertakes to provide the Underwriters at
the closing specified in the Underwriting Agreement certificates in such
denominations and registered in such names as required by the Underwriters to
permit prompt delivery to each purchaser.
Insofar as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers, and controlling persons of the
Registrant pursuant to the provisions described in Item 14 or otherwise, the
Registrant has been advised that in the opinion of the Securities and Exchange
Commission such indemnification is against public policy as expressed in the
Securities Act and is, therefore, unenforceable. In the event that a claim for
indemnification against such liabilities (other than the payment by the
Registrant of expenses incurred or paid by a director, officer, or controlling
person of the Registrant in the successful defense of any action, suit, or
proceeding) is asserted by such director, officer, or controlling person in
connection with the securities being registered, the Registrant will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by it is against public policy as expressed in the Securities
Act and will be governed by the final adjudication of such issue.
The undersigned Registrant hereby undertakes that: (1) for purposes of
determining any liability under the Securities Act, the information omitted from
the form of prospectus as filed as part of the registration statement in
reliance upon Rule 430A and contained in the form of prospectus filed by the
Registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities Act
shall be deemed to be part of the registration statement as of the time it was
declared effective, and (2) for the purpose of determining any liability under
the Securities Act, each post-effective amendment that contains a form of
prospectus shall be deemed to be a new registration statement relating to the
securities offered therein, and this offering of such securities at that time
shall be deemed to be the initial bona fide offering thereof.
II-4
<PAGE> 6
SIGNATURES
Pursuant to the requirements of the Securities Act of 1933, the Registrant
has caused this Amendment to the Registration Statement to be signed on its
behalf by the undersigned, thereunto duly authorized, in the City of Palo Alto,
County of Santa Clara, State of California, on the twenty-eighth day of January,
1997.
COULTER PHARMACEUTICAL, INC.
By: /s/ MICHAEL F. BIGHAM
------------------------------------
Michael F. Bigham
President and Chief Executive
Officer
(Principal Executive Officer)
Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed below by the following persons in the
capacities and on the dates indicated.
II-5
<PAGE> 7
<TABLE>
<CAPTION>
SIGNATURE TITLE DATE
- ------------------------------------- ---------------------------------- ------------------
<C> <S> <C>
/s/ MICHAEL F. BIGHAM President, Chief Executive Officer January 28, 1997
- ------------------------------------- and Director (Principal
Michael F. Bigham Executive Officer)
/s/ WILLIAM G. Vice President and Chief Financial January 28, 1997
HARRIS* Officer (Principal Financial and
- ------------------------------------- Accounting Officer)
William G. Harris
/s/ BRIAN ATWOOD* Director January 28, 1997
- -------------------------------------
Brian Atwood
/s/ DONALD L. Director January 28, 1997
LUCAS*
- -------------------------------------
Donald L. Lucas
/s/ ROBERT Director January 28, 1997
MOMSEN*
- -------------------------------------
Robert Momsen
/s/ ARNOLD ORONSKY* Director January 28, 1997
- -------------------------------------
Arnold Oronsky
/s/ SUE Director January 28, 1997
VAN*
- -------------------------------------
Sue Van
/s/ GEORGE J. SELLA, Director January 28, 1997
JR.*
- -------------------------------------
George J. Sella, Jr.
/s/ JOSEPH R. Director January 28, 1997
COULTER*
- -------------------------------------
Joseph R. Coulter, III
*By: /s/ MICHAEL F. BIGHAM
- -------------------------------------
Michael F. Bigham
Attorney-in-Fact
</TABLE>
II-6
<PAGE> 8
EXHIBIT 23.1
CONSENT OF ERNST & YOUNG LLP, INDEPENDENT AUDITORS
We consent to the reference to our firm under the captions "Selected
Consolidated Financial Data" and "Experts" and to the use of our report dated
October 31, 1996 (except for Note 10, as to which the date is January 24, 1997)
with respect to the consolidated financial statements of Coulter Pharmaceutical,
Inc. and our report dated November 27, 1996 with respect to the Antibody
Therapeutics Business Operations of Coulter Corporation, in Amendment No. 3 to
the Registration Statement (Form S-1) and related Prospectus of Coulter
Pharmaceutical, Inc. for the registration of 2,875,000 shares of its common
stock.
/s/ Ernst & Young LLP
Palo Alto, California
January 24, 1997
II-7
<PAGE> 9
INDEX TO EXHIBITS
<TABLE>
<CAPTION>
SEQUENTIALLY
EXHIBIT NUMBERED
NUMBER DESCRIPTION OF DOCUMENT PAGE
- ------- ----------------------------------------------------------------------
<C> <S> <C>
1.1** Form of Underwriting Agreement........................................
3.1** Amended and Restated Certificate of Incorporation of the Registrant...
3.2** Form of Amendment to Certificate of Incorporation to be filed prior to
the offering..........................................................
3.3** Form of Amended and Restated Certificate of Incorporation of the
Registrant to be filed upon the closing of the offering...............
3.4** Bylaws of the Registrant..............................................
3.5** Bylaws of the Registrant to be effective upon the closing of the
offering..............................................................
4.1 Reference is made to Exhibits 3.1 through 3.5.........................
4.2** Specimen stock certificate............................................
4.3** Amended and Restated Investors' Rights Agreement, dated April 18,
1996, between the Registrant and certain investors....................
4.4** Warrant Agreement to purchase Common Stock, dated December 6, 1996,
between the Registrant and Lease Management Services, Inc. ...........
5.1** Opinion of Cooley Godward LLP.........................................
10.1** Form of Indemnity Agreement to be entered into between the Registrant
and its officers and directors........................................
10.2** 1996 Equity Incentive Stock Option Plan...............................
10.3** Form of Equity Incentive Stock Option.................................
10.4** Form of Nonstatutory Stock Option.....................................
10.5** 1996 Employee Stock Purchase Plan.....................................
10.6** Assignment Agreement, dated February 24, 1995, between the Registrant,
Coulter Corporation and certain investors.............................
10.7 + Manufacturing Agreement, dated August 20, 1996, between Lonza
Biologics PLC and the Registrant......................................
10.8** Equipment Lease Financing Agreement, dated December 6, 1996, between
the Registrant and Lease Management Services, Inc. ...................
10.9 +** First Amendment to Manufacturing Agreement, dated November 21, 1996,
by and between Lonza Biologics PLC and the Registrant.................
10.10+** Development Agreement, dated November 15, 1995, by and between Nordion
International, Inc. and the Registrant................................
10.11+** Patent License Agreement, dated March 15, 1996, by and between the
Region Wallone, the Universite Catholoique de Louvain and Coulter
Pharma Belgium, SA....................................................
11.1** Statement regarding computation of loss per share.....................
21.1** Subsidiaries of the Registrant........................................
23.1 Consent of Ernst & Young LLP. Reference is made to page II-7..........
23.2** Consent of Cooley Godward LLP. Reference is made to Exhibit 5.1.......
24.1 Power of Attorney. Reference is made to page II-5.....................
27.1** Financial Data Schedule...............................................
</TABLE>
- ------------------------------
** Previously filed.
+ Portions omitted pursuant to a request of confidentiality filed separately
with the Commission.
<PAGE> 1
EXHIBIT 10.7
THIS AGREEMENT IS MADE THE 20th day of August 1996
BETWEEN
LONZA BIOLOGICS PLC (formerly known as Celltech Biologics plc) of 228 Bath Road,
Slough, Berkshire SL 1 4DY, England (hereinafter referred to as "Lonza"),
AND
COULTER PHARMACEUTICAL, INC. of 550, California Avenue, Suite 200, Palo Alto, CA
94306-1440, USA (hereinafter referred to as the "Customer").
WHEREAS
A. Customer is the proprietor of a murine hybridoma cell line known as
Bl, which produces IgG2a Anti-CD20 murine monoclonal antibody; and
B. Lonza has expertise in the development of manufacturing processes using
such cell lines; and
C. Customer and Lonza have entered into an agreement dated 28 April 1995
which, as subsequently amended, is herein referred to as the
"Evaluation Agreement" to carry out a programme of work to evaluate the
growth and productivity of cell line B1 in Lonza's proprietary
hybridoma media and develop a cell culture process for the cell line ;
and
D. Under the Evaluation Agreement, a sub-clone of cell line B1 known as
B1R1 was developed, and the parties agreed that this sub-clone be used
for completion of services under the Evaluation Agreement; and
E. Customer now requires Lonza to perform further Services relating to the
Cell Line as described in this Agreement.
NOW THEREFORE it is hereby agreed by and between the parties as follows:
1. In this agreement, its recitals and Schedules hereto, words and phrases
defined in the Standard Terms for Contract Services set out in Schedule
5 hereto shall have the meanings set out therein.
2. Subject to the Standard Terms for Contract Services set out in Schedule
5 hereto and the Special Terms set out in Schedule 4 Lonza agrees to
carry out the Services and the Customer agrees to pay the Price as
provided in Schedule 3 together with any additional costs and expenses
that fall due hereunder.
1.
<PAGE> 2
3. 3.1 Any notice or other communication to be given under this Agreement
shall be delivered personally or sent by first class pre-paid post or
facsimile transmission addressed as follows:
If to the Customer to Coulter Pharmaceutical, Inc.
550 California Avenue
Suite 200
Palo Alto
CA 94306-1440
USA
For the attention of: Vice President, R&D
Facsimile: 415 842 7303
If to Lonza to Lonza Biologics plc
228 Bath Road
Slough
Berkshire SLI 4DY
England
For the attention of: Chief Executive
Facsimile: 01753 777001
or to such other destination as either party hereto may
hereafter notify to the other in accordance with the
provisions of this clause.
3.2 All such notices or other communications shall be deemed to have been
served as follows:
3.2.1 if delivered personally, at the time of such delivery;
3.2.2 if sent by first class pre-paid post, five (5) business days
(Saturdays, Sundays and Bank or other public holidays
excluded) after being placed in the post;
3.2.3 if sent by first class pre-paid post, five (5) business days
(Saturdays, Sundays and Bank or other public holidays
excluded) after being placed in the post;
3.2.4 if sent by facsimile upon receipt of the transmission
confirmation slip showing completion of the transmission
3.2.5 if by express mail or by courier within two (2) days after
being despatched.
2.
<PAGE> 3
AS WITNESS the hands of the duly authorised representatives of the parties
hereto the day and year first before written
Signed for and on behalf of /s/ SIMON STURGE
LONZA BIOLOGICS PLC ------------------------------
CEO
------------------------------
Title
Signed for and on behalf of /s/ MICHAEL F. BIGHAM
COULTER PHARMACEUTICAL, INC. ------------------------------
President and CEO
------------------------------
Title
3.
<PAGE> 4
SCHEDULE 1
For the purposes of this Agreement:
"Cell Line" shall mean the mouse hybridoma cell line referred to as B1R1
recloned by Lonza from cell line B1 supplied by Customer.
"Product" shall mean the IgG2a anti-CD20 murine monoclonal antibody produced by
the Cell Line.
A. SPECIFICATION FOR BULK PURIFIED PRODUCT
[*]
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
4.
<PAGE> 5
[*]
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
5.
<PAGE> 6
[*]
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
6.
<PAGE> 7
[*]
*Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
7.
<PAGE> 8
B. SPECIFICATION FOR A MASTER OR WORKING CELL BANK
[*]
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
8.
<PAGE> 9
SCHEDULE 2
SERVICES
1. Supply of Customer Materials and Customer Information.
2. Activities to be undertaken by Lonza:
Stage 1 Master, Working and Extended Cell Bank Creation and Analysis
Stage 2 Purification Development
Stage 3 Production of Product at Pilot Scale
Stage 4 GMP Documentation
Stage 5 Production of Product to GMP at 2000 litre scale
Stage 6 Manufacturing and Control Data Packages
1. SUPPLY OF CUSTOMER MATERIALS AND CUSTOMER INFORMATION
(a) The Customer has supplied to Lonza the following:
i At least [*] containing approximately
[*].
ii A reference standard of Product for Process
development studies and for bulk purified Product
release testing.
(b) The Customer shall supply to Lonza the following:
i Information and materials including standards and a
typical [*].
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
9.
<PAGE> 10
2. ACTIVITIES TO BE UNDERTAKEN BY LONZA.
1. Stage 1 Master, Working and Extended Cell Bank Creation and
Analysis.
1.1 Objective
To create and characterise a master cell bank (MCB), working
cell bank (WCB), and an extended cell bank (ECB) from cells
grown on from the WCB.
1.2 Activities
1.2.1 Send ampoules of the [*] to Testing Laboratories,
for [*] testing [*] testing and [*] analysis.
1.2.2 Prepare documentation, as approved by Lonza's QA
Department for the preparation of the cell banks.
Establish a [*] and [*] according to the principles
of GMP. The MCB will be derived from [*] and the WCB
will be derived from [*]. The cell banking system
was designed to meet the requirements of the [*] and
the [*].
1.2.3 Establish standard maintenance, storage and release
procedures for the MCB and WCB on and off the Lonza
site.
1.2.4 Characterise the MCB and WCB:
- Assess [*].
- For each cell bank, assess cell bank
viability from [*] distributed
throughout the bank.
- Assess [*]
*Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
10.
<PAGE> 11
- Practice following the guidelines of the UK
GLP Compliance Programme).
- Characterise the Product following [*].
- Evaluate growth of cells from the MCB and
WCB following Lonza's [*].
- Prepare an [*].
1.2.5 Issue report of activities to the Customer. The
report shall include:
- a description of preparation of the cell
banks;
- a history of the Cell Line at Lonza;
- [*];
- an assessment of stability of Product [*];
- details of cell growth characteristics for
the Cell Line i.e. [*];
- details of materials and methods used for
activities under sections 1.2.2, 1.2.3 and
1.2.4;
- a summary of Lonza's storage and control
procedures for the cell banks.
- Testing Laboratory Reports (as described in
section 1.2. 1).
1.3 Cell Bank Characterisation
Additional cell bank characterisation will be required in order to
support regulatory applications to conduct clinical trials, or market
Product. Lonza can arrange for such testing at Lonza's approved
contractors on the Customer's behalf on terms to be agreed or
alternatively deliver ampoules of the Cell Line to the Customer so that
the Customer can have the appropriate tests completed.
*Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
11.
<PAGE> 12
1.4 Timescale
Stage 1 may commence as soon as the [*]. Therefore, if requested by the
Customer, Stage 1 can commence before completion of the stability tests
undertaken in activity 1.2.5 of the Evaluation Agreement, on the
understanding that the Customer will pay for all work undertaken by
Lonza under Stage 1 in the event that the Cell Line is shown
subsequently to be unstable and the Customer decides to terminate the
Contract in accordance with Schedule 5 Clause 9.1.
Stage 1 shall be complete with the issue of the report of activities
and it is estimated that this [*] from the start of Stage 1. It is
estimated that the [*] will be established [*] from the start of
Stage 1, the [*] will be established [*] from the start of Stage 1 and
the ECB will be established [*] from the start of Stage 1.
2. Stage 2 Purification Development
2.1 Objective
To establish a purification process suitable for manufacture of the
Product.
2.2 Activities
2.2.1 Either carry out a [*], or use [*].
2.2.2 [*].
2.2.3 Determine the [*].
2.2.4 Evaluate [*].
2.2.5 [*].
*Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
12.
<PAGE> 13
2.2.6 For each [*].
2.2.7 [*].
2.2.8 [*].
2.2.9 Deliver a sample of Product produced at laboratory scale to
the Customer for evaluation.
2.2.10 Issue a report of activities to the Customer. This report will
include the following information:
- step yields for each chromatography and buffer exchange
operation;
- copies of SDS-PAGE, IEF and HPLC analysis results;
- materials and methods used for activities under Stage
2;
- an outline of the recommended manufacturing process
including an estimate of the expected yield for the
Product at the chosen production scale.
2.3 Timescale
Stage 2 shall be complete with the issue of the report of activities
(section 2.2.10) and it is estimated that this report will be issued
[*] from the start of Stage 2.
Stage 2 may commence as soon as the [*] is available (activity 1.2.4
of the Evaluation Agreement).
3. Stage 3 Production of Product at Pilot Scale.
3.1 Objective
3.1.1 To [*].
*Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
13.
<PAGE> 14
3.1.2 To evaluate the ability of the Process to produce Product
that meets key parameters of the draft Specification.
3.2 Activities
3.2.1 [*].
3.2.2 [*].
3.2.3 [*].
3.2.4 [*].
3.2.5 Test Product against the following aspects of the draft
Specification:
[*].
3.2.6 Review requirements (if any) for Process modifications in
order to meet Specification for GMP manufacture of subsequent
batches and advise Customer of any proposed modifications.
3.2.7 Deliver Product to Customer. Quantities available depend on
the amount of Product required for activities 3.2.3-3.2.5.
3.3 Timescale
Stage 3 shall be complete upon delivery of Product to the Customer. It
is estimated that Product will be delivered [*] from commencement of
Stage 3.
4. Stage 4 GMP Documentation.
4.1 Objective
To prepare GMP documentation for use in manufacture of Product for
Phase II/III clinical trials.
Note: The process cannot be considered as fully optimised.
4.2 Activities
*Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
14.
<PAGE> 15
4.2.1 Prepare documentation approved by Lonza's QA department. The
documentation shall cover:
- Cell Banking.
[*].
- Materials specifications (as required).
- Sampling protocols.
- Product specifications.
4.3 Timescale
It is estimated that Stage 4 will take [*] from the commencement of
work and shall be complete on notification by Lonza to the Customer
that the documentation has been approved by Lonza's QA department.
Stage 4 will commence on the establishment of the MCB (Stage 1, section
1.2.2).
5. Stage 5 Production of Product to GMP at 2000 litre scale.
5.1 Objectives
5.1.1 To manufacture [*] batches of Product at 2000 litre scale in
an airlift fermenter in accordance with the principles of Good
Manufacturing Practice (GMP) it being understood and
acknowledged that the Customer intends that these batches
serves as manufacturing consistency batches to support a
Biologics Licence Application and/or an EMEA marketing
authorisation request.
5.1.2 To evaluate further the ability of the Process to produce
Product meeting the draft Specification.
5.2 Activities
Subject to first agreeing with the Customer any Process modifications
advised by Lonza under Stage 3 activity 3.2.6, Lonza shall carry out
the following activities for each of the [*] batches:
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
15.
<PAGE> 16
5.2.1 After receiving adequate [*].
5.2.2 [*].
5.2.3 [*].
5.2.4 [*].
5.2.5 [*].
5.2.6 Test Product against the draft Specification.
5.2.7 Undertake Quality Assurance review of lot documentation.
5.2.8 Review requirements (if any) for Process modifications in
order to meet Specification for manufacture of subsequent
batches. Any such Process modifications are subject to
agreement prior to implementation.
5.2.9 Issue lot release for Product.
5.2.10 Deliver Product to Customer.
5.3 Timescale
Stage 5 shall be complete upon delivery of the [*] batch of Product
to the Customer. It is estimated that Product from the first batch will
be delivered six (6) months from commencement of Stage 5.
6. Stage 6 Manufacturing and Control Data Packages.
6.1 Objective
To prepare Manufacturing and Control Data Packages ("data packages")
covering the work carried out in the Evaluation Agreement and in Stages
1-5 of this Agreement for submission to the Customer as an amendment to
the appropriate sections of the Customer's existing IND and CTX
documents.
6.2 Activities
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
16.
<PAGE> 17
6.2.1 Prepare data packages, as required by the Customer, for the
purpose of submission as amendments to the appropriate
sections of the Customers' existing IND and CTX documents.
The data packages will cover the items detailed in Appendices
1 and of this schedule.
For Product Licence, specific DNA and virus clearance
studies, plus bulk Product stability studies will be required,
which are outside the scope of this Agreement.
6.2.2 Submit amendments to the Customer.
6.3 Timescale
Stage 6 shall be complete with the submission of amendments to the
Customer, and that activity will be complete [*] from the
commencement of Stage 6.
Note: Additional cell bank characterisation is in addition to Stage 1
of the Services and to be agreed between Lonza and Customer.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
17.
<PAGE> 18
APPENDIX 1 TO SCHEDULE 2
Manufacturing and Control Data Packages
(USA - Type II Drug Master File)
INDEX
1. Production and Control Information
1.1 Facilities: refer to BB-MF 2500
1.2 Flow diagram of production process
1.3 Starting Materials
1.3.1 Raw Materials
1.3.2 Preparation and testing of cell banks
1.3.2.1 Construction and serum free adaptation of cell
lines
1.3.2.2 Preparation, derivation and description of cell
banks
1.3.2.3 Cell bank testing
1.4 Manufacture of bulk product
[*]
2. Product Testing and Final Release
2.1 In process testing procedures
2.2 Final product testing and release
2.2.1 Final product specification
2.2.2 Test methods
2.2.3 Lot release
2.2.4 Photographs: IEF, SDS-PAGE and HPLC scans
2.3 Environmental monitoring
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
18.
<PAGE> 19
3. Process Development
3.1 Development of cell lines
3.2 Development of fermentation process
3.3 Development of purification process
4. Process Validation
4.1 DNA and virus clearance
4.2 Removal of protein contaminants
5. Stability and Expiration (if available)
6. Attachments
6.1 Construction of the cell line and serum free adaptation
6.2 Preparation and analysis of cell banks
6.3 DNA and virus clearance reports
6.4 Lot analysis
6.5 Environmental impact policy
6.6 Index to DMF Type 1 BB-MF 2500
6.7 Letter of authorisation to reference BB-MF 2500
19.
<PAGE> 20
APPENDIX 2 TO SCHEDULE 2
Manufacturing and Control Data Packages
(Europe - CTX APPLICATION)
Part II C. Control of Starting Materials
1. Active Ingredient
1.1 Specifications and routine tests
1.1.1 Specifications
1.1.2 Routine test methods
1.2 Nomenclature
1.3 Development Genetics
1.3.1 Fusion and cloning of the cell line.
1.3.2 Stability of cell line
1.4 Cell Bank System
1.4.1 Preparation and description of the cell banks
[*]
1.5 Manufacture
1.5.1 Manufacture site
1.5.2 Flow diagram of process
1.5.3 Process description
1.5.4 Quality Control during manufacture
1.5.4.1 Control of starting materials
1.5.4.2 In process controls
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
20.
<PAGE> 21
1.5.4.3 Environmental monitoring
1.6 Description and proof of structure
1.7 Analytical Development
1.7.1 Validation of relevant methods using during development
1.7.2 Validation and comments on the choice of routine tests
1.7.3 Characterisation of the reference material
1.8 Process validation
1.8.1 Viral clearance data
1.8.2 DNA clearance data
1.9 Impurities
1.9.1 Recognised potential impurities arising from the cell line
or during the manufacturing process
1.9.2 Analytical methods used to detect impurities and their
limits of detection
1.9.3 Consistency of the impurity profile
1.10 Batch Analysis
(Stability in part II-F)
21.
<PAGE> 22
SCHEDULE 3
PRICE AND TERMS OF PAYMENT
1. Price
In consideration for Lonza carrying out the Services as detailed in
Schedule 2 the Customer shall pay Lonza as follows:
Stage Price ((pound) Sterling)
----------------------------------------------------------------------
Stage 1 Master, Working and Extended Cell [*]
Bank Creation and Analysis
External Testing of Pre-Seed Stock [*]
Stage 2 Purification Process Development [*]
Stage 3 Production of Product at Pilot Scale [*]
Stage 4 GMP Documentation [*]
Stage 5 Production of Product to GMP at [*]
2000 litre scale x [*] batches
Stage 6 Manufacturing and Control Data
Packages [*]
---------
TOTAL PRICE (Pound Sign) 2,149,000
Note:
1 These prices do not include testing of the cell banks. Lonza can
arrange testing of cell banks at an additional price comprising the
cost charged to Lonza by the Testing Laboratories plus a [*]
administration charge.
2 The price for Stage 5 does not include specific virus or DNA clearance
studies on the GMP batch. A list of the recommended further work
required for BLA submission is available from Lonza.
3 (a) Without prejudice to Clause 4 of Schedule 5 hereto, and
subject to the
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
22.
<PAGE> 23
provisions set out below Lonza shall be entitled to receive an
additional payment for Services performed pursuant to Stage 3
of the Services as follows:
i. the event that Lonza notifies the Customer that
Product deliverable pursuant to Stage 3.2.7 of the
Services is ready for delivery to Customer on or
before 21 March 1996, the Price for Stage 3 of the
Services shall be increased by [*], which additional
sum shall be due to Lonza concurrently with the
payment due pursuant to Clause 2.1.3 of this
Schedule 3.
ii. In the event that Lonza notifies the Customer that
Product deliverable pursuant to Stage 3.2.7 of the
Services is ready for delivery to Customer after 21
March 1996 but before 19 April 1996, the Price for
Stage 3 of the Services shall be increased by [*],
which additional sum shall be due to Lonza
concurrently with the payment due pursuant to
Clause 2.1.3 of this Schedule 3.
(b) Without prejudice to Clause 4 of Schedule 5 hereto and subject
to the provisions set out below Customer shall be entitled to
a credit against the sums due to Lonza for performance of
Stage 3 of the Services as follows:
i. In the event that Lonza notifies the Customer that
Product deliverable pursuant to Stage 3.2.7 of the
Services is ready for delivery to Customer after 13
June 1996 but before 13 July 1996, the credit against
the Price of Stage 3 of the Services to which
Customer shall be entitled shall be [*].
ii. In the event that Lonza notifies the Customer that
Product deliverable pursuant to Stage 3.2.7 of the
Services is ready for delivery to Customer on or
after 13 July 1996, the credit against the Price of
Stage 3 of the Services to which Customer shall be
entitled shall be [*].
4. (a) Without prejudice to Clause 4 of Schedule 5 hereto, and
subject to the provisions set out below Lonza shall be
entitled to receive an additional payment for Services
performed pursuant to Stage 5 of the Services as follows:
i. In the event that Lonza notifies the Customer that
Product deliverable from the first batch to be
delivered pursuant to Stage 5.2.9 of the Services is
ready for delivery to Customer on or before 11 July
1996, the Price for Stage 5 of the Services for the
first batch
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
23.
<PAGE> 24
to be delivered shall be increased by [*], which
additional sum shall be due to Lonza concurrently
with the payment due pursuant to Clause 2.1.5(a)
of this Schedule 3.
ii. In the event that Lonza notifies the Customer that
Product deliverable from the first batch to be
delivered pursuant to Stage 5.2.9 of the Services for
the first batch to be delivered is ready for delivery
to Customer after 11 July 1996 but before 9 August
1996, the Price for Stage 5 of the Services shall be
increased by [*], which additional sum shall be due
to Lonza concurrently with the payment due pursuant
to Clause 2.1.5(a) of this Schedule 3.
(b) Without prejudice to Clause 4 of Schedule 15 hereto and
subject to the provisions set out below Customer shall be
entitled to a credit against the sums due to Lonza for
performance of Stage 5 of the Services as follows:
i. In the event that Lonza notifies the Customer that
Product deliverable from the first batch to be
delivered pursuant to Stage 5.2.9 of the Services is
ready for delivery to Customer after 3 October 1996
but before 1st November 1996, the credit against the
Price of Stage 5 of the Services to which Customer
shall be entitled for the first batch to be delivered
shall be [*].
ii. In the event that Lonza notifies the Customer that
Product deliverable from the first batch to be
delivered pursuant to Stage 5.2.9 of the Services is
ready for delivery to Customer on or after 1st
November 1996, the credit against the Price of Stage
5 of the Services to which Customer shall be entitled
for the first batch to be delivered shall be [*].
2. Payment
2.1 Payment by the Customer of the Price for each stage shall be
made against Lonza's invoices to be dated as of the first date
Lonza is entitled to payment in each case, as follows:
2.1.1 For Stage 1
[*] upon commencement of Stage 1.
[*] upon completion of Stage 1.
2.1.2 For Stage 2
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
24.
<PAGE> 25
[*] upon commencement of Stage 2.
[*] upon completion of Stage 2.
2.1.3 For Stage 3
[*] upon delivery of Product.
2.1.4 For Stage 4
[*] on completion of Stage 4.
2.1.5 For Stage 5
(a) [*] on lot release of the first batch of
Product from 2000 litre fermenter;
(b) [*] on lot release of the [*] batch of
Product from 2000 litre fermenter,
(c) [*] on lot release of the [*] batch of
Product from 2000 litre fermenter.
2.1.6 For Stage 6
[*] on issue of Manufacturing Data Packages.
2.2 Payment or credit of any amounts due pursuant to Notes 3 and 4
of Clause 1 of this Schedule 3 shall be made as therein
provided.
2.3 For any payment due and made by the Customer before 31 March
1997, the Customer may, at its option, make payment to Lonza
in US Dollars, such amount to be calculated at a currency
exchange rate of US$1.55: 1.00 pounds sterling. All payments
made after 31 March 1997 shall be made in Pounds Sterling
unless otherwise agreed.
For the avoidance of doubt, where any additional payment or
credit is due pursuant to Notes 3 and 4 of Clause 1 of this
Schedule 3 at the same time as any payment is made pursuant to
Clause 2.1 of this Schedule 3, the said additional payment or
credit shall be accounted for in the same currency as for the
payment made pursuant to the said Clause 2.1.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
25.
<PAGE> 26
SCHEDULE 4
SPECIAL TERMS
1. Definitions of GMP and GLP
1.1 Definition of GMP
For the purposes of this document, Good Manufacturing Practice
(GMP) will mean Good Manufacturing Practices and General
Biological Products Standards as promulgated under the US
Federal Food and Drug and Cosmetic Act at 21CFR, (chapters
210, 211, 600 and 610) and the Commission of the European
Communities Rules Governing Medicinal Products in the European
Community (Volume IV : Good Manufacturing Practice for
Medicinal Products, 1992) as the same may be amended or
re-enacted from time to time. Lonza's operational quality
standards are defined in internal GMP policy documents and are
based on Lonza's interpretation of the GMP legislation for
bulk clinical grade Biologicals. Additional product-specific
development, documentation and validation work may be required
to support regulatory applications to conduct clinical trials,
or market a product.
1.2 Definition of GLP
For the purposes of this document Good Laboratory Practice
(GLP) will mean practices as recommended in the guidelines of
the UK Compliance Programme.
2. Cell-Bank Access
Always provided Lonza's ability to perform the Services is not
prejudiced thereby, the Customer's authorised representative may have
access at times to be reasonably agreed to the banks containing the
Cell Line at Lonza's premises and may remove all or part of said cell
banks, as required.
3. Technology Transfer
At the Customer's request, Lonza agrees to enter into good faith
negotiations for the grant of a non-exclusive licence to the Customer
on commercially reasonable terms to manufacture Product under certain
Patent Rights and Lonza Know-How. Such grant shall be subject to
agreement on applicable terms and conditions and shall apply only to
Patent Rights and Lonza Know-How used by Lonza in the
26.
<PAGE> 27
operation of the Process for production of Product to GMP (Schedule 2
Stage 5) and only to the extent Lonza is able to grant a licence
thereto at the time of signature of such agreement.
For the avoidance of doubt the Patent Rights and Lonza Know-How which
may be the subject of any such licence grant shall be limited to the
Patent Rights and Lonza Know-How used by Lonza in the operation of the
Process for production of Product to GMP (Schedule 2 Stage 5) and
relating to [*].
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
27.
<PAGE> 28
SCHEDULE 5
STANDARD TERMS FOR CONTRACT SERVICES
COULTER PHARMACEUTICAL, INC.
1. Interpretation
1.1 In these Standard Terms, unless the context requires
otherwise:
1.1.1 "Affiliate" means any Company, partnership or other
entity which directly or indirectly controls, is
controlled by or is under common control with the
relevant party to this Agreement. "Control" means the
ownership of more than 50% of the issued share
capital or the legal power to direct or cause the
direction of the general management and policies of
the party in question.
1.1.2 "Agreement" means this agreement as herein dated
between Lonza and a Customer incorporating these
Standard Terms.
1.1.3 "Cell Line" has the meaning set forth in Schedule 1.
1.1.4 "Customer" means Coulter Pharmaceutical, Inc. of 550,
California Avenue, Suite 200, Palo Alto, CA
94306-1440, USA.
1.1.5 "Customer Information" means all technical and other
information, relating to the Cell Line, the Process
and the Product disclosed by the Customer to Lonza,
and not known to Lonza prior to disclosure by the
Customer.
1.1.6 "Customer Tests" means the tests to be carried out on
the Product following receipt of the Product by the
Customer, particulars of which are set out in
Schedule 1.
1.1.7 "Lonza Know-How" means all technical and other
information relating to the Process known to Lonza
from time to time other than Customer Information.
1.1.8 "Patent Rights" means all patents and patent
applications of any kind throughout the world
relating to the Process which from time to time Lonza
is the owner of or (except for any patents and patent
applications owned by the Customer or licensed to the
Customer by third party and licensed to Lonza
hereunder) is entitled to use.
28.
<PAGE> 29
1.1.9 "Price" means the price specified in Schedule 3 for
the Services.
1.1.10 "Process" means the process developed or utilized by
Lonza under this Agreement for the production of the
Product from the Cell Line, including any
improvements thereto from time to time.
1.1.11 "Product" has the meaning set forth in Schedule 1.
1.1.12 "Services" means all or any part of the services the
subject of the Agreement (including, without
limitation, cell culture evaluation, purification
evaluation, master, working and extended cell bank
creation, and sample and bulk production),
particulars of which are set out in Schedule 2.
1.1.13 "Special Term" means any term additional or
supplemental to these Standard Terms from time to
time agreed in writing between Lonza and the
Customer. Particulars of any Special Terms at the
date of the Agreement are set out in Schedule 4.
1.1.14 "Specification" means the specification for Product,
particulars of which are set out in Schedule 1.
1.1.15 "Terms of Payment" means the terms of payment
specified in Schedule 3.
1.1.16 "Testing Laboratories" means any third party
instructed by Lonza to carry out tests on the
Cell Line or the Product.
1.2 Unless the context requires otherwise, words and phrases
defined in any other part of the Agreement shall bear the same
meanings in these Standard Terms, references to the singular
number include the plural and vice versa, references to
Schedules are references to schedules to the Agreement, and
references to Clauses are references to clauses of these
Standard Terms.
1.3 In the event of a conflict between any of the terms of
Schedules 1-4 and these Standard Terms, the terms of Schedules
1-4 shall prevail.
2. Applicability of Standard Terms
No variation of or addition to these Standard Terms and the Special
Terms or any other term of an Agreement shall be effective unless in
writing and signed for and on behalf of Lonza and the Customer.
29.
<PAGE> 30
3. Supply of the Cell Line
3.1 Prior to the date of the Agreement the Customer supplied to
Lonza the Customer Information, together with cell line B1 and
full details of any hazards known to Customer and relating to
cell line B1, its storage and use. Property in the cell Line
B1 and the Cell Line supplied to Lonza shall remain vested in
the Customer.
3.2 The Customer hereby grants Lonza the non-exclusive right to
use the Cell Line, the Product and the Customer Information
for the purpose of the Agreement. Lonza hereby undertakes not
to use the Cell Line, the Product or the Customer Information
(or any part thereof) for any other purpose.
3.3 Lonza shall :
3.3.1 at all times keep the Cell Line secure and safe from
loss and damage in such manner as Lonza shall in its
sole discretion determine:
3.3.2 not part with possession of the Cell Line or the
Product, save for the purpose of tests at the Testing
Laboratories; and
3.3.3 procure that all Testing Laboratories are subject to
obligations of confidence substantially in the form
of those obligations of confidence imposed on Lonza
under these Standard Terms.
3.4 Lonza shall not be liable for any loss, damages, costs or
expenses of any nature, whether direct or consequential,
occasioned by the carrying out (in whole or in part) of tests
or the failure to carry out tests by Testing Laboratories (A
"Testing Laboratory Breach"). Lonza agrees to use commercially
reasonable efforts to enforce any rights Lonza may have
against a Testing Laboratory in the event that either Lonza or
the Customer supers any loss, damage, costs or expenses of any
nature occasioned by a Testing Laboratory Breach. In the event
Lonza recovers damages against a Testing Laboratory Lonza
shall pay to the Customer after deduction of any out-of-pocket
legal expenses such proportion of the amount of damages as the
parties shall agree and such agreement shall take account of
the loss suffered by both Lonza and the Customer.
3.5 The Customer warrants to Lonza that:
3.5.1 the Customer is and shall at all times throughout the
duration of the Agreement remain entitled to supply
the Cell Line and Customer Information to Lonza; and
30.
<PAGE> 31
3.5.2 the use by Lonza of the Cell Line and the Customer
Information in accordance with this Agreement will
not infringe any rights (including, without
limitation, any intellectual or industrial property
rights) vested in any third party.
Lonza warrants that as of the date of this Agreement Lonza's
legal or corporate departments have not received notice of nor
are aware of any claim or demand and Lonza is not party to any
court proceedings in which a third party is claiming
infringement of its intellectual property rights by Lonza's
use of the Process and Lonza agrees to notify the Customer at
any time during the term of this Agreement if it receives any
such notice or demand and of the steps it intends to take as a
result of such notice or demand.
3.6 The Customer undertakes to indemnify and to maintain Lonza
promptly indemnified against any loss, damages, costs and
expenses of any nature (including court costs and legal fees
on a full indemnity basis), whether direct or consequential,
and whether or not foreseeable or in the contemplation of
Lonza or the Customer, that Lonza may suffer arising out of or
incidental to any breach of the warranties given by the
Customer under Clause 3.5 above.
3.7 The obligations of the Customer and Lonza under Clauses 3.3,
and 3.6 shall survive the termination for whatever reason of
the Agreement.
4. Provision of the Services
4.1 Lonza shall carry out the Services as provided in Schedule 2.
4.2 The timescales set down for the performance of the Services
(including without limitation the dates for production and
delivery of Product) and the quantities of Product for
delivery set out in Schedule 2 are estimated only.
4.3 The Customer shall not be entitled to cancel any unfulfilled
part of the Services or to refuses to accept the Services on
grounds of late performance, late delivery or failure to
produce the estimated quantities of Product for delivery.
Lonza shall not be liable for any loss, damage, costs or
expenses of any nature, whether direct or consequential,
occasioned by:
4.3.1 any delay in performance or delivery howsoever
caused; or
4.3.2 any failure to produce the estimated quantities of
Product for delivery.
31.
<PAGE> 32
4.4 Lonza shall comply with all statutory, regulatory and similar
legislative requirements from time to time applicable to the
Services under the laws of European Union, United Kingdom and
USA. If the Customer requests Lonza to comply with any other
statutory, regulatory or similar legislative requirements (the
Foreign Requirements") Lonza shall use reasonable commercial
endeavours to do so provided that:
4.4.1 the Customer shall be responsible for informing Lonza
in writing of the precise Foreign Requirements which
the Customer is requesting Lonza to observe;
4.4.2 such Foreign Requirements do not conflict with any
mandatory requirements under the laws of England;
4.4.3 Lonza shall be under no obligation to ensure that
such written information complies with the applicable
Foreign Requirements; and
4.4.4 all costs and expenses incurred by Lonza in complying
with such Foreign Requirements shall be charged to
the Customer in addition to the Price.
4.5 Delivery of Product shall be ex-works. Risk in and title to
Product shall pass on delivery. Transportation of Product,
whether or not under any arrangements made by Lonza on behalf
of the Customer, shall be made at the sole risk and expense of
the Customer.
4.6 Unless otherwise agreed Lonza shall package and label Product
for delivery ex-works. It shall be the responsibility of the
Customer to inform Lonza in writing in advance of any special
packaging and labelling requirements for Product. All
reasonable additional costs and expenses of whatever nature
incurred by Lonza in complying with such special requirements
shall be charged to the Customer in addition to the Price.
5. Transportation of Product and Customer Tests
5.1 If requested by the Customer, Lonza will (acting as agent of
the Customer for such purpose) arrange the transportation of
Product from Lonza's premises to the destination indicated by
the Customer together with insurance cover for Product in
transit at its invoiced value. All additional costs and
expenses of whatever nature incurred by Lonza in arranging
such transportation and insurance shall be charged to the
Customer in addition to the Price.
32.
<PAGE> 33
5.2 Where Lonza has made arrangements for the transportation of
Product, the Customer or its designee shall diligently examine
the Product as soon as practicable after receipt. Notice of
all claims (time being of the essence) arising out of:
5.2.1 damage to or total or partial loss of Product in
transit shall be given in writing to Lonza and the
carrier within three (3) days of delivery; or
5.2.2 non-delivery shall be given in writing to Lonza
within ten (10) days after the date of Lonza's
despatch notice.
5.3 The Customer shall make damaged Product available for
inspection and shall comply with the requirements of any
insurance policy covering the Product notified by Lonza to the
Customer. Lonza shall offer the Customer all reasonable
assistance (at the cost and expense of the Customer) in
pursuing any claims arising out of the transportation of
Product. At any time, if requested by the Customer, Lonza
shall supply the Customer with Product samples retained by
Lonza prior to shipment of Product for use by the Customer in
confirming whether Product meets the Specification (always
provided that such supply of Product samples does not
prejudice Lonza's ability to meet GMP or regulatory
requirements regarding retention of Product samples).
5.4 Immediately upon receipt of Product or Product samples, the
Customer or its appointed agent shall carry out the Customer
Tests. If the Customer Tests show that the Product fails to
meet Specification, the Customer shall give Lonza written
notice thereof within sixty (60) days from the date of
delivery of the Product ex-works, and shall return such
Product to Lonza's premises for further testing. In the
absence of such written notice Product shall be deemed to have
been accepted by the Customer as meeting Specification. If
Lonza is satisfied that Product returned to Lonza fails to
meet Specification and that such failure is not due (in whole
or in pan) to acts, or omissions of the Customer or any third
party after delivery, of such Product ex-works, Lonza shall in
its sole discretion refund that part of the Price that relates
to the production of such Product or replace such Product at
its own cost and expense. Notwithstanding the foregoing, if
the Customer determines following acceptance of the Product
from Lonza that the Product has been adulterated within the
meaning of the United States Federal Food, Drug and Cosmetic
Act by Lonza, then, subject to the Customer providing Lonza
evidence of its determination and samples of adulterated
Product and subject to Lonza's right to dispute such
33.
<PAGE> 34
determination in accordance with Clause 5.5, Lonza shall in
its sole discretion refund that part of the Price that relates
to the production of such Product or replace such Product at
its own cost and expense.
5.5 If there is any dispute concerning whether Product returned to
Lonza fails to meet Specification or whether such failure is
due (in whole or in part) to acts or omissions of the
Customer or any third party after delivery of such Product
ex-works, such dispute shall be referred for decision to an
independent expert (acting as an expert and not as an
arbitrator) to be appointed by agreement between Lonza and the
Customer or, in the absence of agreement by the President for
the time being of the Association of the British
Pharmaceutical Industry. The costs of such independent expert
shall be borne equally between Lonza and the Customer. The
decision of such independent expert shall be in writing and,
save for manifest error on the face of the decision, shall be
binding on both Lonza and the Customer.
5.6 The provisions of Clauses 5.4 and 5.5 shall be the sole remedy
available to the Customer in respect of Product that fails to
meet Specification or that is adulterated.
6. Price and Terms of Payment
6.1 The Customer shall pay the Price in accordance with the Terms
of Payment.
6.2 Unless otherwise indicated in writing by Lonza, all prices and
charges are exclusive of value added tax or of any other
applicable taxes, levies, imports, duties and fees of whatever
nature imposed by or under the authority of any government or
public authority, which shall be paid by the Customer. All
invoices are strictly net and payment must be made within
thirty (30) days of date of invoice. Payment shall be made
without deduction, deferment, set-off, lien or counterclaim of
any nature.
6.3 Time for payment shall be of the essence. In default of
payment on due date:
6.3.1 interest shall accrue on any amount overdue at the
rate of 2% above the Base Rate from time to time of
Midland Bank plc, interest to accrue on a day to day
basis both before and after judgement; and
6.3.2 Lonza shall, at its sole discretion, and without
prejudice to any other of its accrued rights be
entitled to suspend the provision of the Services or
if the default of payment continues for One hundred
and fifty (150) days after the date of invoice to
treat the Agreement as
34.
<PAGE> 35
repudiated by notice in writing to the Customer
exercised at any time thereafter provided that such
right to suspend Services or treat the Agreement as
repudiated shall not apply in circumstances where the
Customer has withheld payment for amounts disputed in
good faith (it being agreed that this proviso shall
apply to disputed amounts and not to any other
amounts due for payment forming part of the same or
another invoice).
7. Warranty and Limitation of Liability
7.1 Lonza warrants that:
7.1.1 the Services shall be performed in accordance with
Clause 4.1; and
7.1.2 the Product shall meet Specification, save with
respect to the first batch of Product delivered
pursuant to Schedule 5 Stage 5 where Lonza shall be
obliged only to use its reasonable endeavours to
produce Product that meets Specification.
7.2 Clause 7.1 is in lieu of all conditions, warranties and
statements in respect of the Services and/or the Product
whether expressed or implied by statute, custom of the trade
or otherwise (including but without limitation any such
condition, warranty or statement relating to the description
or quality of the Product, its fitness for a particular
purpose or use under any conditions whether or not known to
Lonza) and any such condition, warranty or statement is hereby
excluded.
7.3 Without prejudice to the terms of Clauses 3.4, 5.6, 7.1, 7.2
and 7.4 and, subject to Clause 7.6, the liability of Lonza for
any loss or damage suffered by the Customer as a direct result
of any breach of the Agreement or of any other liability of
Lonza (including misrepresentation and negligence) in respect
of the Services (including without limitation the production
and/or supply of the Product) shall be limited to the payment
by Lonza of damages which shall not exceed [*]. The
limitation of liability set forth in the preceding sentence
shall not apply to any breach by Lonza of Clauses 3.2, 8.1,
8.2 and 8.3 of this Schedule 5.
7.4 Subject to Clause 7.6, Lonza shall not be liable for the
following loss or damage howsoever caused (even if foreseeable
or in the contemplation of Lonza or the Customer):
7.4.1 loss of profits, business or revenue whether suffered
by the Customer or any other person; or
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
35.
<PAGE> 36
7.4.2 indirect or consequential lost whether suffered by
the Customer or any other person.
7.5 The Customer shall indemnify and maintain Lonza promptly
indemnified against all claims, actions, costs, expenses
(including court costs and legal fees on a full indemnity
basis) or other liabilities whatsoever in respect of:
7.5.1 any liability under the Consumer Protection Act 1987,
unless, such liability is caused by the negligent act
or omission of Lonza in the production and/or supply
of the Product; and
7.5.2 any product liability (other than that referred to in
Clause 7.5.1) in respect of Product, unless such
liability is caused by the negligent act or omission
of Lonza in the production and/or supply of Product;
and
7.5.3 any negligent or wilful act or omission of the
Customer in relation to the use, processing, storage
or sale of the Product
7.6 Nothing contained in these Standard Terms shall purport to
exclude or restrict any liability for death or personal injury
resulting directly from negligence by Lonza in carrying out
the Services or any liability for breach of the implied
undertakings of Lonza as to title.
7.7 The obligations of the Customer and Lonza under this Clause 7
shall survive the termination for whatever reason of the
Agreement.
8. Customer Information, Lonza Know-How and Patent Rights
8.1 The Customer acknowledges that Lonza Know-How and Lonza
acknowledges that Customer Information with which it is
supplied by the other pursuant to the Agreement is supplied,
subject to Clause 8.4, in circumstances imparting an
obligation of confidence and each agrees to keep such Lonza
Know-How or such Customer Information secret and confidential
and to respect the other's proprietary rights therein and not
at any time for any reason whatsoever to disclose or permit
such Lonza Know-How or such Customer Information to be
disclosed to any third party.
8.2 The Customer and Lonza shall each procure that all their
respective employees, consultants and contractors having
access to confidential Lonza Know-How or confidential Customer
Information shall be subject to the same obligations of
confidence as the principals pursuant to Clause 8.1 and shall
enter into secrecy agreements in support of such obligations.
Insofar as this is not reasonably practicable, the principals
shall take all reasonable
36.
<PAGE> 37
steps to ensure that any such employees, consultants and
contractors are made aware of such obligations.
8.3 Lonza and the Customer each undertake not to disclose or
permit to be disclosed to any third party, or otherwise make
use of or permit to be made use of, any trade secrets or
confidential information relating to the technology, business
affairs or finances of the other, any subsidiary, holding
company or subsidiary or any such holding company of the
other, or of any suppliers, agents distributors, licensees or
other customers of the other which comes into its possession
under this Agreement.
8.4 The obligations of confidence referred to in this Clause 8
shall not extend to any information which :
8.4.1 is or becomes generally available to the public
otherwise than by reason of a breach by the recipient
party of the provisions of this Clause 8;
8.4.2 is known to the recipient party and is at its free
disposal prior to its receipt from the other,
8.4.3 is subsequently disclosed to the recipient party, as
a matter of right without being made subject to an
obligation of confidence by a third party;
8.4.4 Lonza or the Customer may be required to disclose
under any statutory, regulatory, or similar
legislative requirement, subject to the imposition of
obligations of secrecy whether possible in that
relation provided that the party required to make the
disclosure shall first notify the other party who
shall be allowed to take what action he considers
necessary with respect to the proposed disclosure; or
8.4.5 is developed by an employee of the recipient party,
independently and without access to or use or
knowledge of the information supplied by the
disclosing party.
8.5 The Customer acknowledges that:
8.5.1 Lonza Know-How and the Patent Rights are vested in
Lonza or Lonza is otherwise entitled thereto: and
8.5.2 the Customer shall not at any time have any right,
title, licence or interest in or to Lonza Know-How,
the Patent Rights or any other
37.
<PAGE> 38
intellectual property rights relating to the Process
which are vested in Lonza or to which Lonza is
otherwise entitled.
8.6 Lonza acknowledges that, subject to Clause 4.5 above and save
as expressly stated herein. Lonza shall not by virtue of this
Agreement be granted any right, title or interest in the Cell
Line or the Product expressed by the Cell Line.
8.7 The Customer shall not represent that it has any right, title,
or interest in or to Lonza Know-How, the Patent Rights or any
other intellectual property rights vested in Lonza or its
Affiliates and shall not seek or apply to register in its own
name any such rights. The Customer shall do all such acts and
things and sign all such deeds and documents as Lonza may in
its sole discretion reasonably require in respect of any
registration being made by Lonza or its Affiliates in
connection with such rights.
8.8 The obligations of Lonza and the Customer under this Clause 8
shall survive the termination for whatever reason of the
Agreement.
9. Termination
9.1 If it becomes apparent to either Lonza or the Customer at any
stage in the provision of the Services that it will not be
possible to complete the Services for scientific or technical
reasons, a sixty (60) day period shall be allowed for
discussion to resolve such problems. If such problems are not
resolved within such period, Lonza and the Customer shall each
have the right to terminate the Agreement forthwith by notice
in writing.
9.2 Lonza and the Customer may each terminate the Agreement
forthwith by notice in writing to the other upon the
occurrence of any of the following events:
9.2.1 if the other commits a material breach of the
Agreement which (in the case of a breach capable of
remedy) is not remedied within the time permitted
within Clause 6.3.2 for default of payment by the
Customer or otherwise within thirty (30) days of the
receipt by the other of notice identifying the breach
and requiring its remedy; or
9.2.2 if the other ceases for any reason to carry on
business or compounds with or convenes a meeting of
its creditors or has a receiver or manager appointed
in respect of all or any part of its assets or is the
subject of an application for an administration order
or of any proposal for a voluntary arrangement or
enters into liquidation
38.
<PAGE> 39
(whether compulsorily or voluntarily) or undergoes
any analogous act or proceedings under foreign law.
9.3 Notwithstanding the provisions of Clause 4.3 and Clause 10 of
this Schedule 5, if the Services listed in Stages 1-6 of
Schedule 2 as of the date of this Agreement have not been
completed by [*] the Customer may terminate the
Agreement at any time thereafter by written notice to Lonza.
9.4 In the event of termination of the Agreement by either party
under Clause 9 or by the Customer under Clause 9.3 and
provided that Lonza is not also in material breach of the
Agreement at the same time whereby the Customer exercises his
right to termination the Agreement pursuant to Clause 9.2.1
then:
(a) Customer shall pay to Lonza all amounts outstanding
and remaining to be paid for every stage of the
Services completed prior to termination and, for any
stage of the Services which remains incomplete upon
termination, a termination sum calculated by
reference to all costs incurred by Lonza (including
a reasonable profit) in carrying out activities for
any such stage of the Services and all expenses
reasonably incurred by Lonza in giving, effect to
such termination, including the costs of terminating
any commitments made pursuant to this Agreement (such
termination sum not to exceed the Price for each such
stage of the Services), and
(b) Lonza shall deliver to the Customer any Product made
in accordance with the terms of this Agreement and a
report of all activities completed prior to
termination, and
(c) Lonza shall be entitled to retain all amounts paid by
the Customer for every stage of the Services
completed prior to termination and any amount paid
for any stage of the Services which remains
incomplete upon termination.
9.5 Upon the termination of the Agreement:
9.5.1 for whatever reason Lonza shall promptly return all
Customer Information to the Customer and shall
dispose of or return to the Customer the Cell Line
and any materials therefrom, as directed by the
Customer,
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
39.
<PAGE> 40
9.5.2 by Lonza pursuant to Clause 9.2 the Customer shall
promptly return to Lonza all Lonza Know-How it has
received from Lonza;
9.5.3 for whatever reason the Customer shall not thereafter
use or exploit the Patent Rights or the Lonza
Know-How in any way whatsoever other than for its own
internal purposes to meet regulatory requirements for
the Product (save in circumstances where Lonza
terminates the Agreement pursuant to Clause 9.2 when
no such use or exploitation is permitted);
9.5.4 for whatever reason Lonza may thereafter use or
exploit the Patent Rights or the Lonza Know-How in
any way whatsoever without restriction; and
9.5.5 for whatever reason Lonza and the Customer shall do
all such acts and things and shall sign and execute
all such deeds and documents as the other may
reasonably require to evidence compliance with this
Clause 9.5.
9.6 Termination of the Agreement for whatever reason shall not
affect the accrued rights of either Lonza or the Customer
arising under or out of this Agreement and all provisions
which are expressed to survive the Agreement shall remain in
full force and effect.
10. Force Majeure
10.1 If Lonza is prevented or delayed in the performance of any of
its obligations under the Agreement by Force Majeure and shall
give written notice thereof to the Customer specifying the
matters constituting Force Majeure together with such evidence
as Lonza reasonably can give and specifying the period for
which it is estimated that such prevention or delay will
continue, Lonza shall be excused from the performance or the
punctual performance of such obligations as the case may be
from the date of such notice for so long as such cause of
prevention or delay shall continue and Lonza shall use its
reasonable efforts, so far as it is able, to stop the Force
Majeure. It is agreed that in the event of any delay in the
performance of Lonza's obligations for reasons of Force
Majeure under this clause, the dates applicable for the
payment of any additional sums for Lonza's Services under
Notes 3 and 4 to Clause 1 of Schedule 3 shall not change but
the dates applicable for the allowance of any credit against
the Price for Stages 3 and 5 of Schedule 2 as provided in
Notes 3 and 4, to Clause 1 of Schedule 3 shall be revised to
40.
<PAGE> 41
allow for each day's delay for reasons of Force Majeure under
this Clause 10.
10.2 The expression "Force Majeure" shall be deemed to include any
cause affecting the performance by Lonza of the Agreement
arising from or attributable to acts, events, non-happenings,
omissions or accidents beyond the reasonable control of Lonza.
11. Governing Law, Jurisdiction and Enforceability
11.1 The construction, validity and performance of the Agreement
shall be governed by the laws of England, to the jurisdiction
of whose courts Lonza and the Customer submit.
11.2 No failure or delay on the part of either Lonza or the
Customer to exercise or enforce any rights conferred on it by
the Agreement shall be construed or operate as a waiver
thereof nor shall any single or partial exercise of any
rights, power or privilege or further exercise thereof operate
so as to bar the exercise or enforcement thereof at any time
or times thereafter.
11.3 The illegality or invalidity of any provision (or any part
thereof) of the Agreement or these Standard Terms shall not
affect the legality, validity or enforceability of the
remainder of its provisions or the other pans of such
provision as the case may be.
12. Miscellaneous
12.1 Neither party shall be entitled to assign, transfer, charge or
in any way make over the benefit and/or the burden of this
Agreement without the prior written consent of the other which
consent shall not be unreasonably withheld or delayed.
12.2 The text of any press release or other communication to be
published by or in the media concerning the subject matter of
the Agreement shall require the written approval of Lonza and
the Customer.
12.3 The Agreement embodies the entire understanding of Lonza and
the Customer and there are no promises, terms, conditions or
obligations, oral or written, expressed on implied, other than
those contained in the Agreement. The terms of the Agreement
shall supersede previous agreements (if any) which may exist
or have existed between Lonza and the Customer relating to the
Services.
41.
