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Prepared by MERRILL CORPORATION

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THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH

THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES

EXCHANGE ACT OF 1934, AS AMENDED.

EXHIBIT 10.36

AMENDMENT #1 TO THE COLLABORATION

AGREEMENT

BETWEEN

ONYX PHARMACEUTICALS, INC.

AND WARNER-LAMBERT COMPANY

THIS

AMENDMENT #1 to the Collaboration

Agreement (the “Amendment”)

is made and entered into on August 6, 2001 (the “Amendment Date”), by and

between ONYX PHARMACEUTICALS, INC., a Delaware

corporation having its principal place of business at 3031 Research Drive,

Richmond, California 94806 (“Onyx”), and the Warner-Lambert Company, a

Delaware corporation and a wholly-owned subsidiary of Pfizer Inc, having a

place of business at 2800 Plymouth Road, Ann Arbor, MI  48105 ("Warner").  Onyx and Warner may be referred to herein

individually as a “Party” and collectively as the “Parties.”

RECITALS

A.            Onyx and Warner-Lambert entered into a

Collaboration Agreement dated October 13, 1999 (the “Collaboration Agreement”)

for the further development of the novel replicating virus, ONYX-015,

and the research, development and commercialization of two additional

adenovirus products.

B.            Pursuant to the Collaboration Agreement,

Onyx and Warner have further developed ONYX-015.  The Parties are conducting Phase II and Phase III trials of

ONYX-015 for local/regional administration targeting head and neck cancer, and

Phase II trials of ONYX-015 for intravenous administration aimed at eradicating

metastatic tumors. Onyx and Warner have also continued conducting research on

two adenovirus products.

C.            The Parties desire to amend the

Collaboration Agreement so that, at least for an interim period of time, Onyx

may pursue the development, regulatory approval and commercialization of IT

ONYX-015 (as defined below) at its sole expense and for its sole benefit, while

Warner may pursue the development and regulatory approval of IV ONYX-015 (as

defined below) while also continuing to research and possibly develop Systemic

ONYX-015, also at its sole expense.  The

Parties shall also continue their research related to new adenovirus products,

and any subsequent development and commercialization of such products, under

the terms of Section 2.7 of the Amendment, as well as under the original terms

of the Collaboration Agreement.

D.            If Warner obtains regulatory approval for

IV ONYX-015 or Systemic ONYX-015, then the Parties shall once again bring all

ONYX-015 Products, including IT ONYX-015, under the original terms of the

Collaboration Agreement, with reconciling payments as provided herein to

approximate such original terms.

ARTICLE 1

DEFINITIONS

Except as expressly provided herein, defined terms

will have the meanings as set forth in the Collaboration Agreement.

1.1          "Development

Option" means Warner's right to elect to resume

Development of IV ONYX-015, all as more particularly set forth in Section

3.4(a) hereof.

1.2          "Development Option Period"

means the period of time within which Warner may exercise its Development

Option, as more particularly set forth in Section 3.4(a) hereof.

1.3          "Filing of NDA Notice"

means a written notice from Onyx to Warner wherein Onyx notifies Warner that it

intends to file an NDA or a foreign equivalent thereof for IT ONYX-015.

1.4          “GMPs”

means those

current Good Manufacturing Practices for manufacturing of finished

pharmaceuticals set forth in 21 CFR Parts 210 and 211, as amended from time to

time.

1.5          “IV

ONYX-015” means

intravenous administration of Local/Regional ONYX-015 for systemic therapy

1.6          "IT

ONYX-015"

means Local/Regional ONYX-015, including process improvements thereof, used for

direct injection of head and neck cancer tumors, as well as for liver

metastases of colorectal cancer through hepatic artery infusion, oral

leukoplakia via mouthwash or direct injection, pancreatic cancer via direct

injection or regional bathing, glioblastoma via direct injection or

steriotactic delivery, Barrett's esophageal cancer via bathing the esophagus,

ovarian cancer via intraperitoneal injection, and cerebral sarcoma via direct

injection.

1.7          "Local/Regional

ONYX-015 has the

meaning as set forth in Section 1.34 of the Collaboration Agreement, and

includes both IV ONYX-015 and IT ONYX-015.

1.8          “ONYX-015

Products” means

both Local/Regional ONYX-015 and Systemic ONYX-015.

1.9          "Resumption

Date" means

the date upon which Warner provides notice that it will resume its Development

of IV ONYX–015 pursuant to the exercise of the Development Option.

1.10        “Revised

Collaboration Reconciliation Payment(s)” means those payments made by the Parties upon the

Revised Collaboration Date pursuant to Section 6.3.

1.11        “Revised

Collaboration Date”

means the first day of the second calendar month following the date on which

Warner receives the first Regulatory Approval sufficient to market IV ONYX-015

in the United States.

1.12        “Supply

Availability Date”

shall have the meaning given to it in Section 5.2(b).

ARTICLE 2

MANAGEMENT OF THE COLLABORATION

2.1          Management of Licensed Products other

than Local/Regional ONYX-015.   The management of the Collaboration with respect to all Licensed

Products other than Local/Regional ONYX-015 shall continue as provided in

Article 2 of the Collaboration Agreement.

2.2          Local/Regional ONYX-015 Withdrawn from

Supervision by Joint Committee. Upon the Amendment Date, the Development Team for

Local/Regional ONYX-015 shall be disbanded. 

Onyx shall have sole management responsibility for the Development of IT

ONYX-015, as further set forth in Article 3 below.  Warner shall have sole management responsibility for the

Development of IV ONYX-015, as further set forth in Article 3 below.  If Warner determines to commence Development

of Systemic ONYX-015, a Development Team shall be created for that product and

Development shall proceed in accordance with Section 2.3 of the Collaboration

Agreement (including Warner’s ultimate control over issues related to such

Development.)

2.3          Joint Marketing Committee for IV

ONYX-015.  If, following the completion of  Phase III Clinical Trials of IV ONYX-015,

Warner decides to seek Regulatory Approval of IV ONYX-015 in the United States,it

shall so notify Onyx.  The two Parties

shall then form a Joint Marketing Committee pursuant to Section 2.4 of the

Collaboration Agreement, which shall proceed to develop a Marketing Plan and

Budget for IV ONYX-015, and shall prepare to oversee the operational aspects of

the product’s marketing and sales in the Shared Territory following receipt of

Regulatory Approval in the United States.

2.4          Joint Marketing Committee for IT

ONYX-015.  If  at

any time  following the Revised

Collaboration Date, the Parties decide to seek Regulatory Approval of IT

ONYX-015 (or if following the Revised Collaboration Date, Onyx has completed

the Filing of an NDA Notice), then the Parties shall form a Joint Marketing

Committee pursuant to Section 2.4 of the Collaboration Agreement, which shall

proceed to develop a Marketing Plan and Budget for IT ONYX-015, and shall

prepare to oversee the operational aspects of the product’s marketing and sales

in the Shared Territory following receipt of Regulatory Approval in the United

States.

2.5          Committee Meetings Venues. 

As of the Amendment Date, any committee meetings held pursuant to

Article 2 of the Collaboration Agreement will alternate between the east coast

and the west coast of the United States, at sites mutually agreed upon by the

Parties.

2.6          Return of Local/Regional ONYX-015 to

Collaboration. Upon

the Revised Collaboration Date,  both

IT ONYX-015 and IV ONYX-015 shall automatically be brought back under the terms

of the Collaboration Agreement.  In such

event, the Development Team for Local/Regional ONYX-015 shall be re-established

for the management of continuing Development, including any approvals for

additional indications, and the Joint Marketing Committee shall thereafter

oversee the operational aspects of the marketing and sales of Local/Regional

ONYX-015.

2.7          Support of

the Research Program.  Sections 3.2, 3.3 and 7.2(a) of the

Collaboration Agreement are hereby amended and superseded to provide as

follows:

                                (a)           Personnel, Resources, and Term.

The Research Term, unless otherwise extended by mutual agreement of the

Parties, will be amended as of the Amendment Date to conclude December 31, 2002

("Amended Research Term."). 

During the Amended Research Term, Onyx will maintain, at Warner's cost,

a total of [ * ] FTEs, at the annualized rate of [ * ] per FTE per year (“FTE

Rate”), devoted to work under the Research Plan, who shall be persons holding

at least a bachelor's degree in a scientific discipline (except for technicians

working in Onyx's animal facility, who need not hold such a degree).  The parties may mutually agree to increase

the number of FTEs maintained at Onyx devoted to work under the Research Plan

at Warner’s cost.  The scientific

priorities and direction of such staff shall be determined from time to time by

the Research Management Committee. 

Warner’s obligation to pay Onyx for the cost of [ * ] FTEs at the FTE Rate

until December 31, 2002 shall survive any termination or expiration of the

Collaboration Agreement.

ARTICLE 3

DEVELOPMENT

3.1          Development of Licensed Products other

than Local/Regional ONYX-015. The Development of all Licensed Products other than

Local/Regional ONYX-015 shall continue as provided in Article 4 of the

Collaboration Agreement.

3.2          Development of IT ONYX-015.

(a)           Upon the Amendment Date, Onyx shall have the exclusive

right worldwide to conduct Development activities directed toward obtaining

Regulatory Approval of IT ONYX-015.  The

cost of all such activities shall be borne exclusively by Onyx.  Such activities shall include, but shall not

be limited to, pre-clinical testing and toxicology studies, human clinical

trials, formulation, bulk production, fill/finish, manufacturing process

development, manufacturing scale-up and validation, qualification and

certification and preparation of regulatory filings.

(b)           Commencing with the Amendment Date, and until the

Revised Collaboration Date, Onyx shall have rights with respect to IT ONYX-015

which it has with respect to a Terminated Product under the Collaboration

Agreement (including, without limitation, the rights described in Section 4.7

of the Collaboration Agreement), except that for so long as Warner holds rights

to IV ONYX-015, Onyx shall not conduct or facilitate any clinical trial of the

IV ONYX-015 without the prior consent of Warner.

                3.3          Development

of IV ONYX-015.

(a)           Warner

Development Option and Development Rights. Upon the Amendment Date, and subject to the Warner

diligence obligations set forth in Section 3.4(b) herein, Warner shall have the

exclusive option worldwide, in its sole discretion, to recommence development

activities ("Development Option"), and upon the exercise of such

option, the exclusive right worldwide to conduct those development activities

directed toward obtaining Regulatory Approval of IV ONYX-015.  The cost of all such activities shall be

borne exclusively by Warner.  Such activities

shall include pre-clinical testing and toxicology studies, human clinical

trials, formulation, bulk production, fill/finish, manufacturing process

development, manufacturing scale-up and validation, qualification and

certification and preparation of regulatory filings.

(b)           Clinical

Trials for IV ONYX-015. Warner agrees to forego conducting clinical trials for IV ONYX-015

(including, but not limited to, stopping the accrual of new patients for such

clinical trials) until Onyx has obtained adequate clinical supply of

Local/Regional ONYX-015 to support both Onyx’s clinical trials of IT ONYX-015

and Warner’s clinical trials of IV ONYX-015, as provided in Section

5.2(b).  Notwithstanding the foregoing,

Warner shall be entitled to complete the treatment protocol for patients

already enrolled in clinical trials for IV ONYX-015.  If necessary, Warner will file its own IND pursuant to which

Warner will endeavor to complete such treatments for such patients.

(c)           Systemic ONYX-015.  Until the

Revised Collaboration Date, if Warner develops Systemic ONYX-015, then all

costs attributed to the Development of Systemic ONYX-015 shall be borne

exclusively by Warner.

(d)           Intravenous Administration for

Systemic Therapy. As used in this Amendment, the term "intravenous

administration for systemic therapy" means the intravenous administration

of virus for the treatment of dispersed metastatic cancer, cancer at unknown

locations, or where there is no action taken to target a specific regional

delivery.  By contrast, the regional

administration of Local/Regional ONYX-015, for example, by means of the hepatic

artery for treatment of liver metastases, shall not be included within systemic

therapy.  In the event of any

uncertainty about this distinction, the Parties shall seek to reach agreement

though the Steering Committee or their designated officers under Section 14.1

of the Collaboration Agreement.

(e)           Other Methods of Delivery of

Local/Regional ONYX-015.  If either Party

desires to use a method of delivery for Local/Regional ONYX-015 other than the

methods of delivery currently implemented or contemplated for IT ONYX-015 or IV

ONYX-015 as set forth herein, then such Party shall notify the other of such

intent, and the Parties shall negotiate in good faith and thereafter agree in

writing regarding the rights and responsibilities of the Parties in connection

with such novel delivery methods.

3.4          IV ONYX-015 Development Option Period, Notices, and Exercise

Methods.

                                (a)           Development Option Period.  As of the Amendment Date, Warner shall be

relieved of all diligence obligations for Local/Regional ONYX-015.  Onyx shall inform Warner in writing upon

achievement of the Supply Availability Date. 

Such Supply Availability Date notice shall also include a packet of

up-to-date information about ONYX-015, including but not limited to information

regarding the progress of the IT ONYX-015 development program being conducted

by Onyx, as well as any safety, efficacy or other information as would be

reasonably deemed to be material to Warner's development decision ("Supply

Availability Date Notice").  Warner

shall thereupon have [ * ] after the date of receipt of the

Supply Availability Date Notice (including the information packet) within which

to decide, in its sole discretion, whether or not it will exercise its

Development Option to recommence the Development of IV ONYX-015

("Development Option Period").

                                (b)           Exercise of Option; Warner Diligence.  If Warner intends to recommence Development,

it shall provide Onyx with a written notice within the Option Period.  The date of such notice shall be known as

the Resumption Date.  Subject to

subparagraph 3.4(c), Warner shall have a period of [ * ] after the Resumption

Date within which to commence, and subsequently pursue, the Development of IV

ONYX–015 ("Resumption Period"). 

Warner shall be deemed to be diligent within such Resumption Period if,

prior to the end of the Resumption Period, the Development program has

progressed to such a point that the first patient in a human clinical trial has

been enrolled.  Thereafter, Warner shall

be deemed to be diligent if, for such Development of IV ONYX-015, it spends at

the rate of at least [ * ] during each consecutive twelve (12)-month period

beginning with the twelve (12)-month period that commences the day after the

conclusion of the Resumption Period.

 

                                (c)           Extensions to Development Option

Period.

 

(i)            Prior to Exercise of IV ONYX-015

Development Option.  If, at any time prior to the exercise of

Warner's Development Option, any clinical trial of IT ONYX–015 is suspended or

delayed, or any aspect of the Development of IV ONYX-015 cannot be recommenced,

because of:  (i) any novel concerns

related to the safety or efficacy of Local/Regional ONYX-015 (i.e., safety or

efficacy concerns that were not initially communicated to Warner by Onyx in the

Supply Availability Date Notice information packet), (ii) the FDA or any other

governmental authority or obligation of law requires suspension or delay, or

(iii) the lack of availability of Local/Regional ONYX-015, then such Option

Period will be extended for [ * ] longer than the length of time of the

suspension, delay, or period of lack of availability, or, in the event of novel

safety or efficacy concerns, for up to an additional [ * ] in order for Warner to

assess such novel safety and efficacy information.

(ii)           After Exercise of Development Option.

(1)           If Warner has already exercised its Development

Option, and any clinical trial or other aspect of the Development of IV

ONYX-015 is thereafter suspended or delayed because of (i) the FDA or any other

governmental authority or obligation of law requires suspension or delay, or

(ii) the lack of availability of Local/Regional ONYX-015, then Warner may halt

such Development, and Warner shall be deemed to have another option

("Second Development Option"), for [ * ] longer than the length

of time of the suspension, delay, or period of lack of availability in which to

consider whether or not to recommence Development ("Second Development

Option Period"), and the Resumption Period shall be deemed suspended for

the length of such Second Development Option Period.  If Warner does intend to proceed, it shall provide Onyx with a

written notice to such effect within the Second Development Option Period, and

the Resumption Period and Warner’s diligence obligations under subparagraph

3.4(b) shall resume upon the date of such notice.  The parties shall negotiate in good faith to determine whether

any additional extension to the Resumption Period is required as it pertains to

this subparagraph 3.4(c)(ii)(1).

(2)           If Warner has already exercised its Development Option

and any clinical trial or other aspect of Development of IV ONYX-015 is

thereafter suspended or delayed due to concerns related to the safety or

efficacy of Local/Regional ONYX-015, then Warner may halt Development and shall

have up to [ * ] in which to consider whether or not to recommence

Development.  The Resumption Period

shall be suspended during such [ * ] period.  If Warner does intend to proceed with Development, it shall

provide Onyx with a written notice to such effect, and a plan to resume

Development of IV ONYX-015 within the [ * ] period, and the Resumption Period and

Warner’s diligence obligations under subparagraph 3.4(b) shall resume upon the

date of such notice.

                3.5          Onyx Remedy in the Event of Warner decision not to Develop

IV ONYX-015.  If at any time Warner notifies Onyx that it

does not intend to proceed with the Development of IV ONYX-015, or if, after

Warner has commenced Development pursuant to Section 3.4, Onyx can show that,

subject to subparagraph 3.4(c)(ii), Warner has failed to be diligent with such

Development even after [ * ] after Warner's receipt of written

notice from ONYX to such effect, then IV ONYX-015 shall be deemed a Terminated

Product under the Collaboration Agreement and thereafter all Local/Regional

ONYX-015 Products shall be Terminated Products under the Collaboration

Agreement with Onyx maintaining all rights thereto.  In such event however, Warner shall still retain rights to

Systemic ONYX-015, the Pro-Drug Product and Gene Product set forth in the

Collaboration Agreement.

3.6          INDs

and Drug Approval Applications.

                (a)           Transfer of

IT ONYX-015 INDs and Relevant Data.  Within sixty (60) days following the Amendment Date, Warner shall

assign and transfer the IT ONYX-015 INDs to Onyx, and shall provide copies of

all correspondence and notes of conversations with the FDA and any other

regulatory agency relating to IT ONYX-015. 

Warner shall use commercially reasonable efforts to assist Onyx in the

transfer of all regulatory responsibilities with respect to IT ONYX-015

                (b)           IV ONYX-015 IND.            In

the event Warner wishes to file an IND for IV ONYX-015, it shall have the right

to cross-reference the INDs held by Onyx for the purpose of developing IT

ONYX-015.  Onyx shall use commercially

reasonable efforts to assist Warner the requisite information with respect to

IT ONYX-015.

                (c)           Drug Approval Applications.  Until the

Revised Collaboration Date, Onyx shall be responsible for the preparation and

filing of, and shall own, all Drug Approval Applications and other regulatory

submissions related to IT ONYX-015 filed in any regulatory jurisdiction.  Warner shall be responsible for the

preparation and filing of, and shall own, all Drug Approval Applications and

other regulatory submissions relating to IV ONYX-015 filed in any regulatory jurisdiction.  As long as Warner is developing IV ONYX-015,

Onyx will provide Warner with copies of its Drug Approval Applications for IT

ONYX-015.  Warner will promptly review such

submission and in any event will have fifteen (15) days to comment on such Drug

Approval Application. Onyx will deliver to Warner copies of amendments to such

initial application, and of subsequent Drug Approval Applications concurrent

with their filing with such regulatory authority.  Warner will provide Onyx with a copy of the initial Drug Approval

Application to be filed for IV ONYX-015 prior to its submission to the

appropriate regulatory authority. Onyx will promptly review such submission and

in any event will have fifteen (15) days to comment on such Drug Approval

Application. Warner will deliver to Onyx copies of amendments to such initial

application, and of subsequent Drug Approval Applications concurrent with their

filing with such regulatory authority.

3.7          Effect

of Regulatory Approval of IV ONYX-015 or Systemic ONYX-015. In the event Warner receives Regulatory

Approval of IV ONYX-015 or Systemic ONYX –015in the United States: a) the

marketing of all ONYX-015 Products shall be governed by the original terms of

the Collaboration Agreement as of the Revised Collaboration Date; and b) all

INDs and Drug Approval Applications held by Onyx for IT ONYX-015 shall be

transferred to Warner on such Revised Collaboration Date. In the event Warner

receives Regulatory Approval of IV ONYX-015 or Systemic ONYX-015in

another country outside of the United States prior to receiving Regulatory

Approval of the product in the United States: a) the marketing of all ONYX-015

Products in such country shall be governed by Section 4.3 of this Amendment;

and b) INDs and Drug Approval Applications held by Onyx for IT ONYX-015 for

such country shall be transferred to Warner within forty-five (45) days of

Onyx’s receipt of notice of such Regulatory Approval.

 

ARTICLE 4

COMMERCIALIZATION

4.1          Commercialization

of Licensed Products other than ONYX-015 Products. All Licensed Products other than ONYX-015

Products shall remain subject to the Commercialization terms of the original

Collaboration Agreement.

4.2          Commercialization

of IT ONYX-015 Prior to Regulatory Approval of IV ONYX-015 in any Country. 

From the Amendment Date until the Revised Collaboration Date, except as

set forth in Section 4.3, Onyx shall have the sole right to sell and promote IT

ONYX-015. In such period of time, Onyx shall bear all Pre-Marketing Expenses

and other costs associated with the commercialization of IT ONYX-015, and Onyx

shall retain all revenues derived therefrom for its own account. Onyx shall

seek input from Warner in Pre-Market planning and launch strategies for such IT

ONYX-015, provided, however, that all final decisions for such Pre-Marketing

planning and launch strategies shall be Onyx’s.  Onyx may market IT ONYX-015 with its own sales force, or may

engage a Third Party in such effort, provided, however, that, Onyx shall not

enter into any marketing or promotion agreement with a Third Party that would

conflict with Warner’s rights under Section 4.3 or would, following the Revised

Collaboration Date, conflict with Warner’s marketing rights or Onyx’s

obligations in co-promotion of Licensed Products with Warner according to the

terms of the Collaboration Agreement.

4.3          Commercialization

of ONYX-015 Products if Warner Obtains Regulatory Approval in any Country Prior

to Obtaining Approval in the United States.  If Warner

obtains Regulatory Approval of IV ONYX-015 or Systemic ONYX-015 in any country

other than the United States prior to obtaining Regulatory Approval for IV

ONYX-015 or Systemic ONYX-015 in the United States, then: (i) in all countries

where Warner receives such approval, Warner shall have the exclusive right to Commercialize

all ONYX-015 Products, and shall pay Onyx royalties as provided in Section 7.5

of the Collaboration Agreement; and (ii) until the Revised Collaboration Date,

Onyx shall have the exclusive right to Commercialize IT ONYX-015 products in

all countries of the world where Onyx has received Regulatory Approval and

where Warner has not yet received Regulatory Approval for IV ONYX-015.  If Onyx was selling IT ONYX-015 in any

country other than the United States where Warner commences marketing ONYX-015

Products, the Parties shall cooperate to effect such transfer of

commercialization activity in an economic manner, but Warner shall not be

obligated to assume any employees, agreements or other commitments made by

Onyx.  If Warner receives its first

Regulatory Approval for IV ONYX-015 in a country other than the United States,

then Warner shall pay to Onyx, within thirty (30) days following the receipt of

such Regulatory Approval, any milestone payments associated with such

approval(s) set forth in Section 7.4(a)(i) and (ii) of the Collaboration

Agreement, together with milestone payments (if any) that would then be due

under Section 7.4(d) of the Collaboration Agreement.  If the first Regulatory Approval for IV ONYX-015 is for Systemic

ONYX-015, Warner shall also pay the milestone payments set forth in Section

7.4(a)(ii)(1) and (2) of the Collaboration Agreement.  Following such initial Regulatory Approval for IV ONYX-015,

milestone payments shall be made in accordance with the original terms of

Section 7.4 of the Collaboration Agreement.

4.4          Commercialization

of ONYX-015 Products if Warner Obtains Regulatory Approval of IV ONYX-015 in

the United States.  Regulatory Approval of IV ONYX-015 or

Systemic ONYX-015 in the United States shall trigger the Revised Collaboration

Date.  Following such date,

Commercialization of all ONYX-015 Products shall occur in accordance with the

original terms of the Commercialization Agreement, subject, however, to the

reconciling payments set forth in Article 6 of this Amendment.  Prior to the Revised Collaboration Date,

Warner shall bear all costs it incurs in preparation for Commercialization of

ONYX-015 Products, including without limitation Pre-Marketing Expenses for IV

ONYX-015, for its own account, but subject to Article 6 of this Amendment.  If Warner determines to seek Regulatory

Approval for IV ONYX-015 or Systemic ONYX-015 in the United States, the Parties

shall consult as to Pre-Marketing activities related to such product, and although

each Party shall bear its own marketing expenses prior to the Revised

Collaboration Date, the Parties shall coordinate their marketing efforts

through the Joint Marketing Committee.

 

ARTICLE 5

MANUFACTURING

AND SUPPLY

5.1          Manufacture

of Supplies for all Licensed Products other than Local/Regional ONYX-015. 

The manufacture of all Licensed Products other than Local/Regional

ONYX-015 shall remain subject to the manufacture and supply terms of the

Collaboration Agreement set forth in Article 8 therein.

5.2          Clinical

Supply of Local/Regional ONYX-015.

              (a)           Rights to Manufacture. From the Amendment Date, Onyx shall

control all issues relating to, and shall have the right and responsibility to

manufacture or have manufactured by Third Parties, clinical supplies of

Local/Regional ONYX-015 for use by Onyx. 

Warner shall have the right to manufacture clinical supplies of

Local/Regional ONYX-015 for Warner’s use if it so desires.  If Warner decides to so establish its own clinical

supply of Local/Regional ONYX-015, Warner may request, and Onyx shall use

commercially reasonable efforts to provide, technical assistance in

transferring the manufacturing process of Local/Regional ONYX-015 to a Warner

facility (or to a facility of a Warner Affiliate).  In no event shall Onyx be obligated to provide on-site technical

assistance in excess of [ * ] engineers for [ * ] at a Warner facility

(or to a facility of a Warner Affiliate). 

Warner shall bear all costs of Onyx’s technical assistance.

              (b)           Available Supply.  As of the Amendment Date and until the Supply Availability

Date, all clinical material of Local/Regional ONYX-015 shall be dedicated to

Onyx’s use, except for the completion of the treatment protocol of those

patients accrued by Warner in clinical trials prior to the Amendment Date.  In this regard, the Parties recognize that

Onyx entered into a supply agreement with Xoma (US) LLC (“Xoma”) on January 29,

2001 for the purpose of securing an increased supply of clinical material of

Local/Regional ONYX-015. Onyx shall notify Warner when either: Xoma has successfully

manufactured three (3) batches of Local/Regional ONYX-015 at commercial scale

and has locked-down the manufacturing process for the product; or when Xoma’s

development scale runs indicate supply availability; or when other Third Party

manufacturers have provided similar assurances of supply (“Supply Availability

Date”). At such time, Warner may request an audit of any Third Party

manufacturing facility supplying such Local/Regional ONYX-015 clinical supply

pursuant to Section 5.6.

              (c)           Forecasts; Ordering Clinical

Supply.  Within [ * ] after the Supply Availability Date,

in the event Warner wishes to obtain clinical supply of Local/Regional ONYX-015

from Onyx, Warner shall provide Onyx with its first rolling non-binding [ * ]

forecast, on a per quarter basis, of its clinical supply needs of

Local/Regional ONYX-015.   No later than

[ * ]

prior to each requested date of delivery, Warner shall provide Onyx with

binding purchase orders of its clinical supply needs, provided, however, that

Warner’s first purchase order for clinical supply may be submitted no later

than [ *

] in advance of its requested date of delivery. All clinical

material of Local/Regional ONYX-015 supplied to Warner by Onyx shall be

governed by this Amendment. Any purchase order terms (other than those of

quantity, date of delivery, and a mutually-agreed price) that differ from those

of this Amendment shall have no effect.

5.3          Cost

of Clinical Supply.  All clinical material of Local/Regional

ONYX-015  supplied to Warner by Onyx

shall be at a mutually agreed price, which shall be reasonable in view of the

Cost of Manufacture and the costs incurred by Onyx in the establishment of its

manufacturing capability for Local/Regional ONYX-015, including, without

limitation, process development costs and its payments to contract

manufacturers such as space fees, capacity reservation fees and

milestones.  Warner shall pay Onyx

amounts due and invoiced within twenty (20) days following receipt of the

related invoice (which shall not be prior to the receipt of the shipment

covered by such invoice).

5.4          Shipment;

Acceptance.

                (a)           Shipment

Procedures. Onyx shall ship Warner’s orders of clinical supply of

Local/Regional ONYX-015 to a destination specified by Warner.  Title and risk of loss to all materials

shipped shall pass to Warner FCA the manufacturing facility.  All customs, duties, costs, insurance

premiums and other expenses of such transportation and delivery, shall be at

Warner’s expense.  Onyx shall provide a

certificate of analysis to Warner with every shipment.

                (b)           Rejection of Shipment.  Warner may reject any shipment of

Local/Regional ONYX-015 that: (a) does not conform to specifications; or (b) is

adulterated or misbranded within the meaning of the U.S. Federal Food, Drug and

Cosmetic Act.  Any notice of rejection

must be submitted to Onyx within thirty (30) days of receipt of such shipment,

with a report of analysis providing Warner’s basis for rejection.   If no such notice of rejection is

submitted, Warner shall be deemed to have accepted such delivery of product. In

the event Warner rejects shipment of the product, Onyx shall notify Warner

whether or not it accepts Warner’s basis for rejection.  If Onyx disagrees with Warner’s

determination that product does not meet specifications, the product shall be

submitted to a mutually acceptable third party laboratory.  The fees and expenses of such laboratory

testing shall be borne entirely by the Party against whom such findings are

made.  Whether or not Onyx accepts

Warner’s basis for rejection of product, upon notice of rejection, Onyx shall

use commercially reasonable efforts to replace such rejected product.  In the event that the rejected lot is

determined not to meet specifications, any moneys paid for the rejected lot

shall be credited against the cost of a replacement lot or returned to Warner

in the event Onyx is unable to manufacture a replacement lot.

                (c)           Shortages of Supply. 

After the

Supply Availability Date, Onyx shall continue to use commercially reasonable

efforts to satisfy both Onyx’s and Warner’s clinical supply requirements for

Local/Regional ONYX-015.  In the event a

shortage of clinical supply of Local/Regional ONYX-015 occurs after the Supply

Availability Date, the Parties shall confer about the allocation of available

clinical supply.  In the event the

Parties cannot agree, priority shall be given first to those clinical trials

which have already commenced.   Any

clinical supply of Local/Regional ONYX-015 remaining available after the needs

of ongoing clinical trials have been met shall be allocated equally (50%/50%)

between Onyx and Warner.

5.5          GMPs;

Specifications.  All supplies of Local/Regional ONYX-015

shipped by Onyx to Warner hereunder shall be manufactured in full compliance

with then current GMPs in the United States. 

In the event Warner requires clinical or commercial supplies of

Local/Regional ONYX-015 to be manufactured to specifications which differ from

those required by Onyx for Local/Regional ONYX-015 for its own use, it shall so

notify Onyx.  Onyx shall use commercially

reasonable efforts to manufacture or procure Local/Regional ONYX-015 that meet

Warner’s specifications, but any additional investments of expenses required to

achieve such Warner specifications shall be borne by Warner.  If any such incremental expenditure would be

required to satisfy Warner specifications, Onyx shall notify Warner and obtain

Warner’s prior approval for such expenditure.

5.6          Warner

Audits of [ * ] Manufacturing Facilities.  Onyx shall [ * ]

for Warner to audit any [ * ] manufacturing facilities utilized in

the manufacture of Local/Regional ONYX-015 to confirm [ * ] manufacturer’s ability

to manufacture Local/Regional ONYX-015 to Warner’s specifications, and for

general quality assurance purposes.

5.7          Supply

of Local/Regional ONYX-015.

                (a)           Prior to the Revised Collaboration Date. Commencing with the Amendment Date and

until the Revised Collaboration Date, Onyx shall have the right and

responsibility to supply its own requirements of clinical and /or commercial IT

ONYX-015, at its own expense, and Warner shall be relieved of such

responsibility.  Onyx may contract with

Third Parties as it desires to provide for such supply, provided, however,that

such agreements shall be made assignable to Warner following the Revised

Collaboration Date.  In the event Warner

decides to enter Phase III clinical trials for IV ONYX-015, the Parties shall

confer as to plans for commercial supply of Local/Regional ONYX-015 in the

event Warner obtains Regulatory Approval for IV ONYX-015.  If Warner desires for Onyx to supply it with

commercial supplies of Local/Regional ONYX-015 in any countries outside of the

Shared Territory following the date on which Warner obtains the right to

Commercialize Local/Regional ONYX-015 in such countries and prior to the

Revised Collaboration Date, then Warner and Onyx shall negotiate a Supply

Agreement for such supply on commercially reasonable arm’s-length terms.  Warner may also establish its own capacity

for the manufacture of such commercial supplies.

(b)           Subsequent

to the Revised Collaboration Date.  Following the Revised Collaboration Date,

Warner shall be reestablished as the Party with the sole right and

responsibility to supply commercial quantities of Local/Regional ONYX-015 on a

worldwide basis.  Onyx and Warner shall

negotiate, in good faith, the basis for Warner's assumption of any Third Party

manufacturing arrangements that have been put in place by Onyx prior to that

date, and Warner shall thereafter supply commercial quantities of

Local/Regional ONYX-015 to the Collaboration on the terms set forth in the

original Collaboration Agreement.  In

the event of such assignment and assumption, Warner and Onyx shall negotiate a

basis for either the crediting or the reimbursement of Onyx for the cost of

certain appropriate capital expenditures made or contract manufacturing fees

paid by Onyx in respect of the transferred arrangements ([ * ] of payment).  Warner may decline to assume any such Third

Party agreement in Warner’s sole discretion, in which case Onyx shall continue

to purchase Local/Regional ONYX-015 from such Third Party supplier(s) to the

extent of its contractual obligations, and shall resell such material to Warner

at Onyx’s fully-allocated cost.  If Onyx

has established manufacturing capacity for Local/Regional ONYX-015 in its own

facilities, then the Parties shall negotiate reasonable, arm’s-length terms for

Onyx to supply material to Warner for use in the Collaboration, or if Warner

prefers not to acquire material from such facility, then the Parties shall

negotiate to determine whether or not certain[ * ] by Warner.

ARTICLE 6

RECONCILING PAYMENTS

6.1          Development

Costs to Date.  Thirty (30) days after the Amendment Date,

Onyx will invoice Warner for those Development Costs incurred by Onyx between

December 31, 2000 and the Amendment Date, and subject to the terms of Section

7.3(a) of the Collaboration Agreement, Warner will pay Onyx such amount within

forty-five (45) days of receipt of the invoice.  Thirty (30) days after the Amendment Date, Warner shall also

notify Onyx of the Development Costs incurred by Warner up to the Amendment

Date. The total Development Costs incurred by Warner (including such

Development Costs of Onyx that were reimbursed by Warner) prior to the

Amendment Date will be referred to as the “1999-2001 Development Costs”.

6.2          Interim

Costs Accounting.

                (a)           Development Costs and Pre-Marketing Expenses of

Local/Regional ONYX-015.  Between the Amendment Date and

the Revised Collaboration Date, Onyx shall maintain clear, accurate and detailed

records of Development Costs attributed to the Development (“Interim IT

ONYX-015 Development Costs”) and Pre-Marketing Expenses attributed to the

Pre-Marketing (“Interim IT ONYX-015 Pre-Marketing Expenses”) of IT ONYX-015.  Onyx shall have sole responsibility for the

payment of such Development Costs and Pre-Marketing Expenses until and unless

Warner obtains Regulatory Approval in the United States for IV ONYX-015, at

which time the Parties shall reconcile amounts due pursuant to Section 6.3.

                (b)           Development Costs and Pre-Marketing Expenses of IV

ONYX-015. Between

the Amendment Date and the Revised Collaboration Date, Warner shall maintain

clear, accurate and detailed records of Development Costs attributed to the

Development of IV ONYX-015 (“Interim IV ONYX-015 and/or Systemic ONYX–015

Development Costs”) and Pre-Marketing Expenses attributed to the Pre-Marketing

of IV ONYX-015 (“Interim IV ONYX-015 or Systemic ONYX–015 Pre-Marketing

Expenses”). Warner shall have sole responsibility for the payment of such

Development Costs and Pre-Marketing Expenses until and unless it obtains

Regulatory Approval in the United States for IV ONYX-015 or Systemic ONYX-015,

at which time the Parties shall reconcile amounts due pursuant to Section 6.3.

                (c)           Other Licensed Products. 

 Any costs attributed to the Development of

Licensed Products other than ONYX-015 Products (“Other Licensed Products

Interim Costs”) shall be paid by Warner until the sum of the Other Licensed

Products Interim Costs plus the 1999-2001 Development Costs equals forty

million dollars ($40,000,000). Thereafter, further Other Licensed Products

Interim Costs shall be borne by the Parties in accordance with Section

7.3(a)(ii) and Section 7.3(b) of the Collaboration Agreement, subject to

Section 4.10 of the Collaboration Agreement.

6.3          Revised

Collaboration Reconciliation Payments. Upon the Revised Collaboration Date, each Party shall

provide the other with an accounting of its actually incurred interim

Development Costs and Pre-Marketing Expenses.

                (a)           Within

forty-five (45) days following the Revised Collaboration Date, the Parties

shall make a reconciling payment to bring the Development Costs incurred by

each Party through the Revised Collaboration Date into alignment with the

allocation of Development Costs provided for in Section 7.3 of the original

Collaboration Agreement.  In particular:

(i)            “Total Development Costs” at that point

shall equal the sum of the 1999-2001 Development Costs, Interim IT ONXY-015

Development Costs, Interim IV ONYX-015 and/or Systemic ONYX-015 Development

Costs, and Other Licensed Product Interim Costs.

(ii)           If the sum borne by Warner through the

Revised Collaboration Date (i.e., the 1999-2001 Development Costs plus the

Interim IV ONYX-015 and/or Systemic ONYX-015 Development Costs and the share of

Other Licensed Product Interim Costs paid by Warner pursuant to Section 6.2(c)

of the Amendment) exceeds the sum of (x) $40,000,000 plus (y) 75% of the amount

of Total Development Costs in excess of $40,000,000, then Onyx shall pay Warner

the amount of such excess.

(iii)         If the

sum borne by Warner through the Revised Collaboration Date is less than the sum

of (x) $40,000,000 plus (y) 75% of the amount of Total Development Costs in

excess of $40,000,000, then Warner shall pay Onyx the amount of such shortfall.

The reconciling payment

determined under this Section 6.3(a) shall not include any provision for

interest.

                (b)           Pre-Marketing Expenses Payment.  The Parties shall [ * ] in the aggregate Interim IT ONYX-015

Pre-Marketing Expenses and Interim IV and/or Systemic ONYX-015 Pre-Marketing

Expenses. If the Interim IT ONYX-015 Pre-Marketing Expenses exceeded the

Interim IV and/or Systemic ONYX-015 Pre-Marketing Expenses, then Warner shall

pay Onyx [

* ] within thirty (30) days after the Revised Collaboration

Date.  If the Interim IV and/or Systemic

ONYX-015 Pre-Marketing Expenses exceeded the Interim IT ONYX-015 Pre-Marketing

Expenses, then [ * ] of such excess amount shall be treated as a “Warner

Pre-Marketing Advance” and shall be recovered by Warner pursuant to Section

7.6(d) of the Collaboration Agreement.

(c)           Milestone

Payments.

                                (i)            IT ONYX-015. Within thirty (30) days of the Revised

Collaboration Date, each of the Local/Regional ONYX-015 Milestones set forth in

Section 7.4(a)(i) of the Collaboration Agreement achieved by Onyx in connection

with IT ONYX-015 prior to the Revised Collaboration Date and not previously

paid shall be paid to Onyx by Warner on the Revised Collaboration Date without

interest.  After the Revised

Collaboration Date, then any Local/Regional ONYX-015 Milestones achieved by

Onyx in connection with IT ONYX-015 after the Revised Collaboration Date shall

be paid to Onyx by Warner in accordance with the terms of Section 7.4 of the

Collaboration Agreement.

                                (ii)           IV ONYX-015.  Each of the Local/Regional

ONYX-015 Milestones set forth in Section 7.4(a)(i) of the Collaboration

Agreement achieved by Warner in connection with IV ONYX-015 prior to the

Revised Collaboration Date and not previously paid shall be paid to Onyx by Warner

on the Revised Collaboration Date without interest.  Additionally, any Local/Regional ONYX-015 Milestones achieved by

Warner in connection with IV ONYX-015 after the Revised Collaboration Date

shall be paid to Onyx by Warner in accordance with the terms of Section 7.4 of

the Collaboration Agreement.

                                (iii)         Systemic ONYX-015. Each of the Systemic ONYX-015 Milestones

set forth in Section 7.4(a)(ii) of the Collaboration Agreement achieved prior

to the Revised Collaboration Date shall be paid to Onyx by Warner on the

Revised Collaboration Date without interest, unless already paid by Warner

under this Amendment.  Any Systemic

ONYX-015 Milestones achieved by Warner after the Revised Collaboration Date

shall be paid to Onyx by Warner in accordance with the terms of Section 7.4 of

the Collaboration Agreement.

                (d)           Milestones

for Research Program, Patent Matters, Pro-Drug Products and Gene Products. 

The Milestones for the Research Program, Patent Matters, Pro-Drug

Products and Gene Products shall remain subject to the terms of the

Collaboration Agreement as set forth in Section 7.4 therein.

ARTICLE 7

LICENSES AND INTELLECTUAL PROPERTY

7.1          Adjustment

of Licenses.  The licenses set forth in Article 6 of the

Collaboration Agreement shall continue in effect except as set forth in this

Section 7.1.

                (a)           As of the Amendment Date and until

the Revised Collaboration Date, the rights of Warner under Section 6.1 of the

Collaboration Agreement are hereby modified to exclude any license rights with

respect to IT ONYX-015 in any country where Warner has not received Regulatory

Approval for the sale of IV ONYX-015, except that Warner shall be permitted to

carry out Development activities related to IV ONYX-015 as set forth in this

Agreement, including the manufacture of Local/Regional ONYX-015 for that

purpose.

                (b)           As

of the Amendment Date and until the Revised Collaboration Date, Onyx shall have

the license rights set forth in Section 6.7 of the Collaboration Agreement with

respect to IT ONYX-015.  If Warner loses

its rights to Develop and Commercialize all ONYX-015 Products, the license

rights of Onyx under Section 6.7 shall then be for all uses of ONYX-015

Products.

7.2          Defense

of Third Party Intellectual Property Claims. In the event of any Third Party allegations of infringement

relating to Local/Regional ONYX-015 prior to the Resumption Date, anywhere in

the world, Onyx (rather than Warner) shall be the Defending Party under Section

10.6(a) of the Collaboration Agreement. 

The original allocation of responsibility under Section 10.6(a) shall be

restored as of the Resumption Date.

7.3          Trademarks.  Onyx shall have sole control over all matters relating

to the use of, and shall own, all trademarks used in the sale of IT ONYX-015

prior to the Revised Collaboration Date. 

Onyx shall consult with Warner prior to the selection of any such

trademarks.  All such trademarks shall

be registered by Onyx in its name as owner in all countries.  Promptly following the Revised Collaboration

Date, Onyx shall transfer such trademarks (excluding any Onyx corporate

trademarks or trade names) to Warner, if so requested by Warner, at the expense

of Warner.  Onyx shall be responsible

for the prosecution, defense, and maintenance of trademarks selected by it for

IT ONYX-015 prior to the Revised Collaboration Date.  Any costs associated with the defense of trademark infringement

claims related to the sale by Onyx of IT ONYX-015 prior to the Revised

Collaboration Date, or liabilities or costs of settlement arising therefrom,

shall be borne by Onyx.

ARTICLE 8

PUBLICATION; PUBLICITY

8.1          Publications.       

Notwithstanding the Collaboration Agreement, as of the Amendment Date, Onyx

shall have the right to publish clinical trial results and other data related

to IT ONYX-015 without the prior consent of Warner, provided that, in

connection with publications authored by Onyx employees, agents or consultants,

or resulting from studies funded by Onyx, Onyx gives at least thirty (30) days

prior notice to Warner (ten (10) days in the event of a poster presentation) of

the proposed publication to allow for Warner to comment thereon, and in

connection with publications resulting from studies neither sponsored nor

managed by Onyx, Onyx uses its best efforts to transmit such publications to

Warner as soon as is reasonably possible.

8.2          Publicity.              

Onyx may issue a press release regarding this Amendment (“First Press Release”)

provided however, that the content thereof must be mutually agreed upon in

writing by the parties in advance of the anticipated release date. Any

subsequent press releases regarding this Amendment or the Collaboration

Agreement disclosing information about the Amendment or Collaboration Agreement

beyond that disclosed in the First Press Release [ * ] in advance of any anticipated

publication date and must be [ * ] prior to issuing such release.  Information disclosed in press releases [ * ]

may thereafter be freely disclosed by Onyx. 

Onyx may publicize its activities related to IT ONYX-015 without the

prior written consent of Warner, so long as Onyx [ * ] of the anticipated

release date.  If Warner loses its

rights to Develop and Commercialize all Local/Regional ONYX-015 Products

pursuant to Section 3.5, then Onyx shall have unlimited rights with respect to

publication and publicity as they apply to all Local/Regional ONYX-015

Products. Upon the Revised Collaboration Date, the original terms of Sections

9.2 and 9.3 of the Collaboration Agreement shall apply to publicity and

publication.

ARTICLE 9

INDEMNIFICATION

9.1          Continuing

Indemnification. The

terms of indemnification set forth in Article 13 of the Collaboration Agreement

shall apply to the activities of Parties with respect to all Licensed Products

other than ONYX-015 Products.   Prior to

the Amendment Date, and after the Revised Collaboration Date, the terms of

indemnification as stated in Article 13 of the Collaboration shall also apply

to the activities of the Parties with respect to ONYX-015 Products.

9.2          Warner

Indemnification for IV ONYX-015. Warner hereby agrees to save, defend and hold Onyx and

its agents and employees harmless from and against any and all suits, claims,

actions, or demands by a Third Party for damages, liabilities, expenses and/or

loss, including reasonable legal expenses and attorneys’ fees (collectively,

“Losses”), resulting directly from the Development, manufacture, use, handling,

storage, sale or other disposition of IV ONYX-015 or Systemic ONYX-015 by

Warner, its agents or sublicensees, occurring after the Amendment Date and

prior to the Revised Collaboration Date, but only to the extent such Losses do

not result from the negligence or willful misconduct of Onyx or are covered by

the Onyx indemnity in Section 9.4.

9.3          Onyx

Indemnification.  Onyx hereby agrees to save, defend and hold

Warner and its agents and employees harmless from and against any and all

Losses resulting directly or indirectly from the Development, manufacture, use,

handling, storage, sale or other disposition of Local/Regional ONYX-015 by

Onyx, its agents or sublicensees, occurring after the Amendment Date and prior

to the Revised Collaboration Date,  but

only to the extent such Losses do not result from the negligence or willful

misconduct of Warner.

9.4          Onyx

Indemnification for Manufacture. Onyx hereby agrees to save, defend and hold Warner

and its agents and employees harmless from and against any and all Losses

resulting directly from the failure of Local/Regional ONYX-015 supplied by

Onyx, its agents or contractors to Warner pursuant to Article 5 to meet the

specifications for such product agreed between the Parties at the time of such

supply.

9.5          Notice

of Claim.  In the event that a Party is seeking

indemnification under this Article 9, it shall inform the other Party of a

claim as soon as reasonably practicable after it receives notice of the claim,

shall permit the indemnifying Party to assume direction and control of the

defense of the claim (including the right to settle the claim solely for

monetary consideration), and shall cooperate as requested in the defense and

settlement of the claim.  The

indemnified Party shall not voluntarily make any payment or incur any expense

in connection with any claim or suit without the consent of the Indemnifying

Party.

ARTICLE 10

REPRESENTATIONS

AND WARRANTIES

10.1        Warner

Representation and Warranty.   In addition to those representations and warranties made by Warner

in Article 13 of the Collaboration Agreement, Warner hereby represents and

warrants to Onyx that:

                (a)           This

Amendment is a legal and valid obligation upon Warner and enforceable in

accordance with its terms, and has been approved by all necessary corporate

action.

                (b)           Warner

is not aware of any claims pending or threatened by Third Parties or any facts

that could reasonably give rise to any Third Party claims for damages,

liabilities, injuries, expenses and/or loss resulting from activities performed

under the clinical trial agreements or IRB agreements assigned to Onyx pursuant

to Section 3.6.

10.2        Onyx

Representation and Warranty. In addition to those representations and warranties

made by Onyx in Article 13 of the Collaboration Agreement, Onyx hereby

represents and warrants to Warner that this Amendment is a legal and valid

obligation upon Onyx and enforceable in accordance with its terms, and has been

approved by all necessary corporate action.

ARTICLE 11

DISPUTE RESOLUTION

The terms of Section 14.1 and Section 2.6 of the Collaboration Agreement shall

continue to govern the Parties with regard to dispute resolution.  However, commencing with the Amendment Date

and continuing to the Revised Collaboration Date, Onyx shall have exclusive

decision-making and dispute resolution authority with regard to the Development

and Commercialization of IT ONYX-015 during such period.  If Warner loses its rights to Develop and

Commercialize all Local/Regional ONYX-015 Products pursuant to Section 3.5,

then Onyx shall thereafter have exclusive decision-making and dispute

resolution authority with regard to the Development and Commercialization of

all Local/Regional ONYX-015 Products.

ARTICLE

12

 

MISCELLANEOUS

 

12.1        Amendment;

Continued Force and Effect.  This is an

amendment of the Collaboration Agreement as provided for in Section 14.15 of

the Collaboration Agreement.  The

Collaboration Agreement, as hereby amended, shall continue in full force and

effect.

12.2        Notices.

 The address for notices to Warner set forth

in Section 14.6 of the Collaboration Agreement is hereby revised as follows:

	

  If to Warner, addressed

  to:

  	

  George

  M. Milne, Jr., Ph.D.

  

  President, Strategic & Operations Management,

  

  Pfizer Inc. 

  50 Pequot Avenue 

  New London, CT 06320

  
	

   

  	

   

  
	

   

  	

  Facsimile:860-732-7029

  
	

   

  	

   

  
	

  With a copy to:

  	

  Joshua

  A. Kalkstein 

  Assistant General Counsel, PGRD 

  Pfizer Inc. 

  50 Pequot Avenue 

  New London, CT 06320

  
	

   

  	

   

  
	

   

  	

  Facsimile: 860-732-7384

  

 

12.3        Assignment

Section 14.2(b) of

the Collaboration Agreement is hereby amended so that that in the event Warner

no longer has any right to develop or commercialize a Licensed Product, Onyx

may freely assign its rights and obligations under the Collaboration Agreement.

IN WITNESS WHEREOF, the Parties have executed this Amendment in duplicate

originals by their proper officers as of the Amendment Date.

 

	

  ONYX PHARMACEUTICALS, INC.

  	

   

  	

  WARNER-LAMBERT COMPANY

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

  By:

  	

  /s/ Hollings C. Renton

  	

   

  	

  By: 

  	

  /s/ Peter B. Corr

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

  Name:

  	

  Hollings C. Renton

  	

   

  	

  Name:

  	

  Peter B. Corr, Ph.D.

  	

   

  
	

   

  	

   

  	

  Sr. Vice President, Pfizer Inc.

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

  Title:  

  	

  Chairman and Chief  Executive

  Officer

  	

   

  	

  Title:

  	

  Executive Vice President, Pfizer Global  R&D

  And President, Worldwide Development 

  	

   

  

 

[ * ] = CERTAIN CONFIDENTIAL

INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED

AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO

RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.Prepared by MERRILL CORPORATION

[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN

THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH

THE SECURITIES AND EXCHANGE COMMISSION PURUANT TO RULE 24B-2 OF THE SECURITIES

EXCHANGE ACT OF 1934, AS AMENDED.

EXHIBIT 10.37

AMENDMENT

#3 TO THE RESEARCH, DEVELOPMENT AND MARKETING COLLABORATION AGREEMENT

BETWEEN

ONYX

PHARMACEUTICALS, INC.

AND WARNER-LAMBERT COMPANY

THIS

AMENDMENT #3 to the Research, Development and Marketing Collaboration

Agreement dated as of July 31,

1997 (“Third

Amendment”) is made and entered into on August 6, 2001 (the “Amendment

Date”), by and between Onyx Pharmaceuticals, Inc.,

a Delaware corporation having its principal place of business at 3031 Research

Drive, Richmond, California 94806 (“Onyx”), and the Warner-Lambert Company, a

Delaware corporation and a wholly-owned subsidiary of Pfizer Inc, having a

place of business at 2800 Plymouth Road, Ann Arbor, MI  48105 ("Warner").

RECITALS

 

                WHEREAS, Onyx and Warner entered into a Research

Development and Marketing Collaboration Agreement dated July 31, 1997

(“Agreement”); and

 

                WHEREAS,the

parties subsequently amended the Agreement on August 2, 1999 and March 1, 2000;

and

 

WHEREAS,

the parties wish to further amend some of the terms and conditions under which

they will proceed with the collaboration as a result of the acquisition by

Pfizer Inc. (“Pfizer”) of Warner;

 

NOW

THEREFORE, in consideration of the

foregoing and other good and valuable consideration, the parties hereby agree

as follows:

 

1.             Except

as expressly provided herein, defined terms will have the meanings set forth in

the Agreement.

2.             The

definition of Field in Article 1 of the Agreement is deleted and replaced in

its entirety with the following:

“Field shall mean

research, drug discovery and development of [ * ].

 

For the avoidance of

doubt intellectual property, including patents, developed by Pfizer against

targets in the Field prior to and subsequent to the acquisition of Warner

including, but not limited to, compounds, assays, cell lines, reagents,

clinical data, etc., shall be contributed to the Collaboration; provided,

however, that there will be no obligation to contribute intellectual property

regarding targets outside the Field.”

3.             Section

2.4 is deleted and Article 6.0 (Licenses and Royalties) is amended as follows:

A.            New  Sections 6.3 and 6.4 are added and inserted

after Section 6.2:

 

“6.3 (a) Grant of

Research Licenses within the Field. Onyx and Warner each grant to the other

a nonexclusive, irrevocable, worldwide, royalty-free, perpetual license,

including the right to grant sub-licenses to Affiliates, to make and use the

other’s Confidential Information, Know-How and Patents for all research

purposes other than the sale or manufacture for sale of products or processes;

 

 (b) Grant of Research Licenses outside the

Field. Onyx and Warner each grant to the other a nonexclusive, irrevocable,

worldwide, royalty-free, perpetual license, including the right to grant

sub-licenses to Affiliates, to make and use the other’s confidential information,

know-how and patents covering the target [ * ], developed during the Term of the

Research Collaboration pursuant to the Research Plan, for all research purposes

other than the sale or manufacture for sale of products or processes.”

 

“6.4. Materials.  Onyx and Warner shall, upon each other’s

written request, [ * ] of Warner Patents and Know-How or Onyx Patents and

Know-How and which are licensed under this Article 6.0.”

 

B.            All

other Sections within Article 6.0 will be renumbered to reflect these

insertions, i.e. “Royalties Payable by Warner” will become Section 6.5.

4.             New

Section 6.15 is added and inserted after the renumbered Section  “Restrictions on Payment” as follows:

“6.15 Acquisition and

Assignment.  In the event that either

Onyx or Warner is acquired or assigns the Agreement to a third party, such

third party’s confidential information, know-how and patents shall not be

subject to the licenses granted under this Agreement.”

 

5.             Article

2.0 is amended. The following sentence is added to Section 2.1.

 “Warner

will provide Onyx with a list of all Collaboration Compounds within sixty (60)

days after the end of the Term of the Research Collaboration and a list of all

Collaboration Compounds within sixty (60) days after the one year anniversary

of the Term of the Research Collaboration. 

The Research Management Committee may elect to meet to discuss these

lists.”

6.             Article

3.0 is amended. The following sentence is added to the end of Section 3.1.

 “During

the one year after the Term of the Research Collaboration the Research

Management Committee will provide each other with reports, quarterly after the

Effective Date of this Third Amendment. 

The Research Management Committee may also agree to convene by

teleconference or other media to discuss the results disclosed in the reports.

7.             Section

5.4 (Warner’s Re-engagement Option) is deleted from the Agreement.

8.             Article

10.0 is amended.  A new Section 10.1 (c)

is added as follows:

“(c)  Notwithstanding the foregoing, Onyx will

have the right to disclose Confidential Information of Warner’s to third

parties in connection with a potential assignment of Onyx’s rights under the

Agreement, in addition to a potential equity investment, merger or acquisition

or collaboration, provided, however, that the third party will be required to

sign a confidentiality agreement with Onyx, prior to such disclosure and also

provided that Warner receives a copy of such agreement prior to disclosure.”

 

9.             Article

12.0 is amended. A sentence is added within Section 12.2 (Assignment)  so that Section 12.2 reads in its entirety

as follows:

“This Agreement shall

not be assignable by either party without the prior written consent of the

other party, such consent not to be unreasonably withheld.  In no event will any assignment relieve the

assigning party of its obligations hereunder. 

This Agreement shall be binding upon and, subject to the terms of the

foregoing sentence, inure to the benefit of the parties’ successors, legal

representatives and assigns.  If either

party wishes to assign this Agreement, they will so notify the other party in

writing.  The party receiving the notice

of intention to assign will have 30 days in which to object to such assignment

by the assigning party.  Notwithstanding

the foregoing, Warner may assign this Agreement to any of its wholly-owned

subsidiaries or any entity succeeding to a majority of its Parke-Davis

business, and either party may assign this Agreement to its successor in

connection with any merger, consolidation or sale of all or substantially all

of its assets.”

 

10.          Section

12.7 is amended as follows regarding notices to Warner:

“...To

Warner:

George

M. Milne, Jr., Ph.D.

President, Strategic & Operations

Management,

Pfizer Inc.

50 Pequot Avenue

New London, CT 06320

 

With copy to:

 

Joshua A. Kalkstein
        Assistant General Counsel, PGRD
        Pfizer Inc.
        50 Pequot Avenue

New London, CT 06320

 

11.          A

new Section 12.17 is added as follows:

“12.7  Diligence.  Warner shall use reasonably diligent efforts to exploit

Collaboration Compounds, Collaboration Lead Compounds and Collaboration

Products, commercially employing similar efforts applied to other products

similarly situated.”

 

Except as specifically

stated in this Third Amendment all terms and conditions of the amended

Agreement remain in full force and effect.

 

IN

WITNESS WHEREOF, each of the parties has

caused its duly authorized representative to execute and deliver this Third

Amendment as of the date set forth above.

 

 

	

  WARNER LAMBERT COMPANY

  	

   

  	

  ONYX

  PHARMACEUTICALS, INC.

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

  By 

  	

          /s/ 

  Peter B. Corr

  	

   

  	

  By 

  	

          /s/ Hollings C. Renton

  	

   

  
	

  (Signature)

  	

   

  	

  (Signature)

  	

   

  
	

   

  	

   

  	

   

  	

   

  
	

  Peter B. Corr, Ph.D.

  	

   

  	

  Hollings C. Renton

  	

   

  
	

  Sr. Vice President,

  Pfizer Inc.

  	

   

  	

  Chairman and Chief

  Executive Officer

  	

   

  
	

  Executive Vice

  President, Pfizer Global R&D

  	

   

  	

   

  	

   

  
	

  And President, Worldwide

  Development

  	

   

  	

   

  	

   

  
	

  Name and Title

  	

   

  	

  Name and Title

  	

   

  
	

   

  	

   

  	

   

  	

   

  
						

 

[ * ] = CERTAIN CONFIDENTIAL

INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED

AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURUANT TO

RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.

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