Miscellany

COLLABORATION AGREEMENT

Pfizer Inc, a Delaware corporation, having an office at 235 East 42nd Street, New York, New York 10017 and its Affiliates (Pfizer), and ArQule Inc., a Delaware corporation, having an office at 19 Presidential Way, Woburn, MA 01801-5140 and its Affiliates (ArQule), enter into this Collaboration Agreement as of December 19, 2001 (Effective Date) to design, synthesize and provide Pfizer with pharmacologically relevant compounds, suited for incorporation into Pfizers screening file, together with related materials and information, on the terms and subject to the conditions set forth herein. This Agreement shall supercede the Technology Acquisition Agreement between Pfizer and ArQule dated as of July 19, 1999 (1999 Agreement), which 1999 Agreement shall terminate and be of no further force or effect as of the Effective Date.

1.
 
Definitions. Whenever used in this Agreement, the terms defined in this Section 1 shall have the meanings so specified.

 
1.1
 
Affiliate means any corporation or other legal entity owning, directly or indirectly, fifty percent (50%) or more of the voting capital shares or similar voting securities of Pfizer or ArQule; any corporation or other legal entity fifty percent (50%) or more of the voting capital shares or similar voting rights of which is owned, directly or indirectly, by Pfizer or ArQule; or any corporation or other legal entity fifty percent (50%) or more of the voting capital shares or similar voting rights of which is owned, directly or indirectly, by a corporation or other legal entity which owns, directly or indirectly, fifty percent (50%) or more of the voting capital shares or similar voting securities of Pfizer or ArQule.
 

 
1.2
 
Agreement Period means the period beginning on the Effective Date and ending seven (7) years later, unless terminated earlier pursuant to Section 8.
 

 
1.3
 
AMAP System means the AMAP Parallel Synthesis System described in Exhibit A and located at ArQules Medford, MA production facility (Medford), that functions as a combinatorial chemistry synthesis platform comprising Library Protocols, automated transformations, robotic chemical process workstations, workflow procedures, compound purification systems, analytical systems, user interface software, library design software and information management software.
 

 
1.4
 
ArQule Confidential Information means all information about any element of the ArQule Technology which is disclosed by ArQule to Pfizer, and designated Confidential in writing by ArQule at the time of disclosure or within thirty (30) days following disclosure.
 

 
1.5
 
ArQule Design Tools means the design tools and informatics systems described on and made part of this Agreement as Exhibit B.
 

 
 
 
[*]=CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO THE OMITTED PORTIONS. OMITTED TEXT IS INDICATED BY A *.

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1.6
 
ArQule Technology means all Related Technology (including but not limited to ArQules AMAP Parallel Synthesis System and ArQule Design Tools), which is or was developed by employees of or consultants to ArQule alone or jointly with third parties prior to the Effective Date, or acquired by purchase, license, assignment or other means from third parties by ArQule prior to the Effective Date; and improvements related solely to the foregoing.
 

 
 
 
Notwithstanding the foregoing, ArQule Technology shall not include any Related Technology that ArQule does not have the right to license, sublicense, or practice without the consent of or payment to a third party.
 

 
1.7
 
Calendar Quarter means any calendar quarter during the Agreement Period, provided, however, that the first Calendar Quarter of the Agreement shall mean the time period including any remaining days in 2001 on and following the Effective Date and the first calendar quarter in 2002.
 

 
1.8
 
Collaboration Program is the program to produce Pfizer Compounds as conducted by Pfizer and ArQule pursuant to the Project Plan.
 

 
1.9
 
Library Protocols means the documented compound library synthesis protocols that ArQule has fully validated in connection with the Collaboration Program on the AMAP System, together with associated know-how and trade secrets.
 

 
1.10
 
Party means ArQule or Pfizer, and Parties means ArQule and Pfizer.
 

 
1.11
 
Pfizer Compounds means the compounds produced or designed, their intermediates, and the protocols used to produce those compounds, pursuant to the Collaboration Program, and all * related to such compounds.
 

 
1.12
 
Pfizer Confidential Information means all information about any element of Pfizer Technology which is disclosed by Pfizer to ArQule and designated Confidential in writing by Pfizer at the time of disclosure or within thirty (30) days following disclosure.
 

 
1.13
 
Pfizer Technology means all Related Technology that is or was developed by employees of or consultants to Pfizer alone or jointly with third parties prior to the Effective Date, or acquired by purchase, license, assignment or other means from third parties by Pfizer prior to the Effective Date; and improvements related solely to the foregoing.
 

 
 
 
Notwithstanding the foregoing, Pfizer Technology shall not include any Related Technology that Pfizer does not have the right to license, sublicense, or practice without the consent of or payment to a third party.


153639

AMENDED AND RESTATED

CANCER COLLABORATION AGREEMENT

THIS AMENDED AND RESTATED CANCER COLLABORATION AGREEMENT (the Amended and Restated Agreement) is made and entered into as of December 15, 2003 (the Amendment Effective Date) by and between EXELIXIS, INC., a Delaware corporation having its principal place of business at 170 Harbor Way, P.O. Box 511, South San Francisco, California 94083-0511 (Exelixis), and BRISTOL-MYERS SQUIBB COMPANY, a Delaware corporation headquartered at 345 Park Avenue, New York, New York, 10154 (BMS).  Exelixis and BMS are sometimes referred to herein individually as a Party and collectively as the Parties.

RECITALS

A.                                    BMS is a multinational health care company that has expertise and capability in developing and marketing human pharmaceuticals and has research and development programs.

B.                                    Exelixis is a multinational biotechnology company that has expertise and proprietary technology relating to genetic model systems, functional genomics and computational biology and is applying such technology to discover and validate targets for drug discovery in a variety of disease areas.

C.                                    BMS and Exelixis desire to establish a collaboration to apply such Exelixis technology and expertise to the identification and characterization of biochemical pathways and targets in specific research areas relevant to cell growth and proliferation, to generate small molecule therapeutic or prophylactic compounds directed against such targets, and to provide for the development and commercialization of novel therapeutic and prophylactic products based on such research.

D.                                    Exelixis and BMS entered into the Cancer Collaboration Agreement (the Agreement) on July 17, 2001 (the Effective Date) and subsequently amended the Agreement pursuant to a Letter Amendment effective December 7, 2001 (the First Amendment).

E.                                      Exelixis and BMS now wish to amend further the Agreement and to restate the amended agreement.

NOW, THEREFORE, the Parties agree as follows:

1.                                      DEFINITIONS

The following terms shall have the following meanings as used in this Amended and Restated Agreement:

1.1                               Abandoned DVT means [ * ].

1.2                               Abandoned ET means [ * ].

1.3                               Abandoned Target means an Abandoned DVT or an Abandoned ET.

1.4                               Affiliate means, with respect to a particular Party, a person, corporation, partnership, or other entity that controls, is controlled by or is under common control with such Party.  For the purposes of the definition in this Section 1.4, the word control (including, with correlative meaning, the terms controlled by or under the common control with) means the actual power, either directly or indirectly through one (1) or more intermediaries, to direct or cause the direction of the management and policies of such entity, whether by the ownership of at least fifty percent (50%) of the voting stock of such entity, or by contract or otherwise.

1.5                               Assay means [ * ].

1.6                               Back-up Compound means, [ * ].

1.7          BMS Collaboration Product means [ * ].

1.8                               BMS DVT Product means [ * ].

1.9                               BMS ET Product means [ * ].

1.10                        BMS Know-How means all Information Controlled by BMS (other than BMS Patents) and its Affiliates during the term of the Agreement or this Amended and Restated Agreement that is necessary or reasonably useful for Exelixis to exercise the rights licensed or granted to it under Sections 5.3 and 5.5 hereof and/or to perform its obligations to the Collaboration under this Amended and Restated Agreement.

1.11                        BMS Patents means all Patents Controlled by BMS and its Affiliates, including Patents Controlled jointly with Exelixis, during the term of the Agreement or this Amended and Restated Agreement that are necessary or reasonably useful for Exelixis to exercise the rights licensed or granted to it under Section 5.3 (or which may be acquired by it under Section 5.5 hereof) and/or to perform its obligations to the Collaboration under this Amended and Restated Agreement.

1.12                        BMS Product means [ * ].

1.13                        BMS Selected DVT means [ * ].

1.14                        BMS Selected ET means [ * ].

1.15                        BMS Selected Target means [ * ].

1.16                        BMS Sole Product means [ * ].

1.17                        Collaboration means all the activities performed by or on behalf of Exelixis or BMS in the course of performing work contemplated in Article 2 or Section 3.1 or 3.5.

1.18        Collaboration Compound means [ * ].

RESTRUCTURED AND RESTATED HspE7 COLLABORATION AGREEMENT

AMONG

STRESSGEN DEVELOPMENT CORPORATION AND

STRESSGEN BIOTECHNOLOGIES CORPORATION

AND

F.HOFFMANN-LA ROCHE LTD AND HOFFMANN-LA ROCHE INC.

December 1, 2003

This RESTRUCTURED AND RESTATED HSPE7 COLLABORATION AGREEMENT (Agreement) is made as of December 1, 2003 (the Effective Date) by and among, on the one hand, STRESSGEN DEVELOPMENT CORPORATION, a Barbados corporation, with its principal office at Whitepark House, White Park Road, P.O. Box 806E, Bridgetown, Barbados (Stressgen), and STRESSGEN BIOTECHNOLOGIES CORPORATION, a corporation organized under the laws of Yukon Territory, Canada, with its principal office at #350 4243 Glanford Avenue, Victoria, BC Canada V8Z 4B9 (SBC), and, on the other hand, F.HOFFMANN-LA ROCHE LTD, a Swiss corporation, with its principal office at Grenzacherstrasse 124, CH-4070-Basel Switzerland and HOFFMANN-LA ROCHE INC., a New Jersey corporation, with its principal office at 340 Kingsland Street, Nutley, New Jersey 07110 (collectively, Roche).

RECITALS

1.                                      Stressgen and SBC own intellectual property rights related to, among other products, HspE7 (as defined below), which is now in Phase II clinical trials.

2.                                      Roche has expertise in the development and commercialization of pharmaceutical products.

3.                                      Roche, Stressgen and SBC have entered into that certain HspE7 Collaboration Agreement, effective June 21, 2002, pursuant to which the Parties were to co-develop HspE7 for certain specified indications, share in the development costs associated therewith, and have Roche commercialize HspE7 worldwide (the Prior Agreement).

4.                                      The Parties now desire to restructure their collaborative efforts with respect to HspE7, to provide that Stressgen take the lead in the manufacture, continued clinical development and commercialization of HspE7 for certain indications, that Roche be granted an exclusive option to obtain exclusive, worldwide rights to such product, and that Roche be granted a license to develop and commercialize a second generation

1

HspE7 product for certain indications, and have prepared this Agreement to govern such restructured arrangement.

AGREEMENT

NOW, THEREFORE, in consideration of the premises and the mutual covenants and agreements contained in this Agreement, the Parties, intending to be legally bound, do hereby agree as follows:

ARTICLE 1

DEFINITIONS

The following capitalized terms, whether used in the singular or the plural, shall have the following meanings as used in this Agreement unless otherwise specifically indicated:

1.1                               Affiliate shall mean (a) an entity which owns, directly or indirectly, a controlling interest in a Party, by stock ownership or otherwise, (b) any entity which a Party owns a controlling interest, by stock ownership or otherwise; or (c) any entity, under direct or indirect common control of a Party.  For purposes of this paragraph, controlling interest and control mean ownership of greater than fifty percent (>50%) of the voting stock permitted to vote for the election of the board of directors or any other arrangement resulting in control or the right to control the management and the affairs of the Party.  For purposes of this Agreement, Genentech, Inc., 1 DNA Way, South San Francisco, California, and Chugai Pharmaceutical Company, Ltd., 1-9 Kyobashi 2-chome, Chuo-ku, Tokyo, 104-8301, Japan, shall not be deemed an Affiliate of Roche.

1.2                               BLA Filing shall mean a Biologics Licensing Application or New Drug Application filed with the FDA, or the equivalent application to the equivalent agency in any other country, the filing of which is necessary to market and sell a Target Product, including all amendments and supplements to any of the foregoing.

COLLABORATION AGREEMENT

        THIS COLLABORATION AGREEMENT (the "Agreement") is made by and between Corgentech Inc., a Delaware corporation having its principal place of business at 650 Gateway Boulevard, South San Francisco, CA 94080 ("Corgentech") and Bristol-Myers Squibb Company, a Delaware corporation headquartered at 345 Park Avenue, New York, New York 10154 ("BMS"), effective as of the date signed by the last Party to sign below (the "Effective Date"). Corgentech and BMS are sometimes referred to herein individually as a "Party" and collectively as the "Parties."

RECITALS

        WHEREAS, Corgentech is a biotechnology company engaged in the research, development and commercialization of pharmaceutical products consisting of transcription factor decoy molecules delivered to various tissues using proprietary devices and other technologies;

        WHEREAS, Corgentech is developing a proprietary transcription factor decoy known as the "E2F Decoy" and proprietary devices for delivering such decoy to vascular tissue for the prevention of graft failure, restenosis and atherosclerosis;

        WHEREAS, BMS is a worldwide, research-based pharmaceutical company, engaged in the discovery, development, manufacturing and marketing of new therapies and treatment programs that can improve people's health and extend their lives;

        WHEREAS, BMS and Corgentech desire to collaborate in the development and commercialization of the E2F Decoy and related delivery devices for the prevention of graft failure, restenosis, atherosclerosis, and such other human diseases and conditions as may be mutually agreed upon by the Parties in accordance with this Agreement;

        WHEREAS, Corgentech desires to appoint BMS its exclusive distributor for products including the E2F Decoy and related delivery devices in the United States, subject to Corgentech's right to co-promote such product as provided herein;

        WHEREAS, Corgentech and BMS desire to co-promote products including the E2F Decoy and related delivery devices in the United States for such purposes, and BMS desires to obtain an exclusive license to commercialize such products outside of the United States for such purpose; and

        WHEREAS, Corgentech desires to grant to BMS rights to such products on the terms set forth below, and BMS desires to receive such rights on the terms set forth below.

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

ARTICLE 1

DEFINITIONS

        The following terms shall have the following meanings as used in this Agreement:

        1.1    "Act" means the United States Food, Drug and Cosmetic Act, as amended.

        1.2    "Affiliate" means an individual, trust, business trust, joint venture, limited liability company, partnership, corporation, association or any other entity which (directly or indirectly) is controlled by,

1

controls or is under common control with a Party. For the purposes of this definition, the term "control" (including, with correlative meanings, the terms "controlled by" and "under common control with") as used with respect to a Party, shall mean the possession, directly or indirectly, of the power to direct, or cause the direction of, the management or policies of such person or entity, whether through the ownership of voting securities, by contract or otherwise.

        1.3    "Alliance Managers" shall have the meaning assigned in Section 2.8.

        1.4    "Allowable Expenses" means, subject to Sections 3.2(b), 3.5(h), 3.8(h), 5.4, 6.5(d), 6.18, 7.7, 10.4(c), 11.4(c), 11.9 and 15.2 the following expenses relating to Commercialization of Licensed Product in the Co-Promotion Territory: (a) Manufacturing Costs of Licensed Product intended for commercial sale in the Co-Promotion Territory, (b) Distribution Costs, (c) Third Party Royalties (other than Third Party Royalties payable by either Party pursuant to Section 10.4(c)(iii)) with respect to the Commercialization of Licensed Product in the Co-Promotion Territory or the manufacture of Licensed Product sold in the Co-Promotion Territory, (d) Sales and Marketing Costs, (e) Patent Costs (to the extent not otherwise reimbursed under Section 11.4(c)), (f) Trademark Costs (to the extent not otherwise reimbursed under Section 11.9(c)), and (g) Regulatory Expenses. The components of Allowable Expenses shall be calculated in accordance with the applicable definition thereof and the applicable terms of this Agreement, and consistent with the relevant plans and budgets approved from time to time.

        1.5    "Annual Plan and Budget" shall have the meaning assigned in Section 3.2.

        1.6    "Approval" means: (a) in the Co-Promotion Territory, receipt from the FDA of approval to market a Licensed Product; and (b) in the Royalty Territory, approval from the applicable Regulatory Authority in a given country or countries to market a Licensed Product in such country or countries, including receipt of pricing/reimbursement approval, where applicable.

        1.7    "ANDA" means an Abbreviated New Drug Application, or equivalent thereof outside of the United States.

        1.8    "AVG" means arterial-venous grafts, typically composed of a synthetic material, that are implanted into end stage renal disease patients to connect arterial and venous vessels so as to provide an access conduit for hemodialysis.

        1.9    "BMS Know-How" means Information which (a) BMS discloses to Corgentech under this Agreement, (b) is within the Control of BMS, and (c) is necessary or useful in the development, manufacture, use or sale of Licensed Product. Notwithstanding anything herein to the contrary, BMS Know-How shall exclude BMS Patents.

        1.10    "BMS Patent" means the rights granted by any governmental authority under a Patent that covers a method, apparatus, material or article of manufacture necessary or useful in the research (to the extent included in the Development Plan), development, manufacture, use or sale of Licensed Product, and that is Controlled by BMS during the term of this Agreement, including without limitation BMS' interest, if any, in any Joint Patents.

        1.11    "BMS Technology" means the BMS Patents and BMS Know-How.

        1.12    "Business Day" means a day that is not a Saturday, Sunday or a day on which banking institutions in New York, New York are required by law to remain closed.

        1.13    "BWH License" means the License Agreement between Corgentech (as Caber Corp.) and The Brigham and Women's Hospital, Inc. (BWH#A5288) dated January 1, 1999, as amended and restated.

        1.14    "CABG" means coronary artery bypass grafts, typically composed of saphenous veins (although other vessels can be used), that are implanted into patients having one or more occluded or

2

stenosed coronary arteries and that serve to bypass such occlusion or stenosis and to provide blood flow to otherwise ischemic tissue.

        1.15    "Call Center" means the customer support center established by the Parties under the direction of the JCC in cooperation with the RWG, in the Co-Promotion Territory.

        1.16    "CE Marking" means the letters "CE" which a manufacturer affixes to certain products for access to certain European markets to indicate that the manufacturer has conformed with all the obligations required by the European Medical Devices Directive 93/42/EEC and other applicable directives. The letters "CE" are an abbreviation of a French phrase "Conformit Europenne."

        1.17    "Clinical Costs" means the FTE Costs (charged in accordance with Section 3.8(f)) and out-of-pocket costs incurred by a Party or any of its Affiliates in accordance with GAAP after the Effective Date during the term of and pursuant to this Agreement (which costs may include costs accrued in accordance with GAAP prior to, but unpaid as of, the Effective Date for services and/or supplies to be provided after the Effective Date, to the extent such accrued expenses have been included in Exhibit B of the Disclosure Letter) by Corgentech in connection with (i) Phase I, Phase I/II, Phase II and Phase III Clinical Trials of a Licensed Product conducted in any country throughout the world for the purpose of obtaining Approval for a Licensed Product in the Co-Promotion Territory or the EU and (ii) Phase IIIB Clinical Trials for the Co-Promotion Territory or the EU. Subject to the foregoing, Clinical Costs shall include, without limitation, such costs in connection with the following activities:

        (a)   the preparation for and conduct of clinical trials (except for related Manufacturing Costs otherwise included in Development Costs);




        (b)   data collection and analysis, and report writing; and




        (c)   clinical laboratory work.

Clinical Costs shall not include costs incurred (whether or not accrued as of the Effective Date) in connection with Phase IV Clinical Trials.

        1.18    "Commercialize" means to promote, market, distribute, sell and provide product support for a product, and "Commercializing" and "Commercialization" shall be interpreted accordingly.

        1.19    "Committee" means the Joint Steering Committee, Joint Development and Regulatory Committee, Joint Commercialization Committee, Joint Manufacturing Committee or Joint Finance Committee.

        1.20    "Competing Product" means, on a country-by-country basis, with respect to any country in the Territory any pharmaceutical product that, as its primary mechanism of action, directly binds to the transcription factor known as E2F and that either (a) has been Approved for any of the same indications for which Licensed Products have been Approved in such country in the Field, or (b) if known to the Party that controls such product, is used in such country in any of the same indications for which Licensed Products have been Approved in such country in the Field at a level that is equal to or greater than [*] of the level of sales of Licensed Products in such country for such indication (calculated on a unit basis using data provided by IMS International (or other mutually acceptable data source)).

        1.21    "Confidential Information" shall have the meaning assigned such term in Section 12.1.

        1.22    "Control" means, with respect to any Information or intellectual property right, possession by a Party of the ability to grant the right to access or use, or to grant a license or a sublicense to, such Information or intellectual property right as provided for herein without violating the terms of any agreement or other arrangement with any Third Party.

Collaboration Agreement
between
APPLIED BIOSYSTEMS AND CEPHEID

THIS AGREEMENT (Agreement) is made as of the 11th day of October, 2002 (the Effective Date) and is by and between Applera Corporation, a Delaware corporation, acting through its Applied Biosystems Group, with a place of business at 850 Lincoln Center Drive, Foster City, CA 94404, U.S.A. (ABI), and Cepheid, a California corporation with its principal place of business at 904 Caribbean Drive, Sunnyvale, CA 94089 (Cepheid). Cepheid and ABI are sometimes referred to herein individually as a Party, and collectively as the Parties.

1.     Background

1.1   Supply to the USPS. ABI and Cepheid will each independently and working collaboratively seek to develop and manufacture Products for use in Bio-Threat Agent Detection Systems. These Bio-Threat Agent Detection Systems are intended to be provided to the USPS through agreements among the USPS, Northrop Grumman Security Services (Northrop Grumman), ETG (Environmental Technology Group, now known as Smiths-Detection Edgewood, Inc.), and/ or Cepheid, and potentially others. These Bio-Threat Agent Detection Systems are intended to be used in conjunction with the mail sorting machines used by the USPS, in order for the USPS to test for particular bio-threat agents identified as being of interest to the USPS.

1.2   ABI Materials. The systems that are being provided are based on an assay called the 5 nuclease detection process, a process employing in part the polymerase chain reaction (PCR), herein called Real-Time PCR. Due to licensing constraints imposed by Roche Molecular Systems, Inc. and F. Hoffman La Roche Ltd (collectively, Roche), the owner of some of the patents for the Real-Time PCR process, certain rules must be followed in order for Cepheid and the USPS to be properly licensed under the Real-Time PCR patents as contemplated by this Agreement. [***]ABI owns other rights related to the Real-Time PCR process [***].

1.3   Intellectual Property Objectives. It is the Parties intention that through this Agreement and the parties existing Thermal Cycler Supplier Agreement obtained from ABI, under which Cepheid is authorized by ABI under certain of the PCR Rights to manufacture and sell thermal cyclers, and under which Cepheid manufactures and sells its GeneXpert thermal cycler instrument, the Bio-Threat Agent Detection Systems to be sold to the USPS will be fully licensed or otherwise manufactured and sold with all necessary authority under all PCR related intellectual property rights of ABI as well as Roche.

1.4   Prior Work by Cepheid. Cepheid has been working in collaboration with the USPS and Northrop Grumman to develop an initial assay to be used in conjunction with the GeneXpert Module in order to test for certain strains of Bacillus anthracis (anthrax) of interest to the USPS. Those parties have undertaken significant initial validation studies in order to satisfy the requirements of the USPS and, as part of those development activities, certain Third Party Materials have been and are being used. Cepheid and ABI now wish to develop and employ Products in which ABI PCR Materials will be used instead of such Third Party Materials so that certain anticipated advantages of ABI PCR Materials may be realized, but recognize that the already validated initial assay will be used during the initial period of implementation by the USPS. The parties will use their respective commercially reasonable efforts to demonstrate to the USPS that Products using ABI PCR Materials will meet or exceed all USPS requirements and specifications and that such Products should be accepted instead of those using the initial materials. It should be noted, however, that the ultimate decision as to whether to switch to ABI PCR Materials may be within the discretion of the USPS. The Parties have begun to explore the use of ABI PCR Materials and have determined to engage in the Joint Development Program to

The symbol [***] is used to indicate that a portion of the exhibit has been omitted and filed separately with the commission. Confidential treatment has been requested with respect to the omitted portion.

develop, qualify and validate them for use as the reagent components of Products, so that a new, validated assay using ABI materials and employing their anticipated advantages may be substituted for the initial assay as soon as feasible, preferably within six months of the Effective Date.

1.5   Special Format Assay. An important feature of this program for the USPS is the special format of the reagent kit for performing the assay. Cepheid has developed a method of drying the liquid reagents into a pelletized form. The dried pellets can be placed into a proprietary self-contained cartridge developed by Cepheid, in which the reagents can be reconstituted at the time that the assay is to be performed. The cartridge itself has significant added value, in that it is the vessel in which the anthrax spores are cracked and in which Real-Time PCR is performed.

1.6   Purpose. The Parties wish to enter into this Agreement to set forth the terms and conditions under which development of the initial validated system described above will be completed, development of second generation Products will be undertaken, and designated systems will be manufactured and supplied to the USPS by ABI, either directly or through Cepheid as a distributor of ABI, or Northrop Grumman or another Third Party or Third Parties distributors or subdistributors.

Now therefor, the Parties, in consideration of the mutual obligations hereinafter set forth and intending to be legally bound, hereby agree as follows:

2.     Definitions. Within the meaning of this Agreement:

2.1   ABI PCR Materials means reagents or reagent components, including labeled and unlabeled oligonucleotides (such as, without limitation, primers and probes) used in or useful for Real Time PCR, and the polymerase used for the Real Time PCR that ABI supplies to Cepheid as the packer of Cartridges pursuant to the Cartridge Packing Agreement for incorporation and use by the USPS in the Bio-Threat Agent Detection Systems of which Products are a component, and that ABI manufactures itself or that, on or after the date that Second Generation Products are fully substituted for initial Products as the Products that are manufactured and sold to the USPS pursuant to the Distributor Agreement, ABI sources itself or selects and designates as the Materials to be included in Products. Without limiting the scope of other materials excluded from the definition of ABI PCR Materials, the Parties understand and agree that specifically excluded from ABI PCR Materials are reagent and reagent components (but not the polymerase, which in all cases is included in ABI PCR Materials) that Cepheid has obtained from the supplier or suppliers used by Cepheid for such materials as of the Effective Date, even if ABI obtains such reagents and reagent components from such suppliers or other suppliers and supplies them to Cepheid pursuant to the Cartridge Packing Agreement, except for such of such reagent and reagent components, if any, as ABI specifically selects and designates to be included in Second Generation Products.

2.2   Affiliate of a Party or other person or entity means any corporation, firm, partnership or other entity, whether de jure or de facto, which directly or indirectly owns, is owned by or is under common ownership with such Party or other person or entity to the extent of more than fifty percent of the equity having the power to vote on or direct the affairs of the entity, or such lesser percentage which is the maximum allowed to be owned by a foreign corporation in a particular jurisdiction.

2.3   Authorized Use means use by the USPS for the detection of anthrax, and such other bio-threat agents as the Parties may agree in writing are bio-threat agents to be detected by Products, in the environment in accordance with the label license set forth in Section 6.3, or such other label license or limitations as ABI may designate (provided that the Authorized Use stated on the label license set forth in Section 6.3 is not diminished) or the Parties may agree upon in writing and which is applicable to the USPS use of Products. Authorized use shall not mean use for human diagnostic or therapeutic purposes.

The symbol [***] is used to indicate that a portion of the exhibit has been omitted and filed separately with the commission. Confidential treatment has been requested with respect to the omitted portion.


196671

hTG COLLABORATION AGREEMENT

          THIS hTG COLLABORATION AGREEMENT  (the hTG Collaboration Agreement) is made and entered into effective as of November 8, 2002 (the Effective Date) by and between SANGSTAT MEDICAL CORPORATION, a Delaware corporation having its principal place of business at 6300 Dumbarton Circle, Fremont, California, 94555 (SMC), and THERAPEUTIC HUMAN POLYCLONALS, INC., a California corporation having its principal place of business at 101 North Wilmot Road, Tucson, Arizona, 85711 (THP).  SMC and THP are sometimes referred to herein individually as a Party and collectively as the Parties.

RECITALS

          A.           SMC has expertise useful in the discovery, development and commercialization of therapeutic products, including antibody products, in the areas of transplantation, immunology, hematology and oncology.

          B.          THP possesses and is developing proprietary genetic-engineering technology, intellectual property and expertise relating to genetically modified animals, such as rabbits, that may produce human polyclonal antibodies for use as human therapeutics.

          C.          SMC and THP intend to establish a collaboration under which THP will develop  genetically-modified rabbits meeting certain milestone criteria for intended use by SMC in development of polyclonal antibody products within the collaboration, with assistance from SMC as may be required to meet the milestone criteria.

          D.          THP desires to grant to SMC, and SMC desires to receive, the right to evaluate certain THP technology under the Research License and an option to obtain an exclusive, royalty-bearing, worldwide, field-restricted license to that technology.  Under the collaboration and above referenced license, SMC will use commercially reasonable efforts to develop and, if the option is exercised, commercialize polyclonal antibody products [**], with such assistance from THP as may be required to use the THP Technology therefor.

          E.           Concurrent with execution of this hTG Collaboration Agreement, the Parties are entering into (i) the Stock Purchase Agreement, pursuant to which SMC is purchasing equity in THP, and (ii) the Hematology Alliance Agreement, under which the Parties are establishing a collaboration pursuant to which they intend to research and develop possible antibody products based on use of THP Technology in conjunction with antigens relating to hematological diseases.

          Now, Therefore, for and in consideration of the mutual covenants contained herein and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties agree as follows:

** This redacted material has been omitted pursuant to a request for confidential treatment, and the material has been filed separately with the Securities and Exchange Commission.

1

1.          DEFINITIONS

             Any capitalized term used in this hTG Collaboration Agreement that is not otherwise defined herein will have the meaning set forth in Appendix 1.

2.          OVERVIEW AND MANAGEMENT OF THE hTG PROGRAM

             2.1.     Scope.  Initially, THP will conduct further genetic engineering and related work using its technology and expertise in an effort to achieve the F2A+ Milestone as soon as practicable.  Prior to achieving the F2A+ Milestone, THP may prepare certain transgenic rabbits that, while not fully meeting the criteria to qualify as a F2A Animal, are nonetheless useful for research purposes under the hTG Program.  SMC will test those animals as requested by THP and will provide THP the results of any testing to further THPs efforts to create useful transgenic rabbits and achieve the F2A+ Milestone.  The Parties will reasonably cooperate in all efforts of THP to reach the F2A+ Milestone.  Promptly after THP has produced the transgenic animals pursuant to the F2A+ Milestone, SMC will undertake efforts to further evaluate such F2A Animals to determine whether it will exercise the hTG Commercial Option and THP will supply SMC with initial breeding pairs of such THP Animals as are reasonably needed for SMCs activities under the hTG Program. During the term of this hTG Collaboration Agreement, THP will supply to SMC, from time to time, any THP Animals that are improvements over previously supplied F2A Animals in accordance with Section 4.6 hereto.  THP will supply to SMC sufficient quantities of improvement THP Animals so that SMC, at its own expense, can establish a breeding colony of these THP Animals for use in the hTG Program.  If SMC elects not to exercise the hTG Commercial Option before the end of the hTG Commercial Option Period, SMC will return all THP Animals and THP Know-How in its possession under this Agreement to THP, unless the Hematology Alliance Agreement or a Hematology Commercial License Agreement is still in effect, in which case the THP Animals and THP Know-How will be covered by such Hematology Alliance Agreement or Hematology Commercial License Agreement(s).  The majority of the research and development efforts conducted after achievement of the F2A+ Milestone, including the development of hTG Antibody Products, will be conducted and directed by SMC with collaborative efforts from THP.  The goal of these efforts is, if the hTG Antibody Products have the appropriate technical characteristics, to seek to obtain the requisite Regulatory Approvals for at least one (1) hTG Antibody Product in an expeditious manner.  The Parties will manage the hTG Program through a committee (the Steering Committee) as discussed below.

             2.2.      Formation and Composition of the Steering Committee.  Promptly after the Effective Date, the Parties will form a Steering Committee by each Party designating an equal number of its employees (minimum of two (2) and a maximum of three (3) unless otherwise agreed in writing by the Parties) as its representatives on the Steering Committee.  The Parties will endeavor to designate employees with the appropriate skills and experience necessary to perform the tasks and supervisory functions of the Steering Committee, and with seniority sufficient to facilitate decision-making on behalf of the Parties with respect to the hTG Program.  An alternate representative designated by a Party may serve temporarily in the absence of one of that Partys designated representatives, and a Party may replace any of its representatives on the Steering Committee in the designating Partys discretion.  Each Party will designate one of its representatives on the Steering Committee as a Project Liaison. Each Project Liaison will serve as the liaison between the Parties and the Steering Committee, and such liaison function will include the reporting of the respective progress of each Party under the hTG Program.  A Project Liaison may also serve as an Alliance Liaison under the Hematology Alliance Agreement.

Collaboration Agreement
between
Applied Biosystems and Cepheid

THIS AGREEMENT ("Agreement") is made as of the 11th day of October, 2002 (the "Effective Date") and is by and between Applera Corporation, a Delaware corporation, acting through its Applied Biosystems Group, with a place of business at 850 Lincoln Center Drive, Foster City, CA 94404, U.S.A. ("ABI"), and Cepheid, a California corporation with its principal place of business at 904 Caribbean Drive, Sunnyvale, CA 94089 ("Cepheid"). Cepheid and ABI are sometimes referred to herein individually as a "Party," and collectively as the "Parties".

1. Background

1.1 Supply to the USPS. ABI and Cepheid will each independently and working collaboratively seek to develop and manufacture Products for use in Bio-Threat Agent Detection Systems. These Bio-Threat Agent Detection Systems are intended to be provided to the USPS through agreements among the USPS, Northrop Grumman Security Services ("Northrop Grumman"), ETG (Environmental Technology Group, now known as Smiths-Detection Edgewood, Inc.), and/ or Cepheid, and potentially others. These Bio-Threat Agent Detection Systems are intended to be used in conjunction with the mail sorting machines used by the USPS, in order for the USPS to test for particular bio-threat agents identified as being of interest to the USPS.

1.2 ABI Materials. The systems that are being provided are based on an assay called the 5' nuclease detection process, a process employing in part the polymerase chain reaction ("PCR"), herein called Real-Time PCR. Due to licensing constraints imposed by Roche Molecular Systems, Inc. and F. Hoffman La Roche Ltd ("collectively, Roche"), the owner of some of the patents for the Real-Time PCR process, certain rules must be followed in order for Cepheid and the USPS to be properly licensed under the Real-Time PCR patents as contemplated by this Agreement. [***]ABI owns other rights related to the Real-Time PCR process [***].

1.3 Intellectual Property Objectives. It is the Parties' intention that through this Agreement and the parties' existing Thermal Cycler Supplier Agreement obtained from ABI, under which Cepheid is authorized by ABI under certain of the PCR Rights to manufacture and sell thermal cyclers, and under which Cepheid manufactures and sells its GeneXpert thermal cycler instrument, the Bio-Threat Agent Detection Systems to be sold to the USPS will be fully licensed or otherwise manufactured and sold with all necessary authority under all PCR related intellectual property rights of ABI as well as Roche.

1.4 Prior Work by Cepheid. Cepheid has been working in collaboration with the USPS and Northrop Grumman to develop an initial assay to be used in conjunction with the GeneXpert Module in order to test for certain strains of Bacillus anthracis ("anthrax") of interest to the USPS. Those parties have undertaken significant initial validation studies in order to satisfy the requirements of the USPS and, as part of those development activities, certain Third Party Materials have been and are being used. Cepheid and ABI now wish to develop and employ Products in which ABI PCR Materials will be used instead of such Third Party Materials so that certain anticipated advantages of ABI PCR Materials may be realized, but recognize that the already validated initial assay will be used during the initial period of implementation by the USPS. The parties will use their respective commercially reasonable efforts to demonstrate to the USPS that Products using ABI PCR Materials will meet or exceed all USPS requirements and specifications and that such Products should be accepted instead of those using the initial materials. It should be noted, however, that the ultimate decision as to whether to switch to ABI PCR Materials may be within the discretion of the USPS. The Parties have begun to explore the use of ABI PCR Materials and have determined to engage in the Joint Development Program to develop, qualify and validate them for use as the reagent components of Products, so that a new, validated assay using ABI materials and employing their anticipated advantages may be substituted for the initial assay as soon as feasible, preferably within six months of the Effective Date.

1.5 Special Format Assay. An important feature of this program for the USPS is the special format of the reagent kit for performing the assay. Cepheid has developed a method of drying the liquid reagents into a pelletized form. The dried pellets can be placed into a proprietary self-contained cartridge developed by Cepheid, in which the reagents can be reconstituted at the time that the assay is to be performed. The cartridge itself has significant added value, in that it is the vessel in which the anthrax spores are cracked and in which Real-Time PCR is performed.

1.6 Purpose. The Parties wish to enter into this Agreement to set forth the terms and conditions under which development of the initial validated system described above will be completed, development of second generation Products will be undertaken, and designated systems will be manufactured and supplied to the USPS by ABI, either directly or through Cepheid as a distributor of ABI, or Northrop Grumman or another Third Party or Third Parties distributors or subdistributors.

Now therefor, the Parties, in consideration of the mutual obligations hereinafter set forth and intending to be legally bound, hereby agree as follows:

2. Definitions. Within the meaning of this Agreement:

2.1 "ABI PCR Materials" means reagents or reagent components, including labeled and unlabeled oligonucleotides (such as, without limitation, primers and probes) used in or useful for Real Time PCR, and the polymerase used for the Real Time PCR that ABI supplies to Cepheid as the packer of Cartridges pursuant to the Cartridge Packing Agreement for incorporation and use by the USPS in the Bio-Threat Agent Detection Systems of which Products are a component, and that ABI manufactures itself or that, on or after the date that Second Generation Products are fully substituted for initial Products as the Products that are manufactured and sold to the USPS pursuant to the Distributor Agreement, ABI sources itself or selects and designates as the Materials to be included in Products. Without limiting the scope of other materials excluded from the definition of ABI PCR Materials, the Parties understand and agree that specifically excluded from ABI PCR Materials are reagent and reagent components (but not the polymerase, which in all cases is included in ABI PCR Materials) that Cepheid has obtained from the supplier or suppliers used by Cepheid for such materials as of the Effective Date, even if ABI obtains such reagents and reagent components from such suppliers or other suppliers and supplies them to Cepheid pursuant to the Cartridge Packing Agreement, except for such of such reagent and reagent components, if any, as ABI specifically selects and designates to be included in Second Generation Products.

2.2 "Affiliate" of a Party or other person or entity means any corporation, firm, partnership or other entity, whether de jure or de facto, which directly or indirectly owns, is owned by or is under common ownership with such Party or other person or entity to the extent of more than fifty percent of the equity having the power to vote on or direct the affairs of the entity, or such lesser percentage which is the maximum allowed to be owned by a foreign corporation in a particular jurisdiction.

2.3 "Authorized Use" means use by the USPS for the detection of anthrax, and such other bio-threat agents as the Parties may agree in writing are bio-threat agents to be detected by Products, in the environment in accordance with the label license set forth in Section 6.3, or such other label license or limitations as ABI may designate (provided that the Authorized Use stated on the label license set forth in Section 6.3 is not diminished) or the Parties may agree upon in writing and which is applicable to the USPS' use of Products. Authorized use shall not mean use for human diagnostic or therapeutic purposes.

2.4 "Background ABI Intellectual Property" means all Intellectual Property Rights that are owned by, either partially or wholly, ABI, or are licensed to, or otherwise controlled by, ABI, excluding only Collaboration Joint Intellectual Property.

2.5 "Background Cepheid Intellectual Property" means all Intellectual Property Rights that are owned by, either partially or wholly, Cepheid, or are licensed to, or otherwise controlled by, Cepheid, excluding only Collaboration Joint Intellectual Property.

2.6 "Bio-Threat Agent Detection System" means the combination of Cartridges, GeneXpert Modules and Materials, and other associated materials, if any, obtained by Cepheid from Third Parties, capable of carrying out Real-Time PCR based analysis for the purpose of environmental detecting or identifying designated pathogens or biological agents, including without limitation viral and bacterial agents. The initial implementation of a Bio-Threat Agent Detection System is intended to be within the system being developed for the USPS by a consortium led by Northrop Grumman.

2.7 "Cartridge" means a closed or substantially closed plastic device containing, among other things, pelletized or dried reagents that is intended for single or multiple use sample preparation and PCR based DNA analysis and that is intended and suitable for insertion into, or use as a part of, or is a part or component of, or an attachment to, an instrument designed to hold such device and/or facilitate or enable its use, which instrument Cepheid manufactures or has manufactured, including without limitation the instrument currently named Cepheid's GeneXpert Instrument that includes one or more GeneXpert Modules, or that can be used alone or with other instruments or devices for such purpose.

2.8 "Cartridge Packing Agreement" means the cartridge packing agreement to be executed by the Parties concurred with or shortly after the execution and delivery of this Agreement, as more fully described in Section 3.2.

2.9 "Collaboration ABI Intellectual Property" means all Intellectual Property Rights arising out of work performed under this Agreement or in furtherance of this Agreement during the term of this Agreement that are conceived solely by one or more employees or agents of ABI or its Affiliates, or solely by one or more employees or agents of ABI or its Affiliates and one or more employees or agents of a Third Party.

2.10 "Collaboration Cepheid Intellectual Property" means all Intellectual Property Rights arising out of work performed under or in furtherance of this Agreement during the term of this Agreement that are conceived solely by one or more employees or agents of Cepheid or its Affiliates, or solely by one or more employees or agents of Cepheid or its Affiliates and one or more employees or agents of a Third Party.

2.11 "Collaboration Joint Intellectual Property" means all Intellectual Property Rights arising out of work performed by Cepheid under this Agreement or in furtherance of this Agreement, or out of work performed by ABI under this Agreement, that are jointly conceived by one or more employees or agents of Cepheid or its Affiliates and by one or more employees or agents of ABI or its Affiliates.

2.12 "Confidential Information" means confidential knowledge, Know-how, practices, processes, products, materials, equipment or information that a receiving Party has a reasonable basis to believe is confidential to the disclosing Party or is treated by the disclosing Party as confidential. Notwithstanding the above, Confidential Information will not include, and nothing in Section 9 will in any way restrict the rights of either Party to use, disclose or otherwise deal with, any information which:

BEEN REDACTED AND HAVE BEEN SEPARATELY FILED WITH THE COMMISSION.]


                             COLLABORATION AGREEMENT

         THIS COLLABORATION AGREEMENT (this "AGREEMENT") effective as of July 1,
2000 (the "EFFECTIVE DATE"), is entered into among DELTAGEN, INC., a Delaware
corporation with a place of business at 1003 Hamilton Avenue, Menlo Park, CA
94025, U.S.A. ("DELTAGEN"), and PFIZER INC, a Delaware corporation with a place
of business at 235 East 42nd Street, New York, New York 10017. Pfizer's
wholly-owned subsidiaries and Controlled Pfizer  . . .