Document:

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                                                                   Exhibit 10.28
                                  CONFIDENTIAL

***PORTIONS OF THE EXHIBIT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.
THE COMPLETE EXHIBIT, INCLUDING THE PORTIONS FOR WHICH CONFIDENTIAL TREATMENT
HAS BEEN REQUESTED, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.

                     FUNDED RESEARCH COLLABORATION AGREEMENT

THIS AGREEMENT is made December 22, 1998, ("Effective Date") by and between
ProdiGene, Inc., a Delaware company having a principal place of business at 1500
Research Parkway, Suite 220, College Station, Texas 77845 (hereinafter
"ProdiGene") and Genencor International, Inc., a Delaware company having a
principal place of business at 4 Cambridge Place, 1870 South Winton Road,
Rochester, New York 14618 (hereinafter "GCI")(collectively the "Parties").

WHEREAS, the Parties have entered into a Confidentiality Agreement
("Confidentiality Agreement" incorporated herein and attached hereto as APPENDIX
A) dated March 25, 1997, including the addendum dated August 4, 1997, an
Agreement for the Provision of Samples ("Samples Agreement" incorporated herein
and attached hereto as APPENDIX B) dated April 30, 1997, and an Agreement
Related to Plant Expression of Enzymes dated October 10, 1997, ("Enzymes
Agreement");

WHEREAS, the Parties wish to expand the scope of their collaboration and have
entered into negotiations related thereto;

WHEREAS, as a result of these discussions, the Parties desire to enter into a
relationship as set forth herein to further the development of an expression
system for the commercial exploitation of certain enzymes for industrial use;

NOW THEREFORE, the Parties agree as follows:

                                 I. DEFINITIONS

        1.1 "Elected Research Program" shall mean a field of research elected or
specified hereunder by the Parties for the allocation of FTEs during the Term of
this Agreement.

        1.2 "Target Compound" shall mean a compound designated in an Elected
Research Program for transgenic expression in plants. Such Target Compounds may
comprise proteins, including microbial, plant or animal enzymes, or other
compounds determined as suitable for expression in plants.

        1.3 The "Exclusive Collaboration Field" shall mean ***, and technology
related to their production, manufacture, purification, application and/or use.

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        1.4 "Affiliate" shall mean any corporation or business entity directly
or indirectly owned or controlled by a Party by virtue of ownership of at least
fifty percent (50%) of the stock and having the right to vote for directors
thereof or otherwise control the management of the corporation or business
entity.

        1.5 "Exclusivity Period" shall mean a three year period commencing at
the Effective Date. In the event that GCI exercises its Exclusivity Option under
this Agreement, the Exclusivity Period shall be a five year period commencing at
the Effective Date.

        1.6 "FTE" shall mean a one-year allocation to an Elected Research
Program of a scientist having a doctorate, masters or equivalent experience
applicable to the expression of heterologous proteins in plants, or persons with
technical expertise appropriate to conduct or participate in an Elected Research
Program who are under the guidance of such scientist.

        1.7 "Project Form" shall mean (i) when executed by one Party, that
Party's proposal to initiate an Elected Research Program, and (ii) when executed
by both Parties, the Parties mutual agreement to engage in an Elected Research
Program. A Project Form shall include identification of the Target Compounds,
Elected Research Program Field, the duration of the Elected Research Program,
resource and FTE allocation, timelines, milestones, success criteria and market
opportunities. The Project Form shall be in the form provided in APPENDIX C.

        1.8 "Elected Research Program Field" shall mean the field of research
proposed for an Elected Research Program to which research exclusivity of
Section 2.9 applies.

        1.9 "Steering Committee" shall mean a committee made up of two (2)
representatives from each of ProdiGene and GCI who shall be designated by
ProdiGene and GCI, respectively.

        1.10 "Background Technology" shall mean any technology, data, results,
biological materials, processes, reports, or other information owned or
controlled by either Party as of the Effective Date.

        1.11 "Background Patent Rights" shall mean any patent or patent
application, both foreign and domestic, including any and all divisions,
continuations, continuations-in-part, reissues, re-examination applications,
extensions, supplementary protection certificates, certificates of addition,
inventor's certificates, including international counterparts thereof owned
and/or controlled as of the Effective Date by either Party.

        1.12 "Invention(s)" shall mean any technology, data, discoveries,
results, biological materials, processes, reports, or other information
conceived and/or reduced to practice which result from an Elected Research
Program pursuant to this Agreement.

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        1.13 "Net Sales" shall mean the gross amount invoiced with respect to a
product to a Party or Affiliate thereof, less:

               ***

                        II. ELECTION OF RESEARCH PROGRAMS

               2.1 Initiation and Administration of Elected Research Programs.
The Steering Committee shall meet promptly after the execution of this Agreement
and at least quarterly thereafter to discuss the initiation of Elected Research
Program(s). The initiation of Elected Research Program(s) shall be pursuant to
agreement of the Parties as memorialized in a Project Form according to the
procedure provided below.

               (a) A Party may propose an Elected Research Program by
        completing, signing and forwarding to the other Party a Project Form
        which describes the proposed Elected Research Program.

               (b) The Party receiving a completed Project Form shall consider
        in good faith the proposed research as described in the Project Form and
        respond in writing to the proposing Party within 30 days of receipt of
        the executed Project Form in accordance with the following:

                      (i) If the receiving Party agrees to participate in the
               proposed Elected Research Program, it shall give notice by
               returning a duly executed copy of the Project Form to the
               proposing Party. The fully executed Project Form shall be
               sufficient memorialization of the mutual agreement of the Parties
               to perform the research described therein and shall be the basis
               for an Elected Research Program to which the terms of this
               Agreement apply; or

                      (ii) If the receiving Party does not agree to participate
               in the proposed Elected Research Program, it may decline to
               execute the Project Form or, alternatively, may notify the
               proposing Party that the receiving Party agrees to pursue the
               proposed Elected Research Program only under modified conditions.

               (c) Elected Research Program(s) which are initiated as provided
        in subsection (b) above shall commence immediately upon mutual execution
        of the applicable Project Form and shall be performed essentially as
        provided in the Project Form. The terms of this Agreement, including
        those provided in sections 2.4 through 2.9, shall govern all Elected
        Research Program(s), except as provided in Section 2.2 herein.

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        2.2 The Parties may mutually agree to the allocation of FTEs funded as
provided herein to the research program described in the Enzymes Agreement. In
such event, the terms of the Enzymes Agreement shall continue to control such
research program despite funding under this Agreement. Notwithstanding the
above, FTEs allocated hereunder to the Enzymes Agreement research program shall
be funded at the rates provided in this Agreement.

        2.3 Elected Research Programs may pertain to the following subject
matter:

               (a) Elected Research Program(s) Pursuant to Mutual Agreement. The
        Parties may agree to initiate an Elected Research Program(s) related to
        any plan of research within the Exclusive Collaboration Field, or such
        other research field as the Parties may mutually agree upon, provided
        that at least *** Elected Research Programs shall be initiated during
        the Term.

               (b) GCI Elected Research Programs. GCI may elect to initiate an
        Elected Research Program comprising a Target Compound from within the
        Elected Research Program Fields listed in Sections 2.3(b)(i) through
        2.3(b)(v). For the avoidance of ambiguity, the programs provided in this
        subsection with respect to Target Compound(s) are not intended to be
        limiting in any way with respect to potential programs which may be
        elected under Section 2.3(a):

               ***

               (c) Exploratory Programs. The Parties may mutually agree to
        initiate a program intended to analyze, on an exploratory basis, the
        commercial and/or technical feasibility or desirability of plant
        expression of certain genes. Exploratory programs shall not exceed the
        transgenic expression and/or analysis of *** genes. Allocation to such
        programs shall not exceed *** of the total funding provided pursuant to
        Section 5.1(a) or 5.5.

        2.4 ProdiGene and GCI agree to submit quarterly reports to the Steering
Committee detailing progress relating to their responsibilities pursuant to an
Elected Research Program and any pertinent findings, results, conclusions or
other information resulting from an Elected Research Program.

        2.5 With respect to the conduct of an Elected Research Program, the
Steering Committee will make decisions including:

               (a) reviewing the general direction and course of the research;

               (b) determining appropriate allocation of funding to Elected
        Research Program(s) provided hereunder and communicating the agreement
        of the Parties related to such allocation;

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               (c) approving changes in the direction of the research;

               (d) reviewing and approving achievement of any milestones;

               (e) reviewing and advising with regard to patents and patent
        strategy;

               (f) making recommendations to respective management of the
        Parties or making decisions, if appropriate, on all decision points
        throughout the course of the research; and

               (g) review of the progress and/or desirability of Elected
        Research Programs.

        2.6 Termination of Elected Research Programs. Elected Research Programs
may be terminated as follows:

               (a) Upon completion of the Elected Research Program as described
        in the Project Form;

               (b) Upon mutual agreement of the Parties that technology, market,
        regulatory or other considerations suggest that continued investment of
        time, resources or money related to an Elected Research Program to
        develop and commercialize a Target Compound may be unsuitable or
        undesirable. Pursuant to this sub-section, the Parties may elect to hold
        discussions toward a mutually acceptable resolution, including
        alternative target proteins, the transfer or modification between the
        Parties of rights to commercialize products, or termination of the
        Elected Research Program, as appropriate.

               (c) Upon sixty (60) days notification to ProdiGene, GCI may elect
        to cancel an Elected Research Program. In the event that GCI elects to
        cancel an Elected Research Program under this subsection, ProdiGene may
        continue such program, provided that such continuance is not
        inconsistent with the terms of this Agreement, including Article 3
        hereof. GCI agrees to negotiate in good faith with ProdiGene for a
        license to intellectual property exclusively licensed to GCI under
        Section 2.3(c) in the event that such license is necessary for the
        continuance or commercialization of the results of such canceled program
        by ProdiGene.

        2.7 Intellectual Property Rights and Commercialization in Elected
Research Programs. Intellectual property rights developed during or related to
Elected Research Programs shall be treated as follows:

               (a) To the extent that either Party owns or controls Background
        Technology or Background Patent Rights, such Background Technology and
        Background Patent Rights shall remain the sole property of that Party to
        exploit in

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        any manner it chooses at its sole discretion, except to the extent
        provided for herein.

               (b) Each Party agrees to promptly, but no later than 30 days
        after the submission of an invention disclosure to a Party's legal
        department or counsel, advise the other Party in writing of any
        Invention(s) made pursuant to this Agreement.

               (c) Invention(s) made as a result of an Elected Research Program
        and any patents, copyrights or other intellectual property based on such
        Invention(s) shall be owned jointly by the Parties. Subject to Section
        2.7(d) hereof, rights to commercialize such Invention(s) shall be as
        follows:

                      (i) To the extent that Invention(s) are specific to
               genetically modified plants and related genetic materials (e.g.,
               genes, plasmids, expression vectors, and processes for producing
               transgenic plants capable of expressing a desired protein), GCI
               grants to ProdiGene an exclusive license to make, use, sell,
               offer to sell, have made, import and export, with the right to
               sublicense, products and processes specific to genetically
               modified plants and related genetic biomaterials embodying such
               Invention(s), subject to the payment of a royalty or other
               mutually agreed upon compensation to GCI and to the rights of GCI
               pursuant to part (ii) hereof. Notwithstanding the above, GCI
               shall retain the right to use Inventions under this subsection
               for internal research purposes only.

                      (ii) To the extent that Invention(s) relate to the
               Exclusive Collaboration Field, ProdiGene hereby grants to GCI an
               exclusive license to make, use, sell, offer to sell, have made,
               import and export, with the right to sublicense, products or
               processes embodying such Invention(s), subject to the payment of
               a royalty or other mutually agreed upon compensation to
               ProdiGene, which royalty or other compensation will be the
               greater of *** of Net Sales of a product embodying such
               Invention(s) or *** of the gross margin received by GCI ***
               calculated in accordance with U.S. Generally Accepted Accounting
               Principles. Notwithstanding the above, ProdiGene shall retain the
               right to use Inventions under this subsection for internal
               research purposes only.

                      (iii) To the extent that Invention(s) are not encompassed
               within subsections (i) or (ii) of this Section, the Parties shall
               each have the right to make, use, sell, offer to sell, have made,
               import and export, with the right to sublicense, such
               Invention(s), subject to further agreement between the Parties.

                      (iv) In the event that ProdiGene is subject to a sale of
               substantially all of its business assets or equity to a third
               party, GCI shall be granted a non-exclusive, royalty bearing
               license to make, use, sell, offer to sell, have

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               made, import and export, with the right to sublicense, products
               or processes embodying such Invention(s) for any Inventions
               described in subsection 2.7(c)(i).

               (d) Royalty or compensation due to a Party pursuant to Section
        2.7(c) shall be the subject of a written agreement between the Parties
        and shall take into consideration the existence of, or filing of
        applications for, intellectual property, the nature of the Invention(s)
        and its relative contribution to the product sold. In addition, or
        alternatively, to the royalty or compensation provided for in Section
        2.7(c), the Parties may elect to enter into a separate supply agreement
        pursuant to which ProdiGene supplies raw materials and/or other goods
        useful for the production of protein products to GCI for processing and
        eventual sale. Any controversy arising between the Parties which is
        related to royalty or other compensation to which a Party may be
        entitled under Sections 2.7(c) may, upon request of a Party (the
        Requesting Party), be subject to arbitration in accordance with the
        Licensing Agreement Arbitration Rules of the American Arbitration
        Association with the following modifications:

                        (i)     Arbitration will be before a panel of three
                                neutral, independent, disinterested, unbiased
                                arbitrators, bound by the Rules of Ethics of the
                                ABA and AAA for neutral arbitrators and none
                                shall have ex Parte communications with either
                                of the Parties. The arbitration panel will be
                                composed of one member selected by each Party
                                and a neutral third arbitrator selected by those
                                members, provided that each of the arbitrators
                                will be subject to the consent of both Parties
                                and must possess significant experience in
                                licensing matters related to biotechnology, and
                                in particular to technology related to
                                transgenic plants and their use to produce
                                heterologous proteins;

                        (ii)    Because prompt disposal of the dispute is
                                important to both Parties, judgment shall be
                                provided within *** of the request for
                                arbitration. The judgment shall be supported by
                                findings of fact and conclusions of law.
                                Judgment by the arbitration panel may be entered
                                in any court having competent jurisdiction
                                thereof. In the event that judgment is not
                                entered by the arbitration panel within *** of
                                the request, no obligation shall remain to
                                continue the arbitration; and

                        (iii)   If judgment rendered by the arbitration panel is
                                equivalent to a standing offer previously
                                rejected by the Requesting Party, the Requesting
                                Party shall pay all expenses incurred by the
                                other Party during the arbitration.

               (e) Preparation, filing, prosecution, maintenance and taking such
        other actions as are reasonably necessary or appropriate with respect to
        the development of intellectual property protection arising from an
        Elected Research Program as well as the costs thereof shall be
        undertaken by the Party having the right to commercialize the
        Invention(s) pertaining to such filed patents pursuant to Section
        2.7(c). The Parties shall cooperate in the preparation and filing of any
        patent application relating to the Invention(s) including having any of
        their employees who are named as inventors review and comment on such
        patent applications and the prosecution related thereto, as well as
        having such employees execute necessary documents for the filing of such
        patent applications worldwide.

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        Each Party shall endeavor in good faith to coordinate its efforts with
        those of the other Party to minimize or avoid interference with the
        prosecution of the other Party's patent applications. Each Party shall
        provide the other with a copy of any patent application which relates to
        the Research, at least 20 days prior to filing the first of such
        applications in any jurisdiction, for review and comment by the other
        Party. In the event that Invention(s) are made as contemplated in
        Section 2.7(c)(iii) for which it is appropriate to file a patent
        application(s), the Parties, through the Steering Committee, will agree
        which Party is most appropriate to prepare, file and prosecute that
        patent application(s) based on the nature of the Invention(s) and the
        relative expertise of the Parties.

               (f) Either Party may discontinue its obligation to prepare, file,
        prosecute and maintain (including the costs related thereto) a
        particular patent or patent application filed by it pursuant to this
        Agreement by providing the other with thirty (30) days advance written
        notice (the "Discontinuance Election") of any decision to cease
        preparation, filing, prosecution and maintenance of that patent or
        patent application (a "Discontinued Patent"). In such case, the other
        Party may, at its sole discretion, continue preparation, filing and
        prosecution or maintenance of the Discontinued Patent at its sole
        expense. In such case, the acquiring Party shall own exclusively any
        such patent or patent application and patents maturing therefrom and the
        commercialization rights provided in Section 2.7(c); and the other shall
        execute such documents and perform such acts as may be reasonably
        necessary for the other Party to file or to continue prosecution or
        maintenance, including assigning ownership of such patent or patent
        application and maintaining such patents until such assignment of
        ownership is completed. The Discontinuance Election may be on a
        country-by-country basis or for a patent application or patent series in
        total.

               (g) ProdiGene represents and warrants to the best of its
        knowledge with respect to its Background Patent Rights that ProdiGene
        has title or right to the Background Patent Rights, and the grant of any
        license to GCI contemplated in this Agreement under such rights does not
        require the consent of a third party and is not encumbered by any
        agreement, assignment or other encumbrance that is inconsistent with the
        provisions of this Agreement and does not create any obligation on the
        part of GCI to any third party. Further, ProdiGene represents and
        warrants to the best of its knowledge with respect to the Background
        Technology, that it has ownership or license under such technology owned
        or controlled by ProdiGene and such ownership or licensure is not
        encumbered by any agreement, assignment or other encumbrance that
        prohibits ProdiGene from fulfilling its obligations under this Agreement
        or creates any obligation on the part of GCI to any third party.
        ProdiGene makes no representation or warranty regarding the freedom to
        operate, including with respect to any results of any Elected Research
        Program, under third party issued patents not encompassed within the
        Background Patent Rights and/or the Background Technology.

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        2.8 Confidentiality, Treatment of Samples and Publications.
Confidentiality, samples and publications pursuant to this Agreement or any
Elected Research Program shall be treated as follows:

               (a) The Parties agree that confidential information owned or
        developed by either Party and disclosed pursuant to this Agreement shall
        be considered within the terms of the Confidentiality Agreement;
        provided that the period of permissible disclosure thereunder shall be
        the term of this Agreement and the period of confidentiality provided in
        said Confidentiality Agreement will extend for five (5) years from the
        expiration of this Agreement.

               (b) The Parties agree that the terms of the Samples Agreement,
        except as specifically modified herein, will control with respect to any
        samples or materials provided from GCI to ProdiGene under this
        Agreement; provided that the Parties' obligations thereunder will extend
        for five (5) years from the expiration of this Agreement.

               (c) In the event that the terms of either of said Confidentiality
        Agreement or said Samples Agreement are inconsistent with the terms
        provided expressly herein, the terms of this Agreement shall control.

               (d) Neither Party will publish any material arising from any
        Elected Research Program without prior written approval of the other
        Party. Such approval shall not be unreasonably withheld but may be
        subject to a delay of up to (3) months total for assessment of the
        proposed publication and to enable preparation and filing of appropriate
        patent application(s). Both Parties will procure that any person
        involved or interested in an Elected Research Program will not publish
        or communicate material arising therefrom without first complying with
        the provisions of this Section.

        2.9 Research Exclusivity. ProdiGene agrees that it will not perform
research and/or development or enter into any commercial agreement in or related
to an Elected Research Program with any third party during the term of such
Elected Research Program, after which ProdiGene, subject to its obligations of
confidentiality, exclusivity and to proprietary rights granted to GCI hereunder,
may continue such research without regard to GCI.

                        III. EXCLUSIVITY OF COLLABORATION

        3.1 In consideration of payment pursuant to Section 5.4, ProdiGene
agrees that it will not perform research and/or development or enter into any
commercial agreement in the Exclusive Collaboration Field with any third party
during the Exclusivity Period. ProdiGene further agrees that it will not engage
in discussions with any third party regarding the Exclusive Collaboration Field
during the Exclusivity Period.

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        3.2 ProdiGene hereby grants to GCI an option to extend the Exclusivity
Period for an additional two years (Exclusivity Option). GCI shall exercise the
Exclusivity Option, at its sole discretion, by notifying ProdiGene in writing
prior to the expiration of the Exclusivity Period of its intent to exercise the
Exclusivity Option. Upon exercise of the Exclusivity Option and in consideration
of the extended Exclusivity Period conferred thereby, GCI shall pay to ProdiGene
the amount provided in Section 5.5.

        3.3 The exclusivity provided in this Article applies to any
collaboration between ProdiGene and any third party, but shall not apply to ***

                          IV. PRECEDENCE OF AGREEMENTS

        In the event of any conflict between the terms of the Enzymes Agreement
or any other agreement between the Parties and this Agreement, this Agreement
shall be controlling.

                                  V. PAYMENTS

        5.1 Payments for Elected Research Program(s):

               (a) GCI shall pay to ProdiGene $2,500,000 USD  during the three
        year period immediately following the Effective Date as funding for
        Elected Research Programs. Funding provided in this Section shall be
        pursuant to the agreement of the Parties, and shall include payment for
        FTEs required to adequately staff Elected Research Program(s) and
        technical milestones, if any, which are appropriate to Elected Research
        Program(s). The funding provided in this Section shall constitute a
        total of at least *** FTEs and no more than *** FTEs over the Term.

               (b) Allocation of FTEs shall be not less than *** per annum and
        not more than *** per annum during the Term. The funding rate for FTEs
        allocated during the Term shall be as follows:

                      (i) FTEs allocated during 1999 shall be at a rate of ***
               per FTE;

                      (ii) FTEs allocated during 2000 shall be at a rate of ***
               per FTE;

                      (iii) FTEs allocated during 2001 or thereafter shall be at
               a rate of *** per FTE.

               (c) Payment under Section 5.1(a) shall comprise two payments per
        year, the first payment being on the Effective Date or annual
        anniversary thereof (First Payment Date) and the second payment being
        six months after the Effective Date or annual anniversary thereof
        (Second

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        Payment Date) during the Term. The amount of each payment shall be as
        follows:

                      (i) Within 30 days of the First Payment Date, GCI shall
               pay to ProdiGene the prorated amount of the projected FTE
               allocation for the six month period immediately following the
               First Payment Date.

                      (ii) Within 30 days of the Second Payment Date, GCI shall
               pay to ProdiGene the prorated amount of the projected FTE
               allocation for the six month period immediately following the
               Second Payment Date, adjusted for the actual allocation of FTEs
               made in the previous six month period.

               (d) Agreed upon payments for technical milestones met during the
        Term with respect to Elected Research Program(s) shall be paid within 30
        days of confirmation that such technical milestone has been met.

        5.2 At quarterly intervals, ProdiGene will provide to GCI a statement
detailing the resource and time expenditures which correspond to the payments
made to ProdiGene by GCI under Section 5.1 or 5.5.

        5.3 Any work performed by GCI shall be at GCI's sole expense.

        5.4 In consideration of the Exclusivity Period as provided in Section
3.1, GCI shall pay to ProdiGene *** within 30 days of the execution of this
Agreement.

        5.5 In the event that GCI exercises its Exclusivity Period Option under
Section 3.2, GCI shall pay to ProdiGene a total of $2,000,000 USD during the
extended Exclusivity Period as funding for Elected Research Program(s) during
the extended Exclusivity Period. Funding provided in this Section shall be
pursuant to the agreement of the Parties, and shall include payment for FTEs
required to adequately staff Elected Research Program(s) and technical
milestones, if any, which are appropriate to Elected Research Program(s). The
funding provided in this Section 5.1(a) shall constitute a total of at least ***
FTEs during the extended Exclusivity Period. Payment to ProdiGene pursuant to
this Section 5.5 shall be in accordance with Section 5.1(c).

                            VI. TERM AND TERMINATION

        6.1 The Term of this Agreement shall be for three (3) years from the
Effective Date, such term to be automatically renewable for a period of two (2)
years upon exercise of the Exclusivity Option provided in Section 3.2.

        6.2 The Term of any Elected Research Program shall be the Term of this
Agreement or the period of time for which FTEs are allocated, whichever is
greater.

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Accordingly, the Parties may agree in writing that the term of an Elected
Research Program shall extend beyond the term of this Agreement.

        6.3 Termination of the Agreement may occur upon the following:

               (a) Upon a material breach of the Agreement by the other Party.
        In the event that a Party wishes to terminate this Agreement due to a
        material breach, the terminating Party shall serve a written notice on
        the other Party thereby allowing the other Party sixty (60) days to
        remedy such breach. In the event that such breach has not been remedied
        within the prescribed sixty (60) days, the Agreement shall terminate
        automatically;

               (b) In the event that either Party becomes subject to Bankruptcy,
        insolvency, liquidation or similar proceedings, the other Party shall be
        entitled to terminate this Agreement forthwith;

               (c) Upon one-hundred eighty (180) days notice by GCI to
        ProdiGene; or

               (d) Upon failure of the Parties to reach and successfully
        consummate the sale of an equity interest in ProdiGene to GCI within
        one-hundred eighty (180) days of the Effective Date, GCI shall have the
        right, but not the obligation, to terminate immediately, provided that
        GCI must provide notice to ProdiGene of such termination within two
        hundred and ten (210) days of the Effective Date. In the event that GCI
        terminates under this subsection 6.3(d) and the failure of the Parties
        to reach and successfully consummate the sale of an equity interest is
        due to: (i) a failure of ProdiGene to obtain the necessary consents of
        its shareholders and/or Board of Directors to effectuate such sale to
        GCI or (ii) the terms of such issuance not being substantially similar
        to the Class B Convertible Preferred Shares rights, privileges and
        preferences as provided in ProdiGene's Certificate of Incorporation as
        filed with the Delaware Secretary of State and authenticated on August
        28, 1998, ProdiGene shall refund, in its entirety, any payments made
        under Section 5.4 hereof.

        6.4 Expiration of Term or termination of this Agreement pursuant to this
Article shall not effect the vested rights of either Party under Articles 2, 4
and 7.

                               VII. MISCELLANEOUS

        7.1 Hold Harmless. With respect to GCI's rights under Section 2.7(c),
ProdiGene shall hold GCI harmless for any activities thereunder which would
otherwise infringe ProdiGene's Background Technology or Background Patent
Rights.

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        7.2 Indemnification. Except as specifically provided herein, GCI agrees
to indemnify and to hold ProdiGene, its officers, directors, and employees
harmless from liabilities assessed to GCI or its affiliates which arise solely
as a result of GCI's conduct under this Agreement or GCI's use of the results of
this Agreement, except for liabilities caused by the negligence of ProdiGene.
Furthermore, ProdiGene agrees to indemnify and to hold GCI, its officers,
directors, and employees harmless from liabilities of any kind assessed to
ProdiGene or its affiliates which arise solely as a result of ProdiGene's
conduct under this Agreement or ProdiGene's use of the results of this
Agreement, except for liabilities caused by the negligence of GCI.
Indemnification hereunder is limited to research activities conducted under this
Agreement.

        7.3 Force Majeure. Each of the Parties hereto shall be excused from
performance of its obligations and shall not be liable for damages to the other
to the extent that such performance is prevented by circumstances beyond its
effective control. Such excuse from performance shall continue so long as the
condition responsible for such excuse continues and for a thirty (30) day period
thereafter.

        For purposes of this Agreement, circumstances beyond the effective
control of a Party which excuse that Party from performance shall include but
shall not be limited to, act of God, regulations or laws of any government,
injunction or judgment of any court, war, civil commotion, destruction of
facility or materials by fire, earthquake, storm or other casualty, labor
disturbance, epidemic and failure of public utilities or common carrier.

        7.4 Relationship. ProdiGene and GCI are independent contractors. Nothing
in this Agreement or the course of dealing of the Parties shall be construed to
constitute the Parties hereto as partners, joint ventures or as agents or
distributors for one another, or as authorizing any Party to obligate the other
in any manner.

        7.5 Non-Assignment. This Agreement shall not be assignable by any Party
without the other Parties' prior written consent. In the event that such consent
is given, this Agreement and the covenants herein contained shall be binding and
inure to the benefit of ProdiGene and GCI and their heirs, assigns, successors
and legal representatives. In the event that either Party hereto undergoes a
divestiture or sale of assets or equity to a third party, the acquiring party
takes such assets or equity subject to the rights and obligations provided in
this Agreement and shall agree in writing to the terms hereof.

        7.6 Entire Agreement/Amendment. This Agreement and the attachments
hereto constitute and contain the entire agreement of the Parties respecting the
subject matter hereof. This Agreement may only be amended by mutual written
agreement of the Parties.

        7.7 Warranty of Right and Authority. Each of the Parties represents and
warrants to the other that it has the full right and authority to enter into
this Agreement, and that it is

                                       13
<PAGE>   14

not aware of any impediment which would inhibit its ability to perform the terms
and conditions imposed on it by this Agreement. Nothing contained herein shall
be interpreted as a warranty, express or implied as to the patentability,
enforceability or validity of any patent application or patent owned or
controlled by either Party.

        7.8 Further Acts and Instruments. Each Party agrees to execute,
acknowledge and deliver such further instruments and do all such other acts as
may be necessary or appropriate to effect the purpose and intent of this
Agreement.

        7.9 Severability. In the event any one or more of the provisions of this
Agreement should for any reason be held by any court or authority having
jurisdiction over this Agreement or either of the Parties hereto to be invalid,
illegal or unenforceable, such provision shall be reformed within the
jurisdiction of such court or authority to as nearly approximate the intent of
the parties as possible, and if the provision is unreformable the Parties shall
meet to discuss what steps should be taken to remedy the situation; otherwise
and elsewhere this Agreement shall not be affected.

        7.10 Captions. The captions to this Agreement are for convenience only
and are to be of no force or effect in construing or interpreting the provisions
of this Agreement.

        7.11 Counterparts. This Agreement may be executed in two counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument.

        7.12 Limitation of Liability. No Party shall be liable to another for
indirect, incidental, consequential or special damages, including but not
limited to lost profits, arising from or relating to any breach of this
Agreement, regardless of any notice of the possibility of such damages. In no
event shall either Party be liable for damages relating to lost profits or
reasonable royalties or special damages due and payable to a third party on the
basis of the other's sale of a product developed hereunder.

        7.13 Publicity. Either Party's use of the other Party's name or
disclosure of the existence or nature of this Agreement or the relationship
created thereby to any third party shall be only with the prior written consent
of the other Party, which consent will not be unreasonably withheld.

        7.14 Interpretation. This Agreement has been jointly prepared by the
Parties and their respective legal counsel and shall not be strictly construed
against either Party.

        7.15 Notices. Representatives for the receipt of payments, notices,
records, reports and other information pursuant to this agreement shall be as
follows:

                                       14
<PAGE>   15
        For GCI:

        Attn: Legal Department
        Genencor International, Inc.
        1870 S. Winton Rd.
        4 Cambridge Place
        Rochester, NY  14618

        For ProdiGene:

        Attn:
        ProdiGene, Inc.
        1500 Research Parkway
        Suite 220
        College Station TX  77845

        7.16 Controlling Law. This Agreement shall be governed and construed in
accordance with the Laws of the State of Delaware, excluding any choice of law
rules which may direct the application of the law of any other jurisdiction.
Questions effecting the construction and effect of any patent rights arising
hereunder shall be determined by the laws of the country in which such patent
rights have been applied for and/or granted.

        IN WITNESS WHEREOF, the parties have caused this Agreement to be
executed by their duly authorized representatives.

GENENCOR INTERNATIONAL, INC.               PRODIGENE

By:     /s/ STUART L. MELTON               By:    /s/ JOHN A. HOWARD
   --------------------------------           -----------------------------

Name:    Stuart L. Melton                  Name:    John A. Howard
     ------------------------------             ---------------------------

Title:    Senior Vice President            Title:     President and CEO
      -----------------------------              --------------------------

                                       15

<PAGE>   16

                                                                      APPENDIX A

                            CONFIDENTIALITY AGREEMENT

THIS AGREEMENT, effective this 25th day of March, 1997 ("Effective Date"), by
and between ProdiGene, Inc., and Genencor International, Inc.

WHEREAS, the Parties to this Agreement desire that certain confidential
information and associated documents be disclosed to each other in connection
with discussions regarding a business proposal to start a company which will
produce protein products in plants, and the Parties wish to ensure that the
information which may be disclosed is treated in the strictest confidence.

THE PARTIES AGREE AS FOLLOWS

1.      "Confidential information" shall include, but not be limited to, all
        knowledge, know-how, practices, processes, data and related information
        received from the other party, whether such information is supplied to
        the other party in oral, written, graphic, photographic or other
        tangible form.

2.      The receiving party shall not provide the confidential information, or
        any part thereof, received from the disclosing party to any third party,
        even if such third party is under obligations of confidentiality.

3.      The receiving party shall not use the confidential information, or any
        part thereof, received from the disclosing party for any purpose except
        as contemplated herein; provided, however, that to be subject to the
        confidentiality and non-use provisions

<PAGE>   17

        of this agreement, information disclosed other than in written or
        tangible form must be summarized with particularity in writing by the
        disclosing party and furnished to the other party within thirty days of
        first disclosure hereunder.

4.      Confidential information supplied shall not be reproduced in any form
        except as required to accomplish the intent of this agreement.

5.      Unless otherwise specified in writing, all documents and materials
        containing or embodying confidential information shall remain the
        property of the disclosing party. Upon request of the disclosing party,
        the receiving party agrees to return or destroy all documents and
        materials containing or embodying any confidential information of the
        disclosing party, as well as copies thereof, except for one copy, which
        disclosing party may keep in its legal department solely to monitor its
        obligations hereunder.

6.      The foregoing provisions of confidentiality shall not apply to
        confidential information which:

        a)     is now, or which hereafter, through no act or failure to act on
               the part of the receiving Party, becomes generally known or
               available to the public without breach of this Agreement;

        b)     is known to the receiving Party at the time of disclosure of such
               Confidential Information, as evidenced by the written record of
               the receiving Party;

        c)     is independently developed by the receiving Party, provided that
               the person or persons developing same have not received, either
               directly or indirectly, the Confidential Information received and
               provided such independent development is documented;

        d)     is disclosed with the written approval of the disclosing Party;

        e)     is required to be disclosed by law; provided that the party
               subject to such requirement shall immediately inform the other
               party and cooperate with the other party, at the other party's
               expense, in interposing an objection so such requirement;

        f)     is rightfully received by the Receiving Party from a third party
               without a duty of confidentiality; or

        g)     is disclosed by the Disclosing Party to a third party without a
               duty of confidentiality on the third party.

7.      Notwithstanding any termination of this Agreement the provisions of
        confidentiality shall apply for a period of five (5) years from the
        Effective Date.

<PAGE>   18

8.      This Agreement shall in no way be construed as the granting of a license
        to the receiving Party, either directly or indirectly, under any
        Intellectual Property and/or Technical Materials owned or controlled by
        the disclosing Party. For the purposes of this Agreement, Intellectual
        Property shall be defined as patents, patent applications, Plant Variety
        Protection Certificates and/or copyrights and any inventions,
        improvements and/or discoveries whether or not patentable, including all
        know-how, show-how, trade secrets, research plans and priorities, market
        interests and product ideas. Technical Material shall be defined as
        computer software, computer simulations, computer models and related
        reports, arrays, germplasm, cultures, cell lines, plants, plant parts,
        seeds, pollen, proteins, peptides, and metabolites, DNA and RNA
        sequences, genes, probes and plasmids. Furthermore, nothing in this
        Agreement shall be interpreted so as to oblige either Party to enter
        into a further agreement. Neither party has any obligation under this
        Agreement to purchase any service or item from the other party, or to
        deal exclusively with the other party in any field.

9.      This Agreement is not assignable without the consent in writing of both
        Parties.

10.     The parties do not intend to create any agency or partnership between
        them by this Agreement.

11.     A receiving party shall adhere to the U.S. Export Administration Laws
        and Regulations and shall not export or re-import any technical data or
        products received from the disclosing Party or the direct products of
        such technical data to any prescribed country listed in the U.S. Export
        Administration Regulations unless properly authorized by the U.S.
        Government.

12.     The Parties agree to inform all personnel receiving the Confidential
        Information of the terms of this Agreement.

13.     This Agreement is made under and shall be construed according to the
        laws of the State of New York.

PRODIGENE, INC.                          GENENCOR INTERNATIONAL, INC.

By:  /s/ ROBERT C. DOSE                  By:  /s/  WAYNE PITCHER
    ------------------------                ---------------------------
    Robert C. Dose
    Executive Vice President
                                             Wayne Pitcher
                                             -----------------------------------
                                             Printed Name

                                             Sr. Vice President, Research &
                                             Development Title

Date:  3/25/97                           Date:  May 1, 1997

<PAGE>   19

                     AMENDMENT TO CONFIDENTIALITY AGREEMENT

            THIS AGREEMENT, made by and between ProdiGene, Inc., and Genencor
International, Inc. (the "Parties").

WHEREAS, the Parties have entered into a Confidentiality Agreement dated March
25, 1997 (the "Confidentiality Agreement") covering information and associated
documents which are disclosed in connections with discussions regarding a
business proposal to start a company which will produce protein products in
plants;

WHEREAS, as a part of those discussions, Genencor desires to review and analyze
certain information of ProdiGene comprising unpublished Patent Applications and
privileged Attorney Opinions;

NOW THEREFORE, the Parties agree to amend the Confidentiality Agreement as
follows:

1.      Confidentiality with respect to the Patent Applications will extend for
        ten years from the Effective Date.

2.      Attorney Opinions will be maintained solely within the Legal Department
        of Genencor.

3.      Except as specifically indicated herein, the Confidentiality Agreement
        remains unmodified in all other respects.

IN WITNESS WHEREOF, the Parties have caused this Amendment to be executed by
their authorized representative and effective as of the date of signature.

GENENCOR INTERNATIONAL, INC.                  PRODIGENE, INC.

Address:                                      Address:

4 Cambridge Place                             1500 Research Parkway, Suite 220
1870 South Winton Road                        College Station, Texas  77845
Rochester, NY  14618

By:  /s/ WAYNE H. PITCHER                     By:  /s/ JOHN A. HOWARD
     --------------------------------             ------------------------------
     Wayne H. Pitcher                             John H. Howard

Title:  Sr. Vice President, Technology        Title: President
        ------------------------------               ---------------------------

Date:  7/28/97                                Date:  8/4/97
       -------------------------------               ---------------------------

<PAGE>   20

                                                                      APPENDIX B

                       AGREEMENT FOR PROVISION OF SAMPLES

            This Agreement, entered into this 30th day of April, 1997,
("Effective Date"), by and between GENENCOR INTERNATIONAL INC., a corporation of
the State of Delaware, having a principal place of business at 4 Cambridge
Place, 1870 South Winton Rd., Rochester, New York 16418 ("GENENCOR"); and
PRODIGENE, a corporation having a place of business at 1500 Research Parkway,
Suite 220, College Station, Texas 77845 ("PRODIGENE")(collectively the
"Parties").

                                   WITNESSETH:

            WHEREAS, GENENCOR has developed certain technology related to
identification, expression, secretion, purification and of enzymes and proteins
derived from plant, animal and microbial sources, including DNA which encodes
such enzymes and proteins and PRODIGENE has developed certain technology related
to the expression of certain DNA encoding proteins in plants;

            WHEREAS, the Parties are desirous of working together for the
purpose of determining the usefulness of PRODIGENE's plant expression technology
to express GENENCOR's DNA and wish to effect transfer of GENENCOR's DNA (the
"SAMPLES") to PRODIGENE to facilitate initial experimentation and analysis
related thereto (the "EVALUATION");

            WHEREAS, after initial analysis of the SAMPLES for suitability in
PRODIGENE's plant expression systems, the Parties are hopeful of discussing the
suitability of a longer term relationship, and the possibility of a business
relationship between the Parties directed to commercial scale expression of
GENENCOR's DNA to produce proteins in plants;

            NOW, THEREFORE, the parties agree as follows:

1.      GENENCOR shall provide the SAMPLES to PRODIGENE for the purposes of the
        EVALUATION on a non-exclusive basis. Any material, including any cell,
        vehicles, constructs, vectors, plasmids, protein or other medium
        incorporating the SAMPLES or a component thereof, as well as any
        material that could not have been made but for the SAMPLES, are
        expressly understood to be part of the SAMPLES, together with all
        documentation and descriptions of the SAMPLES.

2.      a.     PRODIGENE agrees not to supply the SAMPLES to other laboratories,
               either within or outside of PRODIGENE, nor to any other
               individual or organization other than employees of PRODIGENE, and
               not to use the SAMPLES directly or indirectly, for any commercial
               purpose, including the filing of a patent application, without
               GENENCOR's prior written approval. Any employees of PRODIGENE
               having access to SAMPLES will be previously notified of and agree
               to be bound by the terms of this Agreement. No employee or third
               party will be allowed access to the

<PAGE>   21

               SAMPLES unless such employee or third party is bound by an
               employment, confidentiality or other agreement requiring
               assignment of all invention, patents, and copyrights to
               PRODIGENE.

        b.     PRODIGENE will not use, directly or indirectly, the SAMPLES in
               any research programs without GENENCOR's prior written approval
               if the terms of such program entitles any third party to any
               right, option or interest in such research program or its
               results, including the right to review and/or publish such
               results.

3.      a.     PRODIGENE's EVALUATION of the SAMPLES will be only for research
               purposes and particularly only for the following research
               purposes: TESTING OF THE SUITABILITY OF GENENCOR'S DNA IN
               PRODIGENE'S PLANT EXPRESSION SYSTEMS.

        b.     Upon GENENCOR's request, PRODIGENE will provide a list of all
               individuals allowed access to the SAMPLES.

        c.     PRODIGENE acknowledges that the SAMPLES are the confidential and
               proprietary property of GENENCOR and agrees to take all care
               necessary to prevent any disclosure, unauthorized use or transfer
               of the SAMPLES, or any information relating to such, to any party
               who is not bound by this Agreement.

4.      PRODIGENE will not analyze, attempt to analyze, or have analyzed the
        composition or formulation of the SAMPLES to identify or reverse
        engineer the composition of the SAMPLES or production systems thereof,
        except as necessary under this Agreement.

5.      PRODIGENE will not publish or publicly disclose results of experiments
        using the SAMPLES without the prior written consent of GENENCOR. If the
        research utilizing the SAMPLES results in a useful discovery, whether
        patentable or not, made as a result of PRODIGENE's research using the
        SAMPLES, PRODIGENE will promptly notify GENENCOR in writing.

6.      It is specifically contemplated that confidential information of both
        Parties may be disclosed pursuant to this Agreement, including data and
        information relating to the SAMPLES, the EVALUATION and/or technical or
        commercial information related thereto (the INFORMATION). Such
        confidential information shall be treated as Confidential Information as
        per the Confidentiality Agreement between the Parties having an
        Effective Date of March 25, 1997.

7.      At the conclusion of the EVALUATION, the Parties shall discuss the
        possibility of a definitive agreement involving using PRODIGENE's plant
        expression technology to produce enzyme and protein products for
        GENENCOR on a commercial scale. Such discussions may include the
        creation of a research and development agreement for applying
        PRODIGENE's plant expression technology to GENENCOR's business and may
        include provisions for GENENCOR

<PAGE>   22

        receiving exclusive rights to PRODIGENE's technology, the selection of
        specific products to be developed by the Parties, seed production and
        supply, extraction/purification and packaging, specific intellectual
        property provisions related to the research to be undertaken, and
        royalties or other mutually agreed upon consideration between the
        Parties.

8.      In consideration for GENENCOR's supply of SAMPLES hereunder, PRODIGENE
        grants GENENCOR a non-exclusive, royalty-free license for internal
        research purposes to each useful discovery, whether patentable or not,
        made as a result of PRODIGENE's research using the SAMPLES. Furthermore,
        PRODIGENE hereby grants GENENCOR a first right of refusal to obtain an
        exclusive, worldwide, royalty-bearing license under any discovery and
        any patents based on inventions using the SAMPLES, the royalty rate to
        be a reasonable royalty determined based on the nature of the discovery,
        taking into consideration its relative contribution to the overall
        products(s) to be commercialized under such license. The royalty, along
        with such other standard terms and conditions as may be reasonable under
        the circumstances, shall be negotiated in good faith by the parties and
        documented in a written agreement. PRODIGENE's obligations under this
        provision are limited by the legal ability of PRODIGENE to grant
        licenses to such inventions as of the Effective Date hereof.

9.      The SAMPLES are experimental in nature and are not for human use.
        PRODIGENE agrees to handle the SAMPLES with appropriate safety
        precautions. GENENCOR will supply any available Material Safety Data
        Sheet (MSDS) for the SAMPLES and PRODIGENE will follow all handling
        precautions shown there. GENENCOR hereby disclaims all express and
        implied warranties of any kind with respect to the SAMPLES. PRODIGENE
        agrees to hold GENENCOR harmless from any and all liability and/or
        damages (including costs of defense) resulting from your use of the
        SAMPLES, including any use in violation of this Agreement.

10.     Nothing contained in this Agreement shall be construed as granting a
        license or other right to PRODIGENE under any proprietary rights of
        GENENCOR or of granting a license or other right to GENENCOR under any
        proprietary rights of PRODIGENE.

11.     The EVALUATION of the SAMPLES under this Agreement shall be for a period
        of eighteen (18) months from the Effective Date. At the conclusion of
        the EVALUATION, PRODIGENE will, upon written request of GENENCOR, either
        return or destroy any unused SAMPLES, at GENENCOR's option.

12.     The parties' obligations under this Agreement shall extend for five (5)
        years from the Effective Date hereof.

13.     All additions or modifications of this Agreement must be made in writing
        and must be signed by both Parties. This Agreement is made under and
        shall be construed according to the laws of the State of New York.

<PAGE>   23

            IN WITNESS WHEREOF, the parties have caused this Agreement to be
executed by their authorized representative and effective as of the Effective
Date.

GENENCOR INTERNATIONAL, INC.                  PRODIGENE

Address:                                      Address:

4 Cambridge Place                             1500 Research Parkway, Suite 220
1870 South Winton Road                        College Station, Texas  77845
Rochester, NY  14618

By:  /s/ WAYNE PITCHER                        By:  /s/ ROBERT C. DOSE
     ------------------------------------          -----------------------------
                                                   Robert C. Dose

Sr. Vice President, Research &
Development Title                             Executive Vice President Title
-----------------------------------------     ----------------------------------

Date:  May 1, 1997                            Date:  May 7, 1997
       ----------------------------------            ---------------------------

<PAGE>   24

                                                                      APPENDIX C

                                  PROJECT FORM

            This Project Form is submitted under the Parties' Funded Research
Collaboration Agreement (the "Agreement") as a proposal for an Elected Research
Program. Capitalized terms in this form have the same meaning as in the
Agreement. Upon execution of this form by both Parties, this Project Form shall
establish an Elected Research Program.

I.      Target Compound:

II.     Technical Description of the Proposed Elected Research Program Including
        Technical Milestones

III.    Elected Research Program Field:

IV.     Projected FTE Allocation:           Total FTEs
        -------------------------   --------
                                            FTEs in Year 1
                                    --------
                                            FTEs in Year 2
                                    --------
                                            FTEs in Year 3
                                    --------

V.      Projected Completion Date: ___/___/___

VI.     Market Justification include consideration of market size, market
        penetration, competitive alternatives, etc. . .)

VII.    Technical Milestone Payments<PAGE>   1
                                                                   EXHIBIT 10.29
                                  CONFIDENTIAL

***PORTIONS OF THE EXHIBIT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.
THE COMPLETE EXHIBIT, INCLUDING THE PORTIONS FOR WHICH CONFIDENTIAL TREATMENT
HAS BEEN REQUESTED, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.

                             COLLABORATION AGREEMENT

               THIS AGREEMENT is made May 14, 1999, ("Effective Date") by and
between Xgene Corporation having a principal place of business at 863A Mitten
Road, Burlingame, California 94010 (hereinafter "Xgene") and Genencor
International, Inc., a Delaware company having a principal place of business at
4 Cambridge Place, 1870 South Winton Road, Rochester, New York 14618
(hereinafter "GCI") (collectively the "Parties").

               WHEREAS, GCI has developed expertise, knowledge and experience
related to, among others, specialty biochemicals for use in personal care and
skin therapies, including their production, purification, manufacture and
application;

               WHEREAS, Xgene has developed expertise, knowledge and experience
related to the development of artificial skin and assays related thereto;

               WHEREAS, the Parties have entered into discussions related to the
development of artificial skin assays by Xgene for use by GCI in developing
products for personal care and skin therapy treatments, including products
having low allergenicity;

               NOW THEREFORE, the Parties agree as follows:

                                       I.
                                   DEFINITIONS

        1.1 The "Research" shall mean the work performed under this Agreement by
one or more of the Parties as essentially detailed in Appendix A.

        1.2 "Background Technology" shall mean any technology, data, results,
biological materials, processes, reports, or other information owned or
controlled by either Party as of the Effective Date.

        1.3 "Background Patent Rights" shall mean any patent or patent
application, foreign and domestic, including any and all divisions,
continuations, continuations-in-part, reissues, re-examination applications,
extensions, supplementary protection certificates, certificates of addition,
inventor's certificates, including international counterparts thereof owned
and/or controlled as of the Effective Date by either Party.

        1.4 "Inventions" shall mean any technology, data, discoveries, results,
biological materials, processes, reports, or other information, whether
patentable or not, which result

<PAGE>   2

directly and substantially from the Research as described in Appendix A during
the Term of this Agreement.

        1.5 "Term" shall be 12 months or the achievement of Milestone 2,
whichever occurs earlier. In the event that an Elected Assay is incorporated
into the Research, the Term shall be extended for a mutually agreed upon time
period to allow for completion of the development of the Elected Assay.

        1.6 "Xgene Core Business" shall mean the development and use of human
skin reconstituted by cell-sorted skin equivalent methodology, both in vitro
and in vivo, for any purpose.

                                       II.
                          RESEARCH PROGRAM AND PAYMENT

        2.1 Xgene shall commence performance of the Research promptly upon the
Effective Date and shall proceed as provided for in Appendix A. Xgene agrees to
commit reasonable facilities and resources to its allocated employees as is
reasonably necessary to carry out the Research. The Research may be redirected
in accordance with modifications and extensions only to the extent that Xgene
and GCI mutually agree upon in writing.

        2.2 Payment for the Research shall be as follows:

               (a) GCI shall pay to Xgene *** within 30 days of the Effective
Date.

               (b) If, within 9 months of the Effective Date, Xgene has
developed an *** assay useful for the development and testing of products having
activity against human papilloma virus (Milestone 1), GCI shall pay to Xgene
***. Payment under this subsection shall be contingent upon receipt by GCI of a
written report from Xgene conclusively showing that Milestone 1 has been met and
GCI's agreement that the conclusions made in such written report are reasonable
in light of the results of the Research. Payment under this subsection shall be
due within 30 days of such agreement by GCI.

               (c) If, within 12 months of the Effective Date, Xgene has
developed an *** assay useful for the development and testing of products having
activity against human papilloma virus (Milestone 2), GCI shall pay to Xgene
***. Payment under this subsection shall be contingent upon receipt by GCI of a
written final report from Xgene conclusively showing that Milestone 2 has been
met and GCI's agreement that the conclusions made in such written report are
reasonable in light of the results of the Research. Payment under this
subsection shall be due within 30 days of such agreement by GCI.

        2.3 Xgene agrees that it will not perform research and/or development or
enter into any commercial agreement with any third party during the Term of this
Agreement which relates to the subject matter of (i) the Research or (ii) any
Elected Assay under Article 3.2(b) hereto without GCI's written consent;
provided that Xgene may perform research and/or development or enter into a
commercial agreement with any third party which relates to *** and the effect of
*** properties of skin.

                                       2
<PAGE>   3

        2.4 Xgene agrees to perform its tasks under this agreement in accordance
with standard and accepted scientific standards for such research. Xgene agrees
to submit monthly reports, in electronic and paper copy, detailing progress
relating to their responsibilities pursuant to the Research and any pertinent
findings, results, conclusions or other information resulting from the Research
to GCI. Xgene shall provide to GCI a final report summarizing the research
performed and providing conclusions and description of the developed assays
which derive from the Research within sixty (60) days of the achievement of
Milestone 2 or completion of an Elected Assay.

        2.5 Should technology, market, regulatory or other considerations
suggest to either Party that continued investment of time, resources or money
towards the Research may be unsuitable or undesirable, the Parties may elect to
hold discussions toward a mutually acceptable resolution, including alternative
target proteins, the transfer or modification between the Parties of rights to
commercialize products, or termination of the Agreement, as appropriate.

                                      III.
                     ELECTION OF ADDITIONAL RESEARCH ASSAYS

        3.1 GCI shall have the right, at any time during the Term and for a
period of three (3) months thereafter, to request that Xgene initiate the
development of additional assays pursuant to this Agreement (Elected Assays).
Elected Assays may relate to the development and testing of products for use as
personal care or therapeutic treatments for normal skin types, aging skin types,
or specific clinical skin related conditions, as will be mutually agreed upon
between the parties.

        3.2 Identification of Elected Assays

               GCI may request that an Elected Assay be incorporated within the
Research by providing a written request to Xgene to develop the Elected Assay.
Elected Assays shall be incorporated into the Research pursuant to either of the
following:

               (a) Election by Mutual Agreement

               The Parties may mutually agree to the development of an Elected
Assay. In such case, subsequent to Xgene's receipt of the written request from
GCI, the Parties shall meet and discuss the specifics of the proposed Elected
Assay and come to mutual agreement regarding the identification of the assay, an
appropriate time line, a description of the condition or therapy upon which the
Elected Assay is to be based and a specific set of deliverables which are
expected to result from the research concerning the Elected Assay. Xgene shall
provide written acknowledgment to GCI of its agreement or refusal to perform the
research related to developing the Elected Assay within 30 days of GCI's
request.

               (b) GCI Elected Assays

               GCI may elect, within its sole discretion, to incorporate any of
the following as within the Research, which election is hereby agreed to by
Xgene:

                                       3
<PAGE>   4

               (i) The development of an assay related to ***;

               (ii) The development of an assay related to ***;

               (iii) The development of an assay for ***.

               An election under this subsection 3.2(b) shall be considered
effective as of the date the written request from GCI is received by Xgene, who
shall then be considered to have agreed to develop the Elected Assay.

        3.3 As consideration for each Elected Assay to be developed, GCI shall
make payment to Xgene as follows:

               (a) *** within *** of the date that Xgene agrees in writing to
develop the Elected Assay under Section 3.2(a) or of GCI's election under
Section 3.2(b);

               (b) *** upon completion of the Elected Assay, provided that,
payment under this subsection shall be contingent upon receipt by GCI of a
written final report from Xgene conclusively showing that the Elected Assay has
been successfully completed and GCI's agreement that the conclusions made in
such written report are reasonable in light of the results of the Research.
Payment under this subsection shall be due within *** of such agreement by GCI.

        3.4 Notwithstanding Section 2.2, to the extent that GCI has not elected
an Elected Assay provided in Section 3.2(b), Xgene may consider offers from
third parties to participate in a development agreement related to such Elected
Assay. In the event that Xgene has received a written letter of intent from a
third party that provides for Xgene to develop an assay which includes such GCI
Elected Assay, Xgene shall provide to GCI written notice of such third party
offer explaining the assay to be developed and providing sufficient detail for
GCI to consider its interest in developing such assay (Election Notification
Letter). Within sixty (60) days of its receipt of the Notification Letter, GCI
shall exercise its option to incorporate the specific Elected Assay into the
Research. Failure of GCI to exercise its option within the relevant time frame
shall be considered as GCI's consent for Xgene to develop the assay provided in
its letter to GCI with such third party.

                                       IV.
                          INTELLECTUAL PROPERTY RIGHTS

        4.1 To the extent that either Party owns or controls Background
Technology or Background Patent Rights, such Background Technology and
Background Patent Rights shall remain the sole property of that Party to exploit
in any manner it chooses at its sole discretion, except to the extent
specifically provided for herein.

                                       4
<PAGE>   5

        4.2 Ownership of Intellectual Property from the Research

               (a) Xgene shall own any Inventions produced during the Research
which relate to the Xgene Core Business or otherwise to assays using artificial
skin for the development of skin treatment compositions and to file patent
applications based thereon and prosecute same.

               (b) GCI shall own all Inventions related to therapies or
personal care treatments relevant to human papilloma virus or the condition
to be reproduced by an Elected Assay.

               (c) All Inventions not falling under subsections (a) or (b) shall
be owned by the inventor thereof.

        4.3 Xgene agrees to promptly advise GCI in writing of any Invention(s)
made pursuant to this Agreement, but in any event no later than 30 days after
the submission of an invention disclosure to its legal department or counsel.

        4.4 Preparation, filing, prosecution, maintenance and taking such other
actions as are reasonably necessary or appropriate with respect to the
development of Invention(s) as well as the costs thereof shall be undertaken by
the Party owning the Invention(s) pertaining to such filed patents and/or patent
applications. Xgene shall provide GCI with a copy of any patent application
which relates to the Research, at least 20 days prior to filing the first of
such applications in any jurisdiction, for review and comment by GCI.

        4.5 Xgene represents and warrants to the best of its knowledge that with
respect to its Background Patent Rights that Xgene has title or right to its
Background Patent Rights and Background Technology, and that the grant of any
license or right to GCI contemplated in this Agreement under such rights does
not require the consent of a third party and is not encumbered by any agreement,
assignment or other encumbrance that it inconsistent with the provisions of this
Agreement.

                                       V.
                                    LICENSES

        5.1 Xgene grants to GCI a non-exclusive, royalty-free, world wide
license to use any assays or artificial skin which are conceived pursuant to
this Agreement for any purpose. Xgene further grants to GCI a non-exclusive,
royalty free, world wide license under any Inventions owned by Xgene pursuant to
this Agreement to make, sell, use, have made, have sold, import, export or offer
for sale therapeutic and/or non-therapeutic product(s) for any application. GCI
shall have the right to sublicense under the licenses granted in this Section
5.1 for the purpose of developing, testing or confirming properties of
experimental and/or commercial products produced by GCI, to the extent Xgene may
legally confer such sublicensing rights.

        5.2 Xgene shall pay to GCI a royalty based on Xgene's or its
sublicensee's commercialization of Xgene's Inventions. The royalty shall be at
least *** of the Net Revenue received by Xgene for such commercialization,
provided that, Net Revenue shall be defined

                                       5
<PAGE>   6

subject to mutual agreement of the Parties. In lieu of a royalty, the Parties
may agree to *** or such other arrangement as may be mutually agreed upon
between the Parties.

        5.3 With respect to any assay or other means of testing products
relevant to human papilloma virus or to the condition to be reproduced by an
Elected Assay which results from this Agreement, GCI shall have exclusive rights
to use such assay for the development of therapeutic or non-therapeutic
compounds for the treatment of skin for a one year period. The one year period
shall commence upon receipt by GCI from Xgene of a final written report
identifying and describing the assay and providing information sufficient to
confirm that the assay has been successfully developed.

                                       VI.
                          RENEWAL, TERM AND TERMINATION

        6.1 The Term of this Agreement shall be as provided in Section 1.5. In
the event of expiration of the Agreement due to either the non-achievement of
any milestone or expiration of Term, GCI's obligations regarding any unmet
milestones shall lapse.

        6.2 Should this Agreement expire due to failure to reach a milestone,
the Parties may agree to engage in further good faith negotiations toward a
mutually agreeable resolution or continuance of the Research, which resolution
may include redefining the direction and/or the scope of the Research.

        6.3 Termination of the Agreement may occur upon the following:

               (a) Upon a material breach of the Agreement by the other Party.
In the event that a Party wishes to terminate this Agreement due to a material
breach, the terminating Party shall serve a written notice on the other Party
thereby allowing the other Party sixty (60) days to remedy such breach. In the
event that such breach has not been remedied within the prescribed sixty (60)
days, the Agreement shall terminate automatically;

               (b) In the event that either Party becomes subject to Bankruptcy,
insolvency, liquidation or similar proceedings, the other Party shall be
entitled to terminate this Agreement forthwith.

        6.4 Expiration of Term or termination of this Agreement pursuant to this
Article shall not effect the rights of either Party under Articles 4, 5 and 7.

                                      VII.
             CONFIDENTIALITY, TREATMENT OF SAMPLES AND PUBLICATIONS

        7.1 Treatment of Confidential Information

               (a) In order for the Parties to perform the work contemplated
hereunder, it may be necessary for each Party to disclose certain proprietary
information and/or data which is necessary to achieve the objectives of the
Research (the "CONFIDENTIAL INFORMATION").

                                       6
<PAGE>   7

A recipient shall protect the CONFIDENTIAL INFORMATION against unauthorized
disclosure using the same degree of care, but no less than a reasonable degree
of care, as the recipient uses to protect its own CONFIDENTIAL INFORMATION of a
like nature; provided that:

               (b) A recipient shall be obligated to protect only such
CONFIDENTIAL INFORMATION disclosed under this Agreement as is: (a) disclosed in
tangible form clearly labeled as confidential at the time of disclosure, or (b)
disclosed initially in nontangible form identified as confidential at the time
of disclosure and, within thirty days following the initial disclosure,
summarized and designated as confidential in a written memorandum delivered to
the recipient.

               (c) The obligations of non-disclosure do not apply to
CONFIDENTIAL INFORMATION disclosed under this Agreement which: (a) was in the
recipient's possession before receipt from the discloser as demonstrated by
written documentation; or (b) is or becomes a matter of public knowledge through
no fault of the recipient; or (c) is rightfully received by the recipient from a
third party without a duty of confidentiality; or (d) is disclosed by the
discloser to a third party without a duty of confidentiality on the third party;
or (e) is independently developed by the recipient as demonstrated by written
documentation; or (f) is disclosed under operation of law; or (g) is disclosed
by recipient with the discloser's prior written approval. Such "CONFIDENTIAL
INFORMATION" may be designated as such by the receiving Party upon notice to the
disclosing Party.

               (d) The obligation of non-disclosure shall continue for a period
of five (5) years from the Effective Date hereof, regardless of termination of
this Agreement.

        7.2 Treatment of Samples

               (a) GCI may supply Xgene with reasonable research quantities of
the biological material for use in the Research (Biological Material). Any
material, including any cell, vehicles, constructs, vectors, plasmids, protein
or other medium incorporating the Biological Material or a component thereof, as
well as any material that could not have been made but for the Biological
Material, are expressly understood to be part of the Biological Material,
together with all documentation and descriptions of the Biological Material.

               (b) Xgene agrees not to supply the Biological Material to other
laboratories, nor to any other individual or organization other than employees
of the Xgene, and not to use the Biological Material, directly or indirectly,
for any commercial purpose without GCI's prior written approval. Any employee of
Xgene having access to Biological Material will be previously notified of and
agree to be bound by the terms of this Agreement. No employee or third party
will be allowed access to the Biological Material unless such employee or third
party is bound by an employment, confidentiality or other agreement requiring
assignment of all invention, patents and copyrights to Xgene.

               (c) Xgene will not use, directly or indirectly, the biological
Material in any research programs other than as contemplated herein without
GCI's prior written approval.

                                       7
<PAGE>   8

               (d) Xgene acknowledges that the Biological Material is the
confidential and proprietary property of GCI and agree to take reasonable care
necessary to prevent any disclosure, unauthorized use or transfer of the
Biological Material, or any information relating to such, to any party who is
not bound by this Agreement.

               (e) Xgene will not analyze, attempt to analyze, or have analyzed
the composition or formulation of the Biological Material except as specifically
provided herein.

               (f) Xgene acknowledges that the Biological Material is
experimental in nature and is not for human use. Xgene agrees to handle the
Biological Material with appropriate safety precautions. GCI hereby disclaims
all express and implied warranties of any kind with respect to the Biological
Material. Xgene agrees to hold GCI harmless from any and all liability and/or
damages (including costs of defense) resulting from Xgene' use of the Biological
Material, including any use in violation of this Agreement.

        7.3 Neither Party will publish any material arising from the Research
without prior written approval of the other Party. Such approval shall not be
unreasonably withheld but may be subject to a delay of up to (3) months total
for assessment of the proposed publication and to enable preparation and filing
of appropriate patent application(s). Both Parties will procure that any person
involved or interested in the Research will not publish or communicate material
arising therefrom without first complying with the provisions of this Section
7.3.

                                      VIII.
                                  MISCELLANEOUS

        8.1 Hold Harmless

               With respect to GCI's rights under Article 5, Xgene shall hold
GCI harmless for any activities thereunder which would otherwise infringe
Xgene's Background Technology or Background Patent Rights. GCI shall hold Xgene
harmless for any and all claims resulting from GCI's use of Xgene technology or
products and from the use of any therapeutic or other product developed, sold or
licensed by GCI which is developed using Xgene technology or products.

        8.2 Force Majeure

               Each of the Parties hereto shall be excused from performance of
its obligations and shall not be liable for damages to the other to the extent
that such performance is prevented by circumstances beyond its effective
control. Such excuse from performance shall continue so long as the condition
responsible for such excuse continues and for a thirty (30) day period
thereafter. For purposes of this Agreement, circumstances beyond the effective
control of a Party which excuse that Party from performance shall include but
shall not be limited to, act of God, act, regulations or laws of any government,
injunction or judgment of any court, war, civil commotion, destruction of
facility or materials by fire, earthquake, storm or other casualty, labor
disturbance, epidemic and failure of public utilities or common carrier.

        8.3 Relationship

                                       8
<PAGE>   9

               Xgene and GCI are independent contractors. Nothing in this
Agreement or the course of dealing of the parties shall be construed to
constitute the parties hereto as partners, joint ventures or as agents or
distributors for one another, or as authorizing any Party to obligate the other
in any manner.

        8.4 Non-Assignment

               This Agreement and the covenants herein contained shall be
binding and inure to the benefit of Xgene and GCI hereto and their heirs,
assigns, successors and legal representatives. This Agreement shall not be
assignable by any Party without the other Parties' prior written consent.

        8.5 Entire Agreement/Amendment

               This Agreement and the attachments hereto constitute and contain
the entire agreement of the Parties respecting the subject matter hereof. This
Agreement may only be amended by mutual written agreement of the Parties.

        8.6 Warranty of Right and Authority

               Each of the Parties represents and warrants to the other that it
has the full right and authority to enter into this Agreement, and that it is
not aware of any impediment which would inhibit its ability to perform the terms
and conditions imposed on it by this Agreement. Nothing contained herein shall
be interpreted as a warranty, express or implied as to the patentability,
enforceability or validity of any patent application or patent owned or
controlled by either Party.

        8.7 Further Acts and Instruments

               Each Party agrees to execute, acknowledge and deliver such
further instruments and do all such other acts as may be necessary or
appropriate to effect the purpose and intent of this Agreement.

        8.8 Severability

               In the event any one or more of the provisions of this Agreement
should for any reason be held by any court or authority having jurisdiction over
this Agreement or either of the parties hereto to be invalid, illegal or
unenforceable, such provision shall be reformed within the jurisdiction of such
court or authority to as nearly approximate the intent of the parties as
possible, and if the provision is unreformable the parties shall meet to discuss
what steps should be taken to remedy the situation; otherwise and elsewhere this
Agreement shall not be affected.

        8.9 Captions

               The captions to this Agreement are for convenience only and are
to be of no force or effect in construing or interpreting the provisions of this
Agreement.

                                       9
<PAGE>   10
        8.10 Counterparts

               This Agreement may be executed in two counterparts, each of which
shall be deemed an original, but all of which together shall constitute one and
the same instrument.

        8.11 Limitation of Liability

               No Party shall be liable to another for indirect, incidental,
consequential or special damages, including but not limited to lost profits,
arising from or relating to any breach of this Agreement, regardless of any
notice of the possibility of such damages. In no event shall either Party be
liable for damages relating to lost profits or reasonable royalties or special
damages due and payable to a third party on the basis of the other's sale of a
product developed hereunder.

        8.12 Publicity

               Either Party's use of the other Party's name or disclosure of the
existence or nature of this Agreement or the relationship created thereby to any
third party shall be only with the prior written consent of the other Party,
which consent will not be unreasonably withheld.

        8.13 Interpretation

               This Agreement has been jointly prepared by the Parties and their
respective legal counsel and shall not be strictly construed against either
Party.

        8.14 Notices

               Representatives for the receipt of payments, notices, records,
reports and other information pursuant to this agreement shall be as follows:

               For GCI:

               Attn:  Legal Department
               Genencor International, Inc.
               925 Page Mill Road
               Palo Alto CA  94304

               For Xgene:

               Xgene Corporation
               863A Mitten Road
               Burlingame, California 94010

        8.15 Controlling Law

               This Agreement shall be governed and construed in accordance with
the Laws of the State of New York, excluding any choice of law rules which may
direct the application of the law of any other jurisdiction. Questions effecting
the construction and effect of any patent rights

                                       10
<PAGE>   11

arising hereunder shall be determined by the laws of the country in which such
patent rights have been applied for and/or granted.

        8.16 Negation of Warranties

               Nothing in this Agreement shall be construed as:

               (a) an express or implied warranty or representation by Xgene as
to the validity or scope of any Background Technology, Background Patent Rights
or proprietary technology of Xgene;

               (b) a warranty or representation that anything made, used, sold
or otherwise disposed of under any license granted in this Agreement is or will
be free from infringement of patents, copyrights, and other rights of third
parties;

               (c) granting by implication, estoppel, or otherwise any licenses
or rights under patents or other rights owned or controlled by Xgene other than
those necessary for GCI to exercise its rights under Article 5 and 8.

        8.17 EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, NEITHER PARTY
MAKES ANY REPRESENTATIONS AND EXTENDS NO WARRANTIES OF ANY KIND, EITHER
EXPRESSED OR IMPLIED. THERE ARE NO EXPRESS OR IMPLIED WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR THAT THE RIGHTS OF USE
OF A LICENSED PRODUCT OR TECHNOLOGY WILL NOT INFRINGE ANY PATENT, COPYRIGHT OR
OTHER RIGHTS OF ANY THIRD PARTIES.

               IN WITNESS WHEREOF, the parties have caused this Agreement to be
executed by their duly authorized representatives.

GENENCOR INTERNATONAL, INC.                    XGENE CORPORATION

By: /s/ WAYNE H. PITCHER                       By:  /S/ SCOTT MCFARLANE
   ------------------------------                 -----------------------------

Name:  Wayne H. Pitcher                        Name:  Scott McFarlane
     ----------------------------                   ---------------------------

Title:  Senior VP, Technology                  Title:  Chief Financial Officer
      ---------------------------                    --------------------------

                                       11
<PAGE>   12

                                   APPENDIX A

                                XGENE CORPORATION
                DETECTION OF POSSIBLE ANTI-VIRAL ACTIVITY AGAINST
                            HUMAN PAPILLOMAVIRUSES IN

                              CULTURE *** FROM ***

SPECIFIC AIMS

            The objective of this project is to ascertain if the culture ***
from ***, obtained in large amounts by Genencor, Inc, possess an antiviral
activity against human papillomaviruses (HPV), as previously suggested. This
contract covers the development of a reliable model system that recapitulates
HPV infection in a differentiated skin epithelium, including known effects on
differentiation of the epidermis. In the first stage, a mouse animal model will
be utilized along the lines of that already developed by the primary
investigator, and adapted for recapitulation of normal HPV life cycle. In the
second stage, a multi-well in vitro tissue culture assay will be developed for
screening of *** fractions that may possess the anti-viral activity. If the
anti-viral activity is indeed detected some aspects of the mechanism of its
biological activity might be discerned by this research as well. We will
identify alterations in the normal viral lifecycle by monitoring epithelial cell
differentiation, and thereby localize the anti-viral activity to a specific
stage in the interaction of the virus with its host.

BACKGROUND AND SIGNIFICANCE

            Human papillomaviruses infect epidermal cells causing benign
neoplasms known as warts. The common wart (verruca vulgaris) is a firm papule
with a hyperkeratotic surface that often appears on the hands and fingers. Flat
warts are more subtle in appearance, being only slightly raised papules, often
appearing in linear arrangement on the hands or face. Plantar warts appear on
the plantar aspect of the foot, are covered by a thick callus, and are usually
painful. The most serious medical studies on warts have been conducted on
venereal warts (condyloma acuminatum) that can appear on the rectum, perineal
region, inguinal folds, external genitalia, vagina, and urethra. Their
prevalence is quite high, with genital forms of HPV infection being the most
common sexually transmitted disease. Approximately 1% of sexually active adults
have genital warts, while another 10-20% have latent infections. Of greater
concern than the appearance of warts is their connection to carcinoma. HPV
infection is a major cause of cervical cancer, and even flat warts have been
linked to squamous cell carcinoma. Currently treatment is limited to destructive
painful procedures that burn away the tissue in the infected area. Physical
methods of treatment, such as cryotherapy with liquid nitrogen,
electrodisiccation, surgical excision, and laser therapy are therefore limited
to destruction of infected tissue, as are the chemical methods, such as
salicylic acid, and podophyllin.(1-2)

                                       12
<PAGE>   13

            A serendipitous discovery may have provided us with a new anti-viral
to warts. Large scale culturing of *** at Genencor leads to the creation of
large volumes of *** as a byproduct of the industrial process, and this *** was
noticed to possess an HPV anti-viral activity. Documentation of this observation
as fact would lead to a valuable new product for Genencor. Firstly, the initial
observation of this activity belongs to Genencor as its sole intellectual
property, and secondly Genencor is uniquely positioned to take advantage of this
observation since it is the largest producer of the *** and has excellent
personnel and facilities for fractionation and purification of the activity.

            What has been missing is a biological assay to evaluate the *** and
partially purified fractions. This contract provides the missing assay by
funding a well known research dermatologist from Stanford in their new corporate
structure, Xgene Corporation. The problem with the assay stems from the present
state of the models used for studying HPV infection. Following infection of
basal cells, HPV episomes are maintained at 20-50 copies per cell, and it is not
until non-dividing daughter cells begin to migrate to the terminally
differentiated layers that late gene expression is induced. It is unlikely that
anti-viral activity could be assessed without inducing at least some of the
normal differentiation program of epithelial cells, where the viral lifecycle
progresses towards production of new viral particles. The epithelial cell of the
skin is the keratinocyte, and normal human keratinocytes (NHK) are the natural
host for HPV. Currently, cultures of keratinocytes cannot be brought to
differentiation unless grown in raft cultures, a cumbersome technique where
keratinocytes are grown on top of a dermal layer and the whole construct is
raised to an air-liquid interface to induce the differentiation of the
keratinocytes.(3)

            This contract with Xgene Corporation is to provide Genencor, Inc.
with a biological assay to assess anti-viral activity. Xgene is uniquely
positioned to provide workable assays for HPV anti-viral activity since it has
an intellectual property position on technology to recapitulate the normal
differentiation pattern of keratinocytes in a reconstituted human skin model.
While in the Dermatology Department at Stanford University, Dr. Hoeffler and his
laboratory developed a unique method for reconstituting full-thickness human
skin that allows for normal differentiation of the epidermis (patent
pending(4)). Importantly, tissue cultured cells are used in these
reconstitutions, thus offering the unique opportunity to go from separated
tissue culture cell populations back to a reconstituted organ, a unique feat in
organotypic modeling of skin. The plan is to use keratinocyte cell lines that
maintain the HPV episome in these skin reconstitutions, thus providing a
uniformly HPV infected skin on which to assay for anti-viral activity.

RESEARCH DESIGN AND METHODS

            Phase I  The novel skin reconstitution system is termed a CSSE (cell
sorted skin equivalent), and has been proven to provide a full-thickness skin
that maintains many of the aspects of normal skin, including a normal
differentiation pattern of the epithelium. In the first phase we will set up the
CSSE grown on the backs of severe immunocompromised mice (SCDDs) because this is
the system that is currently available for achieving normal keratinocyte
differentiation in the epidermis. SCIDs have been noted to have nearly double
the success rate of nude mice for the grafting of

<PAGE>   14

endogenously infected skin tissue.(5) A mixed cell slurry containing
approximately ***, and an approximately equal number of keratinocytes is placed
into a silicone chamber (CRD chamber, Renner) implanted directly on mouse muscle
fascia. After 1 week the upper part of the chamber is removed to allow drying of
the wound and exposure to an air interface, a crucial step in triggering full
epidermal differentiation.

            We will utilize keratinocyte cell lines that already have
incorporated the HPV viral episome, making the reconstituted skin more uniformly
infected with BPV than might be achieved by direct infection. Another advantage
is that we do not need to handle live BPV virus, which is notoriously difficult
to grow, prepare, and maintain. Examples of epithelial cell lines we could use
are *** and ***, which maintain episomal HPV-31 and HPV-16, respectively. Both
HPV types are associated with the anogenital region, and we need to determine if
the CSSE will accurately reconstitute with these epithelial cell lines. If not,
the reconstitutions will be conducted with similar keratinocyte cell lines
derived from common skin warts. These reconstitutions are likely to be
successful because results from keratinocytes immortalized with HPV E6-E7 genes
do reconstitute in the CSSE model. Somewhat similar methods have also been
successful that did not have the advantage of normal epidermal differentiation,
for example HPV 11 infected foreskin keratinocytes implanted in renal capsules
of athymic mice (9,10). In our experiments, biopsies will be taken, thin
sectioned and stained with hematoxylin/eosin, then immunostained using antibody
reagents to a variety of skin differentiation markers, including ***.

            Importantly, it has been shown that keratin 10 expression is delayed
in HPV infected skin, and is a consistent feature of the abnormal
differentiation in warts.(11) This offers the opportunity to further simplify
our assay for HPV infection in a second phase of the contract, but these
observations must first be reproduced in the CSSE model on SCIDs in order to
verify the use of persistently HPV infected epithelial cells for
reconstitutions. Using uninfected keratinocytes, we have consistently found that
keratin 10 staining in the CSSE is present in the entire differentiated
epidermis, and specifically excludes the basal keratinocyte layer alone, which
expresses keratin 5 and 14 instead. If keratin 10 expression is delayed during
HPV infection then there should be several cell layers above the basal layer
that will remain negative for keratin 10 expression. Perhaps the entire spinous
layer will remain negative, and only the granular layers will stain with the
keratin 10 antibody. If we can verify this result in the CSSE on SCIDs, we can
then attempt to extend this result to an in vitro tissue culture assay.

            The benchmarks for the phase I study are (1) establishing the
usefulness of persistently HPV-infected epithelial cells to provide an active
HPV infection in a reconstituted skin model, (2) establishing a panel of
immuno-reagents to be used in the characterization of the HPV infected skin, and
showing the expected effects of HPV infection on keratinocyte cell
differentiation (3) providing an initial test for determining if the *** has a
HPV anti-viral activity. Phase I should only be used to test the crude *** since
multiple animal tests would greatly increase the cost of this phase of the
study. In order to keep down costs, and improve the efficiency of the anti-HPV
viral assay and to make it practical for screening multiple column fractions, a
second phase is proposed.

<PAGE>   15

Thus purification and characterization of the HPV anti-viral activity can be
conducted during the second phase methodology.

            Phase II  The objective is to provide an in vitro tissue culture
method for screening the HPV anti-viral activity contained in *** and in
fractions. Although a single source for the anti-viral activity has been
identified (***), optimizations are likely necessary to optimize that source.
Variables created by culture conditions, including nutrients, growth period,
batch size etc. should be tested to guarantee reproducibility and optimize
activity. Likewise, storage conditions and fractionation procedures can be quite
varied and will likely create numerous fractions to test.

            We envision 96 well tissue culture trays containing an in vitro
version of the CSSE created using chronically infected epithelial cell lines
***, or others.(12, 13) Spontaneous cell sorting of fibroblasts and epithelial
cells will create a dermal/epidermal junction that contains the cell surface
markers required to signal the epidermal cells to be basal in character, ie.,
have the characteristics of basal keratinocytes along the basement membrane zone
(BMZ). Any epidermal layers above this will consist of transit amplifying cells
that will express differentiation markers. An air-liquid interface is required
for full keratinocyte differentiation, but may not be required for an assay of
antiviral activity. Fewer cells will be used in the tissue culture well than in
the chambers used on the animals and so only 2 or 3 keratinocyte layers will be
present above the fibroblast layer. This is done so that scoring the assay can
be read on the plates from above for positive or negative staining, rather than
requiring thin sectioning of reconstituted tissue. In the CSSE in situ we found
that only the basal layer keratinocytes express K5 and K14, and even the
keratinocytes just above them have turned these genes off, and are now
expressing K1 and K10. This pattern should reproduce in vitro, and would allow
us to develop a rapid screening method. As noted previously, K10 expression is
delayed in HPV infected epithelial cells. Immunostaining for K10 could be used
as at least part of the assay for antiviral activity; active HPV infection will
give a negative staining for K10, but inhibition of HPV infection by the
anti-viral activity will yield positive K10 staining. Additionally,
proliferating cell nuclear antigen (PCNA) is normally confined to the dividing
cells of the basal layer, but positive staining for PCNA is found in the upper
layers of benign warts.(14) Inhibition of HPV infection by the antiviral
activity would yield negative PCNA staining in upper keratinocyte layers. These
assays, in conjunction with direct staining for HPV viral proteins, may provide
an accurate measure of anti-viral activity. Antibody reagents have been
developed by others for the HPV L1 protein and for E1-E4 (the fusion protein of
the El and E4 regions that are also late gene products, and were mislabeled
E-regions rather than L, or late regions).

            The benchmarks for the phase II study are (1) demonstrating that the
persistently HPV-infected epithelial cells can be used to reconstitute skin in
vitro in a variation of the CSSE reconstituted skin model, (2) determining which
immuno-reagents will be used to score for HPV infected skin in this model, and
(3) showing that the assay positive fractions correlate with their performance
in the animal model.

            Phase III  High through-put screening in vitro for fractions that
have anti-viral activity. This phase is separate because it offers the greatest
price flexibility,
<PAGE>   16

dependent upon the number of fractions to be screened. Once a reproducibly
active preparation can be made, the fraction should be retested in the Phase I
style animal model to fully characterize effects of the anti-viral on normal
keratinocyte differentiation.

BUDGET

            Phase I $50,000 to conduct the CSSE animal model experiments using
the persistently infected cell lines. Included in the cost is the use of 3 SCID
mice at the end of the study, proven successful to do a preliminary test on the
***.

            Phase II *** to reduce the animal model assay to a 96 well tissue
culture assay for rapid screening of anti-viral activity. Costs are incurred to
create a practical screening method for productive HPV infection. Since current
methodology does not establish good precedents, a new method must be developed.
Multiple trials of culture conditions are anticipated increasing the cost above
that needed to do the first phase.

            Phase III Charge per assay cost set at *** per tissue culture assay
well. A 96 well assay will cost *** to set up and score for activity. Any SCID
mouse assays still needed will cost *** per mouse including administration of
the test fraction, biopsy, and thin sectioning. Hematoxylin/eosin staining and
staining with antibody reagents are *** each for approximately 6 thin sections
each. This cost structure guaranteed for the first year only.

            Xgene Corporation makes no future claim to ownership of the ***
anti-viral activity, and no royalty or license is requested. Genencor, Inc.
makes no future claim to the in vitro CSSE skin model or to its use for modeling
HPV infection.

REFERENCES

            1. Lookingbill, D.P., Marks, J.G. (eds): Principles of Dermatology.
2nd Ed. Philadelphia, W.B. Saunders, 1992, pp. 66-72.

            2. Cobb, M.W. Human papillomavirus infection. (1990) J.Am. Acad.
Dermatol. 20, 547-566.

            3. Meyers, C., Frattini, M.G., Hudson, J.B., and Laimins, L.A.
(1992) Biosynthesis of human papilomavirus from a continuous cell line dependent
upon epithelial differentiation. Science 257, 971-973.

            4. Nelson, C., Wang, C.K., Hoeffler, W.K. Skin equivalent and
methods of forming and using same. U.S. Patent Application.

            5. Sexton, C.J. Williams, A.T., Topley, P., Shaw, R.J., Lovegrove,
C., Leigh, I., and Staples, J.N. (1995) Development and characterization of a
novel xenograft model permissive for human papillomavirus DNA amplification and
late gene expression. J. Gen. Virol. 76, 3107-3112.

<PAGE>   17

            6. Bedell, M.A., Hudson, J., Golub, T., Turyk, M., Hosken, M.,
Wilbank, G., and Laimains, L.A. (1991) Amplification of human papillomavirus
genomes in vitro is dependent upon epithelial differentiation. J. Virol. 65,
2254-2260.

            7. Frattini, M.A., Lim, H.B., and Laimins, L.A. (1996) In vitro
synthesis of oncogenic human papillomaviruses requires episomal genomes for
differentiation-dependent late expression. Proc. Natl. Acad. Sci.93, 3062-3067.

            8. Stanley, M.A., Browne, H.M., Appleby, M., and Minson, A. (1989)
Properties of a non-tumorigenic human keratinocyte cell line. Internatl. J. of
Cancer 43, 672-676.

            9. Kreider, J.W., Howlett, M.K., Lill, N.L., Bartlett, G.L., Zaino,
RJ, Sedlacek, T.V., and Mortel, R. (1986) In vivo transformation of human skin
with human papillomavirus type II from condylomata acuminata. J,Virol. 59,
369-376.

            10. Kreider, J.W., Howlett, M.K., Leure-Dupree, A.E., Zaino, R.J.,
and Weber, J.A. (1987) Laboratory production in vivo of infectious human
papilloma type 11. J.Virol. 61, 590-593.

            11. Proby, C.M., Churchill, L., Purkis, P., Glover, M., Sexton, C.,
and Leigh, I.M. (1993) Keratin 17 expression as a marker for epithelial
transformation in viral warts. American J. Path. 143, 1667-1678.

            12. Braun, L., Mikumo, R., Mark, H., and Lauchlan, S. (1993)
Analysis of the growth properties and physical state of the human papillomavirus
type 16 genome in cell lines derived from primary cervical tumors. Am. J.
Pathol. 143, 832-844.

            13. Sterling, J., Stanley, M., Gatward, G., and Minson, T. (1990)
Production of human papillomavirus type 16 virions in a keratinocyte cell line.
J. Virol. 177, 415-417.

            14. Pennys, N.S., Bogaert, M., Serfling, U., and Sisto, M. (1992)
PCNA expression in cutaneous keratinous neoplasia and verucca vulgaris. American
J. Path. 141, 139-142.
<PAGE>   18

December 9, 1999

                                                             VIA FEDERAL EXPRESS
Warren Hoeffler
XGENE CORPORATION
P.O. Box 1310
2028 Howard Avenue
San Carlos, CA 94070

Dear Mr. Hoeffler:

Thank you for meeting with us on November 1 to review progress in our
collaboration, including the results of your Phase I efforts. The ability to
reconstitute the *** model with persistently infected HPV cells is an
encouraging step towards developing an *** screening system.

As you are aware, the Collaboration Agreement provides for payment of Milestone
1 upon development of an *** assay useful for the development and testing of
products having activity against human papilloma virus. Phase I of the research
plan attached to the Collaboration Agreement roughly corresponds to Milestone 1
and provides that work will be done which:

        (1) establishes the usefulness of persistently HPV-infected epithelial
        cells to provide an active HPV infection in a reconstituted skin model,
        (2) establishes a panel of immuno-reagents to be used in the
        characterization of the HPV infected skin, and showing the expected
        effects of HPV infection on keratinocyte cell differentiation, and (3)
        provides an initial test for determining if the *** has a HPV anti-viral
        activity.

The HPV-infected cell line, HUC18, showed the ability to reconstitute the CSSE
model comparably to the control cell line as demonstrated by histological
analysis corresponding to point (1) of Phase I. However, work was not completed
with respect to points (2) and (3) of Phase I. Specifically, although
reconstituted HUC18 skin patches expressed E2 viral protein, this particular
staining reagent did not distinguish the HUC18 reconstituted cells from those of
the control cell line as a measure of viral infection. In addition, initial
tests of the crude *** on HUC18 reconstituted skin suggests that the material is
selectively cytotoxic for virally infected vs. control skin and these results
were supported by preliminary toxicity tests of *** on in vitro cultured cells.
However, these test results require further analysis and validation.

Despite Xgene not having completed the testing requires for Milestone 1 under
the Collaboration Agreement, Genencor has agreed to make the payment regarding
Milestone 1. This payment was made to Xgene on November 10, 1999. In
consideration for Genencor making early payment on Milestone 1, you have agreed
that the results not met yet with respect to Milestone 1 will be incorporated
into the requirements for Milestone 2. Specifically, Xgene will provide results
in two areas to validate the interpretation of the phase I experiments: (1) a
primary keratinocyte line will be included in the CSSE model as an appropriate
control for distinguishing viral gene expression, or another antibody will be
identified that distinguishes HPV-infected skin cells from virally-transformed
"control" cells, and (2) the application of *** on HUC-18 reconstituted skin in
the CSSE model will be repeated using appropriate control mice and time points.

All other conditions of the contract and the Milestones will remain in effect.
Thus, Xgene's achievement of Milestone 2 will continue to include the primary
objectives of Phase II, i.e., providing an in vitro tissue culture method
for screening the HPC anti-viral activity contained in *** and fractions.

<PAGE>   19
December 9, 1999
Page 2

Please provide your acknowledgement by signing below and returning the executed
copy to us.

Sincerely yours,

/s/ MICHAEL V. ARBIGE

Michael V. Arbige, Ph.D.
Senior Vice President, Technology

MVB/CLS/klg
Encl.

By:     /s/ WARREN HOEFFLER
    ---------------------------
       Warren Hoeffler
       XGENE CORPORATION

                                       2

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