Document:

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                                                                   Exhibit 10.15

VRI004 (4/30/93)

                         AMENDMENT TO LICENSE AGREEMENT

      This amendment is entered into between the President and Fellows of
Harvard College (hereinafter HARVARD) having offices at the Office for
Technology and Trademark Licensing, 124 Mt. Auburn Street, Suite 440, Cambridge,
Massachusetts, 02138 and Virus Research Institute (hereinafter LICENSEE), a
corporation, having offices at 61 Moulton Street, Cambridge, MA 02139.

      WHEREAS HARVARD and LICENSEE have entered into a License Agreement
effective as of May 1, 1992 with respect to certain patents and technology
directed to cholerae (the "License Agreement");

      WHEREAS the parties desire to amend such License Agreement.

      NOW THEREFORE, in consideration of the foregoing premises, and the mutual
promises and other good and valuable consideration, the parties agree as
follows:

      1. Section 1.4 of the License Agreement is deleted in its entirety and
rewritten as follows:

      -- "NET SALES" means the total received by LICENSEE from sale of LICENSED
      PRODUCTS less transportation charges and insurance, sales taxes, use
      taxes, excise taxes, value added taxes, customs duties or other imports,
      to the extent itemized on invoice, normal and customary quantity and cash
      discounts (to the extent allowed), allowances and credits on account of
      rejection or return of LICENSED PRODUCTS. In the event that a LICENSED
      PRODUCT includes, a component which has therapeutic and/or prophylactic
      activity ("Active Component(s)") covered by a PATENT RIGHT (Patented
      Component(s)) and Active Components not covered by a PATENT RIGHT
      (Unpatented Component(s)) (such PRODUCT being a Combined Product), then
      NET SALES shall be the amount which is normally received by LICENSEE from
      a sale of the Patented Component(s) when sold separately in an arm's
      length transaction with an unaffiliated third party. If the Patented
      Component(s) are not sold separately, then NET SALES upon which royalty is
      paid shall be the NET SALES of the Combined Product multiplied by a
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      fraction, the numerator of which is the cost for producing the Patented
      Components and the denominator of which is the cost for producing the
      Combined Product.

      2. Add the following Section 1.6 to the License Agreement.

      --1.6 The term "SUBLICENSEE" shall mean any non-AFFILIATE third party
      licensed by LICENSEE to make, have made, use or sell any product or use
      any process under PATENT RIGHTS.--

      3. Paragraphs 2.2(c), 2.2(d), 2.2(e) and 2.2(f) of the License Agreement
are deleted in the entirety.

      4. Paragraph 2.2(g) of the License Agreement is renumbered as Paragraph
2.2(c).

      5. The following paragraph is added to the License Agreement as Paragraph
2.5.

      --2.5 LICENSEE has provided HARVARD with a development plan for developing
      and obtaining regulatory approval of the LICENSED PRODUCT selected by
      LICENSEE, which development plan includes milestones.

      LICENSEE shall exert reasonable efforts under the circumstances to achieve
      such milestones. In the event LICENSEE subsequently indicates in writing
      to HARVARD that such milestones cannot be met or fails to meet such
      milestones, LICENSEE shall promptly notify HARVARD, and LICENSEE and
      HARVARD shall promptly enter into good faith negotiations to reconsider
      such milestones. In the event that the parties cannot agree to the
      milestones within sixty (60) days after beginning good faith negotiations,
      the matter shall be submitted to arbitration to determine the milestones
      and the time period therefor which should be met pursuant to this Section.
      The arbitrator in setting and determining milestones shall consider the
      state of technology; the efforts exerted by LICENSEE, the business
      circumstances of LICENSEE and the public interest objectives to HARVARD'S
      licensing program; and technical and regulatory problems. Thereafter,
      LICENSEE shall exert reasonable efforts to achieve such milestones.

      In the event that LICENSEE cannot meet the milestones set by arbitration
      because of technological or regulatory problems, HARVARD shall not
      unreasonably deny an extension of time to meet
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      the milestones, upon a showing by LICENSEE that it has made good faith
      reasonable efforts to meet the milestones.

      If LICENSEE (i) falls to meet the milestones established by agreement of
      the parties and (ii) fails to obtain extensions of such milestones
      established by arbitration and (111) LICENSEE has not exerted good faith
      reasonable efforts to meet such milestones, as its sole and exclusive
      remedy HARVARD shall have the right to terminate or convert the licenses
      to non-exclusive licenses by providing to LICENSEE sixty (60) days prior
      written notice.

      Notwithstanding anything else to the contrary, in the event that LICENSEE
      and/or its AFFILIATE(s) and/or SUBLICENSEE(s) have expended at least two
      hundred fifty thousand dollars ($250,000) in research and developing a
      LICENSED PRODUCT and LICENSEE intends to continue development of a
      LICENSED PRODUCT, the rights and licenses granted hereunder shall not
      terminate and shall be converted to a non-exclusive right and license, and
      further provided that LICENSEE or a SUBLICENSEE or an entity on its behalf
      spends at least one hundred thousand dollars ($100,000) per year in
      pursuing development of PRODUCT for commercial sale.

      LICENSEE shall ensure that for any PRODUCT being developed or
      commercialized by a SUBLICENSEE, such SUBLICENSEE shall assume the
      obligations imposed on LICENSEE under this paragraph.

      The efforts of an AFFILIATE, SUBLICENSEE or collaborator of LICENSEE shall
      be considered as efforts of LICENSEE. - -

      6. Rewrite Paragraph 3.2 of the License Agreement in its entirety to read
as follows:

      --3.2 LICENSEE shall pay HARVARD, during the term of the license granted
      in Section 2.1, (i) a royalty of four percent (4%) of the NET SALES of the
      LICENSED PRODUCTS sold by LICENSEE and its AFFILIATES to commercial
      organizations, and two percent (2%) of the NET SALES of the LICENSED
      PRODUCTS sold by LICENSEE and its AFFILIATES to non-profit or government
      agencies, or (ii) twenty-five percent (25%) of royalties received by
      LICENSEE or its AFFILIATES from a SUBLICENSEE for all LICENSED PRODUCTS
      covered by a PATENT RIGHT licensed to LICENSEE, and twenty-five percent
      (25%) of upfront license and license maintenance fees received from a
      SUBLICENSEE for a license under PATENT RIGHTS, in the case where the
      SUBLICENSEE is a commercial organization, and ten percent (10%) of such
      royalties and fees where the SUBLICENSEE, is a government or non-profit
      organization.--

      7.    Delete Paragraph 4.1 of the License Agreement in its entirety.
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      8. Rewrite Paragraph 4.2 of the License Agreement in its entirety to read
as follows:

      --4.2 LICENSEE shall provide written annual reports within sixty (60) days
      after June 30 of each calendar year which shall include but not be limited
      to: reports of progress on research and development, regulatory approvals,
      manufacturing, sublicensing, marketing and sales during the preceding
      twelve (12) months as well as plans for the coming year. --

      9. Rewrite Paragraph 8.4 of the License Agreement in its entirety to read
as follows:

      --8.4 In the event that the licenses granted to LICENSEE under this
      Agreement are terminated, any granted sub-licenses shall remain in full
      force and effect as a direct license from HARVARD to the SUBLICENSEE,
      provided that the SUBLICENSEE is not then in breach of its sub-license
      agreement and the SUBLICENSEE agrees to be bound (as a licensee) to
      HARVARD (as a licensor) under the terms and conditions of the sub-license
      agreement. --

      10. In Paragraph 9.3(a) of the License Agreement, delete the last sentence
in its entirety.

      11. Delete Paragraphs 9.3(b), 9.3(c), 9.3(d) and 9.3(e) of the License
Agreement and in lieu thereof insert the following:

      (b) LICENSEE'S indemnification under (a) above shall not apply to any
      liability, damage, loss or expense to the extent to apply to any
      liability, damage, loss or expense to the extent that it is attributable
      to the negligent activities or willful misconduct of the Indemnitees.

      (c) HARVARD shall notify LICENSEE promptly of any claim or threatened
      claim under this Paragraph 9.3 and shall fully cooperate with all
      reasonable requests of LICENSEE with respect thereto.

      (d) LICENSEE agrees, at its own expense, to provide attorneys reasonably
      acceptable to HARVARD to defend against any actions brought or filed
      against any party indemnified hereunder with respect to the subject of
      indemnity contained herein, whether or not such actions are rightfully
      brought and LICENSEE shall have the right to control the defense,
      settlement or compromise of any such claim or action.
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      (e) At such time as any PRODUCT is being commercially distributed or sold
      (other than for research purposes or for the purpose of obtaining
      regulatory approvals) by LICENSEE, or by an AFFILIATE, SUBLICENSEE or
      agent of LICENSEE (hereunder "Other Seller"), LICENSEE shall itself or in
      the alternative shall ensure that Other Seller either (i) at its sole cost
      and expense, procure(s) and maintain(s) comprehensive general liability
      insurance in amounts not less than $2,000,000 per incident and $2,000,000
      annual aggregate and naming the Indemnitees as additional insureds or (ii)
      pay(s) for the procurement and maintenance by HARVARD of insurance in the
      amounts and in the form set forth in this paragraph. Such comprehensive
      general liability insurance shall provide (i) product liability coverage
      and (ii) broad form contractual liability coverage for LICENSEE'S
      indemnification under Paragraph 9.3(a) of this Agreement. LICENSEE shall
      ensure that if LICENSEE or the Other Seller elects to self-insure all or
      part of the limits described above (including deductibles or retentions
      which are in excess of $250,000 annual aggregate) such self-insurance
      program must be acceptable to HARVARD and the Risk Management Foundation.
      The minimum amounts of insurance coverage required under this Paragraph
      9.3(c) shall not be construed to create a limit of LICENSEE'S liability
      with respect to its indemnification under Paragraph 9.3(a) of this
      Agreement. At such time, or at any time, LICENSEE can request that HARVARD
      ascertain whether Risk Management Foundation has in effect Uniform
      Indemnification and Insurance Provisions more favorable than those of this
      Agreement, in which event LICENSEE and HARVARD shall amend this Agreement
      to include such more favorable provisions.

      (f) LICENSEE shall provide HARVARD with written evidence of such insurance
      upon request of HARVARD. LICENSEE shall provide HARVARD with written
      notice of at least thirty (30) days prior to the cancellation, non-renewal
      or material change in such insurance; if LICENSEE does not obtain
      replacement insurance providing comparable coverage within such thirty
      (30) days period, HARVARD shall have the right to terminate this Agreement
      effective at the end of such thirty (30) day period by written notice to
      LICENSEE.

      (g) LICENSEE shall itself maintain, or shall ensure that Other Seller
      maintains or that payments are made for the maintenance by HARVARD of, as
      the case may be, such comprehensive general liability insurance beyond the
      expiration or termination of this Agreement during (i) the period that any
      LICENSED PRODUCT is being commercially distributed or sold (other than for
      research purposes or the purpose of obtaining regulatory approvals) by
      Other Seller and (ii) a reasonable period after the period referred to in
      (g) (i) above which shall in no event
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      be less than ten (10) years. The obligations of (g)(ii) above can be
      satisfied by the purchase of insurance by LICENSEE or a third party which
      covers claims resulting from occurrences during such period of (g)(ii)
      above for LICENSED PRODUCT commercially distributed or sold by LICENSEE or
      Other Seller during the period referred to in (g)(i) above.

      12. Except as modified herein, the License Agreement and the terms,
conditions and obligations thereof remain in full force and effect as originally
written.

      IN WITNESS WHEREOF, the parties hereto intending to be bound have set
their hands and seal effective as of the date first above written.

      PRESIDENT AND FELLOWS                 VIRUS RESEARCH INSTITUTE
      OF HARVARD COLLEGE

By:   /s/ Joyce Brinton                     BY: /s/ [ILLEGIBLE]
      ---------------------------               --------------------------
        Joyce Brinton, Director

TITLE: Office for Technology and            TITLE: President
       Trademark Licensing                         -----------------------
       Harvard University
       -------------------------

DATE:   7/9/93                              DATE:  7/23/93
      -------------------------                    -----------------------
<PAGE>

                                LICENSE AGREEMENT

This Agreement is made and entered into between the President and Fellows of
Harvard College (hereinafter HARVARD) having offices at the Office for
Technology and Trademark Licensing, 124 Mt. Auburn Street, Suite 440, Cambridge,
Massachusetts, 02138 and Virus Research Institute (hereinafter LICENSEE), a
corporation of Cambridge, MA, having offices at 61 Moulton Street, Cambridge, MA
02139

Whereas HARVARD and The General Hospital Corporation (GENERAL) doing business as
Massachusetts General Hospital are or will be the Owners by assignment, of the
entire right, title and interest in the following United States patent
applications, and in the foreign patent applications corresponding thereto, and
in the inventions described and claimed therein and any patents issuing thereon,
and whereas GENERAL and HARVARD have agreed to cooperate in the patent and
license administration of such patent applications:

      U.S.S.N. 629,602 - "Improved Vaccines"; filed December 18, 1990;
      Inventors: John Mekalanos and Samuel Miller.

      U.S.S.N. 629,102 - "Vibrio Cholerae Strains Defective in irgA Expression
      and Cholera Vaccines Derived Therefrom"; filed December 18, 1990;
      Inventors: John Mekalanos and Stephen Calderwood.

      U.S.S.N. 000,000 - "Doubly-Attenuated Strain of Vibrio Cholerae to Deliver
      Heterlogous Antigens for Vaccination" to be filed in 1992; Inventors: John
      Mekalanos and Stephen Calderwood (serial number and filing date to be
      inserted when available;

Whereas GENERAL has agreed HARVARD is its sole licensing agent for these jointly
owned patent applications; and

Whereas HARVARD is the Owner by assignment of the entire right, title and
interest in the following United States Patents or Patent Applications and in
the foreign patent applications corresponding thereto, and in the inventions
described and contained therein:

      U.S.S.N. 043,907 - "Cholera Vaccines"; filed April 29, 1987 and its CIP
      USSN 5,098,998, filed April 29, 1988; Inventors: John Mekalanos and Ronald
      Taylor.
<PAGE>

      U.S. 4,882,278 - "Non-Toxic Vibrio Cholera Mutants"; issued November 21,
      1989; Inventor: John Mekalanos.

      U.S.S.N 000,000 - "Peruvian Strain of Cholera Vaccine"; to be filed in
      1992; Inventor: John Mekalanos (serial number and filing date to be
      inserted when available); and

Whereas HARVARD and GENERAL are the Owners by assignment from the inventors of
the BIOLOGICAL MATERIAL as defined in Appendix B and have the right to license
the BIOLOGICAL MATERIAL; and

Whereas HARVARD and the GENERAL are committed to a policy that ideas or creative
works produced at HARVARD and the GENERAL should be used for the greatest
possible public benefit; and

Whereas HARVARD accordingly believes that every reasonable incentive should be
provided for the prompt introduction of such ideas into public use, all in a
manner consistent with the public interest; and

Whereas LICENSEE is desirous of obtaining an exclusive worldwide license in
order to practice the above referenced inventions covered by PATENT RIGHTS and
to use the BIOLOGICAL MATERIAL in the United States and in certain foreign
countries, and to manufacture, use and sell in the commercial market the
products made in accordance therewith; and

Whereas HARVARD is desirous of granting such a license to LICENSEE in accordance
with the terms of this Agreement. Now therefore, in consideration of the
foregoing premises, the parties agree as follows:

                                    ARTICLE I

                                   DEFINITIONS

1.1   PATENT RIGHTS shall mean any and all United States patents or patent
      applications listed above and attached hereto in Appendix A, the
      inventions described and claimed therein, and any divisions,
      continuations, continuations-in-part directed to subject matter
      specifically described in the application and patents listed in Appendix
      A, patents issuing thereon or reissues thereof; and any and all foreign
      patents and patent applications corresponding thereto; which will be
      automatically incorporated in and added to this Agreement and shall
      periodically be added to Appendix A and made a part thereof. To the extent
      HARVARD's obligations to third parties permit, PATENT RIGHTS shall also
      include all IMPROVEMENT INVENTIONS. IMPROVEMENT INVENTIONS shall mean any
      inventions or discoveries that enhance, substitute for, or are useful with
      the products, procedures or processes described in PATENT RIGHTS to the
      extent they are (i) dominated by any claims of a pending and/or issued
      patent or

                                       2

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      patent application which is then included in the PATENT RIGHTS, and
      HARVARD's ownership interest in any United States or foreign patents and
      patent application thereon, and (ii) made (i.e., conceived and reduced to
      practice) by Dr. John Mekalanos solely or jointly with others directly
      supervised in his laboratory at Harvard Medical School. IMPROVEMENT
      INVENTIONS shall not include inventions assignable to GENERAL.

1.2   LICENSED PRODUCTS shall mean products covered in whole or in part by an
      issued, unexpired claim or a pending claim contained in PATENT RIGHTS
      which has not been declared invalid by a court of competent jurisdiction.

1.3   LICENSED PROCESSES shall mean processes covered in whole or in part by an
      issued, unexpired claim or a pending claim contained in PATENT RIGHTS
      which has not been declared invalid by a court of competent jurisdiction.

1.4   NET SALES shall mean the amount billed or invoiced on sales of LICENSED
      PRODUCTS less:

      (a)   Customary trade, quantity or cash discounts and non-affiliated
            brokers' or agents' commissions actually allowed and taken;

      (b)   Amounts repaid or credited by reason of rejection or return; and/or

      (c)   To the extent separately stated on purchase orders, invoices or
            other documents of sale, taxes levied on and/or other governmental
            charges made as to production, sale, transportation, delivery or use
            and paid by or on behalf of LICENSEE.

1.5   AFFILIATES shall mean any company, corporation, or business (i) in which
      LICENSEE directly or indirectly owns or controls at least fifty percent
      (50%) of the voting stock, or (ii) which directly or indirectly owns or
      controls at least fifty percent (50%) of the voting stock of LICENSEE or
      (iii) the majority ownership of which is directly or indirectly under
      common control with LICENSEE.

1.6   BIOLOGICAL MATERIAL shall mean the materials supplied by HARVARD and
      GENERAL (identified in Appendix B).

                                        3

<PAGE>

1.7   TECHNOLOGY shall mean any and all information or PATENT RIGHTS, or
      BIOLOGICAL MATERIAL supplied by HARVARD and GENERAL to LICENSEE.

                                      GRANT

2.1   For the term of this Agreement, HARVARD hereby grants to LICENSEE and
      LICENSEE accepts, subject to the terms and conditions hereof, a worldwide
      license under PATENT RIGHTS and a worldwide license to use the BIOLOGICAL
      MATERIAL, to make and have made, to use and have used, to sell and have
      sold the LICENSED PRODUCTS, and to practice the LICENSED PROCESSES. Such
      license shall include the right to grant sublicenses. In order to provide
      LICENSEE with a period of exclusivity, HARVARD agrees it will not grant
      licenses to others except as required under Paragraph 2.2 (a) or as
      permitted in paragraph 2.2 (b). LICENSEE agrees during the period of
      exclusivity of this license in the United States that any LICENSED PRODUCT
      produced for sale in the United States will be manufactured substantially
      in the United States.

2.2   The granting and acceptance of this license is subject to the following
      conditions:

      (a) HARVARD's "Statement of Policy in Regard to Inventions, Patents and
      Copyrights" dated March 17, 1986, Public Law 96-517, Public Law 98-620 and
      HARVARD's and GENERAL's obligations under agreements with other sponsors
      of research. Any right granted in this Agreement greater than that
      permitted under Public Law 96-517 or Public Law 98-620 shall be subject to
      modification as may be required to conform to the provisions of that
      statute.

      (b) HARVARD's and GENERAL's right to make and to use and to grant
      non-exclusive licenses to make and to use, for academic research purposes
      only and for GENERAL's internal inpatient care purposes and not for any
      commercial purpose, the subject matter described and claimed in PATENT
      RIGHTS, or the BIOLOGICAL MATERIAL.

      (c) LICENSEE shall use reasonable effort to effect introduction of the
      LICENSED PRODUCTS into the commercial market as soon as practicable,
      consistent with sound and reasonable business practices and judgment;
      thereafter, until the expiration of this Agreement, LICENSEE shall
      endeavor to keep LICENSED PRODUCTS reasonably available to the public.

      (d) HARVARD shall have the right to terminate or render non-exclusive any
      license granted hereunder if in HARVARD's reasonable judgement, LICENSEE:

                                        4

<PAGE>

      (i) has not, within five years from the date of this Agreement, commenced
      clinical trials of a LICENSED PRODUCT or LICENSED PROCESS in the country
      or countries where licensed; and/or

      (ii) is not, within one year of the date of this Agreement, demonstrably
      engaged in on-going research, development, or marketing or licensing
      programs as appropriate, directed toward commercial use of the LICENSED
      PRODUCT or LICENSED PROCESSES.

In making this determination HARVARD shall take into account the normal course
of such programs conducted with sound and reasonable business practices and
judgment and shall take into account the reports provided hereunder by LICENSEE.

(e) All sublicenses granted by LICENSEE hereunder shall include a requirement
that the sublicensee use its good faith efforts to bring the subject matter of
the sublicense into commercial use as quickly as is reasonably possible
consistent with sound and reasonable business practices and judgement and shall
bind the sublicensee to meet LICENSEE's obligations to HARVARD under this
Agreement. Royalties charged for sublicenses by LICENSEE shall not be in excess
of normal trade practice. Copies of all sublicense agreements shall be provided
to HARVARD.

(f) In the event that LICENSEE is in default of its obligations under Section
2.2 (c) or (e) or Article III, and such default remains unresolved following
notice as provided in Section 8.2 or LICENSEE fails to meet the milestones
specified in Section 2.2 (d) and HARVARD does not thereafter exercise it right
to terminate this license, and LICENSEE is thereafter unable or unwilling to
grant sublicenses, either as suggested by HARVARD or a potential sublicensee or
otherwise, HARVARD may directly license such potential sublicensee unless
LICENSEE reasonably satisfies HARVARD that such sublicense would be contrary to
sound and reasonable business practice, and that the granting of such sublicense
would not materially increase the availability to the public of products
manufactured under this license.

(g) HARVARD shall have the right to terminate this Agreement if LICENSEE does
not have commitments for a minimum of one million dollars ($1,000,000) of
investment capital within six (6) months of the signing of this Agreement, and
three million dollars ($3,000,000) of total funding within thirty-six (36)
months of the signing of this Agreement.

                                       5

<PAGE>

2.3   HARVARD hereby grants to LICENSEE the right to extend the licenses granted
      or to be granted in paragraph 2.1 to an AFFILIATE subject to the terms and
      conditions hereof.

2.4   All rights reserved to the United States Government and others under
      Public Law 96-517 and 98-620 shall remain and shall in no way be affected
      by this Agreement.

                                   ARTICLE III

                                    ROYALTIES

3.1   LICENSEE shall pay to HARVARD a non-refundable license fee in the sum of
      $200,000 in two equal installments, the first upon execution of this
      Agreement, and the second six months after the signing of this Agreement.

3.2   LICENSEE shall pay HARVARD, during the term of the license granted in
      Section 2.1, a royalty of four percent (4%) of the NET SALES of all
      LICENSED PRODUCTS sold by LICENSEE and its AFFILIATES or sublicensees to
      commercial organizations, and two percent (2%) of the NET SALES of all
      LICENSED PRODUCTS sold by LICENSEE and its AFFILIATES or sublicensees to
      non-profit or government agencies. In the case of sublicenses, LICENSEE
      shall also pay to HARVARD twenty-five percent (25%) of non-royalty
      sublicense income (e.g., license issue fees, license maintenance fees,
      etc.) from commercial organizations, and ten percent (10%) of all such
      income from government or non-profit organizations. If this license is
      converted to a non-exclusive one and if other non-exclusive licenses are
      granted, this royalty shall not exceed the royalty being paid by other
      licensees during the term of the non-exclusive license. On sales between
      LICENSEE and its AFFILIATES or sublicensees for resale, the royalty shall
      be paid on the resale.

3.3   HARVARD shall have the right to terminate or render non-exclusive this
      license in the event that LICENSEE does not pay to HARVARD at least the
      following amounts in license maintenance fees and/or minimum royalties:

             First calendar year                 -$10,000
             Next calendar year                  -$15,000
             Next calendar year                  -$20,000
             and each year thereafter.

      In the event that actual royalties are not at least equal to the above
      amounts for the specified periods, LICENSEE shall have the right to pay
      any difference between such minimum amounts and the actual royalties paid
      in satisfaction of its obligations under this Section 3.3.

                                        6

<PAGE>

3.4   In the event that LICENSEE is required to pay royalties to one or more
      third parties under patents other than PATENT RIGHTS covering LICENSED
      PRODUCTS or LICENSED PROCESSES, LICENSEE shall be entitled to a credit
      against royalties due HARVARD in an amount equal to fifty percent (50%) of
      royalties paid to such third parties, provided that in no event shall the
      royalties otherwise due HARVARD be reduced by more than one-half.

3.5   In the event that the royalties paid to HARVARD are so significant a
      factor in the return realized by LICENSEE as to diminish LICENSEE's
      capability to respond to competitive pressures in the market, HARVARD
      agrees to consider a reasonable reduction in the royalty paid to HARVARD
      as to each LICENSED PRODUCT for the period during which such market
      condition exists. Factors determining the size of the reduction will
      include profit margin on LICENSED PRODUCTS and on analogous products,
      prices of competitive products, total prior sales by LICENSEE, and
      LICENSEE's expenditures on LICENSED PRODUCT development.

                                   ARTICLE IV

                                    REPORTING

4.1   Prior to signing this Agreement, LICENSEE has provided to HARVARD a
      written research and development plan under which LICENSEE intends to
      bring the subject matter of the licenses granted hereunder into commercial
      use upon execution of this Agreement. Such plan includes projections of
      sales and proposed marketing efforts.

4.2   LICENSEE shall provide written annual reports within sixty (60) days after
      June 30 of each calendar year which shall include but not be limited to:
      reports of progress on research and development, regulatory approvals,
      manufacturing, sublicensing, marketing and sales during the preceding
      twelve (12) months as well as plans for the coming year. If progress
      differs from that anticipated in the plan provided under Section 4.1,
      LICENSEE shall explain the reasons for the difference and propose a
      modified plan for HARVARD's review and approval. LICENSEE shall also
      provide any reasonable additional data HARVARD requires to evaluate
      LICENSEE's performance.

4.3   LICENSEE shall report to HARVARD the date of first sale of LICENSED
      PRODUCTS (or results of LICENSED PROCESSES) in each country within thirty
      (30) days of occurrence.

4.4   Commencing with the calendar year half in which Net Sales first occur,
      LICENSEE agrees to submit to HARVARD within sixty (60) days after the
      calendar half years ending June 30 and December 31, reports setting forth
      for the preceding six (6) month period the amount of the LICENSED PRODUCTS
      sold by LICENSEE, its AFFILIATES and sublicensees in each country, the NET
      SALES thereof, and the amount of royalty due thereon and with each such
      royalty

                                            7

<PAGE>

      any non-royalty sublicense income and pay the amount of royalty due. Such
      report shall be certified as correct by an officer of LICENSEE and shall
      include a detailed listing of all deductions from NET SALES, sublicensee
      income or from royalties as specified herein. Such report shall also
      specify which PATENT RIGHTS are used in or by each LICENSED PRODUCT
      generating royalty income. If no royalties are due to HARVARD for any
      reporting period, the written report shall so state. If royalties for any
      calendar year do not equal or exceed the minimum royalties established in
      paragraph 3.3, LICENSEE shall include the balance of the minimum royalty
      with the payment for the half year ending December 31. All royalties due
      hereunder shall be payable in United States dollars. Conversion of foreign
      currency to U.S. dollars shall be made at the conversion rate existing in
      the United States on the, last business day in the reporting period as
      reported in the Wall Street Journal. All such reports shall be maintained
      in confidence by HARVARD, except as required by law, including Public Law
      96-517 and 98-620.

4.5   If by law, regulation, of fiscal policy of a particular country,
      conversion into United States dollars or transfer of funds of a
      convertible currency to the United States is restricted or forbidden,
      LICENSEE shall give HARVARD prompt notice in writing and shall pay the
      royalty and other amounts due through such means or methods as are lawful
      in such country as HARVARD may reasonably designate. Failing the
      designation by HARVARD of such lawful means or methods within thirty (30)
      days after such notice is given to HARVARD, LICENSEE shall deposit such
      royalty payment in local currency to the credit of HARVARD in a recognized
      banking institution designated by HARVARD, or if none is designated by
      HARVARD within the thirty (30) day period described above, in a recognized
      banking institution selected by LICENSEE and identified in a written
      notice to HARVARD by LICENSEE, and such deposit shall fulfill all
      obligations of LICENSEE to HARVARD with respect to such royalties.

                                    ARTICLE V

                                 RECORD KEEPING

5.1   LICENSEE shall keep, and shall require its AFFILIATES and sublicensees to
      keep accurate and correct records of LICENSED PRODUCTS made, used or sold
      under this Agreement, appropriate to determine the amount of royalties due
      hereunder to HARVARD. Such records shall be retained for at least three
      (3) years following a given reporting period. They shall be available
      during normal business hours for inspection at the expense of HARVARD by
      HARVARD's Internal Audit Department or by a Certified Public Accountant
      selected by HARVARD and approved by LICENSEE for the sole purpose of
      verifying reports and payments hereunder. Such accountant shall not
      disclose to

                                        8

<PAGE>

      HARVARD any information other than information relating to accuracy of
      reports and payments made under this Agreement. In the event that any such
      inspection shows an under reporting and underpayment in excess of five
      percent (5%) for any twelve (12) month period, then LICENSEE shall pay the
      cost of such examination.

                                   ARTICLE VI

               DOMESTIC AND FOREIGN PATENT FILING AND MAINTENANCE

6.1   LICENSEE shall reimburse HARVARD for all reasonable expenses HARVARD and
      GENERAL have incurred and shall incur for the preparation, filing,
      prosecution and maintenance of PATENT RIGHTS for which HARVARD or GENERAL
      has not been, and is not eligible to be reimbursed by any third party.
      HARVARD and GENERAL shall take responsibility for the preparation, filing,
      prosecution and maintenance of any and all patent applications and patents
      included in PATENT RIGHTS using patent counsel reasonably acceptable to
      LICENSEE, provided however that HARVARD and GENERAL shall first consult
      with LICENSEE as to the preparation, filing, prosecution and maintenance
      of such patent applications and patents and shall furnish to LICENSEE
      copies of documents relevant to any such preparation, filing, prosecution
      or maintenance.

6.2   HARVARD, GENERAL, and LICENSEE shall cooperate fully in the preparation,
      filing, prosecution and maintenance of PATENT RIGHTS and of all patents
      and patent applications licensed to LICENSEE hereunder, executing all
      papers and instruments or requiring members of HARVARD and GENERAL to
      execute such papers and instruments so as to enable HARVARD and GENERAL to
      apply for, to prosecute and to maintain patent applications and patents in
      HARVARD's and/or GENERAL's name in any country. Each party shall provide
      to the other prompt notice as to all matters which come to its attention
      and which may affect the preparation, filing, prosecution or maintenance
      of any such patent applications or patents.

6.3   If LICENSEE elects not to pay the expenses of a patent application or
      patent included within PATENT RIGHTS in a particular country, LICENSEE
      shall notify HARVARD not less than sixty (60) days prior to such action
      and shall thereby surrender its rights under such patent or patent
      application in such country. LICENSEE agrees that it shall not exercise
      this right for the purpose of avoiding the payment of royalties otherwise
      due in such country.

                                        9

<PAGE>

                                   ARTICLE VII

                                  INFRINGEMENT

7.1   With respect to any PATENT RIGHTS under which LICENSEE is exclusively
      licensed pursuant to this Agreement, LICENSEE or its sublicensee shall
      have the right to prosecute in its own name and at its own expense any
      infringement of such patent, so long as such license is exclusive at the
      time of the commencement of such action. HARVARD agrees to notify LICENSEE
      promptly of each infringement of such patents of which HARVARD is or
      becomes aware. Before LICENSEE or its sublicensees commences an action
      with respect to any infringement of such patents, LICENSEE shall give
      careful consideration to the views of HARVARD and to potential effects on
      the public interest in making its decision whether or not to sue and in
      the case of a LICENSEE sublicense, shall report such views to the
      sublicensee.

7.2   If LICENSEE or its sublicensee elects to commence an action as described
      above and HARVARD and/or GENERAL is a legally indispensable party to such
      action, HARVARD and/or GENERAL shall have the right to assign to LICENSEE
      all of HARVARD's and/or GENERAL's right, title and interest in each patent
      which is a part of the PATENT RIGHTS and is the subject of such action
      (subject to all HARVARD's and/or GENERAL's obligations to the government
      and others having rights in such patent). In the event that HARVARD and/or
      GENERAL makes such an assignment, such assignment shall be irrevocable,
      and such action by LICENSEE on that patent or patents shall thereafter be
      brought or continued without HARVARD and/or GENERAL as a party' if HARVARD
      and/or GENERAL is no longer an indispensable party. Notwithstanding any
      such assignment to LICENSEE by HARVARD and/or GENERAL and regardless of
      whether HARVARD and/or GENERAL is or is not an indispensable party,
      HARVARD and/or GENERAL shall cooperate fully with LICENSEE, at LICENSEE's
      expense, in connection with any such action. In the event that any patent
      is assigned to LICENSEE by HARVARD and/or GENERAL, pursuant to this
      paragraph, such assignment shall require LICENSEE to continue to meet its
      obligations under this Agreement as if the assigned patent or patent
      application were still licensed to LICENSEE.

7.3   If LICENSEE or its sublicensee elects to commence an action as described
      above, LICENSEE may reduce, by up to 50%, the royalty due to HARVARD
      earned under the patent subject to suit by the amount of the expenses and
      costs of such action, including attorney fees. In the event that such
      expenses and costs exceed the amount of royalties withheld by LICENSEE for
      any calendar year, LICENSEE may to that extent reduce the royalties due to
      HARVARD from LICENSEE in succeeding calendar years, but never by more than
      50% of the royalty due in any one year.

                                       10

<PAGE>

7.4   Recoveries or reimbursements from such action shall first be applied to
      reimburse LICENSEE and HARVARD and GENERAL for litigation costs not paid
      from royalties (if any) and then to reimburse HARVARD for royalties
      withheld. Any remaining recoveries or reimbursements shall be distributed
      two-thirds to LICENSEE and one-third to HARVARD.

7.5   In the event that LICENSEE and its sublicensee, if any, elect not to
      exercise their right to prosecute an infringement of the PATENT RIGHTS
      pursuant to the above paragraphs. HARVARD and/or GENERAL may do so at its
      own expense, controlling such action and retaining all recoveries
      therefrom.

                                  ARTICLE VIII

                            TERMINATION OF AGREEMENT

8.1   This Agreement, unless extended or terminated as provided herein, shall
      remain in effect for the life of the last to expire of PATENT RIGHTS
      licensed hereunder.

8.2   In the event that one party to this Agreement shall be in default in the
      performance of any obligations under this Agreement, and if the default
      has not been remedied within ninety (90) days after the date of notice in
      writing of such default, the party giving such notice may terminate this
      Agreement by written notice.

8.3   In the event that LICENSEE shall cease to carry on its business, HARVARD
      shall have the right to terminate this entire Agreement by giving LICENSEE
      written notice of such termination.

8.4   Any sublicenses granted by LICENSEE under this Agreement shall provide for
      termination or assignment to HARVARD, at the option of HARVARD, of
      LICENSEE's interest therein upon termination of this Agreement.

8.5   LICENSEE shall have the right to terminate this Agreement by giving thirty
      (30) days advance written notice to HARVARD to that effect. Upon
      termination, a final report shall be submitted and any royalty payments
      and unreimbursed patent expenses due to HARVARD become immediately
      payable.

8.6   Sections 8.5, 9.2, 9.3 and 9.4 of this Agreement shall survive
      termination.

                                       11

<PAGE>

                                   ARTICLE IX

                                     GENERAL

9.1   HARVARD represents and warrants that the entire right, title, and interest
      in the patent applications or patents comprising the PATENT RIGHTS have
      been or will be assigned to it and/or GENERAL and that HARVARD has the
      authority to issue the licenses under said PATENT RIGHTS set forth herein.
      HARVARD does not warrant the validity of the PATENT RIGHTS licensed
      hereunder and makes no representations whatsoever with regard to the scope
      of the licensed PATENT RIGHTS or that such PATENT RIGHTS may be exploited
      by LICENSEE, an AFFILIATE, or sublicensee without infringing other
      patents.

9.2   EXCEPT AS PROVIDED IN SECTION 9.1, HARVARD EXPRESSLY DISCLAIMS ANY AND ALL
      IMPLIED OR EXPRESS WARRANTIES AND MAKES NO EXPRESS OR IMPLIED WARRANTIES
      OF MERCHANTABILITY OR FITNESS OF THE TECHNOLOGY, LICENSED PROCESSES OR
      LICENSED PRODUCTS CONTEMPLATED BY THIS AGREEMENT.

9.3   (a) LICENSEE shall indemnify, defend and hold harmless HARVARD and GENERAL
      and their directors, governing board members, trustees, officers, faculty,
      medical and professional staff, employees, students, and agents and their
      respective successors, heirs and assigns (the "Indemnitees"), against any
      liability, damage, loss or expenses (including reasonable attorneys' fees
      and expenses of litigation) incurred by or imposed upon the Indemnities or
      any one of them in connection with any claims, suits, actions, demands or
      judgments arising out of any theory of product liability (including, but
      not limited to, actions in the form of tort, warranty, or strict
      liability) concerning any product, process or service used or sold
      pursuant to any right or license granted under this Agreement. LICENSEE's
      indemnification under this Section shall apply to any liability, damage,
      loss or expense whether or not it is attributable to the negligent
      activities of the Indemmties.

      (b) LICENSEE agrees, at its own expense, to provide attorneys reasonably
      acceptable to HARVARD to defend against any actions brought or filed
      against any party indemnified hereunder with respect to the subject of
      indemnity contained herein, whether or not such actions are rightfully
      brought.

      (c) At such time as any such product, process, service is being
      commercially distributed or sold (other than for the purpose of obtaining
      regulatory approvals) by LICENSEE or by a sublicensee, AFFILIATE or agent
      of LICENSEE, LICENSEE shall, at its sole cost and expense, procure and
      maintain comprehensive general liability insurance in amounts not less
      $2,000,000 per incident and $2,000,000 annual aggregate and naming the
      Indemnitees as additional insureds. During clinical trials of any such
      product, process or service, LICENSEE shall, at its sole cost and expense,
      procure and maintain

                                       12

<PAGE>

      comprehensive general liability insurance in such equal or lesser amount
      as HARVARD shall require, naming the Indemnitees as additional insureds.
      Such comprehensive general liability insurance shall provide (i) product
      liability coverage and (ii) broad form contractual liability coverage for
      LICENSEE's indemnification under this Agreement. If LICENSEE elects to
      self-insure all or part of the limits described above (including
      deductibles or retentions which are in excess of $250,000 annual
      aggregate) such self-insurance program must be acceptable to HARVARD and
      the Risk Management Foundation of the Harvard Medical Institutions, Inc.
      The minimum amounts of insurance coverage required shall not be construed
      to create a limit of LICENSEE's liability with respect to its
      indemnification under this Agreement.

      (d) LICENSEE shall provide HARVARD with written evidence of such insurance
      upon request of HARVARD. LICENSEE shall provide HARVARD with written
      notice at least fifteen (15) days prior to the cancellation, non-renewal
      or material change in such insurance; if LICENSEE does not obtain
      replacement insurance providing comparable coverage within such fifteen
      (15) day period, HARVARD shall have the right to terminate this Agreement
      effective at the end of such fifteen (15) day period without notice or any
      additional waiting periods.

      (e) LICENSEE shall maintain such comprehensive general liability insurance
      beyond the expiration or termination of this Agreement during (i) the
      period that any product, process, or service, relating to, or developed
      pursuant to, this Agreement is being commercially distributed or sold by
      LICENSEE or by a sublicensee, AFFILIATE or agent of LICENSEE and (ii) a
      reasonable period after the period referred to in (e) (i) above which in
      no event shall be less than fifteen (15) years.

9.4   LICENSEE shall not use HARVARD's or GENERAL's name or any adaptation of it
      in any advertising, promotional or sales literature without the prior
      written assent of HARVARD or GENERAL, as the case may be.

9.5   Without the prior written approval of HARVARD, the entire license granted
      pursuant to this Agreement shall not be transferred by LICENSEE to any
      party other than to a successor to the business interest of LICENSEE
      relating to the PATENT RIGHTS. This Agreement shall be binding upon the
      successors, legal representatives and assignees of HARVARD and LICENSEE.

9.6   The interpretation and application of the provisions of this Agreement
      shall be governed by the laws of the Commonwealth of Massachusetts.

9.7   LICENSEE agrees to comply with all applicable laws and regulations. In
      particular, it is understood and acknowledged that the transfer of certain
      commodities and technical data is subject to United States laws and
      regulations controlling the export of such commodities and technical data,
      including all Export Administration Regulations of the United States
      Department of Commerce. These laws and regulations, among other things,
      prohibit or require a

                                       13

<PAGE>

      license for the export of certain types of technical data to certain
      specified countries. LICENSEE hereby agrees and gives written assurance
      that it will comply with all United States laws and regulations
      controlling the export of commodities and technical data, that it will be
      solely responsible for any violation of such by LICENSEE or its AFFILIATES
      or sublicensees, and that it will defend and hold HARVARD and GENERAL
      harmless in the event of any legal action of any nature occasioned by such
      violation.

9.8   Written notices required to be given under this Agreement shall be
      addressed as follows:

      If to HARVARD:          Office of Technology and
                              Trademark Licensing
                              Harvard University
                              124 Mt. Auburn Street
                              Suite 440
                              Cambridge, MA 02138

      CC:                     Office of Technology Licensing
                              and Industry Sponsored Research
                              333 Longwood Ave.
                              Boston, MA 02115

                              Director
                              Office of Technology Affairs
                              Massachusetts General Hospital
                              13th Street, Building 149
                              Charlestown, MA 02129

      If to LICENSEE:         Virus Research Institute
                              61 Moulton Street
                              Cambridge, MA 02139
                              Attn: John Littlechild, President

or such other address as either party may request in writing.

9.9   Should a court of competent jurisdiction later consider any provision of
      this Agreement to be invalid, illegal, or unenforceable, it shall be
      considered severed from this Agreement. All other provisions, rights and
      obligations shall continue without regard to the severed provision,
      provided that the remaining provisions of this Agreement are in accordance
      with the intention of the parties.

                                       14

<PAGE>

9.10  In the event of any controversy or claim arising out of or relating to any
      provision of this Agreement or the breach thereof, the parties shall try
      to settle such conflicts amicably between themselves. Subject to the
      limitation stated in the final sentence of this section, any such conflict
      which the parties are unable to resolve shall be settled through
      arbitration conducted in accordance with the rules of the American
      Arbitration Association. The demand for arbitration shall be filed within
      a reasonable time after the controversy or claim has arisen, and in no
      event after the date upon which institution of legal proceedings based on
      such controversy or claim would be barred by the applicable statute of
      limitation. Such arbitration shall be held in Boston, Massachusetts. The
      award through arbitration shall be final and binding. Either party may
      enter any such award in a court having jurisdiction or may make
      application to such court for judicial acceptance of the award and an
      order of enforcement, as the case may be. Notwithstanding the foregoing,
      either party may, without recourse to arbitration, assert against the
      other party a third-party claim or cross-claim in any action brought by a
      third party, to which the subject matter of this Agreement may be
      relevant.

9.11  This Agreement constitutes the entire understanding between the parties
      and neither party shall be obligated by any condition or representation
      other than those expressly stated herein or as may be subsequently agreed
      to by the parties hereto in writing.

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

The effective date of this Agreement is May 1, 1992.

PRESIDENT AND FELLOWS OF HARVARD COLLEGE

By: /s/ Joyce Brinton
   ------------------------------------------------

                Joyce Brinton, Director
     Office for Technology and Trademark Licensing
                  Harvard University

Name and Title:
               ------------------------------------

Virus Research Institute

By: /s/ [ILLEGIBLE]
    -----------------------------------------------

Name and Title: President
               ------------------------------------

                                            15

<PAGE>

                                   APPENDIX A

U.S.S.N. 629,602 - "Improved Vaccines"; filed December 18, 1990; Inventors: John
Mekalanos and Samuel Miller.

U.S.S.N. 629,102 - "Vibrio Cholerae Strains Defective in irgA Expression and
Cholera Vaccines Derived Therefrom"; filed December 18, 1990; Inventors: John
Mekalanos and Stephen Calderwood.

U.S.S.N. 000,000 - "Doubly-Attenuated Strain of Vibrio Cholerae to Deliver
Heterlogous Antigens for Vaccination" to be filed in 1992; Inventors: John
Mekalanos and Stephen Calderwood (serial number and filing date to be inserted
when available).

U.S.S.N. 043,907 - "Cholera Vaccines"; filed April 29, 1987 and its CIP USSN
5,098,998, filed April 29, 1988; Inventors John Mekalanos and Ronald Taylor.

U.S. 4,882,278 - "Non-Toxic Vibrio Cholera Mutants"; issued November 21, 1989;
Inventor: John Mekalanos.

U.S.S.N. 000,000 - "Peruvian Strain of Cholera Vaccine"; to be filed in 1992;
Inventor: John Mekalanos (serial number and filing date to be inserted when
available).
<PAGE>

                                   Appendix B

                              Biological Materials

1.    All strain and plasmid inventions described in the following patents,
      patent applications and unfiled patent applications.

      a.    U.S. Patent No. 4,882,278
      b.    U.S. Patent Application Serial No. 629,602
      c.    U.S. Patent Application Serial No. 629,102
      d.    U.S. Patent Application Serial No. 043,907
      e.    Unfiled Patent Application entitled "Doubly-Attenuated Strain of
            Vibrio Cholerae to Deliver Heterologous Antigens for Vaccination"
      f.    Unfiled Patent Application entitled "Cholera Vaccine Strains derived
            from a 1992 Peruvian Isolate of Vibrio Cholerae and other El Tor
            Strains"

2.    The following, recently constructed Vibrio Cholerae Strains

      a.   Peru 1,2,3,4 and 5; each derived from wild-type C6709
      b.   Bang 1,2,3,4 and 5; each derived from wild-type P27459
      c.   Bah 1,2,3,4 and 5; each derived from wild-type E7946
      d.   Any additional Vibrio Cholerae strains derived from items 2(a)- 2(c)
           above.

3.    All progeny, mutants, derivatives and replications of the biological
      materials in Sections 1 and 2 above which are developed by Dr. John
      Mekalanos solely or jointly with others directly supervised in his
      laboratory at Harvard Medical School, but only to the extent that Harvard
      is able to license such biological materials consistent with its
      obligations to third parties.<PAGE>
                                                                   Exhibit 10.16

                      LICENSE AND CLINICAL TRIALS AGREEMENT

      Agreement ("AGREEMENT"), effective as of February 27, 1995 ("Effective
Date") between VIRUS RESEARCH INSTITUTE, INC., a Delaware corporation, with its
principal place of business at 61 Moulton Street, Cambridge, Massachusetts 02138
(hereinafter referred to as "VRI") and the JAMES N. GAMBLE INSTITUTE OF MEDICAL
RESEARCH, an Ohio non-profit corporation, with its principal place of business
at 2141 Auburn Avenue, Cincinnati, Ohio 45219 (hereinafter referred to as
"GAMBLE").

                                   WITNESSETH:

      WHEREAS, GAMBLE is the owner of certain rights in technology as defined
herein; and

      WHEREAS, GAMBLE desires to have such rights utilized to promote the public
interest by granting a license thereunder;

      WHEREAS, VRI is engaged in the development, production, marketing and sale
of products similar to the technology which is the subject of this AGREEMENT and
has the strategic commitment to facilitate the transfer of such technology for
the public interest; and

      WHEREAS, VRI desires to obtain a license to said rights upon the terms and
conditions hereinafter set forth;

      WHEREAS, VRI desires to utilize GAMBLE's services with respect to the
conduct of certain of the clinical trials and laboratory services needed to
obtain FDA approval for GAMBLE'S rotavirus vaccines.

      NOW THEREFORE, in consideration of the mutual covenants herein contained
and intending to be legally bound hereby, the parties hereto agree as follows:

1. DEFINITIONS.

      1.1 "Invention(s)" shall mean rotavirus vaccines, developed from rotavirus
strain 89-12, including that which was safety tested by Lou Potash, Ph.D. of
PRI/DynCorp for GAMBLE and received by GAMBLE on 12/2/93 or modification of
rotavirus strain 89-12 generated by natural or site-directed mutagenesis, that
stimulate neutralizing antibody to multiple serotypes of human rotavirus, and
methods for vaccinating humans against rotavirus illness caused by rotaviruses
of different serotypes using rotavirus strain 89-12 and for expanding the titers
and memory of the cells that express the pre-existing neutralizing antibodies
induced following primary vaccination against rotavirus disease using solely
rotavirus strain 89-12. The Invention(s) include inactivated vaccines using
rotavirus strain 89-12.

      1.2 "Technical Information" shall mean vaccine production information and
the results of the safety and identity testing conducted by Lou Potash, Ph.D.,
of PRI/DynCorp and received by GAMBLE on 12/2/93 and information regarding the
history, culture, adaptation and attenuation of rotavirus strain 89-12; and
scientific, technical and medical information related to 89-12, generated by or
on behalf of GAMBLE or obtained from Dr. Potash as part of the quality assurance
process during the term of this AGREEMENT.

      1.3 "Patent Rights" shall mean any current or fixture United States or
foreign patent applications which are set forth in Appendix A attached hereto
and arising from Inventions owned by or assigned to GAMBLE, together with any
divisions and continuations (related to rotavirus strain 89-12)
continuations-in-part (related solely to rotavirus strain 89-12 and improvements
thereto), patents issuing

                                                                               1
<PAGE>

thereon and reissues thereof and extensions thereof; provided that in the case
of future patent applications and patents, inclusion in Patent Rights shall be
subject to reimbursement by VRI to GAMBLE of the cost of Research and
Development with respect thereto. Nothing in this Agreement gives VRI rights to
Improvements in a vaccine which does not employ rotavirus strain 89-12.

      1.4 "Licensed Products" shall mean any product which is covered in whole
or in part by a Valid Claim in the Patent Rights and/or which incorporates or
utilizes to a significant degree Technical Information.

      1.5 "Licensed Process" shall mean any process which is covered in whole or
in part by a Valid Claim in the Patent Rights and/or which incorporates or
utilizes to a significant degree Technical Information.

      1.6   "Territory" shall mean the entire world.

      1.7 "Net Sales" shall mean the gross revenue received by VRI, its
Affiliates from the sales of Licensed Products or Licensed Processes to
independent third parties less:

            (a) Transportation charges or allowances separately stated and
invoiced;

            (b) Trade, quantity, cash, rebates or other allowances and discounts
and brokers', distributors', or agents' commissions actually allowed and taken;

            (c) Credits or allowances made or given on account of rejects or
returns;

            (d) Medicare and Medicaid disallowed reimbursements;

            (e) Taxes levied on and/or other governmental charges made as to
production, sale, transportation, delivery or use and paid by or on behalf of
Licensee.

            Licensed Products shall be considered "sold" when invoiced.

      1.8 "Sublicensee" shall mean any corporation, partnership or business
organization which is not an Affiliate to which VRI grants a license to enable
said party to sell Licensed Products or utilize Licensed Processes.

      1.9 "Affiliate" shall mean any corporation or other business entity
controlled by, controlling, or under common control with VRI. For this purpose
"control" means direct or indirect beneficial ownership of at least fifty
percent (50%) interest in the income or stock of such corporation or other
business.

      1.10 "Valid Claim" shall mean a claim of an issued patent or pending
patent application which has not been pending for more than five (5) years from
the relevant U.S. priority date, January 3, 1992, which has not lapsed or become
abandoned or been declared invalid or unenforceable by a court of competent
jurisdiction or an administrative agency from which no appeal can be or is
taken.

                                                                               2
<PAGE>

2. GRANT

      2.1 GAMBLE hereby grants to VRI the exclusive right and license under
Patent Rights and Technical Information to make, have made, use, lease, have
leased, sell, and have sold the Licensed Products and to practice the Licensed
Processes in the Territory for the term of this AGREEMENT unless this AGREEMENT
is sooner terminated according to the terms hereof. VRI shall have the right to
extend the grant set forth in this Section 2.1 to its Affiliates.

      2.2 Notwithstanding the provision of Section 2.1, GAMBLE shall retain the
right to make, use and practice the Invention(s) and the Technical Information
for its own non-commercial, research purposes. GAMBLE shall have the right to
convey to other non-profit organizations at no charge other than shipping fees,
the Invention(s) and Technical Information for use in non-commercial, basic
research, provided that such organizations have entered into agreements in
substantially the form attached as Appendix B.

      2.3 VRI agrees that any Licensed Products subject to obligations under
Public Laws 96-517 or 98-620 and which are intended for sale in the United
States shall be manufactured substantially in the United States. In the event
that VRI determines that compliance with the foregoing obligation is
commercially impracticable, GAMBLE agrees that it will cooperate with VRI in
attempting to obtain from the U.S. Government a waiver of such obligation.

      2.4 (a) VRI will have the right, subject to the terms of this AGREEMENT,
to enter into sublicensing agreements with any other entity (other than an
Affiliate to whom the license may be extended in accordance with Section 2.1)
for the rights, privileges and licenses granted hereunder.

            (b) VRI agrees that any sublicenses granted by it shall provide that
the obligations to GAMBLE contained in the following provisions of this
AGREEMENT shall be binding upon the Sublicensee: Sections 2.4 (c), 8 and 10. VRI
further agrees to attach a copies of such provisions to each sublicense
agreement.

            (c) VRI agrees to forward to GAMBLE a copy of any and all fully
executed sublicense agreements within thirty (30) days of execution thereof, and
further agrees to forward to GAMBLE annually a copy of such reports received by
VRI from its Sublicensee during the preceding twelve (12) month period under the
sublicenses as shall be pertinent to a royalty accounting under said sublicense
agreements. VRI may delete from copies of sublicense agreements provided to
GAMBLE hereunder commercial, research and development, manufacturing, financial
and other provisions unrelated to VRI's or the Sublicensee's obligations to
GAMBLE.

            (d) In the event that this AGREEMENT is terminated prior to its
normal expiration, any sublicense granted by VRI shall remain in full force and
effect from and after that date as a direct license between GAMBLE and the
Sublicensee, to the extent that the royalty obligations of VRI in individual
countries have not ceased pursuant to the terms of this AGREEMENT and the
Sublicensee's agreement to be bound by the terms and conditions set forth in
this AGREEMENT.

      2.5 (a) In addition to the license granted herein, GAMBLE grants to VRI an
exclusive option to obtain a world-wide, exclusive royalty-bearing license to
any improvement(s) on the Invention(s) that (i) are not subject to prior
commitments to other parties; (ii) relate to the diagnosis, treatment and/or
prevention of human rotavirus illnesses employing strain 89-12; (iii) which are
not specifically included in the Invention(s) or Patent Rights; and (iv) provide
a significant commercial advantage, herein collectively ("Improvements").

            (b) Such option shall extend for a period of sixty (60) days from
the date VRI receives written notice from GAMBLE disclosing such Improvement.
During such sixty (60) day period,

                                                                               3
<PAGE>

GAMBLE shall reasonably make available to VRI any other information in its
possession or control which would be useful to VRI in evaluating the
improvement. In the event VRI decides to exercise its option, VRI shall do so by
notifying GAMBLE in writing during such sixty (60) day period. Upon exercise of
VRI's option, GAMBLE and VRI shall enter into a license agreement containing
substantially the same provisions as the applicable provisions of this AGREEMENT
except for the initial license fee which shall be at least an amount sufficient
to reimburse GAMBLE for its costs relating to the development of the
Improvement, plus GAMBLE's actual patent costs relating thereto.

            (c) The written notice to GAMBLE of VRI's exercise of its option
hereunder shall include instructions to GAMBLE as to whether VRI wishes GAMBLE
to have a patent application prepared and filed with respect to any such
improvement VRI shall pay for all patent costs relating to any Improvement to
which VRI exercises its option.

            (d) In the event that VRI does not exercise its option hereunder or
if the parties have not entered into a license agreement as described in Section
2.5 (b)(1) above at the close of sixty (60) days from VRI's notice of exercise,
GAMBLE shall be free to offer a license for the Improvement on terms of its own
choosing to a third party, provided the terms are not more favorable than those
terms offered to VRI. VRI will grant a sublicense under Patent Rights to such
third party, if required, royalty-free, to permit such party to develop and sell
such Improvement.

       2.6 As soon as reasonably possible following the Effective Date of this
AGREEMENT, but in no event later than thirty (30) days alter the Effective Date,
GAMBLE shall provide to VRI copies of all Technical Information directly
relating to the Invention(s) in its possession and control on the Effective
Date. In addition, GAMBLE shall transfer to VRI all supplies of rotavirus strain
89-12 and the master and working cellbanks except as may be necessary for GAMBLE
to conduct such basic research as may be agreed upon by the parties. Upon
termination of this AGREEMENT, as a result of a breach by VRI or by VRI pursuant
to Section 7.4, VRI shall return all Technical Information to GAMBLE.

3. CLINICAL TRIALS AND DUE DILIGENCE

       3.1 (a) GAMBLE and VRI will cooperate with one another to complete all
pre-clinical studies necessary for the continued support of the Investigational
New Drug application ("IND") filed with the U.S. Food and Drug Administration
(FDA) and for foreign equivalents filed with respect to a Licensed Product. VRI
shall consult with GAMBLE, shall provide GAMBLE with drafts of the regulatory
submission prior to its filing, and shall not unreasonably refuse to comply with
any request by GAMBLE for any changes thereto, but all regulatory filings shall
be submitted in the name of VRI and VRI shall have the final authority with
respect to their content. GAMBLE shall cooperate with VRI in responding to any
comments of the FDA with respect to its regulatory filing.

            (b) Following approval under FDA regulations that clinical trials
may commence under the IND for which approval has been granted, GAMBLE,
recognizing the need for expeditious handling of all matters for which GAMBLE is
responsible herein, agrees that GAMBLE will use reasonable efforts to promptly
conduct the clinical trials and necessary laboratory work provided for in the
IND, subject to the following:

                  (1) In consultation with and subject to the approval of VRI,
GAMBLE will use reasonable efforts to design and draft the protocols with
respect to Phase I clinical trials;

                  (2) In consultation with, and subject to the approval of VRI,
GAMBLE will use reasonable efforts to design and draft the protocols with
respect to Phase II clinical trials;

                                                                               4
<PAGE>

                  (3) GAMBLE will use reasonable efforts to conduct the initial
Phase II clinical trials and, subject to consultation with and the approval of
VRI, conduct and/or participate in confirmatory or other Phase II clinical
trials, together with all laboratory work; as required;

                  (4) if other sites are required in connection with Phase II
clinical trials, VRI will consult with GAMBLE regarding the use and selection of
other sites and GAMBLE will use reasonable efforts to assist VRI in selecting
such additional sites;

                  (5) GAMBLE and VRI will use reasonable efforts to jointly
design and draft protocols for Phase III clinical trials and GAMBLE may, at
GAMBLE's option, participate as one of multiple centers for the clinical trials;
Dependent upon FDA requirements, GAMBLE will use reasonable efforts to conduct
all laboratory work required therefore; provided, however, that if GAMBLE's
laboratory capabilities are not sufficient for the central lab work required for
Phase III clinical trials, GAMBLE will use reasonable efforts to assist VRI in
selecting and approving an appropriate central laboratory and will use
reasonable efforts to supervise that laboratory in its performance of such work;

                  (6) promptly after completion of the above-described clinical
trials, GAMBLE will cooperate with VRI in preparation and submission to the FDA
of an appropriate application for approval with respect to the Licensed Product
(PLA/NDA) and in the submission of regulatory filings in foreign countries;

                  (7) if the PLA/NDA is not approved, GAMBLE will cooperate with
VRI at VRI's expense in taking any further action required to obtain its
approval;

                  (8) GAMBLE will use reasonable efforts to conduct all trials
with the prior approval and ongoing review of all appropriate and necessary
review authorities and in accordance with applicable federal, state and local
laws and regulations and will provide VRI with written evidence of review and
approval of each trial by the appropriate Institutional Review Board prior to
the initiation of each trial and of that Board's continuing review and approval
of each trial whenever it is reviewed, but at least once per year;

                  (9) GAMBLE will furnish VRI with the data resulting from the
clinical trials within a reasonable time alter completion of each trial,
provided that GAMBLE will permit representatives of VRI to examine GAMBLE's
facilities, validate case reports against original data in its files and monitor
work performed, at reasonable times and in a reasonable manner at mutually
agreed upon times during the term of this AGREEMENT, to determine the adequacy
of the facilities and whether the clinical trials are being conducted in
compliance with the protocol and relevant FDA regulations;

                  (10) GAMBLE will retain original records of the clinical
trials conducted by GAMBLE including the original of all volunteer consent forms
in strict accordance with all federal regulations.

                  (11) GAMBLE shall compile clinical trial data and provide
copies of the complete data set to VRI in a timely manner. GAMBLE will cooperate
with VRI in the analysis of the clinical data.

                  (12) GAMBLE is conducting the adult and child phases of the
Phase I clinical trials described in the protocols entitled "Reactivity and
Immunogenicity of Live, Attenuated Rotavirus Vaccine Candidate Strain 89-12."
and attached as Appendix C, and will make reasonable efforts to conduct the
infant phase of the Phase I clinical trial, and Phase II and Phase III clinical
trials.

                                                                               5
<PAGE>

                  (13) Gilbert M. Schiff M.D. shall be responsible for
supervising the adult clinical trials at GAMBLE and shall be designated as
"Principal Adult Investigator." David I. Bernstein, M.D. shall be responsible
for supervising the pediatric clinical trials at GAMBLE and shall be designated
as "Principal Pediatric Investigator." In the event that either such
investigator is disabled or no longer employed at GAMBLE, then GAMBLE shall have
the right to appoint another such investigator, subject to approval by VRI which
shall not be unreasonably withheld.

                  (14) GAMBLE and VRI agree to conduct the clinical trials
according to the protocols. However, if at any future date, changes in the
protocol appear desirable, such changes may be made through prior written mutual
agreement between GAMBLE and VRI. The clinical trials may be suspended or
terminated, as appropriate, at any time by GAMBLE if in the reasonable medical
judgment of either: the Principal Adult or Pediatric Investigator, or
responsible institutional review board(s) or in the medical and/or regulatory
judgment of VRI the health or safety of patients will be adversely affected and
it is appropriate to do so. Any action taken by GAMBLE or its investigators or
employees based on any such medical judgment shall not be deemed a breach of
this AGREEMENT.

                  (15) GAMBLE agrees that the rights and welfare of the human
subjects shall be protected in accordance with the protocols and all applicable
federal and state laws. GAMBLE shall be responsible for obtaining appropriate
institutional review board approval for the protocols and any subsequent changes
to the protocols, and for obtaining informed consent of each human subject
participating in the protocols. GAMBLE shall retain records of the clinical
trials including the original of all volunteer consent forms in accordance with
all federal regulations.

                  (16) In order to maintain subject confidentiality, no
information relative to subject name or address shall be provided to VRI. All
patient information will be identified in code. Any audits conducted by VRI
shall be undertaken in conjunction with GAMBLE in order to ensure
confidentiality.

                  (17) VRI shall promptly advise GAMBLE of adverse reactions or
side effects relating to clinical trials which may become known to VRI and,
similarly GAMBLE shall promptly advise VRI of adverse reactions or side effects
relating to clinical trials which may become known to GAMBLE.

            (c) If GAMBLE fails to perform any of its obligations under this
Section 3.1 and any such failure is not cured following sixty (60) days written
notice to GAMBLE, VRI may terminate GAMBLE's services relating to the
obligations in the relevant Section (Sections 3.1 (b) (1-17)) of this Section
and VRI shall thereafter have the right to hire a third party contractor at
VRI's expense to perform and control the performance of such services.
Termination of services provided herein in Sections 3.1 (b) (1-17) shall not
affect the rights and obligations of GAMBLE under any other Section. Upon
termination of GAMBLE's services for the foregoing reasons VRI will be obligated
to pay GAMBLE for all pre-approved costs of the studies incurred by GAMBLE and
not capable of cancellation. Such payment will be made within 30 days of
submission of billing by GAMBLE to VRI. At VRI's request, GAMBLE will assist VRI
in selecting and approving such third party contractors to perform functions
described in this Section 3.1.

            (d) Notwithstanding the foregoing, VRI, as sponsor of the
development program may terminate GAMBLE services in conducting clinical trials
for commercial reasons at any time with 30 days' notice subject to VRI's payment
of all non-cancelable, pre-approved costs within 30 days of GAMBLE's billing to
VRI.

                                                                               6
<PAGE>

      3.2 VRI agrees to pay GAMBLE for all fees and expenses that GAMBLE expects
to reasonably incur in conducting the trials described in Section 3.1 above,
provided that the amounts of such fees and costs have been approved by VRI in
writing in advance. VRI agrees to pay 40% of the approved budget for each study
in phase I, II and III upon initiation of each study and the remaining 60% at
agreed upon milestones during the course of each study, so that full payment for
each study is made by the conclusion of that study. Irrespective of the amount
advanced, VRI shall pay all costs incurred by GAMBLE in conducting the trials
described in Section 3.1, provided such expenses have been approved in advance
by VRI. If the monies advanced by VRI exceed expenses for a study, GAMBLE shall
refund the difference. VRI shall have the trials monitored by its own staff or
outside contractors at its election and shall have the data resulting from the
studies compiled and analyzed. VRI shall have any such VRI staff or outside
contractors execute a confidentiality agreement, prior to such staff or outside
contractors involvement in the clinical trials.

      3.3 GAMBLE and/or its investigators will have the right to publish the
results of the clinical trials described in Section 3.1 above and performed by
GAMBLE, provided that VRI is provided with a preprint and/or abstract of any
proposed publication at least forty-five (45) days in advance of submission of
the proposed publication. In the event that, as a result of reviewing such
abstract or preprint, VRI determines that such publication would result in
disclosure of an Invention as to which VRI has rights under Sections 2.1, 2.4
and/or 2.5 hereof or includes any VRI Confidential Information (as hereinafter
defined), GAMBLE agrees to delay publication for a sufficient period to enable a
patent application to be filed with respect thereto at VRI's expense and delete
VRI confidential information, VRI acknowledges and agrees that GAMBLE and/or its
investigators will be entitled to appropriate credit, and to be included as
co-authors for those directly involved in the study, in accordance with
prevailing scientific standards.

      3.4 In lieu of VRI paying minimum royalties and subject to obtaining FDA
or foreign regulatory approval for the 89-12 rotavirus vaccine VRI agrees to use
reasonable efforts to bring one or more Licensed Products to the marketplace
through a program of development; production, distribution, and marketing
consistent with sound and reasonable business practices and judgments. VRI
agrees to provide GAMBLE annually with a business development plan (which will
include strategy, major milestones for clinical development, FDA registration,
commercialization, and financial performance data) for the upcoming fiscal year,
the first plan due no later than one hundred eighty (180) days from the
Effective Date hereof and each subsequent plan due no later than December 31 in
subsequent years. In the event GAMBLE believes VRI is not exerting reasonable
efforts GAMBLE shall advise VRI and state the efforts which it believes would
meet this requirement. If VRI disagrees the parties will attempt to resolve the
matter by good faith discussions. If they still cannot agree the matter shall be
submitted to arbitration pursuant to Section 12 to determine the efforts to be
exerted by VRI. After the arbitration decision, in the event VRI fails to exert
the efforts required by the arbitration, GAMBLE shall have the right to
terminate this AGREEMENT upon giving VRI thirty (30) days prior written notice
and the opportunity to cure within said thirty (30) days or alternatively VRI
may resume minimum royalty payments in lieu of preparation of a business plan
and using reasonable efforts; however, in such event, resumption of payment of
minimum royalties under this Section 3.4 does not entitle VRI to an exclusive
license agreement.

4. PAYMENTS.

      4.1 (a) VRI agrees to pay GAMBLE in partial consideration for the license
granted hereunder a licensing fee in the total amount of $50,000 payable in two
equal installments, as follows:

            (1)   upon signing of this AGREEMENT                      $25,000
            (2)   upon filing of the PLA/NDA for a Licensed           $25,000
                  Product with the FDA

                                                                               7
<PAGE>

      4.2 (a) VRI shall pay the following running royalties to GAMBLE during the
term of this AGREEMENT as set forth below:

                  (1) Five percent (5%) on the Net Sales by VRI or its
Affiliates of Licensed Products or any use of Licensed Processes in the United
States (other than sales to Sublicensees for resale) where the manufacture, use
or sale of such Licensed Products or any use of such Licensed Processes is
covered by a Valid Claim of Patent Rights; or four percent (4%) on such Net
Sales in countries other than the United States (other than sales to
Sublicensees for resale) where the manufacture, use or sale of Licensed Products
or any use of Licensed Processes is covered by a Valid Claim of Patent Rights in
the country of sale; or one percent (1%) of Net Sales for five (5) years from
first commercial sale in a country, on a country by country basis, on any other
sales by VRI or its Affiliates of Licensed Products (other than sales to
Sublicensees for resale) where no Patent Rights have been nor are intended to be
filed with respect to such products; or two percent (2%) of Net Sales of
Licensed Products sold to the United States Government or sold to State or other
agencies at equivalent prices to those established for sale to the United States
Government.

                  (2) From any royalties received from its Sublicensees, VRI
shall pay GAMBLE thirty (30%) of royalties received by VRI from a Sublicensee
for sale of Licensed Products. Reporting and payment of such royalties shall be
made in accordance with the provisions of Section 5.

                  (3) If royalties for Licensed Products or Licensed Processes
covered by a Valid Claim of Patent Rights cease to be paid because a patent
application has been pending for more than five (5) years from the relevant U.S.
priority date, then a royalty of 1% of Net Sales will be payable until the end
of the fifth year on the market in that country. No royalty will be payable
following the fifth anniversary of first marketing in that country unless a
valid and enforceable patent subsequently issues. If a valid and enforceable
patent issues royalties will be payable from the date of issue until the expiry
of said valid and enforceable patent at the full applicable royalty rate for
that country as set forth in Section 4.2(1).

      4.3 (a) Subject to Section 3.4, during the exclusive period of the
AGREEMENT, VRI shall pay a minimum annual royalty commencing on the expiration
of calendar year 1999 and continuing through calendar year 2003, as follows:

                         1999                     $100,000
                         2000                     $200,000
                         2001                     $300,000
                         2002                     $400,000
                         2003                     $500,000

            (b) If the royalties earned and paid to GAMBLE pursuant to Section
4.2 (a) for any of the above calendar years are not at least equal to the
applicable minimum royalties, VRI shall have the right to pay any difference
between such minimum royalty amounts and the royalties paid to GAMBLE in full
satisfaction of such obligation under this Section 4.3, which payment, if any,
shall be made with the quarterly royalty payment due for the last quarter of the
applicable calendar year. Waiver of any minimum royalty payment by GAMBLE shall
not be construed as a waiver of any such subsequent payment. If VRI fails to
make any such minimum royalty payment, GAMBLE shall have the right, at its
option, to convert the License for the Licensed Products and Licensed Processes
under Section 2.1 to a non-exclusive license. Royalty rates for non-exclusive
licenses shall be fifty percent (5 0%) of the exclusive rates set forth in
Section 4.2(a).

                                                                               8
<PAGE>

      4.4 (a) In the event that a Licensed Product under this AGREEMENT is sold
in any country in a combination package or kit containing other active products
not licensed hereunder, the Net Sales in each such country for purposes of
determining royalty payments on the combination package, shall be calculated
using one of the following methods:

                  (1) By multiplying the net selling price of that combination
package by the fraction A/A+B, where A is the net selling price in such
country during the royalty-paying period in question, of the Licensed Product
sold separately or Licensed Process used separately, and B is the net selling
price in such country during the royalty period in question, of the other active
products sold separately or used separately.

                  (2) In the event that no such separate sales are made of the
Licensed Product or any of the active products in such combination package in
such country during the royalty-paying period in question, Net Sales for the
purposes of determining royalty payments, shall be calculated by dividing the
net selling price in such country of the combination package by the number of
functions performed by the combination package sold where such package contains
active agents or other proprietary technology other than those licensed under
this AGREEMENT.

      4.5 Payment of royalties specified in Section 4.2 (a) shall be made by VRI
to GAMBLE within sixty (60) days after March 31, June 30, September 30 and
December 31 each year during the term of this AGREEMENT covering the quantity of
Licensed Products sold or Licensed Processes used by VRI during the preceding
calendar quarter. The last such payment shall be made within sixty (60) days
after termination or expiration of this AGREEMENT.

      4.6 All payments to be made under this Section shall be paid in United
States dollars at such a place and in such a way, as GAMBLE may reasonably
designate, without deduction of exchange, collection or other charges.
Conversion of foreign currency to U.S. dollars shall be made at the conversion
rate published by the Bank of Boston on the last day of the calendar quarter
with respect to which payments are due.

      4.7 Only a single royalty shall be paid with respect to any Licensed
Product or Licensed Process, under Section 4.2(a) irrespective of the number of
Valid Claims of Patent Rights utilized.

      4.8 In the event that VRI is required to pay royalties to one or more
third parties under patents other than Patent Rights in order to make, use, sell
or have sold Licensed Products or Licensed Processes, VRI shall be entitled to a
credit against royalties due GAMBLE under Section 4.2(a) in an amount equal to
fifty percent ( 50%) of the royalties paid to such third parties. However, in no
event shall royalties payable to GAMBLE under Section 4.2(a) hereunder be
reduced by more than forty percent (40%).

      4.9 If the transfer of or the conversion into the United States dollar
equivalent of any remittance due hereunder is not lawful or permissible in any
county, such remittance shall be made thereof in the currency of the country to
the credit and account of GAMBLE or its nominee in any commercial bank located
in that country. Prompt notice shall be given to GAMBLE and GAMBLE may provide a
nominee if so desired.

      4.10 If VRI exercises its option for the rights to improvements, VRI shall
reimburse GAMBLE for the cost of the development program to make such
Improvements.

5. REPORTS AND RECORDS

      5.1 VRI shall maintain true books of account containing an accurate record
of all data necessary for the determination of the amounts payable under Section
4 hereof. Said records shall be kept at VRI's principal place of business or the
principal place of business of the appropriate division of VRI to

                                                                               9
<PAGE>

which this AGREEMENT relates. Said records shall be available for inspection by
a certified public accountant selected and paid by GAMBLE once each year during
regular business hours and for six (6) years thereafter following the end of the
calendar year to which they pertain in order for GAMBLE to ascertain the
correctness of any report and/or payment made under this AGREEMENT. The
provision of this Section 5.1 shall survive termination of this AGREEMENT.

      5.2 (a) Commencing with the calendar quarter in which Net Sales first
occurs, sixty (60) days after March 31, June 30, September 30 and December 31,
of each year in which this AGREEMENT is in effect, VRI shall deliver to GAMBLE
full, true and accurate reports of its activities and those of its
Sublicensee(s), if any, relating to this AGREEMENT during the preceding three
month period. These reports shall include at least the following:

                        (1)   Gross Sales for Licensed Products or Licensed
                              Processes;

                        (2)   Net Sales for Licensed Products or Licensed
                              Processes

                        (3)   Expenses, defined in Section 1.7, used to
                              calculate Net Sales;

                        (4)   Calculation of royalties due based on Net Sales;

                        (5)   Any adjustments to amounts due pursuant to this
                              AGREEMENT; and

                        (6)   Amounts due to GAMBLE for the applicable quarters.

      5.3 With each such report, VRI shall pay to GAMBLE the royalties due and
payable as provided for in Section 4.5. If no royalties are due under Section
4.2(a), VRI shall so report.

6. PATENT PROSECUTION AND INFRINGEMENT.

      6.1 GAMBLE shall apply for and maintain during the term of this AGREEMENT
any Patent Rights in the United States and in the European Union, Australia,
Brazil, Canada, Japan and South Korea, and Mexico. The prosecution, filing and
maintenance of all patents, with the exception of fee payments, shall be the
primary responsibility of GAMBLE, using patent counsel selected by GAMBLE and
reasonably acceptable to VRI, provided, however, that VRI shall be given a
reasonable opportunity to advise GAMBLE on such matters, particularly as they
pertain to patent prosecution in foreign countries, and GAMBLE shall furnish to
VRI copies of any documents relevant to such prosecution, filing and maintenance
in sufficient time in advance for VRI or its patent counsel to comment thereon.
VRI shall pay all reasonable patent fees and costs, including reasonable counsel
fees, incurred by GAMBLE pursuant to this Section.

      6.2 VRI has reimbursed GAMBLE the sum of $24,277, representing 50% of
foreign phase filing costs for the countries and listed in Section 6.1. VRI
shall reimburse GAMBLE the sum of $78,558 upon VRI signing this AGREEMENT for
the remaining 50% of the foreign phase filing costs and for its U.S. patent fees
and costs arising from the Patent Rights invoiced by patent counsel to GAMBLE
prior to October 10, 1994. All fees and costs incurred by GAMBLE after the
Effective Date relating to the filing, prosecution and maintenance of all Patent
Rights shall be paid by VRI within 30 days of receipt of invoice from GAMBLE.
The foregoing notwithstanding, VRI shall will have the right to discontinue
payment of any such fees or costs with respect to the Patent Rights in any
particular country or countries, if after a good faith assessment of the cost of
patent filing, the enforceability of intellectual property rights and the

                                                                              10
<PAGE>

commercial value of the market, in a specific country, VRI believes that making
such payments would not be commercially practical. VRI shall provide timely
notice of VRI's intention not to pay a fees so, if GAMBLE desires, GAMBLE may
pay such fee.

      6.3 If at any time during the term of this AGREEMENT, VRI furnishes to
GAMBLE reasonably convincing written evidence of an infringement of a patent
included in the Patent Rights which adversely and substantially affects the
commercial operations of VRI under the license granted hereunder, GAMBLE shall
have the right, but not the obligation, to prosecute, at its own expense any
such infringement and shall have the right for such purpose to join VRI as a
party plaintiff at GAMBLE's expense. VRI independently shall have the right to
join any such suit or action brought by GAMBLE and, in such event, shall pay
one-half of the cost of such suit or action from the date of joining. Provided
that VRI has joined in the action and shared the costs thereof as stated in the
preceding sentence, no settlement, consent judgment or other voluntary final
disposition of the suit may be entered into without the consent of VRI, which
consent will not unreasonably be withheld. Any recovery or damages derived from
such action shall first be used to reimburse GAMBLE for all legal expenses
relating to such action. If VRI has not joined the action, GAMBLE is entitled to
all recovery or damages still remaining; however, if VRI has joined the action,
any recovery or damages still remaining shall be applied toward (i)
reimbursement of GAMBLE for the amount of royalties not received by GAMBLE from
the infringing party as a result of such infringement, and (ii) compensation of
VRI for its lost profits or a reasonable royalty on the sales of the infringer,
whichever is applicable; provided, however that if such remaining amount of
recovery or damages is insufficient to compensate GAMBLE fully for such
royalties and to compensate VRI fully for such lost profits or reasonable
royalty, then such amount of recovery or damages still remaining shall be
apportioned pro rata between GAMBLE and VRI in proportion to (a) the amount of
royalties not received by GAMBLE from the infringing party as a result of such
infringement, as compared with (b) VRI's lost profits or reasonable royalty on
the sales of the infringer. Any recovery or damages still remaining after the
above-mentioned applications shall be distributed two-thirds (2/3) to GAMBLE and
one-third (1/3) to VRI.

      6.4 If after said three (3) months, GAMBLE fails to cause such
infringement to terminate or to bring a suit or action to compel termination,
VRI shall have the right, but not the obligation, to prosecute, at its own
expense any such infringement and shall have the right for such purpose to join
GAMBLE as a party plaintiff at VRI's expense. GAMBLE independently shall have
the right to join any such suit or action brought by VRI and, in such event,
shall pay one-half of the cost of such suit or action from the date of joining.
Provided that GAMBLE has joined in the action and shared the costs thereof as
stated in the preceding sentence, no settlement, consent judgment or other
voluntary final disposition of the suit may be entered into without the consent
of GAMBLE, which consent will not unreasonably be withheld. Any recovery or
damages derived from such action shall first be used to reimburse VRI (and
GAMBLE if it joined in the action) for all legal expenses relating to such
action. If GAMBLE has not joined the action, VRI is entitled to all recovery or
damages still remaining; however, if GAMBLE has joined the action, any recovery
or damages still remaining shall be applied toward (i) reimbursement of GAMBLE
for the amount of royalties not received by GAMBLE from the infringing party as
a result of such infringement, and (ii) compensation of VRI for its lost profits
or a reasonable royalty on the sales of the infringer, whichever is applicable;
provided, however that if such remaining amount of recovery or damages is
insufficient to compensate GAMBLE fully for such royalties and to compensate VRI
fully for such lost profits or reasonable royalty, then such amount of recovery
or damages still remaining shall be apportioned pro rata between GAMBLE and VRI
in proportion to (a) the amount of royalties not received by GAMBLE from the
infringing party as a result of such infringement, as compared with (b) VRI's
lost profits or reasonable royalty on the sales of the infringer. Any recovery
or damages still remaining after the above-mentioned applications shall be
distributed two-thirds (2/3) to GAMBLE and one-third (1/3) to VRI.

      6.5 In any infringement suit that either party may institute to enforce
the Patent Rights pursuant to this AGREEMENT, the other party hereto shall,
cooperate in all respects and, to the extent

                                                                              11
<PAGE>

possible, have its employees testify when requested and make available relevant
records, papers, information, samples and the like.

      6.6 In the event that a declaratory judgment action alleging invalidity or
non-infringement of any of the Patent Rights shall be brought against VRI,
GAMBLE, at its sole option shall have the right, within sixty (60) days after
GAMBLE receives notice from VRI of such action, to intervene and participate in
action at its own expense.

7. TERM AND TERMINATION.

      7.1 Unless earlier terminated as provided herein, this AGREEMENT shall
remain in full force and effect for the life of the last to expire patent issued
under the Patent Rights. Upon expiration, VRI shall have a fully paid-up,
non-cancelable license.

      7.2 Subject to Section 16, if VRI shall cease to carry on its business,
this AGREEMENT shall terminate ninety (90) days after VRI ceases to do business,
unless, within ninety (90) days VRI has identified a qualified successor
licensee reasonably acceptable to GAMBLE willing to assume the obligation of VRI
hereunder, in which case the assignment of this AGREEMENT to such successor
licensee shall be subject to the written assumption by such successor of VRI's
obligations hereunder and to the written approval of GAMBLE, which shall not be
unreasonably withheld.

      7.3 Should VRI fail to pay GAMBLE such royalties other than minimum
royalties as are due and payable hereunder, GAMBLE shall have the right to
terminate this AGREEMENT on thirty (30) days written notice, or to convert this
AGREEMENT from an exclusive to a non-exclusive license upon expiration of the
thirty (30) day period.

      7.4 VRI shall have the right to terminate this AGREEMENT at any time upon
six (6) months written notice to GAMBLE, and upon payment of all amounts due
GAMBLE through the effective date of termination. If this AGREEMENT is
terminated, VRI will provide GAMBLE with information and data necessary for
GAMBLE to pursue the development of Licensed Products or Licensed Processes and
a right to reference VRI's regulatory filings with the FDA.

      7.5 Upon any material breach or default of this AGREEMENT by VRI or
GAMBLE, the non-breaching party shall have the right to terminate this AGREEMENT
and the rights, privileges and license hereunder granted upon ninety (90) days
written notice to the other party. Such termination shall become effective
immediately at the conclusion of such notice period unless the breaching party
shall have cured any such breach or default prior to the expiration of the
ninety (90) day period.

      7.6 Upon termination of this AGREEMENT for any reason, nothing herein
shall be construed to release either party from any obligation that matured
prior to the effective date of such termination. VRI and any Sublicensee thereof
may, after the effective date of such termination, sell all Licensed Products
which are in inventory at the time of termination, and complete and sell
Licensed Products which VRI can clearly demonstrate were in the process of
manufacture at the time of such termination, provided that VRI shall pay to
GAMBLE the royalties thereon as required by Section 4 of this AGREEMENT and
shall submit the reports required by Section 5 hereof on the sales of Licensed
Products.

                                                                              12
<PAGE>

8. INDEMNIFICATION AND INSURANCE.

      8.1 VRI shall defend, indemnify and hold harmless GAMBLE and its trustees,
officers, medical and professional staff, employees, and agents and their
respective successors, heirs and assigns, against all losses, damages, expenses,
including attorney's fees and against any claims, suits, actions, demands or
judgments brought against any one or more of them, arising out of any theory of
product liability (including, but not limited to, actions in the form of tort,
warranty, or strict liability) or negligence concerning any product, process or
service made, used or sold pursuant to any right or license granted under this
AGREEMENT. VRI shall have the right to control the defense settlement and/or
compromise of any such claims or actions.

      8.2 VRI's obligations under Section 8.1 above shall not apply to any
liability, damage, loss or expense to the extent that it is directly
attributable to the negligence or intentional misconduct of GAMBLE or of any of
its trustees, officers, medical and professional staff, employees, agents or
their respective successors, heirs or assigns.

      8.3 VRI shall add, at VRI's expense, GAMBLE as an additional insured on
VRI's clinical trial insurance policy, which provides limits of liability of
$2,000,000 per incident and aggregate, effective upon the Effective Date of this
AGREEMENT, to provide insurance coverage for GAMBLE for the clinical trials.

      8.4 VRI, at VRI's expense, shall maintain policies of comprehensive
general liability insurance and will obtain product liability insurance in
amounts not less than $1,000,000 per incident and $2,000,000 annual aggregate
and shall add GAMBLE as an additional insured on VRI's policy, which provides
such limits of liability. Such insurance shall provide (i) product liability
coverage, (ii) negligence, and (iii) broad form contractual liability coverage,
for VRI's indemnification under Section 8.1 of this AGREEMENT. The minimum
amounts of insurance coverage required under these provisions shall not be
construed to create a limit of VRI's liability with respect to VRI's
indemnification obligation under Section 8.1 of this AGREEMENT. VRI shall
maintain such comprehensive general liability insurance and product liability
insurance beyond the expiration or termination of this AGREEMENT and for a
reasonable period after the termination of the clinical trials, which in no
event shall be less than fifteen (15) years after the clinical trials.

      8.5 This Section 8 shall survive expiration or termination of this
AGREEMENT.

9. REPRESENTATIONS

      9.1 Subject to any prior rights of the U.S. government, GAMBLE represents
that patent applications or patents included in the Patent Rights have been
assigned to it and that GAMBLE has the authority and power to issue licenses
under said Patent Rights and that GAMBLE has the right to disclose Technical
Information to VRI and to enter into and perform this AGREEMENT.

      9.2 GAMBLE does not warrant the validity of the Patent Rights licensed
hereunder and makes no representation whatsoever with regard to the scope of the
Patent Rights or that such Patent Rights may be exploited by VRI, its
Affiliates, or Sublicensees without infringing other patents, except that GAMBLE
represents that as of the Effective Date it is not aware of any patent or patent
application not a part of the Patent Rights licensed hereunder that would be
infringed by the exercise by VRI, its Affiliates or Sublicensees, of the rights
granted to them hereunder.

                                                                              13
<PAGE>

10. CONFIDENTIALITY.

      10.1 Confidential Information. As used in this AGREEMENT, "Confidential
Information" means all information transmitted by a party hereto or obtained by
a party hereto in connection with the performance of the clinical trials and
other services described in Section 3 hereof or of any such other services to be
provided by the parties as described herein, subject to the exceptions specified
below. "Confidential Information" means information of any type, not generally
known, about the business processes, services, products, suppliers, customers,
clients or plans of GAMBLE or VRI ("the parties hereto") of any client of The
parties hereto (regardless of whether the parties hereto have executed a
confidentiality agreement with such customer), which is used or useful in the
conduct of business of the parties hereto, or which confers or tends to confer a
competitive advantage over one who does not possess such information. Such
information includes, but is not limited to, information relating to trade
secrets, Technical Information, patent applications, know-how, research,
development, design, engineering, quality control or service techniques,
information about existing, new or envisioned products, processes or services
and their development, performance, scientific, engineering or technical
information, laboratory notebooks, notes, computer programs, source codes,
object codes, software manuals, sketches, drawings, reports, formulae, gels,
slides, sequences, biological materials living or otherwise, photographs,
negatives, prototypes, models, correspondence, and other documents and things,
and information relating to purchasing, sales, marketing, licensing, contracts
with third parties, and pricing, whether or not in writing and whether or not
labeled or identified as confidential or proprietary. Confidential Information
may be disclosed in writing or orally or may be obtained by observation or
inspection. All data, materials, information, and records developed by a party
hereto in the course of performing this AGREEMENT shall be considered
Confidential Information. However, Confidential Information shall not include
information that a party hereto can demonstrate: (i) is in or enters the public
domain through no fault of such party; (ii) is disclosed to a party hereto by a
third party entitled to disclose it; (iii) was known to a party hereto before
the date of this AGREEMENT; or (iv) is required by law to be disclosed, provided
reasonable advance notice of such requirement is given to a party hereto before
such disclosure.

      10.2 Confidentiality. Without prior written consent the parties hereto
will not disclose the other party's Confidential Information to any third party
other than employees, agents or others of the parties hereto who must
necessarily be informed thereof, but only if and to the extent that any such
person has a need for such information. A party hereto will only use
Confidential Information for the purpose of fulfilling its obligations under
this AGREEMENT. The parties hereto agree that they will take such reasonable
steps as may be necessary to prevent the disclosure or use of any such materials
by their officers, employees or agents except as provided herein, including but
not limited to obtaining and enforcing appropriate confidentiality agreements
with such persons. All obligations of confidentiality and nondisclosure set
forth in this AGREEMENT shall survive the termination or expiration of this
AGREEMENT.

      10.3 The parties agree that clinical trial data generated by GAMBLE under
the terms of the AGREEMENT will not be published by VRI prior to its publication
by GAMBLE's principal investigators. To the extent not published, the results of
the clinical trials will be held in confidence by GAMBLE. Subject to the
foregoing, VRI will have the unrestricted right to use or disclose such clinical
trial data.

                                                                              14
<PAGE>

11. NOTICES.

      11.1 Reports, notices and other communications from VRI to GAMBLE as
provided hereunder shall be sent by certified mail to:

                   James N. Gamble Institute of Medical Research
                   2141 Auburn Avenue
                   Cincinnati, OH 45219
                   Attention: President

            or other individuals or addresses as shall hereafter be furnished by
written notice to VRI.

      11.2 Reports, notices and other communications from GAMBLE to VRI as
provided hereunder shall be sent to by certified mail to:

                   Virus Research Institute, Inc.
                   61 Moulton Street
                   Cambridge, MA 02138
                   Attention: President

            or other individuals or addresses as shall hereafter be furnished by
written notice to GAMBLE.

12. ARBITRATION.

      12.1 (a) Any controversy, dispute or claim arising out of, or relating to,
any provisions, the interpretation or the performance of this AGREEMENT or any
breach thereof which cannot otherwise be resolved by good faith negotiations
between the parties shall be resolved by final and binding arbitration under the
rules of the American Arbitration Association, or the Patent Arbitration Rules,
if applicable, which are in effect as of the Effective Date of this AGREEMENT.
In the event that VRI initiates, requests and/or files for arbitration, the
arbitration shall be conducted in Cincinnati, Ohio. In the event that GAMBLE
initiates, requests and/or files for arbitration, the arbitration shall be
conducted in Boston, Massachusetts.

            (b) The arbitration shall be subject to the following terms:

                  (1) The number of arbitrators shall be three (3).

                  (2) The arbitrators shall be independent; impartial third
parties having no direct or indirect personal or financial relationship to any
of the parties to the dispute, who has have agreed to accept the appointment as
arbitrator on the terms set out in this Section 12.1.

                  (3) The arbitrators shall be active or retired attorneys, law
professors, or judicial officers with at least five (5) years experience in
general commercial matters and a familiarity with the laws governing proprietary
rights in intellectual property and in particular patent law.

                  (4) The arbitrators shall be selected as follows:

                        (i) Each party shall submit a description of the inner
to be arbitrated to the American Arbitration Association at the appropriate
Regional Office in Cincinnati, Ohio or Boston, Massachusetts, depending upon
where the arbitration is to be held. Said Association shall submit to the
parties a list of the arbitrators available to arbitrate any dispute between
them. Thereafter,

                                                                              15
<PAGE>

each party shall select; in numerical order, those persons on said list
acceptable as arbitrators and return the same to the Association. The first
three arbitrators acceptable to both parties shall be deemed the selected
arbitrators with respect to the dispute then at issue under this AGREEMENT. In
the event of a failure to select three mutually agreeable arbitrators, the
Association shall be requested to submit as man subsequent lists of arbitrators
as shall be necessary to effect a mutual selection.

                        (ii) If the method of selection set out in Section 12.1
(b)(4)(a) fails for any reason, then either party may petition any state or
federal court in Massachusetts or Ohio having jurisdiction for appointment of
the arbitrators in accordance with applicable law, provided that the arbitrators
must satisfy the requirements of Sections 12.1 (b)(2) and 12.1 (b)(3) above and
be acceptable to each party hereto.

                  (5) The arbitrators shall announce the award in writing
accompanied by written findings explaining the facts determined in support of
the award, and any relevant conclusions of law.

                  (6) Unless otherwise provided in this Section 12.1 or extended
by agreement of the parties, each party shall submit an initial request for
designation of arbitrators within thirty (30) days after any request for
arbitration, the dispute shall be submitted to the arbitrators within sixty (60)
days after the arbitrators are selected, and a decision shall be rendered within
thirty (30) days after the dispute is submitted.

                  (7) The fees of the arbitrators and any other costs and fees
associated with the arbitration shall be paid in accordance with the decision of
the arbitrators.

                  (8) The arbitrators shall have no power to add to, subtract
from, or modify any of the terms or conditions of this AGREEMENT. Any award
rendered in such arbitration may be enforced by either party in either the
courts of the Commonwealth of Massachusetts or Ohio or in a United States
District Court for the District of Massachusetts or Ohio, to whose jurisdiction
for such purposes GAMBLE and VRI each hereby irrevocably consents and submits.

      12.2 Notwithstanding the foregoing, nothing in this Section shall be
construed to waive any rights or timely performance of any obligations existing
under this AGREEMENT.

13. RESTRICTIONS ON USE OF NAMES.

      VRI shall not use the names of GAMBLE, its related entities and its
employees, or any adaptations thereof, in any advertising, promotional or sales
literature, without the prior written consent of GAMBLE; provided however, that
VRI (a) may refer to publications by employees of GAMBLE in the scientific
literature or (b) may state that a license from GAMBLE has been granted as
herein provided.

14. INDEPENDENT CONTRACTOR.

      For the purpose of this AGREEMENT and all services to be provided
hereunder, both parties shall be, and shall be deemed to be, independent
contractors and not agents or employees of the other. Neither party shall have
authority to make any statements, representations or commitments or any kind, or
to take any action, that will be binding on the other party.

                                                                              16
<PAGE>

15. SEVERABILITY.

      If any one or more of the provisions of this AGREEMENT shall be held to be
invalid, illegal or unenforceable, the validity, legality or enforceability of
the remaining provisions of this AGREEMENT shall not in any way be affected or
impaired thereby.

16. NON-ASSIGNABILITY.

      Neither this AGREEMENT nor any part hereof shall be assignable by either
party without the express written consent of the other provided that either VRI
or GAMBLE may assign this AGREEMENT in connection with the merger, consolidation
or sale of substantially all of its assets or the sale of that portion of its
business to which the Inventions relate or as set forth in Section 7.2 and
further provided that neither party shall unreasonably withhold its consent to
any other assignment by the other party to an assignee which can reasonably
demonstrate its qualifications to carry out the obligations of VRI or GAMBLE
hereunder. Any other attempted assignment without such consent shall be void.

17. ENTIRE AGREEMENT.

      This instrument contains the entire AGREEMENT between the parties hereto.
No verbal agreement, conversation or representation between any officers,
agents, or employees of the parties hereto either before or after the execution
of this AGREEMENT shall affect or modify any of the terms or obligations herein
contained.

18. MODIFICATIONS IN WRITING.

      No change, modification, extension, termination or waiver of this
AGREEMENT, or any of the provisions herein contained, shall be valid unless made
in writing and signed by a duly authorized representative of each party.

19. GOVERNING LAW.

      The validity and interpretation of this AGREEMENT and the legal relations
of the parties to it shall be governed by the laws of the State of Ohio.

20. CAPTIONS.

      The captions are provided for convenience and are not to be used in
construing this AGREEMENT.

21. PATENT MARKING

      VRI agrees to mark and have marked all Licensed Products sold by it under
the license granted herein, if practical, with the word "Patent" or "Patents"
and the number of the patent or patents applicable thereto.

                                                                              17
<PAGE>

      IN WITNESS WHEREOF, the parties hereto have caused this AGREEMENT to be
executed in quadruplicate by their duly authorized representatives as of the
date first above written.

JAMES N. GAMBLE INSTITUTE                  VIRUS RESEARCH INSTITUTE, INC.
(GAMBLE)                                   (VRI)

By: /s/ Gilbert M. Schiff                  By: /s/ William A. Packer
    ---------------------------------          ---------------------------------
    Gilbert M. Schiff M.D.                     William A. Packer

Title: President                           Title: President

WITNESSED BY:                              W1TNESSED BY:

/s/ [ILLEGIBLE]                            /s/ [ILLEGIBLE]
-------------------------------------      -------------------------------------

                                                                              18
<PAGE>

                                   APPENDIX A

            LIST OF PATENT APPLICATIONS INCLUDED IN THE PATENT RIGHTS

1.)   U.S. Serial No. 07/614,310, filed November 16, 1990, entitled "Human
      Rotaviruses, Vaccines and Methods," and invented by Richard L. Ward.

2.)   U.S. Serial No. 07/816,974, filed January 3, 1992, entitled "Human
      Rotaviruses, Vaccines and Methods," and invented by Richard L. Ward
      (Division of U.S. Serial No. 07/614,310).

3.)   Serial No. PCT/U.S. 91/08191, filed November 4, 1990, entitled "Human
      Rotaviruses, Vaccines and Methods," and invented by Richard L. Ward.

U.S. Patent Application Serial Number                     08/143975
U.S. Patent Application Serial Number                     08/114114
Brazilian Patent Application Serial Number                9106982
European Patent Application Serial Number                 92900590.8
Mexican Patent Application Serial Number                  9303196
Australian Application Serial Number                      90603/91
Canadian Application Serial Number                        2096315
S. Korean Application Serial Number                       93701493
Japanese Application Serial Number                        501860/92

                                                                              19
<PAGE>

                                   APPENDIX B

                          MATERIALS TRANSFER AGREEMENT

THIS AGREEMENT entered the          day of      19  , by and between the James
N. Gamble Institute of Medical Research ("Provider"), a non-profit corporation
having a place of business at 2141 Auburn Ave., Cincinnati, Ohio 45219 and ***
("Recipient"), a corporation having a place of business at              .

1.    Subject to availability Provider agrees to provide the following material
      to recipient: ***. Such material and any related biological material or
      associated know-how and data that will be received by Recipient from
      Provider, and any substance that is replicated or derived therefrom are
      covered by this Agreement. All such materials shall hereinafter be
      referred to as the "Material(s)."

2.    The Materials will be used by Recipient in connection with the research
      described in Appendix A and only for non-commercial purposes. The
      Materials shall not be used in research that is subject to consulting or
      licensing obligations to another institution, corporation or business
      entity, unless written permission is obtained in advance from Provider.

3.    Recipient shall not distribute, release or disclose the Materials to any
      other person or entity and shall ensure that no one will be allowed to
      take or send the Materials to any other location, unless written
      permission is obtained in advance from Provider. Recipient agrees to
      maintain the confidentiality of any propriety information of Provider
      regarding the Materials.

4.    The Materials are supplied solely for scientific research purposes, for
      use in animals and/or in vitro. THE MATERIALS SHALL NOT BE USED IN HUMANS.

5.    No right or license is granted under the Agreement either expressly or by
      implication. It is understood that any and all proprietary rights,
      including but not limited to patent rights, in and to the Materials shall
      be and remain in Provider.

6.    Recipient agrees to provide Provider with an advance copy at least thirty
      (30) days in advance of any written submission (abstract or paper) or oral
      presentation that makes reference to the Materials. If in the opinion of
      Provider any such publication describes a patentable development, Provider
      shall have an opportunity to request that Recipient delay the submission
      or public presentation until after a U.S. patent application has been
      filed. In no event shall the delay be unreasonable. If a publication does
      result from work using the Materials, Recipient agrees to acknowledge
      Provider and/or give credit to Provider's scientists, as scientifically
      appropriate, based on any direct contribution they may have made to the
      work.

                                                                              20
<PAGE>

7.    Recipient agrees not to sequence or clone any Material provided by
      Provider without the written permission of Provider.

8.    In the event that use of the Material results in an invention,
      improvement, substance, or information whether or not patentable and
      patents, if any, which result therefrom ("Developed Technology"),
      Recipient agrees to disclose promptly to Provider all such inventions,
      improvements or substances.

9.    Recipient shall assign all right, title and interest in and to Developed
      Technology to Provider. Recipient agrees to cooperate and assist Provider
      in obtaining patent protection for Developed Technology.

10.   Recipient agrees to execute, acknowledge and deliver all such further
      papers as may be necessary to perform its obligation under this Agreement

11.   Recipient acknowledges that the Materials are provided WITHOUT WARRANTY OF
      MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR ANY OTHER WARRANTY,
      EXPRESS OR IMPLIED. PROVIDER MAKES NO REPRESENTATION THAT THE USE OF THE
      MATERIALS WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK OR OTHER
      PROPRIETARY RIGHT.

12.   In no event shall Provider be liable for any use of the Materials by
      Recipient. Recipient hereby agrees to defend, indemnify and hold harmless
      Provider, its officers, directors, trustees, employees and agents from any
      loss, claim, damage, expense or liability, of whatsoever kind or nature
      (including attorney's fees), which may arise from or in connection with
      this Agreement or the use, handling or storage of the Materials.

13.   Recipient shall report to Provider a summary of the results of Recipient's
      work utilizing the Materials.

14.   Upon the request of Provider, Recipient shall promptly return to Provider
      the Materials furnished to Recipient under this Agreement.

15.   Recipient agrees to comply with all government and National Institutes of
      Health regulations and guidelines which are applicable to the Recipient's
      use of the Materials.

16.   This Agreement is not assignable, whether by operation of law or
      otherwise, without the prior written consent of Provider.

                                                                              21
<PAGE>

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

RECIPIENT'S                                  AUTHORIZED REPRESENTATIVE
INVESTIGATOR                                 FOR RECIPIENT

BY: ____________________________             BY: ____________________________

________________________________             ________________________________
Typed Name                                   Typed Name

________________________________             ________________________________
Title                                        Title

PROVIDER'S                                   AUTHORIZED REPRESENTATIVE
INVESTIGATOR                                 FOR PROVIDER

BY: ____________________________             BY: ____________________________

________________________________             ________________________________
Typed Name                                   Typed Name

________________________________             ________________________________
Title                                        Title

                                                                              22
<PAGE>

                                   APPENDIX C

                                    PROTOCOL

                REACTIVITY AND IMMUNOGENICITY OF LIVE, ATTENUATED
                        ROTAVIRUS VACCINE CANDIDATE 89-12

A copy of the protocol will be attached to the execution copy of this AGREEMENT

                                                                              23

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