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Sample Business Contracts

License Agreement - Isis Innovation Ltd., University of Oxford and TolerRx Inc.

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                             DATED DECEMBER 5, 2000


                           (1) ISIS INNOVATION LIMITED

          (2) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF
                                     OXFORD

                                (3) TOLERRX, INC


                         Licence of Certain Improvements
                       to anti-CD4 and anti-CD8 Antibodies

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[*******] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH
THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER
THE SECURITIES ACT OF 1933, AS AMENDED.

THIS AGREEMENT dated December 5, 2000 is made BETWEEN:

(1)  ISIS INNOVATION LIMITED whose registered office is at University Offices,
     Wellington Square, Oxford OX1 2JD, England ("the Licensor");

(2)  THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD whose
     administrative offices are at Wellington Square, Oxford OX1 2JD, England
     ("the University"); and

(3)  TOLERRX, INC, a Delaware Corporation whose principal place of business is
     at 675 Mass Ave., Cambridge, MA 02139 ("the Licensee"):-

1.   1.     SUBJECT-MATTER

     1.1    This Agreement relates to the intellectual property and know how
            described in the Schedule.

     1.2    For the purposes of this Agreement, the following definitions apply:

            (a)  "Affiliate" means with respect to a party, an entity that
                 controls, is controlled by or is under common control with a
                 party. As used herein, "control" means possession, of the power
                 to direct or cause the direction of the management and policies
                 whether through the ownership of voting securities, by contract
                 or otherwise.

            (b)  "Antibody(ies)" means, individually and collectively, any and
                 all antibodies (or portions thereof) encoded by genetic
                 material of a Cell Line.

            (c)  "Cell Line(s)" means, individually and collectively (i) the
                 cell lines and cell banks of the Schedule and genetic material
                 contained therein.

            (d)  "Know-How" means the know-how described in the Schedule.

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            (e)  "Licensed Patents" means any patent application or patent
                 anywhere in the world that is owned by the Licensor and that
                 claims Licensed Technology.

            (f)  "Licensed Product" means any product or composition that is or
                 includes one or more Antibodies.

            (g)  "Licensed Technology" means, individually and collectively,
                 Cell Lines, Antibodies and Know-How.

            (h)  "Net Sales" means the gross selling price of the Licensed
                 Product in the form in which it is sold or leased to a customer
                 after regulatory approval thereof by Licensee or its
                 sublicensee (as recorded in the standard customer pricing
                 records of the Licensee or the Licensee's sub-licensee if and
                 to the extent that such records are applicable to the Licensed
                 Product in question), after deducting:

                 (i) transportation charges or allowances, including freight
                 pickup allowances, and shipping packaging costs, if any; (ii)
                 trade, quantity or cash discounts, if any, allowed or paid;
                 (iii) credits or allowances, if any, given or made on account
                 of returns, any and all Federal, state or local government
                 rebates, whether in existence now, or enacted at any time
                 during the term of this Agreement, rejections, recalls or
                 destruction (voluntarily made or requested or made by an
                 appropriate government agency, sub-division or department) for
                 the Licensed Product; (iv) any tax, excise or other
                 governmental charge upon or measured by the production, sale,
                 transportation, delivery or use of the Licensed Product,
                 exclusive of income tax; (v) any government mandated surcharge,
                 levy, tax or

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                 assessment to fund a compensation program or reserve for
                 persons injured or alleged to be injured by the Licensed
                 Product; and (vi) a reasonable allowance for bad debt.

            It is understood that a Licensed Product may be marketed in a
            combination package containing other products or materials or in
            combination with active ingredients that are not Antibodies. In such
            a case "Net Sales", for the purpose of determining royalty payments
            on the combination package, shall be calculated by multiplying the
            Net Sales of that combination package by the fraction A/(A+B); where
            A is the gross selling price, during the royalty-paying period in
            question, of the Licensed Product marketed separately and B is the
            aggregate of the gross selling prices, during the royalty-paying
            period in question, of the other products or materials marketed
            separately. In the event that no such separate sales or leases are
            made of the Licensed Product or any of the other products or
            materials in such combination package during the royalty-paying
            period in question, "Net Sales," for the purpose of determining
            royalty payments, shall be calculated by multiplying the Net Sales
            of the combination package by the fraction C/(C+D); where C is the
            standard fully-absorbed cost to the Licensee of the Licensed
            Product, and D is the aggregate of the standard, fully-absorbed
            costs to the Licensee of the other products or materials, such costs
            being determined by using the Licensee's standard accounting
            procedures, which shall be in accordance with generally accepted
            practice.

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2.   GRANT

 2.1 (a)    Subject to Section 2.1(b), Licensor reserves the right to grant to
            the University of Oxford ("University") a licence for the University
            and every employee, student, agent and appointee of the University
            to use and publish (notwithstanding clause 2.3) the Licensed
            Technology and any Licensor Improvement made under clause 2.8 for
            academic and research purposes: and this will include the right for
            the University to use the Licensed Technology as enabling technology
            in other research projects (including projects which benefit from
            third-party funding received from commercial entities).

     (b)    Notwithstanding anything herein to the contrary, Licensor and
            University agree, (i) not to disclose or publish sequence
            information with respect to Antibody and/or Cell Line to any person
            or entity other than Licensee or as permitted by Section 2.5(b);
            (ii) not to transfer Antibody or Cell Line to any person or entity
            other than Licensee or students or employees of University, provided
            that any student or employee agrees not to transfer Antibody or Cell
            Line, or as permitted by Section 2.5(b).

2.2  (a)    The Licensor grants to the Licensee:

          (i)   a licence to use the Cell Lines and the Licensed Patents to the
     extent that the Licensed Patents relate to the Cell Lines worldwide; and

          (ii)  a licence in, to and under the Antibodies and the Licensed
     Patents to the extent that the Licensed Patents relate to the Antibodies
     worldwide to make, have made, use, sell, offer to sell, and import Licensed
     Product (together, the "Licences"). Subject only to clause 2.1, the Licence
     shall be exclusive.

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     (b)    Licensor agrees to provide Licensee with samples of the Cell Lines
            and vectors of the Schedule and with the Know-How.

2.3  During the term of this Agreement, it is contemplated that each party will
     disclose to the other proprietary and confidential technology, inventions,
     technical information, biological materials and the like which are owned or
     controlled by the party providing such information or which that party is
     obligated to maintain in confidence and which is designated by the party
     providing such information as confidential ("Confidential Information").
     For this purpose, Confidential Information includes the Licensed Technology
     to the extent that such Licensed Technology is not disclosed by any patents
     or published patent applications. Subject to subclause 2.4 and 2.5, each
     party agrees to retain the other party's Confidential Information in
     confidence and not to disclose any such Confidential Information to a third
     party without the prior written consent of the party providing such
     information and to use the other party's Confidential Information only for
     the purposes of this Agreement, which obligation shall terminate five (5)
     years after the expiration or termination of this Agreement.

2.4  The obligations of confidentiality will not apply to Confidential
     Information which:

     (i)    was known to the receiving party or generally known to the public
            prior to its disclosure hereunder; or

     (ii)   subsequently becomes known to the public by some means other than a
            breach of this Agreement;

     (iii)  is subsequently disclosed to the receiving party by a third party
            having a lawful right to make such disclosure;

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     (iv)   is required by law or BONA FIDE legal process to be disclosed,
            provided that the party required to make the disclosure takes all
            reasonable steps to restrict and maintain confidentiality of such
            disclosure and provides reasonable notice to the party providing the
            Confidential Information; or

     (v)    is approved for release by the parties, or

     (vi)   is independently developed by the employees or agents of either
            party without any knowledge of the Confidential Information provided
            by the other party.

     (vii)  is disclosed to a government body, agency or authority as required
            by applicable law, rule, or regulation or in order to obtain
            regulatory approval for or authorization to market and sell Licensed
            Product.

2.5   (a)        Notwithstanding the foregoing, the parties shall have the right
                 to disclose Confidential Information to a third party who
                 undertakes an obligation of confidentiality and non-use with
                 respect to such information, at least as restrictive as
                 Licensee's obligation under subclause 2.4 and 2.5.

       (b)       Notwithstanding the foregoing, the University and every
                 employee, student, agent and appointee of the University shall
                 have the right to:

                 (i)   disclose Confidential Information, to the extent that it
                       relates to the Licensed Technology, to other employees
                       and students of the University for academic and research
                       purposes only so long as such employees and students of
                       the University are subject to obligations of
                       confidentiality; and

                 (ii)  transfer Antibody to any academic collaborator to use
                       solely for academic and research purposes (not including
                       commercially funded

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                       research purposes) for in vitro research provided that
                       the academic collaborator signs a material transfer
                       agreement in the form of the University material transfer
                       agreement attached as Exhibit A.

2.6  Each of University, Licensor and Licensee warrants and represents to the
     other that it has the full right and authority to enter into this
     Agreement, and that it is not aware of any impediment which would inhibit
     its ability to perform the terms and conditions imposed on it by this
     Agreement.

2.7  Licensor warrants and represents that except for rights of Cambridge
     University (i) it owns all right, title and interest in and to Licensed
     Technology, (ii) it has not licensed or assigned any right or interest in
     or to Licensed Technology to any third party; (iii) it has the right to
     grant the rights granted hereunder; (iv) that, so far as it is aware, after
     a reasonable investigation, the granting of such rights does not require
     the consent of a third party; and (v) that, so far as it is aware, after a
     reasonable investigation, there are and will be no outstanding agreements,
     assignments or encumbrances entered into or incurred by the Licensor
     inconsistent with the provisions of this Agreement.

2.8  The Licensor will communicate to the Licensee any improvements which the
     Licensor and the University makes to the Licensed Technology, to the extent
     that the Licensor is aware of the improvements made by the University (the
     "Licensor Improvements"). The Licensor and the Licensee may enter into
     negotiations with respect to the Licensee licensing the Licensor
     Improvements from the Licensor. Subject to clause 2.1, neither the Licensor
     nor the University will grant rights to exploit or use the Licensor
     Improvements, even if the Licensee does not enter into a licence in respect
     of the

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     Licensor Improvements, so long as the Licensor Improvements remain
     confidential for the purposes of clause 2.3.

2.9  At the request of the Licensee in writing, the Licensor agrees to grant to
     the Licensee a non-exclusive, [*******] licence to use any improvements
     which:

     (a) are made to the Licensed Technology by academic collaborators in
         accordance with a material transfer agreement entered into under clause
         2.5(b)(ii); and

     (b) have been assigned by the University to the Licensor.

     The Licensee may, at any time, subject to negotiating the terms of the
     licence with the Licensor, request the Licensor to convert the
     non-exclusive [*******] licence to an exclusive, [*******] licence.

3.   UNDERTAKINGS BY AND RIGHTS OF THE LICENSEE

3.1  Except as provided in Section 9.6, the Licensee will not assign the
     Licence. The Licensee may grant sub-licences, and may disclose to
     sub-licensees such of the Licensed Technology as is necessary for the
     exercise of the rights sub-licensed. Immediately following the grant of
     each sub-licence, the Licensee will forward to the Licensor in writing a
     note of the name and address of the sub-licensee, a description of the
     technology sub-licensed and its intended applications, and confirmation of
     the duration of the sub-licence. By controlling the wording of its
     contracts with sub-licensees, the Licensee will ensure that the
     sub-licensees are subject to the confidentiality obligations of this
     Agreement in order to protect the intellectual property rights in the
     Licensed Technology, and the interests of the Licensor therein; and that in
     no circumstances do the terms of any sub-licence in force from time to time
     conflict with the terms of this Agreement.

                                  * Confidential treatment requested:
                                    material has been omitted and filed
                                    separately with the Commission.

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3.2  The Licensee will be responsible for the design and construction of the
     Licensed Products and the Licensor shall have no responsibility or
     liability in that respect.

3.3  The Licensee will ensure that the Licensed Products and the packages
     associated with them are marked suitably with any relevant patent or patent
     application numbers of Licensed Patents to satisfy the laws of each of the
     countries in which the Licensed Products are sold or supplied and in which
     they are covered by the claims of any patent or patent application of
     Licensed Patents, to the intent that the Licensor shall not suffer any loss
     or loss of damages in an infringement action.

3.4  The Licensee agrees not to change its name to or trade under any name which
     includes the word "Oxford".

3.5  (a) Taking into account the complexity, and stage of development of the
     Licensed Technology, the Licensee shall select and use reasonable
     commercial efforts under the circumstances to research, develop and then
     commercialize the Licensed Technology. The efforts of a sublicensee of
     Licensee or a person or entity performing work for Licensee under a
     contract negotiated at arm's length shall be considered as efforts of
     Licensee.

     (b) In the event that Licensor reasonably believes that Licensee is not
     making reasonable commercial efforts under the circumstances to research,
     develop and then commercialize the Licensed Technology pursuant to
     subclause 3.5(a), then Licensor shall provide written notice to Licensee
     which specifies Licensor's basis for such belief and what additional
     efforts Licensor believes should be made by Licensee. Upon receipt of such
     written notice, Licensor and Licensee shall enter into good faith
     negotiations in order to reach mutual agreement as to what efforts by
     licensee shall

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     satisfy the requirements of subclause 3.5(a), and if such mutual agreement
     is not reached within thirty (30) days after receipt of such written
     notice, then the parties agree to submit to arbitration pursuant to
     subclause 9.8 to determine the efforts which should be exerted by Licensee.
     Thereafter, Licensee shall exert the efforts determined by the parties or
     in such arbitration.

(c)  Within sixty (60) days after the end of each calendar year, Licensee shall
     provide Licensor with a report detailing progress made and steps taken
     during the calendar year in:

     (i)    applying for and defending any patent, design, trade mark, copyright
            and other registrations which may be available for the protection of
            the Licensed Technology;

     (ii)   taking legal action against any misappropriation or infringement of
            the Licensed Technology of which the Licensee becomes or is made
            aware;

     (iii)  developing the Licensed Technology in order to facilitate its
            commercial exploitation;

     (iv)   promoting and marketing Licensed Products.

3.6  In the event that the Licensed Technology includes potentially patentable
     subject matter (an "Invention"), Licensee shall file, prosecute and
     maintain patent applications and patents directed to Inventions in the name
     of the Licensor through patent counsel selected by Licensee and approved by
     the Licensor (which approval shall not be unreasonably withheld or delayed)
     who shall consult with and keep Licensor advised with respect thereto.
     After the Effective Date of this Agreement, Licensee shall bear the cost
     and expense for the filing, prosecution and maintenance of Licensed Patents
     in

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     the United States, European Patent Office and subsequent national filings
     which derive from it, and Japan and any other foreign countries mutually
     agreed by the Licensee and the Licensor. If, in good faith, the Licensor
     believes a patent may be granted in a country but the Licensee is unwilling
     to bear the cost and expense for filing, prosecuting and maintaining the
     patent in that country, the Licensor may instruct the patent counsel
     selected by the Licensee at its own cost to file, prosecute or maintain the
     Licensed Patents in that country, and the country in question shall be
     removed from the scope of this Agreement.

3.7  With respect to any Licensed Patents, each patent application, office
     action, response to office action, request for terminal disclaimer, and
     request for reissue or re-examination of any patent issuing from such
     application shall be provided to Licensor. Licensor shall have the right to
     take any action that in its judgement is necessary to preserve such
     Licensed Patents.

3.8  Licensor and the University shall cooperate with Licensee with respect to
     filing, prosecution and maintenance of Licensed Patents and shall use
     reasonable endeavours to cause the inventors to cooperate.

3.9  (a) If any of the Licensed Technology or Licensed Patents under which
     Licensee is licensed hereunder is infringed by a third party, Licensee
     shall have the right and option but not the obligation to bring an action
     for infringement, at its sole expense, against such third party in the name
     of Licensor and/or in the name of Licensee, and to join Licensor as a party
     plaintiff if required. Licensee shall promptly notify Licensor of any such
     infringement and shall keep Licensor informed as to the prosecution of any
     action for such infringement. No settlement, consent judgment or other
     voluntary final disposition

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     of the suit which adversely affects Licensed Technology or Licensed Patents
     may be entered into without the consent of Licensor, which consent shall
     not unreasonably be withheld.

(b)  Any recovery of damages by Licensee for any such suit shall be applied
     first in satisfaction of any unreimbursed expenses and legal fees of
     Licensee relating to the suit and the remainder thereof shall be retained
     by Licensee and treated as Net Sales subject to royalty under this
     Agreement.

3.10 In the event that Licensee elects not to pursue an action for infringement,
     upon written notice to Licensor by Licensee that an unlicensed third party
     is an infringer of Licensed Technology or Licensed Patents, Licensor shall
     have the right and option, but not the obligation at its cost and expense
     to initiate infringement litigation and to retain any recovered damages.

3.11 In any infringement suit either party may institute to enforce the rights
     in Licensed Technology or Licensed Patents pursuant to this Agreement, the
     other party hereto shall, at the request of the party initiating such suit,
     cooperate in all respects and, to the extent possible, have its employees
     testify when requested and make available relevant records, papers,
     information, samples, specimens, and the like. All reasonable out-of-pocket
     costs incurred in connection with rendering cooperation requested hereunder
     shall be paid by the party requesting cooperation.

3.12 The Licensee will communicate to the Licensor any improvements which the
     Licensee makes to the Licensed Technology (the "Licensee's Improvements").
     The Licensee and the Licensor may enter into negotiations with respect to
     the Licensor licensing the

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     Improvements from the Licensee, but Licensee shall not be under any
     obligation to enter into such a license.

4.   4.     PAYMENT

     4.1    The Licensee agrees to pay to the Licensor the sum of [*******] US
            dollars (US $[*******]) on the signature of this Agreement.
            Thereafter, for so long as any Licensed Products are used or
            marketed by the Licensee and its sub-licensees, the Licensee will
            pay to the Licensor a royalty equal to [*******] of the Net Sales
            of all such Licensed Products.

     4.2    The Licensee will pay to the Licensor the following non-refundable
            non-creditable milestone payments within sixty (60) days after the
            occurrence of the specified events with the total milestones due
            under this Section 4.2 being [*******]



            EVENT                                                      AMOUNT
                                                                  
            Initiation of Phase II trials for a Licensed              [*******]
            Product
            Initiation of Phase III trials for a Licensed             [*******]
            Product


     4.3    The Licensee shall provide the Licensor with a royalty report within
            sixty (60) days after the close of each calendar quarter for each
            Licensed Product marketed, and for each Licensed Product brought
            into use by or within the groups of the Licensee and sub-licensees.
            Each report shall state the Net Sales and provide a calculation of
            the royalties due, and shall be accompanied by payment to the
            Licensor of the royalties due.

     4.4    In marketing the Licensed Products, the Licensee will not accept or
            solicit any non-monetary consideration without the prior written
            consent of the Licensor.

                                        * Confidential treatment requested:
                                          material has been omitted and filed
                                          separately with the Commission.

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            The use by the Licensee of a commercially reasonable quantity of
            Licensed Products for promotional sampling shall not violate this
            prohibition.

     4.5    In the case of a Licensed Product which is not marketed, but rather
            manufactured by the Licensee or a sub-licensee for use by that
            party, or within that party's group, the term "Net Sales" shall mean
            [*******] of the gross selling price of the Licensed Product in the
            form in which it is normally sold, as recorded in the standard
            customer pricing records of the Licensee or the sub-licensee or
            sub-sub-licensee if and to the extent that such records are
            applicable to the Licensed Product in question, or as ascertained by
            applying reasonable uplifts to the standard, fully-absorbed cost of
            the Product to the Licensee, sub-licensee or sub-sub-licensee if and
            to the extent that those records are not so applicable. For the
            avoidance of doubt, this clause shall not apply to Licensed Product
            used by the Licensee or within the Licensee's group solely for the
            purposes of internal research or solely for the purposes of internal
            quality control.

     4.6    For the purpose of calculating running-earned royalties under this
            clause, a Licensed Product shall be regarded as sold or leased by
            the Licensee or a sub-licensee when invoiced, or if not invoiced,
            when shipped or delivered by the Licensee or sub-licensee. If a
            Licensed Product marketed by the Licensee or a sub-licensee is sold
            to an Affiliate for re-sale, the royalty on each such Licensed
            Product so re-sold shall be calculated on the highest of the prices
            at which it is (i) marketed or sold to an Affiliate for re-sale or
            (ii) re-sold; provided, however, that in no event shall royalty be
            paid more than once on each Licensed Product.


                                        * Confidential treatment requested:
                                          material has been omitted and filed
                                          separately with the Commission.

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     4.7    If the Licensee or a sub-licensee is obliged to pay royalties to
            third parties (other than the Licensee's Affiliate, for the right to
            make, use or sell a Licensed Product, then the Licensee shall be
            entitled to deduct from the royalty payment due to the Licensor a
            portion of the royalty payment actually made to such third party as
            the Licensee has negotiated with the Licensor, but in any event, not
            greater than [*******] of the royalty payment due to the Licensor.

     4.8    For the avoidance of doubt, any payment made by a [*******] relevant
            for the purposes of calculating Net Sales.

     4.9    All payments provided for under this clause 4 shall be made to the
            Licensor in US dollars without any deductions apart from any tax
            which is required to be withheld under applicable local law. Any
            exchange of currency made to calculate sales for the purpose of this
            clause 4 shall be determined as at the last business day of each
            quarter, using the average of the average daily buying and selling
            rates quoted by Barclays Bank plc during that quarter. Where the
            Licensee is required to withhold tax under applicable local law, the
            Licensee shall deduct such tax, pay it to the relevant taxing
            authority, and supply the Licensor with a Certificate of Tax
            Deduction at the time of payment to the Licensor. The parties shall
            co-operate under any applicable Double Taxation Treaty so that, if
            possible, payments are made gross or, if payment gross is not
            possible, the Licensor obtains appropriate relief under the Treaty.


                                        * Confidential treatment requested:
                                          material has been omitted and filed
                                          separately with the Commission.

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     4.10   Where the Licensee is obliged to make a payment to the Licensor
            under this Agreement which attracts value-added, sales, use, excise
            or other similar taxes or duties, the Licensee shall be responsible
            for paying such taxes and duties.

     4.11   In the event that full payment of any amount due from the Licensee
            to the Licensor under this Agreement is not made by any of the dates
            stipulated, the Licensee shall be liable to pay interest on the
            amount unpaid at the rate of two percent (2%) over the base rate for
            the time being of Barclays Bank plc, from the date when payment was
            due until the date of actual payment.

     4.12   The Licensee and the Licensee's sub-licensees shall keep complete
            and accurate accounts of all Licensed Products used and marketed;
            and will permit the Licensor through an independent certified
            accountant to audit such accounts on at least thirty (30) days'
            written notice and no more than once each calendar year solely for
            the purpose of determining the accuracy of the royalty reports and
            payments. The Licensee's obligation and that of the Licensee's
            sub-licensees concerning audit of their accounts shall terminate as
            to any report three (3) years after the date of that report.

5.   5.     DURATION AND TERMINATION

     5.1    Subject to clause 5.2, this Agreement shall take effect on the date
            of signature and (subject to the remaining sub-clauses of this
            clause) shall continue in force until the expiration of the period
            of ten (10) years from the date on which a Licensed Product is first
            put on the market by the Licensee or one of its sub-licensees, after
            which time Licensee shall have a fully paid-up license under Section
            2.2 and no further royalties will be due.

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     5.2    Insofar as the rights and obligations in this Agreement concern
            territories in which the commercial practice of the Licensed
            Technology is covered by a claim being prosecuted in a patent
            application filed by the Licensee that is a Licensed Patent, or by a
            valid claim of an unexpired patent which issues in response to such
            an application, the royalty obligations shall extend for those
            territories beyond the period defined in clause 5.1 if and for so
            long as the commercial practice of the Licensed Technology is
            covered in those territories.

     5.3    If Licensee commits a material breach of clause 2.3, 3.1, 3.6 and 4
            of this Agreement or fails to exert the efforts determined by the
            parties or by arbitration under clause 3.5(b), and such breach or
            failure is not remedied within the period allowed by notice given by
            Licensor in writing calling on the Licensee to remedy such failure
            (such period being not less than thirty (30) days), the Licensor may
            by further written notice terminate this Agreement immediately.

     5.4    The Licensee may terminate this Agreement at any time by serving not
            less than three (3) months' written notice on the Licensor.

     5.5    The Licensor shall have the right to terminate this Agreement by
            serving written notice on the Licensee in the event that Licensee
            files a voluntary petition in bankruptcy, is adjudicated a bankrupt,
            makes a general assignment for the benefit of creditors, or fails to
            discharge within 30 days an involuntary petition in bankruptcy filed
            against it. Such notice may terminate this Agreement either
            immediately or at the end of such period as the Licensor shall
            select.

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     5.6    Clauses 2.3, 2.4, 2.5, 4 (in relation to any payments which have
            fallen due but not been made), 5.1, 5.2, 5.6, 5.8, 5.9 6, 7, 8, 9.4
            and 9.8 shall survive the termination or expiration of this
            Agreement, for whatever reason.

     5.7    This Agreement may be terminated only as set forth in this clause 5.

     5.8    Upon any termination of this Agreement, Licensee, at its option,
            shall be entitled to finish any work-in-progress which is completed
            within six (6) months of termination of this Agreement and to sell
            any completed inventory of a Licensed Product covered by this
            Agreement which remains on hand as of the date of the termination,
            so long as Licensee pays to Licensor the royalties applicable to
            said subsequent sales in accordance with the same terms and
            conditions as set forth in this Agreement.

     5.9    In the event that this Agreement and/or the rights and licenses
            granted under this Agreement to Licensee are terminated, any
            sublicense granted under this Agreement shall remain in full force
            and effect as a direct license between Licensor and the sublicensee
            under the terms and conditions of this Agreement, subject to the
            sublicensee agreeing to be bound to Licensor under such terms and
            conditions within thirty (30) days after Licensor provides written
            notice to the sublicensee of the termination of Licensee's rights
            and licenses under this Agreement. At the request of Licensee,
            Licensor will acknowledge to a sublicensee, Licensor's obligations
            to the sublicensee under this paragraph.

6.   LIABILITY

     6.1    (a)  The Licensee agrees to indemnify the Licensor and the
            University and hold the Licensor and the University harmless from
            and against any and all claims,

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            damages and liabilities asserted by third parties and arising
            directly or indirectly from use of the Licensed Technology or the
            sale of Licensed Products by the Licensee and its sub-licensees and
            sub-sub-licensees.

            (b)  Licensee's indemnification under (a) shall not apply to any
            liability, damage, loss or expense to the extent that it is directly
            and solely attributable to the intentional misconduct of the
            Indemnitees.

            (c)  Licensee shall have the right to control the defense,
            settlement or compromise of any such action and shall select counsel
            for such defense.

            (d)  Licensor and the University shall notify Licensee promptly of
            any claim or threatened claim under this subclause 6.1(a) and shall
            fully cooperate with all reasonable requests of Licensee with
            respect thereto.

     6.2    The Licensor makes no representation or warranty that advice given
            to the Licensee pursuant to this Agreement by any employee, student,
            agent or appointee of the Licensor or of the University, or the use
            of any works, designs or information which they, the Licensor or the
            University provide in connection with this Agreement, will not
            result in infringement of third-party rights.

     6.3    The Licensee undertakes to make no claim against any employee,
            student, agent or appointee of the Licensor or of the University
            which seeks to enforce against any of them any liability whatsoever
            in connection with this Agreement or its subject-matter. It is
            understood that this Clause 6.3 does not prevent Licensee from
            asserting a claim(s) against Licensor or University.

19
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     6.4    The liability of any party for any breach of this Agreement, or
            arising in any other way out of the subject-matter of this
            Agreement, will not extend to loss of business or profit or to any
            indirect or consequential damages or losses.

     6.5    Except in the case of fraud or intentional misconduct or intentional
            breach of this Agreement or a breach of a warranty where Licensor
            had knowledge that the warranty was untrue or by the investigation
            undertaken by the University the Licensor would have known that the
            warranty was untrue, Licensor's maximum liability with respect to
            payment of damages awarded to the Licensee by a court of law under
            or otherwise in connection with this Agreement or its subject
            matter, shall be the return of all royalty, milestone and up-front
            payments paid by the Licensee under this Agreement, together with
            interest on the balance of such moneys from time to time
            outstanding, accruing from day to day at two percent over the
            Barclays Bank plc base rate from time to time in force and
            compounded annually as at 31 December and if the damages awarded
            exceed such amount, such excess may be credited against future
            royalties and milestones owed by Licensee under this Agreement, as
            and when they become due.

     6.6    The University's maximum liability with respect to payment of
            damages awarded to the Licensee by a court of law under or otherwise
            in connection with this Agreement or its subject matter, shall not
            exceed the return of all royalty, milestone and up-front payments
            paid by the Licensee to the Licensor under this Agreement less any
            return of those royalties, milestones or up-front payments by the
            Licensor to the Licensee under clause 6.5, together with interest on
            the balance of such moneys from time to time outstanding, accruing
            from day to day

20
<Page>

            at two percent over the Barclays Bank plc base rate from time to
            time in force and compounded annually as at 31 December and if the
            damages awarded exceed such amount, such excess may be credited
            against future royalties and milestones owed by Licensee under this
            Agreement less any return of those royalties, milestone or up-front
            payments by the Licensor to the Licensee under clause 6.5, as and
            when they become due.

     6.7    If any sub-clause of this clause 6 is held to be invalid or
            unenforceable under any applicable statute or rule of law, then it
            shall be deemed to be omitted, and if as a result any party becomes
            liable for loss or damage which would otherwise have been excluded,
            then such liability shall be subject to the remaining sub-clauses of
            this clause 6.

7.   FORCE MAJEURE

     If the performance by either party of any of its obligations under this
     Agreement (other than an obligation to make payment) shall be prevented by
     circumstances beyond its reasonable control, then such party shall be
     excused from performance of that obligation for the duration of the
     relevant event.

8.   NOTICES

     The Licensor's representative for the purpose of receiving payments and
     notices shall until further notice be:

               The Managing Director
               Isis Innovation Limited
               Ewert House
               Ewert Place
               Summertown
               Oxford OX2 7DD
               England

21
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     The Licensee's representative for the purpose of receiving notices shall
     until further notice be:

               TOLERRX, Inc.
               675 Mass. Ave.
               Cambridge, MA 02139
               Attn: CEO

9.   GENERAL

     9.1    Clause headings are inserted in this Agreement for convenience only,
            and they shall not be taken into account in the interpretation of
            this Agreement.

     9.2    Nothing in this Agreement shall create, imply or evidence any
            partnership or joint venture between the Licensor and the Licensee
            or the relationship between them of principal and agent.

     9.3    This Agreement constitutes the entire agreement between the parties
            with regard to the Licence. Specifically, but without limitation,
            this Agreement does not impose or imply any obligation on the
            Licensor or the University to conduct development work: any
            arrangements for such work shall be the subject of a separate
            agreement between the University and the Licensee. Any variation of
            this Agreement shall be in writing and signed by authorised
            signatories for both parties.

     9.4    This Agreement shall be governed by English Law. Except as provided
            in Section 9.8, Licensee submits to the non-exclusive jurisdiction
            of the English courts with respect to any dispute which may arise
            out of or in connection with this Agreement.

22
<Page>

     9.5    If any one or more clauses or sub-clauses of this Agreement would
            result in this Agreement being prohibited pursuant to any applicable
            competition law, then it or they shall be deemed to be omitted. The
            parties shall uphold the remainder of this Agreement, and shall
            negotiate an amendment which, as far as legally feasible, maintains
            the economic balance between the parties.

     9.6    This Agreement shall not be assignable by either of the parties
            without the prior written consent of the other party (which consent
            shall not be unreasonably withheld), except that Licensee without
            the consent of Licensor may assign this Agreement to an Affiliate or
            to a successor in interest or to a transferee of all or
            substantially all of the portion of the business to which this
            Agreement relates.

     9.7    Subject to the limitations on assignment herein, this Agreement
            shall be binding upon and inure to the benefit of said successors in
            interest and assigns of Licensee and Licensor. Any such successor or
            assignee of a party's interest shall expressly assume in writing the
            performance of all the terms and conditions of this Agreement to be
            performed by said party.

     9.8    Any dispute, controversy or claim arising under subclause 3.5(b) of
            this Agreement will be submitted to mediation in accordance with the
            WIPO Mediation Rules. The place of mediation will be London. The
            language to be used in the mediation will be English. If, and to the
            extent that, any such dispute, controversy or claim has not been
            settled pursuant to the mediation within 60 days of the commencement
            of the mediation, it will, upon the filing of a request for
            arbitration by either party, be referred to and finally determined
            by arbitration

23
<Page>

            in accordance with the WIPO Arbitration Rules. The arbitral tribunal
            will consist of a sole arbitrator. The place of arbitration will be
            London.

     9.9    The parties to this Agreement intend that by virtue of the Contracts
            (Rights of Third Parties) Act 1999 the people referred to in clause
            6.3 will be able to enforce the terms of clause 6.3 of this
            Agreement as if the people referred to in clause 6.3 were a party to
            it.

24
<Page>

AS WITNESS the hands of authorised signatories for the parties on the date first
mentioned above

SIGNED for and on behalf of
Name: D. J. Ringler
     ------------------------
Positions: President
          -------------------
Signature: /s/ D. J. Ringler
          -------------------

SIGNED for and on behalf of
ISIS INNOVATION LTD
Name: T. Cook
      -----------------------
Position: Director
         --------------------
Signature: /s/ T. Cook
          -------------------

SIGNED for and on behalf of
THE CHANCELLOR
MASTER AND SCHOLARS OF THE
UNIVERSITY OF OXFORD:
Name: S.R. Clements
     ------------------------
Position: Director
         --------------------
Signature: /s/ S.R. Clements
          -------------------


Please note that these signatures are subject to the underlying documents having
been changed as we discussed and are conditional upon us receiving signed copies
of the original documents in agreed form.

<Page>

THIS AMENDMENT AGREEMENT, dated December 19, 2002 (the "Effective Date") is made
BETWEEN:

         (1)     ISIS INNOVATION LIMITED, a company registered in England (No.
         02199542), whose registered office is at University Offices, Wellington
         Square, Oxford OX1 2JD, England (the "Licensor"); and

         (2)     THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF
         OXFORD whose administrative offices are at the University Offices,
         Wellington Square, Oxford OX1 2JD, England ("the University"); and

         (3)     TOLERRX, INC., a Delaware corporation whose principal place of
         business is at 300 Technology Square, Cambridge, MA 02139 (the
         "Licensee").

WHEREAS, the parties have entered into a License Agreement dated December 5,
2000 that is directed to Anti-CD4 and Anti-CD8 Antibodies (the "License
Agreement"); and

WHEREAS, the parties wish to amend the License Agreement.

In consideration of the sum of $1 (United States) paid by each party hereto to
each of the other parties, IT IS AGREED as follows:

1.   All defined terms of the License Agreement shall have the same meaning in
     this Amendment Agreement.

  2. Clause 3.1 of the License Agreement shall be replaced in its entirety with
     the following:

     3.1 The Licensee:

            3.1.1  will not assign the License, except as provided in clause 9.6
of this Agreement.
            3.1.2  may grant sub-licenses, and may disclose to sub-licensees
such of the Licensed Technology as is necessary for the exercise of the rights
sub-licensed.
            3.1.3  will, immediately following the grant of each sub-license,
forward to the Licensor in writing a note of the name and address of the
sub-licensee, a description of the technology sub-licensed and its intended
applications, and confirmation of the duration of the sublicense.
            3.1.4  will ensure that any and all sub-licensees are subject to
reasonable obligations of confidentiality sufficient to protect the intellectual
property rights in the Licensed Technology and the interests of the Licensor
therein
            3.1.5, will, except in respect of the Genentech Agreement, take
reasonable steps to ensure that the terms of any sublicense in force from time
to time do not conflict with the terms of this Agreement.
            3.1.6  will ensure that the terms of the Genentech Agreement do not
conflict with clauses 2.1 and 2.5(b) of this Agreement.
            3.1.7  acknowledges that, notwithstanding the above clauses 3.1.5
and 3.1.6, clause 5.9 will remain in full force and effect, and Licensee's
obligations

<Page>

to Licensor and University under clause 4.4 and clause 6 will remain in full
force and effect.
            3.1.8  agrees that nothing in any sub-license in force from time to
time absolves the Licensee of its obligations to pay royalties under this
Agreement, or its other obligations as set out in this Agreement.

  3. Clause 3.3 of the License Agreement shall be replaced in its entirety with
the following:

     3.3 The Licensee will take reasonable endeavours to ensure that the
     Licensed Products and the packages associated with them are marked suitably
     with any relevant patent or patent application numbers of Licensed Patents
     to satisfy the laws of the countries in which the Licensed Products are
     sold or supplied and in which they are covered by the claims of any patent
     or patent application of Licensed Patents, to the intent that the Licensor
     shall not suffer any loss or loss of damages in an infringement action. For
     the avoidance of doubt, in respect of the Genentech Agreement, reasonable
     endeavours shall be limited to requesting that Genentech mark Licensed
     Products and the packages associated with them as described in this clause
     3.3. The Parties Acknowledge that the Licensee has no power to force
     Genentech to comply with such a request.

4.   Clause 3.4 of the License Agreement shall be replaced in its entirety with
the following:

     3.4    No right, express or implied is granted by this License for the
     Licensee or any of its sublicensees to use in any manner the names "Oxford"
     or "Isis" or any other trademark or trade name of the University or Isis
     without the prior written consent of the University and/or Isis. The
     Licensee agrees not to change it name to or trade under any name that
     includes the word "Oxford".

5.   Clause 4.1 of the License Agreement will be replaced in its entirety with
the following:

     4.1(a) The Licensee agrees to pay to the Licensor the sum of [*******] the
            receipt of which is acknowledged. For so long as any Licensed
            Products are used or marketed by the Licensee and its sublicensees,
            subject to clauses 4.1 (b) and (c), the Licensee will pay to the
            Licensor a royalty equal to [*******] of the Net Sales of all such
            Licensed Products.

     4.1(b) In regard to royalty payments with respect to Licensed Product for
            which royalties are due under clause 4.1(a) of this Agreement that
            are sold pursuant to an agreement between Licensee and Genentech,
            Inc. (the "Genentech Agreement") (which for the avoidance of doubt
            includes any sublicense under the Genentech Agreement), such royalty
            payments shall be (i) calculated based on net sales of Licensed
            Product where net sales are determined as defined in the Genentech
            Agreement (and not Net Sales as defined in the License Agreement),
            both in the case where TolerRx is receiving royalty payments under
            the Genentech Agreement and in the case where


                                        * Confidential treatment requested:
                                          material has been omitted and filed
                                          separately with the Commission.

                                        2
<Page>

            TolerRx is receiving a share of Operating Profits and Losses under
            the Genentech Agreement.

     4.1(c) In the event that royalties based on Licensed Product pursuant to
            the Genentech Agreement are reduced thereunder as a result of
            commercialization of a product by a third party, then, with respect
            to Licensed Products to which such reduction applies, the royalty
            rate under clause 4.1(a) of the License Agreement [*******].

6.   Clause 4.3 of the License Agreement shall be replaced in its entirety with
the following:

     4.3.1  Except as provided in clause 4.3.2, the Licensor shall provide the
            Licensor with a royalty report within sixty (60) days after the
            close of each calendar quarter for each Licensed Product brought
            into use by or within the groups of the Licensee and sub-licensees.
            Each report shall state the Net Sales and provide a calculation of
            the royalties due, and shall be accompanied by payment to the
            Licensor of the royalties due.

     4.3.2  In respect of royalty payments and royalty reports as to royalties
            due under the Genentech Agreement, such sales and reports will be
            due thirty (30) days after such payments and reports from Genentech
            become due with respect to Genentech Sales.

7.   Clause 4.12 of the License Agreement shall be replaced in its entirety with
the following:

     4.12.1 Except as provided in clause 4.12.2, the Licensee and the Licensee's
            sub-licensees shall keep complete and accurate accounts of all
            Licensed Products used and marketed and will permit the Licensor
            through an independent certified accountant to audit such accounts
            on at least thirty days' written notice and no more than once each
            calendar year solely for the purpose of determining the accuracy of
            the royalty reports and payments. The Licensee's obligation and that
            of the Licensee's sub-licensees concerning audit of their accounts
            shall terminate as to any report three (3) years after the date of
            that report

     4.12.2 Where the Licensee enters into a sub-license with Genentech, the
            Licensor expressly agrees to waive the audit-rights set out in
            sub-clause 4.12.1 above in respect of Genentech and its
            sub-licensees. However, upon the written request of the Licensor,
            Licensee agrees to exercise the audit rights of the Licensee under
            the Genentech Agreement. The Licensor retains the right to audit the
            Licensee and to inspect any records of audits carried out by the
            Licensee upon Genentech

8.          The Licensee agrees to provide the Licensor with a true copy of the
Genentech Agreement within thirty (30) days of signing thereof by all parties
thereto.


                                        * Confidential treatment requested:
                                          material has been omitted and filed
                                          separately with the Commission.

                                        3
<Page>

9.   The License Agreement is amended as provided herein with effect from the
date of this Amendment Agreement. All other terms and provisions of the License
Agreement shall be unaffected by this Amendment Agreement.

10.  All references in the License Agreement to the "Agreement" shall be deemed
to include this Amendment Agreement.

11.  This Amendment Agreement shall be governed by English Law. The Licensee
     submits to the non-exclusive jurisdiction of the English courts with
     respect to any dispute which may arise out of or in connection with this
     Amendment Agreement.

     AS WITNESS the hands of authorized signatories for the parties on the date
first mentioned above.

     SIGNED for and on behalf of
     ISIS INNOVATION LIMITED:

Name:       Mr. T. Hockaday
Position:   Executive Director
            Isis Innovation Ltd
Signature:  /s/ T. Hockaday

SIGNED for and on behalf of
THE CHANCELLOR, MASTERS
AND SCHOLARS OF THE
UNIVERSITY OF OXFORD:

Name:       Dr. Richard Liwicki
Position:   Associate Director
            Research Services
            University of Oxford
Signature:  /s/ Richard Liwicki

SIGNED for and on behalf of
TOLERRX, INC.:

Name: Douglas J. Ringler
Position: President and Chief Executive Officer
Signature: /s/ Douglas J. Ringler

                                        4