10-Q
MEDICINES CO /DE filed this form 10-Q on 15 May 2002
- velhartice.info
<PAGE>

                                                                               1

                                                                    EXHIBIT 10.2

          Confidential Materials omitted and filed separately with the
        Securities and Exchange Commission. Asterisks denote omissions.

                      STUDY AND EXCLUSIVE OPTION AGREEMENT

entered into on this 5th day of March 2002 (the "Effective Date")

by and between

ASTRAZENECA AB, a company incorporated under the laws of Sweden with its
registered office at S-151 85 Sodertalje, Sweden ("ASTRAZENECA")

and

THE MEDICINES COMPANY, a company incorporated under the laws of Delaware with
its registered office at One Cambridge Center, Cambridge, Massachusetts 02142,
United States ("TMC");

WITNESSETH

WHEREAS, ASTRAZENECA performs research, development and marketing of
pharmaceutical compounds and products inter alia in the cardiovascular therapy
area; and

WHEREAS, ASTRAZENECA has developed the intravenous product Clevidipine for
indications such as the control of blood pressure; and

WHEREAS, TMC performs development of pharmaceutical compounds and marketing of
pharmaceutical products particularly in the cardiovascular therapy area; and

WHEREAS, TMC may be interested in acquiring a license to develop and
commercialise Clevidipine provided that the product fulfils certain clinical
criteria; and



WHEREAS, ASTRAZENECA has expressed its interest to license Clevidipine to TMC
and finds it to be in the mutual interest of the Parties that TMC may perform a
certain clinical study to evaluate whether Clevidipine fulfils the criteria
desired.


<PAGE>
                                                                               2

NOW THEREFORE, the Parties hereto agree to the following.

1.          DEFINITIONS

In this Agreement the following expressions shall have the following meanings:

1.1.        "Adverse Event" shall mean the development of an undesirable medical
            condition or the deterioration of a pre-existing medical condition
            following or during exposure to a pharmaceutical product whether or
            not considered causally related to such product.

1.2.        "Affiliate" with respect to a Person shall mean any other Person
            that directly, or indirectly through one or more intermediaries,
            controls, is controlled by or is under common control with such
            Person. For the purposes of this Article 1.2 only, "control" and,
            with correlative meanings, the terms "controlled by" and "under
            common control with", shall mean (a) the possession, directly or
            indirectly, of the power to direct the management or policies of a
            Person, whether through the ownership of voting securities, by
            contract or otherwise, and/or (b) the ownership, directly or
            indirectly, of more than fifty percent (50%) of the voting
            securities or other ownership interest of a Person.

1.3.        "CDA" shall mean the Confidential Disclosure Agreement entered into
            by and between the Parties on 9 April 2001, as subsequently amended
            on 21 August 2001.

1.4.        "Compound" shall mean ASTRAZENECA's proprietary compound named
            Clevidipine with the chemical structure as shown in Schedule 1,
            attached hereto.

1.5.        "Confidential Information" shall mean any and all information, data
            and know-how, whether oral or in writing or software stored relating
            to the Compound or the Product and disclosed by or on behalf of
            ASTRAZENECA or its Affiliates hereunder.

1.6.        "Effective Date" shall have the meaning defined above.

1.7.        "FTE Day" shall have the meaning defined in the License Agreement.


<PAGE>
                                                                               3

1.8.        "Intellectual Property Rights" shall mean know how, patents, trade
            marks, service marks, trade names, registered designs, design
            rights, copyright (including rights in computer software) and any
            rights or property similar to any of the foregoing in any part of
            the world whether registered or not registered together with the
            right to apply for the registration of any such rights.

1.9.        "License Agreement" shall mean the License Agreement providing for
            an exclusive license to the Product (as therein defined) by and
            between the Parties, attached hereto as a Schedule 2.

1.10.       "License Agreement Effective Date" shall have the meaning defined in
            Article 9.1.3.

1.11.       "License Agreement Notice" shall have the meaning defined in Article
            9.1.1.

1.12.       "Party" or "Parties" shall mean TMC and/or ASTRAZENECA.

1.13.       "Person" shall mean an individual, sole proprietorship, partnership,
            limited partnership, limited liability partnership, corporation,
            limited liability company, business trust, joint stock company,
            trust, unincorporated association, joint venture or other similar
            entity or organisation, including a government or political
            subdivision, department or agency of a government.

1.14.       "Pilot Study" shall mean the clinical study to be carried out
            according to the study outline attached hereto as a Schedule 3.

1.15.       "Product" shall mean any pharmaceutical formulation or product for
            intravenous application containing the Compound as the sole active
            ingredient in a finished dosage form suitable for administration to
            patients.

1.16.       "Results" shall mean any inventions, formulae, products, processes,
            techniques, discoveries, improvements, information, data and
            knowledge developed, generated or reduced to practice under or in
            connection with the Pilot Study and any Intellectual Property Rights
            related thereto.


<PAGE>
                                                                               4

1.17.       "Samples" shall mean samples of the Product in 100 ml bottles
            containing 0.5 mg/ml of Compound in 20 % lipid emulsion for clinical
            use.

1.18.       "Trigger" shall mean a result of the Pilot Study demonstrating that
            the Compound is statistically significantly better (p<=0.05) than
            nitroglycerin in preserving creatinine clearance, such statistically
            significantly better result measured as change in 24 hours
            creatinine clearance before and after on pump CABG in at least 100
            patients.

2.          THE PILOT STUDY

2.1.        ASTRAZENECA shall supply to TMC, or shall cause its
            manufacturer of Product to supply to TMC, whichever ASTRAZENECA
            elects, within forty-five (45) days from the date of delivery to
            ASTRAZENECA from ASTRAZENECA's manufacturer of the complete number
            of Samples indicated below in this Article 2.1 ordered from such
            manufacturer or the date when such number of Samples is ready for
            delivery from such manufacturer, whichever day ASTRAZENECA elects,
            Samples in a total quantity of 700 bottles. Any such delivery to
            TMC shall be made free of charge to TMC at TMC's designated
            facility. ASTRAZENCA shall reimburse TMC any cost for 20%
            Intralipid to be used as placebo in the Pilot Study.  Such cost
            should not exceed New Zealand Dollars [**].

2.2.        The Parties acknowledge that TMC has as of the Effective Date
            received under the CDA the information it will need to carry out the
            Pilot Study. In addition thereto ASTRAZENECA may at its own
            discretion, from time to time during the term of this Agreement,
            disclose Confidential Information to TMC in such manner as shall be
            agreed between the Parties to enable TMC to carry out the Pilot
            Study.

2.3.        The Pilot Study shall be carried out entirely by TMC. TMC shall be
            fully and solely responsible for the reporting of any Adverse Events
            emanating from or relating to the Pilot Study. TMC shall perform its
            obligations under this Agreement to the best of its abilities in a
            manner appropriate to assure that the Results are true, accurate and
            correct.


<PAGE>
                                                                               5

            TMC shall have the right to use CROs and other sub-contractors for
            the purposes of carrying out the Pilot Study, provided that TMC
            shall notify ASTRAZENECA without unreasonable delay following any
            such appointment of a CRO or other sub-contractor. TMC shall ensure
            that all of its CROs or other sub-contractors will comply with all
            terms and conditions of this Agreement and TMC shall remain fully
            responsible for the compliance by such CROs or other sub-contractors
            with the terms and conditions of this Agreement as if such CROs or
            other sub-contractors were TMC hereunder.

2.4.        The Parties shall use their best reasonable efforts to initiate and
            complete without unreasonable delay following the Effective Date a
            study protocol setting forth a detailed description of the Pilot
            Study, to be based in all substantial parts on the study outline set
            forth in Schedule 3. Such study protocol shall be attached hereto as
            the Schedule 3, thereby replacing and superseding the version of
            Schedule 3 attached hereto at the Effective Date, and, for the
            avoidance of doubt, the Pilot Study shall be carried out according
            to such study protocol. Should the Parties not have been able
            despite such best reasonable efforts to agree on a study protocol
            within four (4) months of the Effective Date, then upon the request
            in writing by either

            Party within thirty (30) days of the expiration of such four months
            period this Agreement shall immediately terminate.

2.5.        Tottie Nordlander at ASTRAZENECA, or whoever ASTRAZENECA assigns and
            notifies TMC in writing about, shall be ASTRAZENECA's primary
             person during the term of this Agreement. TMC shall where
            necessary, advisable or useful discuss with Tottie Nordlander any
            important aspects of the performance of the Pilot Study.

2.6.        TMC shall keep ASTRAZENECA continually updated about the conduct of
            the Pilot Study by means of meetings and written reports, whichever
            would be suitable for the purpose of keeping ASTRAZENECA
            sufficiently informed. No less than once every fourth (4th) week TMC
            shall submit to ASTRAZENECA a written report summarising progress on
            the Pilot Study during the period concerned. Within sixty (60) days
            of completion of clean file


<PAGE>
                                                                               6

            of the Pilot Study TMC shall submit to ASTRAZENECA a final report,
            in a format consistent with the International Committee on
            Harmonization guidelines for a clinical study report, summarising
            the work performed and the Results achieved during the Pilot Study
            ("the Final Report").

            Any such report contemplated in this Article 2.6 may be submitted to
            ASTRAZENECA's  person as stated in Article 2.5.

2.7.        TMC shall carry out the Pilot Study in accordance with any
            applicable law or other regulation including but not limited to Good
            Laboratory Practice and Good Clinical Practice as from time to time
            set forth by the European Union. TMC shall during its performance of
            the Pilot Study allow ASTRAZENECA to comment on any aspect of the
            Pilot Study and shall take into reasonable account any such comment
            made by ASTRAZENECA; provided always, however, that any such comment
            is given by ASTRAZENECA without any warranty or guarantee as to the
            results. For the avoidance of doubt, such ASTRAZENECA's right to
            comment shall not prejudice TMC's right to manage and determine the
            conduct of the Pilot Study, subject always to what is stated in this
            Agreement and in Schedule 3.

            Assistance by ASTRAZENECA to TMC in relation to Fresenius

2.8.        At the Effective Date Astra Hassle AB, subsequently merged into
            ASTRAZENECA, and Fresenius (as defined in the License Agreement) are
            parties to a Development and Commercial Supply Contract of 28
            December 1995 providing for the supply by Fresenius to ASTRAZENECA
            of Product. Should Fresenius agree with TMC on the supply of Product
            to TMC and with ASTRAZENECA to release ASTRAZENECA from any
            obligation under said Contract, then ASTRAZENECA will, provided
            always that the termination of such Contract or TMC's entering into
            any such arrangement will not incur any expenses or liability on
            ASTRAZENECA, agree to assign its rights under the Contract to TMC,
            or to terminate the Contract with Fresenius, whichever TMC desires
            and notifies ASTRAZENECA in writing of.


<PAGE>
                                                                               7

            It is explicitly understood and agreed by the Parties that
            ASTRAZENECA shall have no obligations whatsoever to transfer or
            supply, other than as explicitly provided for under Article 2.1, any
            quantity of Compound or Product to TMC.

2.9.        ASTRAZENECA undertakes, upon having received written notice from
            TMC, for a period of three (3) months starting sixty (60) days upon
            ASTRAZENECA's receipt of such TMC's notice, to assist TMC, by
            telephone, e-mail or other appropriate means as agreed by the
            Parties, in TMC's discussions with Fresenius (as defined in the
            License Agreement) in connection with Fresenius' restart of the
            formulation program regarding the Product. Such ASTRAZENECA's
            assistance shall be given to an extent necessary and reasonable and
            shall not, together with any such assistance provided for under
            Article 3.1, 3.2 and 3.5.1 under the License Agreement, exceed in
            total [**]. It is acknowledged that ASTRAZENECA may at its
            discretion carry out any such assistance for up to [**] percent
            ([**]%) of such [**] by using Third Party consultants.

            For any services or assistance performed by ASTRAZENECA pursuant to
            this Article 2.9, TMC shall reimburse ASTRAZENECA for ASTRAZENECA's
            out-of-pocket costs for such activities plus [**] U.S. Dollars
            ($[**]) [**]. Should ASTRAZENECA use a Third Party consultant(s) for
            carrying out assistance for a certain FTE Day, or part thereof,
            then, for the avoidance of doubt, the FTE Day rate now stated shall
            apply thereon, and the out-of-pocket costs for consultants, if any,
            as indicated above in this paragraph, shall apply only to costs for
            consultants which would typically have been incurred should the
            assistance have been actually carried out by an employee(s) of
            ASTRAZENECA or its Affiliates.

            ASTRAZENECA shall invoice TMC for all assistance during each
            relevant time period within thirty (30) days of the expiration of
            each calendar half-year.

            Submission of first draft of the Supply Agreement


<PAGE>
                                                                               8

2.10.       Due to the fact that the Supply Agreement (as defined in the License
            Agreement) has not been entered into on the Effective Date,
            ASTRAZENECA shall no later than three (3) months of the Effective
            Date provide to TMC a first draft on the Supply Agreement. Should
            ASTRAZENECA fail to do so, then TMC's sole remedy therefor shall be
            ASTRAZENECA's loss of right, as stated in Article 4.3.3, second
            paragraph, of the License Agreement, to terminate the License
            Agreement.

3.          REMUNERATION

            As the sole consideration for TMC's right to carry out the Pilot
            Study hereunder TMC shall carry itself any costs and shall be solely
            responsible for any cost for, connected to or arising from the
            performance of the Pilot Study.

4.          UNDERTAKINGS OF TMC

            In consideration of ASTRAZENECA supplying the Samples and disclosing
            the Confidential Information to TMC, TMC hereby undertakes:

4.1.        to use the Samples and the Confidential Information solely and
            exclusively for the Pilot Study, and not to use the Samples, the
            Confidential Information or the Results for any other purpose
            whatsoever; and

4.2.        to maintain confidential the Results, the Confidential Information
            and the Samples and not to disclose directly or indirectly the
            Results, nor the Confidential Information or give any part of the
            Samples to any other Person, save as permitted by Article 5.

5.          PERMITTED DISCLOSURES

5.1.        Notwithstanding Article 4:

5.1.1.      TMC may supply Samples and/or disclose Confidential Information to
            any of its Affiliates who need to receive the Samples and/or know
            the Confidential Information in order to fulfil the Pilot Study,
            provided that TMC shall procure that, prior to such supply of
            Samples and/or disclosure of Confidential Information, each
            Affiliate to which Samples are to be supplied and/or


<PAGE>
                                                                               9

            Confidential Information is to be disclosed is made aware of the
            obligations contained in this Agreement and undertakes, in a manner
            legally enforceable by ASTRAZENECA, to adhere to such terms of this
            Agreement as if it were a party to it; and

5.1.2.      TMC may supply Samples and/or disclose Confidential Information to
            its directors and employees (and those of its Affiliates to whom
            disclosure may be made in accordance with Article 5.1.1) and
            professional advisers, and to such CROs or other sub-contractors
            provided for under Article 2.3, who need to receive such Samples
            and/or know the Confidential Information in order to fulfil the
            Pilot Study, provided that TMC shall procure that prior to such
            disclosure each of those directors, employees, professional advisers
            and sub-contractors to whom Samples are to be supplied and/or
            Confidential Information is to be disclosed is made aware of the
            obligations of confidentiality and non-use herein contained and
            undertakes, in a manner legally enforceable by ASTRAZENECA, to
            adhere to such terms of this Agreement as if he or she were a party
            to it.

5.2.        Nothing in Article 4 shall preclude the supply of Samples or the
            disclosure of any Confidential Information required by any
            government or regulatory authority or court entitled by law to
            receipt and/or disclosure of the same, or which are required by law
            to be so supplied and/or disclosed, provided that TMC promptly
            notifies ASTRAZENECA when such requirement to supply and/or disclose
            has arisen, to enable ASTRAZENECA to seek an appropriate protective
            order or other secrecy order and to make known to the said
            governmental or regulatory authority or court the proprietary nature
            of the Samples and/or the Confidential Information and to make any
            applicable claim of confidentiality in respect thereof. TMC agrees
            to co-operate in any appropriate action, which ASTRAZENECA may
            decide to take. If TMC is advised to make a supply and/or disclosure
            in accordance with this Article 5 it shall only make such supply
            and/or disclosure to the extent to which it is obliged.

6.          EXCEPTIONS


<PAGE>
                                                                              10

            The provisions of Article 4 shall not apply to any Samples or
            Confidential Information which TMC can demonstrate to the reasonable
            satisfaction of ASTRAZENECA:

6.1.        was already in the possession of TMC and at TMC's free use and
            disposal or in the public domain prior to its disclosure by
            ASTRAZENECA hereunder; or

6.2.        is purchased or otherwise legally acquired by TMC at any time from a
            third party having good title thereto and the right to disclose the
            same; or

6.3.        comes into the public domain, otherwise than through the fault of
            TMC; or

6.4.        is independently generated by TMC without any recourse or reference
            to the Samples or the Confidential Information.

7.          PUBLICATION

7.1.        ASTRAZENECA recognises that TMC may wish to publish or disclose the
            Results, or part thereof, in a lecture, paper in a scientific
            journal, thesis or by other means. It is expressly agreed, however,
            that without ASTRAZENECA's approval in writing TMC may not make any
            publications or disclosure of the Results unless and until TMC has
            provided License Agreement Notice to ASTRAZENECA.

            Should TMC have given License Agreement Notice to ASTRAZENECA, then
            TMC may make publication or disclosure of the Results according to
            the following. In order to avoid loss of patent or other
            Intellectual Property Rights as a result of premature disclosure of
            patentable or other information, TMC shall before any publication or
            disclosure submit to ASTRAZENECA for review at least sixty (60) days
            prior to submission for publication or disclosure any manuscript,
            pre-publications and other pre-disclosure material in its form
            intended for publication or disclosure which contains, or does
            possibly contain, any part of the Results. If ASTRAZENECA within its
            sole discretion determines anything in the received material
            patentable or subject to any other Intellectual Property Rights, TMC
            shall upon ASTRAZENECA's request


<PAGE>
                                                                              11

            delay publication or disclosure for an additional period of ninety
            (90) days from the day of such ASTRAZENECA's request.

            Should ASTRAZENECA by the reasons mentioned above in this paragraph
            reasonably determine that it would need a further period of delay of
            the publication or disclosure concerned, then upon ASTRAZENECA's
            notice in writing to TMC, to be provided prior to the expiration of
            the last 90-days period mentioned in the first paragraph of this
            Article 7.1, TMC shall delay such publication or disclosure for a
            period specified in ASTRAZENECA's notice but not to exceed ninety
            (90) days from the date of such notice.

7.2.        For the avoidance of doubt, such publications contemplated under
            this Article 7 may never, unless exempted from obligations of
            confidentiality according to Article 6, contain Confidential
            Information.

8.          INTELLECTUAL PROPERTY RIGHTS

8.1.        In consideration of ASTRAZENECA supplying the Samples and disclosing
            the Confidential Information to TMC, TMC hereby agrees that any
            Results shall be the exclusive property of ASTRAZENECA, and TMC
            hereby assigns any right and title to any Results to ASTRAZENECA.

8.2.        If any further document or action is necessary, advisable or useful
            for the purpose of confirming, effecting or perfecting ASTRAZENECA's
            rights according to Article 8.1 or for ASTRAZENECA's applications
            for patents or any other Intellectual Property Rights, TMC agrees to
            execute, at ASTRAZENECA's expense, any and all such further
            documents and actions as now mentioned. TMC further undertakes to
            execute any documents and take such actions as provided in this
            Article 8.2 also in relation to any of ASTRAZENECA's Affiliates.

8.3.        Notwithstanding TMC's general reporting obligations under Article
            2.6, TMC warrants that it will promptly disclose to ASTRAZENECA in
            writing any Results.


<PAGE>
                                                                              12

9.          EXCLUSIVE OPTION

9.1.        Entering into effect of the License Agreement

9.1.1.      Should the Final Report, or other report compiled upon completion of
            the Pilot Study containing information sufficient to make the
            appropriate determinations whether the Trigger has been reached,
            whichever is communicated earlier to ASTRAZENECA, show that the
            result of the Pilot Study meets the Trigger, then either Party may
            require that the License Agreement shall enter into force by
            providing written notice thereon ("License Agreement Notice") to the
            other Party.

9.1.2.      Should the Final Report or such other report mentioned in Article
            9.1.1 show that the result of the Pilot Study does not meet the
            Trigger, then TMC may anyhow, at its discretion, require that the
            License Agreement shall enter into force by providing License
            Agreement Notice to ASTRAZENECA.

9.1.3.      Upon the first Party, or, in the situation contemplated by Article
            9.1.2, ASTRAZENECA, receiving License Agreement Notice by the other
            Party ("License Agreement Effective Date") the License Agreement
            shall enter into force in accordance with its terms and conditions.

9.2.        License Agreement not entering into effect

            Should, in the situation contemplated by Article 9.1.1, neither
            Party, or, in the situation contemplated by Article 9.1.2, should
            not TMC, have given License Agreement Notice within ninety (90) days
            of ASTRAZENECA's receipt of the Final Report or such other report
            mentioned in Article 9.1.1, then the License Agreement shall not
            enter into force.

10.         CONFIDENTIALITY MEASURES

10.1.       As part of TMC's undertaking set out in Article 4 to secure the
            confidentiality attaching to the Confidential Information, the
            Samples and the Results, TMC agrees:


<PAGE>
                                                                              13

10.2.       to keep separate all Samples, Confidential Information and Results
            from all other documents and records held by TMC; and

10.3.       to keep all documents and any other material bearing or
            incorporating any of the Confidential Information, the Samples or
            the Results at TMC's usual place of business, namely 5 Sylvan Way,
            Parsippany, New Jersey 07054, United States.

10.4.       not to use, reproduce, transform or store any of the Confidential
            Information, Samples or Results in any externally accessible
            computer or electronic information retrieval system or transmit it
            in any form or by any means whatsoever outside of TMC's usual place
            of business; and

10.5.       to make copies of the Confidential Information, Samples or Results
            only to the extent that the same are strictly required for the
            Purpose; and

10.6.       to notify ASTRAZENECA promptly of the date of, and the circumstances
            involved in, the loss or unauthorised disclosure, if any, of the
            Samples or the Results or any documents, drawings, descriptions,
            writings or formulae comprised in, containing or relating to the
            Confidential Information.

10.7.       Notwithstanding what is stated in Articles 10.3 and 10.4, should TMC
            let, to the extent necessary for the conduct of the Pilot Study,
            such keeping of documents or materials as mentioned in Article 10.3
            or such storage in computer or electronic information retrieval
            systems mentioned in Article 10.4 be made at the premises, or within
            the computer or other such systems, of a CRO or other sub-contractor
            as permitted under Article 2.3, then such keeping or storage shall
            not be considered a violation of such Articles 10.3 or 10.4 provided
            that TMC shall procure that prior to such keeping or storage such
            CRO or other sub-contractor is made aware of the obligations of
            confidentiality and non-use herein contained and undertakes, in a
            manner legally enforceable by ASTRAZENECA, to adhere to such terms
            of this Agreement as if it was a party to it.


<PAGE>
                                                                              14

11.         PUBLICITY AND ANNOUNCEMENTS.

11.1.       Subject to Article 11.2 no press release, announcement or any other
            communication to any Third Party concerning the transaction
            contemplated by this Agreement, the financial terms of this
            Agreement, the subject matter of this Agreement or any ancillary
            matters shall be made or permitted or authorized to be made by
            either Party without the prior written approval of the other, such
            approval not to be unreasonably withheld or delayed and such
            approval to be given by an authorized representative of the Party in
            question. Notwithstanding the above, TMC may make the press
            announcement set forth in Schedule 4 at the Effective Date or in
            immediate connection therewith.

11.2.       Either Party may make an announcement concerning the transaction
            contemplated by this Agreement or any ancillary matter if required
            by law, existing contractual obligations or any securities exchange
            or Regulatory Authority or governmental body to which either Party
            is subject or submits, wherever situated, provided that the Party
            required to make such announcement notifies the other Party of the
            details of the announcement prior to making such announcement and in
            sufficient time for the other Party to consider and comment on the
            announcement, and takes advantage of all provisions to keep
            confidential as many terms of the Agreement as possible.

12.         NO GRANT OF RIGHTS

            Nothing in this Agreement shall be interpreted expressly or implied
            as granting either Party any licence or other rights, except as
            expressly set out in this Agreement.

13.         DISCLAIMER

13.1.       Any Samples so furnished by ASTRAZENECA to TMC hereunder are to be
            treated by TMC as potentially hazardous in handling and use and
            ASTRAZENECA gives no warranty or representation regarding the safety
            or efficacy of the Compound.


<PAGE>
                                                                              15

            ASTRAZENECA represents to TMC that to the best of its knowledge it
            has disclosed to TMC all its knowledge at the Effective Date
            regarding the characteristics of the Compound. Except for the
            representation given in the preceding sentence, ASTRAZENECA
            disclaims any representation or warranty with respect to the
            Compound and ASTRAZENECA shall have no responsibility or liability
            for the use of the Compound by TMC, Principal Investigator, or by
            other TMC's employees or students.

13.2.       ASTRAZENECA makes no representation that the Compound will not
            infringe any patent or other proprietary rights of any third party.

14.         INDEMNITY

14.1.       TMC shall be responsible for and shall indemnify ASTRAZENECA and its
            directors, officers, other employees, agents and consultants
            (collectively the "Indemnified Party") against any and all
            liability, loss, damage, cost and expense (including legal costs)
            incurred or suffered by the Indemnified Party arising out of the
            Pilot Study or arising out of any other activities to be carried out
            by TMC, its Affiliates or sub-contractors pursuant to this Agreement
            except where such liability, loss, damage, cost and expense has been
            incurred or suffered as a result of gross negligence or misconduct
            on the part of ASTRAZENECA.

14.2.       An Indemnified Party that intends to claim indemnification under
            Article 14.1 shall notify TMC promptly of any such liability, loss,
            damage, cost and expense and permit TMC to control the defence and
            disposition thereof and further agrees to reasonably cooperate at
            TMC's expense with TMC in the handling thereof. The Indemnified
            Party shall not compromise or settle the claim. TMC agrees to keep
            ASTRAZENECA informed of the progress in the defence and disputation
            of such claims and to consult with ASTRAZENECA with regard to any
            settlement thereof which TMC proposes to enter into and will provide
            ASTRAZENECA with suitable information regarding the same.


<PAGE>
                                                                              16

15.         TERM AND TERMINATION

15.1.       This Agreement shall enter into force on the Effective Date and
            shall expire (i) in accordance with what is stated in Article 2.4;
            or (ii) at the License Agreement Effective Date; or (iii) at the
            date when it can be determined, pursuant to Article 9.2, that the
            License Agreement will not enter into effect, whichever of (i)
            through (iii) that is the earliest to occur.

            Should, however, TMC not have provided to ASTRAZENECA the Final
            Report within fifteen (15) months of the date of delivery to TMC of
            such number of Samples indicated in Article 2.1, then ASTRAZENECA
            shall have the right to terminate this Agreement forthwith by giving
            written notice to TMC.

15.2.       If either party is in material default hereunder, the other party
            may terminate this Agreement at any time upon thirty (30) days'
            prior written notice to the defaulting party, whereupon this
            Agreement shall so terminate unless the fault is rectified by the
            defaulting party within said notice period.

15.3.       To the extent permitted by law, if either Party shall become
            insolvent or shall make assignment for the benefit of creditors, or
            proceedings in bankruptcy shall be instituted against a Party, or
            proceedings in voluntary bankruptcy of a Party shall be instituted
            by that Party, or a receiver or trustee of all, or substantially
            all, of the property of a Party shall be appointed, the other Party
            shall be entitled to terminate this Agreement by giving written
            notice to this effect to the first Party whereupon this Agreement
            shall immediately terminate.

            Upon termination

15.4.       Upon termination or expiration of this Agreement, or at the request
            of ASTRAZENECA, TMC shall

            (i)   return to ASTRAZENECA any tangible Confidential Information,
                  including any reproduction thereof furnished by or on behalf
                  of ASTRAZENECA or its Affiliates; and


<PAGE>
                                                                              17

            (ii)  return to ASTRAZENECA any Samples delivered by or on behalf of
                  ASTRAZENECA or its Affiliates, unless, and to the extent, such
                  Samples have been used in the course of TMC's performance of
                  the Pilot Study; and

            (iii) deliver to ASTRAZENECA any Results not already reported or
                  delivered to ASTRAZENECA including, without limitation, any
                  draft reports developed by such time should the Final Report
                  not have been delivered to ASTRAZENECA.

15.5.       Survival

15.5.1.     What is stated in Articles 1, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15,
            20 and 21 shall survive termination or expiration of this Agreement.

15.5.2.     What is stated in Article 2.9 shall survive until the expiration of
            the three-months period therein stated, provided that TMC has given
            notice as contemplated therein prior to the date of termination or
            expiration of this Agreement.

15.5.3.     What is stated in Articles 4 and 10 shall survive termination or
            expiration of this Agreement and shall continue to be in force for a
            period of five (5) years following such termination or expiration.

16.         ASSIGNMENT

16.1.       Save as provided in Articles 16.2 and 16.3, a party may not assign,
            transfer, charge or deal in any other manner with this Agreement or
            any of its rights under it, nor purport to do any of the same, nor
            sub-contract any or all of its obligations under this Agreement
            without having obtained the prior written consent of the other
            party.

16.2.       ASTRAZENECA shall be entitled to assign its rights under this
            Agreement to an Affiliate. Any assignment made pursuant to this
            Article 16.2 shall be on the condition that no such assignment shall
            relieve ASTRAZENECA of any of its obligations under this Agreement.


<PAGE>
                                                                              18

16.3.       Each Party shall be entitled to assign its rights under this
            Agreement to an acquiror of all or substantially all of its capital
            or stock assets related to the pharmaceutical business described in
            this Agreement, whether through purchase, merger, consolidation or
            otherwise.

17.         AGREEMENT TO PREVAIL

            This Agreement shall not affect the validity of the CDA, provided,
            however, that in case of any inconsistency between this Agreement
            and the CDA what is stated in this Agreement shall prevail.

18.         SEVERANCE

            If any provision of this Agreement shall be found by any court or
            administrative body of competent jurisdiction to be invalid or
            unenforceable, such invalidity or unenforceability shall not affect
            the other provisions of this Agreement which shall remain in full
            force and effect.

19.         DAMAGES

            Each of the Parties agrees that damages may not be an adequate
            remedy for breach of this Agreement and accordingly ASTRAZENECA
            shall be entitled to injunctive or other equitable relief and no
            proof of special damages shall be necessary for the enforcement of
            this Agreement.

20.         GOVERNING LAW AND ARBITRATION

20.1.       The Parties shall use their reasonable efforts to settle amicably
            any dispute arising out of or in connection with this Agreement. In
            case the Parties are not able to settle such dispute between
            themselves, such dispute shall be finally resolved by arbitration in
            accordance with the Rules of the International Chamber of Commerce.
            The arbitration proceedings shall be held in London. Any proceedings
            shall be held in the English language.

20.2.       The validity, construction and interpretation of this Agreement and
            any determination of the performance which it requires shall be
            governed by the laws of England.


<PAGE>
                                                                              19

21.         NOTICES

            Any notice permitted or required under this Agreement shall be in
            writing and directed to the following respective addresses and shall
            be deemed given, in case of lack of proof of earlier receipt, four
            (4) days upon dispatch if sent by prepaid registered mail.

            If to ASTRAZENECA:

            Address: AstraZeneca AB, S-151 85 Sodertalje, Sweden
            Facsimile: +46-8 553 290 00
            For the attention of: President & CEO

            If to TMC:

            Address: The Medicines Company, 5 Sylvan Way, Parsippany,
            New Jersey 07054, United States
            Facsimile: +1-973-656-9898
            For the attention of: Clive Meanwell, Executive Chairman

                        with a copy to

            Steven D. Singer
            Hale and Dorr, LLP
            60 State Street
            Boston MA 02109
            United States

22.         AGENCY, PARTNERSHIP OR JOINT VENTURE EXCLUDED

22.1.       Nothing in this Agreement shall be construed so as to constitute
            either Party to be the agent of the other.


<PAGE>
                                                                              20

22.2.       Nothing in this Agreement and no action taken by the Parties
            pursuant to this Agreement shall constitute a partnership or joint
            venture of any kind between the Parties.

23.         ENTIRE AGREEMENT

            Each of the Parties acknowledges and agrees that in entering into
            this Agreement, and the documents referred to in it, it does not
            rely on, and shall have no remedy in respect of, any statement,
            representation, warranty or understanding (whether negligently or
            innocently made) of any person or entity (whether party to this
            Agreement or not) other than as expressly set out in this Agreement
            as a warranty. Nothing in this Article shall either operate to limit
            or exclude any liability for fraud.

24.         VARIATION

            No variation of this Agreement or any of the documents referred to
            in it shall be valid unless it is in writing and signed by or on
            behalf of each of the Parties.

25.         WAIVER

            Failure or delay by either Party to exercise any right or remedy
            under this Agreement shall not be deemed to be a waiver of that
            right or remedy, or prevent it from exercising that or any other
            right or remedy on that occasion or on any other occasion.

IN WITNESS WHEREOF, the Parties have executed this Agreement on the Effective
Date.


ASTRAZENECA AB (publ)                         THE MEDICINES COMPANY

/s/ Hamish Cameron                            /s/ Clive Meanwell
---------------------------------             ----------------------------------
Name: Dr. Hamish Cameron                      Name: Clive Meanwell
Title: Vice President, Head                   Title: Executive Chairman
       Cardiovascular Therapy Area


<PAGE>


                                   SCHEDULE 1

                                    Compound

SCHEDULE 1, COMPOUND

CHEMICAL STRUCTURE, CHEMICAL NAME AND MOLECULAR FORMULA

Chemical structure

[BOX]

Figure 1. Chemical structure of clevidipine

Chemical name

Butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-
pyridinedicarboxylate.

Molecular weight

456.3 g/mol.

Molecular formula

C(21)H(23)Cl(2)NO(6)


<PAGE>


                                   SCHEDULE 2

                               License Agreement



<PAGE>
Schedule 2

                                LICENSE AGREEMENT

                 Entered into by and between AstraZeneca AB and
          The Medicines Company on the License Agreement Effective Date


<PAGE>
                                TABLE OF CONTENTS



<TABLE>
<CAPTION>
Article                                                                   Page
-------                                                                   ----
<S>                                                                       <C>
1.    Definitions                                                           2
2.    Grant of License                                                     11
3.    Development and Commercialisation                                    14
4.    Supply Matters                                                       23
5.    Exchange of Information                                              25
6.    Consideration                                                        28
7.    Intellectual Property - Prosecution and Maintenance                  35
8.    Claims Regarding Infringement and Invalidity                         37
9.    Trademark                                                            42
10.   Indemnity                                                            45
11.   Confidentiality                                                      47
12.   Adverse Events                                                       49
13.   Representation and Warranty                                          50
14.   Term and Termination                                                 53
15.   Consequences of Termination                                          55
16.   Force Majeure                                                        58
17.   General Provisions                                                   59
           - Assignment                                                    59
           - Severance                                                     60
           - Notices                                                       60
           - Contact Information                                           61
           - Agency, Partnership or Joint Venture Excluded                 62
           - Entire Agreement                                              62
           - Agreement to Supersede earlier Agreements                     62
           - Amendments                                                    62
           - Publicity and Announcements                                   62
           - Waiver                                                        63
           - No Benefit to Third Parties                                   63
18.   Governing Law and Arbitration                                        63
</TABLE>




                                     - i -


<PAGE>
                                                                               1


Schedule 2
                                LICENSE AGREEMENT

This Agreement is entered into on the License Agreement Effective Date

by and between

ASTRAZENECA AB, a company incorporated under the laws of Sweden with its
registered office at S-151 85 Sodertalje, Sweden ("ASTRAZENECA") and

THE MEDICINES COMPANY, a company incorporated under the laws of Delaware with
its registered office at One Cambridge Center, Cambridge, Massachusetts 02142,
United States ("TMC");

                                   WITNESSETH

WHEREAS, ASTRAZENECA performs research, development and marketing of
pharmaceutical compounds and products inter alia in the cardiovascular therapy
area; and

WHEREAS, ASTRAZENECA has developed the intravenous product Clevidipine for
indications such as the control of blood pressure; and

WHEREAS, TMC performs development of pharmaceutical compounds and marketing of
pharmaceutical products particularly in the cardiovascular therapy area; and

WHEREAS, ASTRAZENECA has expressed an interest to license Clevidipine to TMC and
TMC has expressed an interest to license said compound; and

WHEREAS, it is a mutual objective of the Parties to maximise the sales of the
Product.

NOW THEREFORE, the Parties hereto agree to the following.


<PAGE>
                                                                               2


1.          DEFINITIONS

When used in this Agreement the following expressions shall have the meanings
defined herein. The singular form of the defined expression shall include the
plural form thereof and vice versa.

1.1.        "Adverse Event" shall mean the development of an undesirable medical
            condition or the deterioration of a pre-existing medical condition
            following or during exposure to a pharmaceutical product whether or
            not considered causally related to such product.

1.2.        "ANDA Act" shall have the meaning defined in Article 8.3.1(a).

1.3.        "Affiliate" with respect to a Person shall mean any other Person
            that directly, or indirectly through one or more intermediaries,
            controls, is controlled by or is under common control with such
            Person. For the purposes of this Article 1.3 only, "control" and,
            with correlative meanings, the terms "controlled by" and "under
            common control with", shall mean (a) the possession, directly or
            indirectly, of the power to direct the management or policies of a
            Person, whether through the ownership of voting securities, by
            contract or otherwise, and/or (b) the ownership, directly or
            indirectly, of more than fifty percent (50%) of the voting
            securities or other ownership interest of a Person.

1.4.        "Agreement" shall mean this document including any and all
            schedules, appendices and other addenda to it as may be changed,
            added and/or amended from time to time in accordance with the
            provisions of this Agreement.

1.5.        "ASTRAZENECA IP" shall mean the ASTRAZENECA Patent Rights, the
            ASTRAZENECA Know-How and, subject to what is stated in Article 9.1,
            the ASTRAZENECA Trademark.


<PAGE>
                                                                               3


1.6.        "ASTRAZENECA Indemnified Party" shall have the meaning defined in
            Article 10.1.1.

1.7.        "ASTRAZENECA Know-How" shall mean any Know-How relating to the
            Compound and/or the Product, developed, acquired or licensed by
            ASTRAZENECA prior to the License Agreement Effective Date and in
            ASTRAZENECA's possession at the License Agreement Effective Date.

1.8.        "ASTRAZENECA Patent Rights" shall mean the patents and patent
            applications as set out in Schedule A and any Patent Rights claiming
            priority thereto.

1.9.        "ASTRAZENECA Trademark" shall mean the trademark Clevelox(TM) which
            ASTRAZENECA as of the License Agreement Effective Date has
            registered for the Product in the countries set forth in Schedule B.

1.10.       "Combination Product" shall mean any pharmaceutical product in a
            finished dosage form which comprises the Compound and at least one
            other active pharmaceutical ingredient.

1.11.       "Commercially Reasonable Efforts" shall mean with respect to the
            efforts to be expended by a Party with respect to any objective, the
            use of reasonable, diligent, good faith efforts to accomplish such
            objective as such Party would normally use to accomplish a similar
            objective under similar circumstances, it being understood and
            agreed that with respect to the research, development or
            commercialisation of Product, such efforts shall be substantially
            equivalent to those efforts and resources commonly used by a Party
            for a product owned by it or to which it has rights, which product
            is at a similar stage in its development or product life and is of
            similar market potential taking into account efficacy, safety,
            Regulatory Authority-approved labelling, the competitiveness of
            alternative products in the marketplace, the patent and other
            proprietary position of the Product, the likelihood of regulatory
            approval given the regulatory structure involved,


<PAGE>
                                                                               4


            the profitability of the Product taking into account the royalties
            payable to licensors of patent or other intellectual property
            rights, alternative products and other relevant commercial factors.
            Commercially Reasonable Efforts shall be determined on a
            country-by-country basis for the Product, and it is anticipated that
            the level of effort will change over time (including, to the extent
            appropriate, the reduction or cessation of active promotional
            efforts), reflecting changes in the status of the Product and the
            market(s) involved

1.12.       "Compound" shall mean ASTRAZENECA's proprietary compound named
            Clevidipine with the chemical structure as shown in Schedule C,
            attached hereto, including all salts, esters, complexes, chelates,
            hydrates, isomers, stereoisomers, crystalline and amorphous forms,
            prodrugs, solvates, metabolites and metabolic precursors (whether
            active or inactive) thereof.

1.13.       "Confidential Information" shall mean (i) in the case of TMC being
            the receiving Party, ASTRAZENECA IP, and (ii) in the case of
            ASTRAZENECA being the receiving Party TMC IP, and (iii) in the case
            of either Party being the receiving Party, data generated by either
            or both Parties hereunder and trade secrets and/or confidential
            information relating to technology, including but not limited to
            compound(s), composition(s), formulation(s) and/or manufacturing
            information, and/or relating to the business affairs, including but
            not limited to commercial forecasts, plans, programs, customers,
            assets, financial projections, costs and customer lists and/or
            finances of the Disclosing Party, supplied or otherwise made
            available to the Receiving Party or coming into Receiving Party's
            possession in relation to the performance of this Agreement.

1.14.       "Disclosing Party" shall mean the Party which discloses Confidential
            Information to the other Party.

1.15.       "Documents" shall mean reports, research notes, charts, graphs,
            comments, computations, analyses, recordings, photographs, paper,
            notebooks, books, files, ledgers, records, tapes, discs, diskettes,
            CD-ROM, computer programs


<PAGE>
                                                                               5


            and documents thereof, computer information storage means, samples
            of material, other graphic or written data and any other media on
            which Know-How can be permanently or temporarily stored.

1.16.       "European Union" shall mean the countries that are, whether at the
            License Agreement Effective Date or at any time thereafter, members
            of the European Union.

1.17.       "European Economic Area" shall mean the European Union plus Norway,
            Iceland and Liechtenstein.

1.18.       "FDA" shall mean the United States Food and Drug Administration or
            any successor agency thereto.

1.19.       "FTE Day" shall mean the equivalent of one person employed by
            ASTRAZENECA or TMC, as applicable, or their respective Affiliates
            full time for one day.

1.20.       "Filing of an NDA" shall mean the date of acceptance for review by
            the competent registration body in a given country of an NDA.

1.21.       "Force Majeure" shall mean any cause preventing either Party from
            performing any or all of its obligations which arises from or is
            attributable to acts, events, omissions or accidents beyond the
            reasonable control of the Party so prevented, act of God, war, riot,
            civil commotion, malicious damage, accident, breakdown of plant or
            machinery, fire, flood or storm.

1.22.       "Fresenius" shall mean Fresenius Kabi Nutrition AB, S-751 74
            Uppsala, Sweden.

1.23.       "Launch" or "Launched" shall mean the first invoiced commercial sale
            by TMC, its Affiliates, sub-licensees or distributors, however not
            including sales made by one such entity to another such entity, of
            the Product in a country following NDA Approval in such country.


<PAGE>
                                                                               6


1.24.       "Know-How" shall mean technical and other information, which is not
            subject to published patent rights and which is not in the public
            domain, including, but not limited to, information comprising or
            relating to concepts, discoveries, data, designs, formulae, ideas,
            inventions, methods, models, assays, research plans, procedures,
            designs for experiments and tests and results of experimentation and
            testing, including results of research or development, processes,
            including manufacturing processes, specifications and techniques,
            laboratory records, chemical, pharmacological, toxicological,
            clinical, analytical and quality control data, trial data, case
            report forms, data analyses, reports, manufacturing data or
            summaries and information contained in submissions to and
            information from ethical committees and regulatory authorities.
            Know-How includes Documents containing Know-How, including but not
            limited to any rights including trade secrets, copyright, database
            or design rights protecting such Know-How. The fact that an item is
            known to the public shall not be taken to preclude the possibility
            that a compilation including the item, and/or a development relating
            to the item, is not known to the public.

1.25.       "License Agreement Effective Date" shall have the meaning defined in
            the Option Agreement.

1.26.       "Major Market" shall mean each of [**] and [**]. Further [**] shall
            constitute one Major Market.

1.27.       "NDA" shall mean a fully completed marketing license application
            comparable to a New Drug Application filed with the FDA, including
            all supporting documentation and data required for such application
            to be accepted for review by the competent health regulatory
            authorities for any country requesting approval for
            commercialisation of the Product for a particular indication in such
            country. NDA as herein defined shall for this purpose include
            applications for pricing or reimbursement approval where
            appropriate.


<PAGE>
                                                                               7


1.28.       "NDA Approval" shall mean the approval by the competent registration
            body for a given country of an NDA.

1.29.       "Net Sales" shall mean the gross sales of Product by a Party or its
            Affiliates, and, regarding sales in the United States, its
            sub-licensees or distributors, to Third Parties after deduction of:

            a)    [**] and/or [**];

            b)    amounts [**] determined in good faith;

            c)    [**] such sales; and

            d)    [**] the Product.

            In the event the Product is sold as part of a Combination Product,
            the Net Sales from the Combination Product, for the purposes of
            determining royalty payments, shall be determined by multiplying the
            Net Sales of the Combination Product (as defined in the standard Net
            Sales definition), during the applicable royalty reporting period,
            by the fraction, A/A+B, where A is the average sale price of the
            Product when sold separately in finished form and B is the average
            sale price of the other product(s) included in the Combination
            Product when sold separately in finished form, in each case during
            the applicable royalty reporting period or, if sales of both the
            Product and the other product(s) did not occur in such period, then
            in the most recent royalty reporting period in which sales of both
            occurred, as adjusted, as necessary, for inflation from the date
            when both the Product and all other product(s) last were sold and
            the date of determination of Net Sales under this Article 1.29. In
            the event that such average sale price


<PAGE>
                                                                               8


            cannot be determined for both the Product and all other products(s)
            included in the Combination Product, Net Sales for the purposes of
            determining royalty payments shall be calculated by multiplying the
            Net Sales of the Combination Product by the fraction of C/C+D where
            C is the fair market value of the Product and D is the fair market
            value of all other pharmaceutical product(s) included in the
            Combination Product. In such event, the selling Party shall in good
            faith make a determination of the respective fair market values of
            the Product and all other pharmaceutical products included in the
            Combination Product, and shall notify the other Party of such
            determination and provide the other Party with data to support such
            determination. The other Party shall have the right to review such
            determination and supporting data, and to notify the selling Party
            if it disagrees with such determination. If the other Party does not
            agree with such determination and if the Parties are unable to agree
            in good faith as to such respective fair market values, then such
            matter shall be referred to arbitration pursuant to Article 18.1.

            Net Sales shall exclude (i) the transfer of a commercially
            reasonable quantity of free samples of Product to be given out to
            customers for promotional purposes; (ii) the transfer of Product for
            use in clinical trials; and (iii) the sales or transfers of Product
            among a Party and its Affiliates, and, in the United States, its
            sub-licensees or distributors, unless the receiver is the consumer
            or user of the Product; however, the resale or transfer of such
            Product to a Third Party shall be included in Net Sales.

            Product sold or otherwise transferred (x) in other than an arms
            length transaction or for other property (e.g. barter); or (y) where
            no separate price has been decided for the Product but a price is
            decided jointly for the Product plus at least one other product,
            shall be deemed invoiced at its fair market price in the country of
            sale or transfer.

            It is acknowledged that sub-licensees of a Party or its Affiliates
            and conventional distributors whose function is to purchase and
            resell Product,


<PAGE>
                                                                               9


            will be considered Third Parties when referring to Product sold
            outside the United States. The Parties agree further that for the
            purpose of the first paragraph of this Article 1.29 the Net Sales of
            the Product outside the United States by TMC or its Affiliates to
            such sub-licensees and distributors shall be the Net Sales received
            by TMC or its Affiliates from such sub-licensee or distributor for
            the Product or [**] percent ([**]%) of the actual gross sales, less
            deductions under subsections (a) through (d) above, of the Product
            by such sublicensee or distributor, whichever amount is the higher.

1.30.       "Option Agreement" shall mean the Study and Exclusive Option
            Agreement entered into by and between the Parties on 5 March 2002.

1.31.       "Party" or "Parties" shall mean TMC and/or ASTRAZENECA.

1.32.       "Patent Rights" shall mean patent applications and patents, utility
            models, utility certificates, certificates of addition and all
            foreign counterparts of them in all countries, including any
            divisional applications and patents, refilings, renewals,
            continuations, continuations-in-part, patents of addition,
            extensions (including patent term extensions), reissues,
            substitutions, confirmations, registrations, revalidations, pipeline
            and administrative protections and additions, and any equivalents of
            the foregoing in any and all countries of or to any of them, as well
            as any supplementary protection certificates and equivalent
            protection rights in respect of any of them.

1.33.       "Person" shall mean an individual, sole proprietorship, partnership,
            limited partnership, limited liability partnership, corporation,
            limited liability company, business trust, joint stock company,
            trust, unincorporated association, joint venture or other similar
            entity or organization, including a government or political
            subdivision, department or agency of a government.

1.34.       "Procedure" shall have the meaning defined in Article 3.5.1.


<PAGE>
                                                                              10


1.35.       "Product" shall mean any pharmaceutical formulation or product for
            intravenous application containing the Compound as the sole active
            ingredient in a finished dosage form suitable for administration to
            patients. Apart from in this Article 1.35, and unless the context
            clearly requires otherwise in this Agreement, when mentioned in this
            Agreement Product shall be deemed to include Combination Product.

1.36.       "Phase III Clinical Trial" shall mean a large scale, pivotal
            multicentre, human clinical trial to be conducted in a number of
            patients estimated to be sufficient to establish safety or efficacy
            in the particular claim and indication and at a standard suitable to
            obtain NDA Approval.

1.37.       "Receiving Party" shall mean the Party which receives Confidential
            Information from the other Party.

1.38.       "Results" shall have the meaning defined in Article 7.8.

1.39.       "Supply Agreement" shall have the meaning described in Article
            4.3.1.

1.40.       "TMC IP" shall mean TMC Know-How and TMC Patent Rights.

1.41.       "TMC Indemnified Party" shall have the meaning defined in Article
            10.2.1.

1.42.       "TMC Know-How" shall mean any Know-How relating directly to the
            Compound and/or the Product developed, acquired or licensed by TMC
            during the term of this Agreement.

1.43.       "TMC Patent Rights" shall mean any Patent Rights directly relating
            to the Compound and/or the Product developed, acquired or licensed
            by TMC during the term of this Agreement.

1.44.       "TMC Trademark" shall have the meaning defined in Article 9.1.

1.45.       "Territory" shall mean any country in the world except Japan.


<PAGE>
                                                                              11


1.46.       "Third Party" shall mean any Person not including the Parties or the
            Parties' respective Affiliates.

2.          GRANT OF LICENSE

2.1.        License Grant. ASTRAZENECA hereby grants to TMC an exclusive license
            in the Territory under the ASTRAZENECA IP to perform research on,
            have research performed on, develop, have developed, use, have used,
            make, have made, import, have imported, market, have marketed, sell
            and have sold the Compound and the Product for all indications.
            Notwithstanding the foregoing, TMC's license to the ASTRAZENECA
            Trademark included in the license now granted shall be subject to
            what is stated in Article 9.1.

2.2.        Grant to TMC's Affiliates. TMC's Affiliates shall have the benefit
            and burden of the licenses and rights set out in Article 2.1 for the
            same purposes and under the same conditions as set forth herein,
            provided that TMC shall remain fully responsible for the compliance
            by such Affiliates with the terms and conditions of this Agreement
            as if such Affiliates were TMC hereunder.

2.3.        Right to Sublicense. TMC shall have the right to grant sub-licenses
            to the rights granted under Article 2.1, provided that TMC shall
            notify ASTRAZENECA of each such sublicense without unreasonable
            delay following any such grant of sub-license. TMC shall ensure that
            all of its sub-licensees will comply with all terms and conditions
            of this Agreement and TMC shall remain fully responsible for the
            compliance by such sub-licensees with the terms and conditions of
            this Agreement as if such sub-licensees were TMC hereunder.

2.4.        Right to Appoint Distributors. TMC shall also have the right to
            appoint distributors in the Territory for the sale of the Product.
            TMC shall at all


<PAGE>
                                                                              12


            times ensure that its distributors act fully in compliance with the
            terms and conditions of this Agreement.

2.5.        Duration of License Grant. The licenses set out in Article 2.1 shall
            continue in accordance with what is stated therein on a
            country-by-country basis until royalty payment is no longer due in
            the country concerned in accordance with what is stated in Article
            6.4, except for the license to the ASTRAZENECA Trademark which shall
            be governed by what is stated in Article 6.5. The licenses set out
            in Article 2.1 shall, subject again to what is stated in Article 6.5
            regarding the license to the ASTRAZENECA Trademark, thereafter
            continue on a non-exclusive basis and become fully paid up and
            royalty-free in the country concerned.

2.6.        First Right of Refusal of TMC regarding Japan. Should ASTRAZENECA
            within its sole discretion at any time determine that ASTRAZENECA
            will not Launch the Product in Japan and/or that ASTRAZENECA will
            not license, transfer or otherwise dispose of its interest in the
            ASTRAZENECA IP regarding Japan, then ASTRAZENECA shall offer to TMC,
            by providing written notice, the first right to negotiate a license
            on exclusive rights to commercially exploit the Compound and the
            Product under the ASTRAZENECA IP in Japan on terms similar to those
            under this Agreement. Should TMC wish to exercise such right, then
            TMC shall notify ASTRAZENECA hereof in writing no later than ninety
            (90) days upon receipt of ASTRAZENECA's notice. In reasonable
            connection with such notice the Parties shall enter into good faith
            negotiations using their reasonable endeavours to reach a mutually
            acceptable agreement providing for such TMC's commercial
            exploitation as mentioned in this Article 2.6.

2.7.        TMC Grant of Rights to ASTRAZENECA Regarding Japan.

2.7.1.      In consideration of the rights granted by ASTRAZENECA hereunder, TMC
            hereby grants to ASTRAZENECA, at no cost or remuneration, a
            sub-licensable non-exclusive license under the TMC IP to perform
            research on,


<PAGE>
                                                                              13


            have research performed on, develop, have developed, use, have used,
            make, have made, import, have imported, market, have marketed, sell
            and have sold the Compound and the Product for all indications in
            Japan.

2.7.2.      TMC shall for the purpose of the license granted in Article 2.7.1
            make available to ASTRAZENECA, upon ASTRAZENECA's request, any
            Filings of an NDA in the Territory, any NDA Approvals obtained in
            the Territory and any related documents and any TMC's correspondence
            with any regulatory authorities in the Territory regarding any such
            Filing of an NDA, NDA Approval or related issues, and shall allow
            ASTRAZENECA to make cross-references to any such Filing of an NDA or
            NDA Approval in the Territory. For any services or assistance
            performed by TMC pursuant to this Article 2.7.2, ASTRAZENECA shall
            reimburse TMC for TMC's out-of-pocket costs for such activities plus
            [**] U.S. Dollars ($[**]) per FTE Day.

2.7.3.      Should TMC have selected the TMC Trademark in the Territory, then
            the license under Article 2.7.1 shall include an exclusive right and
            license for ASTRAZENECA to utilize the TMC Trademark in Japan.
            Should ASTRAZENECA use the TMC Trademark in connection with the
            sales and marketing of Product in Japan, then ASTRAZENECA shall pay
            to TMC a running royalty of [**] percent ([**]%) on the annual Net
            Sales of the Product in Japan.

2.8.        Section 365(n) of Title 11. All rights and licenses granted under or
            pursuant to any section of this Agreement, including amendments
            hereto, are, for all purposes of Section 365(n) of Title 11 of the
            United States Bankruptcy Code ("Title 11"), licenses of rights to
            "intellectual property" as defined in Title 11. The Parties shall
            retain and may fully exercise all of their respective rights under
            this Agreement pursuant to Title 11. Rejection of this Agreement
            pursuant to Section 365 of Title 11 constitutes a material breach of
            this Agreement and entitles the aggrieved Party to terminate this
            Agreement for material breach upon written notice. Upon bankruptcy
            of


<PAGE>
                                                                              14


            either Party, the non-bankrupt Party shall further be entitled to a
            complete duplicate of (or complete access to, as appropriate) any
            such intellectual property, and such, if not already in its
            possession, shall be promptly delivered to the non-bankrupt Party,
            unless the bankrupt Party elects to continue, and continues, to
            perform all of its obligations under this Agreement.

3.          DEVELOPMENT AND COMMERCIALIZATION

3.1.        Transfer of ASTRAZENECA Know-How. Without unreasonable delay
            following the License Agreement Effective Date, ASTRAZENECA shall
            make available and transfer to TMC the following ASTRAZENECA
            Know-How.

            a)    a description of the process used by ASTRAZENECA for the
                  manufacturing of the Compound intended for Phase III Clinical
                  Trials and a summary report of the development of such
                  process;

            b)    a description of the process, available to AstraZeneca at the
                  License Agreement Effective Date, for the manufacture of the
                  [**] to be used for the manufacturing of the Compound;

            c)    a description of the analytical methods and validation reports
                  for the starting materials and intermediates to be used in the
                  manufacturing of the Compound.

                  It is acknowledged that at the License Agreement Effective
                  Date some of those analytical methods are not fully developed
                  and validated, and such development and validation will not be
                  continued or completed by ASTRAZENECA. ASTRAZENECA


<PAGE>
                                                                              15


                  will, however, provide a summary report of the status of these
                  methods at the License Agreement Effective Date;

            d)    the description of the tentative test-methods used by
                  ASTRAZENECA for validating the bulk Compound manufactured, and
                  a brief summary of the validation done thereon by ASTRAZENECA;

            e)    to the extent available to ASTRAZENECA at the License
                  Agreement Effective Date, reference and analytical standard
                  compounds to be used as reference material in the conduct of
                  comparative analyses in relation to the manufacturing process
                  with the Compound. It is explicitly understood that no such
                  compound may be used for any other purpose than the purpose
                  now stated;

            f)    a description of all ASTRAZENECA Know-How relating to clinical
                  trials conducted by ASTRAZENECA using the Product prior to the
                  License Agreement Effective Date.

            g)    reports, the names of which are set forth in Schedule D,
                  containing ASTRAZENECA Know-How relating to the manufacturing
                  of the Compound.

            Any documents contemplated by this Article 3.1 shall be in English
            when transferred to TMC.

3.2.        Third Party Manufacturers.

3.2.1.      It is acknowledged that TMC may present the ASTRAZENECA Know-How
            described under Article 3.1 to Third Party manufacturers for the
            purposes permitted under Article 11.2.4. TMC shall notify
            ASTRAZENECA in writing regarding the date of submission of such
            information to any such Third Party manufacturer(s). ASTRAZENECA
            shall in this connection assist TMC to address questions raised
            about such


<PAGE>
                                                                              16


            ASTRAZENECA Know-How by no more than three (3) of such Third Party
            manufacturer(s) selected by TMC, during a period of three (3) months
            from the date of presentation of such ASTRAZENECA Know-How to the
            Third Party manufacturer concerned. ASTRAZENECA shall also provide
            TMC with advice on the technical merits of proposals regarding
            manufacturing of the Compound brought forward by such Third Party
            manufacturer(s). Any assistance provided under this Article 3.2.1
            may be given by telephone or e-mail or by other appropriate means as
            agreed by the Parties.

3.2.2.      ASTRAZENECA undertakes to participate in no more than one (1)
            meeting in person with one Third Party manufacturer, selected by
            TMC, to outline details of the manufacturing synthesis regarding the
            Compound, provided that such meeting shall take place at
            ASTRAZENECA's manufacturing site in Sodertalje, Sweden.

3.2.3.      ASTRAZENECA further undertakes, should TMC not have exercised its
            right under Article 2.9 of the Option Agreement, upon having
            received written notice from TMC, for a period of three (3) months
            starting sixty (60) days upon ASTRAZENECA's receipt of such notice,
            to assist TMC, by telephone, e-mail or other appropriate means as
            agreed by the Parties, in TMC's discussions with Fresenius in
            connection with Fresenius' restart of the formulation program
            regarding the Product. The Parties agree, however, that TMC may not
            give such notice contemplated above in this Article 3.2.3 later than
            eight (8) months of the License Agreement Effective Date.

3.2.4.      ASTRAZENECA agrees to provide reasonable assistance to the Third
            Party manufacturer selected by TMC, by telephone, e-mail or other
            appropriate means as agreed by the Parties, in connection with the
            start-up of manufacturing operations for the Product for a period of
            twelve (12) months following commencement of process development by
            such contract manufacturer or fifteen (15) months of the License
            Agreement Effective Date, whichever is the earliest to occur.


<PAGE>
                                                                              17


3.3.        Duration of and Compensation for Assistance by ASTRAZENECA.

3.3.1.      The Parties agree that any assistance to be provided by ASTRAZENECA
            under Articles 3.1, 3.2 and 3.5.1 shall be given to an extent
            necessary and reasonable and shall be given only within the first
            four (4) years of the License Agreement Effective Date and shall not
            in total exceed [**]. It is acknowledged that ASTRAZENECA may at its
            discretion carry out any such assistance for up to [**] percent
            ([**]%) of such [**] by using Third Party consultants.

3.3.2.      For any services or assistance performed by ASTRAZENECA pursuant to
            Article 3.3.1, TMC shall reimburse ASTRAZENECA for ASTRAZENECA's
            out-of-pocket costs for such activities plus [**] U.S. Dollars
            ($[**]) [**]. Should ASTRAZENECA use a Third Party consultant(s) for
            carrying out assistance for a certain FTE Day, or part thereof,
            then, for the avoidance of doubt, the FTE Day rate now stated shall
            apply thereon, and the out-of-pocket costs for consultants, if any,
            as indicated above in this paragraph, shall apply only to costs for
            consultants which would typically have been incurred should the
            assistance have been actually carried out by an employee(s) of
            ASTRAZENECA or its Affiliates.

3.3.3.      ASTRAZENECA shall invoice TMC for all assistance during each
            relevant time period within thirty (30) days of the expiration of
            each calendar half-year.

3.4.        Development of Product.

3.4.1.      TMC shall, subject to the obligations stated in this Article 3 and
            in Article 5, carry out the development work permitted hereunder
            within its sole discretion and at its own cost and expense.


<PAGE>
                                                                              18


3.4.2.      TMC shall use Commercially Reasonable Efforts to develop Product up
            until the stage of Filing of an NDA in each country of the
            Territory.

3.5.        Regulatory Filings.

3.5.1.      TMC shall be responsible for the preparation, submission and
            prosecution of all Filings of an NDA in each country in which TMC,
            its Affiliates, sub-licensees or distributors will sell Product.
            TMC, its Affiliates, sub-licensees or distributors shall be the
            owner and party of record for all such filings, applications and
            approvals. ASTRAZENECA agrees to provide assistance requested by TMC
            as reasonably necessary for preparation and prosecution of such
            filings and applications in the European Union (it being
            contemplated that such filings and applications will be done by
            using the then most efficient centralised procedure for applying for
            and obtaining multi-country NDAs in the European Union (the
            "Procedure")), and in the United States. TMC shall reimburse
            ASTRAZENECA for any costs and expenses incurred in such assistance.
            TMC shall be responsible for any costs associated with preparation,
            submission and prosecution of all such Filing of an NDA and NDA
            Approvals required.

3.5.2.      TMC shall, at its own expense, use Commercially Reasonable Efforts
            in Filing of an NDA and prosecution thereof and in obtaining NDA
            Approvals in its own name or in the name of its Affiliate(s) in each
            Major Market and other country of the Territory.

3.5.3.      Regarding any country in the European Union where TMC makes a Filing
            of an NDA, TMC shall for such purpose use the Procedure, unless TMC
            can clearly establish that Filing of an NDA regarding one or more
            separate countries within the European Union would be more
            advantageous to the Product from a regulatory or commercial
            perspective.


<PAGE>
                                                                              19


3.5.4.      TMC shall promptly inform ASTRAZENECA in writing of any Filing of an
            NDA and of any NDA Approval, and shall in immediate connection
            therewith provide ASTRAZENECA with a written summary of any such
            Filing of an NDA and NDA Approval, or with a copy thereof, whichever
            ASTRAZENECA may elect.

3.5.5.      Following NDA Approval in a certain Major Market or other country of
            the Territory TMC shall use its Commercially Reasonable Efforts to
            Launch the Product in such Major Market or other country

3.6.        Marketing and Sales of Product.

3.6.1.      Regarding any country of the Territory where the Product is
            Launched, TMC shall promptly inform ASTRAZENECA writing of the
            occurrence of such Launch.

3.6.2.      TMC shall, in each Major Market or other country of the Territory
            where the Product has been Launched, at its own expense, or the
            expense of its Affiliates, sub-licensees or distributors, use
            Commercially Reasonable Efforts to market and sell the Product.

3.6.3.      For the avoidance of doubt, what is stated regarding the obligations
            of TMC in this Article 3 or elsewhere in this Agreement shall always
            be subject to what is stated in Articles 2.2 and 2.3, such that any
            of TMC's obligations may be performed by one or more of TMC's
            Affiliates or sublicensees. Further, in accordance with what is
            stated in Article 2.4, any of TMC's obligations under this Article
            3.6 and under Article 3.7 may be performed by one or more of TMC's
            distributors.

3.7.        Specific Time Limits for Performance. Notwithstanding what is stated
            in Articles 3.4.2, 3.5.2, 3.5.5 and 3.6.2, and without limiting the
            general performance criteria stated therein, the following
            performance criteria stated in this Article 3.7 shall apply to the
            situations herein described.


<PAGE>
                                                                              20


3.7.1.      Time Limit for entering into Phase III Clinical Trials.

            TMC shall no later than [**] have made the first dosing of a patient
            in a Phase III Clinical Trial regarding the Compound.

3.7.2.      Time Limit for Filing of an NDA.

            (a)   TMC shall no later than [**] have made a Filing of an NDA in
                  the United States.

            (b)   TMC shall no later than [**] or [**] after having made a
                  Filing of an NDA in the United States, whichever is the
                  earlier, have made a Filing of an NDA in at least three (3)
                  additional Major Markets, provided, however, that if such
                  Filing of an NDA has been made in the European Union then such
                  one (1) Major Market shall be sufficient.

            (c)   TMC shall no later than [**] or [**] after having made the
                  last Filing of an NDA under Article 3.7.2(b), whichever is the
                  earlier, have made a Filing of an NDA in all Major Markets.

3.7.3.      Time Limit for Launch of the Product

            TMC shall no later than [**] following NDA Approval in any Major
            Market Launch the Product in the country(ies) concerned.

3.8.        Remedy for Failure.

3.8.1.      Non-Compliance.

            Should TMC at any time not comply with the applicable criteria of
            performance as set forth in Articles 3.4.2, 3.5.2, 3.5.5, 3.6.2,
            3.7.1, 3.7.2 or 3.7.3, then TMC shall promptly so notify ASTRAZENECA
            in writing.


<PAGE>
                                                                              21


            (i)   In case of non-compliance with the performance criteria set
                  forth in Articles 3.4.2 or 3.7.1 ASTRAZENECA shall have the
                  right, by giving ninety (90) days written notice to TMC, to
                  require the license granted hereunder to terminate regarding
                  the Compound and the Product, subject to Article 3.8.3.

            (ii)  In case of non-compliance with the performance criteria set
                  forth in Articles 3.5.2, 3.5.5, 3.6.2, 3.7.2 (a) or 3.7.3,
                  ASTRAZENECA shall have the right, by giving ninety (90) days
                  written notice to TMC, to require the license granted
                  hereunder to terminate regarding the Compound and the Product
                  in the Major Market or other country concerned, subject to
                  Article 3.8.3.

            (iii) In case of non-compliance with the performance criteria set
                  forth in Article or 3.7.2 (b) or (c), ASTRAZENECA shall have
                  the right, by giving ninety (90) days written notice to TMC,
                  to require the license granted hereunder to terminate
                  regarding the Compound and the Product in any Major Market(s)
                  other than the Major Market(s) regarding which the performance
                  criteria concerned was fulfilled (and, in the case of
                  non-compliance with Article 3.7.2 (c), the Major Market(s)
                  regarding which such criteria had been fulfilled under Article
                  3.7.2 (b)), subject to Article 3.8.3.

            (iv)  If ASTRAZENECA makes a request under (i), (ii) or (iii) above,
                  and provided that TMC has not remedied the default concerned
                  within the ninety-days period stated, then, provided that
                  ASTRAZENECA notifies TMC in writing hereof within thirty (30)
                  days upon the expiration of such ninety-days period, the
                  license regarding the Major Market or other country
                  contemplated by such notice for the Compound and the Product
                  shall terminate and what is stated in Article 15.1 shall apply
                  regarding such Major Market or other country subject to
                  Article 3.8.3.


<PAGE>
                                                                              22


3.8.2.      Non-compliance regarding the European Union

            Should TMC have failed to comply with any such criteria of
            performance referred to under Article 3.8.1, and should such
            non-compliance relate to the European Union, then TMC shall anyway
            be considered to have fulfilled such performance criteria provided
            always that the countries within the European Union to which such
            non-compliance relate are less than five (5). Notwithstanding what
            is stated in Article 1.16, European Union for the purpose of this
            Article 3.8.2 shall constitute only those countries being members of
            European Union at the License Agreement Effective Date.

3.8.3.      Reasonable Delay or Other Non-Compliance.

            a)    Should TMC upon receipt of notice from ASTRAZENECA according
                  to Article 3.8.1 (i) through (iii) be able to show that the
                  delay or other non-compliance in the country(ies) concerned is
                  justifiable from a clinical, scientific or regulatory
                  perspective, then the Parties shall meet and consult whether
                  the situation so occurred could be reasonably solved. Should
                  the Parties, despite such consultations, not be able to find a
                  mutually acceptable solution within three (3) months upon
                  having entered into such consultations, then ASTRAZENECA may
                  terminate the license regarding the country(ies) concerned by
                  giving TMC a notice of same in writing, whereupon the license
                  regarding such country(ies) shall immediately terminate and
                  what is stated in Article 15.1 shall apply regarding such
                  country(ies).

            b)    Should, following the initiation of the consultations pursuant
                  to the first paragraph of this Article 3.8.3, either Party
                  reasonably believe that a solution to the situation arisen may
                  be solved through such consultations, but not within the
                  initial three-month timeframe, then such Party may notify the
                  other Party hereof; and the three-months period provided for
                  in Article 3.8.3 a) shall be extended with a time-


<PAGE>
                                                                              23


            period as requested by such Party in such notice but with no more
            than three (3) months from the date of the notice.

3.9.        The remedies stated in Article 3.8 shall be ASTRAZENECA's sole
            remedy in case of any failure by TMC to comply with what is stated
            in this Article 3.

4.          SUPPLY MATTERS

4.1.        Transfer of Bulk Compound to TMC. ASTRAZENECA undertakes to supply
            to TMC [**] approximately ten (10) kilograms of bulk Compound no
            later than ninety (90) days after the License Agreement Effective
            Date. The transport of such entire quantity of bulk Compound shall
            be entirely at TMC's risk and expense. It is explicitly understood
            that this quantity of Compound was manufactured by ASTRAZENECA at an
            earlier date, and was not made for the purpose of the supply now
            stated, and that ASTRAZENECA gives no guarantee whatsoever as to the
            characteristics of the Compound or the Compound's fitness for any
            particular purpose.

4.2.        Assignment of Agreement with Fresenius. Unless such Contract has
            been assigned or terminated in accordance with what is stated in
            Article 2.8 of the Option Agreement, Astra Hassle AB, subsequently
            merged into ASTRAZENECA, and Fresenius are at the License Agreement
            Effective Date parties to a Development and Commercial Supply
            Contract of 28 December 1995 providing for the supply by Fresenius
            to ASTRAZENECA of Product. Should Fresenius agree with TMC on the
            supply of Product to TMC and with ASTRAZENECA to release ASTRAZENECA
            from any obligation under said Contract, then ASTRAZENECA will,
            provided always that the release or termination of such Contract or
            TMC's entering into any such arrangement will not incur any expenses
            or liability on ASTRAZENECA, agree to assign its rights under the
            Contract to TMC, or


<PAGE>
                                                                              24


            to terminate the Contract with Fresenius, whichever TMC desires and
            notifies ASTRAZENECA in writing of.

            It is explicitly understood and agreed by the Parties that
            ASTRAZENECA shall have no obligations whatsoever to transfer or
            supply, other than as explicitly provided under Article 4.1, any
            quantity of Compound or Product to TMC.

4.3.        Supply of Compound and Product by TMC.

4.3.1.      TMC undertakes to supply ASTRAZENECA's Affiliate in Japan,
            AstraZeneca KK, at TMC's [**], AstraZeneca KK's entire need of
            Product for clinical trials, sale, promotion and marketing in Japan,
            pursuant to the Supply Agreement between TMC and AstraZeneca KK,
            attached hereto, subject to what is stated in Article 4.3.3, as a
            Schedule E.

4.3.2.      TMC further undertakes to supply ASTRAZENECA, subject to Article
            15.1 (i), at TMC's [**] and otherwise under terms to be as
            consistent as possible with those under the Supply Agreement,
            ASTRAZENECA's entire need of Product for clinical trials, sale,
            promotion and marketing in any country where the license granted
            under Article 2 has been terminated pursuant to Article 3.8;
            provided always that such TMC's obligation shall not become
            effective unless and until TMC has Launched the Product in at least
            with one (1) country of the Territory.

4.3.3.      The Supply Agreement may not have been entered into on the License
            Agreement Effective Date due to the Parties' desire to expeditiously
            enter into the Option Agreement, not delaying such procedure by
            awaiting the completion of the Supply Agreement. The parties
            acknowledge the substantial need for ASTRAZENECA to rely on TMC for
            its supply of the Product for the countries mentioned in Articles
            4.3.1 and 4.3.2 and that


<PAGE>
                                                                              25


            entering into the Supply Agreement is a substantial prerequisite to
            ASTRAZENECA for entering into the Option Agreement. Should
            regardless hereof the Supply Agreement not have been concluded
            within six (6) months of the License Agreement Effective Date for
            other reasons than ASTRAZENECA's lack of good faith in conducting
            such negotiations or unnecessary delays caused by ASTRAZENECA, then
            ASTRAZENECA shall have the right to terminate this Agreement
            forthwith by giving written notice to TMC.

            Should ASTRAZENECA have failed, however, to provide to TMC in
            accordance with what is stated in Article 2.10 of the Option
            Agreement a first draft of the Supply Agreement, then,
            notwithstanding what is stated in the first paragraph of this
            Article 4.3.3, ASTRAZENECA shall not have the right to terminate
            this License Agreement.

5.          EXCHANGE OF INFORMATION

5.1.        Obligation of TMC to Share Information. In addition to the
            obligations specifically requiring TMC to inform ASTRAZENECA
            regarding particular events, TMC undertakes to keep ASTRAZENECA
            informed about the progress of the development work regarding the
            Compound hereunder. For this purpose:

5.1.1.      the Parties will, up until the date when Filing of an NDA has been
            made in the last Major Market, meet at least once a year to review
            TMC's progress and efforts in the development work contemplated
            herein. Such meeting will take place on a location to be agreed by
            the Parties, or, should the Parties not be able to agree,
            alternately with each Party at a site to be determined by the Party
            hosting the meeting. In advance of such meeting, TMC will provide
            ASTRAZENECA a reasonable written summary of such development work,
            including, without limitation, summaries of protocol


<PAGE>
                                                                              26


            designs of any clinical trials conducted or to be conducted, any
            changes to same and any Results developed during the period
            concerned;

5.1.2.      TMC shall further in advance of such meeting provide ASTRAZENECA in
            writing a timetable for the expected Filings of an NDA, expected NDA
            Approvals and expected Launches during the one-year period, or other
            shorter applicable period, to come. In connection therewith TMC
            shall provide to ASTRAZENECA in writing, for the same period of
            time, a non-binding marketing plan and sales forecast for the
            Product in any Major Market where the Product by that time has been
            Launched or is expected to be Launched during the applicable period
            immediately to come;

5.1.3.      TMC shall notify ASTRAZENECA forthwith and provide particulars of
            any halt or substantial delay in any development program or clinical
            trial, any obstacles in the Product reaching the market and any
            substantial changes anticipated in the sales potential of the
            Product;

5.1.4.      TMC shall notify ASTRAZENECA forthwith regarding, and provide copies
            of, any correspondence with the regulatory authorities in the
            Territory that could reasonably be of any significance regarding the
            possibility, time frame or scope of any Filing of an NDA or any NDA
            Approval by ASTRAZENECA in Japan or which may otherwise relate to
            such Filing of an NDA or NDA Approval.

5.2.        Obligation of AstraZeneca to Share Information. ASTRAZENECA shall
            keep TMC informed about the progress of the clinical trials, sale,
            promotion and marketing of Product in any country in which
            ASTRAZENECA has rights to sell Product. For this purpose:

5.2.1.      ASTRAZENECA shall at least once each year provide TMC in writing a
            timetable for the expected Filings of an NDA, expected NDA Approvals
            and expected Launches during the one-year period to come.


<PAGE>
                                                                              27


5.2.2.      ASTRAZENECA shall notify TMC forthwith regarding, and provide copies
            of, any correspondence with the regulatory authorities in any Major
            Market that could reasonably be of any significance regarding the
            possibility, time frame or scope of any Filing of an NDA or any NDA
            Approval by TMC in any country for which TMC has yet to file an NDA
            or receive NDA Approval.

6.          CONSIDERATION

In consideration of the rights granted hereunder TMC shall pay to ASTRAZENECA
the remuneration stated in this Article 6.

6.1.        Milestone Payments.

6.1.1.      Within thirty (30) days of the License Agreement Effective Date TMC
            shall pay to ASTRAZENECA the amount of One million U.S. Dollars 
            (U.S. $1,000,000).

6.1.2.      Within thirty (30) days of the date of TMC's Filing of an NDA in the
            first Major Market, TMC shall pay to ASTRAZENECA the amount of [**]
            U.S. Dollars (U.S. $[**]).

6.1.3.      Within thirty (30) days of TMC's receipt of NDA Approval in the
            first Major Market TMC shall pay to ASTRAZENECA the amount of [**]
            U.S. Dollars (U.S. $[**]).

6.1.4.      Within thirty (30) days of the TMC's receipt of NDA Approval in the
            second Major Market, TMC shall pay to ASTRAZENECA the amount of [**]
            U.S. Dollars (U.S. $[**]).

6.1.5.      Within thirty (30) days of the TMC's receipt of NDA Approval in the
            third Major Market, TMC shall pay to ASTRAZENECA a final milestone
            payment in the amount of [**] U.S. Dollars (U.S. $[**]).


<PAGE>
                                                                              28


6.2.        Royalty Rate.

6.2.1.      Following Launch of the Product, on a country-by-country basis for
            the period set out in Article 6.4 TMC shall pay to ASTRAZENECA,
            subject to what is stated in Article 6.2.2, a running royalty on the
            annual Net Sales of the Product as follows:



<TABLE>
<CAPTION>
                             Annual Net Sales                       Royalty Rate
                             ----------------                       ------------
<S>                                                             <C> 

                
                                  [**]                                   [**]


</TABLE>




<PAGE>
                                                                              29


            The relevant royalty rate so stated shall apply to the amount of
            annual Net Sales within the applicable layer only.

            For convenience of example only and without limiting the above, the
            royalty rate of [**]% shall apply to the amount of annual Net Sales
            under $[**] and should the annual Net Sales exceed $[**] then the
            royalty rate of [**]% shall apply only to the amount of annual Net
            Sales exceeding $[**] (and up to $[**]).

6.2.2.      Notwithstanding the royalty rates set forth in Article 6.2.1, on the
            Net Sales of the Product during the time period starting on the
            License Agreement Effective Date and ending on December 31, 2007,
            the running royalty rate shall be reduced to [**] percent ([**]%) of
            the rate otherwise stated in Article 6.2.1.

6.2.3.      For the purpose of Article 6.2.1 the term "annual" shall refer to
            calendar years, provided, however, that for the purpose of
            determining what royalty rates to apply during the first or last
            calendar year of the royalty payment period pursuant to Article 6.4,
            which parts may not constitute a full calendar year, the following
            shall apply.

            a)    The applicable royalty rate under each of items (a) through
                  (i) of Article 6.1.1, subject to what is stated in Article
                  6.2.2, shall apply to the Net Sales exceeding the amount "A"
                  in the following formula.

                  NM
            TA x ---- = A
                  12

            where "NM" is the "number of full months" of sales attracting
            royalty hereunder, regardless of the number of countries in which
            sales are being made, during the calendar year concerned; and where
            "TA" is the applicable "threshold amount" under the respective items
            (a) through (i) of Article 6.2.1.


<PAGE>
                                                                              30


            b)    For convenience of example only and without limiting the above
                  standing, the following calculation shows the application of
                  the provision stated. If Launch occurs in the first country
                  three months before the end of the calendar year, the formula
                  will read, regarding the royalty rate of [**]% under 6.2.1(a):
                  $[**] x 3/12 = $[**]. The royalty rate of [**]% under 6.2.1(b)
                  will then become applicable on any Net Sales exceeding $[**]
                  (and up to $[**]) and a royalty rate of [**]% will be
                  applicable on any Net Sales up to and including $[**].
                  Notwithstanding the foregoing, as this example is with respect
                  to sales in the first country in which Launch occurs, the
                  above stated royalty rates may be reduced by [**] percent
                  ([**]%) pursuant to Article 6.2.2.

6.3.        Minimum Royalty. Notwithstanding what is stated in Article 6.2,
            during the second through fourth full calendar years following
            Launch in the first Major Market the aggregate annual royalty amount
            due by TMC to ASTRAZENECA for sales of the Product shall, regardless
            of the actual Net Sales amount accrued during such calendar year,
            not go below the following amounts during the years specified.

6.3.1.      Second full calendar year following Launch: [**] U.S. Dollars
            ($[**]);

6.3.2.      Third full calendar year following Launch: [**] U.S. Dollars ($[**])

6.3.3.      Fourth full calendar year following Launch: [**] U.S. Dollars
            ($[**])

6.3.4.      Should the Net Sales by TMC for any calendar year not generate the
            relevant royalty amount indicated under this Article 6.3, then TMC
            shall pay


<PAGE>
                                                                              31


            the difference between the minimum royalty amount stated and the
            amount actually generated within thirty (30) days after the date
            when the royalty payment for the last full quarter of the calendar
            year concerned is due according to Article 6.6.1.

6.4.        Duration of Royalty Payments. Royalties under Article 6.2 shall be
            payable on a country by country basis for the longer of :

            a)    the life of ASTRAZENECA Patent Rights which are necessary to
                  continue to manufacture, use or sell the Product in such
                  country; or

            b)    a period of ten (10) years from Launch in that country
                  (provided always that in the case of a country within the
                  European Economic Area such ten (10) years period shall run
                  from the date of Launch anywhere in the European Economic
                  Area);

6.5.        ASTRAZENECA Trademark Royalty. Unless the license to the ASTRAZENECA
            Trademark has been reverted pursuant to Article 9.1, TMC shall,
            following expiration of the period indicated under Article 6.4 on a
            country-by-country basis, and for as long as TMC sells the Product
            in any country in the Territory, in consideration of the exclusive
            license in the Territory to use the ASTRAZENECA Trademark in
            connection with the sales and marketing of the Product pay to
            ASTRAZENECA an annual running royalty on the Net Sales of the
            Product of [**] percent ([**]%).

6.6.        Reports.

6.6.1.      TMC shall deliver to ASTRAZENECA within sixty (60) days after the
            end of each calendar quarter ending March 31, June 30, September 30
            and December 31, a written report showing its computation of the
            remuneration due to ASTRAZENECA under this Agreement during such
            calendar quarter including (i) the quantity of the Product sold by
            or on behalf of TMC during such calendar quarter; and (ii) the total
            remuneration due in respect thereof and at the same time make the
            payment of the remuneration due. Any


<PAGE>
                                                                              32


            payment to be made hereunder shall be made in U.S. Dollars. Each
            such report mentioned in this Article 6.6.1 shall include the rates
            of exchange used for conversion to U.S. Dollars from the currency in
            which such sales were made.

6.6.2.      In the event that ASTRAZENECA, its Affiliates or sublicenses sells
            Product pursuant to Article 2.7.3, then ASTRAZENECA shall deliver to
            TMC within sixty (60) days after the end of each calendar quarter
            ending March 31, June 30, September 30 and December 31, a written
            report showing its computation of the remuneration due to TMC under
            this Agreement during such calendar quarter including (i) the
            quantity of the Product sold by or on behalf of ASTRAZENECA during
            such calendar quarter; and (ii) the total remuneration due in
            respect thereof and at the same time make the payment of the
            remuneration due. Any payment to be made hereunder shall be made in
            U.S. Dollars. Each such report mentioned in this Article 6.6.2 shall
            include the rates of exchange used for conversion to U.S. Dollars
            from the currency in which such sales were made.

6.7.        Taxes.

6.7.1.      The payments to be made hereunder by either Party shall be net
            payments i.e. without deduction of any bank or transfer charges.

6.7.2.      ASTRAZENECA shall pay any and all taxes levied on account of, or
            measured exclusively by, all payments it receives under this
            Agreement, including without limitation Swedish Value Added Tax
            ("mervardesskatt"). Amounts payable from TMC to ASTRAZENECA under
            this Agreement shall be paid by TMC without deduction for any tax,
            provided however that TMC may withhold income tax as required by
            internal laws of any applicable jurisdiction. In the case of such
            withholding being applicable, ASTRAZENECA may apply for the
            reduction of rate of withholding tax (including under the
            U.S./Sweden tax treaty) with the assistance of TMC and provided
            evidence of acceptance of this claim is submitted to TMC,


<PAGE>
                                                                              33


            TMC shall apply this rate accordingly. If applicable laws require
            that taxes be withheld, TMC will deduct those taxes from the
            remittable payments, make timely payment of the taxes to the proper
            taxing authority and send proof of such payment to ASTRAZENECA
            within sixty (60) days following that payment.

6.7.3.      TMC shall pay any and all taxes levied on account of, or measured
            exclusively by, all payments it receives under this Agreement.
            Amounts payable from ASTRAZENECA to TMC under this Agreement shall
            be paid by ASTRAZENECA without deduction for any tax, provided
            however that ASTRAZENECA may withhold income tax as required by
            internal laws of any applicable jurisdiction. In the case of such
            withholding being applicable, TMC may apply for the reduction of
            rate of withholding tax (including under the U.S./Sweden tax treaty)
            with the assistance of ASTRAZENECA and provided evidence of
            acceptance of this claim is submitted to ASTRAZENECA, ASTRAZENECA
            shall apply this rate accordingly. If applicable laws require that
            taxes be withheld, ASTRAZENECA will deduct those taxes from the
            remittable payments, make timely payment of the taxes to the proper
            taxing authority and send proof of such payment to TMC within sixty
            (60) days following that payment.

6.8.        Exchange Rates. For the purpose hereof, the rate of exchange to be
            used for conversion hereunder to U.S. Dollars shall be the average
            rate of exchange for the period to which the payment relates, as
            published by the Wall Street Journal.

6.9.        Books and Audit. Each Party shall keep complete and accurate books
            and records with respect to its sale of the Product and remuneration
            payable hereunder. Each Party shall have the right to have such
            pertinent books and records of the other Party inspected and
            examined once each calendar year for the purpose of determining the
            accuracy of payments made hereunder. Such inspection and examination
            shall be conducted by an independent,


<PAGE>
                                                                              34


            certified, public accountant selected by the Party requesting such
            examination. Such accountant shall not disclose to such Party any
            information except for information necessary to verify the accuracy
            of the records and payments made pursuant to this Agreement. The
            charges of the independent, certified, public accountant shall be
            paid by the Party requesting examination except if the payments
            pursuant to this Agreement have been understated by more than five
            percent (5%) in which case the Party who has underpaid will bear the
            cost and pay the shortfall in payment pursuant to this Agreement
            with interest to the other Party. Should instead the payments have
            been overstated the Party who has overpaid may deduct any such
            amount from the royalty payments due hereunder until such amount has
            been recovered by such Party.

6.10.       Wire Transfer Instructions.

6.10.1.     Unless otherwise instructed by ASTRAZENECA, all payments by TMC
            hereunder shall be made from the United States by wire transfer in
            the requisite amount to the following account of ASTRAZENECA.

            Bank Name:  [**]
            Account No: [**]
            Swift:      [**]

6.10.2.     Unless otherwise instructed by TMC, all payments by ASTRAZENECA
            hereunder shall be made from Sweden by wire transfer in the
            requisite amount to the following account of TMC.

            Bank Name:  [**]
            Account No: [**]
            Bank Code:  [**]


<PAGE>
                                                                              35


6.11.       Interest. If any sum payable pursuant to this Agreement shall not
            have been paid to a Party by the due date then (without prejudice to
            any other claim or remedy of such Party) the Party owing such sum
            shall pay interest thereon to the other Party at an annual rate of
            LIBOR + three percent (3%) from time to time published in respect of
            the period starting on the due date of payment and ending on the
            actual date of payment.

            "LIBOR" shall mean the thirty (30) days US dollar BBA London
            Interbank Offered Rate as published by Reuter.

7.          INTELLECTUAL PROPERTY - PROSECUTION AND MAINTENANCE

7.1.        Any and all ASTRAZENECA IP vested in ASTRAZENECA shall as between
            ASTRAZENECA and TMC remain vested in ASTRAZENECA.

7.2.        Any and all TMC IP vested in TMC shall as between TMC and
            ASTRAZENECA remain vested in TMC.

7.3.        ASTRAZENECA shall, during the term of this Agreement be responsible
            for the filing, prosecution and maintenance of the ASTRAZENECA
            Patent Rights and the ASTRAZENECA Trademark in the Territory. Should
            registration of the ASTRAZENECA Trademark be necessary or
            appropriate in any country, then ASTRAZENECA shall be responsible
            for obtaining such registration.

            TMC shall reimburse ASTRAZENECA for any out-of-pocket expenses
            (including fees to outside counsel and consultants) incurred by
            ASTRAZENECA in relation to any action taken by ASTRAZENECA pursuant
            to this Article 7.3.

7.4.        TMC shall have the right to give comments and recommendations as to
            the overall strategy regarding the filing, prosecution and
            maintenance of the


<PAGE>
                                                                              36


            ASTRAZENECA Patent Rights and the ASTRAZENECA Trademark; and before
            taking any significant step in the filing, prosecution or
            maintenance of the ASTRAZENECA Patent Rights or the ASTRAZENECA
            Trademark, ASTRAZENECA shall allow TMC to comment on the action
            proposed to be taken and ASTRAZENECA shall consider any such
            comments.

7.5.        In the event that ASTRAZENECA should decide to permit any pending
            patent application or any patent included in the ASTRAZENECA Patent
            Rights to lapse by any action, inaction or failure to take any
            action or to pay any fee when due, ASTRAZENECA shall promptly inform
            TMC of such decision, but no later than fifteen (15) days prior to
            such action, inaction or failure to pay, provided that such period
            is available to ASTRAZENECA, so that TMC might, for the avoidance of
            doubt at TMC's expense, seek such patent protection or prevent any
            such lapse.

7.6.        ASTRAZENECA shall not be liable to TMC in contract, tort,
            negligence, breach of statutory duty or otherwise for any economic
            loss or other loss of turnover, profits, savings, business or
            goodwill or any loss, damage, costs or expenses of any nature
            whatsoever incurred or suffered by TMC because of ASTRAZENECA's
            actions pursuant to or as a consequence of this Article 7.

            PATENT TERM EXTENSIONS

7.7.        Should ASTRAZENECA not be able to lawfully apply for patent term
            extensions, including, but not limited to, Supplementary Protection
            Certificates, relating to the ASTRAZENECA Patent Rights in the
            Territory in its own name, or should ASTRAZENECA otherwise require,
            TMC shall co-operate with ASTRAZENECA in any issue regarding the
            gaining of such patent term extension by assisting ASTRAZENECA with
            any actions or documents needed for such purpose.


<PAGE>
                                                                              37


            Should in any country in the Territory any decision have to be made
            as to what product, claim or otherwise to apply for such patent term
            extension regarding, then ASTRAZENECA shall have the right to make
            such decision at its own discretion.

7.8.        Rights to the Results. Any patents and other intellectual property
            rights, information, ideas, knowledge, data or know-how relating
            solely to the Compound, and/or the Product developed during the term
            of this Agreement (hereinafter referred to as "Result(s)") shall as
            between TMC and ASTRAZENECA be TMC IP and the sole property of TMC.
            TMC shall have the sole management of, and shall bear the cost of,
            any Results. ASTRAZENECA shall be given the reasonable opportunity
            to comment on important aspects of the prosecution of any patent
            applications, and shall use its reasonable endeavours to assist TMC
            in the prosecution of any patent applications.

8.          CLAIMS REGARDING INFRINGEMENT AND INVALIDITY

8.1.        Notification of Claim. If a Third Party notifies ASTRAZENECA or TMC,
            or their respective Affiliates or sub-licensees, that any act by
            TMC, or its Affiliates or sub-licensees, utilizing the ASTRAZENECA
            IP allegedly infringes in the Territory any Patent Rights or other
            intellectual property rights owned by or licensed to the Third
            Party, ASTRAZENECA or TMC shall promptly notify the other in
            writing.

8.2.        Defence of Claimed Infringement.

8.2.1.      ASTRAZENECA shall have no obligation to defend or settle any claim
            by a Third Party that the manufacture, sale or other use of the
            Product by TMC resulting from the use or exercise of the license
            granted hereunder under the ASTRAZENECA IP infringes any Patent
            Rights or other intellectual


<PAGE>
                                                                              38


            property rights owned by or licensed to a Third Party, subject to
            the provisions of Article 10.

8.2.2.      If a Third Party makes an infringement claim or files an
            infringement action against ASTRAZENECA, its Affiliates or
            sub-licensees, or TMC, its Affiliates or sub-licensees, arising out
            of TMC's, its Affiliates' or sub-licensees' manufacture, sale or
            other use of the Product in the Territory, or if a Third Party
            challenges any of the ASTRAZENECA IP, then TMC shall defend or
            settle the claim or action at its expense, subject to the provisions
            of Article 10.

8.2.3.      ASTRAZENECA may join such proceedings mentioned under sub-section
            8.2.2 voluntarily, subject always to TMC's, its Affiliates' or
            sub-licensees', right to decide the conduct over such litigation.
            Any such joining of the proceedings shall be at ASTRAZENECA's cost
            and expense. ASTRAZENECA shall for such purpose have the right to
            independently retain legal counsel and consultants, at its sole cost
            and expense.

8.2.4.      It is understood between the Parties that any proposed settlement
            will be subject to ASTRAZENECA's prior written approval, which
            approval shall not be unreasonably withheld. Such approval might be
            withheld primarily on the grounds that ASTRAZENECA reasonably
            determines that the settlement proposed is overly burdensome,
            financially or strategically, that ASTRAZENECA determines that TMC's
            conduct of the defence has a reasonable chance of succeeding or that
            ASTRAZENECA intends to continue such defence itself.

            Should ASTRAZENECA withhold such approval, then ASTRAZENECA shall
            have the right, but not the obligation (other than in the case that
            ASTRAZENECA has announced to TMC its intention to continue such
            defence itself), to continue the defence of the claim or action at
            its own expense. In such case TMC, its Affiliates or sub-licensees
            shall, at ASTRAZENECA's request and at ASTRAZENECA's expense for
            TMC's,


<PAGE>
                                                                              39


            its Affiliates' or sub-licensees' costs and expenses, assist in the
            prosecution of such action, including, but not limited to,
            consenting to being joined in such action as a voluntary plaintiff.

8.2.5.      Should TMC reasonably believe that the Third Party rights
            contemplated by Article 8.2.1 are valid in a certain country(ies)
            and that infringement is likely to be occurring in such
            country(ies), TMC may seek and enter into a licence thereto from
            such Third Party on appropriate commercial terms, whereby any
            remuneration and any costs and expenses (including but not limited
            to reasonable external legal costs) for such license shall be shared
            equally between TMC and ASTRAZENECA according to the following.

            TMC may deduct an amount equivalent to [**] percent ([**]%) of TMC's
            payments to such Third Party pursuant to such arrangement as
            indicated in the first paragraph of this Article 8.2.5 from the
            royalty payments to be made by TMC to ASTRAZENECA on the Net Sales
            in the country concerned pursuant to Article 6.2 to cover
            ASTRAZENECA's obligation to carry [**] percent ([**]%) of such
            payments and costs. This deduction shall be subject to the proviso
            that the royalty payments due to ASTRAZENECA shall not be reduced in
            total by more than [**] percent ([**]%) in any calendar year, and
            any residue not offset may be carried forward by TMC until such time
            as it has recovered ASTRAZENECA's [**] per cent ([**]%) share of
            such costs and expenses, or until the royalty payment obligations of
            TMC hereunder expire, whichever is the earlier.

8.3.        Third Party Infringement. If a Third Party shall, in the reasonable
            opinion of either Party, infringe any ASTRAZENECA Patent Rights or
            ASTRAZENECA Trademark in the Territory, then the Party having such
            opinion shall promptly notify the other Party.

8.3.1.      Further, each Party shall within five (5) working days or as soon as
            reasonably possible thereafter advise the other Party of receipt of
            any notice of:


<PAGE>
                                                                              40


            a)    any certification filed under the U.S. "Drug Price Competition
                  and Patent Term Restoration Act of 1984" ("ANDA Act"),
                  claiming that any ASTRAZENECA Patent Rights are invalid or
                  claiming that the ASTRAZENECA Patent Rights will not be
                  infringed by the manufacture, use or sale of a product for
                  which an application under the ANDA Act is filed or;

            b)    any equivalent or similar certification or notice in any other
                  jurisdiction.

8.3.2.      TMC, its Affiliates or sub-licensees shall have the initial sole
            right to commence an action for infringement in the Territory
            against the Third Party, in its own name, together with the right to
            enforce and collect any judgement thereon. ASTRAZENECA may join such
            proceedings voluntarily, subject always to TMC's, its Affiliates' or
            sub-licensees' right to decide the conduct over such litigation. Any
            such joining of the proceedings shall be at ASTRAZENECA's cost and
            expense. ASTRAZENECA shall for such purpose have the right to
            independently retain legal counsel and consultants, at its sole cost
            and expense.

8.3.3.      Any monetary recovery (whether by settlement or judgement) in
            connection with an infringement action commenced by TMC, its
            Affiliates or sub-licensees shall be applied first to reimburse TMC,
            its Affiliates or sub-licensees for their out-of-pocket expenses
            (including reasonable attorneys fees) incurred in prosecuting such
            action and the expenses of ASTRAZENECA borne by TMC hereunder. Any
            balance remaining shall be allocated among ASTRAZENECA and TMC in a
            manner reasonably calculated to correspond to the distribution of
            profits, in accordance with what would normally be provided for
            under this Agreement, on the sales of Product to which such recovery
            pertains.

8.3.4.      Should neither TMC, nor its Affiliates or sub-licensees, take
            appropriate and diligent action with respect to any such
            infringement or challenge as contemplated in this Article 8.3 within
            forty-five (45) days, or, in the case of


<PAGE>
                                                                              41


            a certification filed under the ANDA Act or similar certification or
            notice as contemplated under Article 8.3.1, within twenty (20) days,
            after receiving notice of any infringement or possible infringement
            or challenge, then ASTRAZENECA shall have the right, but not the
            obligation, to take such action, at its own expense, in its own
            name, and the right to enforce and collect any judgement thereon.

            a)    Should ASTRAZENECA elect to take such action then TMC, its
                  Affiliates or sub-licensees, shall, at ASTRAZENECA's request
                  and at ASTRAZENECA's expense for TMC's, its Affiliates' or
                  sub-licensees', costs and expenses, assist in the prosecution
                  of such action, including, but not limited to, consenting to
                  being joined in such action as a voluntary plaintiff.

            b)    If the recovery of such action as contemplated in this Article
                  8.3.4 exceeds ASTRAZENECA's out-of-pocket expenses
                  (including reasonable attorneys fees) for prosecuting the
                  action, then such excess recovery shall be shared by the
                  Parties on a [**] basis.

8.3.5.      ASTRAZENECA, its Affiliates or sub-licensees shall have the sole
            right to commence an action for infringement of the ASTRAZENECA IP
            in Japan or in any other country in which the license granted to TMC
            hereunder has reverted to ASTRAZENECA pursuant to Article 3.8
            against the Third Party, in its own name, together with the right to
            enforce and collect any judgement thereon. TMC may join such
            proceedings voluntarily, subject always to ASTRAZENECA's, its
            Affiliates' or sub-licensees' right to decide the conduct over such
            litigation. Any such joining of the proceedings shall be at TMC's
            cost and expense. TMC shall for such purpose have the right to
            independently retain legal counsel and consultants, at its sole cost
            and expense. Any monetary recovery (whether by settlement or
            judgement) in connection with an infringement action commenced by
            ASTRAZENECA shall be retained by ASTRAZENECA.


<PAGE>
                                                                              42


9.          TRADEMARK

9.1.        Should TMC not within twelve (12) months of the License Agreement
            Effective Date notify ASTRAZENECA that TMC wishes to maintain its
            exclusive license to the ASTRAZENECA Trademark as granted under
            Article 2.1, or should TMC within such twelve-months period notify
            ASTRAZENECA in writing that TMC does not wish to maintain such
            exclusive license to the ASTRAZENECA Trademark, then upon the
            expiration of such twelve-months period or the date of such written
            notice, whichever is the earlier,

            (a)   the exclusive license insofar as it relates to the ASTRAZENECA
                  Trademark under Article 2.1 shall immediately cease and the
                  ASTRAZENECA Trademark shall cease to be a part of the
                  ASTRAZENECA IP for all purposes of this Agreement;

            (b)   all rights so granted in the ASTRAZENECA Trademark to TMC
                  shall revert to ASTRAZENECA;

            (c)   TMC shall immediately return to ASTRAZENECA any ASTRAZENECA
                  Know-How relating to the ASTRAZENECA Trademark and grant to
                  ASTRAZENECA a non-exclusive, perpetual, remuneration-free and
                  world-wide license to use any Know-How developed by TMC
                  relating to the ASTRAZENECA Trademark for the purpose of
                  commercialising the Product.

            Should the rights have been so reverted, then TMC shall select a
            trademark of its own, not being confusingly similar to the
            ASTRAZENECA Trademark, to use in connection with the sales,
            marketing and distribution of the Product and shall be the owner and
            party of record of such trademark (the "TMC Trademark"). TMC shall
            have sole responsibility for clearance and registration of said TMC
            Trademark. TMC shall be responsible for all


<PAGE>
                                                                              43


            decisions and costs relating to selection, clearance, registration,
            defence and maintenance of the TMC Trademark.

9.2.        Utilisation of the ASTRAZENECA Trademark

9.2.1.      Unless the license to the ASTRAZENECA Trademark has been reverted
            pursuant to Article 9.1, TMC shall, as soon as reasonably possible
            upon completion of the item concerned, but no later than one (1)
            year prior to the estimated Launch in each country, notify
            ASTRAZENECA in a clearly visible manner how TMC intends to utilise
            the ASTRAZENECA Trademark in connection with the marketing, sales
            and distribution of the Product in the country concerned, including
            but not limited to showing the shape, size and colour of the
            intended logo containing the ASTRAZENECA Trademark, the intended
            packages of the Product and the intended promotional materials
            regarding the Product in such country. TMC may not utilise the
            ASTRAZENECA Trademark in any context without ASTRAZENECA's prior
            written approval, such approval not to be unreasonably withheld.

9.2.2.      Should ASTRAZENECA not approve such TMC's proposal, or part thereof,
            under Article 9.2.1, then ASTRAZENECA shall submit to TMC a
            proposal, within sixty (60) days of having received TMC's proposal,
            on how to utilise the ASTRAZENECA Trademark in this regard.

9.2.3.      Should TMC not accept ASTRAZENECA's proposal, or part thereof,
            provided under Article 9.2.2, then TMC may notify ASTRAZENECA of a
            new proposal on the utilisation of the ASTRAZENECA Trademark, or
            such part thereof, in such way as set forth in Article 9.2.1; such
            proposal to be noticeably different from all previous proposals.
            Should ASTRAZENECA not approve such proposal, then what is stated in
            Article 9.2.2. shall apply.

9.2.4.      Should ASTRAZENECA not within forty-five (45) days of such notice as
            stated in Article 9.2.1 have notified TMC that it objects all or in
            part to such


<PAGE>
                                                                              44


            TMC's proposal, or should ASTRAZENECA after having not approved a
            proposal, or part thereof, fail to present a proposal as stated
            under Article 9.2.2, then the proposal presented by TMC shall be
            considered to have been approved by ASTRAZENECA.

9.3.        TMC shall use the ASTRAZENECA Trademark in accordance with
            applicable laws in any country where TMC markets, sells or
            distributes the Product utilising the ASTRAZENECA Trademark. Unless
            the rights to the ASTRAZENECA Trademark have been reverted pursuant
            to Article 9.1, TMC undertakes to use the ASTRAZENECA Trademark at
            any time when the Product is sold, marketed or distributed in the
            Territory and not to use any trademark other than the ASTRAZENECA
            Trademark in connection with the sales, marketing and distribution
            of the Product. TMC further undertakes not to use any trademark
            being confusingly similar to the ASTRAZENECA Trademark in connection
            with marketing, sales and distribution of any other product.

9.4.        Should in any country of the Territory TMC by legal, regulatory or
            similar reasons be prevented from using the ASTRAZENECA Trademark or
            should usage of the ASTRAZENECA Trademark in connection with the
            sales, marketing and distribution of the Product prove to be
            commercially unreasonable in such country because of such legal,
            regulatory or similar reasons, then TMC shall immediately notify
            ASTRAZENECA hereof in writing and TMC shall not have the obligation
            to use the ASTRAZENECA Trademark for the marketing, sales and
            distribution of the Product in the country concerned. The Parties
            shall in such case meet and in good faith endeavour to find a new
            trademark as similar to the ASTRAZENECA Trademark as possible. Such
            new trademark selected for the country concerned shall for all
            purposes of this Agreement be considered an ASTRAZENECA Trademark.

            TMC shall carry all costs and expenses for the development and
            creation of such new trademark, provided always that should such
            costs be


<PAGE>
                                                                              45


            disproportionately high in relation primarily to the estimated value
            of the Product then TMC may offer ASTRAZENECA to carry all or part
            of such costs, or, should ASTRAZENECA notify TMC in writing that it
            declines to do so, notify ASTRAZENECA that it does not wish to
            maintain the license to the ASTRAZENECA Trademark for the country
            concerned; whereupon what is stated in Articles 9.1. (a) through (c)
            shall apply regarding such country.

9.5.        TMC undertakes, should ASTRAZENECA so require in writing, to mention
            on all packages, package inserts and promotional and advertising
            materials for the Product "Licensed from AstraZeneca AB" or the
            equivalent wording in the major language(s) of the country in which
            the Product is sold, or, should legal, regulatory or similar reasons
            prevent the use of that wording, such other wording as close as
            possible to the wording herein stated.

10.         INDEMNITY

10.1.       Indemnity by TMC.

10.1.1.     TMC shall be responsible for and shall indemnify ASTRAZENECA, its
            Affiliates and its and its Affiliates' directors, officers, other
            employees, agents and consultants (collectively the "ASTRAZENECA
            Indemnified Party") against any and all liability, loss, damage,
            cost and expense (including legal costs) incurred or suffered by the
            ASTRAZENECA Indemnified Party as a result of any claim brought
            against an ASTRAZENECA Indemnified Party by a Third Party (i)
            arising out of the testing, manufacture, sale, use or promotion by
            TMC, its Affiliates or sub-licensees of any Compound or Product
            hereunder; (ii) arising out of any theory of product liability
            (including, but not limited to, actions in the form of tort,
            warranty or strict liability) based on Compounds or Products
            developed by TMC hereunder; or (iii) arising out of any other
            activities to be carried out by TMC, its Affiliates or sub-licensees
            pursuant to this


<PAGE>
                                                                              46


            Agreement to the extent not included in (i) and (ii) above, except
            where such liability, loss, damage, cost and expense has been
            incurred or suffered as a result of a material breach of warranty or
            representation of ASTRAZENECA set out in Article 13 or by gross
            negligence or misconduct on the part of ASTRAZENECA.

10.1.2.     An ASTRAZENECA Indemnified Party that intends to claim
            indemnification under Article 10.1.1 shall notify TMC promptly of
            any such liability, loss, damage, cost and expense and permit TMC to
            control the defence and disposition thereof and further agrees to
            reasonably cooperate at TMC's expense with TMC in the handling
            thereof. The ASTRAZENECA Indemnified Party shall not compromise or
            settle such claim. TMC agrees to keep ASTRAZENECA informed of the
            progress in the defence and disputation of such claims and to
            consult with ASTRAZENECA with regard to any settlement thereof which
            TMC proposes to enter into and will provide ASTRAZENECA with
            suitable information regarding the same.

10.1.3.     TMC will maintain appropriate liability insurance against such
            product and other liability as contemplated under Article 10.1.1 at
            levels appropriate for products and activities of the relevant type.

10.2.       Indemnity by ASTRAZENECA.

10.2.1.     ASTRAZENECA shall be responsible for and shall indemnify TMC, its
            Affiliates and its and its Affiliates' directors, officers, other
            employees, agents and consultants (collectively the "TMC Indemnified
            Party") against any and all liability, loss, damage, cost and
            expense (including legal costs) incurred or suffered by the TMC
            Indemnified Party as a result of any claim brought against the TMC
            Indemnified Party by a Third Party (i) arising out of the testing,
            manufacture, sale, use or promotion by ASTRAZENECA, its Affiliates
            or sub-licensees, of any Compound or Product hereunder; (ii) arising
            out of any theory of product liability (including, but not limited
            to, actions in the form of tort, warranty or strict liability) based
            on Compounds


<PAGE>
                                                                              47


            or Products sold by ASTRAZENECA hereunder; or (iii) which arises as
            a result of a breach of a warranty or representation of ASTRAZENECA
            set out in Article 13, except where such liability, loss, damage,
            cost and expense has been incurred or suffered as a result of a
            material breach of TMC's obligations under this Agreement or by
            gross negligence or misconduct on the part of TMC.

10.2.2.     A TMC Indemnified Party that intends to claim indemnification under
            Article 10.2.1 shall notify ASTRAZENECA promptly of any such
            liability, loss, damage, cost and expense and permit ASTRAZENECA to
            control the defence and disposition thereof and further agrees to
            reasonably cooperate at ASTRAZENECA's expense with ASTRAZENECA in
            the handling thereof. The TMC Indemnified Party shall not compromise
            or settle such claim. ASTRAZENECA agrees to keep TMC informed of the
            progress in the defence and disputation of such claims and to
            consult with TMC with regard to any settlement thereof which
            ASTRAZENECA proposes to enter into and will provide TMC with
            suitable information regarding the same.

10.2.3.     ASTRAZENECA will either maintain appropriate liability insurance or
            be self insured against such liability as contemplated under Article
            10.2.1.

11.         CONFIDENTIALITY

11.1.       Confidential Information. At all times during the term of this
            Agreement and for a period of five (5) years following termination
            or expiration hereof, each Party shall, and shall cause its
            officers, directors, employees and agents to, keep confidential and
            not publish or otherwise disclose and not use, directly or
            indirectly, for any purpose, any Confidential Information provided
            to it by the other Party, provided, that, each Party may disclose
            and use the Confidential Information of the other Party to the
            extent such disclosure or use is expressly permitted by the terms of
            this Agreement,


<PAGE>
                                                                              48


            including without limitation those purposes set forth in Article
            11.2, or is otherwise reasonably necessary for the performance of
            this Agreement.

11.2.       Permitted Use and Disclosure. The Receiving Party may use and/or
            disclose Confidential Information to the extent that such disclosure
            is:

11.2.1.     made in response to a valid order of a court of competent
            jurisdiction or other competent authority provided however that the
            Receiving Party shall first have given notice to the Disclosing
            Party and given the Disclosing Party a reasonable opportunity to
            obtain a protective order requiring that the Confidential
            Information and documents that are the subject of such order be held
            in confidence by such court or authority or, if disclosed, be used
            only for the purpose for which the order was issued; and provided
            further that if a protective order is not obtained, the Confidential
            Information disclosed in response to such court or governmental
            order shall be limited to that information which is legally required
            to be disclosed in response to such court or governmental order;

11.2.2.     made by the Receiving Party to a regulatory authority as required in
            connection with any Filing of an NDA; provided, however, that
            reasonable measures will be taken to assure confidential treatment
            of such information;

11.2.3.     made by the Receiving Party to a patent authority as required in
            connection with any filing or application for Patent Rights; or

11.2.4.     made by the Receiving Party to Third Parties as may be necessary or
            useful in connection with the development, manufacturing, marketing,
            use and sale of the Compound or the Product as contemplated by this
            Agreement, including subcontracting, sublicensing and distribution
            transactions in connection therewith, provided that any such Third
            Party has undertaken confidentiality obligation with respect to the
            Confidential Information disclosed by the Receiving Party to it and
            the results of any such activities. Regardless hereof, TMC may not
            disclose to such Third Party which


<PAGE>
                                                                              49


            compound(s), other than the Compound, that [**] may be used as a
            manufacturing starting material, or intermediate, for.

11.3.       Release from Restrictions. Notwithstanding the foregoing,
            Confidential Information shall not include any information that, as
            determined by competent written proof:

11.3.1.     is or hereafter becomes part of the public domain by public use,
            publication, general knowledge or the like through no wrongful act,
            fault or negligence on the part of the Receiving Party;

11.3.2.     can be demonstrated by documentation or other competent proof to
            have been in the Receiving Party's possession prior to disclosure by
            the Disclosing Party;

11.3.3.     is subsequently received by the Receiving Party from a Third Party
            who is not bound by any obligation of confidentiality with respect
            to the said information;

11.3.4.     is generally made available to Third Parties by the Disclosing Party
            without restriction on disclosure; or

11.3.5.     is independently developed by or for the Receiving Party without
            reference to the Disclosing Party's Confidential Information.

12.         ADVERSE EVENTS

12.1.       Reporting of Adverse Events.

12.1.1.     TMC shall be fully responsible for reporting to the relevant
            regulatory or other competent authorities in the Territory any
            Adverse Event(s) which are or might be attributed to the use or
            application of the Compound or the Product. At ASTRAZENECA's request
            in writing TMC shall inform


<PAGE>
                                                                              50


            ASTRAZENECA of any Adverse Event in the country(ies) contemplated,
            and during the time period contemplated, by such notice.

12.1.2.     ASTRAZENECA shall be fully responsible for reporting to the relevant
            regulatory or other competent authorities in any country outside the
            Territory or for which the license to TMC hereunder has been
            terminated any Adverse Event(s) which are or might be attributed to
            the use or application of the Compound or the Product. At TMC's
            request in writing ASTRAZENECA shall inform TMC of any Adverse Event
            in the country(ies) contemplated, and during the time period
            contemplated, by such notice. For the avoidance of doubt ASTRAZENECA
            may appoint any Affiliate(s) or sub-licensee(s) carrying out the
            marketing of the Product in the country concerned to fulfil any such
            obligation as stated hereunder.

12.1.3.     Without limiting what is stated in Article 12.1, the Parties shall
            at an appropriate point of time during development of the Product
            jointly establish any such Adverse Event reporting procedures,
            including, but not limited to, any agreement regarding safety data
            exchange, as may be required or useful.

13.         REPRESENTATION AND WARRANTY

13.1.       Representations and Warranties of ASTRAZENECA. ASTRAZENECA
            represents and warrants to TMC as follows:

            a)    as of the License Agreement Effective Date it is the sole and
                  exclusive owner of the ASTRAZENECA Patent Rights and
                  ASTRAZENECA Trademark; all of which is free and clear of any
                  liens, charges and encumbrances; and

            b)    as of the License Agreement Effective Date ASTRAZENECA has not
                  previously assigned, transferred, licensed, conveyed or
                  otherwise


<PAGE>
                                                                              51


            encumbered its right, title and interest in the ASTRAZENECA Patent
            Rights or the ASTRAZENECA Trademark; and

            c)    as of the License Agreement Effective Date and to the best of
                  ASTRAZENECA's knowledge, no Person other than ASTRAZENECA or
                  any of its Affiliates, has or shall have any claim of
                  ownership with respect to ASTRAZENECA Patent Rights or the
                  ASTRAZENECA Trademark; and

            d)    as of the License Agreement Effective Date and to the best of
                  ASTRAZENECA's knowledge, the manufacture, use and sale of the
                  Compound does not infringe upon any intellectual property
                  rights of any Third Party, although it is expressly
                  acknowledged by TMC that ASTRAZENECA has made no particular
                  searches or investigations to determinate whether such
                  infringement occurs; and

            e)    as of the License Agreement Effective Date there are no
                  claims, judgements or settlements against or owed by
                  ASTRAZENECA or pending or threatened claims or litigation
                  relating to the ASTRAZENECA Patent Rights or the ASTRAZENECA
                  Trademark; and

            f)    except as insofar relating to any kind of formulation, or work
                  or development related thereto, of the Product, there are no
                  other Patent Rights or Know-How owned or licensed by
                  ASTRAZENECA required to develop and/or commercialise the
                  Product, and ASTRAZENECA shall not assert against TMC any
                  Patent Rights or other intellectual property owned or licensed
                  by ASTRAZENECA as of the License Agreement Effective Date or
                  at any time thereafter which are or may be infringed by the
                  Compound or the Product; and

            g)    as of the License Agreement Effective Date ASTRAZENECA has
                  disclosed to TMC any known interference with the ASTRAZENECA


<PAGE>
                                                                              52


            Patent Rights or re-examination or reissue proceeding concerning
            such ASTRAZENECA Patent Rights; and

            h)    as of the License Agreement Effective Date ASTRAZENECA has no
                  knowledge from which it can reasonably be inferred that the
                  granted ASTRAZENECA Patent Rights or the ASTRAZENECA Trademark
                  are invalid or that the applications for ASTRAZENECA Patent
                  Rights or ASTRAZENECA Trademark will not proceed to grant.

13.2.       Acknowledgement of TMC. TMC is aware that the ASTRAZENECA Patent
            Rights or the ASTRAZENECA Know-How may not sufficiently enable TMC
            to manufacture or conduct any other operational or
            manufacturing-related activities with respect to the formulation of
            the Product, and it is explicitly understood by TMC that TMC will
            have to independently conduct any analysis, evaluation and
            investigation regarding what intellectual property, techniques,
            routes, equipment or other help or assistance that will be required
            for such purpose and it will be entirely at TMC's risk to find such
            intellectual property, techniques, routes, equipment or other help
            or assistance in order to conduct such activities.

13.3.       Representations and Warranties of the Parties. Each Party represents
            and warrants to the other Party that it is a duly organized and
            validly existing corporation under the laws of its jurisdiction of
            incorporation, and has taken all required corporate action to
            authorize the execution, delivery and performance of this Agreement;
            it has the full right, power and authority to enter into this
            Agreement and perform all of its obligations hereunder; the
            execution and delivery of this Agreement and the transactions
            contemplated herein do not violate, conflict with, or constitute a
            default under its Articles of Association or similar organization
            document, its by-laws or the terms or provisions of any material
            agreement or other instrument to which it is a party or by which it
            is bound, or any order, award, judgement or decree to


<PAGE>
                                                                              53


            which it is a party or by which it is bound; and upon execution and
            delivery, this Agreement will constitute the legal, valid and
            binding obligation of it.

13.4.       Limitations. EXCEPT AS OTHERWISE SET FORTH IN THIS AGREEMENT
            ASTRAZENECA EXPRESSLY DISCLAIMS ANY AND ALL IMPLIED OR EXPRESS
            WARRANTIES AND MAKES NO EXPRESS OR IMPLIED WARRANTY, STATUTORY OR
            OTHERWISE, OF ANY KIND, INCLUDING ANY WARRANTIES OF MERCHANTABILITY
            OR FITNESS FOR ANY PARTICULAR PURPOSE REGARDING THE COMPOUND,
            ASTRAZENECA'S CONFIDENTIAL INFORMATION, DOCUMENTS, ASTRAZENECA
            KNOW-HOW, ASTRAZENECA PATENT RIGHTS, OR PRODUCTS.

14.         TERM AND TERMINATION

14.1.       Term. This Agreement shall become effective on the License Agreement
            Effective Date and shall expire when TMC ceases to sell the Product
            in the last country of the Territory or otherwise terminates this
            Agreement as set forth in Article 14.2.

14.2.       Termination by TMC. Should TMC determine that it does no longer
            consider it viable to continue to exercise the rights under this
            Agreement, then TMC may give written notice to ASTRAZENECA,
            whereupon this Agreement shall terminate thirty (30) days of such
            notice, unless ASTRAZENECA, within twenty (20) days of having
            received such notice, requests TMC in writing to enter into good
            faith discussions to see whether TMC's concerns could be reasonably
            overcome. However, upon TMC having given such notice TMC shall not
            be liable for any payments under Articles 6.1.2 through 6.1.5 or for
            any payments under Articles 6.3.1 unless corresponding to the
            royalty amounts actually due, which become due after the expiration
            of the 30-days period mentioned above in this Article 14.2.


<PAGE>
                                                                              54


            Should the Parties not within three (3) months of the date of
            commencement of such good faith discussions mentioned above in this
            Article 14.2 have managed to reach a mutually acceptable solution to
            TMC's concerns, then TMC may terminate this Agreement by giving
            ninety (90) days written notice.

14.3.       Termination for Breach. In the event that either Party (the
            "Breaching Party") shall be in significant default in the
            performance of any of its material obligations under this Agreement,
            in addition to any other right and remedy the other Party (the
            "Complaining Party") may have, the Complaining Party may terminate
            this Agreement by sixty (60) days prior written notice (the "Notice
            Period") to the Breaching Party, specifying the breach and its claim
            of right to terminate, provided always that the termination shall
            not become effective at the end of the Notice Period if the
            Breaching Party cures the breach complained about during the Notice
            Period.

14.4.       Survival of Obligations. Termination or expiration of this Agreement
            shall not relieve either Party from any obligation incurred
            hereunder prior thereto.

14.5.       Survival of Provisions upon Termination and/or Expiration. Subject
            to what is stated in Article 15, the provisions of Articles 1, 7.1,
            7.2, 10, 11, 12, 13, 14.5, 15, 17 and 18 shall survive termination
            or expiration of this Agreement. The provisions of Article 2.5 shall
            survive only upon expiration of this Agreement. The provisions of
            Article 11 shall survive termination or expiration of this Agreement
            and shall continue to be in force for a period of five (5) years
            after termination or expiration of this Agreement.


<PAGE>
                                                                              55


15.         CONSEQUENCES OF TERMINATION

15.1.       Termination and handback of license In addition to any remedy either
            Party may have in law, tort or in contract, subject to what is
            stated in Article 3.9, upon termination of the Agreement or the
            license in a certain country, the following shall apply.

            Upon termination of this Agreement by TMC pursuant to Article 14.2
            or by ASTRAZENECA pursuant to Article 14.3, or by ASTRAZENECA in a
            certain country pursuant to Article 3.8, the license granted under
            Article 2.1 regarding the country(ies) contemplated by the
            termination concerned shall cease, and TMC shall, regarding the
            Territory or the country concerned, whichever is applicable:

            (a)   at the option of ASTRAZENECA, grant to ASTRAZENECA a
                  non-exclusive, world-wide or for the country concerned,
                  whichever is applicable, sub-licensable licence under the TMC
                  IP to develop, have developed, make, have made, use, have
                  used, import, have imported, market, have marketed, sell and
                  have sold the Compound and the Product for any indications.
                  The term of such non-exclusive licence shall continue on a
                  country by country basis for the longer of the life of the TMC
                  Patent Rights, or for ten (10) years from first commercial
                  sale of any resultant product in such country by ASTRAZENECA,
                  its Affiliates, sub-licensees or nominees, whichever is the
                  longer. TMC shall do all such acts and things as may
                  reasonably be necessary to fulfil this obligation. The licence
                  set out in this Article 15.1 (a) shall be royalty-free and
                  free from any other remuneration.

            (b)   return to ASTRAZENECA any ASTRAZENECA Know-How and deliver to
                  ASTRAZENECA a copy of any TMC Know-How;


<PAGE>
                                                                              56


            (c)   deliver to ASTRAZENECA any and all quantities of Product in
                  its possession, power, custody or control subject always to
                  TMC's right to dispose of Product which is the subject of
                  pre-termination date orders pursuant to Article 15.1 (h). For
                  the avoidance of doubt, should this Article 15.1 (c) become
                  applicable because of termination regarding a certain country
                  or countries pursuant to Article 3.8, then the quantities of
                  Product referred to herein shall mean only those quantities
                  clearly designated, by marking, labelling or similar, for the
                  country or countries concerned and which could only be used
                  for the country or countries concerned;

            (d)   ensure that its patent attorneys transfer to ASTRAZENECA a
                  copy of the patent files relating to the TMC Patent Rights
                  which TMC has been prosecuting and maintaining and ASTRAZENECA
                  shall be entitled to prosecute and shall maintain such TMC
                  Patent Rights at its own cost and expense on terms similar to
                  those set out in Article 7.3 and to deal with infringers on
                  terms similar to those set out in Article 8.2 and 8.3. TMC
                  further undertakes to take any action and produce any
                  documents so as to enable ASTRAZENECA to apply for patent term
                  extensions, including, but not limited to, Supplementary
                  Protection Certificates, relating to the TMC Patent Rights in
                  ASTRAZENECA's name.

            (e)   Should this Article 15.1 become applicable because of the
                  termination of the license regarding a certain country or
                  countries pursuant to Article 3.8, then TMC shall,
                  notwithstanding the license granted under Article 15.1 (a), on
                  the request by ASTRAZENECA continue to prosecute, maintain and
                  defend the TMC Patent Rights.

            (f)   commensurate with legislative and regulatory requirements,
                  transfer to ASTRAZENECA or its nominee all NDA Approvals, and
                  regulatory filings for the Compound or Product (including,
                  without limitation,


<PAGE>
                                                                              57


                  all information and documentation used in the Filings of an
                  NDA and NDA approvals referred to in Article 3.5.2 and 3.5.4).
                  In the event that in any country such a transfer is not
                  possible, TMC shall use reasonable endeavours to ensure that
                  ASTRAZENECA has the benefit of the relevant NDA Approvals,
                  NDAs and other related regulatory filings and approvals and,
                  to this end, consents to any regulatory authority
                  cross-referencing to the data and information on file with any
                  regulatory authority as may be necessary to facilitate the
                  granting of second NDA Approvals to and permit Filings of an
                  NDA by ASTRAZENECA, and TMC agrees to complete whatever other
                  procedures that are reasonably necessary in relation to the
                  same to enable ASTRAZENECA (either itself or in conjunction
                  with a Third Party) freely to develop and sell the Product in
                  substitution for TMC;

            (g)   if applicable, assign the TMC Trademark or grant a
                  royalty-free exclusive licence to ASTRAZENECA to use the TMC
                  Trademark for the marketing, sales and distribution of the
                  Product;

            (h)   not after the date of termination itself take any further
                  action to develop, manufacture, have manufactured, use,
                  market, distribute or sell the Compound or Product during the
                  life of the TMC Patent Rights or the ASTRAZENECA Patent
                  Rights, whichever is the longer, except that TMC has the right
                  to dispose of that part of its inventory of Product on hand as
                  of the effective date of termination which is the subject of
                  orders for Product accepted prior to the date of notice of
                  termination for a period of three (3) months after the
                  effective date of termination, and, within thirty (30) days
                  after disposition of such inventory pursuant to the fulfilment
                  of such orders, TMC will forward to ASTRAZENECA a final report
                  and pay all royalties due on the Net Sales of Product during
                  such period; and


<PAGE>
                                                                              58


            (i)   provide ASTRAZENECA, should ASTRAZENECA so require, with
                  reasonable assistance in relation to ASTRAZENECA's appointment
                  of a Third Party manufacturer of Product.

            Upon such termination as stated in this Article 15.1, ASTRAZENECA
            shall have the right to disclose Confidential Information, to Third
            Parties for the purpose only of, and only to the extent necessary
            for, enabling such Third Party to evaluate the financial and
            scientific status of the Compound or Product for the purpose of
            making a financial offer to ASTRAZENECA on the licensing or
            acquisition of the rights returned to ASTRAZENECA and the rights
            licensed to ASTRAZENECA under this Article 15.1, and, if such
            licensing or acquisition occurs, as necessary to exploit or enforce
            such rights.

15.2.       Termination followed by continued license Upon the termination of
            this Agreement by TMC pursuant to Article 14.3, ASTRAZENECA's
            licences granted to TMC under Article 2 shall continue, provided
            that TMC continues to make payments pursuant to Article 6 as if the
            Agreement was still in effect.

16.         FORCE MAJEURE

16.1.       If either Party is prevented or delayed in the performance of any of
            its obligations under this Agreement by Force Majeure, that Party
            shall forthwith serve notice in writing on the other Party
            specifying the nature and extent of the circumstances giving rise to
            Force Majeure, and shall subject to service of such notice and to
            Article 16.3 have no liability in respect of the performance of such
            of its obligations as are prevented by the Force Majeure event
            during the continuation of such events, and for such time after they
            cease as is necessary for that Party, using all reasonable


<PAGE>
                                                                              59


            endeavours, to recommence its affected operations in order for it to
            perform its obligations.

16.2.       If either Party is prevented from performance of its obligations,
            due to Force Majeure, for a continuous period in excess of six (6)
            months, the other Party may terminate this Agreement forthwith on
            service of written notice upon the Party so prevented. In the event
            of termination under this Article 16.2 the provisions of Article 15
            shall not apply immediately and the Parties shall meet to discuss
            the ASTRAZENECA IP and TMC IP and agree on a process for
            arrangements upon termination.

16.3.       The Party claiming to be prevented or delayed in the performance of
            any of its obligations under this Agreement by reason of Force
            Majeure shall use its reasonable endeavours to bring the Force
            Majeure event to a close or to find a solution by which the
            Agreement may be performed despite the continuation of the Force
            Majeure event.

17.         GENERAL PROVISIONS

17.1.       Assignment.

17.1.1.     Subject to Articles 17.1.2 and 17.1.3, neither Party shall without
            the prior written consent of the other Party assign, transfer,
            charge or deal in any other manner with this Agreement or any of its
            rights under it.

17.1.2.     Each Party shall be entitled to assign its rights under this
            Agreement to an acquiror of all or substantially all of its capital
            stock or assets related to the pharmaceutical business described in
            this Agreement, whether through purchase, merger, consolidation or
            otherwise.

17.1.3.     Each Party shall be entitled to assign its rights under this
            Agreement to an Affiliate provided that such Party shall require
            that any such Affiliate to whom it assigns any of its rights under
            this Agreement shall assign such


<PAGE>
                                                                              60


            rights back to the assigning Party immediately prior to it ceasing
            to be an Affiliate of the assigning Party.

17.2.       Severance.

17.2.1.     If any provision of this Agreement shall be found by any court or
            administrative body of competent jurisdiction to be invalid or
            unenforceable, such invalidity or unenforceability shall not,
            provided that the general content of the Agreement remains
            substantially the same as prior to such invalidity or
            unenforceability, affect the other provisions of this Agreement
            which shall remain in full force and effect.

17.2.2.     The Parties agree, in the circumstances referred to in Article
            17.2.1, to attempt to substitute for any invalid or unenforceable
            provision a valid or enforceable provision which achieves to the
            greatest extent possible the same effect as would have been achieved
            by the invalid or unenforceable provision.

17.3.       Notices.

17.3.1.     All notices and other communications given or made in relation to
            this Agreement;

17.3.2.     shall be in English and in writing;

17.3.3.     shall be delivered by hand or sent by first class registered post or
            facsimile;

17.3.4.     shall be delivered or sent to the Party concerned at the relevant
            address or facsimile number, shown in Article 17.4 subject to such
            amendments as may be notified from time to time in accordance with
            this Article by the relevant Party to the other Party by no less
            than three business days notice; and

17.3.5.     shall be deemed to have been duly given or made if addressed in the
            aforesaid manner;


<PAGE>
                                                                              61


17.3.6.     if delivered by hand, upon delivery;

17.3.7.     if posted by first class registered post, four (4) business days
            after posting;

17.3.8.     if sent by facsimile, when a complete and legible copy of the
            communication has been received at the appropriate address

17.4.       Contact Information. Initial details for the purposes of Article
            17.3 are: 

            For ASTRAZENECA

            Address: AstraZeneca AB, S-151 85 Sodertalje, Sweden
            Facsimile: +46-8 553 290 00
            For the attention of: President & CEO

            For TMC

            Address: The Medicines Company, 5 Sylvan Way, Parsippany,
            New Jersey 07054, United States
            Facsimile: +1-973-656-9898
            For the attention of: Clive Meanwell, Executive Chairman

                 with a copy to

            Steven D. Singer
            Hale and Dorr, LLP
            60 State Street
            Boston MA 02109
            United States


<PAGE>
                                                                              62


17.5.       Agency, Partnership or Joint Venture Excluded.

17.5.1.     Nothing in this Agreement shall be construed so as to constitute
            either Party to be the agent of the other.

17.5.2.     Nothing in this Agreement and no action taken by the Parties
            pursuant to this Agreement shall constitute a partnership or joint
            venture of any kind between the Parties.

17.6.       Entire Agreement. Each of the Parties acknowledges and agrees that
            in entering into this Agreement, and the documents referred to in
            it, it does not rely on, and shall have no remedy in respect of, any
            statement, representation, warranty or understanding (whether
            negligently or innocently made) of any Person (whether party to this
            Agreement or not) other than as expressly set out in this Agreement
            as a warranty. Nothing in this Article shall either operate to limit
            or exclude any liability for fraud.

17.7.       Agreement to Supersede earlier Agreements. The Confidential
            Disclosure Agreement entered into by and between the Parties on 9
            April 2001 ceases to have effect from the date of this Agreement,
            except such termination does not affect a Party's accrued rights and
            obligations at the date of termination.

17.8.       Amendments. No amendment to or variation of this Agreement shall be
            valid unless it is in writing and signed by or on behalf of each of
            the Parties.

17.9.       Publicity and Announcements.

17.9.1.     Subject to Article 17.9.2 no press release, announcement or any
            other communication to any Third Party concerning the transaction
            contemplated by this Agreement, the financial terms of this
            Agreement, the subject matter of this Agreement or any ancillary
            matters shall be made or permitted or authorized to be made by
            either Party without the prior written approval of the other, such
            approval not to be unreasonably withheld or delayed and


<PAGE>
                                                                              63


            such approval to be given by an authorized representative of the
            Party in question.

17.9.2.     Either Party may make an announcement concerning the transaction
            contemplated by this Agreement or any ancillary matter if required
            by law, existing contractual obligations or any securities exchange
            or Regulatory Authority or governmental body to which either Party
            is subject or submits, wherever situated, provided that the Party
            required to make such announcement notifies the other Party of the
            details of the announcement prior to making such announcement and in
            sufficient time for the other Party to consider and comment on the
            announcement, and takes advantage of all provisions to keep
            confidential as many terms of the Agreement as possible.

17.10.      Waiver. Failure or delay by either Party to exercise any right or
            remedy under this Agreement shall not be deemed to be a waiver of
            that right or remedy, or prevent it from exercising that or any
            other right or remedy on that occasion or on any other occasion.

17.11.      No Benefit to Third Parties. No Third Party shall be deemed a third
            party beneficiary under this Agreement for any purpose. Without
            limiting the foregoing, the Contracts (Rights of Third Parties) Act
            1999 and any legislation amending or replacing such Act shall not
            apply in relation to this Agreement or any agreement, arrangement,
            understanding, liability or obligation arising under or in
            connection with this Agreement.

18.         GOVERNING LAW AND ARBITRATION

18.1.       Arbitration. The Parties shall use their reasonable efforts to
            settle amicably any dispute arising out of or in connection with
            this Agreement. In case the Parties are not able to settle such
            dispute between themselves, such dispute shall be finally resolved
            by arbitration in accordance with the Rules of the


<PAGE>
                                                                              64


            International Chamber of Commerce. The arbitration proceedings shall
            be held in London. Any proceedings shall be held in the English
            language.

18.2.       Governing Law. The validity, construction and interpretation of this
            Agreement and any determination of the performance which it requires
            shall be governed by the laws of England.

IN WITNESS WHEREOF this License Agreement has entered into force on the License
Agreement Effective Date.

ASTRAZENECA AB                            THE MEDICINES COMPANY
(publ)


<PAGE>
                                                                              65


                                   Schedule A

                            ASTRAZENECA Patent Rights


<PAGE>
                                                                              66


PATENT FAMILY LIST

Family         :   A1262
App./Propr     :   Astra AB
Title          :   Short acting dihydropyridines
Inventors      :   ANDERSSON, Kjell
                   NORDLANDER, Margareta
                   WESTERLUND, Christer



<TABLE>
<CAPTION>
Country             SN     F   App No            App Date        Pat No.           Grant Dt.       Exp. Dt        Status
-------             --    ---  ------            --------        -------           ---------       -------        ------
<S>                 <C>    <C> <C>               <C>             <C>               <C>             <C>            <C>
Argentina           1          329878            24.10.1994      253845            13.12.1999      13.12.2014     Granted
Argentina           2          980104360         01.09.1998                                                       Filed
Austria             1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Australia           1      P   81196/94          03.11.1994      685532            07.05.1998      03.11.2014     Granted
Belgium             1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Brazil              2          PI110048-7        06.05.1997                                                       Filed
Canada              1      P   2174969           03.11.1994                                                       Filed
Switzerland         1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
China P.R.          1      P   94194500.6        03.11.1994      94194500.6        20.11.1999      03.11.2014     Granted
Czech Republ        1      P   PV1273/96         03.11.1994      285691            17.08.1999      03.11.2014     Granted
Germany             1      X   95900347.6        03.11.1994      6942515.2         05.07.2000      03.11.2014     Granted
Denmark             1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Estonia             1      P   P9600051          03.11.1994      03230             20.10.1999      03.11.2014     Granted
Egypt               1          689/94            02.11.1994      20539             31.07.1999      03.11.2004     Granted
European Pat        1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Spain               1      X   95900347.6        03.11.1994      ES2150544         05.07.2000      03.11.2014     Granted
Finland             1      P   961914            03.11.1994                                                       Filed
France              1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Great Britain       1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Greece              1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Hong Kong           1          98114638.2        02.12.1998      1013292           08.12.2000      03.11.2014     Granted
Hungary             1      P   P9601187          03.11.1994      215591            04.12.1998      03.11.2014     Granted
Indonesia           1          P-941873          02.11.1994      ID0004550         06.12.1999      02.11.2014     Granted
Ireland             1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Israel              1          111127            03.10.1994      111127            22.02.2001      03.10.2014     Granted
Iceland             1          4218              30.09.1994      1674              31.12.1997      30.09.2014     Granted
Italy               1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Korea South         1      P   96/702346         03.11.1994                                                       Filed
Lithuania           1      X   95900347.6                                                                         Docketed
Luxembourg          1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Latvia              1      E                                                                                      Docketed
Monaco              1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Mexico              1          948392            28.10.1994      196540            22.05.2000      28.10.2014     Granted
Malaysia            1          PI94002934        04.11.1994      MY111770A         30.12.2000      30.12.2015     Granted
Netherlands         1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
</TABLE>




<PAGE>
                                                                              67




<TABLE>
<S>                 <C>    <C> <C>               <C>             <C>               <C>             <C>            <C>
Norway              1      P   961776            03.11.1994      305656            05.07.1999      03.11.2014     Granted
New Zealand         1      P   275915            03.11.1994      275915            29.09.1997      03.11.2014     Granted
Philippines         1          49112             04.10.1994      1-1994-49112      28.04.2000      28.04.2017     Granted
Poland              1      P   P314128           03.11.1994                                                       Filed
Portugal            1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Russian Fed         1      P   96112152          03.11.1994      2139278           10.10.1999      03.11.2014     Granted
Saudi Arabia        1          94150250          19.10.1994                                                       Filed
Sweden              1          9303657-2         05.11.1993                                                       Inactive
Sweden              1      X   95900347.6        03.11.1994      0726894           05.07.2000      03.11.2014     Granted
Slovak Repub        1      P   PV0559/96         03.11.1994      281467            10.01.2001      03.11.2014     Granted
Thailand            1          024372            04.11.1994                                                       Filed
Taiwan              1          83108995          29.09.1994      NI-078831         15.10.1996      29.09.2014     Granted
Ukraine             1      P   96041753          03.11.1994                                                       Filed
United States       1      P   356224            03.11.1994      5856346           05.01.1999      05.01.2016     Granted
South Africa        1          94/7570           28.09.1994      94/7570           26.07.1995      28.09.2014     Granted
</TABLE>




<PAGE>
                                                                              68


PATENT FAMILY LIST

Family        :   A1279
App./Propr    :   Astra AB
Title         :   Pharmaceutical emulsion
Inventors     :   ANDERSSON, Kjell
                  BYROD, Eva
                  NORDLANDER, Margareta
                  WESTERLUND, Christer
                  HANSSON, Anna-Carin



<TABLE>
<CAPTION>
Country             SN     F   App No            App Date        Pat No.           Grant Dt.       Exp. Dt        Status
-------             --     -   ------            --------        -------           ---------       -------        ------
<S>                 <C>    <C> <C>               <C>             <C>               <C>             <C>            <C>
Argentina           1          330005            04.111994       255314            01.11.2001      01.11.2016     Granted
Argentina           2          990105741         11.11.1999                                                       Filed
Austria             1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Australia           1      P   10371/95          03.11.1994      678650            25.09.1997      03.11.2014     Granted
Belgium             1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Brazil              1      P                                                                                      Inactive
Canada              1      P   2176360           03.11.1994                                                       Filed
Switzerland         1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
China P.R.          1      P   94194111.6        03.11.1994      94194111.6        11.08.2001      03.11.2014     Granted
Czech Republ        1      P   PV1338/96         03.11.1994                                                       Filed
Germany             1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Denmark             1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Estonia             1      P   P9600052          03.11.1994      03223             20.10.1999      03.11.2014     Granted
Egypt               1          710/94            09.11.1994      20764             31.01.2000      09.11.2014     Granted
European Pat        1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Spain               1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Finland             1      P   961999            03.11.1994                                                       Filed
France              1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Great Britain       1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Greece              1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Hong Kong           1          98114639.1        22.12.1998                                                       Filed
Hungary             1      P   P9601268          03.11.1994                                                       Filed
Indonesia           1          P-941957          11.11.1994      ID0004476         01.11.1999      11.11.2014     Granted
Ireland             1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Israel              1          111345            20.10.1994      111345            03.12.2000      20.10.2014     Granted
Iceland             1          4224              21.10.1994                                                       Filed
Italy               1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Korea South         1      P   96/702485         03.11.1994                                                       Filed
Liechtenstei        1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Lithuania           1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Luxembourg          1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Latvia              1      E                                                                                      Docketed
Monaco              1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
</TABLE>




<PAGE>
                                                                              69



<TABLE>
<S>                 <C>    <C> <C>               <C>             <C>               <C>             <C>            <C>
Mexico              1          948732            10.11.1994                                                       Filed
Malaysia            1          PI94003029        14.11.1994                                                       Filed
Netherlands         1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Norway              1      P   961898            03.11.1994                                                       Filed
New Zealand         1      P   276197            03.11.1994      276197            18.09.1997      03.11.2014     Granted
Philippines         1          49235             25.10.1994                                                       Filed
Poland              1      P   P314263           03.11.1994      181462            31.07.2001      03.11.2014     Granted
Portugal            1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Russian Fed         1      P   96112112          03.11.1994      2144358           20.01.2000      03.11.2014     Granted
Saudi Arabia        1          94150314          13.11.1994                                                       Filed
Sweden              1      X   95900965.5        03.11.1994      0727997           13.02.2002      03.11.2014     Granted
Slovak Repub        1      P   PV0597/96         03.11.1994                                                       Filed
Thailand            1          024457            11.11.1994                                                       Filed
Ukraine             1      P   96051803          03.11.1994      40633             15.08.2001      03.11.2014     Granted
United States       1      P   08/364953         03.11.1994      5739152           14.04.1998      14.04.2015     Granted
South Africa        1          94/8180           18.10.1994      94/8180           26.07.1995      18.10.2014     Granted
</TABLE>




<PAGE>
                                                                              70


PATENT FAMILY LIST

Family         :   A2004
Appl./Propr    :   AstraZeneca AB
Title          :   NEW MANUFACTURING PROCESS



<TABLE>
<CAPTION>
Country             SN     F   App No            App Date        Pat No.           Grant Dt.       Exp. Dt        Status
-------             --     -   ------            --------        -------           ---------       -------        ------
<S>                 <C>    <C> <C>   <C>         <C>             <C>               <C>             <C>            <C>  
Australia           1      P   20105/00          22.11.1999                                                       Filed
Canada              1      P   2349195           22.11.1999                                                       Filed
European Pat        1      X   99963732.5        22.11.1999                                                       Filed
Hong Kong           1          [**]              [**]                                                             Filed
New Zealand         1      P   511503            22.11.1999                                                       Filed
United States       1      P   09/508260         22.11.1999                                                       Filed
South Africa        1      P   2001/3434         22.11.1999                                                       Filed
</TABLE>




<PAGE>
                                                                              71


                                   Schedule B

                             Trademark Registrations


<PAGE>
                                                                              72


                             Trademark Family Report

TRADEMARK              :  CLEVELOX

TM Family Number       :  A02243
TM Attorney            :  MST
Project Resp. RPT      :  MST
Project Description    :  Clevidipine
Project Number         :  20298
Project Cost Centre    :  20298
Therapeutic Area       :  Cardio vascular
Owner                  :



<TABLE>
<CAPTION>
Country                      SN     Appl De            Reg. Dt        Reg No            Expir. Dt               Status
-------                      --     -------            -------        ------            ---------               ------
<S>                          <C>    <C>                <C>            <C>               <C>                     <C>
United Arab Emi              1                                                                                  Inactive
Argentina                    1      05.12.1997                                                                  Inactive
Austria                      1      24.11.1997         06.02.1998     173947            29.02.2008              Registered
Australia                    1      26.11.1997         26.11.1997     749529            26.11.2007              Registered
Brazil                       1                                                                                  Inactive
Benelux                      1      21.11.1997         21.11.1997     622377            21.11.2007              Registered
Canada                       1      16.12.1997                                                                  Filed
Switzerland                  1      21.11.1997         02.04.1998     450528            21.11.2007              Registered
China P.R.                   1      28.11.1997         14.02.1999     1246211           14.02.2009              Registered
Colombia                     1      03.12.1997                                                                  Filed
Czech Repub                  1      03.12.1997         27.05.1999     217843            03.12.2007              Registered
Germany                      1      22.11.1997         30.01.1998     39756082          30.11.2007              Registered
Denmark                      1      21.11.1997         15.09.1998     199802513         15.09.2008              Registered
Egypt                        1      01.12.1997                                                                  Filed
Spain                        1      26.11.1997         20.05.1998     2128403           26.11.2007              Registered
Finland                      1      21.11.1997         13.11.1998     211790            13.11.2008              Registered
France                       1      24.11.1997         24.11.1997     97705657          24.11.2007              Registered
Great Britian                1      21.11.1997         21.11.1997     2151563           21.11.2007              Registered
Greece                       1      17.11.1997         17.11.1999     135252            17.11.2007              Registered
Hong Kong                    1      08.12.1997         08.12.1997     3239/99           08.12.2004              Registered
Hungary                      1      27.11.1997         08.02.1999     155530            27.11.2007              Registered
Indonesia                    1      12.12.1997         12.12.1997     427623            12.12.2007              Registered
Ireland                      1      30.10.1997         21.11.1997     208749            21.11.2007              Registered
Israel                       1      24.11.1997         07.02.1999     116095            24.11.2004              Registered
India                        1      26.11.1997                                                                  Filed
Iceland                      1      24.11.1997         28.01.1998     210/1998          28.01.2008              Registered
Italy                        1      25.11.1997         18.05.2000     813581            25.11.2007              Registered
Japan                        1      09.01.1998         02.04.1999     4257306           02.04.2009              Registered
Japan                        2      17.04.2000         07.09.2001     4504229           07.09.2011              Registered
South Korea                  1      27.11.1997         27.11.1998     431337            27.11.2008              Registered
Mexico                       1      04.12.1997         04.12.1997     568689            04.12.2007              Registered
Malaysia                     1      28.11.1997                                                                  Filed
Norway                       1      21.11.1997         18.06.1998     190954            18.06.2008              Registered
</TABLE>




<PAGE>
                                                                              73




<TABLE>
<S>                          <C>    <C>                <C>            <C>               <C>                     <C>
New Zealand                  1      25.11.1997         25.11.1997     285223            25.11.2004              Registered
Pakistan                     1      25.11.1997                                                                  Filed
Poland                       1      25.11.1997         06.03.2001     123629            25.11.2007              Registered
Portugal                     1      25.11.1997         15.05.1998     327385            15.05.2008              Registered
Romania                      1      05.12.1997         05.12.1997     33325             05.12.2007              Registered
Russian Federat              1      03.12.1997         24.02.1999     172676            03.12.2007              Registered
Saudi Arabia                 1      12.01.1998         12.01.1998     474/30            22.09.2007              Registered
Sweden                       1      21.11.1997         06.08.1999     332270            06.08.2009              Registered
Singapore                    1      15.12.1997                                                                  Filed
Slovak Republic              1      25.11.1997         14.12.1999     188597            25.11.2007              Registered
Thailand                     1      09.12.1997         09.12.1997     80071             09.12.2007              Registered
Turkey                       1      26.12.1997         26.12.1997     195964            26.12.2007              Registered
Taiwan                       1      04.12.1997         16.10.1998     820735            16.10.2008              Registered
United States                1      21.11.1997                                                                  Inactive
United States                2      19.04.2001                                                                  Filed
Vietnam                      1      05.01.1998         07.05.1999     30808             05.01.2008              Registered
South Africa                 1      01.12.1997         01.12.1997     97/18422          01.12.2007              Registered
</TABLE>




<PAGE>
                                                                              74


                                   Schedule C

                                    Compound


<PAGE>
                                                                              75


SCHEDULE C, COMPOUND

CHEMICAL STRUCTURE, CHEMICAL NAME AND MOLECULAR FORMULA

Chemical structure

[CHEMICAL STRUCTURE GRAPH]

Figure 1. Chemical structure of clevidipine

Chemical name

Butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-

pyridinedicarboxylate.

Molecular weight

456.3 g/mol.

Molecular formula

C(21)H(23)Cl(2)NO(6)


<PAGE>
                                                                              76


                                   Schedule D

                                     Reports

REPORTS TO BE TRANSLATED AND SENT TO TMC



<TABLE>
<CAPTION>
REPORT                                 PAGES               COMMENT
------                                 -----               -------
<S>                                    <C>                 <C>
[**]                                   7
[**]                                   10+6
[**]                                   12
[**]                                   15
[**]                                   21
[**]                                   9
[**]                                   2
[**]                                   2
[**]                                   2
[**]                                   24
[**]                                   15                  Written in
                                                           English
[**]                                   7
[**]                                   17
[**]                                   15
[**]                                   6
[**]                                   33
[**]                                   6
[**]                                   17                  Written in
                                                           English

[**]                                   5                   Written in
                                                           English

[**]                                   22                  Clevidipine,
                                                           delivered batch
                                                           401/97
[**]                                   26
[**]                                   28
[**]                                   23
[**]                                   10-20
</TABLE>




<PAGE>
                                                                              77


                                   Schedule E

                                Supply Agreement


<PAGE>


                                   SCHEDULE 3

                                 Study outline

                        Subsequently the Study protocol


<PAGE>


                      PROTOCOL SYNOPSIS - CLEVIDIPINE CABG



<TABLE>
<S>                                         <C>
NAME OF SPONSOR:                            AstraZeneca and The Medicines Company

NAME OF ACTIVE INGREDIENT:                  Clevidipine

TITLE OF STUDY:                             [**]

STUDY CENTERS:                              [**]

PHASE OF DEVELOPMENT:                       [**]

OBJECTIVES:                                 [**]

METHODOLOGY:                                [**]

NUMBER OF PATIENTS:                         [**]

DIAGNOSIS AND MAIN CRITERIA FOR INCLUSION:  [**]

TEST PRODUCT(S), DOSE, MODE OF
ADMINISTRATION:                             [**]

REFERENCE THERAPY, DOSE, MODE OF
ADMINISTRATION:                             [**]

DURATION OF TREATMENT:                      [**]

CRITERIA FOR EVALUATION:

Efficacy:                                   [**]

                                            [**]

                                            [**]

                                            [**]

                                            [**]

                                            [**]

                                            [**]

Safety:                                     [**]

SAMPLE SIZE:                                [**]
</TABLE>




<PAGE>


                                   SCHEDULE 4

                               Press announcement


<PAGE>


Contact:        Peyton Marshall                   Jill Sawdon
                Chief Financial Officer           Director of Corporate
                The Medicines Company             Communications
                (617) 225-9099 (ph)               The Medicines Company
                (617) 225-2397 (fx)               (617) 225-9099 (ph)
                                                  (617) 225-2397 (fx)

FOR IMMEDIATE RELEASE

      THE MEDICINES COMPANY ANNOUNCES ACQUISITION OF RIGHTS TO CLEVIDIPINE

      PHASE 3 DRUG CANDIDATE TO BE TESTED FOR USE IN HOSPITAL HYPERTENSION
      PATIENTS

PARSIPPANY, NJ, March 6, 2002 - The Medicines Company (NASDAQ: MDCO) announced
today that it has entered into an agreement with AstraZeneca PLC for the
licensing, development and commercialization of clevidipine, an intravenous,
short-acting calcium channel blocker. Clevidipine will be developed in Phase 3
by The Medicines Company for the short-term control of high blood pressure in
the hospital setting. AstraZeneca has completed clinical pharmacology,
dose-finding and efficacy studies that demonstrate that clevidipine has a short
duration of action, a short plasma half life, and a selective effect on blood
pressure.

The agreement covers all worldwide territories except Japan. The Medicines
Company will perform further clinical development and has the right to
commercialize the product in all other territories worldwide including the
United States. Financial terms of the agreement were not disclosed.

"Acquisition of the rights to clevidipine is consistent with our execution of a
strategy to build a franchise in acute hospital care," said Clive Meanwell,
M.D., Ph.D., Executive Chairman of The Medicines Company. He went on to state,
"Commercially, the product's pharmacological and clinical attributes make it an
ideal candidate for Phase 3 testing in a range of hospital indications including
malignant hypertension, and the control of blood pressure during and after
cardiac surgery, percutaneous coronary intervention and other acute
interventions where precise control of blood pressure is clinically important.
An estimated 18.2 million surgical procedures are performed annually on
hypertensive patients in the United States. These patients are often treated
with multiple medications that have been shown to increase the duration of a
patient's stay in the Intensive Care Unit and require a physician's attention.
We believe clevidipine has the potential to demonstrate a substantial
pharmacoeconomic benefit by reducing complex treatment with multiple medications
and patients' time in the ICU."

Dave Stack, President and CEO of The Medicines Company, added, "This is a
perfect fit with our current U.S. sales configuration. We believe that
clevidipine will be of value to many of the same customers who are currently
adopting ANGIOMAX(R) (bivalirudin) into their practice. This leverages many of
our existing commercial relationships in the U.S. We look forward to forging a
strong relationship with Astra Zeneca and bringing this potentially important
new medicine to patients."


<PAGE>


Clive Meanwell will host a conference call at 8:30 AM (Eastern Time) on March 7,
2002. To participate in the call, please dial 800.472.8325. If you are calling
from outside the United States please call 1.706.679.0816. There will be a
digital replay of the call available until March 9 at midnight Eastern Time. To
listen to the replay, please dial 800.642.1687 in the United States or
1.706.645.9291 outside the United States and enter conference ID #3425937. A
webcast of the call will also be available on The Medicines Company's website,
velhartice.info.

The Medicines Company was founded in 1996 to acquire, develop and commercialize
selected pharmaceutical products in late stages of development and approved
products. In December 2000, the Company received marketing approval from the
U.S. Food and Drug Administration for ANGIOMAX for use as an anticoagulant in
combination with aspirin in patients with unstable angina undergoing coronary
balloon angioplasty. The Company began selling ANGIOMAX in the United States in
January 2001. The Company expects ANGIOMAX to be the cornerstone product of a
planned acute hospital franchise. The Company is also developing a second
product, CTV-05, a proprietary biotherapeutic agent with a potentially broad
range of applications in the treatment of gynecological and reproductive
infections. Additional information about the company and its products can be
found at velhartice.info.

This press release contains forward-looking statements that involve a number of
risks and uncertainties. For this purpose, any statements contained herein that
are not statements of historical fact may be deemed to be forward-looking
statements. Without limiting the foregoing, the words, "believes,"
"anticipates," "plans," "expects," "intends," and similar expressions are
intended to identify forward-looking statements. Important factors that could
cause actual results to differ materially from the expectations described in
these forward-looking statements are set forth under the caption "Certain
Factors that May Affect Future Results" in the Company's Quarterly Report on
Form 10-Q filed with the Securities and Exchange Commission on November 14, 2001
and incorporated herein by reference. These risk factors include risks as to the
commercial success of ANGIOMAX; how long the Company will be able to operate on
its existing capital resources; whether the Company's products (other than
ANGIOMAX for its approved indication and including clevidipine without
limitation) will advance in the clinical trials process, the timing of such
clinical trials, whether the clinical trial results will warrant continued
product development, whether and when, if at all, the Company's products will
receive approval from the U.S. Food and Drug Administration or equivalent
regulatory agencies, and for which indications, and, if such products receive
approval, whether they will be successfully marketed; whether the Company will
be able to develop or acquire additional products; the Company's history of net
losses; and the Company's dependence on third parties, including manufacturers,
suppliers and collaborators. We do not assume any obligation to update any
forward-looking statements.