MEDICINES CO /DE
EXHIBIT 10.18
<DOCUMENT>
<TYPE>EX-10.18
<SEQUENCE>5
<FILENAME>a2130210zex-10_18.txt
<DESCRIPTION>EXHIBIT 10.18
<TEXT>
<Page>

                                                                   EXHIBIT 10.18

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


                                LICENSE AGREEMENT


                 Entered into by and between AstraZeneca AB and
           The Medicines Company as of the 18th day of December, 2003

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                                TABLE OF CONTENTS

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<S>      <C>                                                                  <C>
1.       DEFINITIONS...........................................................2

2.       GRANT OF LICENSE.....................................................11

3.       DEVELOPMENT AND COMMERCIALIZATION....................................15

4.       SUPPLY MATTERS.......................................................25

5.       EXCHANGE OF INFORMATION..............................................27

6.       CONSIDERATION........................................................29

7.       INTELLECTUAL PROPERTY - PROSECUTION AND MAINTENANCE..................39

8.       CLAIMS REGARDING INFRINGEMENT AND INVALIDITY.........................42

9.       TRADEMARK............................................................46

10.      INDEMNITY............................................................47

11.      CONFIDENTIALITY......................................................49

12.      ADVERSE EVENTS.......................................................51

13.      REPRESENTATIONS, WARRANTIES AND COVENANTS............................52

14.      TERM AND TERMINATION.................................................55

15.      CONSEQUENCES OF TERMINATION..........................................57

16.      FORCE MAJEURE........................................................60

17.      GENERAL PROVISIONS...................................................61

18.      GOVERNING LAW AND ARBITRATION........................................65
</Table>

                                       -i-
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                                                                               1

                                LICENSE AGREEMENT


This Agreement is entered into as of the 18th day of December, 2003 (the
"Effective Date")

by and between

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

THE MEDICINES COMPANY, a company incorporated under the laws of Delaware with
its registered office at 8 Campus Drive, Parsippany, New Jersey 07054, 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 an intravenous pharmaceutical compound
designated AR-C69931MX for the selective inhibition of ADP-induced platelet
activation and aggregation; 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 AR-C69931MX to TMC
[**] for intravenous administration [**], 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.

                    License Agreement - The Medicines Company

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

1.2.           "[**]" shall mean ASTRAZENECA's proprietary compound with the
               chemical structure as shown in Schedule E.

1.3.           "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.

1.4.           "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 1.4 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.

1.5.           "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.

                    License Agreement - The Medicines Company

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                                                                               3

1.6.           "ASTRAZENECA IP" shall mean the ASTRAZENECA Patent Rights and the
               ASTRAZENECA Know-How.

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

1.8.           "ASTRAZENECA Know-How" shall mean any Know-How relating to the
               Compound for intravenous administration [**] and/or the Product,
               developed, acquired or licensed by ASTRAZENECA prior to the
               Effective Date and in ASTRAZENECA's possession at the Effective
               Date.

1.9.           "ASTRAZENECA Patent Rights" shall mean the patents and patent
               applications as set out in Schedule A, and any Patents Rights
               derived therefrom.

1.10.          "Baseline Quarter" shall mean the Quarter preceding the Quarter
               in which ASTRAZENECA receives NDA Approval of an [**] Product.

               The definition "NDA Approval" shall, for the purpose of this
               Article 1.10 (and Articles 1.43 and 6.2.3) only, be deemed to
               refer to [**] Product instead of Product.

1.11.          "Combination Product" shall mean any pharmaceutical product which
               has only an intravenous route of administration, and [**], in a
               finished dosage form which comprises the Compound and at least
               one other active pharmaceutical ingredient.

1.12.          "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

                    License Agreement - The Medicines Company

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                                                                               4

               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, 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.

1.13.          "Compound" shall mean ASTRAZENECA's proprietary compound named
               AR-C69931MX with the chemical structure as shown in Schedule C,
               attached hereto, including all salts, esters, complexes,
               chelates, hydrates, isomers, stereoisomers, crystalline and
               amorphous forms and solvates thereof.

1.14.          "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.

                    License Agreement - The Medicines Company

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                                                                               5

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

1.16.          "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 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.

1.17.          "Drug Product" shall mean the Compound in such formulation and
               associated primary packaging of dosage forms for intravenous
               administration as has been developed by ASTRAZENECA as of the
               Effective Date, used for, or intended for use in, human clinical
               trials, as described in the Product Master File, the table of
               contents of which is attached as Schedule B (the "PMF").

1.18.          "Excluded Countries" shall mean [**].

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

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

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

1.22.          "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.

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

                    License Agreement - The Medicines Company

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                                                                               6

1.24.          "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.

1.25.          "[**]" shall mean any of ASTRAZENECA's proprietary compounds
               [**], including all salts, esters, complexes, chelates, hydrates,
               isomers, stereoisomers, crystalline and amorphous forms,
               solvates, metabolites and prodrugs of any such compound.

1.26.          "[**] Product" shall mean any pharmaceutical formulation or
               product which has [**] containing [**] as the sole active
               ingredient in a finished dosage form suitable for administration
               to patients.

1.27.          "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.

                    License Agreement - The Medicines Company

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                                                                               7

1.28.          "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.

1.29.          "Major Market" shall mean each of [**].

1.30.          "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.

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

1.32.          "Net Sales" shall mean (i) the gross sales of Product by a Party
               or its Affiliates, or, regarding sales in the United States, its
               sub-licensees or distributors, to Third Parties, and (ii)
               royalties or other revenues, to the extent not included under
               (i), received by such Party or its Affiliates from its
               sub-licensees of the rights granted hereunder, or from its
               distributors, for sales of the Product outside the United States,
               after deduction of:

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

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

               c)   [**] such sales; and

               d)   [**] the Product.

                    License Agreement - The Medicines Company

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                                                                               8

               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 sales 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 1.32. In the
               event that such average sales price 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.

                    License Agreement - The Medicines Company

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                                                                               9

               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, 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 1.32 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.

1.33.          "PMF" shall have the meaning defined in Article 1.17.

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

1.35.          "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,

                    License Agreement - The Medicines Company

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                                                                              10

               extensions (including patent term extensions and patent term
               restorations), reissues, substitutions, confirmations,
               registrations, revalidations, re-examinations, 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.

1.36.          "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.

1.37.          "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.

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

1.39.          "Product" shall mean any pharmaceutical formulation or product
               which has only an intravenous route of administration, and [**],
               containing the Compound as the sole active ingredient in a
               finished dosage form suitable for administration to patients.
               Apart from in this Article 1.39, and unless the context clearly
               requires otherwise in this Agreement, when used in this
               Agreement, the term "Product" shall be deemed to include
               "Combination Product".

1.40.          "Quarter" shall mean a calendar quarter ending March 31, June 30,
               September 30 or December 31.

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

                    License Agreement - The Medicines Company

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                                                                              11

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

1.43.          "Subsequent Quarter" shall mean the Quarter in which ASTRAZENECA
               receives NDA Approval of an [**] Product or any subsequent
               Quarter.

               The definition "NDA Approval" shall, for the purpose of this
               Article 1.43 (and Articles 1.10 and 6.2.3) only, be deemed to
               refer to [**] Product instead of Product.

1.44.          "Supply Agreement" shall have the meaning described in Article
               4.2.1.

1.45.          "TMC IP" shall mean TMC Know-How, TMC Patent Rights and the TMC
               Trademark.

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

1.47.          "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.

1.48.          "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.

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

1.50.          "Territory" shall mean every country in the world, except the
               Excluded Countries.

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

2.             GRANT OF LICENSE

2.1.           LICENSE GRANT.

                    License Agreement - The Medicines Company

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                                                                              12

2.1.1.         ASTRAZENECA hereby grants to TMC, subject to what is stated in
               Article 2.1.2, 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 and have imported the Compound for intravenous
               administration [**], and 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 Product for all indications [**].

2.1.2.         The license granted under Article 2.1.1 shall not apply to the
               Compound or the Product in relation to any formulation or product
               which contains both the Compound and one or more [**] as active
               ingredients, whether or not such formulation or product contains
               active ingredients in addition to the Compound and the [**], and
               such rights shall, for the avoidance of doubt, be retained by
               ASTRAZENECA.

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 SUB-LICENSE. 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 sub-license
               without unreasonable delay following any such grant of a
               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.

                    License Agreement - The Medicines Company

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                                                                              13

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 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. The licenses set out in Article 2.1 shall 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 THE EXCLUDED COUNTRIES.
               Should ASTRAZENECA within its sole discretion at any time
               determine that ASTRAZENECA will not Launch the Product in one or
               more Excluded Countries and/or that ASTRAZENECA will not license,
               transfer or otherwise dispose of its interest in the ASTRAZENECA
               IP regarding one or more Excluded Countries, 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
               the Excluded Country(ies) concerned 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 THE EXCLUDED
               COUNTRIES.

                    License Agreement - The Medicines Company

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                                                                              14

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, 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 the Excluded Countries.

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 USD [**] ($[**]) per
               FTE Day.

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

               In each Excluded Country where ASTRAZENECA utilises, and for as
               long as ASTRAZENECA utilises, the license granted under this
               Article 2.7.3, ASTRAZENECA shall reimburse TMC its reasonable
               costs for maintaining the TMC Trademark in such Excluded Country.
               Such reimbursement shall be made within thirty (30) days of the
               expiration of each calendar year during which ASTRAZENECA has
               utilised such license.

                    License Agreement - The Medicines Company

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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 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.

3.1.1.         TRANSFER OF ASTRAZENECA KNOW-HOW. Without unreasonable delay
               following the 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 Effective Date, for the manufacture of all intermediates
                    to be used for the manufacturing of the Compound;

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               c)   a description of the analytical methods and validation
                    reports, available to ASTRAZENECA at the Effective Date, for
                    the starting materials and intermediates to be used in the
                    manufacturing of the Compound.

                    It is acknowledged that at the 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 will, however, provide
                    a summary report of the status of these methods at the
                    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 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 the formula and manufacturing process used
                    by ASTRAZENECA for the manufacturing of the Drug Product
                    intended for Phase III Clinical Trials. Where available,
                    ASTRAZENECA will provide TMC with summary reports of the
                    development of such processes;

                    As a prerequisite of ASTRAZENECA providing the ASTRAZENECA
                    Know-How contemplated under this sub-section f) TMC shall
                    notify ASTRAZENECA in writing of the vial strengths and
                    batch size that TMC initially intends to manufacture the
                    Drug Product in and

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                                                                              17

                    ASTRAZENECA's obligations under this sub-section f) shall
                    apply only in relation to such strengths and size.

               g)   a description of the analytical methods used by ASTRAZENECA
                    in the testing and stability assessment of the Drug Product;

                    It is acknowledged that at the 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 will, however, provide
                    a summary report of the status of these methods at the
                    Effective Date.

               h)   stability data and shelf-life recommendations for the Drug
                    Product used in previous clinical trials;

               i)   a description of the Drug Product formulations and processes
                    used in previous clinical trials. This information will be
                    contained within existing reports available at the Effective
                    Date.

               j)   specifications on the Compound and Drug Product used in
                    clinical trials conducted by ASTRAZENECA prior to the
                    Effective Date.

               k)   project-related reports and documentation, which are
                    designated with an asterisk in Schedule D, containing
                    ASTRAZENECA Know-How relating to the manufacturing of the
                    Compound. Additional reports contained in Schedule D will be
                    made available by ASTRAZENECA to TMC upon request by TMC to
                    ASTRAZENECA in writing.

               l)   the PMF and, upon request by TMC to ASTRAZENECA in writing,
                    other relevant reports, if available to ASTRAZENECA,
                    containing ASTRAZENECA Know-How relating to the
                    manufacturing of the Drug Product.

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                                                                              18

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

3.1.2.         Any activities to be carried out by ASTRAZENECA under Article
               3.1.1 shall be made to an extent necessary and reasonable and
               ASTRAZENECA shall not be obligated to devote more than the
               equivalent of [**] FTE Days thereon and under no circumstances to
               carry out such activities beyond the date [**] months from the
               Effective Date. It is acknowledged that ASTRAZENECA may at its
               discretion carry out assistance under Article 3.1.1 for up to
               [**] percent ([**]%) of such FTE Days by using Third Party
               consultants.

3.2.           THIRD PARTY MANUFACTURERS.

3.2.1.         It is acknowledged that TMC may present the ASTRAZENECA Know-How
               described under Article 3.1.1 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 ASTRAZENECA Know-How by no more than three (3) of such
               Third Party manufacturer(s) of the Compound and no more than
               three Third Party manufacturers of the Drug Product 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.

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                                                                              19

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, at ASTRAZENECA's sole
               discretion, shall take place either at ASTRAZENECA's Charnwood
               site at Loughborough, UK, or at the Third Party manufacturer's
               site.

3.2.3.         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 manufacture of the Drug Product.
               Such meeting shall, at ASTRAZENECA's sole discretion, take place
               either at ASTRAZENECA's Charnwood site at Loughborough, UK, or at
               the Third Party manufacturer's site.

3.2.4.         ASTRAZENECA further 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 notice, to assist
               TMC, by telephone, e-mail or other appropriate means as agreed by
               the Parties, in TMC's discussions with Drug Product contractors
               in connection with the formulation program regarding the Product.
               The Parties agree, however, that TMC may not give such notice
               contemplated above in this Article 3.2.4 later than eight (8)
               months after the Effective Date.

3.2.5.         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
               after the Effective Date, whichever is the earliest to occur.

3.3.           DURATION OF AND COMPENSATION FOR ASSISTANCE BY ASTRAZENECA.

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                                                                              20

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

3.3.2.         For any services or assistance performed by ASTRAZENECA pursuant
               to Articles 3.1.2 and 3.3.1, TMC shall reimburse ASTRAZENECA for
               ASTRAZENECA's out-of-pocket costs for such activities plus USD
               [**] ($[**]) per FTE Day. 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.

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.

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                                                                              21

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 in
               accordance with Article 3.3 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), sub-licensee(s) or distributors in each 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.

3.5.4.         TMC shall promptly inform ASTRAZENECA in writing, and by
               facsimile in accordance with Article 17.4.2, 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.

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                                                                              22

3.5.5.         Following NDA Approval in a country of the Territory TMC shall
               use its Commercially Reasonable Efforts to Launch the Product in
               such 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 in writing of the
               occurrence of such Launch.

3.6.2.         TMC shall, in each 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.

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.

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                                                                              23

               a)   TMC shall no later than [**] have made a Filing of an NDA
                    [**].

               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 [**].

               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 [**].

3.7.3.         Notwithstanding what is stated in Article 3.7.2 c), TMC shall not
               be obligated to make a Filing of an NDA in [**]  until the
               [**] patent application no. [**] is granted insofar it
               relates to the Compound to the extent licensed to TMC under this
               Agreement. For the avoidance of doubt, such exemption from those
               obligations now stated shall not relieve TMC from its obligations
               under Article 3.7.2 b).

3.7.4.         TIME LIMIT FOR LAUNCH OF THE PRODUCT

               TMC shall no later than [**] following NDA Approval in any Major
               Market Launch the Product in the Major Market in which such NDA
               Approval was obtained.

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 3.7.4, then TMC shall promptly so notify
               ASTRAZENECA in writing.

               a)   In case of non-compliance with the performance criteria set
                    forth in Article 3.7.1, ASTRAZENECA shall have the right, by
                    giving ninety (90) days written notice to TMC, to require
                    the license granted

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                                                                              24

                    hereunder to terminate regarding the Compound and the
                    Product, subject to Article 3.8.2.

               b)   In case of non-compliance with the performance criteria set
                    forth in Articles 3.4.2, 3.5.2, 3.5.5, 3.6.2, 3.7.2 (a) or
                    3.7.4, 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 3.8.2.

               c)   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) or that was exempted under Article
                    3.7.3), subject to Article 3.8.2.

               d)   If ASTRAZENECA makes a request under (a), (b) or (c) above,
                    and provided that TMC has not remedied the default concerned
                    within the ninety-day period stated, then, provided that
                    ASTRAZENECA notifies TMC in writing hereof within thirty
                    (30) days after the expiration of such ninety-day period,
                    the license regarding the Compound and the Product shall
                    terminate for the Major Market or other country contemplated
                    by such notice and what is stated in Article 15.1 shall
                    apply regarding such Major Market or other country, subject
                    to Article 3.8.2.

3.8.2.         REASONABLE DELAY OR OTHER NON-COMPLIANCE.

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                                                                              25

               a)   Should TMC upon receipt of notice from ASTRAZENECA according
                    to Article 3.8.1 (a) through (c) 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 after
                    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 3.8.2,
                    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 thereof; and the
                    three-month period provided for in Article 3.8.2 a) shall be
                    extended with a time-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 [**] kilograms of bulk Compound
               no later than ninety (90) days after the 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

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                                                                              26

               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. 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 this Article 4.1,
               any quantity of Compound or Product to TMC.

4.2.           SUPPLY OF COMPOUND AND PRODUCT BY TMC.

4.2.1.         TMC undertakes to supply ASTRAZENECA and/or any of its
               Affiliates, at TMC's [**] ASTRAZENECA's and/or its Affiliates
               entire need of Product for clinical trials, sale, promotion and
               marketing in the Excluded Countries, pursuant to the Supply
               Agreement between TMC and ASTRAZENECA, attached hereto, subject
               to what is stated in Article 4.2.3, as Schedule F. In addition
               ASTRAZENECA will reimburse TMC for costs specifically pertaining
               to the development of a formulation necessary only for the
               purpose of enabling ASTRAZENECA to obtain NDA Approval in one or
               more of the Excluded Countries.

4.2.2.         TMC further undertakes to supply ASTRAZENECA, subject to Article
               15.1 (i), at [**] 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 one (1) country of
               the Territory.

4.2.3.         The Supply Agreement has not been entered into on the Effective
               Date due to the Parties' desire to expeditiously enter into this
               Agreement, not delaying such procedure by awaiting the completion
               of the Supply Agreement. The parties acknowledge the substantial
               need for

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                                                                              27

               ASTRAZENECA to rely on TMC for its supply of the Product for the
               countries mentioned in Articles 4.2.1 and 4.2.2 and that entering
               into the Supply Agreement is a substantial prerequisite for
               ASTRAZENECA entering into this Agreement. Should regardless
               hereof the Supply Agreement not have been concluded within six
               (6) months of the 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.

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 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

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                                                                              28

               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.

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.

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.

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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 after the Effective Date TMC shall pay to
               ASTRAZENECA the amount of USD [**] ($[**]).

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

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

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 Articles 6.2.2 and
               6.2.3, a running royalty on the annual Net Sales of the Product
               in the Territory as follows:

<Table>
<Caption>
                   Annual Net Sales in the Territory            Royalty Rate
               <S>                                         <C>
               a)   up to USD [**]                         [**] percent ([**]%)
                    ($ [**])

               b)   above USD [**]                         [**] percent ([**]%)
                    ($ [**]) and up to USD [**]
                     ($[**])
</Table>

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<Table>
               <S>                                         <C>
               c)   above USD [**]                         [**] percent ([**]%)
                    ($ [**]) and up to USD [**]
                    ($ [**])

               d)   above USD [**]                         [**] percent ([**]%)
                    ($ [**]) and up to USD [**]
                    ($ [**])

               e)   above USD [**]                         [**] percent ([**]%)
                    ($ [**])
</Table>

               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, the
               running royalty rate on the Net Sales of the Product during the
               time period starting on the Effective Date and ending on the date
               which is one (1) year after the date of the Launch of the Product
               in the first country in which the Product is Launched, shall be
               reduced to [**] percent ([**]%) of the rate otherwise stated in
               Article 6.2.1.

6.2.3.         In the event that in a country in the Territory ASTRAZENECA
               receives NDA Approval of an [**] Product, and TMC's Net Sales in
               such country for a certain Subsequent Quarter is less than TMC's
               Net Sales in such country in the Baseline Quarter for such
               country, the royalty payable to ASTRAZENECA by TMC under Article
               6.2.1 with respect to Net Sales in such country in the Subsequent
               Quarter concerned shall be reduced by (i), if such reduction in
               Net Sales is [**] percent ([**]%) or less compared to the

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               Net Sales in the Baseline Quarter for such country, a percentage
               equal to such reduction in Net Sales expressed in percent, or
               (ii), if such reduction in Net Sales exceeds [**] percent ([**]%)
               compared to the Net Sales in the Baseline Quarter for such
               country, [**] percent ([**]%). The calculation of the reduction
               in Net Sales under this Article 6.2.3 shall, in case Net Sales in
               such country is not denominated in USD, be conducted in local
               currency. The percentage of each Net Sales reduction contemplated
               in this Article 6.2.3 shall be determined by the fraction (A-B)/A
               multiplied by 100 where A is TMC's Net Sales during the Baseline
               Quarter and B is TMC's Net Sales during the Subsequent Quarter
               concerned.

               The definition "NDA Approval" shall, for the purpose of this
               Article 6.2.3 (and Articles 1.10 and 1.43) only, be deemed to
               refer to [**] Product instead of Product.

               For convenience of example only and without limiting the above
               standing, the following calculation shows the application of the
               provision stated.

               a)   If TMC's Net Sales in country A are $[**] in the
                    Baseline Quarter for such country and $[**] in a
                    Subsequent Quarter the reduction of the royalty payable to
                    ASTRAZENECA would be determined as follows.


                    The reduction in Net Sales is [**]% (($ [**]) /
                    $ [**] = [**]%) and hence the royalty payable to ASTRAZENECA
                    with respect to Net Sales in country A in the Subsequent
                    Quarter concerned shall be reduced by [**]%.

               b)   If TMC's Net Sales in country A are $[**] in the
                    Baseline Quarter for such country and $[**] in a
                    Subsequent Quarter the reduction of the royalty payable to
                    ASTRAZENECA would be determined as follows.

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                                                                              32

                    The reduction in Net Sales is [**]% (($[**]) / $ [**]=
                    [**]%) and hence the royalty payable to ASTRAZENECA with
                    respect to Net Sales in country A in the Subsequent Quarter
                    concerned shall be reduced by [**]%.


               For the purpose of determining what royalty rate to apply with
               respect to Net Sales in one specific country, the following shall
               apply.


               The applicable royalty rate under each of items (a) through (e)
               of Article 6.2.1 shall apply to TMC's Net Sales in one specific
               country exceeding the amount "C" in the following formula.

                                    TA   x   NS   =   C
                                             --
                                            aNS


               where "NS" is TMC's Net Sales in the specific country during the
               calendar year concerned; and where "aNS" is TMC's annual Net
               Sales in the Territory during such calendar year; and where "TA"
               is the applicable "threshold amount" under the respective items
               (a) through (e) of Article 6.2.1.

6.2.4.         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
                    (e) of Article 6.2.1, subject to what is stated in Article
                    6.2.2 and 6.2.3, shall apply to the Net Sales exceeding the
                    amount "A" in the following formula.

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                                                                              33

                                    TA     x    NM    =     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 (e) of
                    Article 6.2.1.

               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, and Net Sales in such three
                    month period are $ [**], royalties payable would be
                    determined as follows:
                    (i)  the [**]% royalty rate under 6.2.1(a) would apply to
                         the first $ [**]of Net Sales ($[**]); and
                    (ii) the [**]% royalty rate under 6.2.1(b) would apply to
                         Net Sales above $ [**] ($[**]).
                    The foregoing notwithstanding, as this example is with
                    respect to sales in the year of first Launch, the above
                    stated royalty rates would 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: USD [**]
               ($[**]);

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6.3.2.         Third full calendar year following Launch: USD [**] ($[**])

6.3.3.         Fourth full calendar year following Launch: USD [**] ($[**])

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 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 6.5.1.

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 [**] years from Launch in that country
                    (provided always that, in the case of a country within the
                    European Economic Area, such [**] year period shall run
                    from the date of Launch anywhere in the European Economic
                    Area).

6.5.           REPORTS.

6.5.1.         TMC shall deliver to ASTRAZENECA within sixty (60) days after the
               end of each Quarter, a written report showing its computation of
               the remuneration due to ASTRAZENECA under this Agreement during
               such Quarter including (i) the quantity of the Product sold by or
               on behalf of TMC during such Quarter; and (ii) the total
               remuneration due in respect thereof; and TMC shall 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 6.5.1 shall include the

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                                                                              35

               rates of exchange used for conversion to U.S. Dollars from the
               currency in which such sales were made.

6.5.2.         In the event that ASTRAZENECA, its Affiliates or sublicensees
               sells Product pursuant to Article 2.7.3, then ASTRAZENECA shall
               deliver to TMC within sixty (60) days after the end of each
               Quarter, a written report showing its computation of the
               remuneration due to TMC under this Agreement during such Quarter
               including (i) the quantity of the Product sold by or on behalf of
               ASTRAZENECA during such 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
               6.5.2 shall include the rates of exchange used for conversion to
               U.S. Dollars from the currency in which such sales were made.

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                                                                              36

6.6.           TAXES.

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

6.6.2.         ASTRAZENECA shall pay any and all taxes levied on account of, or
               measured exclusively by, all payments it receives under this
               Agreement. 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, 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.

6.6.3.         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,

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                                                                              37

               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.

6.6.4.         For the avoidance of doubt, TMC shall be responsible and liable
               for all import duties and levies payable on bulk Compound
               imported to the US and to all related import clearance
               requirements. The value for customs purposes of this material
               provided free of charge should be the manufacturing cost to
               ASTRAZENECA.

6.6.5.         The parties shall cooperate fully to ensure that where legally
               possible no import duties are paid by TMC in respect of Product
               supplied to ASTRAZENECA for sale in the Excluded Countries.

6.6.6.         All payments under this Agreement shall be exclusive of Value
               Added Tax where applicable.

6.7.           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.

6.8.           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,
               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

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               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.

6.9.           WIRE TRANSFER INSTRUCTIONS.

6.9.1.         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:   AstraZeneca AB
               Account No:  [**]
               Bank:        [**]
               Swift:       [**]
               Corr bank:   [**]

6.9.2.         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:   Comerica Bank - California
               Account No:  [**]
               Bank Code:   121137522

6.10.          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

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<Page>

                                                                              39

               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 U.S. 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 and/or its
               Affiliates shall as between ASTRAZENECA and TMC remain vested in
               ASTRAZENECA and/or its Affiliates.

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

7.3.           ASTRAZENECA or its agent shall, during the term of this Agreement
               be responsible for the filing, prosecution and maintenance of the
               ASTRAZENECA Patent Rights (including, without limitation, subject
               to Article 7.7, patent term extension rights).

               TMC shall reimburse ASTRAZENECA or its agent for any
               out-of-pocket expenses (including fees to outside counsel and
               consultants) incurred by ASTRAZENECA or its agent in relation to
               any action taken by ASTRAZENECA or its agent 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 ASTRAZENECA Patent Rights; and before taking
               any significant step in the filing or prosecution of the
               ASTRAZENECA Patent Rights, ASTRAZENECA or its agent shall allow
               TMC to comment on the action proposed to be taken and ASTRAZENECA
               or its agent shall consider any such comments. For purposes of
               this Article 7.4 only, significant step means the filing of a
               dependent application (including but not limited to divisional

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                                                                              40

               or continuation applications); filing for patent term extension;
               or any step taken during an appeal, re-examination, re-issue or
               opposition procedure, provided, however, that no such action now
               mentioned is a response to an office action. Notwithstanding the
               foregoing, ASTRAZENECA or its agent may, at its own discretion,
               ask for TMC's input in relation to such office action.

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 or its agent
               shall promptly inform TMC of such decision, but no later than
               thirty (30) days prior to the date by which such action, inaction
               or failure to pay will result in lapse of the patent application
               or the patent, 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 or its agent's actions pursuant to or as a
               consequence of Articles 7.3 and 7.4.

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 or its
               agent in any issue regarding the gaining of such patent term
               extension by assisting ASTRAZENECA or its agent with any actions
               or documents needed for such purpose.

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               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 or its agent
               shall have the right to make such decision at its own reasonable
               discretion and provided that ASTRAZENECA or its agent shall allow
               TMC to comment on the action proposed to be taken and ASTRAZENECA
               or its agent shall consider any such comments.

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 and that;

               (i)  relate solely to an intravenous route of administration; and

               (ii) do not have [**]; and

               (iii)do not relate to any formulation or product which contain(s)
                    both the Compound and one or more [**]as active ingredients,
                    whether or not such formulation or product contain(s) active
                    ingredients in addition to the Compound and the [**]

               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.

               Any patents and other intellectual property rights, information,
               ideas, knowledge, data or know-how falling outside any or all of
               (i) through (iii) above in this Article 7.8 and relating to the
               Compound and/or the Product

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                                                                              42

               shall, as between TMC and ASTRAZENECA, be the sole property of
               ASTRAZENECA.

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 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.

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               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, to ASTRAZENECA 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, 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 defendant.

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 [**] 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

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               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 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:

               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 of such
               litigation. Any such joining of the proceedings

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                                                                              45

               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 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.

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               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 [**].

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 the Excluded Countries 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 of 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 under this
               Article 8.3.5 shall be retained by ASTRAZENECA.

9.             TRADEMARK

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

9.2.           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,

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               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 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 ASTRAZENECA's representations,
               warranties or obligations under this Agreement 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 or 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

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               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 or
               Products sold by ASTRAZENECA hereunder; or (iii) which arises as
               a result of a material breach of ASTRAZENECA's representations,
               warranties or obligations under this Agreement, except where such
               liability, loss, damage, cost and expense has been incurred or
               suffered as a result of a material breach of TMC's
               representations, warranties or 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

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                                                                              49

               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, 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

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               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, Drug Product 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 and non-use obligations in all
               material respects equal to those undertaken by the Receiving
               Party hereunder with respect to the Confidential Information
               disclosed by the Receiving Party to it and the results of any
               such activities.

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;

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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 ASTRAZENECA of any such
               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.

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12.2.          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.            REPRESENTATIONS, WARRANTIES AND COVENANTS

13.1.          REPRESENTATIONS, WARRANTIES AND COVENANTS OF ASTRAZENECA.
               ASTRAZENECA represents and warrants to, and covenants with, TMC
               as follows:

               a)   as of the Effective Date ASTRAZENECA and/or its Affiliates
                    is the sole and exclusive owner of the ASTRAZENECA Patent
                    Rights; which to the extent covered by the license granted
                    hereunder is free and clear of any liens, charges and
                    encumbrances; and

               b)   as of the Effective Date ASTRAZENECA and/or its Affiliates
                    has not assigned, transferred, licensed, conveyed or
                    otherwise encumbered its right, title and interest in the
                    ASTRAZENECA Patent Rights to the extent covered by the
                    license granted hereunder, to a Third Party; and

               c)   as of the Effective Date ASTRAZENECA has the authority from
                    its Affiliates to grant to TMC the license specified in
                    Article 2.1 of this Agreement; and

               d)   as of the 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; and

               e)   as of the Effective Date and to the best of ASTRAZENECA's
                    knowledge, the manufacture, use and sale of the Compound
                    does not

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                    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

               f)   as of the 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; and

               g)   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 Effective Date or at any
                    time thereafter which are or may be infringed by TMC when
                    utilizing its rights under this Agreement; and

               h)   as of the Effective Date ASTRAZENECA has disclosed to TMC
                    any known interference with the ASTRAZENECA Patent Rights or
                    re-examination or reissue proceeding concerning such
                    ASTRAZENECA Patent Rights; and

               i)   as of the Effective Date ASTRAZENECA has no knowledge from
                    which it can reasonably be inferred that the granted
                    ASTRAZENECA Patent Rights are invalid or unenforceable or
                    that the applications for ASTRAZENECA Patent Rights will not
                    proceed to grant; and

               j)   the agreements in force on the Effective Date between
                    ASTRAZENECA or its Affiliates and Third Parties regarding
                    investigational use of the Compound in laboratory research
                    animals or for testing in vitro will, if possible to
                    ASTRAZENECA, be assigned to TMC by ASTRAZENECA. Regarding
                    those agreements that are not possible for ASTRAZENECA to
                    assign to TMC, ASTRAZENECA

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                    shall keep TMC informed about the results and publications
                    generated by the Third Part(ies) under the agreements
                    concerned. None of the Third Parties to the agreements
                    referred to in this Article 13.1 j) has any license or
                    ownership rights under such agreement(s) in the results of
                    their investigations, or in the Compound, the Product or the
                    ASTRAZENECA IP that will have any material impact on the
                    license granted to TMC under this Agreement.

13.2.          ACKNOWLEDGEMENT OF TMC.

               TMC is aware;


               a)   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; and

               b)   that certain Third Parties have access to the Compound under
                    the agreements referred to in Article 13.1 j) in order to
                    conduct investigations regarding the Compound.

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

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               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 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 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 after
               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 and 6.1.3 or for any payments under Article 6.3 unless

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               corresponding to the royalty amounts actually due, which become
               due after the expiration of the 30-day period mentioned above in
               this Article 14.2.

               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, 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.

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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 [**].

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

               c)   deliver to ASTRAZENECA any and all quantities of Product in
                    its possession, power, custody or control subject always to
                    TMC's right to

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                    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
                    Articles 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, 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) for the
                    Territory or the country concerned, to the extent
                    applicable. In the event that in

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                    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, NDA's 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 for the Territory or the country concerned, to the
                    extent applicable, 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

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               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 of, and 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 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

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

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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 17.4.1 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;

               a)   if delivered by hand, upon delivery;

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

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

17.4.          CONTACT INFORMATION.


17.4.1.        Initial details for the purposes of Article 17.3 are:
               For ASTRAZENECA
               F Address: AstraZeneca AB, SE-151 85 Sodertalje, Sweden
               Facsimile: +46-8 553 290 00
               For the attention of: President & CEO

               For TMC
               Address: The Medicines Company, 8 Campus Drive, Parsippany,
               New Jersey 07054, United States
               Facsimile: +1-973-656-9898
               For the attention of: Clive Meanwell, Executive Chairman

17.4.2.        Any notice pursuant to Article 3.5.4 shall, in addition to being
               delivered in accordance with Articles 17.3 and 17.4.1, be
               delivered to the following address by facsimile.

               AstraZeneca AB,
               Global Intellectual Property,
               Sweden.
               Facsimile: +46 8 553 288 20
               For the attention of: Francis Tierney

               What is stated in Articles 17.3.1, 17.3.2, 17.3.4 and 17.3.5 c)
               shall apply to such notice as well.

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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
               27 February 2003 ceases to have effect from the Effective Date,
               except such termination does not affect a Party's accrued rights
               and obligations thereunder 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

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                                                                              65

               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

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                                                                              66

               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 Agreement has entered into force on the Effective Date.


ASTRAZENECA AB (PUBL)                           THE MEDICINES COMPANY



Signature:/s/Martin Nicklasson                  Signature: /s/ Clive A. Meanwell

Name:  Martin Nicklasson                        Name:  Clive A. Meanwell
Title: EVP, Global Drug Development             Title: Executive Chairman

                    License Agreement - The Medicines Company

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                                                                               1

                                   Schedule A

                            ASTRAZENECA Patent Rights

<Table>
<Caption>
CASE       COUNTRY     APPLICATION NO.        APP. DATE          PATENT NO.            EXPIRY DATE
--------------------------------------------------------------------------------------------------
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

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                                                                               2

<Table>
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

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<Page>

                                                                               3

<Table>
<Caption>
CASE       COUNTRY     APPLICATION NO.        APP. DATE          PATENT NO.            EXPIRY DATE
--------------------------------------------------------------------------------------------------
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

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<Page>

                                                                               4

<Table>
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

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<Page>

                                                                               5

<Table>
<Caption>
CASE       COUNTRY     APPLICATION NO.        APP. DATE          PATENT NO.            EXPIRY DATE
---------------------------------------------------------------------------------------------------
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

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<Page>

                                                                               6

<Table>
<Caption>
CASE       COUNTRY     APPLICATION NO.        APP. DATE          PATENT NO.            EXPIRY DATE
--------------------------------------------------------------------------------------------------
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

                    License Agreement - The Medicines Company

<Page>

                                                                               7

<Table>
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
[**]       [**]        [**]                   [**]               [**]                  [**]
</Table>

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                                                                               8

<Table>
<Caption>
CASE      COUNTRY     APPLICATION NO.         APP. DATE          PATENT NO.            EXPIRY DATE
--------------------------------------------------------------------------------------------------
<S>        <C>         <C>                    <C>                <C>                   <C>
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
[**]      [**]        [**]                    [**]               [**]                  [**]
</Table>

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                                                                               9

<Table>
<Caption>
COUNTRY CODE               COUNTRY
--------------------------------------
<S>                        <C>
AR                         Argentina
AT                         Austria
AU                         Australia
BD                         Bangladesh
BE                         Belgium
BR                         Brazil
BY                         Belarus
CA                         Canada
CH                         Switzerland
CO                         Colombia
CY                         Cyprus
CZ                         Czech Republic
DE                         Germany
DK                         Denmark
EE                         Estonia
EG                         Egypt
EP                         European Patent Office
ES                         Spain
FI                         Finland
FR                         France
GB                         United Kingdom
GR                         Greece
HU                         Hungary
ID                         Indonesia
</Table>

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                                                                              10

<Table>
<S>                        <C>
IE                         Ireland
IL                         Israel
IN                         India
IS                         Iceland
IT                         Italy
LT                         Lithuania
LU                         Luxembourg
LV                         Latvia
MC                         Monaco
MK                         Macedonia
MX                         Mexico
MY                         Malaysia
NL                         Netherlands
NO                         Norway
NZ                         New Zealand
PH                         Philippines
PK                         Pakistan
PL                         Poland
PT                         Portugal
RO                         Romania
RU                         Russia
SA                         Saudi Arabia
SE                         Sweden
SG                         Singapore
SI                         Slovenia
SK                         Slovak Republic
TR                         Turkey
UA                         Ukraine
US                         USA
VE                         Venezuela
</Table>

                    License Agreement - The Medicines Company

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                                                                              11

<Table>
<S>                        <C>
WO                         Patent Co-operation Treaty
ZA                         South Africa
</Table>

                    License Agreement - The Medicines Company

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                                                                               1

                                   Schedule B

                                      [**]

PRODUCT MASTER FILE


Product Monograph

This section represents the current status of the project


CONTENTS:

Clinical Supplies Strategies / Vial Strengths

Health and Safety - Assessment of health risks involved during manufacture


Composition

   - Description and intended use of product

   - Presentations and product numbers

   - Qualitative formulation

   - Quantitative formulation and formulation numbers


Manufacture

   - Manufacturer(s)

   - Manufacturing formula

   - Manufacturing process and filling

   - Equipment and manufacturing facilities

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   - Process flow diagram

   - Standard process instructions

   - In-process controls

   - Control of intermediates

   - Justification of specification for intermediates

   - Test methods for intermediates


Control Tests on Inactive Ingredients

   - Name and address of supplier

   - Specifications and test methods for inactive ingredients

   - Justification of specification for inactive ingredients

   - Test methods for inactive ingredients


Control Tests on Drug Substance

   - Name and address of suppliers and corresponding batch details

   - Statement of current route of synthesis

   - Drug substance specification

   - Product specific parameters


Control Tests on Product

   - Product specification

   - Product release specification

   - Justification for product specification

   - Test methods for product

   - Sampling plan


Packaging (Container / Closure / Device)

   - Description of packaging material and PCKs

   - Manufacturers of packaging materials

   - Specifications of packaging materials

   - Justification of specifications of packaging materials

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   - Test methods for packaging materials


Stability of Drug Substance

   - Shelf-life recommendations


Stability of Product

   - Shelf-life recommendation

   - Compatibility

   - Test methodology used for stability of product

   - Stability reports

Special Notes

Product Development Master Record


This section contains archived / superseded information (eg previous versions of
specifications) and is therefore the development history.


CONTENTS:

Health and Safety - Assessment of health risks involved during manufacture


Composition

   - Description and intended use of product

   - Presentations and product numbers

   - Qualitative formulation

   - Quantitative formulation and formulation numbers


Manufacture

   - Manufacturer(s)

   - Manufacturing formula

   - Standard process instructions

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                                                                               4

Control Tests on Inactive Ingredients

   - Name and address of supplier

   - Specifications and test methods for inactive ingredients

   - Justification of specification for inactive ingredients

   - Test methods for inactive ingredients


Control Tests on Drug Substance

   - Drug substance specification


Control Tests on Product

   - Product specification

   - Product release specification

   - Justification for product specification

   - Test methods for product

   - Sampling plan


Packaging (Container / Closure / Device)

   - Description of packaging material and PCKs

   - Manufacturers of packaging materials

   - Specifications of packaging materials

   - Justification of specifications of packaging materials

   - Test methods for packaging materials


Stability of Drug Substance

   - Shelf-life recommendations


Stability of Product

   - Shelf-life recommendation

   - Test methodology used for stability of product

   - Stability reports

                    License Agreement - The Medicines Company

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                                                                               5

Special Notes


Summary Reports

   - [**]

   - [**]


Placebo Monograph

Composition

   - Presentations and product numbers

   - Qualitative formulation

   - Quantitative formulation and formulation numbers


Manufacture

   - Manufacturer(s)

   - Manufacturing formula

   - Manufacturing process and filling

   - Equipment and manufacturing facilities

   - Process flow diagram

   - Standard process instructions

   - In-process controls

   - Control of intermediates

   - Justification of specification for intermediates

   - Test methods for intermediates


Control Tests on Inactive Ingredients

   - Name and address of supplier

   - Specifications and test methods for inactive ingredients

   - Justification of specification for inactive ingredients

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                                                                               6

   - Test methods for inactive ingredients


Control Tests on Drug Substance

   - Not applicable

   - Name and address of suppliers and corresponding batch details

   - Statement of current route of synthesis

   - Drug substance specification

   - Product specific parameters


Control Tests on Product

   - Product specification

   - Product release specification

   - Justification for product specification

   - Test methods for product

   - Sampling plan


Packaging (Container / Closure / Device)

   - Description of packaging material and PCKs

   - Manufacturers of packaging materials

   - Specifications of packaging materials

   - Justification of specifications of packaging materials

   - Test methods for packaging materials


Stability of Drug Substance - Not applicable

   - Shelf-life recommendations


Stability of Product

   - Shelf-life recommendation

   - Compatibility

   - Test methodology used for stability of product

   - Stability reports

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                                                                               7

Placebo Development Master Record

Contains archived / superseded information


PMF Appendices


Essentially this is the "working area" of the PMF containing:

   - Stability Protocols for Drug Substance

   - Stability Reports (front cover only

   - this references report number with all reports filed in archive)

   - Stability Protocols for Drug Product and Placebo Product

   - Stability Reports (main reports in full, others front cover only

   - this references report number with all reports filed in archive)

   - Protocols and Development Reports (all Investigational Protocols and
     Development Reports referenced)

   - Compatibility with Infusion Fluids and Giving Sets (all Reports / Studies
     referenced)

   - Product Design Report (all Reports referenced)

   - Regulatory Documents (CMC submissions referenced)

   - Cleaning Verification (Reports referenced)

   - Manufacturing Protocols (for clinical trial supplies manufacture at
     Sodertalje (Astra Liquid Production Facility)

   - Primary and Secondary Reference Standards

                                      [**]

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<Page>

                                                                               1

                                   Schedule C


CHEMICAL STRUCTURE [**]


                    [Diagram of proprietary compound deleted]

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                                                                               1

                                   Schedule D

<Table>
<Caption>
REPORT                          AUTHOR              REF      DUE OUT/DATED  CURRENT STATUS     FORMAT      CONTACT        SPINE
------------------------------------------------------------------------------------------------------------------------------------
<S>                             <C>  <C>        <C>         <C>             <C>              <C>         <C>            <C>
[**]                                 [**]       [**]        [**]            [**]             Hard Copy   RAR/MP
[**]                                 [**]       [**]        [**]            [**]
[**]                                 [**]       [**]        [**]            [**]             Hard Copy   RAR/MP
[**]                                 [**]       [**]        [**]            [**]             e-copy      RAR/MP
[**]                                 [**]       [**]        [**]            [**]             e-copy      RAR/MP
[**]                                 [**]       [**]        [**]            [**]             e-copy      RAR/MP
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
[**]                            *    [**]       [**]        [**]            [**]             e-copy
</Table>

                    License Agreement - The Medicines Company

<Page>
                                                                               2

<Table>
<S>                             <C>  <C>        <C>         <C>             <C>              <C>         <C>         <C>
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Yellow
[**]                                 [**]       [**]        [**]            [**]             hard copy   GET
[**]                                 [**]       [**]        [**]            [**]             hard copy   GET
                                     [**]       [**]        [**]            [**]
[**]                                 [**]       [**]        [**]            [**]             hard copy   GET
[**]                                 [**]       [**]        [**]            [**]             hard copy   RAR/MP
[**]                            *    [**]       [**]        [**]            [**]             hard copy               White
[**]                                 [**]       [**]        [**]            [**]
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Blue
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Black-blue tag
[**]                            *    [**]       [**]        [**]            [**]             hard copy               White-blue tag
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Blue
[**]                                 [**]       [**]        [**]            [**]
[**]                                 [**]       [**]        [**]            [**]             hard copy   RAR/MP
[**]                                 [**]       [**]        [**]            [**]             hard copy   RAR/MP
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Green
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Green
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Green
</Table>

                    License Agreement - The Medicines Company

<Page>
                                                                               3

<Table>
<S>                             <C>  <C>        <C>         <C>             <C>              <C>         <C>         <C>
[**]                                 [**]       [**]        [**]
[**]                                 [**]       [**]        [**]            [**]             hard copy   RAR/MP
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Black
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Black
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Black
[**]                                 [**]       [**]        [**]            [**]
[**]                            *    [**]       [**]        [**]            [**]             hard copy               Yellow
[**]                            *               [**]                                         hard copy   [**]
[**]
[**]
[**]
     Likely to be most relevant
</Table>

                    License Agreement - The Medicines Company

<Page>

                                                                               1

                                   Schedule E


                             [Diagram of proprietary
                                compound deleted]

                    License Agreement - The Medicines Company

<Page>

                                                                               1

                                   Schedule F


                                Supply Agreement
              [To be provided upon completion -- See Section 4.2.3]

                    License Agreement - The Medicines Company

</TEXT>
</DOCUMENT>
