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                                                                   Exhibit 10.14

                        COOPERATIVE DEVELOPMENT AGREEMENT

      THIS AGREEMENT, entered into as of the 8th day of November, 2002, by and
between ALTUS BIOLOGICS INC., a corporation organized and existing under the
laws of the State of Delaware and having its principal place of business at 625
Putnam Avenue, Cambridge, MA 02139 (hereinafter called "ALTUS"), and AMANO
ENZYME INC., a corporation organized and existing under the laws of Japan and
having its principal place of business at 1-2-7, Nishiki, Naka-ku, Nagoya, Japan
(hereinafter called "AMANO"),

                                   WITNESSETH:

WHEREAS, ALTUS, through research and development for a long time, acquires and
possesses certain valuable technologies pertaining to certain pharmaceutical
products known as TheraCLEC(TM) Total and a method for manufacturing such
products and continues to develop scientific techniques pertaining to the
products, and owns and controls certain patent rights and trademark rights in
the products, and

WHEREAS, AMANO has, over the years, demonstrated its expertise in development,
manufacturing and worldwide marketing of many kind of enzymes for the commercial
markets especially in food industry and pharmaceutical industry, and has thereby
established a reputation of high regard in such markets, which reputation is
believed by ALTUS to be of great value to the possible success of the joint
development contemplated hereunder, and

WHEREAS, AMANO desires to undertake manufacture of enzyme materials to be used
in the products of ALTUS,

WHEREAS, ALTUS and AMANO are willing to enter into a cooperative development of
certain enzyme materials, which are fit for TheraCLEC(TM) Total, and entire
specifications of which are instructed by ALTUS, and

WHEREAS, ALTUS and AMANO propose to decide at the end of Phase II of the U.S.
clinical trial process whether they will enter into a further manufacturing
agreement.

NOW, THEREFORE, ALTUS and AMANO agree as follows:

ARTICLE 1. DEFINITIONS

1.    The term "Products" shall mean the pharmaceutical products known as
      TheraCLEC(TM) Total, in a certain preparation form or forms intended for
      therapeutic use in humans specified, developed, manufactured, labeled and
      packaged and sold by or on behalf of ALTUS.

2.    The term "Materials" shall mean enzymes used as active ingredients in the
      Products, which are made up of selected [***********] and [******]
      prepared by AMANO in accordance with Specifications developed and
      submitted by ALTUS for use in manufacturing Products.

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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3.    The term "Amano Enzymes" shall mean enzymes including but not limited to
      [**************] and [********], which are discovered, invented,
      developed, produced, sold or otherwise disposed by Amano with its sole
      technologies and which are basis of Materials to be develop hereunder.

4.    The term "Technical Information" shall mean all of the information and
      knowledge now possessed by ALTUS or AMANO and those acquired by ALTUS or
      AMANO during the life of this Agreement, which relate to manufacturing
      process of Materials -or relate to Products.

5.    The term "ALTUS's Development" shall mean any and all works of research
      and development made by ALTUS with respect to Materials and Products to be
      developed hereunder.

6.    The term "AMANO's Development" shall mean any and all works of research
      and development made by AMANO with respect to Materials to be developed
      hereunder.

7.    The term "Joint Development" shall mean any and all technical works of
      research and development jointly made by ALTUS and AMANO with respect to
      Materials to be developed hereunder.

8.    The term "Development" shall mean ALTUS's Development, AMANO's Development
      and/or Joint Development.

9.    The term "ALTUS's Technologies" shall mean any and all technologies now
      possessed by ALTUS and those acquired by ALTUS during the life of this
      Agreement.

10.   The term "AMANO's Technologies" shall mean any and all technologies now
      possessed by AMANO and those acquired by AMANO during the life of this
      Agreement.

11.   The term "Joint Technologies" shall mean any and all technologies jointly
      developed by ALTUS and AMANO as the results of working together during the
      life of this Agreement, which relate to manufacturing process of
      Materials.

12.   The term "Patents" shall mean those patents and patent applications which
      either party owns or controls or which either party may obtain or both the
      parties may jointly obtain hereunder, the application date of which is on
      or before the date of this Agreement or during the life of this Agreement,
      and all of which are useful for or relating to Materials and/or Products.

13.   The term "Specifications" shall mean the written specifications
      established for the characteristics, quality and quality control testing
      procedures for each of Materials as developed by ALTUS, and as amended or
      supplemented from time to time.

14.   The term "Good Manufacturing Practices" shall mean good manufacturing
      practices as defined in applicable laws, regulations and guidelines.

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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ARTICLE 2. PURPOSES

ALTUS and AMANO shall together and individually make Development toward the goal
of successfully manufacturing Materials to be used in Products. ALTUS and AMANO
shall exert [************] to successfully complete Development under the terms
and conditions of this Agreement.

ARTICLE 3. RESPECTIVE CHARGES OF DEVELOPMENT

1.    ALTUS shall take charge of clinical development in the nature and
      characteristic of Materials used for the preparation of Products, and
      chemical reaction and effect against malabsorption resulting from
      pancreatic insufficiency including cystic fibrosis, and carry out such
      development at ALTUS's laboratory and AMANO's facility during the life of
      this Agreement. In the course of ALTUS's Development, ALTUS shall:

      1)    develop and establish ALTUS's Technologies utilized in Materials as
            bulk drug active for Products,

      2)    develop and establish the standard of Specifications of Materials to
            be manufactured by AMANO and prototype manufacturing processes
            therefor,

      3)    transfer to AMANO Specifications to be employed by AMANO and give
            AMANO a technical guidance in the manufacture of Materials,
            particularly TheraCLEC [******] and [**************] and [********],

      4)    inspect and approve AMANO's Development,

      5)    prepare and realize an Investigational New Drug application ("IND")
            to the Food and Drug Administration ("FDA") for Materials and/or
            Products,

      6)    provide assistance to AMANO in establishing Good Manufacturing
            Practices, and

      7)    perfect the regulatory process and retain records pertaining to
            development of the Materials and Products.

2.    AMANO shall take charge of development in the manufacture of Materials and
      carry out such development at AMANO's laboratory during the life of this
      Agreement. In the course of AMANO's Development, AMANO shall:

      1)    arrange production facility located in Japan for Materials, which
            meets requirement of Good Manufacturing Practices,

      2)    establish AMANO's Technologies of [*********************] and
            [*************************] for Materials,

      3)    establish AMANO's Technologies of the [*******] and
            [****************] for materials,

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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      4)    develop technologies manufacturing TheraCLEC [******] and
            [*************] and [********] under AMANO's Technologies in
            accordance with ALTUS's Technologies disclosed to AMANO,

      5)    develop AMANO's Technologies of manufacturing Materials in
            accordance with Specifications and guidance given by ALTUS, and

      6)    support the regulatory process and retain records pertaining to
            development of the Materials.

3.    ALTUS and AMANO shall jointly develop and establish a standard
      manufacturing management protocol for Materials on the basis of quality
      control procedures originally developed by Altus, that may need to be
      modified to fulfill requirements for an FDA regulated product or other
      product.

ARTICLE 4. EXCHANGE OF TECHNICAL INFORMATION

Forthwith after the execution of this Agreement, both parties. shall disclose to
the other party Technical Information owned and possessed in the respective
field of which either party takes charge hereunder from time to time during the
life of this Agreement. All Technical Information that was exchanged between or
developed jointly by the parties [**********************************] shall be
deemed to be information exchanged between or developed jointly by the parties
pursuant to this Article 4. All intellectual property provisions in this
Agreement shall be effective as of the earliest date that the parties began
working together.

ARTICLE 5. SUPPLY OF MATERIALS

1.    ALTUS shall provide AMANO with forecasts setting out the amounts of
      Materials it expects it will require for each month during the [********]
      period from the time of preparation of the relevant forecast. The
      forecasts shall be updated [********]. ALTUS shall prepare a separate
      forecast for the [**********] required for any [*********************].
      Upon ALTUS's request, AMANO shall supply ALTUS with reasonable quantities
      of Materials manufactured by AMANO in accordance with Specifications,
      regardless of fully finished or not, be necessary for ALTUS's Development.

2.    If ALTUS places an order for Materials with AMANO for the purpose of
      ALTUS's Development pursuant to this Agreement that does not exceed the
      amount of Materials set forth in the most recent forecast for the relevant
      month, AMANO shall [**************************************; provided,
      however, if ALTUS places an order for Materials in excess of the volume
      specified in the applicable forecast, supply by AMANO of such excess
      Materials shall be subject to [***********************************] and
      to [************************************************]. Supply of Materials
      by AMANO hereunder may be conducted through AMANO's subsidiary, Amano
      Enzyme USA Co., Ltd. based in U. S. A.

3.    The parties hereto shall make a supply contract or contracts in accordance
      with the terms of this Agreement, on a bona fide basis, from case to case
      relating to the supply of Materials as provided hereinabove. The supply
      contract shall definitely provide terms

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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      and conditions including but not limited to kind of Materials, quantities,
      Specifications, time of shipment, trade terms, price, payment and etc.

4.    AMANO shall not supply [**************] other than to ALTUS without prior
      written consent from ALTUS except as otherwise provided in Article 12.3,
      provided that nothing herein contains any restriction of supplying other
      party than ALTUS with any of Amano Enzymes or materials manufactured
      [***************************************] and/or other technologies of any
      third party.

5.    Being understood that evaluate, use or application of Materials and
      Specifications for medical products are decided by ALTUS at its sole
      discretion, AMANO shall incur no liability on Materials supplied
      hereunder, whatsoever for (a) all or any consequential or indirect losses
      or damages or loss of profit suffered or incurred by ALTUS or any third
      party howsoever caused; or (b) all or any actions, proceedings, demands or
      claims made against ALTUS or any third party by any person whatsoever,
      provided AMANO prepares the Materials in accordance with the
      Specifications and Good Manufacturing Practices. ALTUS shall indemnify and
      hold AMANO harmless from all cost, expense and liability arising out of or
      related to injury to persons or property resulting from ALTUS's use of
      Materials, provided AMANO prepares the Materials in accordance with the
      Specifications and Good Manufacturing Practices. ALTUS halt obtain and
      maintain, at its own expense, during the life of this Agreement and
      thereafter, sufficient insurance covering product liability, tort
      liability and other liability relating to Materials and Products written
      by an insurer satisfactory to AMANO and in which insurance AMANO shall be
      named as additional insured.

ARTICLE 6. JOINT DEVELOPMENT COMMITTEE

1.    ALTUS and AMANO shall, within [**********] after the execution of this
      Agreement, establish a Joint Development Committee ("JDC") to (a)
      elaborate and confirm the plan of Development contemplated herein; (b)
      give each other the progress condition of Development at the time of the
      meeting; (c) oversee the compliance of the facility with Good
      Manufacturing Practices and the transfer of the prototype process of
      manufacturing Materials from ALTUS to AMANO; (d) coordinate Development to
      the manufacturing process of Materials; and (e) to exercise decision
      making authority, and, further, shall make the plan and schedule of
      Development within [**********] after the first meeting of JDC.

2.    The JDC shall be comprised of [*****] ALTUS representatives and [*****]
      AMANO representatives, who will initially be the business and technical
      mangers. Each party may replace its JDC representative at any time, after
      discussion with the other party, with subsequent written notice to the
      other party.

3.    Decisions of the JDC shall be made by consensus approval. In the event the
      parties are unable to agree on any issue, the dispute will be referred to
      the President or a person designated by the President of each party, who
      shall promptly meet in person or by means of telephone or video conference
      and endeavor to resolve the dispute in a timely manner.

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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      In the event such individuals are unable to resolve the dispute, it shall
      be settled by [***************], or as otherwise agreed.

4.    On and after the execution of this Agreement, the JDC shall meet at least
      quarterly at regular intervals, or more often as agreed by the parties, in
      person at such locations as the parties agree, or by means of telephone or
      video conference. With the consent of the parties, other representatives
      of each party may attend JDC meetings as nonvoting observers.

5.    Each party shall each bear the expenses of their respective JDC members
      related to their participation on the JDC and attendance at JDC meetings.

ARTICLE 7. EXPENSES

1.    Each party hereto shall [*************************], including but not
      limited to, the [**************] in its laboratory
      [***********************] for Development from time to time, and such
      party [***********************************************].

2.    During ALTUS's stay in Japan for Development, ALTUS may,
      [***************], use all equipment in AMANO's laboratory, which are
      necessary for Development, and, during AMANO's stay in U.S.A. for
      Development, AMANO may, [****************], use all equipment in ALTUS's
      laboratory, which are necessary for Development.

3.    Each party hereto [**********************], including but not limited to,
      [********* *************] from U.S.A. to Japan and back,
      [**************************************************], which would be
      incurred on ALTUS or AMANO under this Agreement.

ARTICLE 8. PATENTS AND ETC.

1.    Subject to Article 8(4) below, Patents and/or other industrial property
      rights, inventions, discoveries, know-how and other technologies
      (collectively, "Intellectual Property Rights") solely developed, acquired
      or owned by either party during the life of this Agreement
      [*************************************************************
      *********************] Patents and/or other industrial property rights,
      inventions, discoveries, know-how and other technologies in any country
      without a prior written consent of such party.

2.    Each party [*****************************************] of Patents and/or
      other Intellectual Property Rights concerning all discoveries, inventions
      and/or other technologies acquired by such party in the course of or as
      the result of Development. The [***************] of such Intellectual
      Property Rights [******************] shall be ALTUS or AMANO and
      [*********************************************] for such Patents and/or
      other Industrial Property Rights [***************************].

3.    Each party [****************] for its own Intellectual Property Rights
      [***********************].

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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4.    All Intellectual Property Rights which constitute Joint Technologies shall
      be the joint property of both parties. As to Joint Technologies resulted
      from Joint Development, Intellectual Property Rights for such Joint
      Technologies shall be applied and registered, in Japan and in any overseas
      countries, in both the names of ALTUS and AMANO as to the co-owners and
      the parties shall [************] in connection with such registrations;
      provided, however, that either party may refuse to apply for
      co-registration of Intellectual Property Right in case such party has, a
      sufficient reason not to apply or a thought to hold Joint Technologies as
      trade secrets; and that where one party refuses or fails to apply for
      co-registration of such Intellectual Property Rights within 90 days of a
      request for such co-registration by the other party without such a reason
      or a thought, then the other party shall be free at their own expense to
      file an application for registration of the Intellectual Property Rights
      as sole registrant and thereafter utilize such Intellectual Property
      Rights without any requirement to pay a royalty.

5.    Either party may not assign, transfer, sell or otherwise dispose of its
      Intellectual Property Rights and know-how acquired in Joint Development to
      any third party without a prior written consent of the other party. In
      case either party desires to dispose such technologies, the other party
      [***********************************************] as negotiated between
      the parties in good faith.

6.    Subject to the terms of this agreement, the parties [*****************]
      any Intellectual Property Rights they own in accordance with Articles 8(1)
      and (4) above, in any manner they deem fit, and
      [***********************************************], provided that, if
      either party desire to have a third party utilize any Joint Technologies,
      such either party shall obtain a prior written consent of the other party.

ARTICLE 9. PLAN, SCHEDULE AND REPORTS OF DEVELOPMENT

1.    Both the parties apply due diligence to Development in accordance with the
      plan and schedule of Development which should be prepared and amended from
      time to time during the life of this Agreement by mutual consultation.
      Provided, however, that; (a) in the event that Development of either party
      should be delayed by the force majeure or other reasonable causes to such
      party, the other party shall agree to the extension [*****************]
      in the plan and schedule of Development and continue Development during
      such extended period; (b) in case any alteration of a part of whole of the
      plan and schedule of Development is required by any reason, either of the
      parties having or knowing such reason shall notify the other party to that
      effect in advance.

2.    ALTUS and AMANO shall provide the other party with the written report on
      the results of Development [******************] reasonably requested by
      the other party.

ARTICLE 10. NDA APPLICATION

1.    ALTUS shall use best efforts to research, develop and conduct such
      research, development and preclinical and human clinical trials as
      necessary or desirable to obtain all regulatory approvals to manufacture
      and market, and to obtain necessary approval to

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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      market, commence marketing and market Products in U. S. A. and any other
      countries in the world as ALTUS determines are commercially feasible.

2.    Within [**************] following the end of each [**********] period
      during the life of this Agreement, ALTUS shall prepare and deliver to
      AMANO a written report which shall describe, in reasonably sufficient
      detail, (a) the research performed to date employing Materials; (b) the
      progress of the development, and testing of Materials and Products in all
      studies including clinical trials; and (c) the status of obtaining the
      necessary approvals to market Products. In addition, ALTUS shall provide
      AMANO with a minimum of [**********] advance written notice of the
      contemplated filing of an NDA application, written notice of other
      significant regulatory filings and submissions in a timely fashion, and
      written notice of all approvals obtained after obtaining such approvals.

ARTICLE 11. COMMERCIALIZATION

1.    In case that Development of Materials and products contemplated hereunder
      has been completed and Products may be manufactured and sold on a
      commercial basis, [***************************] manufacture and sold
      Products by using all results from ALTUS's Development, AMANO's
      Development and Joint Development as well as Patents and Technical
      Information, and [**********************************************], and
      ALTUS shall [***************] to sell Products throughout the world.

2.    Notwithstanding the above, except as otherwise provided in this Agreement,
      [*********************************************] to manufacture and supply
      Materials [********] by using all results from ALTUS's Development,
      AMANO's Developments and Joint Development as well as Patents and
      Technical Information, and [************
      ***************************************] unless otherwise agreed in
      writing between the parties as to procurement of Materials from other
      manufacturing contractor or contractors than AMANO.

3.    Only ALTUS shall have a right to grant to the third party agreed upon by
      AMANO a license to manufacture Products by using all results from ALTUS's
      Development, Patents and Technical Information. Except as otherwise
      provided in this Agreement, in case ALTUS grants to the third party such a
      license, [*****************************
      *********************************************************************
      ******************************].

4.    In case ALTUS and/or its licensee procure Materials, which employ the
      results from AMANO's Development and Joint Development made hereunder,
      from other manufacturing contractor or contractors than AMANO, ALTUS, such
      licensee or such manufacturing contractor or contractors shall, unless
      otherwise provided herein, pay AMANO a royalty of [***************]
      manufactured and supplied by such manufacturing contractor or contractors
      pursuant to the rate and payment as agreed by AMANO in advance during
      commercialization.

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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5.    AMANO and ALTUS agree and acknowledge that it may be necessary during
      Phase III of the FDA clinical trial process to arrange for a separate
      manufacturer (the "Toll Manufacturer") that will be chosen jointly by
      AMANO and ALTUS to undertake certain manufacturing activities with respect
      to the [*********************************************************], and
      that for this purpose it will be necessary for AMANO and ALTUS to license
      to the Toll Manufacturer all of the necessary technology owned or licensed
      by AMANO and ALTUS. Accordingly, AMANO and ALTUS each agree to license
      such technology to such Toll Manufacturer on terms of confidentiality,
      Intellectual Property Right protection and other matters,
      [********************], reasonably satisfactory to AMANO and ALTUS.

6.    AMANO and ALTUS agree and acknowledge that in order to ensure future
      supply of Materials, it shall be necessary for ALTUS to engage a secondary
      supplier (the "Secondary Supplier"). AMANO and ALTUS therefore agree that,
      whilst it is intended that AMANO shall be the primary supplier of
      Materials, ALTUS may engage the Secondary Supplier which shall be entitled
      to use AMANO's Technologies on terms satisfactory to AMANO to produce
      quantities of Materials for use in clinical during the term of this
      Agreement.

7.    AMANO and ALTUS acknowledge that:

      (a)   ALTUS proposes to proceed with manufacture of the Products if FDA
            approval is obtained; and

      (b)   in order to pursue full-scale manufacture, the primary manufacturer
            of Materials will be required to have established a large facility
            suitable for commercial production of Materials in accordance with
            Good Manufacturing Practices; and

      (c)   the establishment of the production facility will necessarily
            involve considerable investment; and

      (d)   the party invested for such production facility including
            development works must recover such amount as invested from the
            business contemplated herein.

8.    ALTUS shall promptly deliver to AMANO all Phase II reports following
      completion of the Phase II clinical trial ("Phase H Completion") and
      statement showing definite estimation of quantities, prices of Materials
      and the Products to be manufactured and/or sold for [************] period
      commencing from the day entering Phase III. AMANO shall then advise ALTUS
      in writing within [***********] of its receipt of such Phase II reports
      whether AMANO intends to act as primary manufacturer of Materials,
      provided that the primary manufacture shall be deemed a manufacturing
      contractor who works for or on behalf of ALTUS to manufacture Materials.

9.    If AMANO decides to act as primary manufacturer of Materials following
      Phase II Completion, the parties shall proceed to negotiate in good faith
      a Manufacturing Agreement governing the manufacture and supply of
      Materials to be used by ALTUS in Phase III and/or the commercial
      manufacture and supply of Materials by AMANO. At

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

                                       9
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      this stage, the parties tentatively expect the Manufacturing Agreement to
      include the following terms and conditions:

      (a)   AMANO shall supply at least [****] of the Materials used in the
            Products to ALTUS and a royalty shall be payable to AMANO in respect
            of any licensed AMANO's Technologies used in the manufacture of
            Materials manufactured by a Secondary Supplier, in an amount
            [***********************************];

      (b)   AMANO and ALTUS agree that they shall collaborate and share details
            of the process in order to drive down the costs of the Materials.
            Both AMANO and ALTUS shall share equal responsibility through a
            joint development team that will have the function of lowering costs
            of the Materials;

      (c)   AMANO and ALTUS shall negotiate and decide upon the target price of
            the Materials supplied by AMANO to have a target price equal to the
            greater of (i) [****] of the [***************] for the Product, or
            (ii) an amount that provides AMANO with a [****] margin.

10.   If AMANO decides not to act as primary manufacturer of Materials following
      Phase II Completion, ALTUS shall be forced to cease using AMANO as the
      primary manufacturer of Materials and engage an alternative primary
      manufacturer to carry out manufacture of Materials. In this case, AMANO
      agrees that the alternative primary manufacturer shall be entitled to use
      AMANO's Technologies and Joint Technologies for the purpose of manufacture
      of Materials, subject to the terms and conditions in Article 11.4.

11.   Where applicable, commercialization and transactions contemplated in this
      Article shall be executed under the separate agreements or contracts in
      writing to be duly signed by ALTUS and AMANO.

ARTICLE 12. RESTRICTION OF USE

1.    ALTUS and AMANO have provided the other party with some information on the
      subject herein contemplated under Secrecy Agreement dated [************]
      and shall further provide each other with some additional necessary
      information and materials, if available, so as to enable the other party
      to conduct Development.

2.    Neither ALTUS nor AMANO may use the information and materials supplied
      hereunder, which ALTUS and/or AMANO is obligated to keep confidential
      under Article 13 hereof for any purpose other than for fulfilling the
      purpose of this Agreement.

3.    AMANO agrees that it shall manufacture and supply
      [********************************************] to be used for the
      products exclusively to ALTUS during the term of this Agreement.

PORTIONS OF THIS EXHIBIT WERE OMITTED AND HAVE BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE COMMISSION PURSUANT TO THE COMPANY'S APPLICATION REQUESTING
CONFIDENTIAL TREATMENT UNDER RULE 406 OF THE SECURITIES ACT.

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ARTICLE 13. CONFIDENTIALITY

1.    During the life of this Agreement and thereafter, unless otherwise agreed
      upon in writing between the parties hereto, ALTUS and AMANO shall hold in
      confidence any proprietary information provided by the other party and any
      study results, and not to disclose the same to any unauthorized third
      party by publication or otherwise without prior written consent by the
      other party, except for such information and results which:

      (a)   on the date of ALTUS's and AMANO's signing this Agreement is in the
            public domain;

      (b)   after the date of ALTUS's and AMANO's signing this Agreement becomes
            part of the public domain by publication or otherwise, except by
            breach of this Agreement by ALTUS and/or AMANO;

      (c)   ALTUS and/or AMANO can establish by competent proof that the
            information was in its possession on the date of its signing this
            Agreement and was not acquired directly or indirectly from the other
            party; and

      (d)   ALTUS and/or AMANO can establish by competent proof that the
            information was received from a third party after the date of its
            signing this Agreement; provided, however, that such information was
            not obtained by said third party directly or indirectly from the
            other party.

      (e)   is required to be disclosed by ALTUS to the FDA or other
            governmental authorities in order to obtain governmental approvals
            for the Products.

2.    It is mutually understood, however, that ALTUS or AMANO is allowed to
      disclose said information to a minimum number of investigators in their
      institutions to whom it is necessary for it to do so for the purpose of
      this Agreement on condition that such investigators shall be bound by the
      same obligation as provided in this Agreement.

3.    ALTUS and AMANO shall hold in confidence any and all negotiations with the
      other party including all past and future studies.

ARTICLE 14. PERIOD OF AGREEMENT

This Agreement shall become effective on the date first above written in this
Agreement and remain in force for a period of five (5) years thereafter, and
shall not be renewed thereafter unless agreed by both the parties hereto in
writing upon the extension of this Agreement at least six (6) months prior to
the date of expiration of this Agreement.

ARTICLE 15. TERMINATION

1.    If either party fails, refuses or neglects fully and faithfully to keep,
      observe or perform any covenant herein mentioned to be kept, observed or
      performed by either party, then, the other party may notify such party in
      writing of such default stating in such written notice the covenant or
      covenants of this Agreement which such party shall have failed,

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      refused or neglected to keep, observe or perform, and if such party, for a
      period of thirty (30) days after the service upon such party of such
      written notice, continues to fail, refuse or neglect to keep, observe or
      perform any such covenant or covenants, then the other party may cancel or
      terminate this Agreement by serving upon such party a written notice of
      such cancellation and termination hereof.

2.    ALTUS or AMANO may terminate this Agreement by giving the other party a
      written notice in the event of following:

      (a)   liquidation, dissolution, insolvency, bankruptcy or other events
            similar thereto of the other party, or

      (b)   incapability, incompetency or more than six (6) month absence of the
            other party.

3.    Either party hereto shall be entitled to cease any and all activity
      pursuant to this Agreement based on technical, scientific, medical,
      regulatory, economic or commercial factors upon one (1) year notice to the
      other party. In the event that such party gives the other party notice
      pursuant to this Article 15.3, this Agreement shall terminate after such
      one (1) year period has elapsed and such party shall not be required to
      pay any penalty, indemnity, damages or other amount to the other party
      based on the cessation of activity pursuant to this Article 15.3.

ARTICLE 16. EFFECT OF TERMINATION

1.    In case of termination of this Agreement: (i) by AMANO for ALTUS's
      material breach; or (ii) by ALTUS for reasons other than AMANO's material
      breach, ALTUS shall retain a royalty bearing license, for so long as the
      Products are sold, with right to sublicense, to AMANO's Technologies and
      Joint Technologies, to make, have made, use, sell, offer to sell and
      import Materials employing such AMANO's Technologies and Joint
      Technologies, the royalty shall be [****************] of net sales of the
      Products.

2.    In case of termination of this Agreement: (i) by ALTUS for
      [********************]; or (ii) by AMANO as a result of
      [*********************************************************], ALTUS shall
      retain a [***************] license, for so long as the Products are sold,
      with right to sublicense, to AMANO's Technologies and Joint Technologies,
      to make, have made, use, sell, offer to sell and import Materials and
      Products employing such AMANO's Technologies and Joint Technologies as
      developed during the effective period of this Agreement; [******].

3.    Upon the termination as set forth in Article 16.1 or Article 16.2, both
      the parties shall enter into a license agreement where AMANO grants ALTUS
      a license to [***********************************************] Materials
      and Products employing such AMANO's Technologies and Joint Technologies as
      developed during the effective period of this Agreement.

4.    Expiration or termination of this Agreement shall not relieve the parties
      of any obligation accruing prior to such expiration or termination

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5.    The following provisions shall survive termination: Articles 8, 11, 12,
      14, l6 and 17.

ARTICLE 17. ARBITRATION

All disputes, controversies or differences which may arise between the parties
hereto, out of or in relation to or in connection with this Agreement, or the
breach thereof, shall be finally settled by arbitration in:

      (a)   where the relevant claim is brought by ALTUS - Tokyo, Japan in
            accordance with the Commercial Arbitration Rules of The Japan
            Commercial Arbitration Association; or

      (b)   where the relevant claim is brought by AMANO - Massachusetts, United
            States of America, in accordance with the rules and procedures of
            the American Arbitration Association.

In either case, the award rendered by arbitrator(s) shall be final and binding
upon both parties.

ARTICLE 18. NOTICE

Any notice required of permitted to be given under this Agreement by either of
the parties hereto shall be deemed to have been sufficiently given for all the
purposes hereof if mailed by registered mail, postage prepaid, addressed to the
party to be notified at its address shown at the beginning of this Agreement, or
at such other address as may be furnished to the notifying party in writing.

ARTICLE 19. WAIVER

No omission or delay on the part of any party hereto in requiring a due and
punctual fulfillment by any other party hereto of the obligations of such other
parry shall be deemed to constitute a waiver by the omitting or delaying party
of any of its rights to require such due and punctual fulfillment of any other
obligations hereunder whether similar or otherwise or a waiver of any remedy it
might have hereunder.

ARTICLE 20. FORCE MAJEURE

Neither party to this Agreement shall be held responsible for the damages caused
by any delay or failure to perform under this Agreement, which is the result of
any happenings or events which could not have been reasonably avoided. Such
happenings or events shall include but shall not be limited to fire, flood,
explosion, action of the elements, acts of God, accidents, epidemics, inability
to obtain or shortage of material or equipment, riots, or other civil commotion,
war enemy action, or acts, demands or requirements of the Governments of U.S.A.
or Japan.

ARTICLE 21. ASSIGNMENT

Neither this Agreement nor any right or obligation hereunder shall be assignable
in whole or in part, whether by operation of laws, or otherwise by either party
without a prior written consent of the other party. In case of any amalgamation,
merger, consolidation or sale of all or substantially

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all the assets of ALTUS or AMANO without a prior written consent of the other
party, this Agreement and any right hereunder may
[********************************] except where
[*****************************************************************************
***************************], in such case such assignment shall require consent
from the other party, and such consent shall not be unreasonably withheld.

ARTICLE 22. GOVERNING LAW

1.    Irrespective of the place of execution or performance, this Agreement as
      to all matters except with one provided in Article 22 (2) below shall be
      considered as having been entered into in Japan and shall be construed and
      interpreted in accordance with the laws of Japan, excluding its Law
      Regarding Conflict of Laws (horei).

2.    Irrespective of Article 22(I) above, the laws of the United States of
      America (excluding its choice of law rules) shall apply to the extent that
      the provisions contained in this Agreement concern or deal with
      Intellectual Property Rights.

ARTICLE 23. AMENDMENT

This Agreement sets forth the only agreement and understanding of the parties on
the subject of cooperative development and supersedes any prior negotiations,
memorandum or agreement, whether oral or written, and neither of the parties
shall be bound by any conditions, definitions, warranties, or representations
other than as expressly provided in this Agreement, or as duly set forth on or
subsequent to the date hereof in writing and signed by a proper and duly
authorized officer of the party to be bound thereby.

ARTICLE 24. SEPARABILITY

The validity, legality and enforceability of any provision hereof shall not be
affected or impaired in any way by any holding that any other provision or
provisions contained herein are invalid, illegal or unenforceable in any
respect.

ARTICLE 25. LANGUAGE

This Agreement is in the English language only, which language shall control and
any version in any other language shall be for accommodation only and not bind
the parties hereto.

ARTICLE 26. HEADINGS

The heading of articles and paragraphs used in this Agreement are inserted for
convenience of reference only and shall not affect the interpretation of the
respective articles and paragraphs of this Agreement.

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IN WITNESS WHEREOF, the parties have caused this Agreement to be executed on the
day and year first above written. This Agreement is made in English, two copies
and both parties duly signed and retain each other.

ALTUS: ALTUS BIOLOGICS INC

    /s/ Peter Lanciano
-----------------------------------
By Peter Lanciano, President

AMANO: AMANO ENZYME CO., LTD.

    /s/ Motoyuki Amano
-----------------------------------
By Motoyuki Amano; President

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                 Amendment to Cooperative Development Agreement

THIS AMENDMENT, entered into as of the 11th day of October, 2005 (this
"Amendment"), by and between Altus Pharmaceuticals Inc. (formerly known as Altus
Biologics Inc.), a corporation organized and existing under the laws of the
State of Delaware and having its principal place of business at 125 Sidney
Street, Cambridge, Massachusetts 02139, USA ("Altus"), and Amano Enzyme Inc., a
corporation organized and existing under the laws of Japan and having its
principal place of business at 1-2-7, Nishiki, Naka-ku, Nagoya, Japan ("Amano"),
amends the Cooperative Development Agreement dated as of November 8, 2002, by
and between Altus and Amano (the "Agreement"). Capitalized terms used in this
Amendment and not defined in this Amendment shall have the meanings ascribed to
them in the Agreement.

                                   Background

WHEREAS, Altus and Amano desire to amend the Agreement to set forth certain
mutual understandings reached by the parties with respect to the manufacture and
supply of Materials by Amano for use by Altus in certain non-clinical studies
and the phase III clinical trial of the Product (collectively, the "Phase III
Materials") and the engagement of third party contract manufacturers ("CMOs") to
provide manufacturing services in connection with commercial manufacture and
supply; and


WHEREAS, Altus and Amano desire to amend the Agreement to set forth certain
additional understandings in anticipation of (a) the parties entering into a
Manufacturing Agreement for the commercial manufacture and supply of Materials
by Amano (if Amano elects to act as the primary manufacturer of some of the
Materials for commercial supply, it being understood by the parties that Amano
does not currently anticipate that it will elect to act as the initial primary
manufacturer of all of the Materials for commercial supply) and (b) the
engagement of CMOs for the commercial manufacture and supply of Materials for
which Amano does not elect to act as the primary manufacturer for commercial
supply.


NOW, THEREFORE, Altus and Amano agree to amend the Agreement as follows:

1. The parties acknowledge that certain provisions of the Agreement anticipate
that, if Amano elects to act as the primary manufacturer of Materials following
phase II Completion, the parties will negotiate a Manufacturing Agreement to
govern the manufacture and supply of Materials for both the Phase III clinical
study and the commercial supply of Products. Notwithstanding such provisions,
the parties have agreed to proceed with the manufacture and supply of Phase III
Materials as set forth below in this Amendment and to defer negotiation of a
Manufacturing Agreement until promptly after Amano makes its election pursuant
to paragraph 2 below.

2. The parties expect to reach agreement regarding Altus' anticipated needs for
commercial supply and Amano's manufacturing capacity and capabilities prior to
[***************]. With respect to Materials for which Amano has
[*************************], Amano shall make its election as to whether it will
act as the initial primary manufacturer for commercial supply on or about
[***************]. The timing of such election is critical to (a) enabling the
parties to negotiate a Manufacturing Agreement, if Amano elects to act as the
primary manufacturer for

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some of the Materials, and (b) enabling Altus to engage CMOs to assist in the
manufacture of Materials necessary for commercialization, all in a timeframe
that is consistent with Altus' commercial launch goals for the Product. Amano's
right to elect to act as the initial primary manufacturer of any or all of the
Materials for commercial supply shall be subject to Altus' right under the
Agreement to engage a Secondary Supplier for up to [*****] of any such Material.
Amano and Altus expect that the Manufacturing Agreement will provide that if
Amano [****** ***********] the initial primary manufacturer of any or all of the
Materials for commercial supply, but at a later date notifies Altus that it
wishes to become the primary manufacturer of any such Materials, the parties
shall [*********************************************************************] on
mutually agreeable terms; provided that any such transition shall be
accomplished in a manner that does not [**************************************
***].

3. The parties are currently in the process of engaging a CMO selected by the
parties to perform [***********************] in connection with Amano's
manufacture and supply of Phase III Materials. The costs of such CMO's services
shall be borne by [*****].

4. Amano shall supply GMP-compliant Phase III Materials and non-GMP compliant
non-clinical material at the following prices (excluding shipping charges):

         [*******]:    [*********] per kilogram

         [******]:     [********] per kilogram

         [******]:     [********] per kilogram

The currently anticipated requirements and delivery schedule for such Phase III
Materials to be supplied by Amano is set forth in Exhibit A to this Amendment.
Altus shall provide Amano, with updates to the requirements and delivery
schedule set forth in Exhibit A on a [******] basis until such time as Altus
provides Amano with firm purchase order(s) for such Phase III Materials, each of
which shall be provided at least [*****] prior to the final delivery date for
the Phase III Materials covered by such purchase order. Amano shall accept such
purchase order(s) and shall deliver such Phase III Materials in accordance with
such purchase order(s) to Altus' designated location(s); provided that Amano
shall not be required to provide more than [***] of the quantities set forth in
Exhibit A and Amano shall not be required to deliver Phase III Materials other
than [***************************************] set forth in Exhibit A.

5. Promptly after the date of this Amendment, the parties shall enter into a
quality agreement relating to Amano's supply of Phase III Materials, which
agreement shall address operational issues relating to manufacturing quality
typically addressed in pharmaceutical manufacturing quality agreements. The
Phase III Materials that Amano supplies shall conform to the requirements
therefor specified in Exhibit A and in the quality agreement described in this
paragraph 5; provided that the parties acknowledge that, as of the date of this
Amendment, certain aspects of [************************************************
************************************************] and the parties agree to
reasonably cooperate with one another to amend Exhibit A and the quality
agreement as needed to reflect [**************************].

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6. The parties agree that CMOs required to provide manufacturing services in
connection with the commercial manufacture and supply of Materials shall be
selected in accordance with the criteria set forth in Exhibit B and that Amano
and Altus shall work collaboratively through the JDC to select such CMOs and
decide upon the desired logistics with respect to interactions of such CMOs,
Amano and Altus in a timely manner so that Materials can be delivered on or
before Altus' required delivery dates. Because the selection of satisfactory
CMOs in a timely manner is of critical importance to Altus' regulatory and
product development responsibilities, [****************************************]
regarding the selection of any CMO [*******************************************
**************]. Unless otherwise agreed by the parties on a case-by-case basis,
Altus will contract with and supervise any requited CMOs. It is anticipated that
Altus will be responsible for [******************] costs to the extent
[*********************].

7. Amano and Altus shall cooperate with each other to promptly transfer any
necessary manufacturing technology to any CMO selected in accordance with this
Amendment. The manufacturing technology that Amano and Altus would transfer
would include, without limitation, any Technical Information, copies of
documentation possessed by Amano or Altus, and [**********************]
reasonably required to produce the Materials, in each case organized and
delivered in a manner reasonably designed to enable the transferee to make
efficient use of such technology. [*********************************************
********************************************************************************
**************].

8. Amano shall grant licenses to use AMANO's Technologies and Joint Technologies
to Altus with a right to grant sublicenses thereof to any CMOs described in
paragraph 7 of this Amendment reasonably required to enable CMOs to manufacture
Materials for commercial supply to Altus. For the purposes of clarifying Section
4 of Article 11 of the Agreement, Altus shall be responsible for making royalty
payments to Amano under that section and the royalty to be paid by Altus to
Amano with respect to Materials manufactured and supplied by a CMO using AMANO's
Technologies and/or Joint Technologies shall be [***] of [********************
******************************************].

9. If Amano elects to act as the initial primary manufacturer of some of the
Materials for commercial supply, the parties shall negotiate pricing for such
supply in connection with their negotiation of the Manufacturing Agreement
[******************************************************************************
*********************************].

10. The parties acknowledge that substantial communication and cooperation will
be needed in order to facilitate the timely manufacture and supply of Materials
for the Phase III clinical trial of the Product and for commercial supply. The
parties agree to coordinate their activities with respect to such manufacture
and supply matters through the JDC and to use reasonable efforts to undertake
such activities in a manner consistent with the best commercial interests of the
Product.

11. Without limiting Amano's exclusivity obligations set forth in Articles 5.4
and 12.3 of the Agreement, Amano shall not [************************************
********************************************************************************

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********************************************************************************
********************************************************************************
*******************************************************]; provided, however, for
the avoidance of doubt, the parties agree that Amano shall be permitted to
market, sell and supply [*******************************************] provided
in each case such enzymes are [*************************************************
**********************]; and provided further, however, Amano shall be permitted
to continue supplying the enzymes that it currently supplies to customers (other
than Altus) if, [**************************************************************
*******************************************************************************
***********************************************************************].

12. As amended by this Amendment, the Agreement remains in full force and
effect.

EXECUTED by the parties as of the date first written above.

ALTUS PHARMACEUTICALS INC.

By: /s/ Sheldon Berkle
    -------------------------------
Name: Sheldon Berkle
Title: President & CEO

AMANO ENZYME INC.

By: /s/ M. Amano
    -------------------------------
Name:  Motoyuki Amano
Title:  President

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                                    Exhibit A

Currently Anticipated Requirements and Delivery Schedule for Phase III Materials
                            to be Supplied by Amano

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                                    Exhibit B

                                  CMO Criteria

1.    Capacity/Capability

      1.2   [***]

2.    Timing - CRITICAL

      2.2   Ability to meet launch timeline

      2.3   Complete timeline through [***]

3.    Quality

      3.2   [***]

      3.3   Inspection Status and Experience

4.    Cost

      4.2   Capital costs - [***].

      4.3   Product cost (COGs)

      4.4   Start-up cost - For each [***].

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