Document:

<PAGE>
                                                                     Exhibit 4.5

                                                                  EXECUTION COPY

                AMENDED AND RESTATED VOTING STANDSTILL AGREEMENT

     THIS AMENDED AND RESTATED VOTING STANDSTILL AGREEMENT, dated as of May 21,
2004 (this "Agreement"), is entered into by and among ALTUS PHARMACEUTICALS
INC., a Delaware corporation (the "Company") (f/k/a "Altus Biologics Inc."),
VERTEX PHARMACEUTICALS INCORPORATED, a Massachusetts corporation ("Vertex"), and
each of the parties identified on Schedule A hereto (individually, a "Purchaser"
and, collectively, the "Purchasers"), and amends and restates that certain
Voting Standstill Agreement among the Company, Vertex and the other parties
thereto dated September 26, 2001, as amended on December 7, 2001 (the "Prior
Agreement").

     WHEREAS, the Company and certain of the Purchasers (the "Series C
Purchasers") contemporaneously with the execution and delivery of this
Agreement, entered into a Series C Convertible Preferred Stock and Warrant
Purchase Agreement dated as of the date hereof (the "Purchase Agreement") which
provides for the purchase by the Series C Purchasers of shares of the Company's
Series C Convertible Preferred Stock, $.01 par value per share (the "Series C
Convertible Preferred Stock") and warrants exercisable for Series C Convertible
Preferred Stock;

     WHEREAS, as an essential condition and inducement to the Series C
Purchasers to enter into the Purchase Agreement and consummate the transactions
contemplated thereby, and in consideration therefor, Vertex and the Company have
agreed to enter into this Agreement;

     WHEREAS, as of the date hereof, Vertex is the record and/or beneficial
owner of 1,000,100 shares of the Company's common stock, $.01 par value per
share (the "Common Stock"), 450,000 shares of the Company's Redeemable Preferred
Stock, $.01 par value per share (the "Redeemable Preferred Stock"), 87,500
shares of the Company's Series A Convertible Preferred Stock, $.01 par value per
share (the "Series A Convertible Preferred Stock, and together with the Common
Stock and Redeemable Preferred Stock, the "Current Shares"), and warrants to
purchase an aggregate of 4,500,000 shares of Common Stock (the "Warrants");

     WHEREAS, the parties to the Prior Agreement desire to amend and restate the
Prior Agreement in its entirety as set forth therein; and

     WHEREAS, the undersigned parties represent the necessary voting power
required to amend the Prior Agreement pursuant to Section 3.3 thereof.

     NOW, THEREFORE, in consideration of the foregoing and the mutual covenants
and agreements contained herein and in the Purchase Agreement, and for other
good and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, and intending to be legally bound hereby, the parties hereto agree
as follows:
<PAGE>
                                   ARTICLE I

                                VOTING OF SHARES

     1.1 AGREEMENT TO VOTE.

          (a) For purposes of this Agreement, "Shares" shall mean the Current
Shares and any shares of the Company's capital stock currently held by a Vertex
Affiliate (as defined below) or acquired by Vertex or any Vertex Affiliate after
the date hereof, whether upon the exercise of warrants or options, by operation
of law or otherwise, and whether as record or beneficial owner. In the event of
a stock dividend or distribution, or any change in the Company's capital stock
by reason of any stock dividend or distribution, split-up, recapitalization,
combination, exchange of shares or the like, the term "Shares" shall be deemed
to refer to and include the Shares as well as all such stock dividends and
distributions and any shares into which or for which any or all of the Shares
may be changed or exchanged. For purposes of this Agreement, "Vertex Affiliate"
shall mean any person or entity, which controls or is controlled by, or is under
common control with Vertex. For purposes of this definition, "control" means the
possession, directly or indirectly, of the power to direct the management or
policies of a person or entity, whether by ownership of voting securities, by
contract or otherwise, or the ownership, directly or indirectly, of more than
fifty percent (50%) of the voting securities or other interest of a person or
entity.

          (b) If, at the time of any meeting (whether annual or special and
whether or not an adjourned or postponed meeting) of the stockholders of the
Company, however called, or in connection with any written consent of
stockholders of the Company, the number of Shares then owned by Vertex and
Vertex Affiliates exceeds thirty-nine and nine tenths percent (39.9%) of the
voting power of the Company's capital stock entitled to vote or consent, Vertex
shall vote or consent (or cause to be voted or consented), that number of Shares
then owned by Vertex and Vertex Affiliates that exceeds thirty-nine and nine
tenths percent (39.9%) of the voting power of the capital stock entitled to vote
at such meeting or consent with respect to any written consent, in the same
proportion as the votes or consents by holders of voting capital stock other
than Vertex and the Vertex Affiliates are voted or consented for, against and
abstained.

          (c) If, at the time of any meeting (whether annual or special and
whether or not an adjourned or postponed meeting) of the holders of any class or
series of the Company's capital stock, however called, or in connection with any
written consent of the holders of any class or series of the Company's capital
stock, the voting power of the Shares then owned by Vertex and the Vertex
Affiliates exceeds thirty-nine and nine tenths percent (39.9%) of the voting
power of such series or class entitled to vote or consent, Vertex shall vote or
consent (or cause to be voted or consented), that number of Shares then owned by
Vertex and the Vertex Affiliates that exceeds thirty-nine and nine tenths
percent (39.9%) of the voting power of such class or series entitled to vote or
consent, in the same proportion as the votes or consents by holders of such
class or series other than Vertex and the Vertex Affiliates are voted or
consented for, against and abstained.

                                       2
<PAGE>
     1.2 NO OWNERSHIP INTEREST. Nothing contained in this Agreement shall be
deemed to vest in any party other than Vertex any direct or indirect ownership
or incidence of ownership of or with respect to any Shares. All rights,
ownership and economic benefits of and relating to the Shares shall remain
vested in and belong to Vertex, and neither the Company nor any Purchaser shall
have authority to manage, direct, superintend, restrict, regulate, govern, or
administer any of the policies or operations of Vertex or exercise any power or
authority to direct Vertex in the voting of any of the Shares, except as
otherwise provided herein, or in the performance of Vertex's duties or
responsibilities as stockholders of the Company.

     1.3 NO INCONSISTENT AGREEMENTS. Vertex hereby covenants and agrees that it,
except as contemplated by this Agreement, the Purchase Agreement and the Amended
and Restated Stockholders' Voting Agreement (the "Stockholders' Agreement") of
even date herewith among the Company, the Purchasers and certain stockholders of
the Company (a) has not entered, and shall not enter at any time while this
Agreement remains in effect, into any voting agreement, voting trust or similar
agreement with respect to any of the Shares and (b) has not granted, and shall
not grant at any time while this Agreement remains in effect, and the Shares are
not otherwise subject to, a proxy or power of attorney with respect to any of
the Shares which is inconsistent with the obligations of Vertex pursuant to this
Agreement.

                                   ARTICLE II

                    REPRESENTATIONS AND WARRANTIES OF VERTEX

     Vertex hereby represents and warrants to the Company and the Purchasers as
follows:

     2.1 AUTHORIZATION; VALIDITY OF AGREEMENT; NECESSARY ACTION. Vertex has full
power and authority to execute and deliver this Agreement, to perform such
obligations hereunder and to consummate the transactions contemplated hereby.
The execution, delivery and performance by Vertex of this Agreement and the
consummation by it of the transactions contemplated hereby have been duly and
validly authorized by Vertex and no other actions or proceedings on the part of
Vertex are necessary to authorize the execution and delivery by it of this
Agreement and the consummation by it of the transactions contemplated hereby.
This Agreement has been duly executed and delivered by Vertex, and constitutes a
valid and binding obligation of Vertex, enforceable against it in accordance
with its terms.

     2.2 CONSENTS AND APPROVALS; NO VIOLATIONS. None of the execution, delivery
or performance of this Agreement by Vertex nor the consummation by it of the
transactions contemplated hereby nor compliance by it with any of the provisions
hereof will (i) require any filing with, or approval of, any governmental
authority, (ii) result in a violation or breach of, or constitute (with or
without due notice or lapse of time or both) a default (or give rise to any
right of termination, amendment, cancellation or acceleration) under, any of the
terms, conditions or provisions of any note, bond, mortgage, indenture,
guarantee, other evidence of indebtedness, lease, license, contract, agreement
or other

                                       3
<PAGE>
instrument or obligation to which Vertex is a party or by which it or any of its
properties or assets may be bound or (iii) violate any order or law applicable
to it or any of its properties or assets.

     2.3 SHARES. The Current Shares are owned beneficially and of record by
Vertex and constitute all of the shares of the Company's capital stock owned of
record or beneficially by Vertex or any Vertex Affiliate. All of the Current
Shares are issued and outstanding, and, except for the Warrants, Vertex does not
own, of record or beneficially, any warrants, options or other rights to acquire
any shares of capital stock or securities of the Company and has no interest in
or voting rights with respect to any other securities of the Company. Vertex has
sole voting power, sole power of disposition, sole power to issue instructions
with respect to the matters set forth in Article I hereof, and sole power to
agree to all of the matters set forth in this Agreement, in each case with
respect to all of the Current Shares and will have sole voting power, sole power
of disposition, sole power to issue instructions with respect to the matters set
forth in Article I hereof, and sole power to agree to all of the matters set
forth in this Agreement, in each case with respect to all of the Shares, with no
limitations, qualifications or restrictions on such rights, subject to
applicable federal securities laws and the terms of this Agreement.

                                  ARTICLE III

                                  MISCELLANEOUS

     3.1 TERMINATION. This Agreement shall terminate and no party shall have any
rights or duties hereunder upon the earliest to occur of (i) the third
anniversary of the consummation of an underwritten public offering of Common
Stock of the Corporation, (ii) the time upon which the Purchasers collectively
hold less than thirty-five percent (35%) of the shares of the Series B
Convertible Preferred Stock and Series C Convertible Preferred Stock outstanding
on the date hereof and (iii) the time upon which the Purchasers collectively
hold less than thirty-five percent (35%) of the shares of Common Stock issuable
upon conversion of the shares of Series B Convertible Preferred Stock and Series
C Convertible Preferred Stock outstanding on the date hereof. Upon such
termination, no party shall have any further obligations or liabilities
hereunder, provided that no such termination shall relieve any party from
liability for any breach of this Agreement prior to such termination.

     3.2 ENTIRE AGREEMENT; NO THIRD PARTY BENEFICIARIES. This Agreement
constitutes the entire agreement and supersedes all prior agreements and
understandings, both written and oral, among the parties with respect to the
subject matter hereof, and, is not intended to confer upon any Person other than
the parties hereto any rights or remedies hereunder.

     3.3 AMENDMENTS; ASSIGNMENTS; SUCCESSORS. This Agreement may not be amended
except by an instrument in writing signed by the Company, Vertex and the holders
of at least fifty-five percent (55%) of the voting power of the shares of Series
B Convertible Preferred Stock and Series C Convertible Preferred Stock and
Common Stock issued upon conversion of the shares of Series B Convertible
Preferred Stock and

                                       4
<PAGE>
Series C Convertible Preferred Stock, including without limitation accrued but
unpaid dividends thereon (whether or not declared), then held by the Purchasers
voting together as a single class. Any amendment, termination or waiver effected
in accordance with this Section 3.3 shall be binding upon the parties hereto,
even if they do not execute such consent. This Agreement shall inure to the
benefit of and shall be binding upon the parties hereto and their respective
heirs, legal representatives and permitted assigns. Neither this Agreement nor
any of the rights, interests or obligations under this Agreement shall be
assigned delegated or otherwise transferred, in whole or in part, by any of the
parties without prior written notice to the other parties, and any purported
assignment, delegation or transfer without such notice shall be null and void.

     3.4 SEVERABILITY. If any term or other provision of this Agreement is
invalid, illegal or incapable of being enforced by any rule of law, or public
policy, all other conditions and provisions of this Agreement shall nevertheless
remain in full force and effect. Upon such determination that any term or other
provision is invalid, illegal or incapable of being enforced, the parties hereto
shall negotiate in good faith to modify this Agreement so as to effect the
original intent of the parties as closely as possible to the fullest extent
permitted by applicable law in a mutually acceptable manner in order that the
terms of this Agreement remain as originally contemplated to the fullest extent
possible.

     3.5 FAILURE OR INDULGENCE NOT WAIVER; REMEDIES CUMULATIVE. No failure or
delay on the part of any party hereto in the exercise of any right hereunder
will impair such right or be construed to be a waiver of, or acquiescence in,
any breach of any representation, warranty or agreement herein, nor will any
single or partial exercise of any such right preclude other or further exercise
thereof or of any other right. All rights and remedies existing under this
Agreement are cumulative to, and not exclusive to, and not exclusive of, any
rights or remedies otherwise available.

     3.6 GOVERNING LAW; SPECIFIC PERFORMANCE; ENFORCEMENT. This Agreement and
the rights and duties of the parties hereunder shall be governed by, and
construed in accordance with, the Law of the State of Delaware. The parties
agree that irreparable damage would occur in the event that any of the
provisions of this Agreement were not performed in accordance with their
specific terms or were otherwise breached. It is accordingly agreed that the
parties shall be entitled to an injunction or injunctions to prevent breaches of
this Agreement and to enforce specifically the terms and provisions of this
Agreement in the state courts in the State of Delaware, this being in addition
to any other remedy to which they are entitled at law or in equity. In addition,
each of the parties hereto, (a) consents to submit itself to the personal
jurisdiction of the state courts in the State of Delaware in the event any
dispute arises out of this Agreement or any transaction contemplated hereby, (b)
agrees that it will not attempt to deny or defeat such personal jurisdiction by
motion or other request for leave from any such court, (c) agrees that it will
not bring any action relating to this Agreement or any transaction contemplated
hereby in any court other than the state courts in the State of Delaware, (d)
waives any right to trial by jury with respect to any action related to or
arising out of this Agreement or any transaction contemplated hereby and (e)
consents to service of process by delivery pursuant to Section 3.7 hereof.

                                       5
<PAGE>
     3.7 NOTICES. All notices, requests, consents, and other communications
under this Agreement shall be in writing and shall be deemed delivered (i) five
business days after being sent by registered or certified mail, return receipt
requested, postage prepaid or if sent overseas, on the tenth business day, (ii)
one business day after being sent via a reputable overnight courier service
guaranteeing next business day delivery, or if sent overseas on the second
business day after being sent, (iii) at the time of delivery thereof to the
receiving party if delivered by hand and (iv) at the time that receipt thereof
has been acknowledged by electronic confirmation or otherwise, if sent by
telecopier, in each case to the intended recipient as set forth below:

     If to the Company, at 125 Sidney Street, Cambridge, Massachusetts 02139,
Attention:

     President, or at such other address or addresses as may have been furnished
in writing by the Company to the Purchasers and Vertex, with a copy to Mintz,
Levin, Cohn, Ferris, Glovsky and Popeo, P.C., One Financial Center, Boston,
Massachusetts 02111, Attention: Jonathan L. Kravetz, Esq.;

     If to a Purchaser, at the address set forth on Schedule A for such
Purchaser, or at such other address or addresses as may have been furnished to
the Company in writing by such Purchaser. If the Purchaser is holder of Series B
Convertible Preferred Stock, a copy of such notice shall be delivered to
Tomlinson Zisko LLP, 200 Page Mill Road, Second Floor, Palo Alto, California
94306, Attention: Jill E. Fishbein, Esq., and if the Purchaser is a Series C
Purchaser, a copy of such notice shall be delivered to Willkie Farr & Gallagher
LLP, 787 Seventh Avenue, New York, New York 10019, Attention: Steven J. Gartner,
Esq.; or

     If to Vertex, at 130 Waverly Street, Cambridge, Massachusetts 02139,
Attention: General Counsel, or at such other address or addresses as may have
been furnished in writing by Vertex.

     Any party may give any notice, request, consent or other communication
under this Agreement using any other means (including, without limitation,
personal delivery, messenger service, telecopy, first class mail or electronic
mail), but no such notice, request, consent or other communication shall be
deemed to have been duly given unless and until it is actually received by the
party for whom it is intended. Any party may change the address to which
notices, requests, consents or other communications hereunder are to be
delivered by giving the other parties notice in the manner set forth in this
Section.

     3.8 INTERPRETATION. The parties have participated jointly in the
negotiation of this Agreement. In the event that an ambiguity or question of
intent or interpretation arises, this Agreement shall be construed as if drafted
jointly by the parties, and no presumption or burden of proof shall arise
favoring or disfavoring any party by virtue of the authorship of the provisions
of this Agreement.

                                       6
<PAGE>
     3.9 EXPENSES. Except as otherwise provided herein, all costs and expenses
incurred in connection with this Agreement shall be paid by the party incurring
said cost or expense.

     3.10 COUNTERPARTS. This Agreement may be executed in one or more
counterparts, including via facsimile, and by the different parties hereto in
separate counterparts, each of which when executed shall be deemed to be an
original but all of which taken together shall constitute one and the same
agreement.

     3.11 DESCRIPTIVE HEADINGS. The descriptive headings used herein are
inserted for convenience of reference only and are not intended to be part of or
to affect the meaning or interpretation of this Agreement.

     3.12 ATTORNEY'S FEES. If any action at law or in equity (including
arbitration) is instituted to enforce or interpret the terms of this Agreement,
the prevailing party shall be entitled to reasonable attorney's fees, costs and
necessary disbursements in addition to any other relief to which such party may
be entitled.

                  [Remainder of Page Intentionally Left Blank]

                                       7
<PAGE>
     IN WITNESS WHEREOF, each of the parties hereto have caused this Amended and
Restated Voting Standstill Agreement to be duly executed as of the date first
written above.

                                        COMPANY:

                                        ALTUS PHARMACEUTICALS INC.

                                        By: /s/ Peter L. Lanciano
                                            ------------------------------------
                                        Name: Peter L. Lanciano
                                        Title: President and CEO

                                        VERTEX PHARMACEUTICALS
                                        INCORPORATED

                                        By: /s/ Kenneth S. Boger
                                            ------------------------------------
                                        Name: Kenneth S. Boger
                                              ----------------------------------
                                        Title: Sr. Vice President and General
                                               Counsel
                                               ---------------------------------

                                        NOMURA INTERNATIONAL PLC

                                        By: /s/ Denise Pollard-Knight
                                            ------------------------------------
                                        Name: Denise Pollard-Knight
                                              ----------------------------------
                                        Title: Head of Nomura Phase 4 Ventures
                                               ---------------------------------

                                        U.S. VENTURE PARTNERS VIII, L.P.
                                        USVP VIII AFFILIATES FUND, L.P.
                                        USVP ENTREPRENEUR PARTNERS VIII-A, L.P.
                                        USVP ENTREPRENEUR PARTNERS VIII-B, L.P.

                                        By Presidio Management Group VIII,
                                        L.L.C.
                                        The General Partner of Each

                                        By: /s/ Michael P. Maher
                                            ------------------------------------
                                        Name: Michael P. Maher
                                        Title: Attorney In-Fact

                   [Amended and Restated Standstill Agreement]
<PAGE>
                                        CMEA VENTURES LIFE SCIENCES 2000, L.P

                                        By: /s/ David Collier
                                            ------------------------------------
                                        Name: David Collier
                                              ----------------------------------
                                        Title:
                                               ---------------------------------

                                        CMEA VENTURES LIFE SCIENCES 2000,
                                        CIVIL LAW PARTNERSHIP

                                        By: /s/ David Collier
                                            ------------------------------------
                                        Name: David Collier
                                              ----------------------------------
                                        Title:
                                               ---------------------------------

                   [Amended and Restated Standstill Agreement]
<PAGE>
                                        P/S BI BIOMEDICINSK VENTURE III

                                        By: /s/ Jesper Zeuthen
                                            ------------------------------------
                                        Name: Jesper Zeuthen
                                              ----------------------------------
                                        Title: Managing Director

                                        CLARIDEN BANK

                                        By: /s/ Eric Bernhardt
                                            ------------------------------------
                                        Name: Eric Bernhardt
                                        Title: Senior Vice President

                   [Amended and Restated Standstill Agreement]
<PAGE>
                                   Schedule A

                                   Purchasers

WARBURG PINCUS PRIVATE EQUITY VIII, L.P.
466 Lexington Avenue
New York, NY 10017
Attention: Stewart Hen

U.S. VENTURE PARTNERS VIII, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP VIII AFFILIATES FUND, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP ENTREPRENEUR PARTNERS VIII-A, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

USVP ENTREPRENEUR PARTNERS VIII-B, L.P.
2735 Sand Hill Road
Menlo Park, CA 94025
Attention: Michael Maher

NOMURA PHASE4 VENTURES LP
c/o Nomura International plc
Nomura House
1 St. Martin's-le-Grand
London EC1A 4NP
United Kingdom
Attention: Charles Sermon

P/S BI BIOMEDICINSK VENTURE III
Sundkrogsgade 7
P.O. Box 2672
DK-2100 Copenhagen
Denmark
Attention: Jens W. Kindtler
<PAGE>
CLARIDEN BANK
Claridenstrasse 26
CH-8022 Zurich
Switzerland
Attention: Eric Bernhardt

CMEA VENTURES LIFE SCIENCES 2000, L.P.
One Embarcadero Center, Suite 3250
San Francisco, CA 94111
415.352.1520 ext. 200 (voice)
415.352.1524 (fax)
Attention: David Collier and Meryl Schreibstein

CMEA VENTURES LIFE SCIENCES 2000, CIVIL LAW PARTNERSHIP
One Embarcadero Center, Suite 3250
San Francisco, CA 94111
415.352.1520 ext. 200 (voice)
415.352.1524 (fax)
Attention: David Collier and Meryl Schreibstein

KIM FENNEBRESQUE
c/o SG Cowen & Co.
1221 Avenue of the Americas, 10th Floor
New York, NY 10020
(212) 278-4000 (office)
(212) 278-1641 (fax)

DAVID M. MALCOLM
460 Long Ridge
Bedford, NY 10530
(212) 278-4000 (office)
(212) 278-5599 (fax)

STELIOS PAPADOPOULOS
3 Summerset Drive South
Great Neck, NY 11020
(516) 487-5654 (home)
(516) 487-0245 (fax)

PETER REIKES
200 East 64th Street, #23A
New York, NY 10021
(212) 278-4000 (office)
(212) 278-4289 (fax)
<PAGE>
SENGAL M. SELASSIE
187 Gates Avenue
Montclair, NJ 01042
(973) 744-7525 (home)
(973) 744-7569 (fax)
(212) 278-4000 (office)
(212) 278-5454 (fax)

CHRISTOPHER A. WHITE
247 West 87th Street, #18F
New York, NY 10024
(212) 278-4000 (office)
(212) 278-5454 (fax)

NOMURA INTERNATIONAL PLC
Nomura House
1 St. Martin's-le-Grand
London EC1A 4NP
United Kingdom
Attention: Charles Sermon

SG COWEN VENTURES I, L.P.
1221 Avenue of the Americas
New York, NY 10020

PAUL J. LEACH
1134 Federal Avenue East
Seattle, WA 98102

ML INVESTMENTS LLC
One Financial Center
Boston, MA 02111

CHINA DEVELOPMENT INDUSTRIAL BANK INCORPORATED
125, Nanking East Road, Section 5
Taipei 105
Taiwan, R.O.C.
Attn: James Yen

PALLADIN OPPORTUNITY FUND LLC
195 Maplewood Avenue
Maplewood, NJ 07040
Attn: Ira Leiderman
<PAGE>
CDIB BIOTECH USA INVESTMENT, CO.
21 North Skokie Highway, Suite 104
Lake Bluff, IL 60044
Attn:Geoffrey Bonn

BAOTUNG VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

WANTUNG VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

CHUNG-SHAN VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.

CHUNG-SHAN II VENTURE CAPITAL CORPORATION
10F, 261, Sung-Chiang Road
Taipei
Taiwan, R.O.C.
Attn: Joyce Lee, Ph. D.<PAGE>
                                                                     Exhibit 4.6

THESE SECURITIES HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED, AND MAY NOT BE SOLD, PLEDGED OR OTHERWISE TRANSFERRED UNLESS (A)
COVERED BY AN EFFECTIVE REGISTRATION STATEMENT UNDER SUCH ACT OR (B) THE COMPANY
HAS BEEN FURNISHED WITH AN OPINION OF COUNSEL REASONABLY ACCEPTABLE TO THE
COMPANY TO THE EFFECT THAT NO REGISTRATION IS REQUIRED FOR SUCH TRANSFER.

================================================================================

Warrant No. RW-2                                                2,500,000 Shares

                              Amended and Restated
                                     WARRANT
                       To Purchase Shares of Common Stock
                                       of
                              ALTUS BIOLOGICS INC.
                            Dated September 26, 2001

================================================================================

     WHEREAS, Altus Biologics Inc., a Delaware corporation (the "Company"),
intends to provide the Holder an opportunity to increase its equity interest in
the Company through the acquisition of shares of its Common Stock, $.0l par
value per share ("Common Stock"), upon the exercise of a warrant with respect
thereto;

     NOW, THEREFORE, in consideration of the foregoing and other good and
valuable consideration, the receipt of which is hereby acknowledged, the Company
certifies and agrees as follows:

     This Warrant certifies that, for value received, VERTEX PHARMACEUTICALS,
INCORPORATED (the "Holder"), or registered assigns, is entitled to purchase from
the Company TWO MILLION FIVE HUNDRED THOUSAND (2,500,000) shares (the "Shares")
of the fully paid and non-assessable Common Stock of the Company, at a price of
$2.46 per share (the "Exercise Price"), such number of Shares and Exercise Price
per Share subject to adjustment as provided herein and all subject to the
conditions set forth herein. This Warrant may be exercised at any time on or
before the "Expiration Date" which shall mean February 1, 2009. This Warrant
amends and restates in its entirety that certain Warrant No. W-2 for 2,500,000
shares of Common Stock issued February 1, 1999.

     1. EXERCISE OF WARRANT.

     1.1. PROCEDURE. The Holder or any person or entity to whom the Holder has
assigned its rights under this Warrant (collectively referred to as the
"Warrantholder") may exercise this Warrant, at any time or from time to time,
prior to the Expiration Date, on any business day, by surrendering the Warrant,
accompanied by a written notice in the form attached hereto (the
<PAGE>
"Exercise Notice"), to the Company at the address designated in Section 8.4
hereof, exercising the Warrant and specifying the total number of Shares the
Warrantholder will purchase pursuant to such exercise. This Warrant may be
exercised in whole or in part as to any or all of the Shares. A certificate or
certificates for the Shares purchased upon exercise of this Warrant and, in the
event of a partial exercise of this Warrant, a new Warrant of like tenor
representing the balance of the Shares purchasable hereunder, shall be delivered
by the Company to the Warrantholder not later than ten days after payment is
made for the Shares. No fractions of a share of Common Stock will be issued upon
the exercise of this Warrant, but if a fractional share would be issuable upon
exercise, the Company will pay in cash the fair market value thereof as
determined under Section 1.2 below.

     1.2. EXERCISE MECHANICS. The Warrantholder may exercise the Warrant by
paying to the Company, by cash or check, an amount equal to the aggregate
Exercise Price of the Shares being purchased. As used herein, the fair market
value of the Common Stock shall mean the mean between the highest and lowest
quoted selling prices on such date on the securities market where the Common
Stock of the Company is traded, or if there were no sales on the applicable
date, on the next preceding date within a reasonable period (as determined in
the sole discretion of the Board of Directors of the Company) on which there
were sales. In the event that there were no sales in such a market within a
reasonable period, the fair market value shall be as determined in good faith by
the Board of Directors. In the event the Warrantholder disagrees with the fair
market value determined by the Board of Directors, the Company and the
Warrantholder shall use their best efforts to agree upon the selection of an
independent appraiser, who will have 30 days in which to determine the fair
market value of the Common Stock, and whose determination will be final and
binding on all parties concerned. All costs of such determination shall be borne
by the Company.

     2. RECORD HOLDER. A Warrant shall be deemed to have been exercised
immediately prior to the close of business on the date of its surrender for
exercise as provided in Section 1.1 above and the person entitled to receive the
Shares of Common Stock issuable upon such exercise or conversion shall be
treated for all purposes as the holder of such Shares of record as of the close
of business on such date.

     3. PAYMENT OF TAXES. The Company shall pay all taxes and other governmental
charges (other than income taxes) that may be imposed in respect of the issue of
delivery of the Shares or any portion thereof The Company shall not be required,
however, to pay any tax or other charge imposed in connection with any transfer
involved in the issue of any certificate for the Shares or any portion thereof
in any name other than that of the registered holder of the Warrant surrendered
in connection with the purchase of such shares, and in such case the Company
shall not be required to issue or deliver any certificate until such tax or
other charge has been paid or it has been established to the Company's
satisfaction that no tax or other charge is due.

     4. TRANSFER AND EXCHANGE.

     4.1 TRANSFER. Subject to the terms hereof, including, without limitation,
Sections 5.1 and 5.3, the Warrant and all rights thereunder are transferable, in
whole or in part, on the books

                                       2
<PAGE>
of the Company maintained for such purpose at its office designated in Section
8.4 hereof by the registered holder hereof in person or by duly authorized
attorney, upon surrender of the Warrant property endorsed. Upon any partial
exercise or transfer, the Company will issue and deliver to such holder a new
warrant or warrants with respect to the Shares not so exercised, converted or
transferred. Each taker and holder of the Warrant, by taking or holding the
same, consents and agrees that the Warrant when endorsed in blank shall be
deemed negotiable, and that when the Warrant shall have been so endorsed, the
holder may be treated by the Company and all other persons dealing with the
Warrant as the absolute owner of such Warrant for any purpose and as the person
entitled to exercise the rights represented thereby, or to the transfer on the
books of the Company, any notice to the contrary notwithstanding; but until such
transfer on such books, the Company may treat the registered holder of the
Warrant as the owner for all purposes. The term "Warrant" as used herein shall
include the Warrant and, any warrants delivered in substitution or exchange
therefor as provided herein.

     4.2 EXCHANGE. The Warrant is exchangeable for a warrant or warrants for the
same aggregate number of Shares, each new Warrant to represent the right to
purchase such number of Shares as the holder shall designate at the time of such
exchange. The Warrant may be subdivided, at the Warrantholder's option, into
several warrants to purchase the Shares (collectively, also referred to as the
"Warrant"). Such subdivision may be accomplished in accordance with the
provisions of this Section 4.

     5. TRANSFER OF SECURITIES

     5.1. RESTRICTIONS ON TRANSFER. Neither the Warrant nor the Shares shall be
transferable except upon the conditions specified in this Section 5.1, which
conditions are intended to insure compliance with the provisions of the
Securities Act of 1933 (the "1933 Act") in respect to the transfer of the
Warrant and the Shares.

          5.1.1. Unless and until otherwise permitted by this Section 5.1, the
Warrant and each certificate or other document evidencing any of the Shares
shall be endorsed with the legend substantially in the following form:

THESE SECURITIES HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED, AND MAY NOT BE SOLD, PLEDGED OR OTHERWISE TRANSFERRED UNLESS (A)
COVERED BY AN EFFECTIVE REGISTRATION STATEMENT UNDER SUCH ACT, OR (B) THE
COMPANY HAS BEEN FURNISHED WITH AN OPINION OF COUNSEL REASONABLY ACCEPTABLE TO
THE COMPANY TO THE EFFECT THAT NO REGISTRATION IS REQUIRED FOR SUCH TRANSFER.

          5.1.2. Neither the Warrant nor the Shares shall be transferred, and
the Company shall not be required to register any such transfer, unless and
until one of the following events shall have occurred:

                                       3
<PAGE>
               (a) the Company shall have received an opinion of counsel
reasonably acceptable to the Company and its counsel, stating that the
contemplated transfer is exempt from registration under the 1933 Act as then in
effect, and the Rules and Regulations of the Securities and Exchange Commission
(the "Commission") thereunder. Within ten days after delivery to the Company and
its counsel of such an opinion, the Company either shall deliver to the proposed
transferor a statement to the effect that such opinion is not satisfactory in
the reasonable opinion of its counsel (and shall specify in detail the legal
analysis supporting any such conclusion) or shall authorize the Company's
transfer agent to make the requested transfer;

               (b) the Company shall have been furnished with a letter from the
Commission in response to a written request in form and substance acceptable to
counsel for the Company setting forth all of the facts and circumstances
surrounding the contemplated transfer, stating that the Commission will take no
action with regard to the contemplated transfer; the Warrant or the Shares are
transferred pursuant to a registration statement which has been filed with the
Commission and has been effective; or

               (c) the restrictions on transfer imposed by this Section 5.1
shall cease and terminate as to the Warrant and the Shares when (i) such
securities shall have been effectively registered under the 1933 Act and sold by
the holder thereof in accordance with such registration, or (ii) an acceptable
opinion as described in Section 5.1.2(a) or a "no action" letter described in
Section 5.1.2(b) states that future transfers of such securities by the
transferor or the contemplated transferee would be exempt from registration
under the 1933 Act. When the restrictions on transfer contained in this Section
5.1 have terminated as provided above, the holder of the securities as to which
such restrictions shall have terminated or the transferee of such holder shall
be entitled to receive promptly from the Company, without expense to him, new
certificates not bearing the legend set forth in Section 5.1.1 hereof.

     5.2. COOPERATION. The Company shall cooperate in supplying such information
as may be reasonably requested by the Warrantholder to complete and file any
information reporting forms presently or subsequently required by the Commission
as a condition to the availability of an exemption, presently existing or
subsequently adopted, from the 1933 Act for the sale of the Warrant or Shares.

     5.3. PERMITTED TRANSFERS. The Warrantholder may, subject to all applicable
laws and rules, transfer this Warrant and any Shares purchased hereunder only
with the prior written consent of the Company; provided, however, that the
foregoing restriction shall terminate upon the effective date of the initial
registration statement covering a public offering of the Company's Common Stock,
which registration contemplates the registration and continued reporting under
Section 13 or 15(d) of the Securities Exchange Act of 1934. All certificates
evidencing Shares purchased under this Warrant prior to the effective date of
such initial public offering shall bear a legend substantially to the effect of
the foregoing.

     6. ADJUSTMENTS TO EXERCISE PRICE AND SHARES. The Exercise Price in effect
from time to time and the number of Shares shall be subject to adjustment in
certain cases as set forth in this Section 6.

                                       4
<PAGE>
     6.1. SUBDIVISION OR COMBINATION. In the event the outstanding Common Stock
shall be subdivided into a greater number of shares of Common Stock, the
Exercise Price for the Shares shall, simultaneously with the effectiveness of
such subdivision, be proportionately reduced and the number of Shares
proportionately increased, and conversely, in case the outstanding Common Stock
shall be combined into a small number of shares of Common Stock, the Exercise
Price shall. simultaneously with the effectiveness of such combination, be
proportionately increased and the number of Shares proportionately reduced. For
the purposes of this Section 6, a distribution or series of distributions of
Common Stock to holders of Common Stock in which the number of shares
distributed is ten percent (10%) or more of the number of shares of Common Stock
upon which the distribution is to be made shall be deemed to be a subdivision of
Common Stock.

     6.2. ADJUSTMENT FOR REORGANIZATION, CONSOLIDATION OR MERGER.

          6.2.1. In case of any reorganization of the Company (or any other
corporation the stock or other securities of which are at the time receivable on
the exercise of the Warrant) after the date on which this Warrant is first
issued (the "Issuance Date"), or in case, after such date, the Company (or any
such other corporation) shall consolidate with or merge into another corporation
or convey all or substantially all of its assets to another corporation, then
and in each such case the Warrantholder, upon exercise of the Warrant as
provided in Section 1 hereof at any time after the consummation of such
reorganization, consolidation, merger or conveyance, shall be entitled to
receive, in lieu of the stock or other securities and property receivable upon
the exercise of the Warrant prior to such consummation, the stock or other
securities or property to which the Warrantholder would have been entitled upon
such consummation if the Warrantholder had exercised or converted the Warrant
immediately prior thereto; in each such case, the terms of this Warrant,
including the exercise provisions of Section 1, shall be applicable to the
shares of stock or other securities or property receivable upon the exercise of
the Warrant after such consummation.

          6.2.2. The Company shall not effect any consolidation, merger or
conveyance of all or substantially all of its assets unless prior to the
consummation thereof the successor corporation (if other than the Company)
resulting from such consolidation or merger or the corporation into or for the
securities of which the previously outstanding stock of the Company shall be
charged in connection with such consolidation or merger, or the corporation
purchasing such assets, as the case may be, shall assume by written instrument,
in form and substance reasonably satisfactory to the Warrantholder, executed and
delivered in accordance with Section 10.4 hereof, the obligation to deliver to
the Warrantholder such shares of stock, securities or assets as, in accordance
with the foregoing provisions, the Warrantholder is entitled to purchase.

          6.2.3. If a purchase, tender or exchange offer is made to and accepted
by the holders of more than 50% of the outstanding shares of Common Stock of the
Company, the Company shall not effect any consolidation, merger or sale with the
Person having made such offer or with any Affiliate of such Person, unless prior
to the consummation of such consolidation, merger or sale the Warrantholder
shall have been given a reasonable opportunity to then elect to receive either
the stock, securities or assets then issuable upon the exercise of the Warrant
or, if different, the stock, securities or assets, or the equivalent, issued to
previous holders of the Common Stock in

                                       5
<PAGE>
accordance with such offer, computed as though the Warrantholder hereof had been
at the time of such offer, a holder of the stock, securities or assets then
purchasable upon the exercise or conversion of the Warrant. As used in this
paragraph 6.2.3. the term "Person" shall mean and include an individual, a
partnership, a corporation, a trust, a joint venture, an unincorporated
organization and a government or any department or agency thereof. and an
"Affiliate" of any Person shall mean any Person directly or indirectly
controlling, controlled by or under direct or indirect common control with, such
other Person. A Person shall be deemed to control a corporation if such Person
possesses, directly or indirectly, the power to direct or cause the direction of
the management and policies of such corporation, whether through the ownership
of voting securities, by contract or otherwise.

     6.3. ADJUSTMENTS TO EXERCISE PRICE FOR CERTAIN DILUTING ISSUANCES.

          6.3.1 Special Definitions. The following definitions shall apply:

               (A) "Option" shall mean rights, options or warrants to subscribe
          for, purchase or otherwise acquire Common Stock or Convertible
          Securities.

               (B) "Series B Original Issue Date" shall mean the date on which a
          share of Series B Preferred Stock was first issued.

               (C) "Convertible Securities" shall mean any evidences of
          indebtedness, shares or other securities directly or indirectly
          convertible into or exchangeable for Common Stock, but excluding
          Options.

               (D) "Additional Shares of Common Stock" shall mean all shares of
          Common Stock issued (or pursuant to Section 6.3.3 deemed to be issued)
          by the Company after the Series B Original Issue Date, other than:

                    (I) shares of Common Stock issued or issuable upon
               conversion or exchange of any Convertible Securities or exercise
               of any Options outstanding on the Series B Original Issue Date;

                    (II) shares of Common Stock issued or issuable as a dividend
               or distribution on any series of Preferred Stock;

                    (III) shares of Common Stock issued or issuable by reason of
               a dividend, stock split, split-up or other distribution on shares
               of Common Stock that is covered by Subsection 6.1 or 6.2 above;
               and

                    (IV) shares of Common Stock (or Options with respect
               thereto), issued or issuable for compensatory purposes to
               employees or directors of, or consultants to, the Company or any
               of its subsidiaries pursuant to a plan, agreement or arrangement
               approved by the Board of Directors of the Corporation, including,
               for so long as the holders of Series B Preferred Stock are
               entitled to elect a member of the Board of Directors of the
               Corporation, at least one Director who constitutes a "Series B
               Director" as

                                       6
<PAGE>
               that term is defined in that certain Investor Rights Agreement,
               dated as of September 26, 2001, by and between the Company and
               the individuals and entities listed in Exhibit A thereto,
               provided that the maximum number of shares issuable under such
               plan, agreement or arrangement has also been approved by the
               Board of Directors of the Company, including, for so long as the
               holders of Series B Preferred Stock are entitled to elect a
               member of the Board of Directors of the Company, at least one
               Director who constitutes a Series B Director ("Employee
               Options").

          6.3.2 No Adjustment of Exercise Price. No adjustment in the Exercise
Price shall be made as the result of the issuance of Additional Shares of Common
Stock if: (a) the consideration per share (determined pursuant to Subsection
3.3.5 for such Additional Share of Common Stock issued or deemed to be issued by
the Company is equal to or greater than the Exercise Price in effect immediately
prior to the issuance or deemed issuance of such Additional Shares of Common
Stock, or (b) prior to such issuance or deemed issuance, the Company receives
written notice from the holders of a majority in interest of the Shares agreeing
that no such adjustment shall be made as the result of the issuance or deemed
issuance of Additional Shares of Common Stock.

          6.3.3 Deemed Issue of Additional Shares of Common Stock. If the
Company at any time or from time to time after the Series B Original Issue Date
shall issue any Options (excluding Employee Options) or Convertible Securities
or shall fix a record date for the determination of holders of any class of
securities entitled to receive any such Options or Convertible Securities, then
the maximum number of shares of Common Stock (as set forth in the instrument
relating thereto without regard to any provision contained therein for a
subsequent adjustment of such number) issuable upon the exercise of such Options
or, in the case of Convertible Securities and Options therefor, the conversion
or exchange of such Convertible Securities, shall be deemed to be Additional
Shares of Common Stock issued as of the time of such issue or, in case such a
record date shall have been fixed, as of the close of business on such record
date, provided that Additional Shares of Common Stock shall not be deemed to
have been issued unless the consideration per share (determined pursuant to
Subsection 6.3.5 hereof) of such Additional Shares of Common Stock would be less
than the applicable Exercise Price in effect on the date of and immediately
prior to such issue, or such record date, as the case may be, and provided
further that in any such case in which Additional Shares of Common Stock are
deemed to be issued:

               (A) No further adjustment in the Exercise Price shall be made
          upon the subsequent issue of Convertible Securities or shares of
          Common Stock upon the exercise of such Options or conversion or
          exchange of such Convertible Securities;

               (B) If such Options or Convertible Securities by their terms
          provide, with the passage of time or otherwise, for any increase or
          decrease in the consideration payable to the Company, then upon the
          exercise, conversion or exchange thereof, the Exercise Price computed
          upon the original issue thereof (or

                                       7
<PAGE>
          upon the occurrence of a record date with respect thereto), and any
          subsequent adjustments based thereon, shall, upon any such increase or
          decrease becoming effective, be recomputed to reflect such increase or
          decrease insofar as it affects such Options or the rights of
          conversion or exchange under such Convertible Securities;

               (C) Upon the expiration or termination of any such unexercised
          Option or unconverted Convertible Security, the Exercise Price shall
          not be readjusted, but the Additional Shares of Common Stock deemed
          issued as the result of the original issue of such Option or
          Convertible Security shall not be deemed issued for the purposes of
          any subsequent adjustment of the Exercise Price;

               (D) In the event of any change in the number of shares of Common
          Stock issuable upon the exercise, conversion or exchange of any such
          Option or Convertible Security, including, but not limited to, a
          change resulting from the anti-dilution provisions thereof, the
          Exercise Price then in effect shall forthwith be readjusted to such
          Exercise Price as would have obtained had the adjustment which was
          made upon the issuance of such Option or Convertible Security not
          exercised, converted or exchanged prior to such change been made upon
          the basis of such change but no further adjustments shall be made for
          the actual issuance of Common Stock upon exercise of any such Option
          or Convertible Security; and

               (E) No readjustment pursuant to clause (B) or (D) above shall
          have the effect of increasing the Exercise Price to an amount which
          exceeds the lower of (i) the Exercise Price on the original adjustment
          date, or (ii) the Exercise Price that would have resulted from any
          issuances of Additional Shares of Common Stock between the original
          adjustment date and such readjustment date.

     In the event that, after the Series B Original Issue Date, the price at
which Options or Convertible Securities may be exercised or converted is
decreased, or the number of shares into which Options or Convertible Securities
may be exercised or converted is increased, (whether such Options or Convertible
Securities were outstanding on the Series B Original Issue Date or were issued
after the Series B Original Issue Date), then such Options or Convertible
Securities, as so modified, shall be deemed to have been issued after the Series
B Original Issue Date and the provisions of this Subsection 6.3.3 shall apply

          6.3.4 Adjustment of Exercise Price Upon Issuance of Additional Shares
of Common Stock. In the event the Company shall at any time after the Series B
Original Issue Date issue Additional Shares of Common Stock (including
Additional Shares of Common Stock deemed to be issued pursuant to Subsection
6.3.3, but excluding Additional Shares of Common Stock issued in a Qualifying
Public Offering, as defined in the Company's Certificate of Incorporation, as
amended and in effect from time to time), without consideration or for a
consideration per share less than the applicable Exercise Price in effect
immediately prior to such issue, then and in such event, such Exercise Price
shall be reduced, concurrently with such issue, to a price (calculated to the
nearest cent) determined by multiplying such Exercise Price by a fraction, (A)
the numerator of

                                       8
<PAGE>
which shall be (1) the number of shares of Common Stock outstanding immediately
prior to such issue plus (2) the number of shares of Common Stock which the
aggregate consideration received or to be received by the Company for the total
number of Additional Shares of Common Stock so issued would purchase at such
Exercise Price; and (B) the denominator of which shall be the number of shares
of Common Stock outstanding immediately prior to such issue plus the number of
such Additional Shares of Common Stock so issued, provided that, (i) for the
purpose of this Subsection 6.3.4, all shares of Common Stock issuable upon
conversion or exchange of Convertible Securities outstanding immediately prior
to such issue shall be deemed to be outstanding, and (ii) the number of shares
of Common Stock deemed issuable upon conversion or exchange of such outstanding
Convertible Securities shall not give effect to any adjustments to the
conversion or exchange price or conversion or exchange rate of such Convertible
Securities resulting from the issuance of Additional Shares of Common Stock that
is the subject of this calculation.

          6.3.5 Determination of Consideration. For purposes of this Subsection
6.3, the consideration received by the Company for the issue of any Additional
Shares of Common Stock shall be computed as follows:

               (A) Cash and Property: Such consideration shall:

                    (I) insofar as it consists of cash, be computed at the
               aggregate of cash received by the Company, excluding amounts paid
               or payable for accrued interest;

                    (II) insofar as it consists of property other than cash, be
               computed at the fair market value thereof at the time of such
               issue, as determined in good faith by the Board of Directors; and

                    (III) in the event Additional Shares of Common Stock are
               issued together with other shares or securities or other assets
               of the Company for consideration which covers both, be the
               proportion of such consideration so received, computed as
               provided in clauses (I) and (II) above, as determined in good
               faith by the Board of Directors.

               (B) Options and Convertible Securities. The consideration per
          share received by the Company for Additional Shares of Common Stock
          deemed to have been issued pursuant to Subsection 6.3.3, relating to
          Options and Convertible Securities, shall be determined by dividing

                    (x) the total amount, if any, received or receivable by the
               Company as consideration for the issue of such Options or
               Convertible Securities, plus the minimum aggregate amount of
               additional consideration (as set forth in the instruments
               relating thereto, without regard to any provision contained
               therein for a subsequent adjustment of such consideration)
               payable to the Company upon the exercise of such

                                       9
<PAGE>
               Options or the conversion or exchange of such Convertible
               Securities, or in the case of Options for Convertible Securities,
               the exercise of such Options for Convertible Securities and the
               conversion or exchange of such Convertible Securities, by

                    (y) the maximum number of shares of Common Stock (as set
               forth in the instruments relating thereto, without regard to any
               provision contained therein for a subsequent adjustment of such
               number) issuable upon the exercise of such Options or the
               conversion or exchange of such Convertible Securities.

     6.4. NOTICE OF ADJUSTMENT. When any adjustment is required to be made in
the Exercise Price, the Company shall promptly notify the Warrantholder of such
event, of the calculation by which such adjustment is to be made and of the
resulting Exercise Price.

     6.5. DUTY TO MAKE FAIR ADJUSTMENTS IN CERTAIN CASES. If any event occurs as
to which in the opinion of the Board of Directors the other provisions of this
Section 6 are not strictly applicable or if strictly applicable would not fairly
protect the purchase and exercise rights of the Warrant in accordance with the
essential intent and principles of such provisions, then the Board of Directors
shall make an adjustment in the application of such provisions, in accordance
with such essential intent and principles, so as to protect such purchase rights
as aforesaid.

     7. RESERVATION OF SHARES. The Company shall at all times reserve and keep
available out of its authorized but unissued Common Stock the full number of
Shares deliverable upon exercise of the Warrant, Shares as such number may
change from time to time. Also, the Company shall, at its own expense, take all
such actions and obtain all such permits and orders as may be necessary to
enable the Company lawfully to issue the Shares upon the exercise or conversion
of the Warrant.

     8. MISCELLANEOUS.

     8.1. ENTIRE AGREEMENT. This Warrant constitutes the full and entire
understanding and agreements between the parties hereto with respect to the
subjects hereof and thereof.

     8.2. SUCCESSORS AND ASSIGNS. The terms and conditions of this Warrant shall
inure to the benefit of and be binding upon the respective successors and
assigns of the parties hereto, except as expressly provided otherwise herein.

     8.3. GOVERNING LAW. This Warrant shall be governed by and construed under
the laws of the Commonwealth of Massachusetts.

     8.4. NOTICES, ETC. All notices and other communications required or
permitted hereunder shall be in writing and shall be deemed effectively given
upon personal delivery or upon the seventh day following mailing by registered
air mail, postage prepaid, addressed (a) if to the Warrantholder, at 13 Waverly
Street, Cambridge, Massachusetts 02139, Attention: Kenneth S. Boger, Esq. or at
such other address as shall have furnished to the Company in

                                       10
<PAGE>
writing, (b) if to the Company, a copy should be sent to 625 Putnam Street,
Cambridge, MA 02139, Attention: President, or at such other address as the
Company shall have furnished in writing to the Warrantholder, with a copy to
Mintz, Levin Cohn, Ferris, Glovsky and Popeo, P.C., One Financial Center, MA
02111, Attention: Jonathan L. Kravetz, or (c) if to any other Warrantholder, at
such address as such holder shall have furnished to the Company in writing, or,
until such Warrantholder so furnishes an address to the Company, then to and at
the address of the last holder of such Warrant who so furnished an address to
the Company.

     8.5. DELAYS OR OMISSIONS. No delay or omission to exercise any right, power
or remedy accruing to any holder of any securities issued or sold or to be
issued or sold hereunder, upon any breach or default of the Company under this
Warrant, shall impair any such right, power or remedy of such holder nor shall
it be construed to be a waiver of any such breach or default, or an acquiescence
therein, or in any similar breach or default thereafter occurring, nor shall any
waiver of any single breach or default be deemed a waiver of any other breach or
default theretofore or thereafter occurring. Any waiver, permit, consent or
approval of any kind or character on the part of any holder of any breach or
default under this Warrant, or any waiver on the part of any holder of any
provisions or conditions of this Warrant must be in writing and shall be
effective only to the extent specifically set forth in such writing. All
remedies, either under this Warrant or by law or otherwise afforded to any
holder, shall be cumulative and not alternative.

     8.6. SURVIVAL. The representations, warranties, covenants and agreements
made herein shall survive the execution and delivery of this Warrant, except as
expressly provided otherwise herein or therein.

     8.7. WAIVERS AND AMENDMENTS. With the written consent of the record or
beneficial holders of more than 50% in interest of the Shares, the obligations
of the Company and the rights of the Warrantholders may be waived (either
generally or in a particular instance, either retroactively or prospectively and
either for a specified period of time or indefinitely), and with the same
consent the Company, when authorized by resolution of its board of directors,
may enter into a supplemental agreement for the purpose of adding any provisions
to or changing in any manner or eliminating any of the provisions of this
Warrant; provided, however, that no such waiver or supplemental agreement shall
reduce the aforesaid percentage of the Shares, the holders of which are required
to consent to any waiver or supplemental agreement, without the consent of the
record or beneficial holders of all the Shares (treated as if exercised). Upon
the effectuation of each such waiver, consent, agreement of amendment or
modification. the Company promptly shall give written notice thereof to the
record holders of the Warrant and the Shares. This Warrant or any provision
hereof may not be changed, waived, discharged or terminated orally, but only by
a statement in writing signed by the party against which enforcement of the
change, waiver, discharge or termination is sought, except to the extent
provided in this Section 8.7.

     8.8. SEVERABILITY. If one or more provisions of this Warrant are held to be
invalid, illegal or unenforceable under applicable law, such provision shall be
modified in such manner as to be valid, legal and enforceable, but so as to most
nearly retain the intent of the parties. and if such modification is not
possible, such provision shall be severed from this Warrant as if such

                                       11
<PAGE>
provision were not included. in either case, and the balance of this Warrant
shall not in any way be affected or impaired thereby and shall be enforceable in
accordance with its terms.

     8.9. REGISTERED HOLDER. The Company may deem and treat the registered
Warrantholder(s) hereof as the absolute owner(s) of this Warrant
(notwithstanding any notation of ownership or other writing hereon made by
anyone), for the purpose of any exercise or conversion hereof, of any
distribution to the Warrantholder(s) hereof, and for all other purposes, and the
Company shall not be affected by any notice to the contrary. Other than as set
forth herein, this Warrant does not entitle any Warrantholder hereof to any
rights of a stockholder of the Company.

     8.10. TITLES AND SUBTITLES. The titles of the sections and subsections of
this Warrant are for convenience and are not to be considered in construing this
Warrant.

                                       12
<PAGE>
     IN WITNESS WHEREOF, Company has caused this Warrant to be signed by its
duly authorized officer and issued as of the date set forth below.

Dated: September ___, 2001

                                        ALTUS BIOLOGICS INC.

                                        By:
                                            ------------------------------------
                                            Peter Lanciano
                                            President

                                       13
<PAGE>
                               NOTICE OF EXERCISE

                 (To be Executed by the Registered Warrantholder
                        in order to Exercise the Warrant)

     The undersigned hereby irrevocably elects to exercise the right to purchase
___________________ (_____) shares of the Common Stock, $.01 par value, of Altus
Biologics Inc., a Delaware corporation, covered by Warrant No. W-___, according
to the conditions thereof and herewith makes payment of the Exercise Price of
such Shares in full.

     I. Such payment is hereby tendered in the form of $____________________ by
wire transfer or certified or bank check.

     II. The undersigned elects to receive the net value of the Shares pursuant
to Section 1.2 of the Warrant.

                                        Printed Name of Warrantholder:

                                        ----------------------------------------

                                        Signature:

                                        ----------------------------------------

                                        Title (if signing on
                                        behalf of a Warrantholder):

                                        ----------------------------------------

                                        Date:

                                        ----------------------------------------

                                        Address:

                                        ----------------------------------------

                                       14
<PAGE>
                               FORM OF ASSIGNMENT

     For Value Received, the undersigned registered owner of this Warrant issued
by Altus Biologics Inc. hereby sells, assigns and transfers unto the Assignee
named below all of the rights of the undersigned under the within Warrant No.
W-_____, with respect to the number of Shares of Common Stock set forth below:

<TABLE>
<CAPTION>
Name of Assignee   Address   Number of Shares
----------------   -------   ----------------
<S>                <C>       <C>

</TABLE>

and does hereby irrevocably constitute and appoint __________ attorney to make
such transfer on the books of Altus Biologics Inc., maintained for such purpose,
with full power of substitution in the premises.

Dated:
       ------------------------------   ----------------------------------------
                                        Signature of registered owner
Witness:
         ----------------------------

                                       15

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00091-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00091-of-00352.parquet"}]]