Document:

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                                                                    Exhibit 10.3

               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT

         This Agreement is made and entered into as of this 12th day of August,
1998, by and among The Medicines Company, a Delaware corporation (the
"Company"), the individuals and entities listed on SCHEDULE I hereto (the "Old
Investors") and the individuals and entities listed on SCHEDULE II hereto (the
"New Investors"). The Old Investors and the New Investors are collectively
referred to herein as the "Investors".

         WHEREAS, the Company has previously entered into Stock Purchase
Agreements dated September 5, 1996, June 4, 1997 and December 17, 1997,
respectively (the "Old Stock Purchase Agreements") with the Old Investors; and

         WHEREAS, the Company and the Old Investors in connection with the Old
Stock Purchase Agreements, previously entered into a Registration Rights
Agreement dated June 4, 1997, as amended on December 17, 1997 (the "Registration
Rights Agreement"); and

         WHEREAS, the Company and the New Investors have entered into a Stock
Purchase Agreement dated as of August 12, 1998 (the "Purchase Agreement"), and

         WHEREAS, the Company and the Old Investors believe it to be in their
mutual best interests to amend and restate the Registration Rights Agreement;
and

         WHEREAS, the Company and the Investors desire to provide for certain
arrangements with respect to the registration of shares of capital stock of the
Company under the Securities Act of 1933, as amended; and

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Agreement, the parties hereto agree to amend and restate the
Registration Rights Agreement as follows:

1.       DEFINITIONS.

         As used in this Agreement, the following terms shall have the following
meanings:

         (a) the term "Common Stock" means the common stock, $0.001 par value
per share, of the Company;

         (b) the term "Exchange Act" means the Securities Act of 1934, as
amended, or any similar Federal statute, and the rules and regulations of the
SEC Issued under such Act, as they each may, from time to time, be in effect;

         (c) the term "Holder" shall mean any holder of Registrable Securities;

         (d) the term "Initial Public Offering" means the initial underwritten
public offering of equity securities of the Company pursuant to an effective
Registration Statement;

         (e) the term "Initiating Holder" shall mean (i) any Holder or Holders
who in the aggregate are holders of more than 50% of the then outstanding
Registrable Securities, PROVIDED, that as to one (1) of the three (3) requested
registrations covered by Section 2 of this Agreement, Holders requesting
registration shall be deemed to constitute "Initiating Holders" only if such
Holders include Warburg, Pincus Ventures, L.P. ("Warburg"), and as to one (1) of
the three (3) requested registrations covered by Section 2 of this Agreement,

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Holders requesting such registration shall be deemed to constitute "Initiating
Holders" only if such Holders include Biotech Target, S.A. ("Biotech Target"),
and (ii) additionally, commencing three (3) years after the date hereof, New
Investors who in the aggregate are Holders of more than 20% of the shares of
Common Stock issued or issuable upon conversion of the Series III Convertible
Preferred Stock of the Company, par value $1.00 per share (the "Series III
Preferred Stock");

         (f) the terms "register," "registered" and "registration" refer to a
registration effected by preparing and filing a Registration Statement (and any
post-effective amendments filed or required to be filed) in compliance with the
Securities Act and the declaration or ordering of effectiveness of such
Registration Statement;

         (g) the term "Registrable Securities" means (1) any shares of Common
Stock issued or issuable on conversion of the Series III Preferred Stock and the
Series I Convertible Preferred Stock and Series II Convertible Preferred Stock,
each $1.00 par value per share (collectively, the "Preferred Stock"), (ii) any
additional shares of Common Stock acquired by the Investors, excluding shares
acquired by each of Clive A. Meanwell, Peyton Marshall, Wendy Gordon, John
Villiger, Thomas Lategan and Helmut Glersiefen pursuant to the Restricted Stock
Purchase Agreements, and (iii) any capital stock of the Company issued as a
dividend or other distribution with respect to, or in exchange for or in
replacement of, the shares of Common Stock referred to in clause (i), (ii) or
(iii);

         (h) "Registration Expenses" shall mean, with respect to any
registration, all expenses incurred by the Company in compliance with Sections 2
and 3 hereof, including, without limitation, all registration, qualification and
filing fees, printing expenses, fees and disbursements of counsel for the
Company, fees and expenses of one counsel for all the Holders in an amount not
to exceed $25,000 for each such registration (which counsel shall be selected by
Holders owning a majority of the Registrable Securities proposed to be included
in such registration), blue sky fees and expenses (including reasonable fees and
disbursements of a qualified independent underwriter, if any, counsel in
connection therewith and the reasonable fees and disbursements in connection
with blue sky qualifications) and the expense of any regular or special audits
incident to or required by any such registration (but excluding the compensation
of regular employees of the Company, which shall be paid in any event by the
Company), expenses of any comfort letters or costs associated with the delivery
by independent certified public accountants of a comfort letter or comfort
letters, fees and expenses of any special experts retained by the Company in
connection with such registration and fees and expenses of listing the
Registrable Securities on a securities exchange (including reasonable fees and
expenses of underwriter's counsel in connection therewith);

         (i) the term "Registration Statement" means a registration statement
filed by the Company with the SEC for a public offering and sale of Common Stock
(other than a registration statement on Form S-8 or Form S-4, or any other form
for a similar limited purpose, or any registration statement covering only
securities proposed to be issued in exchange for securities or assets of another
corporation);

         (j) "Restricted Stock Purchase Agreements" shall mean the respective
Stock Restriction Agreements between the Company and each of the following: (i)
Clive A. Meanwell dated as of September 5, 1996, (ii) Peyton Marshall dated as
of October 20, 1997, (iii) Wendy Gordon dated as of November 1, 1997, (iv) John
Villiger dated as of March 10, 1997, (v) Thomas Lategan dated as of February 24,
1997, and (vi) Helmut Giersiefen dated as of November 1, 1996 and as amended and
restated on April 4, 1997;

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         (k) the term "SEC" means the Securities and Exchange Commission, or any
other Federal Agency at the time administering the Securities Act;

         (l) the term "Securities Act" means the Securities Act of 1933, as
amended, or any similar federal statute, under the rules and regulations of the
SEC issued under such Act, as they each may, from time to time, be in effect;

         (m) "Selling Expenses" shall mean, with respect to any registration,
all underwriting discounts and selling commissions and stock transfer taxes
applicable to the sale of Registrable Securities and all fees and disbursements
of counsel for each of the Holders other than fees and expenses of one counsel
for all the Holders in an amount not to exceed $25,000 for such registration;
and

         (n) "Stockholders' Agreement" means the Third Amended and Restated
Stockholders' Agreement among the Investors, the Company and certain other
stockholders dated as of the date of this Agreement.

2.       REQUESTED REGISTRATION.

         (a) REQUEST FOR REGISTRATION. If the Company shall receive from an
Initiating Holder at any time or times a written request that the Company effect
any registration with respect to all or a part of the Registrable Securities,
the Company will:

         (i) promptly give written notice of the proposed registration to all
         other Holders of Registrable Securities; and

         (ii) as soon as practicable, use its diligent best efforts to effect
         such registration (including, without limitation, the execution of an
         undertaking to file post-effective amendments, appropriate
         qualification under applicable blue sky or other state securities laws
         and appropriate compliance with applicable regulations issued under the
         Securities Act) as may be so requested and as would permit or
         facilitate the sale and distribution of all or such portion of such
         Registrable Securities as are specified in such request, together with
         all or such portion of the Registrable Securities of any Holder or
         Holders joining in such request as are specified in a written request
         received by the Company within ten (10) business days after written
         notice from the Company is given under Section 2(a)(1) above; provided
         that the Company shall not be obligated to effect, or take any action
         to effect, any such registration pursuant to this Section 2:

                  A. In any particular jurisdiction in which the Company would
                  be required to execute a general consent to service of process
                  in effecting such registration, qualification or compliance,
                  unless the Company is already subject to service in such
                  jurisdiction and except as may be required by the Securities
                  Act or applicable rules or regulations thereunder;

                  B. After the Company has effected three (3) such registrations
                  pursuant to this Section 2 requested by Initiating Holders
                  described in clause (i) of the definition thereof and two (2)
                  such registrations requested by Initiating Holders described
                  in clause (ii) of the definition thereof, and such
                  registrations have been declared or ordered effective and the
                  sales of such Registrable Securities shall have closed;

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                  C. (i) In the case of any registration requested by Initiating
                  Holders described in clause (i) of the definition thereof, if
                  the Registrable Securities requested by all Holders to be
                  registered pursuant to such request do not have, in the good
                  faith judgment of the Board of Directors of the Company, an
                  anticipated aggregate public offering price (before any
                  underwriting discounts and commissions) of at least $5,000,000
                  (or $10,000,000 if such requested registration is the Initial
                  Public Offering) and, as to the Initial Public Offering, if
                  the request is not made by Holders who in the aggregate hold
                  at least sixty-five percent (65%) of the Registrable
                  Securities;

                           (ii) In the case of any registration requested by
                           Initiating Holders described in clause (ii) of the
                           definition thereof, the Registrable Securities
                           requested by such Initiating Holders to be registered
                           do not constitute at least 15% of the Common Stock
                           issued or issuable upon conversion of the Series III
                           Preferred Stock or do not have, in the good faith
                           judgment of the Board of Directors of the Company, an
                           anticipated aggregate public offering price (before
                           any underwriting discounts and commissions) of at
                           least $5,000,000 (or $10,000,000 if such requested
                           registration is in the Initial Public Offering); or

                  D. If at the time of any request to register Registrable
                  Securities pursuant to this Section 2, the Company is engaged
                  or has fixed plans to engage within thirty (30) days of the
                  time of the request in a registered public offering as to
                  which the Holders may include Registrable Securities pursuant
                  to Section 3 or is engaged in any financing, acquisition or
                  other material transaction which, in the good faith
                  determination of the Board of Directors of the Company, would
                  be adversely affected by the requested registration to the
                  material detriment of the Company, then the Company may,, at
                  its option, direct that such request be delayed for the
                  shortest reasonable period of time not in excess of 120 days
                  from the date of such request, such right to delay a request
                  to be exercised by the Company not more than once in any
                  one-year period. In any such event, the Company shall promptly
                  give the Holders written notice of such determination,
                  containing a general statement of the reasons for such
                  postponement and an approximation of the anticipated delay. If
                  the Company shall so postpone the filing of the Registration
                  Statement, the Holders who made the request for registration
                  shall have the right to withdraw the request for registration
                  by giving written notice to the Company within thirty (30)
                  days after receipt of the notice of postponement.

         The Registration Statement filed pursuant to the request of any of the
Initiating Holders may, subject to the provisions of Section 2(b) below, include
other securities of the Company or which are held by Persons who, by virtue of
agreements with the Company, are entitled to include their securities in any
such registration, provided that such Persons shall be subject to the provisions
of Section 2(b) below.

         The Initiating Holders that made the registration request may, at any
time prior to the effective date of the Registration Statement relating to such
registration revoke such request, without liability to any other party, by
providing a written notice to the Company revoking such request.

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         (b) UNDERWRITING. If the Initiating Holders intend to distribute the
Registrable Securities covered by their request by means of an underwriting,
they shall so advise the Company as a part of their request made pursuant to
Section 2.

         If holders of securities of the Company other than Registrable
Securities who are entitled, by contract with the Company or otherwise, to have
securities included in such a registration (the "Other Stockholders") request
such inclusion, the Holders shall offer to include the securities of such Other
Stockholders in the underwriting and may condition such offer on their
acceptance of the further applicable provisions of this Agreement. The Holders
whose shares are to be included in such registration and the Company shall
(together with all Other Stockholders proposing to distribute their securities
through such underwriting) enter into an underwriting agreement in customary
form with the representative of the underwriter or underwriters selected for
such underwriting by the Initiating Holders holding a majority of Registrable
Securities held by the Initiating Holders and reasonably acceptable to the
Company and the price, terms and provisions of the underwriting and the offering
shall be subject to the approval of the Company and such Initiating Holders. Any
affiliate of a Holder may be selected to serve, on an arm's-length basis, as
underwriter for an underwritten offering effected pursuant to this Section 2(b).
Notwithstanding any other provision of this Section 2, if the representative
advises the Holders in writing that marketing factors require a limitation on
the number of shares to be underwritten, the securities of the Company held by
Other Stockholders shall be excluded from such registration to the extent so
required by such limitation. If, after the exclusion of such shares, further
reductions are still required, the number of shares included in the registration
by each Holder shall be reduced on a pro rata basis (based on the number of
shares requested to be included by such Holder), by such minimum number of
shares as is necessary to comply with such request. No Registrable Securities or
any other securities excluded from the underwriting by reason of the
underwriter's marketing limitation shall be included in such registration. If at
least 50% of the Registrable Securities requested to be included in such
registration by the Initiating Holders are excluded by reason of the
underwriter's marketing limitation, the registration shall not be counted for
purposes of paragraph (B) of Section 2(a)(ii). If any of the Holders or any
Other Stockholder who has requested inclusion in such registration as provided
above disapproves of the terms of the underwriting, such person may elect to
withdraw therefrom without liability to any party by written notice to the
Company, the underwriter and the Initiating Holders. The securities so withdrawn
shall also be withdrawn from registration. If the underwriter has not limited
the number of Registrable Securities to be underwritten, the Company may include
its securities for its own account in such registration if the representative so
agrees and if the number of Registrable Securities which would otherwise have
been included in such registration and underwriting will not thereby be limited.

3.       COMPANY REGISTRATION.

         (a) INCLUSION IN REGISTRATION. If the Company shall determine to
register any of its equity securities either for its own account or for the
account of a security holder or holders exercising their respective demand
registration rights (including any such registration pursuant to Section 4, but
excluding any such registration pursuant to Section 2), other than a
registration relating solely to employee benefit plans, or a registration
relating solely to a SEC Rule 145 transaction, or a registration on any
registration form which does not permit secondary sales, the Company will:

         (i) promptly (but in any event at least 15 days prior to the
         anticipated filing date) give to each of the Holders a written notice
         thereof (which shall include a list of the

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         jurisdictions in which the Company intends to attempt to qualify such
         securities under the applicable blue sky or other state securities
         laws); and

         (ii) include in such registration (and any related qualification under
         blue sky laws or other compliance), and in any underwriting involved
         therein, all the Registrable Securities specified in a written request
         or requests, made by any Holder within fifteen (15) days after receipt
         of the written notice from the Company described in clause (1) above,
         except as set forth in Section 3(b) below. Such written request may
         specify all or a part of a Holder's Registrable Securities.

         (b) UNDERWRITING. If the registration of which the Company gives notice
is for a registered public offering involving an underwriting, the Company shall
so advise each of the Holders as a part of the written notice given pursuant to
Section 3(a)(i). In such event, the right of each of the Holders to registration
pursuant to this Section 3 shall be conditioned upon such Holder's participation
in such underwriting and the inclusion of such Holder's Registrable Securities
in the underwriting to the extent provided herein. The Holders whose shares are
to be included in such registration shall (together with the Company and the
Other Stockholders distributing their securities through such underwriting)
enter into an underwriting agreement in customary form with the representative
of the underwriter or underwriters selected for underwriting by the Company.
Notwithstanding any other provision of this Section 3, if the representative
determines that marketing factors require a limitation on the number of shares
to be underwritten, and (x) if such registration is the Initial Public Offering,
the representative may, subject to the allocation priority set forth below,
exclude from such registration and underwriting all of the Registrable
Securities which would otherwise be underwritten pursuant hereto, and (y) if
such registration is other than the Initial Public Offering, the representative
may (subject to the allocation priority set forth below) limit the number of
Registrable Securities to be included in the registration and underwriting to
not less than twenty-five percent (25%) of the securities included therein. The
Company shall so advise all holders of securities requesting registration, and
the number of shares of securities that are entitled to be included in the
registration and underwriting shall be allocated in the following manner: The
securities of the Company held by Other Stockholders of the Company (other than
Registrable Securities, if any are held by such Other Stockholders, and other
than securities held by holders (other than Holders) who by contractual right
demanded such registration ("Demanding Holders")) shall be excluded from such
registration and underwriting to the extent required by such limitation, and, if
a limitation on the number of shares is still required, the number of shares
that may be included in the registration and underwriting by each of the Holders
and the Demanding Holders shall be reduced, on a pro rata basis (based on the
number of shares requested to be included by such Holder), by such minimum
number of shares as is necessary to comply with such limitation. If any of the
Holders or any Other Stockholder disapproves of the terms of any such
underwriting, such person may elect to withdraw therefrom without liability to
any party by written notice to the Company and the underwriter. Any Registrable
Securities or other securities excluded or withdrawn from such underwriting
shall be withdrawn from such registration.

         (c) No registration effected under this Section 3 shall relieve the
Company of its obligation to effect any registration upon request under Section
2 or Section 4, except as otherwise provided herein.

4.       FORM S-3.

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         Following the Initial Public Offering the Company shall use its best
efforts to qualify for registration on Form S-3 (or any equivalent successor
form) for secondary sales. After the Company has qualified for the use of Form
S-3, Holders of Registrable Securities shall have the right to request up to
nine (9) registrations on Form S-3 (one of which may be exercised by War6urg,
one of which may be exercised by Biotech Target, one of which may be exercised
by PharmaBio Development, Inc. ("PharmaBio"), one of which may be exercised by
the MPM Group (as defined in the Stockholders' Agreement)) and five (5) of which
may be exercised by New Investors holding a majority of Registrable Securities
held by all of the New Investors (such requests shall be `in writing and shall
state the number of shares of Registrable Securities to be disposed of and the
intended method of disposition of shares by such Holders), subject only to the
following:

         (i) The Company shall not be required to effect a registration pursuant
         to this Section 4 unless the Holder or Holders of Registrable
         Securities requesting registration propose to dispose of shares of
         Registrable Securities that are expected to have an aggregate price to
         the public (before deduction of underwriting discounts and expenses of
         sale) of more than $3,000,000.

         (ii) The Company shall not be required to effect a registration
         pursuant to this Section 4 within 180 days of the effective date of the
         most recent registration pursuant to this Section 4 in which securities
         held by the requesting Holder could have been included for sale or
         distribution.

         (iii) The Company shall not be required to effect a registration
         pursuant to this Section 4 in any particular jurisdiction in which the
         Company would be required to execute a general consent to service of
         process in effecting such registration, qualification or compliance,
         unless the Company is already subject to service in such jurisdiction
         and except as may be required by the Securities Act or applicable rules
         or regulations thereunder.

         (iv) If at the time of any request to register Registrable Securities
         pursuant to this Section 2, the Company is engaged or has fixed plans
         to engage within thirty (30) days of the time of the request in a
         registered public offering as to which the Holders may include
         Registrable Securities pursuant to Section 3 or is engaged in any
         financing, acquisition or other material transaction which, in the good
         faith determination of the Board of Directors of the Company, would be
         adversely affected by the requested registration to the material
         detriment of the Company, then the Company may, at its option, direct
         that such request be delayed for the shortest reasonable period of time
         not in excess of 120 days from the date of such request, such right to
         delay a request to be exercised by the Company not more than once in
         any one-year period. In any such event, the Company shall promptly give
         the Holders written notice of such determination, containing a general
         statement of the reasons for such postponement and an approximation of
         the anticipated delay.

         The Company shall give prompt written notice to all Holders of
Registrable Securities of the receipt of a request for registration pursuant to
this Section 4 and as soon as practicable, use its diligent best efforts to
effect such registration (including, without limitation, the execution of an
undertaking to file post-effective amendments, appropriate qualification under
applicable blue sky or other state securities laws and appropriate compliance
with applicable regulations issued under the Securities Act) as may be so
requested and as would permit or facilitate the sale and distribution of all or
such portion of

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such Registrable Securities as are specified in such request, together with all
or such portion of the Registrable Securities of any Holder or Holders joining
in such request as are specified in a written request received by the Company
within ten (10) business days after written notice from the Company is given;
provided that if the registration is for an underwritten offering, the terms of
Section 2(b) shall apply to all participants in such offering. Subject to the
foregoing, the Company will use its best efforts to effect promptly the
registration of all shares of Registrable Securities on Form S-3 to the extent
requested by the Holder or Holders thereof for purposes of disposition.

5.       EXPENSES OF REGISTRATION.

         All Registration Expenses incurred in connection with any registration,
qualification or compliance that is proposed or effected pursuant to this
Agreement shall be borne by the Company, and all Selling Expenses shall be borne
by the Holders of the securities so registered pro rata on the basis of the
number of their shares so registered; provided, however, that the Company shall
not be required to pay any Registration Expenses in the event the Registration
Statement is withdrawn at the request of the Initiating Holders (other than as a
result of information concerning the business or financial condition of the
Company which is made known to the Initiating Holders after the date on which
such registration was requested if such withdrawal occurs within 10 days of the
Initiating Holders becoming aware of such information) and each of the
Initiating Holders agrees to bear such Registration Expenses pro rata on the
basis of the number of their shares so included in the registration request (or
on some other basis as they may agree), in which case such registration shall
not be counted as a registration pursuant to Section 2(a)(ii)(B) or 4. In the
event that the Registration Statement is withdrawn and the Initiating Holders
requesting registration fail to pay the expenses as provided in the immediately
preceding sentence, such registration shall be counted as a registration
pursuant to Section 2(a)(ii)(B) or 4.

6.       REGISTRATION PROCEDURES.

         In the case of each registration effected by the Company pursuant to
this Agreement, the Company will keep the Holders, as applicable, advised in
writing of the effectiveness thereof and of any stop order issued or, to the
Company's knowledge, threatened by the SEC and take all reasonable actions
required to prevent the entry of such stop order or to remove it if entered and
promptly notify such Holder of such lifting or withdrawal of such order. At its
expense, the Company will:

         (i) prepare and file with the SEC such amendments and supplements to
         such Registration Statement and the prospectus used in connection
         therewith as may be necessary to keep such Registration Statement
         effective for the period specified in Section 6(vi) and to comply with
         the provisions of the Securities Act with respect to the disposition of
         all securities covered by such Registration Statement during such
         period; provided that the Company will, to the extent practicable, at
         least three days prior to filing a Registration Statement or prospectus
         or any amendment or supplement thereto, furnish to each Holder copies
         of such Registration Statement or prospectus (or amendment or
         supplement) as proposed to be filed (including, upon the request of
         such Holder, documents to be incorporated by reference therein) which
         documents will be subject to the reasonable review and comments of such
         Holder and counsel for the Holders, which review will be completed as
         expeditiously as possible; and the Company will not include any
         statement in any Registration Statement or prospectus (or amendment or
         supplement) with respect to such Holder to which such

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         Holder shall reasonably object in writing except as may be required to
         comply with securities laws and disclosure obligations thereunder;

         (ii) furnish to each Holder and to each underwriter, if any, a signed
         counterpart of: (x) an opinion of counsel for the Company addressed to
         such Holder and underwriter on which opinion such Holder and
         underwriter is entitled to rely, and (y) a "comfort" letter signed by
         the independent public accountants who have certified the Company's
         financial statements included in such Registration Statement, each in
         customary form and covering such matters of the type customarily
         covered by opinions or comfort letters, as the case may be, as the
         managing underwriter therefor reasonably request;

         (iii) immediately notify each Holder at any time when a prospectus
         relating thereto is required to be delivered under the Securities Act,
         upon discovery that, or upon the happening of any event as a result of
         which, the prospectus included in such Registration Statement, as then
         in effect, includes an untrue statement of a material fact or omits to
         state any material fact required to be stated therein or necessary to
         make the statements therein not misleading in the light of the
         circumstances under which they were made, and promptly prepare and
         furnish to such Holder a reasonable number of copies of any supplement
         to or amendment of such prospectus as may be necessary so that, as
         thereafter delivered to the purchasers of such securities, such
         prospectus shall not include an untrue statement of a material fact or
         omit to state a material fact required to be stated therein or
         necessary to make statements therein not misleading in the light of the
         circumstances under which they were made;

         (iv) make available for inspection by any Holder, any underwriter
         participating in any disposition pursuant to such Registration
         Statement and any attorney, accountant or other professional retained
         by any such Holder or underwriter, all financial and other records,
         pertinent corporate documents and properties of the Company as shall be
         reasonably necessary to enable them to exercise their due diligence
         responsibility;

         (v) otherwise use its reasonable best efforts to list all Registrable
         Securities covered by such Registration Statement on any securities
         exchange or I quotation system on which any of the Registrable
         Securities is then listed or traded; to cause all Registrable
         Securities covered by such Registration Statement to be registered with
         or approved by such other governmental agencies or authorities as may
         be necessary to enable the Holders to consummate the disposition of
         such Registrable Securities; to comply with all applicable rules and
         regulations of the SEC, and make available to its securityholders, as
         soon as reasonably practicable, an earnings statement covering the
         period of at least twelve (12) months beginning with the first full
         calendar month of the Company first fiscal quarter commencing after the
         effective date of such Registration Statement, which earnings statement
         shall satisfy the provisions of Section 11(a) of the Securities Act and
         Rule 158 thereunder;

         (vi) keep such registration effective for a period of 120 days or until
         the Holders, as applicable, have completed the distribution described
         in the Registration Statement relating thereto, whichever first occurs;
         provided, however, that (A) in the event such Holders are required to
         refrain from selling securities pursuant to a separate registration
         during such 120-day period pursuant to Section 10 hereof, such 120-day
         period shall be extended for a period of time equal to the period
         during which the Holders refrain from selling any securities in
         accordance with provisions in Section 10 hereof; and in the case of any
         registration of Registrable Securities on Form S-3

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         which are intended to be offered on a continuous or delayed basis, such
         120-day period shall be extended until all such Registrable Securities
         are sold, provided that Rule 415, or any successor rule under the
         Securities Act, permits an offering on a continuous or delayed basis,
         and provided further that applicable rules under the Securities Act
         governing the obligation to file a post-effective amendment permit, in
         lieu of filing a post-effective amendment which (y) includes any
         prospectus required by Section 10(a) of the Securities Act or (z)
         reflects facts or events representing a material or fundamental change
         in the information set forth in the Registration Statement, the
         incorporation by reference of information required to be included in
         (y) and (z) above to be contained in periodic reports filed pursuant to
         Section 13 or 15(d) of the Exchange Act in the Registration Statement;
         and

         (vii) furnish such number of Registration Statements, prospectuses,
         amendments or supplements thereto and other documents incident thereto
         as each of the Holders, as applicable, from time to time may reasonably
         request.

7.       INDEMNIFICATION.

         (a) The Company will indemnify each of the Holders, as applicable, each
of its officers, directors, partners and agents, and each person controlling
each of the Holders within the meaning of Section 15 of the Securities Act or
Section 20 of the Exchange Act, with respect to each registration which has been
effected pursuant to this Agreement, and each underwriter, if any, and each
person who controls any underwriter, against all expenses, claims, losses,
damages and liabilities (or actions, proceedings or settlements in respect
thereof) arising out of or based on any untrue statement (or alleged untrue
statement) of a material fact contained in any prospectus, offering circular or
other document (including any related Registration Statement, notification or
the like), as amended or supplemented, incident to any such registration,
qualification or compliance, or based on any omission (or alleged omission) to
state therein a material fact required to be stated therein or necessary to make
the statements therein not misleading, or any violation by the Company of the
Securities Act, Exchange Act, state securities laws or any rule or regulation
thereunder applicable to the Company and relating to action or inaction required
of the Company in connection with any such registration, qualification or
compliance, and will reimburse each of the Holders, each of its officers,
directors, partners and agents, and each person controlling each of the Holders,
each such underwriter and each person who controls any such underwriter, for any
legal and any other expenses reasonably incurred in connection with
investigating, defending or settling any such claim, loss, damage, liability or
action, provided that the Company will not be liable in any such case to the
extent that any such claim, loss, damage, liability or expense arises out of or
is based on any untrue statement or omission based upon written information
furnished to the Company by the Holders or underwriter and stated to be
specifically for use therein, PROVIDED that the obligations of the Company
hereunder shall not apply to amounts paid in settlement of any such claim, loss,
damage, liability or action if such settlement is effected without the consent
of the Company.

         (b) Each of the Holders will, severally (in the proportion that the
proceeds of the offering received by such Holder bears to the total proceeds of
the offering received by all the Holders) and not jointly, if Registrable
Securities held by it are included in the securities as to which such
registration, qualification or compliance is being effected, indemnify the
Company, each of its directors and officers and each underwriter, if any, of the
Company's securities covered by such a Registration Statement, each person who
controls the Company or such underwriter against all claims, losses, damages and
liabilities (or actions in respect

<PAGE>   11

thereof) arising out of or based on any untrue statement (or alleged untrue
statement) of a material fact contained in any such Registration Statement,
prospectus, offering circular or other document made by such Holder, or any
omission (or alleged omission) to state therein a material fact required to be
stated therein or necessary to make the statements by such Holder therein not
misleading, and will reimburse the Company and such directors, officers,
partners, persons, underwriters or control persons for any legal or any other
expenses reasonably incurred in connection with investigating or defending any
such claim, loss, damage, liability or action, in each case to the extent, but
only to the extent, that such untrue statement (or alleged untrue statement) or
omission (or alleged omission) is made in such Registration Statement,
prospectus, offering circular or other document in reliance upon and in
conformity with written information furnished to the Company by such Holder and
stated to be specifically

<PAGE>   12

for use therein; provided, however, that (i) the obligations of each of the
Holders hereunder shall be limited to an amount equal to the net proceeds to
such Holder of securities sold as contemplated herein., and (ii) the obligations
of each of the Holders hereunder shall not apply to amounts paid in settlement
of any such claim, loss, damage, liability or action if such settlement is
effected without the consent of such Holder.

         (c) Each party entitled to indemnification under this Section 7 (the
"Indemnified Party") shall give written notice to the party required to provide
indemnification (the "Indemnifying Party") promptly after such Indemnified Party
has actual knowledge of any claim as to which indemnity may be sought, and shall
permit the Indemnifying Party to assume the defense of any such claim or any
litigation resulting therefrom; provided that counsel for the Indemnifying
Party, who shall conduct the defense of such claim or any litigation resulting
therefrom, shall be approved by the Indemnified Party (whose approval shall not
unreasonably be withheld) and the Indemnified Party may participate in such
defense at such party's expense (unless the Indemnified Party shall have
reasonably concluded that there may be a conflict of interest between the
Indemnifying Party and the Indemnified Party in such action, in which case the
fees and expenses of counsel shall be at the expense of the Indemnifying Party),
and provided further that the failure of any Indemnified Party to give notice as
provided herein shall not relieve the Indemnifying Party of its obligations
under this Agreement unless the Indemnifying Party is materially prejudiced
thereby. No Indemnifying Party, in the defense of any such claim or litigation
shall, except with the consent of each Indemnified Party, consent to entry of
any judgment or enter into any settlement which does not include as an
unconditional term thereof the giving by the claimant or plaintiff to such
Indemnified Party of a release from all liability in respect to such claim or
litigation. Each Indemnified Party shall furnish such information regarding
itself or the claim in question as an Indemnifying Party may reasonably request
in writing and as shall be reasonably required in connection with the defense of
such claim and litigation resulting therefrom. Any counsel representing the
Holders (as Indemnifying Party or Indemnified Party) shall be selected by the
holders holding a maj9rity of the Registrable Securities included in such
registration.

         (d) In order to provide for just and equitable contribution to joint
liability in any case in which either (i) any Indemnified Party exercising
rights under this Agreement makes a claim for indemnification pursuant to this
Section 7 but it is judicially determined (by the entry of a final judgment or
decree by a court of competent jurisdiction and the expiration of time to appeal
or the denial of the last right of appeal) that such indemnification may not be
enforced in such case notwithstanding the fact that this Section 7 provides for
indemnification in such case, or (ii) contribution under the Securities Act may
be required on the part of any such Indemnified Party in circumstances for which
indemnification Is provided under tills Section 71- then, and in each such case,
each Indemnifying Party and Indemnified Party will contribute to the aggregate
losses, claims, damages or liabilities to which they may be subject (after
contribution from others) in proportion-to the relative fault of the
Indemnifying Party, on the one hand, and each Indemnified Party, on the other
hand; PROVIDED HOWEVER that, in any such case, no person or entity guilty of
fraudulent misrepresentation (within the meaning of Section 11(f) of the
Securities Act) will be entitled to contribution from any person or entity who
was not guilty of such fraudulent misrepresentation and no such Indemnifying
Party will be required to contribute any amount in excess of the public offering
price of all shares sold by it pursuant to such registration statement. The
relative fault of each Indemnifying Party and of the Indemnified Party shall be
determined by reference to, among other things, whether the untrue or alleged
untrue

<PAGE>   13

statement of a material fact or the omission to state a material fact relates to
information supplied by the Indemnifying Party or by the Indemnified Party and
the parties' relative intent, knowledge, access to information, and opportunity
to correct or prevent such statement or omission. The Company and the Investors
agree that it would not be just and equitable if contribution pursuant to this
Section 7 were determined by pro rata allocation or by any other method of
allocation which does not take account of the equitable considerations referred
to above.

         (e) Notwithstanding the foregoing, to the extent that the provisions on
indemnification and contribution contained in the underwriting agreement entered
into in connection with any underwritten public offering contemplated by this
Agreement are in conflict with the foregoing provisions, the provisions in such
underwriting agreement shall be controlling.

         (f) The amount paid or payable by an Indemnified Party as a result of
the losses, claims, damages or liabilities referred to in this Section 7 shall
be deemed to include, subject to the limitations set forth above, any legal or
other expenses reasonably incurred by such Indemnified Party In connection with
investigating or defending any such action or claim in accordance with the
provisions hereof.

         (g) The foregoing indemnity agreement of the Company and the Holders is
subject to the condition that, insofar as they relate to any loss, claim,
liability or damage made in a preliminary prospectus but eliminated or remedied
in the amended prospectus on file with the SEC at the time the Registration
Statement in question becomes effective or the amended prospectus filed with the
SEC pursuant to SEC Rule 424(b) (the "Final Prospectus"), such indemnity
agreement shall not inure to the benefit of any Indemnified Party if a copy of
the Final Prospectus was furnished to the Indemnified Party, the Indemnified
Party was required by the Securities Act to furnish the Final Prospectus to the
person asserting the loss, liability, claim or damage and the Indemnified Party
did not so furnish the final Prospectus at or prior to the time such action is
required by the Securities Act.

8.       INFORMATION BY THE HOLDERS.

         Each of the Holders holding securities included in any registration
shall furnish to the Company such information regarding such Holder and the
distribution proposed by such Holder as the Company may reasonably request in
writing and as shall be reasonably required in connection with any registration,
qualification or compliance referred to in this Agreement.

9.       RULE 144 Reporting.

         (a) With a view to making available the benefits of certain rules and
regulations of the SEC which may permit the safe of restricted securities to the
public without registration, the Company agrees to:

         (i) make and keep public information available as those terms are
         understood and defined in Rule 144 of the Securities Act, at all times
         from and after ninety (90) days following the effective date of the
         first registration under the Securities Act filed by the Company for an
         offering of its securities to the general public;

<PAGE>   14

         (ii) use its best efforts to file with the SEC in a timely manner all
         reports and other documents required of the Company under the
         Securities Act and the Exchange Act at any time after it has become
         subject to such reporting requirements; and

         (iii) so long as the Holder owns any Registrable Securities, furnish to
         the Holder upon request, a written statement by the Company as to its
         compliance with the reporting requirements of Rule 144 (at any time
         from and after ninety (90) days following the effective date of the
         first Registration Statement filed by the Company for an offering of
         its securities to the general public), and of the Securities Act and
         the Exchange Act (at any time after it has become subject to such
         reporting requirements), a copy of the most recent annual or quarterly
         report of the Company, and such other reports and documents so filed as
         the Holder may reasonably request in availing itself of any rule or
         regulation of the SEC allowing the Holder to sell any such securities
         without registration.

10.      "MARKET STAND-OFF" AGREEMENT.

         Each of the Holders agrees, if requested by the Company and an
underwriter of Common Stock (or other securities) of the Company at least five
(5) business days prior to the anticipated beginning of the period referred to
below, not to sell or otherwise transfer or dispose of any Common Stock (or
other securities) of the Company held by such Holder (1) for a period of 180
days in the case of the "Initial Public Offering (except as part of such
offering), and (ii) for a period of 120 days in the case of any offering of
shares of Common Stock other than the Initial Public Offering (except as part of
such offering), in each case following the effective date of a Registration
Statement of the Company filed under the Securities Act, provided that:

         (a) the provisions of this Section-10 shall apply to the Initial Public
Offering and to any Registration Statement filed within two (2) years of the
Company's Initial Public Offering; and

         (b) all officers and directors of the Company and any entities with
which an officer or director is an affiliate which holds securities of the
Company enter into and are bound by similar agreements.

         If requested by the underwriters, the Holders shall execute a separate
agreement to the foregoing effect. The Company may impose stop-transfer
instructions with respect to the shares (o securities) subject to the foregoing
restriction until the end of said 180- t 120-day period, as the case may be. The
provisions of this Section 10 shall be binding upon any transferee who acquires
Registrable Securities, whether or not such transferee is entitled to the
registration rights provided hereunder.

         The Company agrees, if requested, by an underwriter of Common Stock (or
other securities) of the Company in connection with an underwriting hereby, that
(1) it will not effect any sale or distribution of any of its equity securities
or of any security convertible into or exchangeable or exercisable for any
equity security of the Company during the period of 120 days (or 180 days, "in
the case of the Initial Public Offering) beginning on the effective date of a
Registration Statement of the Company filed under the Securities Act without the
written consent of such managing underwriter, other than Common Stock (or other
securities) of the Company being sold, transferred or disposed of (A) pursuant
to such Registration Statement or any other registration requested hereby, (B)
pursuant to any of the Company's

<PAGE>   15

stock plans, (C) in connection with the conversion or exercise of any liens
outstanding securities of the Company, (D) in connection with any collaborative
or licensing arrangement, distribution arrangement or loan facility and (E) in
connection with the acquisition of another entity or assets of another entity by
the Company, and (1i) any agreement entered into after the date of this
Agreement pursuant to which the Company issues or agrees to issue any privately
placed securities shall contain a provision under which holders of such
securities agree not to effect any sale or distribution of any such securities
during the periods described in (1) above (except as part of any such
registration, if permitted).

11.      TERMINATION.

         The registration rights set forth in this Agreement shall not be
available to any Holder IF, IN THE WRITTEN OPINION OF REGULAR, OUTSIDE COUNSEL
TO THE Company, all of the Registrable Securities then owned by such Holder
could be sold in any ninety (90) day period pursuant to Rule 144 under the
Securities Act (without giving effect to the provisions of Rule 144 (k)).

12.      CHANGES IN COMMON STOCK OR PREFERRED STOCK.

         If, and as often as, there is any change in, exchange for or
substitution of the Common Stock or the Preferred Stock by reason of any
reorganization, recapitalization, reclassification, merger, consolidation,
spin-off, partial or complete liquidation, stock dividend, split-up, sale of
assets, distribution to stockholders or combination of the Company's securities
or other similar change in the capital structure of the Company, appropriate
adjustment shall be made in the provisions hereof so that the rights and
privileges granted hereunder shall continue with respect to the Registrable
Securities as so changed.

13.      NOTICES.

         (a) Alt communications under this Agreement shall be in writing and
shall be delivered by hand or mailed by overnight courier or by registered mail
or certified mail, postage prepaid:

         (i) if to an Investor listed on SCHEDULE I hereto, at his, her or its
         address set forth in SCHEDULE I, or at such other address as may have
         been furnished to the Company in writing; or

         (ii) if to an Investor listed on SCHEDULE II hereto, at his, her or its
         address set forth on SCHEDULE II, or at such other address as may have
         been furnished to the Company in writing; or

         (iii) if to the Company, at One Cambridge Center, Cambridge,
         Massachusetts 02142, marked for the attention of Clive A. Meanwell, or
         at such other address as the Company may have furnished in writing to
         the Investors, with a copy (which shall not constitute notice) to Hale
         and Dorr LLP, 60 State Street, Boston, Massachusetts 02109,1 marked for
         the attention of Steven D. Singer, Esq.

         (b) Any notice so addressed shall be deemed to be given: if delivered
by hand, on the date of such delivery; if mailed by courier, on the first
business day following the date of such malting; and if mailed by registered or
certified mail, on the third business day after the date of such mailing.

<PAGE>   16

14.      SUCCESSORS AND ASSIGNS.

         The registration rights set forth in this Agreement shall be assignable
by any Investor, in whole or in part, to any transferee of Registrable
Securities who (i) beneficially owns at least 1% of the outstanding Common Stock
(calculated on an as-converted basis)(within the meaning of Rule 13d-3 under the
Exchange Act) or (ii) acquires 100% of the Registrable Securities owned by the
transferring Investor on the date of such assignment; provided that any such
transferee shall agree in writing to be bound by the obligations of the
Investors under this Agreement. The provisions of this Agreement shall be
binding upon and accrue to the benefit of the parties hereto and their
respective heirs, executors, administrators, successors and permitted assigns;
provided that the Company may not transfer or assign any of its rights or
obligations under this Agreement. Nothing in this Agreement, express or implied,
is intended to confer on any Person other than the parties hereto, and their
respective successors and permitted assigns, any rights, remedies, obligations
or liabilities under or by reason of this Agreement.

15.      TERMINATION OF THE REGISTRATION RIGHTS AGREEMENT.

         Upon the effectiveness of this Agreement, the Registration Rights
Agreement is terminated and shall be superseded by the provisions of this
Agreement.

16.      ENTIRE AGREEMENT; AMENDMENT AND WAIVER.

         This Agreement constitutes the entire understandings of the parties
hereto and supersedes all prior agreements or understandings with respect to the
subject matter hereof among such parties. This Agreement may be amended, and the
observance of any term of this Agreement may be waived, with (and only with) the
written consent of the Holders of at least seventy-five percent (75%) of the
Registrable Securities.

17.      LIMITATION ON ENFORCEMENT OF REMEDIES.

         The Company hereby agrees that it will not assert against the limited
partners of any of the Investors any claim it may have under this Agreement by
reason of any failure or alleged failure by such Investor to meet its
obligations hereunder.

18.      GOVERNING LAW.

         This Agreement shall be construed in accordance with and governed by
the laws of the State of Delaware, without regard to the conflicts of law
principles thereof. Counterparts.

         This Agreement may be executed in one or more counterparts, each of
which shall be deemed an original and all of which together shall be considered
one and the same agreement.

19.      REMEDIES.

         The parties hereto acknowledge and agree that in the event of any
breach of this Agreement, the parties could be irreparably harmed and could not
be made whole by monetary damages. Each party hereto accordingly agrees (i) not
to assert by way of defense or otherwise that a remedy at law would be adequate,
and (ii) that the parties agree, in addition to any other remedy to which they
may be entitled, that the parties may seek the remedy of specific performance of
this Agreement, if appropriate, in any action in court.

<PAGE>   17

         IN WITNESS WHEREOF, the parties hereto have executed this Registration
Rights Agreement as of the date first above written.

                                 THE MEDICINES COMPANY

                                 By: /s/ Peyton J. Marshall
                                    ----------------------------------------
                                 Name: Peyton J. Marshall
                                 Title: Chief Financial Officer

                                 OLD INVESTORS:

                                 Holders of at least 75% of the Registrable
                                 Securities

                                 By: /s/ Peyton J. Marshall
                                    ----------------------------------------
                                    Under Power of Attorney of Holders
                                    attached hereto

                                 NEW INVESTORS:

                                 Counterpart signature pages attached hereto

<PAGE>   18

                                   SCHEDULE I

Warburg, Pincus Ventures, L.P.
466 Lexington Avenue
New York, New York 10017

MPM Medicines L.P.
One Cambridge Center
Cambridge, Massachusetts 02142

Hanseatic Americas LDC
450 Park Avenue
Suite 2302
New York, New York 10022

PharmaBio Development Inc.
Post Office Box 13979
Research Triangle Park, North Carolina 27709-3979

Biotech Target, S.A
c/o Bellevue Asset Management AG
Grafenauweg 4 P.  0.  Box CH-6301 Zug, Switzerland

Helmut Giersiefen
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

John Villiger
The Medicines Company Limited
150 Long Drive, St.  Helters
Auckland, New Zealand

Thomas Lategan
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Wendy Gordon
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Peyton Marshall
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Frederick Oleson
5 Partridge Lane
Concord, Massachusetts 07142

<PAGE>   19

John Maraganore
49 Constellation Wharf
Charlestown, Massachusetts 02129

H & D Investments 97
60 State Street
Boston, Massachusetts 02109
Attention: Paul P.  Brountas, Esq.

Frederick Oleson
5 Partridge Lane
Concord, Massachusetts 07142

John Maraganore
49 Constellation Wharf
Charlestown, Massachusetts 02129

H & D Investments 97
60 State Street
Boston, Massachusetts 02109
Attention: Paul P.  Brountas, Esq.

<PAGE>   20

                                   SCHEDULE II

NAME AND ADDRESS OF PURCHASER

E. M. Warburg, Pincus Ventures, L. P.
466 Lexington Avenue
New York, NY 10017

Biotech Growth S.A.
Grafenauweg 4
CH-6301
Zug Switzerland

Hanseatic Americas LDC
450 Park Avenue, Suite 2302
New York, NY 10022

Clive Meanwell
The Medicines Company
One Cambridge Center
Cambridge, MA 02142

Peyton Marshall
The Medicines Company
One Cambridge Center
Cambridge, MA 02142

Jane J. Avinger
207 Avinger Lane
Davidson, NC 28036

H&D Investments 97
Hale and Dorr LLP
60 State Street
Boston, MA 02109

David Ackert
100 Nyala Farm
Westport, CT 06880

Gary S. Roubin Revocable Trust utd
145 East 81st Street
Penthouse B
New York, NY 10028

<PAGE>   21

                          NAME AND ADDRESS OF PURCHASER

Richard Davis
Tucker Anthony
One Beacon Street
Boston, MA 02108

Charles Schwab and Co., Inc.
FBO: Robert L. Avinger, Jr.
UTA Charles Schwab - 1251-7331
101 South Tyron Street
Charlotte, NC 28280

Bayview Investors, Ltd.
555 California Street, Suite 2600
San Francisco, CA 94104

Morgan Stanley Venture Partners L.P.
1221 Avenue of the Americas, 33rd Fl.
New York, NY 10020

Alta Partners
One Embarcadero Center, Suite 4050
San Francisco, CA 94111

Moore Global Investments, Ltd.
1251 Avenue of the Americas, 53rd Fl.
New York, NY 10020

Remington Investment Strategies, L.P
1251 Avenue of the Americas, 53rd Fl.
New York, NY 10020

Credit Suisse Asset Management
AMPE 3 Utlibergstrasse 231
Postfach 800
Zurich, CH-8070
Switzerland

BancAmerica Robertson Stephens
590 Madison Avenue
New York, NY 10022

<PAGE>   22

                             AMENDMENT NO. 2 TO THE
               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT
               --------------------------------------------------

This Amendment No. 2 to the Amended and Restated Registration Rights Agreement
dated as of this 19th day of October, 1999 (the "Agreement"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

WHEREAS, the Company and the individuals and entities who were signatories
thereto (the "Investors") are parties to the Amended and Restated Registration
Rights Agreement dated as of August 13, 1998, as amended to date (the "Amended
and Restated Registration Rights Agreement"); and

WHEREAS, the Company and certain of the Investors have entered into a Securities
Purchase Agreement of even date herewith with respect to the sale of the Notes
and the Warrants, each as defined therein (the "Securities Purchase Agreement");
and

WHEREAS, the Company and the Investors believe it to be in their mutual best
interests to amend the Amended and Restated Registration Rights Agreement to
provide such Investors with certain rights with respect to the registration
under the Securities Act of 1933, as amended, of the shares of capital stock
issuable upon the conversion of the Notes and/or the exercise of the Warrants;

NOW, THEREFORE, in consideration of the mutual promises and covenants contained
in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 1. Section 1 of the Amended and Restated Registration
Rights Agreement is hereby amended by deleting paragraph (g) of Section 1 in its
entirety and substituting in lieu thereof the following:

         "(g)     the term "Registrable Securities" means (i) any shares of
                  Common Stock issued or issuable on conversion of the Company's
                  Series I Convertible Preferred Stock, Series II Convertible
                  Preferred Stock, Series III Convertible Preferred Stock and
                  Series III-a Convertible Preferred Stock, each $1.00 par value
                  per share (collectively, the "Preferred Stock"), (ii) any
                  additional shares of Common Stock acquired by the Investors,
                  excluding shares acquired by each of Clive A. Meanwell, Peyton
                  Marshall, Wendy Gordon, John Villiger, Thomas Lategan, Helmut
                  Giersiefen, Richard Malcolm and John Nystrom pursuant to the
                  Restricted Stock Purchase Agreements, (iii) any shares of
                  Common Stock issued or issuable upon the exercise of the
                  Common Stock Purchase Warrants issued under the Securities
                  Purchase Agreement dated October 19, 1999 between the Company
                  and the entities and individuals who are signatories thereto,
                  (iv) any shares of Common Stock issued or issuable upon the
                  conversion of the capital stock issued or issuable upon the
                  conversion of the 8% Convertible Notes issued under the
                  Securities Purchase Agreement dated October 19, 1999 between

<PAGE>   23

                  the Company and the entities and individuals who are
                  signatories thereto, and (v) any capital stock of the Company
                  issued as a dividend or other distribution with respect to, or
                  in exchange for or in replacement of, the shares of Common
                  Stock referred to in clause (i), (ii) ,(iii) or (iv);" and

2. RATIFICATION. In all other respects, the Amended and Restated Registration
Rights Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 75% of the Registrable Shares (as defined in
the Amended and Restated Registration Rights Agreement).

                                      -2-
<PAGE>   24

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
2 to the Amended and Restated Registration Rights Agreement as of the date first
above written.

                                  The Medicines Company

                                  By: /s/ Peyton J. Marshall
                                      ---------------------------------------
                                      Name: Peyton J. Marshall
                                      Title: Chief Financial Officer

                                  Holders of at least 75% of the Registrable
                                  Securities

                                  By: /s/ Peyton J. Marshall
                                     -------------------------------
                                      Under Power of Attorney
                                      of Holders attached hereto

                                      -3-

<PAGE>   25

                             AMENDMENT NO. 3 TO THE
               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT
               --------------------------------------------------

         This Amendment No. 3 to the Amended and Restated Registration Rights
Agreement dated as of this 2nd day of March, 2000 (the "Amendment"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

         WHEREAS, the Company and the individuals and entities who were
signatories thereto (the "Investors") are parties to the Amended and Restated
Registration Rights Agreement dated as of August 13, 1998, as amended to date
(the "Amended and Restated Registration Rights Agreement"); and

         WHEREAS, the Company and certain of the Investors have entered into a
Securities Purchase Agreement of even date herewith with respect to the sale of
the Notes and the Warrants, each as defined therein (the "Securities Purchase
Agreement"); and

         WHEREAS, the Company and the Investors believe it to be in their mutual
best interests to amend the Amended and Restated Registration Rights Agreement
to provide such Investors with certain rights with respect to the registration
under the Securities Act of 1933, as amended, of the shares of capital stock
issuable upon the conversion of the Notes and/or the exercise of the Warrants;

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 1. Section 1 of the Amended and Restated Registration
Rights Agreement is hereby amended by deleting paragraph (g) of Section 1 in its
entirety and substituting in lieu thereof the following:

         "(g)     the term "Registrable Securities" means (i) any shares of
                  Common Stock issued or issuable on conversion of the Company's
                  Series I Convertible Preferred Stock, Series II Convertible
                  Preferred Stock, Series III Convertible Preferred Stock and
                  Series III-a Convertible Preferred Stock, each $1.00 par value
                  per share (collectively, the "Preferred Stock"), (ii) any
                  additional shares of Common Stock acquired by the Investors,
                  excluding shares acquired by each of Clive A. Meanwell, Peyton
                  Marshall, Wendy Gordon, John Villiger, Thomas Lategan, Helmut
                  Giersiefen, Richard Malcolm and John Nystrom pursuant to the
                  Restricted Stock Purchase Agreements, (iii) any shares of
                  Common Stock issued or issuable upon the exercise of the
                  Common Stock Purchase Warrants issued under the Securities
                  Purchase Agreement dated October 19, 1999 between the Company
                  and the entities and individuals who are signatories thereto,
                  (iv) any shares of Common Stock issued or issuable upon the
                  conversion of the capital stock issued or issuable upon the
                  conversion of the 8% Convertible Notes issued under the
                  Securities Purchase Agreement

<PAGE>   26

                  dated October 19, 1999 between the Company and the entities
                  and individuals who are signatories thereto, (v) any shares of
                  Common Stock issued or issuable upon the exercise of the
                  Common Stock Purchase Warrants issued under the Securities
                  Purchase Agreement dated March 2, 2000 between the Company and
                  the entities and individuals who are signatories thereto, (vi)
                  any shares of Common Stock issued or issuable upon the
                  conversion of the capital stock issued or issuable upon the
                  conversion of the 8% Convertible Notes issued under the
                  Securities Purchase Agreement dated March 2, 2000 between the
                  Company and the entities and individuals who are signatories
                  thereto, and (vii) any capital stock of the Company issued as
                  a dividend or other distribution with respect to, or in
                  exchange for or in replacement of, the shares of Common Stock
                  referred to in clause (i), (ii) ,(iii), (iv), (v) or (vi);"
                  and

2. RATIFICATION. In all other respects, the Amended and Restated Registration
Rights Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 75% of the Registrable Shares (as defined in
the Amended and Restated Registration Rights Agreement).

                  [Remainder of page intentionally left blank]

                                      -2-

<PAGE>   27

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
3 to the Amended and Restated Registration Rights Agreement as of the date first
above written.

                                  The Medicines Company

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                  Name: Peyton J. Marshall
                                  Title: Chief Financial Officer

                                  Holders of at least 75% of the Registrable
                                  Securities

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                      Under Power of Attorney
                                      of Holders attached hereto

                                      -3-

<PAGE>   28

                             AMENDMENT NO. 4 TO THE
               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT
               --------------------------------------------------

         This Amendment No. 4 to the Amended and Restated Registration Rights
Agreement dated as of this 17 day of May, 2000 (the "Amendment"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

         WHEREAS, the Company and the individuals and entities who were
signatories thereto (the "Investors") are parties to the Amended and Restated
Registration Rights Agreement dated as of August 12, 1998, as amended to date
(the "Amended and Restated Registration Rights Agreement"); and

         WHEREAS, the Company and certain of the Investors have entered into a
Series IV Convertible Preferred Stock Purchase Agreement of even date herewith
with respect to the sale of the Preferred Shares, each as defined therein (the
"Purchase Agreement"); and

         WHEREAS, the Company and the Investors believe it to be in their mutual
best interests to amend the Amended and Restated Registration Rights Agreement
to provide such Investors with certain rights with respect to the registration
under the Securities Act of 1933, as amended, of the shares of capital stock
issuable upon the conversion of the Preferred Shares;

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 1. Section 1 of the Amended and Restated Registration
Rights Agreement is hereby amended by deleting paragraph (g) of Section 1 in its
entirety and substituting in lieu thereof the following:

         "(g) the term "Registrable Securities" means (i) any shares of Common
         Stock issued or issuable on conversion of the Company's Series I
         Convertible Preferred Stock, Series II Convertible Preferred Stock,
         Series III Convertible Preferred Stock and Series IV Convertible
         Preferred Stock, each $1.00 par value per share (collectively, the
         "Preferred Stock"), (ii) any additional shares of Common Stock acquired
         by the Investors [prior to the Initial Public Offering], excluding
         shares acquired by each of Clive A. Meanwell, Peyton Marshall, Wendy
         Gordon, John Villiger, Thomas Lategan, Helmut Giersiefen, Richard
         Malcolm and John Nystrom pursuant to the Restricted Stock Purchase
         Agreements[, and any other shares acquired by an Investor pursuant to
         the Company's 1998 Stock Incentive Plan], (iii) any shares of Common
         Stock issued or issuable upon the exercise of the Common Stock Purchase
         Warrants issued under the Securities Purchase Agreement dated October
         19, 1999 between the Company and the entities and individuals who are
         signatories thereto, (iv) any shares of Common Stock issued or issuable
         upon the exercise of the Common Stock Purchase Warrants issued under
         the Securities Purchase Agreement dated March 2, 2000 between the
         Company and the entities and individuals who are signatories thereto,
         and (v) any capital stock of the Company issued as a

<PAGE>   29

         dividend or other distribution with respect to, or in exchange for or
         in replacement of, the shares of Common Stock referred to in clause
         (i), (ii), (iii) or (iv);" and

2. RATIFICATION. In all other respects, the Amended and Restated Registration
Rights Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 75% of the Registrable Shares (as defined in
the Amended and Restated Registration Rights Agreement).

                  [Remainder of page intentionally left blank]

                                      -2-

<PAGE>   30

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
4 to the Amended and Restated Registration Rights Agreement as of the date first
above written.

                                  The Medicines Company

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                      Name: Peyton J. Marshall
                                      Title: Chief Financial Officer

                                  Holders of at least 75% of the Registrable
                                  Securities

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                      Under Power of Attorney
                                      of Holders attached hereto

                                      -3-<PAGE>   1
                                                                    Exhibit 10.4

               THIRD AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT

         Third Amended and Restated Stockholders' Agreement, dated as of this
12th day of August, 1998 (the "Agreement"), among The Medicines Company, a
Delaware corporation (the "Company"), the individuals and entities listed on
SCHEDULE I hereto (the "Old Investors") and the individuals and entities listed
on Schedule 11 hereto (the "New Investors"). The Old Investors and the New
Investors are collectively referred to herein as the "Investors".

                                 R E C I T A L S

         WHEREAS, pursuant to the terms of a Stock Purchase Agreement, dated as
of August 12,1998, with the Company (the "Purchase Agreement"'), the New
Investors have agreed to purchase, shares of Series III Convertible Preferred
Stock, par value $1.00 par value per share, of the Company (the "Series III
Preferred Stock"); and

         WHEREAS, in connection with the purchase and sale of shares of Series A
Redeemable Preferred Stock, $1.00 par value per share (the "Series A Stock"),
and shares of Common Stock, $0.001 par value per share (the "Common Stock"), of
the Company pursuant to Stock Purchase Agreements dated as of September 5, 1996,
June 4, 1997 and December 17, 1997 (the "Old Purchase Agreements"), the Company
previously entered into Second Amended and Restated Stockholders' Agreement
dated December 17, 1997 (the "Second Amended and Restated Stockholders'
Agreement") with the Old Investors; and

         WHEREAS, the Company has previously exchanged the shares of Series A
Stock and Common Stock sold pursuant to the Old Purchase Agreements for shares
of Series I Convertible Preferred Stock, $1.00 par value per share (the "Series
I Preferred Stock") and Series 11 Convertible Preferred Stock, $1.00 par value
per share (the "Series 11 Preferred Stock" and, collectively with the Series I
Preferred Stock and Series III Preferred Stock, the "Preferred Stock"); and

         WHEREAS, the Company and the Old Investors believe if -to be in their
mutual best interests to amend and restate the Second Amended and Restated
Stockholders' Agreement; and

         WHEREAS, the Investors and the Company desire to promote their mutual
interests by agreeing to certain matters relating to the operations of the
Company and the disposition and voting of the Shares (as hereinafter defined);

         NOW, THEREFORE, in consideration of the mutual covenants and agreements
herein contained and in consideration of the foregoing and of the respective
covenants and undertakings of the Company and the Investors, the parties hereto
hereby agree to amend and restate the Second Amended and Restated Stockholders'
Agreement as follows:

1.       COVENANTS OF THE PARTIES

         (a) LEGENDS. The certificates evidencing the Shares acquired by the
Investors pursuant to the Old Purchase Agreements and the Purchase Agreement
will bear a legend reflecting the restrictions on the transfer of such
securities contained in this Agreement in substantially the following form:

<PAGE>   2

                  "The securities evidenced hereby are subject to the terms of
                  that certain Third Amended and Restated Stockholders'
                  Agreement, dated as of August - 12, 1998, by and among the
                  Company and certain investors identified therein, as amended
                  from time to time, including certain restrictions on transfer.
                  A copy of this Agreement has been filed with the secretary of
                  the Company and is available upon request."

         If any Shares shall cease to be subject to the provisions of this
Agreement, the Company shall, upon the written request of the holder thereof,
issue to such holder a new certificate evidencing such Shares without the legend
required by Section 1(a) hereof endorsed thereon.

         (b) ADDITIONAL INVESTORS. The parties hereto acknowledge that certain
employees of the Company may become stockholders of the Company after the date
hereof. As a condition to the issuance of shares of Common Stock to such
employees, the Company shall require such employees to execute an agreement
containing restrictions substantially similar to those set forth in Sections
3(a), (b), (c), (d) and (e) hereof.

2.       BOARD OF DIRECTORS

         (a) ELECTION OF DIRECTORS.

              (i) As of the date hereof, the Board of Directors of the Company
(the "Board") consists of Clive A. Meanwell, James E.Thomas, Nicholas J.
Lowcock, T. Scott Johnson, Victor Bischoff, Jacques Rejeange, Dennis Gillings
and Faizl Husain. From and after the date hereof, the Investors and the Company
shall take all action within their respective power, including but not limited
to, the voting of all Shares owned by them, required to cause the Board to
consist of at least eight (8) members or such other number as the Board may from
time to time establish, and at all times throughout the term of this Agreement
to include (A) the Chief Executive Officer of the Company, (B) as long as
Warburg, Pincus Ventures, L.P. ("Warburg") and its Permitted Transferees own at
least seven and one-half percent (7.5%) of the Common Stock of the Company,
calculated on an as converted basis, but less than twenty percent (20%,) of the
Common Stock of the Company, calculated on an as converted basis, one
representative designated by Warburg; as long as Warburg and its Permitted
Transferees own at least twenty percent (20'%) of the Common Stock of the
Company, calculated on an as converted basis, two representatives designated by
Warburg (each, a "Warburg Director"), (C) as long as T. Scott Johnson, Ansbert
Gadicke, Hanseatic and MPM Medicines L.P. (collectively, the -MPM Group") and
their Permitted Transferees as a group own at least seven and one-half percent
(7.5%) of the Common Stock of the Company, calculated on an as converted basis,
one representative designated by MPM Medicines L.P. ("MPM") (an "MPM Director");
(D) as long as PharmaBio Development Inc. ("PharmaBio") and its Permitted
Transferees own at least seven and one-half percent (7.5'%) of the Common Stock
of the Company, calculated on an as converted basis, one representative
designated by PharmaBio (a "PharmaBio Director"); (E) as long as Biotech Target,
S.A. ("Biotech Target") and its Permitted Transferees own at least seven and
one-half percent (7.5%) of the Common Stock of the Company, calculated on an as

                                      -2-
<PAGE>   3

converted basis, one representative designated by Biotech Target; as long as
Biotech Target and its Permitted Transferees own at least twenty percent (20%.)
of the Common Stock of the Company, calculated on an as converted basis, two
representatives designated by Biotech Target (each, a "Biotech Target
Director"); and (F) as long as Morgan Stanley Venture Partners 111, L.P., Morgan
Stanley Venture Investors III, L.P. and The Morgan Stanley Venture Partners
Entrepreneur Fund, L.P. (collectively, the "MSVP Investors") and their Permitted
Transferees as a group own at least three and one-half percent (3.5%.) of the
Common Stock of the Company, calculated on an as converted basis, one
representative designated by the MSVP Investors (a "MSVP Director"). From and
after the date hereof (until the death, disability, resignation or removal of
such director in accordance with the terms hereof), James E. Thomas and Nicholas
J. Lowcock shall constitute the Warburg Directors.- T. Scott Johnson shall
constitute the MPM Director; Dennis Gillings shall constitute the PharmaBlo
Director; Victor Bischoff and Jacques Rejeange shall constitute the Biotech
Target Directors; and Fazte Husain shall constitute the MSVP Director.

              (ii) From the date on which the Company completes an underwritten
public offering for shares of Common Stock (the "Initial Public Offering")
pursuant to a registration under the Securities Act, and for as long as any
Investor and its Permitted Transferees own at least twenty percent (20%) of the
Common Stock of the Company, calculated on an as converted basis, other than
Biotech Target, whose rights to designate representatives to the Board shall
terminate upon the completion of an Initial Public Offering, the Company will
nominate and use its best efforts to have two individuals designated by such
Investor elected to the Board. From the date on which the Company completes its
Initial Public Offering and for as long as any Investor and its Permitted
Transferees own at -least ten percent (10%.) of the Common Stock of the Company,
calculated on an as converted basis, other than Biotech Target as provided
above, the Company will nominate and use its best efforts to have one
`individual designated by such Investor elected to the Board.

         (b) REPLACEMENT DIRECTORS. In the event that any Warburg Director, MPM
Director, PharmaBlo Director, Biotech Target Director or MSVP Director (a
"Withdrawing Director") designated in the manner set forth in Section 2(a)
hereof is unable to serve, or once having commenced to serve, is removed or
withdraws from the Board, such Withdrawing Director's replacement (the
"Substitute Director") will be designated by Warburg, MPM, PharmaBio, Biotech
Target or the MSVP Investors, as the case may be. Such Investor (or group of
Investors) shall have the right at any time, by written notice to the other
Investors, to request the removal of any director designated by such Investor
and such Investor shall thereafter have the right to nominate a replacement for
such director. The Investors and the Company agree to take all action within
their respective power, including but not limited to, the voting of capital
stock of the Company owned by them or the execution of a shareholder consent to
cause the removal or election of any director designated by an Investor or group
of Investors pursuant to Section 2(a) promptly following the request for removal
or nomination, as the case may be, by such Investor or group of Investors
pursuant to this Section 2(b).

                                      -3-
<PAGE>   4

         (c) REMOVAL. Each Investor agrees that if, at any time, it is then
entitled to vote for the removal of directors of the Company, it will not vote
any of its Shares in favor of the removal of any director who shall have been
nominated pursuant to Section 2(a) or 2(b), except for bad faith or willful
misconduct, unless the Investor(s) entitled to nominate such director shall have
consented to such removal in writing.

         (d) QUARTERLY MEETINGS. The Board of Directors of the Company will meet
no less frequently than quarterly.

3.       TRANSFER OF STOCK

         (a) RESALE OF SECURITIES. No Investor shall Transfer any Shares other
than in accordance with the provisions of this Section 3 and in compliance with
applicable federal, state and foreign securities laws. Any Transfer or purported
Transfer made in violation of this Section 3 shall be null and void and of no
effect. Notwithstanding anything herein to the contrary, the rights of the
Company and Investors under this Section 3 shall not apply to any pledge of
Shares by an Investor which creates a mere security interest, provided that the
pledgee agrees in writing to be bound by this Agreement as if it were an
Investor.

         (b) AGREEMENT TO BE BOUND. No Transfer of Shares may be made to any
Permitted Transferee unless (1) the certificates representing such Shares
delivered to such Permitted Transferee shall bear the legend set forth in
Section 1, if required by such Section, and (1i) except as otherwise
specifically permitted by the provisions of this Agreement, prior to such
Transfer, such Permitted Transferee (if not already a party to this Agreement)
shall have executed and delivered to the Company an instrument in form and
substance satisfactory to the Company confirming that such transferee has agreed
to be bound as an "Investor" by the terms of this Agreement; provided that the
provisions of clause (ii) above shall not be applied to any Transfer following
the termination of this Agreement pursuant to Section 5 (notwithstanding any
survival of the provisions of Section 2(a)(ii)).

         (c) THE OFFER.

              (i) No Investor shall Transfer any of the Shares owned by him, her
or it to any Person (other than the Company) that is not a Permitted Transferee
of such Investor (a "Proposed Transferee") unless tile Investor desiring to make
the Transfer (hereinafter referred to as the "Transferor") shall have first
delivered a written notice (the "Offer") to the other Investors and the Company
and complied with the provisions of Sections 3(d) and (e). The Offer shall set
forth the number and class or series of Shares proposed to be Transferred to the
Proposed Transferee (the "Subject Shares"), the total number and class or series
of Shares owned by the Transferor, the terms and conditions (including price) of
the proposed sale to such Proposed Transferee, the identity of such Proposed
Transferee and any other material facts relating to the proposed sale to such
Proposed Transferee. In the case of a proposed transaction in which the
consideration consists in part or in whole of consideration other than cash, the
Transferor shall furnish such information relating to such consideration as the
Company and/or the Investors may reasonably request as being necessary for the
Company and/or the Investors to evaluate such

                                      -4-
<PAGE>   5

non-cash consideration, it being understood that such request shall not obligate
such Transferor to deliver any in-formation to the Company and/or the Investors
not provided to such Transferor by the Proposed Transferee.

         (d) RIGHT OF FIRST REFUSAL.

              (i) ACCEPTANCE OF OFFER. Within twenty (20) days after the receipt
of an Offer, the Company may, at its option, elect to purchase all, but not less
than all, of the Subject Shares in accordance with the provisions of this
Agreement and for the price and upon the other terms and conditions set forth in
such Offer. The Company shall exercise such option by giving notice thereof to
the Transferor and to each Investor within such twenty (20) day period.

         In the event that the Company does not exercise its option to purchase
all of the Subject Shares within such twenty (20) day period, it shall provide
notice (the "Company Non-Exercise Notice") of such determination to the
Investors and each Investor shall be entitled to purchase all, but not less than
all, of such Investor's Pro Rata Portion of the Subject Shares in accordance
with the provisions of this Agreement and for the price and upon the other terms
and conditions set forth in such Offer. The Investors may exercise such option
by giving notice thereof to the Transferor and to the Company, within twenty
(20) days after receipt of the Company Non-Exercise Notice from the Company,
setting forth the number of Subject Shares it wishes to purchase. Alternatively,
each Investor may within the same twenty (20) day period notify the Transferor
and the Company of its desire to participate in the sale of the Subject Shares
in accordance with the provisions of Section 3(e) and for the price and upon the
other terms and conditions set forth in such Offer, and the number of Subject
Shares it wishes to sell (such Investor being referred to as a "Selling
Investor").

         If each Investor does not elect during such twenty (20) day period to
purchase the number of Subject Shares permitted to be purchased by such Investor
during such twenty (20) day period (and notwithstanding any election made by
such Investor pursuant to the immediately preceding paragraph to be a Selling
Investor), the Company shall, within five (5) days after the expiration of such
twenty (20) day period, provide written notice to all Investors that elected to
purchase Subject Shares during such twenty (20) day period, informing them that
they have the right to increase the number of Subject Shares that they may elect
to purchase on the same terms as the Subject Shares each such Investor has
previously elected to purchase. Each such accepting Investor will then have a
five-day period from the receipt of such notice from the Company in which to
elect to purchase the number and type of the Subject Shares that Investors have
not previously elected to purchase during the initial period, allocated among
such accepting Investors on the basis of the relative number of Shares that each
such Investor indicated that it wished to purchase during the initial period
(which number of shares shall in no event exceed such Investor's Pro Rata
Portion of the Subject Shares) by delivery of written notice of acceptance to
the Seller prior to the expiration of such five-day period.

         In either event, the notice required to be given by the purchasing
party (the "Purchaser") shall specify a date for the closing of the purchase
which shall not be more than thirty (30) days

                                      -5-
<PAGE>   6

after the date of the giving of such notice or as soon as practicable thereafter
following receipt of all required regulatory approvals.

              (ii) PURCHASE PRICE. The purchase price per share for the Subject
Shares shall be the price per share offered to be paid by the Proposed
Transferee, which price shall be paid in cash or, if so provided la ` the offer
of the Proposed Transferee, cash plus deferred payments of cash in the same
proportions, and with the same terms of deferred payment as therein set forth.

              (iii) CONSIDERATION OTHER THAN CASH. If the Proposed Transferee
has offered to purchase the Subject Shares for consideration other than cash or
cash plus deferred payments of cash, the Purchaser shall pay the cash equivalent
of such other consideration. If the Transferor and the Purchaser cannot agree on
the amount of such cash equivalent within ten (10) days after the beginning of
the twenty (20) day period referred to in the first sentence under Section
3(d)(1), any of such parties may, by three (3) days' written notice to the
other, initiate appraisal proceedings under Section 3(d)(iii)] for determination
of the cash equivalent. The Purchaser may give written notice to the Transferor
revoking an election to purchase the Subject Shares within ten (10) days after
determination of the appraised value, if it chooses not to purchase the Subject
Shares.

              (iv) APPRAISAL PROCEDURE. If any party shall initiate an appraisal
procedure to determine the amount of the cash equivalent of any consideration
for Subject Shares under Section 3(d)(iii), then the Transferor, on the one
hand, and the Purchaser, on the other hand, shall each promptly appoint as an
appraiser an individual who shall be knowledgeable in the industry and mutually
agreeable to the parties, or failing mutual agreement, a member of a nationally
recognized investment banking firm. Each appraiser shall, within thirty (30)
days of appointment, separately investigate the value of the consideration for
the Subject Shares (without regard to the income tax consequences to the
Transferor as a result of receiving cash rather than other consideration) as of
the proposed transfer date and shall submit a notice of an appraisal of that
value to each party. If the appraised values of such consideration (the "Earlier
Appraisals") vary by less than ten percent (10%), the average of the two
appraisals on a per share basis shall be controlling as the amount of the cash
equivalent. If the appraised values vary by more than ten percent (10%), the
appraisers, within ten (10) days of the submission of the last appraisal, shall
appoint a third appraiser who shall be an individual knowledgeable in the
industry and mutually agreeable to the parties, or failing mutual agreement, a
member of a nationally recognized investment banking firm. The third appraiser
shall, within thirty (30) days of his appointment, appraise the value of the
consideration for the Subject Shares (without regard to the income tax
consequences to the Transferor as a result of receiving cash rather than other
consideration) as of the proposed transfer date and submit notice of his
appraisal to each party. The value determined by the third appraiser shall be
controlling as the amount of the cash equivalent unless the value is greater
than the two Earlier Appraisals, in which case the higher of the two Earlier
Appraisals will control, and unless that value is lower than the two Earlier
Appraisals, in which case the lower of the two Earlier Appraisals will control.
If any party falls to appoint an appraiser or if one of the two initial
appraisers fails after appointment to submit his appraisal within the

                                      -6-
<PAGE>   7

required period, the appraisal submitted by the remaining appraiser shall be
controlling. The Transferor and the Purchaser shall each bear the cost of its
respective appointed appraiser. The cost of the third appraisal shall be shared
one-half by the Transferor and one-half by the Purchaser.

              (v) CLOSING OF PURCHASE. The closing of the purchase shall take
place at the office of the Company or such other location as shall be mutually
agreeable and the purchase price, to the extent comprised of cash, shall be paid
at the closing, and cash equivalents and documents evidencing any deferred
payments of cash permitted pursuant to Section 3(d)(1i) above shall be delivered
at the closing. At the closing, the Transferor shall deliver to the Purchaser
the certificates evidencing the Subject Shares to be conveyed, free and clear of
all liens and encumbrances, duly endorsed and in negotiable form with all the
requisite documentary stamps affixed there

         (e) CO-SALE RIGHT.

         (f) GENERAL. In the event that the Company and the Investors do not
exercise their options to purchase all of the Subject Shares within the periods
described in Section 3(d) (the "Option Period") and the Transferor desires to
proceed with the direct or indirect sale of the Subject Shares (the "Take-Along
Shares") to a Proposed Transferee, the Selling Investors shall have the right to
sell to the Proposed Transferee, at the same price per share (calculated on an
as-converted basis) and on the same terms and conditions as are proposed to be
sold by the Transferor and set forth in the applicable Offer, up to a number of
Shares (whether or not the same class or series as the Take-Along Shares)
determined pursuant to Section 3(e)(ii). Any sale by a Selling Investor pursuant
to this Section 3(e) shall not be subject to the provisions of Sections 3(c) or
(d).

              (i) AMOUNT TRANSFERRED BY SELLING INVESTOR. Each Selling Investor
shall have the right to Transfer, pursuant to the Offer, a number of shares of
Common Stock up to the product of (x) the total number of Subject Shares
(calculated on an as-converted basis) offered to be Transferred by the
Transferor or offered to be purchased by the Prospective Transferee as set forth
in the applicable Offer and (y) the Pro Rata Portion of such Investor.

              (ii) AMOUNT TRANSFERRED BY TRANSFEROR. The Transferor shall use
his best efforts to interest the Proposed Transferee in purchasing, in addition
to the Take-Along Shares, the Shares the Selling Investors wish to sell. If the
Proposed Transferee does not wish to purchase all of the Shares made available
by the Transferor and the Selling Investors, then the Take-Along Shares that the
Transferor is entitled to Transfer shall be reduced by the Shares to be
transferred by the Selling Investors.

              (iii) SALE OF SHARES. If the Transferor wishes to Transfer any
Shares to a Proposed Transferee at a price per Share which is less than from
that set forth in the Offer, upon terms different from those previously offered
to the Company and the Investors, or more than ninety (90) days after the
expiration of the Option Period, then, as a condition precedent to such
transaction, such Shares must first be offered to the Company and the Investors
on the same

                                      -7-
<PAGE>   8

terms and conditions as given the Proposed Transferee, and in accordance with
the procedures and time periods set forth in Sections 3(c), (d) and (e). If
Subject Shares are transferred to any Proposed Transferee who is not a party to
this Agreement, the Subject Shares so transferred shall no longer be subject to
any of the restrictions imposed by Sections 3(c), (d) and (e)-

         (g) SUBSCRIPTION RIGHT.

              (i) If at any time after the date hereof, the Company proposes to
issue equity securities of any kind (the term "equity securities" shall include
for these purposes any warrants, options or other rights to acquire equity
securities and debt securities convertible into equity securities) of the
Company (other than the issuance of securities (A) upon the conversion of
outstanding shares of Preferred Stock in accordance with the charter of the
Company, (B) to the public in a firm commitment underwriting pursuant to a
registration statement filed under the Securities Act, (C) pursuant to the
acquisition of another corporation by the Company by merger, purchase of
substantially all of the assets or other form of reorganization, (D) pursuant to
an employee stock option plan, stock bonus plan, stock purchase plan or other
management equity program approved by the Board or (E) in connection with
equipment lease transactions approved by the Board), then, as to each Investor
who then holds in excess of one percent (1%) of the then outstanding Common
Stock of the Company, calculated on an as converted basis, the Company shall:

                    (1) give written notice setting forth in reasonable detail
(a) the designation and all of the terms and provisions of the securities
proposed to be issued (the "Proposed Securities"), including, where applicable,
the voting powers, preferences and relative, participating, optional or other
special rights, and the qualifications, limitations or restrictions thereof and
interest rate and maturity; (b) the cash price and other terms of the proposed
sale of such securities; (c) the amount of such securities proposed to be
issued; and (d) such other information as the Investors may reasonably request
in order to evaluate the proposed issuance; and

                    (2) offer to issue to each such Investor such Investor's
Pro Rata Portion of the Proposed Securities.

              (ii) Each SUCH Investor MUST EXERCISE hereunder within ten (10)
DAYS after RECEIPT OF SUCH notice FROM THE COMPANY. If all of the proposed
securities offered to such Investor are not fully subscribed by such Investor,
the remaining Proposed Securities will be reoffered to any of the Investors
purchasing their full allotment (pro rata among them on the basis of the
relative number of Proposed Securities each such Investor has previously
indicated that it wishes to purchase) upon the terms set forth in this Section
3(f), until all such Proposed Securities are fully subscribed for or until all
such Investors have subscribed for all such Proposed Securities which they
desire to purchase, except that such Investors must exercise their purchase
rights within five (5) days after receipt of all such reoffers. To the extent
that the Company offers two or more securities in units, the Investors must
purchase such units as a whole and will not be given the opportunity to purchase
only one of the securities making up such unit.

                                      -8-
<PAGE>   9

              (iii)

              (iv) Upon the expiration of the offering periods described above,
the Company will be free to sell such Proposed Securities that the Investors
have not elected to purchase during the ninety (90) days following such
expiration on terms and conditions no more favorable to the purchasers of such
Proposed Securities than those offered to such Investors. Any Proposed
Securities offered or sold by the Company after such ninety (90) day period must
be reoffered to the Investors pursuant to this Section 3(c).

              (v) The closing of purchases of Proposed Securities by Investors
exercising their preemptive rights under this Section 3(0 shall take place on
the closing date of such issuance; PROVIDED that, in the event that the Holders
have exercised their preemptive rights as to all of such Proposed Securities,
the issuance of such Proposed Securities to the Investors shall be consummated
within thirty (30) days following the expiration of the last order period
described above. At such closing, the Company shall issue certificates
representing the Proposed Securities to be purchased by each Investor exercising
preemptive rights pursuant to this Section 3(f), free and clear of all liens and
registered in the name of such Investor, against payment by such Investor of the
purchase price for such Proposed Securities.

              (vi) The election by an Investor not to exercise its subscription
rights under this Section 3(f) in any one instance shall not affect its right
(other than in respect of a reduction in its percentage holdings) as to any
subsequent proposed issuance,

4.       NOTICE TO STOCKHOLDERS

         In the event any Investors propose to take action by written consent
pursuant to Section 228 of the Delaware General Corporation Law, the Company (or
the Investor proposing the action) shall provide written notice to all Investors
of the proposed action not less than 24 hours prior to the time at which such
action is to be effective. Such written notice shall describe the material terms
and conditions of the proposed action. If any material change in the facts set
forth in such notice shall occur, the Company (or the Investor proposing the
action) shall promptly give written notice to each Investor. The execution by
any Investor of any written con-sent shall be deemed to be a waiver of the
notice and information rights provided herein with respect to the matters
covered by such written consent.

5.       TERMINATION The Agreement shall terminate upon the earlier of:

         (a) the closing of an Initial Public Offering, except for the
provisions of Section 2(a)(10 which shall remain in full force and effect
following the closing of the Initial Public Offering;

         (b) the date on which the parties to this Agreement who hold sixty-five
percent (65%) of the shares of Common Stock, calculated on an as converted
basis, then covered by this Agreement shall have agreed in writing to terminate
this Agreement; or

                                      -9-
<PAGE>   10

         (c) ten (10) years from the date of this Agreement;

provided that no such termination shall relieve any party to this Agreement of
liability for a breach prior to termination of any of its covenants or
agreements contained in this Agreement.

6.       COVENANTS

         (a) FINANCIAL AND BUSINESS INFORMATION.

              (i) The Company will deliver to each Investor:

                    (1) QUARTERLY STATEMENTS Within 45 days after the close of
each of the first three fiscal quarters of each fiscal year of the Company, a
consolidated balance sheet, statements of income, stockholders equity and cash
flows of the Company and its subsidiaries, if any, as at the close of such
quarter and covering operations for such quarter and the portion of the
Company's fiscal year ending on the last day of such quarter, all in reasonable
detail and prepared in accordance with GAAP, subject to normal year-end audit
adjustments, setting forth in each case in comparative form the figures for the
comparable period of the previous fiscal year.

                    (2) ANNUAL STATEMENTS as soon as practicable after the end
of each fiscal year of the Company, and in any event within ninety (90) days
thereafter, duplicate copies of :

                         (A) a consolidated balance sheet of the Company and its
subsidiaries, if any, at the end of such year; and

                         (B) consolidated statements of income, stockholders'
equity and cash flows of the Company and its subsidiaries, if any, for such
year, setting forth in each case in comparative form the figures for the
previous fiscal year, all in reasonable detail and accompanied by an opinion
thereon of independent certified public accountants of recognized national
standing selected by the Company, which opinion shall state that such financial
statements fairly present the consolidated financial position of the Company and
its subsidiaries, if any, and have been prepared in accordance with GAAP (except
for changes in application In which such accountants concur) and that the
examination of such accountants in connection with such financial statements has
been made in accordance with generally accepted auditing standards, and
accordingly included such tests of the accounting records and such other
auditing procedures as were considered necessary in the circumstances.

              (ii) The Company will deliver to each Investor for so long as such
Investor owns at least two percent (2%) of the outstanding shares of Common
Stock, calculated on as converted basis:

                    (1) MONTHLY STATEMENTS - as soon as practicable, and in any
event within thirty (30) days after the close of each month of each fiscal year
of the Company,

                                      -10-
<PAGE>   11

(A) a statement of expenses accrued for such month, compared to the budget for
such month, (B) (other than with respect to the last month in each fiscal year)
a consolidated balance sheet as at the end of such month and consolidated
statements of income for such month and (C) a narrative describing any material
events that may have occurred during such month.

                    (2) AUDIT REPORTS - promptly upon receipt thereof, one copy
of each other financial report, audit response letter and internal control
letter submitted to the Company by independent accountants in connection with
any annual, interim or special audit made by them of the books of the Company.

                    (3) OTHER REPORTS - promptly upon their becoming available,
one copy of each financial statement, report, notice or proxy statement sent by
the Company to stockholders generally, of each financial statement, report,
notice or proxy statement sent by the Company to the SEC or any successor
agency, if applicable, of each regular or periodic report and any registration
statement, prospectus or written communication (other than transmittal letters)
in respect thereof filed by the Company with, or received by such Person in
connection therewith from, any domestic or foreign securities exchange, the SEC
or any successor agency or any foreign regulatory authority performing functions
similar. to the SEC, of any press release issued by the Company, and of any
material of any nature whatsoever prepared by the SEC or any successor agency
thereto or any state blue sky or securities law commission which relates to or
affects in any way the Company.

                    (4) REQUESTED INFORMATION - with reasonable promptness, the
Company shall furnish to each of such Investors such other data and information
as from time to time may be reasonably requested.

                    (5) ANNUAL BUDGETS - prior to the start of each fiscal year,
consolidated capital and operating expense budgets, cash flow projections and
income and loss projections for the Company and its subsidiaries `in respect of
such fiscal year, all itemized in reasonable detail and prepared on a monthly
basis, and, promptly after preparation, any revisions to any of the foregoing.

                    (6) LITIGATION - promptly after the commencement thereof,
notice of aft actions, suits, claims, proceedings, investigations and inquiries
of the type described in Section 2.07 of the Purchase Agreement, which, if
determined adversely, could have a Material Adverse Effect (as defined in the
Purchase Agreement).

         (b) INSPECTION. In addition to any rights of the Investor under
applicable law, as long as an Investor owns at least two (2%) percent of the
outstanding shares of Common Stock calculated on an as converted basis, the
Company shall permit such Investor or its nominees, assignees, and
representatives to visit and inspect any of the properties of the Company, to
examine all its books of account, records, reports and other papers not
contractually required of the Company to be confidential or secret, to make
copies and extracts therefrom , and to discuss its affairs, finances and
accounts with its officers, directors, key employees and independent public
accountants or any of them (and by this provision the Company authorizes

                                      -11-
<PAGE>   12

said accountants to discuss with such Investor, its nominees, assignees and
representatives the finances and affairs of the Company), all at such reasonable
times and as often as may be reasonably requested.

         (c) CONFIDENTIALITY. As to the portion of the information and other
material furnished under or in connection with this Agreement (whether furnished
before, on or after the date hereof, including without limitation information
furnished pursuant to Section 6(a) and 6(b) hereof) as constitutes or contains
confidential business, financial or other information of the Company or any
subsidiary, each of the Investors covenants for itself and its directors,
officers and partners that it will use due care to prevent its officers,
directors, partners, employees, counsel, accountants and other representatives
form disclosing such information to Persons other than their respective
authorized employees, counsel, accountants, stockholders, partners, limited
partners and other authorized representatives; provided, however, that each
Investor may disclose or deliver any information or other material disclosed to
or received by it (1) should such Investor be advised by its counsel that such
disclosure or delivery is required by law, regulation or judicial or
administrative order or (ii) to any Person to whom such Investor is
contemplating a Transfer of its Shares, so long as (A) such Transfer would not
be in violation of the provisions of this Agreement, and (B) such potential
transferee is advised of the confidential nature of such information and agrees
to be bound by a confidential agreement in form and substance satisfactory to
the Company and consistent with the provisions hereof. In the event of any
termination of this Agreement, each Investor shall return to the Company all
confidential material previously furnished to such Investor or its officers,
directors, partners, employees, counsel, accountants and other representatives,
which is still held by such Investor; provided that such Investor may retain a
copy of such material for archival purposes only if such material relates to its
investment in the Company and not the business of the Company- For purposes of
this Section 6(c), "due care" means at least the same level of care that such
Investor would use to protect the confidentiality of its own sensitive or
proprietary information, and this obligation shall survive termination of this
Agreement.

         (d) CONDUCT OF BUSINESS AND MAINTENANCE OF EXISTENCE. The Company will
continue to engage in business of the same general type as now conducted by it,
and preserve, renew and keep in full force and effect its corporate existence
and take all reasonable action to maintain all rights, privileges and franchises
necessary or desirable in the normal conduct of its business. The Company shall
require all of its employees or consultants to enter into appropriate
confidentiality agreements to protect confidential information relating to the
Company and its business, including trade secrets.

         (e) COMPLIANCE WITH LAWS. The Company will comply in all material
respects with all applicable laws, rules, regulations and orders except where
the failure to comply would not have a material adverse effect on the business,
properties, prospects, profits or condition (financial or otherwise) of the
Company.

         (f) INSURANCE. The Company shall maintain with financially sound and
reputable insurance companies insurance on the business and properties of the
Company (including, without limitation, directors and officers liability
insurance and, at least from and

                                      -12-
<PAGE>   13

after the date of the first commercial sale of the first product by the Company,
product liability coverage), in at least such amounts and against at least such
risks as are usually insured against by companies engaged in similar businesses
and as shall be reasonably acceptable to the Investors. The Company shall be the
loss payee on all such insurance, unless otherwise determined by the Board of
Directors.

         (g) KEEPING OF BOOKS. The Company will keep proper books of record and
account, in which full and correct entries shall be made of all financial
transactions and the assets and business of the Company in accordance with GAAP.

         (h) LOST, ETC. CERTIFICATES EVIDENCING SHARES OF COMMON STOCK OR
PREFERRED STOCK; EXCHANGE. Upon receipt by the Company of evidence reasonably
satisfactory to it of the loss, theft, destruction or mutilation of any
certificate evidencing any shares of Common Stock or Preferred Stock owned by
one of the Investors, and (in the case of loss, theft or destruction) of an
unsecured indemnity satisfactory to it, and upon reimbursement to the Company of
all reasonable expenses incidental thereto, and upon surrender and cancellation
of such certificate, if mutilated, the Company will make and deliver in lieu of
such certificate a new certificate of like tenor and for the number of shares
evidenced by such certificate which remain outstanding. Such Investor's
agreement of indemnity shall constitute(~, indemnity satisfactory to the Company
for purposes of this Section 6(h). Upon surrender of any certificate
representing any shares of Common Stock or Preferred Stock for exchange at the
office of the Company, the Company at its expense will cause to be issued in
exchange therefor new certificates in such denomination or denominations as may
be requested for the same aggregate number of shares of Common Stock or
Preferred Stock, as the case may be, represented by the certificate so
surrendered and registered at such holder may request. The Company will also pay
the cost of all deliveries of certificates for such shares to the office of such
Investor (including the cost of insurance against loss or theft in an amount
satisfactory to the holders) upon any exchange provided in this Section 6(h).

         (i) REPORT DIVIDENDS AND DISTRIBUTIONS. If required by the Internal
Revenue Code of 1986, as amended, the Company shall provide a copy of Internal
Revenue Service Form 1099-DIV to each of the Investors on an annual basis.

7.       INTERPRETATION OF THIS AGREEMENT

         (a) TERMS DEFINED. As used in this Agreement, the following terms have
the respective meaning set forth below:

         AFFILIATE: any person directly or indirectly controlling, controlled by
or under common control with a specified Person.

         AMENDED REGISTRATION RIGHTS AGREEMENT: the Amended and Restated
Registration Rights Agreement among the Company and certain of the Investors
dated as of the date hereof.

         EXCHANGE ACT: the Securities Exchange Act of 1934, as amended.

                                      -13-
<PAGE>   14

         GAAP: United States generally accepted accounting principles,
consistently applied.

         INITIAL PUBLIC OFFERING : as defined in Section 2(a)(10 herein.

         PERMITTED TRANSFEREE: with respect to any Person, means, if such person
is not an individual, any Affiliate of such Person or, in the case of any
individual, any members of such Investor's family, heirs, executors or legal
representatives or trusts for the benefit of such Investor or such Investor's
family or a partnership, corporation or limited liability company wholly owned
by such Investor;

         PERSON: an individual, partnership, limited liability company,
joint-stock company, corporation, trust or unincorporated organization, and a
government or agency or political subdivision thereof.

         PRO RATA PORTION: means, with respect to any Investor at any time, (i)
the number of shares of Common Stock, calculated on an as-converted basis, that
such Investor owns at such time, divided by (ii) the number of shares of Common
Stock, calculated on an as-converted basis, owned by all Investors (other than
in the case of Section 3(d), the shares owned by the Transferor, and in the case
of Section 3(e), the Proposed Transferee (if such Proposed Transferee is an
Investor) at such time.

         SECURITY, SECURITIES: as defined in Section 2(l) of the Securities Act.

         SECURITIES ACT: the Securities Act of 1933, as amended.

         SHARES: all shares of Common Stock, Series I Preferred Stock, Series 11
Preferred Stock and Series III Preferred Stock currently owned (either
beneficially or of record) or subsequently acquired by any of the Investors,
including any shares which an Investor does not own (either beneficially or of
record) but as to which such Investor exercises voting control, and including
without limitation, shares of Common Stock acquired upon conversion of shares of
Preferred Stock.

         TRANSFER: (i) when used as a noun, any sale, assignment,, or other
disposition or encumbrance (other than as contemplated by the Pledge Agreements
between Warburg and certain of the Individual Investors, dated September 5,
1996) or any agreement to do any of the foregoing and (ii) when used as a verb,
to sell assets or otherwise dispose of or agree to do any of the foregoing.

         (b) ACCOUNTING PRINCIPLES. Where the character or amount of any asset
or amount of any asset or liability or item of income or expense is required to
be determined or any consolidation or other accounting computation is required
to be made for the purposes of this Agreement, this shall be done in accordance
with GAAP at the time in effect, to the extent applicable.

                                      -14-
<PAGE>   15

         (c) DIRECTLY OR INDIRECTLY. Where any provision in this Agreement
refers to action to be taken by any Person, or which such Person is prohibited
from taking, such provision shall be applicable whether such action is taken
directly or indirectly by such Person.

         (d) GOVERNING LAW. This Agreement shall be governed by and construed in
accordance with the laws of the State of Delaware applicable to contracts made
and to be performed entirely within such State.

         (e) SECTION HEADINGS. The headings of the sections and subsections of
this Agreement are inserted for convenience only and shall not be deemed to
constitute a part thereof.

8.       MISCELLANEOUS

         (a) NOTICES.

              (i) All communications under this Agreement shall be in writing
and shall be delivered by hand or mailed by overnight courier or by registered
mail or certified mail, postage prepaid:

                    (1) If to an Investor listed on SCHEDULE I hereto, at his,
hers or its address set forth on SCHEDULE 1, or at such other address as may
have been furnished to the Company in writing;

                    (2) If to an Investor listed on SCHEDULE 11 hereto, at his,
hers or its address set forth on SCHEDULE 11, or at such other address as may
have been furnished to the Company in writing; or

                    (3) if to the Company, at One Cambridge Center, Suite 407,
Cambridge, Massachusetts 02142, marked for the attention of Clive Meanwell, or
at such other address as the Company may have furnished in writing to the
Investors, with a copy (which shall not constitute notice) to Hale and Dorr LLP,
60 State Street, Boston, Massachusetts 02109, marked for the attention of Steven
D. Singer, Esq.

              (ii) Any notice so addressed shall be deemed to be given: if
delivered by hand, on the date of such delivery; if mailed by courier, on the
first business day following the date of such mailing; and if mailed by
registered or certified mail, on the third business day after the date of such
mailing.

         (b) REPRODUCTION OF DOCUMENTS. This Agreement and all documents
relating thereto, including, without limitation, (1) consents, waivers and
modifications which may hereafter be executed, (11) documents received by each
Investor pursuant hereto and (111) financial statements, certificates and other
information previously or hereafter furnished to each Investor, may be
reproduced by each Investor by a photographic, photostatic, microfilm,
microcard, miniature photographic or other similar process and each Investor may
destroy any original document so reproduced. All parties hereto agree and
stipulate that any such

                                      -15-
<PAGE>   16

reproduction shall be admissible in evidence as the original itself in any
judicial or administrative proceeding (whether or not the original is in
existence and whether or not such reproduction was made by each Investor in the
regular course of business) and that any enlargement, facsimile or further
reproduction of such reproduction shall likewise be admissible in evidence.

         (c) SUCCESSORS AND ASSIGNS. This Agreement shaft inure to the benefit
of and be binding upon the heirs, executors, administrators, successors and
permitted assigns of each of the parties. Notwithstanding the foregoing, neither
this Agreement nor any right, remedy, obligation or liability arising hereunder
or by reason hereof shall be assignable by the Company or any Investor, except
(1) as specifically provided pursuant to the terms hereof, and (11) in
connection with a Transfer of securities of the Company pursuant to the terms
hereof, in which case any Person acquiring Shares who is required by the terms
of this Agreement to become a party hereto shall thenceforth be an "Investor".
Nothing in this Agreement, expressed or implied, is intended to confer on any
Person other than the parties hereto, and their respective successors and
permitted assigns, any rights, remedies, obligations or liabilities under or by
reason of this Agreement.

         (d) TERMINATION OF THE SECOND AMENDED AND RESTATED STOCKHOLDERS'
AGREEMENT. Upon the effectiveness of this Agreement, the Second Amended and
Restated Stockholders' Agreement is terminated and shall be superseded by the
provisions of this Agreement.

         (e) ENTIRE AGREEMENT; AMENDMENT AND WAIVER. This Agreement, the
Purchase Agreement and the Amended Registration Rights Agreement constitute the
entire understanding of the parties hereto relating to the subject matter hereof
and thereof and supersede all prior understandings among such parties. This
Agreement may be amended, and the observance of any term of this Agreement may
be waived, with (and only with) the written consent of the parties to this
Agreement who hold sixty-five percent (65%) of the shares of Common Stock,
calculated on an as converted basis, then covered by this Agreement; provided
that no amendment which would in any material respect uniquely adversely affect
any particular Investor shall become effective without the prior consent of such
Investor.

         (f) RECAPITALIZATION, ETC. In the event that any capital stock or other
securities are issued in respect of, in exchange for, or in substitution of, any
Shares by reason of any reason of any reorganization, recapitalization,
reclassification, merger, consolidation, spin-off, partial or complete
liquidation, stock dividend, spit-up, sale of assets, distribution to
stockholders or combination of the Shares or any other change in capital
structure of the Company, appropriate adjustments shall be made with respect to
the relevant provisions of this Agreement so as to fairly and equitably
preserve, as far as practicable, the original rights and obligations of the
parties under this Agreement.

         (g) SEVERABILITY. The invalidity or unenforceability of any provisions
of this Agreement in any jurisdiction shall not affect the validity, legality or
enforceability of the remainder of this Agreement in such Jurisdiction or the
validity, legality or enforceability of this Agreement, including any such
provision, in any other jurisdiction, it being Intended that all

                                      -16-
<PAGE>   17

rights and obligations of the parties hereunder shall be enforceable to the
fullest extent permitted by law.

     (h) NO INCONSISTENT AGREEMENT; CONFLICTING CHARTER OR BYLAW PROVISION. The
Issuer will not hereafter enter into any agreement which is inconsistent with or
grant rights superior to the rights granted to the Investors in this Agreement.
Each Investor shall vote its Shares or execute written consents, as the case may
be, and take all other actions necessary, to ensure that the Certificate of
Incorporation, By-laws, and other constituent documents of the Company (i)
facilitate and do not at any time conflict with any provision of this Agreement
and (ii) permit each Investor to receive the benefits to which each such
Investor is entitled under this Agreement. No Investor shall (i) enter into any
agreement or arrangement of any kind with any Person with respect to its Shares
inconsistent with the provisions of this Agreement or for the purpose or with
the effect of denying or reducing the rights of any other Investor under this
Agreement or (ii) act as a member of a group or in concert with any other Person
in connection with the Transfer or voting of its Shares in any manner which is
inconsistent with the provisions of this Agreement.

     (i) COUNTERPARTS. This Agreement may be executed in one or more
counterparts, each of which shall be deemed an original and all of which
together shall be considered one and the same agreement.

     (j) INJUNCTIVE RELIEF. The Company and each of the Investors hereby declare
that it is impossible to measure in money the damages which wilt accrue to the
parties hereto by reason of the failure of the Company or of any of the
Investors to perform any of its obligations set forth in this Agreement.
Therefore, the Company and the Investors shall have the right to specific
performance of such obligations, and if any party hereto shall institute any
action or proceeding to enforce the provisions hereof, each of the Company and
the Investors hereby waives the claim or defense that the party instituting such
action or proceeding has an adequate remedy at law.

                                      -17-
<PAGE>   18

         IN WITNESS WHEREOF, the parties hereto have executed this Third Amended
and Restated Stockholders' Agreement as of the date first above written.

                                       THE MEDICINES COMPANY

                                       By: /s/ Peyton J. Marshall
                                          --------------------------------------
                                          Name: Peyton J. Marshall
                                          Title: Chief Financial Officer

                                       OLD INVESTORS:

                                       Holders of at least 75% of the
                                       Shares held by Old Investors

                                       By: /s/ Peyton J. Marshall
                                          --------------------------------------
                                          Under Power of Attorney
                                          of Holders attached hereto

                                       NEW INVESTORS:

                                       Counterpart signature pages attached
                                       hereto

                                      -18-
<PAGE>   19

                                   SCHEDULE I

Warburg, Pincus Ventures, L.P.
466 Lexington Avenue
New York, New York 10017

MPM Medicines L.P.
One Cambridge Center
Cambridge, Massachusetts 02142

Hanseatic Americas LDC
450 Park Avenue
Suite 2302

New York, New York 10022
PharmaBio Development Inc.
Post Office Box 13979
Research Triangle Park, North Carolina 27709-3979

Biotech Target
c/o Bellevue Asset Management AG
Grafenauweg 4 P. 0. Box CH-6301
Zug, Switzerland

Clive A. Meanwell
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Helmut Giersiefen
[The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 021421

John Villiger
The Medicines Company Limited
150 Long Drive, St. Heliers
Auckland, New Zealand

Thomas Lategan
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Wendy Gordon
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

<PAGE>   20

Peyton Marshall
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Frederick Oleson
5 Partridge Lane
Concord, Massachusetts 07142

John Maraganore
49 Constellation Wharf
Charlestown, Massachusetts 02129

H & D Investments 97
60 State Street
Boston, Massachusetts 02109
Attention: Paul Brountas, Esq.

<PAGE>   21

                                   SCHEDULE II

Name and Address of Purchaser
E. M. Warburg, Pincus Ventures, L. P.
466 Lexington Avenue
New York, NY 10017

Biotech Growth S.A.
Grafenauweg 4
CH-6301
Zug Switzerland

Hanseatic Americas LDC
450 Park Avenue, Suite 2302
New York, NY 10022

Clive Meanwell
The Medicines Company
One Cambridge Center
Cambridge, MA 02142

Peyton Marshall
The Medicines Company
One Cambridge Center
Cambridge, MA 02142

Jane J. Avinger
207 Avinger Lane
Davidson, NC 28036

H&D Investments 97
Hale and Dorr LLP
60 State Street.
Boston, MA 02109

David Ackert
100 Nyala Farm
Westport, CT 06880

Gary S. Roubin Revocable Trust utd
145 East 81st Street
Penthouse B
New York, NY 10028

Richard Davis
Tucker Anthony
One Beacon Street
Boston, MA 02108

<PAGE>   22

Charles Schwab and Co., Inc.
FBO: Robert L. Avinger, Jr.
UTA Charles Schwab - 1251-7331
101 South Tyron Street
Charlotte, NC 28280

Bayview Investors, Ltd.
555 California Street, Suite 2600
San Francisco, CA 94104

Morgan Stanley Venture Partners L.P.
1221 Avenue of the Americas, 33rd Fl.
New York, NY 10020

Alta Partners
One Embarcadero Center, Suite 4050
San Francisco, CA 94111

Moore Global Investments, Ltd.
1251 Avenue of the Americas, 53rd Fl.
New York, NY 10020

Remington Investment Strategies, L.P.
1251 Avenue of the Americas, 53rd Fl.
New York, NY 10020

Credit Suisse Asset Management
AMPE 3 Utlibergstrasse 231
Postfach 800
Zurich, CH-8070
Switzerland

BancAmerica Robertson Stephens
590 Madison Avenue
New York, NY 10022

<PAGE>   23

                             AMENDMENT NO. 2 TO THE
               THIRD AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT
               --------------------------------------------------

This Amendment No. 2 to the Third Amended and Restated Stockholders' Agreement
dated as of this 19 day of October, 1999 (the "Agreement"), among The Medicines
Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

WHEREAS, the Company and the individuals and entities who were signatories
thereto (the "Investors") are parties to the Third Amended and Restated
Stockholders' Agreement dated as of August 12, 1998, as amended to date (the
"Third Amended and Restated Stockholders' Agreement"); and

WHEREAS, the Company and certain of the Investors have entered into a Securities
Purchase Agreement of even date herewith with respect to the sale of the Notes
and the Warrants, each as defined therein (the "Securities Purchase Agreement");
and

WHEREAS, the Company and the Investors believe it to be in their mutual best
interests to amend the Third Amended and Restated Stockholders' Agreement to
exclude the Notes and the Warrants and the shares of capital stock issuable upon
conversion or exercise thereof from the Investors' subscription rights set forth
therein;

NOW, THEREFORE, in consideration of the mutual promises and covenants contained
in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 3(G). Section 3(g) of the Third Amended and Restated
Stockholders' Agreement is hereby amended by inserting immediately following
clause (E) of Section 3(g)(i) the following:

                  "(F) the Common Stock Purchase Warrants issuable under the
                  Securities Purchase Agreement dated October 19, 1999 among the
                  Company and the entities and individuals who are signatories
                  thereto (the "Purchase Agreement") and the shares of Common
                  Stock issuable upon exercise of such Warrants and (G) the 8%
                  Convertible Notes issuable under the Purchase Agreement and
                  the shares of capital stock issued or issuable upon the
                  conversion of such Notes,"

2. RATIFICATION. In all other respects, the Third Amended and Restated
Stockholders' Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 65% of the Common Stock, calculated on an as
converted basis, then covered by the Third Amended and Restated Stockholders'
Agreement.

<PAGE>   24

IN WITNESS WHEREOF, the parties hereto have executed this Amendment No. 2 to the
Third Amended and Restated Stockholders' Agreement as of the date first written
above.

                                            The Medicines Company

                                    By: /s/ Peyton J. Marshall
                                        ---------------------------------------
                                        Name: Peyton J. Marshall
                                        Title: Chief Financial Officer

                                            Holders of at least 65% of the
                                            Common Stock, calculated on an as
                                            converted basis, then covered by the
                                            Third Amended and Restated
                                            Stockholders' Agreement

                                            By: /s/ Peyton J. Marshall
                                                -------------------------------
                                                Under Power of Attorney
                                                of Holders attached hereto

                                      -2-

<PAGE>   25

                             AMENDMENT NO. 3 TO THE
               THIRD AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT
               --------------------------------------------------

         This Amendment No. 3 to the Third Amended and Restated Stockholders'
Agreement dated as of this 2nd day of March, 2000 (the "Amendment"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

         WHEREAS, the Company and the individuals and entities who were
signatories thereto (the "Investors") are parties to the Third Amended and
Restated Stockholders' Agreement dated as of August 12, 1998, as amended to date
(the "Third Amended and Restated Stockholders' Agreement"); and

         WHEREAS, the Company and certain of the Investors have entered into a
Securities Purchase Agreement of even date herewith with respect to the sale of
the Notes and the Warrants, each as defined therein (the "Securities Purchase
Agreement"); and

         WHEREAS, the Company and the Investors believe it to be in their mutual
best interests to amend the Third Amended and Restated Stockholders' Agreement
to exclude the Notes and the Warrants and the shares of capital stock issuable
upon conversion or exercise thereof from the Investors' subscription rights set
forth therein;

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Amendment, the parties hereto agree as follows:

         1. AMENDMENT TO SECTION 3(G). Section 3(g) of the Third Amended and
Restated Stockholders' Agreement is hereby amended by inserting immediately
following clause (F) of Section 3(g)(i) the following:

                  "(G) the Common Stock Purchase Warrants issuable under the
                  Securities Purchase Agreement dated March 2, 2000 among the
                  Company and the entities and individuals who are signatories
                  thereto (the "Purchase Agreement") and the shares of Common
                  Stock issuable upon exercise of such Warrants and (H) the 8%
                  Convertible Notes issuable under the Purchase Agreement and
                  the shares of capital stock issued or issuable upon the
                  conversion of such Notes,"

         2. RATIFICATION. In all other respects, the Third Amended and Restated
Stockholders' Agreement is hereby ratified and confirmed.

         3. COUNTERPARTS. This Amendment may be executed in one or more
counterparts, each of which shall be deemed an original and all of which
together shall be considered one and the same agreement.

<PAGE>   26

         4. EFFECTIVE DATE. This Amendment shall become effective upon approval
by the Company and the holders of at least 65% of the Common Stock, calculated
on an as converted basis, then covered by the Third Amended and Restated
Stockholders' Agreement.

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
3 to the Third Amended and Restated Stockholders' Agreement as of the date first
written above.

                                     The Medicines Company

                                     By: /s/ Peyton J. Marshall
                                        --------------------------------
                                        Name: Peyton J. Marshall
                                        Title: Chief Financial Officer

                                     Holders of at least 65% of the Common
                                     Stock, calculated on an as converted basis,
                                     then covered by the Third Amended and
                                     Restated Stockholders' Agreement

                                     By: /s/ Peyton J. Marshall
                                        ---------------------------------
                                         Under Power of Attorney
                                         of Holders attached hereto

                                      -2-

<PAGE>   27
                             AMENDMENT NO. 4 TO THE
               THIRD AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT
               --------------------------------------------------

         This Amendment No. 4 to the Third Amended and Restated Stockholders'
Agreement dated as of this 17 day of May, 2000 (the "Amendment"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

         WHEREAS, the Company and the individuals and entities who were
signatories thereto (the "Investors") are parties to the Third Amended and
Restated Stockholders' Agreement dated as of August 12, 1998, as amended to date
(the "Third Amended and Restated Stockholders' Agreement"); and

         WHEREAS, the Company and certain of the Investors have entered into a
Series IV Convertible Preferred Stock Purchase Agreement of even date herewith
with respect to the sale of the Preferred Shares, each as defined therein (the
"Purchase Agreement"); and

         WHEREAS, the Company and the Investors believe it to be in their mutual
best interests to amend the Third Amended and Restated Stockholders' Agreement
to exclude the Preferred Shares and the shares of capital stock issuable upon
conversion thereof from the Investors' subscription rights set forth therein;

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Amendment, the parties hereto agree as follows:

         1. AMENDMENT TO SECTION 3(G). Section 3(g) of the Third Amended and
Restated Stockholders' Agreement is hereby amended by inserting immediately
following clause (G) of Section 3(g)(i) the following:

                  "upon the conversion of outstanding shares of Series IV
                  Convertible Preferred Stock, $1.00 par value per share
                  ("Series IV Preferred Stock"),"

         2. AMENDMENT TO SECTION 7. Section 7 of the Third Amended and Restated
Stockholders' Agreement is hereby amended by deleting the definition of "Shares"
contained therein and inserting in lieu thereof the following:

                  "SHARES: all shares of Common Stock, Series I Preferred Stock,
                  Series II Preferred Stock, Series III Preferred Stock and
                  Series IV Preferred Stock currently owned (either beneficially
                  or of record) or subsequently acquired by any of the
                  Investors, including any shares which an Investor does not own
                  (either beneficially or of record) but as to which such
                  Investor exercises voting control, and including without
                  limitation, shares of Common Stock acquired upon conversion of
                  shares of Preferred Stock or Series IV Preferred Stock."

<PAGE>   28

         3. RATIFICATION. In all other respects, the Third Amended and Restated
Stockholders' Agreement is hereby ratified and confirmed.

         4. COUNTERPARTS. This Amendment may be executed in one or more
counterparts, each of which shall be deemed an original and all of which
together shall be considered one and the same agreement.

         5. EFFECTIVE DATE. This Amendment shall become effective upon approval
by the Company and the holders of at least 65% of the Common Stock, calculated
on an as converted basis, then covered by the Third Amended and Restated
Stockholders' Agreement.

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
4 to the Third Amended and Restated Stockholders' Agreement as of the date first
written above.

                                     The Medicines Company

                                     By: /s/ Peyton J. Marshall
                                        ---------------------------------
                                         Name: Peyton J. Marshall
                                         Title: Chief Financial Officer

                                     Holders of at least 65% of the Common
                                     Stock, calculated on an as converted basis,
                                     then covered by the Third Amended and
                                     Restated Stockholders' Agreement

                                     By: /s/ Peyton J. Marshall
                                        ---------------------------------
                                         Under Power of Attorney
                                         of Holders attached hereto

                                      -2-

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