Document:

<PAGE>

                                                                     EXHIBIT 4.2

                             COR THERAPEUTICS, INC.,

                        MILLENNIUM PHARMACEUTICALS, INC.

                                       and

                                U.S. BANK, N.A.,
                                   as Trustee

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

                          FIRST SUPPLEMENTAL INDENTURE

                          DATED AS OF FEBRUARY 12, 2002

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

                                  $300,000,000

                4.50% CONVERTIBLE SENIOR NOTES DUE JUNE 15, 2006

<PAGE>

         FIRST SUPPLEMENTAL INDENTURE, dated as of February 12, 2002, between
COR Therapeutics, Inc., a corporation duly organized and existing under the laws
of the State of Delaware (herein called the "Company"), Millennium
Pharmaceuticals, Inc., a corporation duly organized and existing under the laws
of the State of Delaware (herein called "Parent"), and U.S. Bank, N.A. (formerly
known as Firstar Bank, N.A.), a national banking association, as Trustee (herein
called the "Trustee").

         WHEREAS, pursuant to the Indenture dated as of June 11, 2001 (the
"Indenture"), between the Company and the Trustee, the Company issued
$300,000,000 aggregate principal amount of 4.50% Convertible Senior Notes due
June 15, 2006 (the "Securities");

         WHEREAS, pursuant to the Agreement and Plan of Merger dated as of
December 5, 2001 (the "Merger Agreement") among Parent, PGM Corporation, a
Delaware corporation and wholly owned subsidiary of Parent ("Sub"), and the
Company, Sub has agreed to merge with and into the Company (the "Merger"), with
the Company being the surviving corporation in the Merger, following which the
Company will be a wholly owned subsidiary of Parent;

         WHEREAS, pursuant to the Merger Agreement, as of the effective time of
the Merger (the "Effective Time"), each outstanding share of common stock of the
Company ("Company Common Stock"), other than shares held by the Company, Parent
or Sub, shall be converted into the right to receive 0.9873 validly issued,
fully paid and nonassessable shares of common stock of Parent ("Parent Common
Stock");

         WHEREAS, pursuant to Section 11.11 of the Indenture, as a result of the
Merger, the Company is required to execute and deliver to the Trustee a
supplemental indenture providing (i) that the Securities shall be convertible
into shares of Parent Common Stock and (ii) for adjustments of the Conversion
Rate which shall be as nearly equivalent as may be practicable to the
adjustments provided for in Article 11 of the Indenture;

         WHEREAS, pursuant to the Merger Agreement, Parent agreed to fully and
unconditionally guarantee the obligations of the Company under the Indenture and
the Securities on the terms and conditions set forth herein;

         WHEREAS, Section 8.1 of the Indenture provides that the Company and the
Trustee may amend or supplement the Indenture or the Securities without notice
to or consent of any Holder of Securities to, among other things, (i) comply
with Section 11.11 of the Indenture and (ii) make any other provisions with
respect to matters or questions arising under the Indenture as the Company and
the Trustee may deem necessary or desirable, provided such action shall not, in
the judgment of the Company, adversely affect the interests of any Holder of
Securities in any material respect; and

         WHEREAS, the Company and Parent have complied with all conditions
precedent provided for in the Indenture relating to this First Supplemental
Indenture.

<PAGE>

         NOW, THEREFORE, in consideration of the foregoing premises, it is
mutually covenanted and agreed, for the equal and proportionate benefit of all
Holders of Securities, as follows:

                                  ARTICLE ONE

                                  DEFINITIONS

SECTION 1.1. Capitalized terms used but not defined herein shall have the
meanings ascribed to such terms in the Indenture.

SECTION 1.2. Section 1.1 of the Indenture is hereby amended to add the following
definitions:

         "Effective Time" means the time at which the merger of PGM Corporation,
a Delaware corporation and wholly owned subsidiary of Parent, with and into the
Company, with the Company as the surviving corporation, becomes effective.

         "Parent" means Millennium Pharmaceuticals, Inc., a corporation duly
organized and existing under the laws of the State of Delaware.

                                  ARTICLE TWO

                   CONVERSION RIGHTS OF HOLDERS OF SECURITIES
                          IN CONNECTION WITH THE MERGER

SECTION 2.1. Conversion Rights. The Company and Parent hereby agree in
accordance with Section 11.11 of the Indenture that the holder of each Security
outstanding at the Effective Time shall have the right to convert such Security
into the number of shares of Parent Common Stock equal to 0.9873 multiplied by
the number of shares of Company Common Stock deliverable upon conversion of such
Security immediately prior to the Merger. Parent hereby agrees in accordance
with Section 11.11 of the Indenture to make any subsequent adjustments of the
Conversion Rate which shall be as nearly equivalent as may be practicable to the
adjustments provided for in Article 11 of the Indenture.

                                  ARTICLE THREE

                                    GUARANTEE

SECTION 3.1. Guarantee. Parent hereby fully and unconditionally guarantees, as a
primary obligor and not merely as a surety, to each Holder of Securities and to
the Trustee and its successors and assigns (a) the full and punctual payment of
the principal of (and premium, if any) and interest on, and any payment of the
Repurchase Price with respect to, the Securities, and all other monetary
obligations of the Company under the Indenture (including obligations to the
Trustee) and (b) the full and punctual performance within applicable grace
periods of all other obligations of the Company under the Indenture and the
Securities (all the foregoing being hereinafter collectively called the
"Obligations"). Parent further agrees that the Obligations may be extended or
renewed, in whole or in part, without notice or further assent from it, and that
it

                                       2
<PAGE>

will remain bound under this Article III notwithstanding any extension or
renewal of any Obligation.

         Parent waives presentation to, demand of payment from and protest to
the Company of any of the Obligations and also waives notice of protest for
nonpayment. Parent waives notice of any default under the Securities or the
Obligations. The obligations of Parent under this Section 3.1 shall not be
affected by (a) the failure of any Holder of Securities or the Trustee to assert
any claim or demand or to enforce any right or remedy against the Company or any
other Person under the Indenture, the Securities or any other agreement or
otherwise; (b) any extension or renewal of any Obligation; (c) any rescission,
waiver, amendment, modification or supplement of any of the terms or provisions
of the Indenture, the Securities or any other agreement; (d) the release of any
security held by any Holder of Securities or the Trustee for the obligations or
any of them; (e) the failure of any Holder of Securities or the Trustee to
exercise any right or remedy against any other guarantor of the Obligations; or
(f) any change in the ownership of the Company.

         Parent further agrees that its guarantee under this Section 3.1
constitutes a guarantee of payment, performance and compliance when due (and not
a guarantee of collection) and waives any right to require that any resort be
had by any Holder of Securities or the Trustee to any security held for payment
of the Obligations.

         Except as set forth in Section 3.2 of this First Supplemental
Indenture, the obligations of Parent under this Section 3.1 shall not be subject
to any reduction, limitation, impairment or termination for any reason,
including any claim of waiver, release, surrender, alteration or compromise, and
shall not be subject to any defense, setoff, counterclaim, recoupment or
termination whatsoever or by reason of the invalidity, illegality or
unenforceability of the Obligations or otherwise. Without limiting the
generality of the foregoing, the obligations of Parent under this Section 3.1
shall not be discharged or impaired or otherwise affected by any default,
failure or delay, willful or otherwise, in the performance of the Obligations,
or by any other act or thing or omission or delay to do any other act or thing
which may or might in any manner or to any extent vary the risk of Parent or
would otherwise operate as a discharge of Parent as a matter of law or equity.

         Parent agrees that its guarantee under this Section 3.1 shall remain in
full force and effect until payment in full of all the Obligations. Parent
further agrees that its guarantee under this Section 3.1 shall continue to be
effective or be reinstated, as the case may be, if at any time payment, or any
part thereof, of any Obligation is rescinded or must otherwise be restored by
any Holder of Securities or the Trustee upon the bankruptcy or reorganization of
the Company or otherwise.

         In furtherance of the foregoing and not in limitation of any other
right which any Holder of Securities or the Trustee may have at law or in equity
against Parent by virtue hereof, upon the failure of the Company to pay any
Obligation when and as the same shall become due, whether at maturity, by
acceleration, by redemption or otherwise, or to perform or comply with any other
Obligation, Parent hereby promises to and shall, upon receipt of written demand
by the Trustee, forthwith pay, or cause to be paid, in cash, to the Holders of
Securities or the Trustee an amount equal to the sum of (i) the unpaid principal
amount of such Obligations, (ii) accrued and unpaid

                                       3
<PAGE>

interest on such Obligations (but only to the extent not prohibited by law) and
(iii) all other monetary Obligations of the Company to the Holders of Securities
and the Trustee.

         Parent agrees that it shall not be entitled to any right of subrogation
in relation to the Holders of Securities in respect of any Obligations
guaranteed hereby until payment in full of all Obligations. Parent further
agrees that, as between it, on the one hand, and the Holders of Securities and
the Trustee, on the other hand, (x) the maturity of the Obligations guaranteed
hereby may be accelerated as provided in Section 5.2 of the Indenture for the
purposes of the guarantee under this Section 3.1, notwithstanding any stay,
injunction or other prohibition preventing such acceleration in respect of the
Obligations guaranteed hereby, and (y) in the event of any declaration of
acceleration of such Obligations as provided in Section 5.2 of the Indenture,
such Obligations (whether or not due and payable) shall forthwith become due and
payable by Parent for the purposes of this Section 3.1.

SECTION 3.2. Limitation on Liability. Any term or provision of the Indenture to
the contrary notwithstanding, the maximum aggregate amount of the Obligations
guaranteed under Section 3.1 of this First Supplemental Indenture by Parent
shall not exceed the maximum amount that can be hereby guaranteed without
constituting a fraudulent conveyance or fraudulent transfer under applicable
insolvency laws or similar laws affecting the rights of creditors generally.

SECTION 3.3. Successors and Assigns. This Article III shall be binding on Parent
and its successors and assigns and shall inure to the benefit of the successors
and assigns of the Trustee and the Holders of Securities and, in the event of
any transfer or assignment of rights by any Holder of Securities or the Trustee,
the rights and privileges conferred upon that party in the Indenture and in the
Securities shall automatically extend to and be vested in such transferee or
assignee, all subject to the terms and conditions of the Indenture.

SECTION 3.4. Termination of Guarantee. Article III of this First Supplemental
Indenture, and all of Parent's rights and obligations set forth herein, shall
terminate and no longer be effective upon the consummation of a merger between
the Company and Parent, in which merger Parent is the surviving corporation and,
in connection therewith, assumes all of the rights and obligations of the
Company under the Indenture.

                                  ARTICLE FOUR

                            MISCELLANEOUS AMENDMENTS

SECTION 4.1. Section 8.1 of the Indenture is hereby amended so that the
beginning of the first paragraph thereof reads "Without the consent of any
Holders of Securities, the Company, when authorized by a Board Resolution,
Parent and the Trustee, at any time and from time to time, may enter into one or
more indentures supplemental hereto for any of the foregoing purposes:".

SECTION 4.2. Section 8.2 of the Indenture is hereby amended by inserting a
reference to "Parent" after the first reference to "the Company, when authorized
by a Board Resolution,".

SECTION 4.3. Section 8.6 of the Indenture is hereby amended by inserting a
reference to ", Parent" after the first reference to "the Company".

                                       4
<PAGE>

SECTION 4.4. All references to "the Company" in Section 9.7 of the Indenture are
hereby deleted and replaced with references to "Parent".

                                  ARTICLE FIVE

                   ACCEPTANCE OF FIRST SUPPLEMENTAL INDENTURE

SECTION 5.1. Trustee's Acceptance. The Trustee hereby accepts this First
Supplemental Indenture and agrees to perform the same under the terms and
conditions set forth in the Indenture.

                                  ARTICLE SIX

                            MISCELLANEOUS PROVISIONS

SECTION 6.1. Effectiveness of First Supplemental Indenture. This First
Supplemental Indenture shall be effective as of the Effective Time.

SECTION 6.2. Effect of First Supplemental Indenture. Upon the execution and
delivery of this First Supplemental Indenture by the Company, Parent and the
Trustee, the Indenture shall be supplemented and amended in accordance herewith,
and this First Supplemental Indenture shall form a part of the Indenture for all
purposes, and every Holder of Securities heretofore or hereafter authenticated
and delivered under the Indenture shall be bound thereby.

SECTION 6.3. Indenture Remains in Full Force and Effect. Except as supplemented
or amended hereby, all provisions in the Indenture shall remain in full force
and effect.

SECTION 6.4. Incorporation of Indenture. All the provisions of this First
Supplemental Indenture shall be deemed to be incorporated in, and made a part
of, the Indenture; and the Indenture, as supplemented and amended by this First
Supplemental Indenture, shall be read, taken and construed as one and the same
instrument.

SECTION 6.5. Address of Parent for Notices. Any notice or demand which by any
provisions of the Indenture is required or permitted to be given or served by
the Trustee or by the Holders of Securities on Parent shall be sufficient for
every purpose hereunder if in writing, mailed, first-class postage prepaid, or
telecopied and confirmed by mail, first-class postage prepaid, or delivered by
hand or overnight courier addressed to Parent at 75 Sidney Street, Cambridge,
Massachusetts 02139, Attention: Chief Financial Officer, or at any other address
previously furnished in writing to the Trustee by Parent, and shall be deemed
given when received.

SECTION 6.6. Headings. The headings of the Articles and Sections of this First
Supplemental Indenture are inserted for convenience of reference and shall not
be deemed to be a part thereof.

SECTION 6.7. Counterparts. This First Supplemental Indenture may be executed in
any number of counterparts, each of which so executed shall be deemed to be an
original, but all such counterparts shall together constitute but one and the
same instrument.

SECTION 6.8. Conflict with Trust Indenture Act. If any provision of this First
Supplemental

                                       5
<PAGE>

Indenture limits, qualifies or conflicts with a provision of the Trust Indenture
Act that is required under such Act to be a part of and govern this First
Supplemental Indenture, the latter provision shall control. If any provision of
this First Supplemental Indenture modifies or excludes any provision of the
Trust Indenture Act that may be so modified or excluded, the latter provision
shall be deemed to apply to this First Supplemental Indenture as so modified or
to be excluded, as the case may be.

SECTION 6.9. Successors. All covenants and agreements in this First Supplemental
Indenture by the Company and Parent shall be binding upon and accrue to the
benefit of their respective successors. All covenants and agreements in this
First Supplemental Indenture by the Trustee shall be binding upon and accrue to
the benefit of its successors.

SECTION 6.10. Separability Clause. In case any provision in this First
Supplemental Indenture shall be invalid, illegal or unenforceable, the validity,
legality and enforceability of the remaining provisions shall not in any way be
affected or impaired thereby.

SECTION 6.11. Benefits of First Supplemental Indenture. Nothing in this First
Supplemental Indenture, the Indenture or the Securities, express or implied,
shall give to any Person, other than the parties hereto and thereto and their
successors hereunder and thereunder and the Holders of Securities, any benefit
of any legal or equitable right, remedy or claim under this First Supplemental
Indenture, the Indenture or the Securities.

SECTION 6.12. Trustee Not Responsible for Recitals. The recitals herein
contained are made by the Company and Parent, and not by the Trustee and the
Trustee assumes no responsibility for the correctness thereof. The Trustee makes
no representations as to the validity or sufficiency of this First Supplemental
Indenture.

SECTION 6.13. Certain Duties and Responsibilities of the Trustee. In entering
into this First Supplemental Indenture, the Trustee shall be entitled to the
benefit of every provision of the Indenture relating to the conduct or affecting
the liability or affording protection to the Trustee, whether or not elsewhere
herein so provided, and the Trustee shall not be under any responsibility to
determine the correctness of any provisions contained in this First Supplemental
Indenture relating either to the kind or amount of shares of stock or securities
or property (including cash) receivable by Holders of Securities upon the
conversion of their Securities or to any adjustment to be made with respect
thereto.

SECTION 6.14. GOVERNING LAW. THIS FIRST SUPPLEMENTAL INDENTURE SHALL BE GOVERNED
BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK, THE
UNITED STATES OF AMERICA, WITHOUT REGARD TO THE CONFLICTS OF LAWS PRINCIPLES
THEREOF.

                                       6
<PAGE>

         IN WITNESS WHEREOF, the parties hereto have caused this First
Supplemental Indenture to be duly executed, all as of the day and year first
above written.

                                            COR THERAPEUTICS, INC.

                                            By: /s/ John B. Douglas III
                                                --------------------------------
                                            Name: John B. Douglas III
                                            Title:  President

                                            MILLENNIUM PHARMACEUTICALS, INC.

                                            By: /s/ Kevin P. Starr
                                                --------------------------------
                                            Name: Kevin P. Starr
                                            Title: Chief Operating Officer and
                                                   Chief Financial Officer

                                            U.S. BANK, N.A., Trustee

                                            By: /s/ Frank P. Leslie, III
                                                --------------------------------
                                            Name: Frank P. Leslie, III
                                            Title: Vice President<PAGE>

                                                                     EXHIBIT 4.3

                        MILLENNIUM PHARMACEUTICALS, INC.

                                       and

                                U.S. BANK, N.A.,
                                   as Trustee

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

                          SECOND SUPPLEMENTAL INDENTURE

                          DATED AS OF FEBRUARY 12, 2002

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

                                  $300,000,000

                4.50% CONVERTIBLE SENIOR NOTES DUE JUNE 15, 2006

<PAGE>

         SECOND SUPPLEMENTAL INDENTURE, dated as of February 12, 2002, between
Millennium Pharmaceuticals, Inc., a corporation duly organized and existing
under the laws of the State of Delaware (herein called "Parent"), and U.S. Bank,
N.A. (formerly known as Firstar Bank, N.A.), a national banking association, as
Trustee (herein called the "Trustee").

         WHEREAS, pursuant to the Indenture dated as of June 11, 2001 (as
amended, the "Indenture"), between COR Therapeutics, Inc. (the "Company") and
the Trustee, the Company issued $300,000,000 aggregate principal amount of 4.50%
Convertible Senior Notes due June 15, 2006 (the "Securities");

         WHEREAS, the Company, Parent and the Trustee have entered into a First
Supplemental Indenture, dated as of February 12, 2002 (the "First Supplemental
Indenture"), to the Indenture, which supplemental indenture provides (i) that
the Securities shall be convertible into shares of Parent Common Stock, (ii) for
adjustments of the Conversion Rate which shall be as nearly equivalent as may be
practicable to the adjustments provided for in Article 11 of the Indenture, and
(iii) for a full and unconditional guarantee of the obligations of the Company
under the Indenture and the Securities by Parent on the terms and conditions set
forth therein;

         WHEREAS, pursuant to the Reorganization Agreement dated as of February
12, 2002 (the "Reorganization Agreement") among Parent and the Company, the
Company has agreed to merge with and into Parent (the "Upstream Merger"), with
Parent being the surviving corporation in the Upstream Merger;

         WHEREAS, Section 7.1 of the Indenture requires that, in connection with
the Upstream Merger, Parent execute a supplemental indenture providing that
Parent shall expressly assume all of the obligations of the Company under the
Indenture and the Securities;

         WHEREAS, Section 8.1 of the Indenture provides that the Company, Parent
and the Trustee may amend or supplement the Indenture or the Securities without
notice to or consent of any Holder of Securities to, among other things,
evidence the succession of another Person to the Company and the assumption by
any such successor of the covenants and obligations of the Company herein and in
the Securities; and

         WHEREAS, Parent has complied with all conditions precedent provided for
in the Indenture relating to this Second Supplemental Indenture.

         NOW, THEREFORE, in consideration of the foregoing premises, it is
mutually covenanted and agreed, for the equal and proportionate benefit of all
Holders of Securities, as follows:

                                  ARTICLE ONE

                                  DEFINITIONS

SECTION 1.1. Capitalized terms used but not defined herein shall have the
meanings ascribed to such terms in the Indenture.

<PAGE>

SECTION 1.2. Section 1.1 of the Indenture is hereby amended to add the following
definition:

         "Upstream Merger Effective Time" means the time at which the merger of
the Company with and into Parent, with Parent as the surviving corporation,
becomes effective.

                                  ARTICLE TWO

                                   ASSUMPTION

SECTION 2.1. Assumption. Parent hereby expressly assumes the due and punctual
payment of the principal of, premium, if any, and interest (including Liquidated
Damages, if any, payable pursuant to Section 9.11 of the Indenture) on all of
the Securities as applicable, and the performance or observance of every
covenant of the Indenture on the part of the Company to be performed or
observed.

SECTION 2.2. Substitution of Parent. Pursuant to Section 7.2 of the Indenture,
Parent shall succeed to, and be substituted for, and may exercise every right
and power of, the Company under the Indenture with the same effect as if Parent
had been named as the Company therein.

                                 ARTICLE THREE

                            TERMINATION OF GUARANTEE

SECTION 3.1. Termination of Guarantee. Pursuant to Section 3.4 of the First
Supplemental Indenture, Article III of the First Supplemental Indenture, and all
of Parent's rights and obligations set forth therein, shall terminate and no
longer be effective upon the Upstream Merger Effective Time.

                                  ARTICLE FOUR

                      DELETION OF MISCELLANEOUS AMENDMENTS

SECTION 4.1. Deletion of Miscellaneous Amendments. Sections 4.1 through 4.4,
inclusive, of the First Supplemental Indenture are hereby deleted in their
entirety.

                                  ARTICLE FIVE

                   ACCEPTANCE OF SECOND SUPPLEMENTAL INDENTURE

SECTION 5.1. Trustee's Acceptance. The Trustee hereby accepts this Second
Supplemental Indenture and agrees to perform the same under the terms and
conditions set forth in the Indenture.

                                       2
<PAGE>

                                  ARTICLE SIX

                            MISCELLANEOUS PROVISIONS

SECTION 6.1. Effectiveness of Second Supplemental Indenture. This Second
Supplemental Indenture shall be effective as of the Upstream Merger Effective
Time.

SECTION 6.2. Effect of Second Supplemental Indenture. Upon the execution and
delivery of this Second Supplemental Indenture by Parent and the Trustee, the
Indenture, as amended by the First Supplemental Indenture, shall be supplemented
and amended in accordance herewith, and this Second Supplemental Indenture shall
form a part of the Indenture for all purposes, and every Holder of Securities
heretofore or hereafter authenticated and delivered under the Indenture shall be
bound thereby.

SECTION 6.3. Indenture Remains in Full Force and Effect. Except as supplemented
or amended hereby, all provisions in the Indenture shall remain in full force
and effect.

SECTION 6.4. Incorporation of Indenture. All the provisions of this Second
Supplemental Indenture shall be deemed to be incorporated in, and made a part
of, the Indenture; and the Indenture, as supplemented and amended by the First
Supplemental Indenture and this Second Supplemental Indenture, shall be read,
taken and construed as one and the same instrument.

SECTION 6.5. Headings. The headings of the Articles and Sections of this Second
Supplemental Indenture are inserted for convenience of reference and shall not
be deemed to be a part thereof.

SECTION 6.6. Counterparts. This Second Supplemental Indenture may be executed in
any number of counterparts, each of which so executed shall be deemed to be an
original, but all such counterparts shall together constitute but one and the
same instrument.

SECTION 6.7. Conflict with Trust Indenture Act. If any provision of this Second
Supplemental Indenture limits, qualifies or conflicts with a provision of the
Trust Indenture Act that is required under such Act to be a part of and govern
this Second Supplemental Indenture, the latter provision shall control. If any
provision of this Second Supplemental Indenture modifies or excludes any
provision of the Trust Indenture Act that may be so modified or excluded, the
latter provision shall be deemed to apply to this Second Supplemental Indenture
as so modified or to be excluded, as the case may be.

SECTION 6.8. Successors. All covenants and agreements in this Second
Supplemental Indenture by Parent shall be binding upon and accrue to the benefit
of its successors. All covenants and agreements in this Second Supplemental
Indenture by the Trustee shall be binding upon and accrue to the benefit of its
successors.

SECTION 6.9. Separability Clause. In case any provision in this Second
Supplemental Indenture shall be invalid, illegal or unenforceable, the validity,
legality and enforceability of the remaining provisions shall not in any way be
affected or impaired thereby.

                                       3
<PAGE>

SECTION 6.10. Benefits of Second Supplemental Indenture. Nothing in this Second
Supplemental Indenture, the First Supplemental Indenture, the Indenture or the
Securities, express or implied, shall give to any Person, other than the parties
hereto and thereto and their successors hereunder and thereunder and the Holders
of Securities, any benefit of any legal or equitable right, remedy or claim
under this Second Supplemental Indenture, the First Supplemental Indenture, the
Indenture or the Securities.

SECTION 6.11. Trustee Not Responsible for Recitals. The recitals herein
contained are made by Parent, and not by the Trustee and the Trustee assumes no
responsibility for the correctness thereof. The Trustee makes no representations
as to the validity or sufficiency of this Second Supplemental Indenture.

SECTION 6.12. Certain Duties and Responsibilities of the Trustee. In entering
into this Second Supplemental Indenture, the Trustee shall be entitled to the
benefit of every provision of the Indenture relating to the conduct or affecting
the liability or affording protection to the Trustee, whether or not elsewhere
herein so provided, and the Trustee shall not be under any responsibility to
determine the correctness of any provisions contained in this Second
Supplemental Indenture relating either to the kind or amount of shares of stock
or securities or property (including cash) receivable by Holders of Securities
upon the conversion of their Securities or to any adjustment to be made with
respect thereto.

SECTION 6.13. GOVERNING LAW. THIS SECOND SUPPLEMENTAL INDENTURE SHALL BE
GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK,
THE UNITED STATES OF AMERICA, WITHOUT REGARD TO THE CONFLICTS OF LAWS PRINCIPLES
THEREOF.

                                       4
<PAGE>

         IN WITNESS WHEREOF, the parties hereto have caused this Second
Supplemental Indenture to be duly executed, all as of the day and year first
above written.

                                      MILLENNIUM PHARMACEUTICALS, INC.

                                      By: /s/ Kevin P. Starr
                                          --------------------------------------
                                      Name: Kevin P. Starr
                                      Title: Chief Operating Officer and
                                             Chief Financial Officer

                                      U.S. BANK, N.A., Trustee

                                      By: /s/ Frank P. Leslie, III
                                          --------------------------------------
                                      Name: Frank P. Leslie, III
                                      Title: Vice President

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