Document:

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                                                                     Exhibit 4.6

                        MILLENNIUM PHARMACEUTICALS, INC.

                                       and

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

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

                          SECOND SUPPLEMENTAL INDENTURE

                          DATED AS OF FEBRUARY 12, 2002

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

                                  $300,000,000

             5.00% CONVERTIBLE SUBORDINATED NOTES DUE MARCH 1, 2007

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         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 February 24, 2000 (as
amended, the "Indenture"), between COR Therapeutics, Inc. (the "Company") and
the Trustee, the Company issued $300,000,000 aggregate principal amount of 5.00%
Convertible Subordinated Notes due March 1, 2007 (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.

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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, Articles III and IV 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 5.1 through 5.4,
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-

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                                  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-

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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<Page>

                                  PROTARGA(TM)

              INCORPORATED UNDER THE LAWS OF THE STATE OF DELAWARE

                              CERTIFICATE OF STOCK

                                                       CUSIP 74364D 10 6
                                             SEE REVERSE FOR CERTAIN DEFINITIONS

This
Certifies
that

is the owner of

 FULLY PAID AND NON-ASSESSABLE SHARES OF THE COMMON STOCK, PAR VALUE $.001, OF

                                 PROTARGA, Inc.

transferable on the books of the Corporation in person or by duly
authorized attorney upon surrender of this Certificate properly endorsed. This
Certificate and the shares represented hereby are issued under and shall be
subject to all of the provisions of the Certificate of Incorporation of the
Corporation and any amendments thereto, copies of which are on file with the
Corporation and the Transfer Agent, to all of which the holder by acceptance
hereof assents. This Certificate is not valid until countersigned by the
Transfer Agent and registered by the Registrar.

      WITNESS the facsimile seal of the Corporation and the facsimile signatures
of its duly authorized officers.

Dated:

                           [SEAL OF PROTRARGA, INC.]

/s/ ROBERT DICKEY IV                                     /s/ NIGEL L. WEBB

SENIOR VICE PRESIDENT, FINANCE                           CHAIRMAN, PRESIDENT AND
AND CHIEF FINANCIAL OFFICER                              CHIEF EXECUTIVE OFFICER

COUNTERSIGNED AND REGISTERED:
AMERICAN STOCK TRANSFER & TRUST COMPANY
(New York, N.Y.)                  TRANSFER AGENT
                                  AND REGISTRAR

BY

AUTHORIZED SIGNATURE

<Page>

                                 PROTARGA, INC.

      THE CORPORATION WILL FURNISH WITHOUT CHARGE TO EACH STOCKHOLDER WHO SO
REQUESTS, A STATEMENT OF THE DESIGNATIONS, PREFERENCES AND RELATIVE,
PARTICIPATING, OPTIONAL OR OTHER SPECIAL RIGHTS OF EACH CLASS OF STOCK OR SERIES
THEREOF WHICH THE CORPORATION IS AUTHORIZED TO ISSUE AND THE QUALIFICATIONS,
LIMITATIONS OR RESTRICTIONS OF SUCH PREFERENCES AND/OR RIGHTS.

      The following abbreviations, when used in the inscription on the face of
this certificate, shall be construed as though they were written out in full
according to applicable laws or regulations:

<Table>
<S>                                                       <C>
      TEN COM  -as tenants in common                      UNIF GIFT MIN ACT-____________Custodian___________
      TEN ENT  -as tenants by the entireties                                  (Cust)              (Minor)
      JT TEN   -as joint tenants with right of                              under Uniform Gifts to Minors
                survivorship and not as tenants                             Act_______________
                in common                                                          (State)
</Table>

     Additional abbreviations may also be used though not in the above list.

      For Value Received, ____________________________ hereby sell, assign and
transfer unto

PLEASE INSERT SOCIAL SECURITY OR OTHER
   IDENTIFYING NUMBER OF ASSIGNEE
 _____________________________________
|                                     |
|_____________________________________|

________________________________________________________________________________
      (PLEASE PRINT OR TYPEWRITE NAME AND ADDRESS, INCLUDING ZIP OR POSTAL
                               CODE, OF ASSIGNEE)

________________________________________________________________________________

________________________________________________________________________________

_________________________________________________________________________ Shares
of the Common Stock represented by the within certificate, and do hereby
irrevocably constitute and appoint

_______________________________________________________________________ Attorney
to transfer the said shares on the books of the within named Corporation with
full power of substitution in the premises.

Dated_________________________

                         _______________________________________________________
                         NOTICE: THE SIGNATURE TO THIS ASSIGNMENT MUST
                         CORRESPOND WITH THE NAME AS WRITTEN UPON THE FACE OF
                         THE CERTIFICATE IN EVERY PARTICULAR, WITHOUT ALTERATION
                         OR ENLARGEMENT OR ANY CHANGE WHATEVER.

Signature(s) Guaranteed:

____________________________________________________
THE SIGNATURE(S) MUST BE GUARANTEED BY AN ELIGIBLE
GUARANTOR INSTITUTION (BANKS, STOCKBROKERS, SAVINGS
AND LOAN ASSOCIATIONS AND CREDIT UNIONS WITH
MEMBERSHIP IN AN APPROVED SIGNATURE GUARANTEE
MEDALLION PROGRAM), PURSUANT TO S.E.C. RULE 17Ad-15.

KEEP THIS CERTIFICATE IN A SAFE PLACE. IF IT IS LOST, STOLEN, MUTILATED OR
DESTROYED, THE CORPORATION WILL REQUIRE A BOND OF INDEMNITY AS A CONDITION TO
THE ISSUANCE OF A REPLACEMENT CERTIFICATE.

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