EXHIBIT N0. 10.1



                                                                 Execution Copy


          Confidential Materials omitted and filed separately with the
         Securities and Exchange Commission. Asterisks denote omissions.

             SECOND AMENDMENT TO COLLABORATION AND LICENSE AGREEMENT

         This Second Amendment to Collaboration and License Agreement (this
"Second Amendment") effective as of December 6, 2002 is by and between
Millennium Pharmaceuticals, Inc., a corporation organized and existing under the
laws of the State of Delaware and having its principal office at 75 Sidney
Street, Cambridge, Massachusetts 02139 ("Millennium") and Aventis
Pharmaceuticals Inc., a corporation organized and existing under the laws of the
State of Delaware and having its principal office at Route 202-206, P.O. Box
6800, Bridgewater, New Jersey 08807 ("Aventis").

                                  INTRODUCTION

         WHEREAS, Millennium and Aventis entered into a Collaboration and
License Agreement dated as of June 22, 2000 (as previously amended, the
"Collaboration Agreement");

         WHEREAS, Millennium and Aventis desire to amend certain provisions of
the Collaboration Agreement to implement their mutual determination to allocate
a greater proportion of their Research Program resources to the Pre-EDC Research
Evaluation of Program Compounds, as contemplated by Section 2.1.1(b) of the
Collaboration Agreement;

         WHEREAS, Millennium and Aventis have determined that no new
Scientifically-Qualified Targets will be entered into the Research Program after
December 6, 2002;

         WHEREAS, Millennium and Aventis have determined that, as of December 6,
2002, certain Scientifically-Qualified Targets that have not been designated
Program Targets, and certain Program Targets, will continue to be pursued under
the Research Program, and no other targets will be pursued under the Research
Program after December 6, 2002;

         WHEREAS, Millennium and Aventis have determined that for those
Scientifically-Qualified Targets that have not been designated Program Targets,
and those Program Targets, that will continue to be pursued under the Research
Program after December 6, 2002, any such target will later be removed from the
Research Program if, on a target-by-target basis, the scientific milestones set
forth in EXHIBIT A to this Second Amendment are not achieved by the applicable
dates set forth on EXHIBIT A to this Second Amendment; and

         WHEREAS, at such time as any target is no longer being pursued in, or
is removed from, the Research Program, that target will thereafter become
available for exploitation outside of the Research Program in accordance with
Section 2.7.5 of the Collaboration Agreement (as amended below).

         NOW, THEREFORE, Millennium and Aventis hereby agree as follows:

<PAGE>
                                                                 Execution Copy

         1.     Article 1 of the Collaboration Agreement is hereby amended to
 add the following additional defined terms:

         "DESIGNATED TARGET". Designated Target means any
         Scientifically-Qualified Target that has not been designated a Program
         Target, or any Program Target, that, as of December 6, 2002, the
         Parties have agreed to continue to pursue under the Research Program. A
         complete list of the Designated Targets is attached as EXHIBIT B to the
         Second Amendment to this Agreement.

         "EDC TARGET". EDC Target means a Program Target that is modulated by an
         EDC Compound. The Program Targets that have reached EDC Target status
         as of the date of signature of the Second Amendment to this Agreement
         are listed on EXHIBIT E to the Second Amendment to this Agreement.

         "[**]". [**] means [**] that have the effect of increasing the costs
         and expenses associated with the activities contemplated by this
         Agreement with respect to Program Technology or Program Materials
         (including Scientifically-Qualified Targets and Program Targets) by
         [**] Dollars ($[**]) or less, but that do not (x) have the effect of
         [**] on such activities, or (y) have any of the results set forth in
         clause (1), (2) or (4) of Section 2.5.1 with respect to such Program
         Technology or Program Materials or the Development or Commercialization
         of products resulting from the use of such Program Technology or
         Program Materials.

         "EXEMPT TARGET". Exempt Target means any (a) [**] Exempt Target, (b)
         Non-Designated Exempt Target, (c) [**] Exempt Target, (d) [**] Exempt
         Target, (e) [**] Exempt Target, or (f) [**] Exempt Target.

         "EXTENDED DEVELOPMENT SCHEDULE DESIGNATED TARGET". Extended Development
         Schedule Designated Target shall have the meaning ascribed to it in
         Section 2.7.1(f).

         "NON-DESIGNATED EXEMPT TARGET". Non-Designated Exempt Target means any
         Scientifically-Qualified Target that has not been designated a Program
         Target, or any Program Target, that, as of December 6, 2002, the
         Parties have agreed not to continue to pursue under the Research
         Program. A complete list of the Non-Designated Exempt Targets is
         attached as EXHIBIT C to the Second Amendment to this Agreement.

         "[**] EXEMPT TARGET". [**] Exempt Target means any Designated Target
         (a) that is not a [**] Exempt Target or a [**] Exempt Target, and (b)
         with respect to which, as of [**], [**] with respect to a designated
         Lead Compound that modulates such Designated Target.

         "[**] EXEMPT TARGET". [**] Exempt Target means any Designated Target
         (a) that is not a [**] Exempt Target, a [**] Exempt Target or a [**]
         Exempt Target, and (b) with respect to which, as of the expiration of
         the Research Program Term, [**] such Designated Target has been
         designated.

                                       2

<PAGE>
                                                                 Execution Copy

         "[**] EXEMPT TARGET". [**] Exempt Target means any Designated Target
         (a) that is not a [**] Exempt Target, and (b) with respect to which, as
         of [**] pursuant to a [**] (as defined in the [**]) have not been
         initiated.

         "[**] EXEMPT TARGET". [**] Exempt Target means any Designated Target
         that, as of [**], (a) has not been used for [**], and (b) has not been
         designated an Extended Development Schedule Designated Target.

         "[**] EXEMPT TARGET". [**] Exempt Target means any target that has not
         been designated a [**] Target as of December 6, 2002.

         "SECOND AMENDMENT TO THIS AGREEMENT". The Second Amendment to this
         Agreement means the Second Amendment to Collaboration and License
         Agreement effective as of December 6, 2002 between Millennium and
         Aventis.

         2.     Section 2.4.2 of the Collaboration Agreement is hereby deleted
in its entirety and the following is hereby inserted in its place:

                2.4.2  Each Party shall devote to Research Program activities,
                       as a minimum, the number of FTEs for that Party as set
                       forth in the then applicable Annual Research Plan. Each
                       Party shall expend, over the course of the Research
                       Program, substantially similar amounts in significant
                       out-of-pocket expenditures directly related to the
                       Research Program. All significant out-of-pocket
                       expenditures shall either be expressly provided for in
                       the Annual Research Plan or approved by the Joint
                       Research Committee.

         3. The Collaboration Agreement is hereby amended by inserting the
following new Section 2.5.7 immediately after Section 2.5.6 thereof:

                2.5.7  Notwithstanding anything to the contrary in Section
                       2.5.2, 2.5.3, 2.5.4, 2.5.5 or 2.5.6, either Party may
                       (a) include in the Research Program, without first
                       informing the Joint Research Committee but with the other
                       Party's prior written consent, Program Technology or
                       Program Materials (including Scientifically-Qualified
                       Targets and Program Targets to which only [**] relate,
                       and (b) without first informing the Joint Research
                       Committee but with the other Party's prior written
                       consent, incur [**] relating to Program Technology or
                       Program Materials previously included in the Research
                       Program. The Parties agree that consent by email or other
                       electronic communication is sufficient to constitute the
                       consent under this Section 2.5.7.

         4. Section 2.7.1 of the Collaboration Agreement is hereby amended by
inserting the following new clauses (e), (f), and (g) immediately following
clause (d) thereto:

                (e)    Notwithstanding anything to the contrary in this Section
                       2.7.1 or elsewhere in this Agreement, (i) no
                           new [**] Targets shall be

                                       3
<PAGE>
                                                                 Execution Copy

                       designated after December 6, 2002, and (ii) neither Party
                       shall have any obligation to make available for
                       identification and qualification activities any [**]
                       Exempt Target (or related data, information, material or
                       results).

                (f)    The Parties have agreed to work together to use some
                       or all of the Designated Targets set forth on EXHIBIT
                       D to the Second Amendment to this Agreement for [**].
                       Any Designated Target listed on EXHIBIT D that is not
                       used for [**] or for [**] will automatically be
                       designated a [**] Exempt Target.

                (g)    The Parties agree to discuss in good faith, on or before
                       [**], jointly designating for further development in the
                       Research Program up to [**] Designated Targets that, but
                       for such designation(s), would be [**]Exempt Target(s)
                       as of [**] (each, an "Extended Development Schedule
                       Designated Target"). If the Parties agree to designate
                       any Extended Development Schedule Designated Target(s),
                       the Parties shall document such agreement in writing and
                       the respective dates set forth in the definitions of [**]
                       Exempt Target, [**] Exempt Target, [**] Exempt Target and
                       [**] Exempt Target shall, solely for the purpose of
                       determining whether such Extended Development Schedule
                       Designated Target(s) become Exempt Target(s), each be
                       deemed extended by [**].

         5. Section 2.7.4(a) of the Collaboration Agreement is hereby amended by
inserting the following at the end of such Section immediately prior to the
final period thereof:

         ; PROVIDED, HOWEVER, that, from and after December 6, 2002, neither
         Party shall have the right to designate a Program Target as a Dropped
         Target under this Section 2.7.4(a)

         6. Section 2.7.5 of the Collaboration Agreement is hereby deleted in
its entirety and the following is hereby inserted in its place:

         2.7.5    Disposition of Exempt Targets; Disposition of Targets on
                  Research Program Expiration or Termination.
                  --------------------------------------------------------

         (a)      Each Party shall have the right to exploit, both within and
                  outside of the [**], any [**] Exempt Target. Any such
                  exploitation by a Party shall not require the consent of, nor
                  trigger any duty to account to, the other Party, PROVIDED
                  HOWEVER, that no license grant by either Party is implied by
                  this Section 2.7.5(a).

         (b)      (i)     Each Automatic Distribution Target (as that term is
                          defined in Section 2.7.5(b)(ii)) shall be deemed to be
                          both an Aventis Single-Party Research Target and a
                          Millennium Single-Party Research Target and its use
                          by a Party shall be governed by the relevant
                          provisions set forth in Section 2.7.3 and Article 7,
                          PROVIDED, HOWEVER, that (w) the obligations set forth
                          in Sections 2.12.3 and 2.12.4 will not apply to either
                          Party's activities using any Automatic Distribution
                          Target; (x) the [**] shall not apply to any such
                          Automatic Distribution Target, (y) the [**] set forth
                          in Section 8.3.3 with respect to the Commercialization
                          of any resulting Single-Party Target Product shall
                          only apply in the event that such Party exploits
                          Program

                                       4
<PAGE>
                                                                 Execution Copy

                          Technology Controlled by the other Party in the
                          identification, evaluation, optimization, Development
                          and/or Commercialization of such Single-Party Target
                          Product, and (z) the license grants set forth in
                          Sections 7.1.2(b), 7.1.3(b), 7.2.2(b) and 7.2.3(b)
                          shall, as they apply to any Automatic Distribution
                          Target, be deemed to be non-exclusive license grants
                          rather than exclusive license grants.

                  (ii)     "Automatic Distribution Target" means: any (i) [**]
                           Exempt Target, (ii) [**] Exempt Target, (iii) [**]
                           Exempt Target, and (iv) if the Research Program is
                           [**], other [**] Target that has not been designated
                           a Program Target, or other Program Target with
                           respect to which [**] pursuant to a [**] (as defined
                           in the [**]) have not been initiated.

         (c)      (i)      With respect to any Non-Automatic Distribution Target
                           (as that term is defined in Section 2.7.5(c)(iii)),
                           the Parties shall discuss whether they have an
                           interest in collaborating in the conduct of further
                           validation and drug discovery activities in the [**].
                           In the event that the Parties express such an
                           interest, they shall negotiate in good faith in an
                           effort to reach a final agreement regarding a
                           collaboration with respect to such target, for a
                           period of up [**] from the date on which the Parties
                           acknowledge their mutual interest. If the Parties
                           enter into a final agreement with respect to such
                           Non-Automatic Distribution Target, such Non-Automatic
                           Distribution Target shall no longer be designated a
                           Program Target and the rights and obligations of the
                           Parties with respect to such Non-Automatic
                           Distribution Target ([**] (which shall be allocated
                           to such target in the same manner as accorded
                           Single-Party Research Targets in accordance with the
                           provisions of 2.7.3(b)) shall be governed by the
                           terms of such final agreement and not this Agreement.

                  (ii)     In the event that the Parties (A) do not have a
                           mutual interest in collaborating with respect to any
                           Non-Automatic Distribution Target, or (B) fail to
                           reach a final agreement regarding a collaboration
                           with respect to any Non-Automatic Distribution Target
                           within the [**] period specified above, then the
                           Non-Automatic Distribution Target shall enter a
                           selection pool (the "Selection Pool") from which the
                           Parties shall choose all Non-Automatic Distribution
                           Targets ([**]) for further exploitation. The
                           selection process shall consist of the Parties making
                           alternating selections of the Non-Automatic
                           Distribution Targets in the Selection Pool, as
                           necessary to have selected all such targets (with a
                           flip of the coin determining which Party shall make
                           the first selection). Each Non-Automatic Distribution
                           Target selected from the Selection Pool shall no
                           longer be designated a Program Target but shall be
                           deemed to be an Aventis Single-Party Research Target
                           or a Millennium Single-Party Research Target, as the
                           case may be.  The use of any [**] Exempt Target that
                           is selected from the Selection Pool by a Party shall
                           be governed by the relevant provisions set forth in
                           Section 2.7.3 and Article 7, PROVIDED, HOWEVER, that
                          (1) the [**] shall not apply to any such target; and
                          (2) the

                                       5
<PAGE>
                                                                 Execution Copy

                           obligations set forth in Sections 2.12.3 and 2.12.4
                           will not apply to the Researching Party's activities
                           using that [**] Exempt Target. The use of any [**]
                           Exempt Target that is selected from the Selection
                           Pool by a Party shall be governed by the same
                           provisions as for a [**] Exempt Target, except that
                           (A) instead of the definition of "SPRT Compounds"
                           contained in Section 2.7.3(b), "SPRT Compounds" will
                           mean all Program Compounds Active against the
                           selected [**] Exempt Target; and (B) instead of the
                           limitation on use by the Non-Researching Party
                           contained in the last sentence of Section 2.7.3(b),
                           any rights of the Non-Researching Party to use such
                           SPRT Compounds for drug discovery of Small Molecules
                           directed to the selected [**] Exempt Target will
                           be suspended for a period of [**] following the date
                           on which the [**] Exempt Target is selected from the
                           Selection Pool.

                  (iii)    "Non-Automatic Distribution Target" means: (A) each
                           Program Target that is a [**] Exempt Target or a [**]
                           Exempt Target, and (B) if the Research Program is
                           terminated prior to [**], any other Program Target
                           with respect to which [**] pursuant to a [**] (as
                           defined in the [**]) have been initiated, but that
                           has not achieved the status of an [**] Target.

         (d)      For the avoidance of doubt, nothing in this Section 2.7.5
                  shall affect the Parties' rights with respect to [**] Targets,
                  [**] Compounds, or Backup Compounds. Further, nothing in this
                  Section 2.7.5 shall affect planned or ongoing [**] or [**]
                  intended to [**] pursuant to Section 3.9.1.

         7. Section 2.8.3 of the Collaboration Agreement is hereby amended by
deleting "or" from the end of clause (e) thereto, by deleting the period at the
end of clause (f) thereto and inserting "; or" in its place, and by inserting
the following new clause (g) immediately following clause (f) thereto:

                  (g)      where such activity is undertaken by a Party with
                           respect to an Exempt Target to the extent otherwise
                           permitted by the provisions of this Agreement.

         8. Section 2.10.3 of the Collaboration Agreement is hereby amended by
deleting "[**]" from the third line thereof and inserting "[**]" in place of
such deleted text.

         9. Section 2.10.4 of the Collaboration Agreement is hereby amended by
(a) deleting "[**]" from the third line thereof and inserting "[**]" in place of
such deleted text, and (b) deleting "and (b) Aventis" from the fifth line
thereof and inserting the following in place of such deleted text:

                  or (b) Aventis does exercise the GT Option or the Vaccine
                  Option within the [**] option period for the GT Option or the
                  Vaccine Option, but Aventis

         10. Section 2.11.3 of the Collaboration Agreement is hereby amended by
deleting "[**]" from the third line thereof and inserting "[**]" in place of
such deleted text.

                                       6
<PAGE>
                                                                 Execution Copy

         11. Section 2.11.4 of the Collaboration Agreement is hereby amended by
(a) deleting "[**]" from the third line thereof and inserting "[**]" in place of
such deleted text, and (b) deleting "and (b) Millennium" from the sixth line
thereof and inserting the following in place of such deleted text:

                  or (b) Millennium does exercise the Antibody Option or the
                  Diagnostic Option within the [**] option period for the
                  Antibody Option or the Diagnostic Option, but Millennium

         12. Continuing Effect. Except as otherwise specifically set forth
herein, all terms and conditions of the Collaboration Agreement remain in full
force and effect.

         13. Counterparts. This Second Amendment may be executed in one or more
counterparts, each of which counterparts, when so executed and delivered, shall
be deemed to be an original, and all of which counterparts, taken together,
shall constitute one and the same instrument.


                                       7
<PAGE>
                                                                 Execution Copy


         IN WITNESS WHEREOF, each of the Parties has caused this Second
Amendment to be executed as of the date first set forth above.

                               AVENTIS PHARMACEUTICALS INC.

                               By:     /s/Thomas Hofstaetter

                               Name:   Dr. Thomas Hofstaetter

                               Title:  Sr. VP, Corporate Development

                               Date:   4/22/03

                               MILLENNIUM PHARMACEUTICALS, INC.

                               By:     /s/Kenneth M. Bate

                               Name:   Kenneth M. Bate

                               Title:  CFO - VP

                               Date:   4/19/03


                                       8
<PAGE>
                                                                 Execution Copy

                                    EXHIBIT A

                  Scientific Milestones for Designated Targets
                  --------------------------------------------


     Date                                        Milestone
     ----                                        ---------

On or before [**]                           The Designated Targets [**].

On or before [**]                           A [**] have been initiated.

On or before [**]                           A [**] have been initiated.

On or before expiration of the              An [**]
Research Program Term                       has been designated.


                                       9



<PAGE>
                                                                 Execution Copy



                                    EXHIBIT B

                               Designated Targets
                               ------------------

     Origin
("M" = Millennium     Target      SQT Date        Program
 "A" = Aventis)                                   Target Date

        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]

                                       10
<PAGE>
                                                                 Execution Copy

 Origin
("M" = Millennium     Target      SQT Date        Program
 "A" = Aventis)                                   Target Date
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]
        A             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        M             [**]        [**]            [**]
        A             [**]        [**]            [**]


                                       11
<PAGE>
                                                                 Execution Copy

                                    EXHIBIT C

                          Non-Designated Exempt Targets
                          -----------------------------

    Origin
    ("M" =              Target            SQT Date         Program Target
 Millennium                                                    Date
"A" = Aventis)
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
       JOINT              [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]

                                       12
<PAGE>
                                                                 Execution Copy


 Origin
    ("M" =              Target            SQT Date         Program Target
 Millennium                                                    Date
"A" = Aventis)

         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         M                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]
         A                [**]              [**]               [**]

                                       13

<PAGE>
                                                                 Execution Copy

                                    EXHIBIT D

                        Designated Targets Identified for
                   Potential Use in High Throughput Screening
                             Prior to June 30, 2003
                   ------------------------------------------

  Origin
  ("M" =             Target   SQT Date     Program
 Millennium                               Target Date
"A" = Aventis)
        A             [**]      [**]         [**]
        M             [**]      [**]         [**]
        M             [**]      [**]         [**]
        A             [**]      [**]         [**]
        M             [**]      [**]         [**]

                                       14

<PAGE>
                                                                 Execution Copy

                                    EXHIBIT E

                                   EDC Targets
                                   -----------
[**]

                                       15