EXHIBIT N0. 10.1
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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 00 Xxxxxx
Xxxxxx, Xxxxxxxxx, Xxxxxxxxxxxxx 00000 ("Millennium") and Aventis
Pharmaceuticals Inc., a corporation organized and existing under the laws of the
State of Delaware and having its principal office at Xxxxx 000-000, X.X. Xxx
0000, Xxxxxxxxxxx, Xxx Xxxxxx 00000 ("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:
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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.
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"[**] 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
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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
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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
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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.
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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.
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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/Xxxxxx Xxxxxxxxxxx
Name: Xx. Xxxxxx Xxxxxxxxxxx
Title: Sr. VP, Corporate Development
Date: 4/22/03
MILLENNIUM PHARMACEUTICALS, INC.
By: /s/Xxxxxxx X. Xxxx
Name: Xxxxxxx X. Xxxx
Title: CFO - VP
Date: 4/19/03
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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.
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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 [**] [**] [**]
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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 [**] [**] [**]
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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 [**] [**] [**]
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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 [**] [**] [**]
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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 [**] [**] [**]
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EXHIBIT E
EDC Targets
-----------
[**]
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