Exhibit 10.1
AMENDMENT TO COLLABORATION AND
LICENSE AGREEMENT BY AND
BETWEEN ASTELLAS US LLC (FORMERLY
FUJISAWA HEALTHCARE, INC.)
AND
CV THERAPEUTICS,
INC.
August 30, 2005
Confidential treatment has been requested for
portions of this exhibit. The copy filed herewith omits the
information subject to the confidentiality request. Omissions are
designated as [*]. A complete version of this exhibit has been
filed separately with the Securities and Exchange
Commission.
AMENDMENT TO
COLLABORATION AND LICENSE
AGREEMENT
This Amendment
(“Amendment”) is entered into, effective as of August
30, 2005 (the “Amendment Effective Date”), by and
between Astellas US LLC (“Astellas”,
successor-in-interest to Fujisawa Healthcare, Inc., the original
signatory to the Agreement defined below), and CV Therapeutics,
Inc. (“CVT”) (Astellas and CVT being individually
referred to herein as a “Party” and collectively as the
“Parties”), with reference to the following facts and
circumstances:
WHEREAS, CVT and Fujisawa
Healthcare, Inc. (“FHI”, predecessor-in-interest to
Astellas) entered into that certain Collaboration and License
Agreement dated as of July 10, 2000 (the
“Agreement”);
WHEREAS, in connection with a merger
involving FHI, the Agreement has been assigned to Astellas with
CVT’s consent; and
WHEREAS, the Parties wish to clarify
certain understandings respecting the Agreement, as expressly set
forth in this Amendment,
NOW THEREFORE, in consideration of
the mutual covenants exchanged, the Parties agree as
follows:
1. Definitions . Except as expressly set
forth herein, all capitalized terms used herein and not otherwise
defined shall be as defined in the Agreement.
2. References . Effective as of April 1,
2005, CVT has consented to the assignment of the Agreement to
Astellas, and Astellas has agreed to assume FHI’s rights and
obligations under the Agreement. In connection therewith, all
references in the Agreement or this Amendment to Fujisawa
Healthcare, Inc. or FHI are deemed to be references to Astellas. In
addition, in the Agreement or this Amendment, all references to the
Agreement shall be deemed to mean the Agreement as amended by this
Amendment.
3. Designated Patents . The list of
Designated Patents set forth in Schedule 1.10 of the
Agreement is hereby replaced with the attached restated Schedule
1.10 , which is incorporated herein.
4. Development Costs . In Section 1.11 of
the Agreement, the definition of Development Costs in the Agreement
is hereby amended and restated as follows:
“1.11 “ Development
Costs ” means the directly allocable out-of-pocket costs
of development (but not capital investment costs), plus FTE
Charges, incurred by CVT or FHI in accordance with Section 3.4(a)
in conducting their respective work under this Agreement and the
Development Program in accordance with the
Development Plan, including, without
limitation, costs associated with preparation and filing of
submissions for Regulatory Approvals for Licensed Compounds and/or
Licensed Products. Development Costs do not include any costs
associated with marketing, sales, promotion or distribution of
Licensed Compounds and/or Licensed Products. With respect to the
manufacture and supply of Licensed Compounds and/or Licensed
Products, Development Costs shall only include (i) the directly
allocable out-of-pocket costs (but not capital investment costs),
plus FTE Charges, incurred by CVT in conducting CVT Manufacturing
Activities under Section 3.4(a) up to and in connection with FDA
approval of the first NDA for the first Licensed Product hereunder,
and (ii) the directly allocable out-of-pocket costs (but not
capital investment costs), plus FTE Charges, incurred by FHI in
conducting FHI Manufacturing Activities under Section 3.4(a) up to
and in connection with FDA approval of the first NDA for the first
Licensed Product hereunder, and the Parties specifically agree that
the costs and FTE Charges specifically included within Development
Costs under the foregoing clauses (i) and (ii) shall include all
directly allocable out-of-pocket costs (but not capital investment
costs), plus FTE Charges, incurred by CVT or by FHI in preparing,
conducting or completing the Validation Package, irrespective of
whether the timing of completion of some of said validation
activities relating to the first NDA for the first Licensed Product
is before or after the receipt of FDA approval of the first NDA for
the first Licensed Product. In any event, with respect to the
manufacture and supply of Licensed Compounds and Licensed Products,
Development Costs shall not include the costs of producing any
Licensed Compounds and/or Licensed Products which could be sold
commercially as determined by the Management Committee. In no event
shall such directly allocable out-of-pocket costs include any costs
which are otherwise included in FTE Charges.”
5. FHI Development Technology. Section
1.17 of the Agreement is hereby amended and restated as
follows:
“1.17 “ FHI
Development Technology ” means any and all (a)
Collaborative Clinical Data in the FHI Field; (b) FHI Clinical Data
in the Development Field; (c) FHI Manufacturing Technology in the
Development Field; (d) Improvements to FHI Clinical Data developed
solely by FHI in the Development Field; (e) FHI’s joint
interest in any and all Improvements to the Collaborative Clinical
Data developed jointly by FHI and CVT in the FHI Field; and (f)
Improvements to the FHI Manufacturing Technology developed by FHI
(on its own or with CVT or Third Parties but which are Controlled
by FHI) in the Development Field.”
6. Licensed Compounds . Section 1.29 of
the Agreement is hereby amended and restated as follows:
“1.29 “ Licensed
Compounds ” means the compounds known as CVT 3146, or
regadenoson, and [*], the chemical names and structures of which
are set forth in Schedule 1.29 hereto.”
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[*]
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Certain
information on this page has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has
been requested with respect to the omitted portions.
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In addition, a new Schedule 1.29 ,
attached hereto, is hereby added to the Agreement and incorporated
herein.
7. Net Sales . The introductory paragraph
of Section 1.37 of the Agreement is hereby amended and restated as
follows:
“1.37 “Net Sales”
means, collectively, the gross invoiced sales price of all Licensed
Products sold by FHI (or for the purposes of Section 3.7(e) and
Section 8.2(b) only, CVT or its Affiliates or sublicensees), or its
Affiliates or its Sublicensees to Third Party purchasers after
deduction of the following items whether currently in effect or
which become effective during the Term as they pertain to the
Licensed Products:”
In addition, the final paragraph of Section 1.37
of the Agreement is hereby amended and restated as
follows:
“No deductions shall be made
from Net Sales for commissions paid to individuals whether they are
with independent sales agencies or are regularly employed by FHI
(or for the purposes of Section 3.7(e) and Section 8.2(b) only, CVT
or its Affiliates or sublicensees), and/or its Affiliates or its
Sublicensees and are on its or their payroll, or for the cost of
collections. Licensed Products shall be considered
“sold” when billed out or invoiced. Sales by FHI (or
for the purposes of Section 3.7(e) and Section 8.2(b) only, CVT or
its Affiliates or sublicensees), or its Affiliates or Sublicensees
of a Licensed Product to a Third Party distributor of such Licensed
Product in any given country shall be considered a sale to a Third
Party purchaser. Sale or transfer to an Affiliate or Sublicensee
for re-sale by such Affiliate or Sublicensee shall not be
considered a sale for the purpose of this provision, but the resale
by such Affiliate or Sublicensee to a Third Party shall be a sale
for such purposes.”
8. Cost of Goods . A new Section 1.53 of
the Agreement is hereby added as follows:
“1.53 “ Cost of
Goods ” shall have the meaning ascribed in Section
3.4(c)(ii).”
9. CVT Manufacturing Contracts . A new
Section 1.54 of the Agreement is hereby added as
follows:
“1.54 “ CVT
Manufacturing Contracts ” shall have the meaning ascribed
in Section 3.4(e).”
10. FHI Manufacturing Contracts . A new
Section 1.55 of the Agreement is hereby added as
follows:
“1.55 “ FHI
Manufacturing Contracts ” shall have the meaning ascribed
in Section 3.4(d).”
11. FHI Manufacturing Technology . A new
Section 1.56 of the Agreement is hereby added as
follows:
“1.56 “ FHI
Manufacturing Technology ” means Information and
Improvements Controlled by FHI as of the Effective Date or during
the Term that (i) are necessary or useful for the commercial
manufacture of Licensed Compounds and/or Licensed Products; and
(ii) specifically result from the CVT Manufacturing Activities or
FHI Manufacturing Activities under the Agreement, including any
such Information or Improvements Controlled by FHI and arising
under any CVT Manufacturing Contracts or FHI Manufacturing
Contracts, or contained in the Validation Package, provided that in
any case with respect to such CVT Manufacturing Activities or FHI
Manufacturing Activities (to include work on the Validation
Package), such activities are Paid by CVT. For avoidance of doubt,
FHI Manufacturing Technology or Improvements thereto shall only
include the Information or Improvements arising under any CVT
Manufacturing Contracts or FHI Manufacturing Contracts that are
developed prior to FDA approval of the first NDA for the first
Licensed Product hereunder or, as to Information or Improvements
developed while preparing, conducting or completing the Validation
Package, that have been developed as of completion of said
Validation Package activities, irrespective of whether the timing
of completion is before or after the receipt of FDA approval of the
first NDA for the first Licensed Product.”
12. Paid by CVT . A new Section 1.57 of
the Agreement is hereby added as follows:
“1.57 “ Paid by
CVT ” shall mean with respect to any CVT Manufacturing
Activities or any FHI Manufacturing Activities, that (A) CVT has
contributed its twenty five percent (25%) share of Development Cost
payments under Sections 3.4(c)(i) or (ii); or (B) FHI may deduct
twenty five percent (25%) of the Cost of Goods under Section
3.4(c)(ii); or (C) CVT under said Section 3.4(c)(ii) does not owe
its share because the Validation Batches or other batches could be
and were sold commercially.”
13. Validation Batches . A new Section
1.58 of the Agreement is hereby added as follows:
“1.58 “ Validation
Batch(es) ” shall have the meaning ascribed in Section
3.4(c)(ii).”
14. Validation Package . A new Section
1.59 of the Agreement is hereby added as follows:
“1.59 “ Validation
Package ” shall mean the validation of the manufacturing
process for the first Licensed Product for the first NDA,
including, without limitation, preparation of validation protocols
and process documentation, the manufacture of validation batches
and associated batch records, and any and all validation reports
and other validation-associated documentation, including any of the
foregoing that is included in the first NDA for the first Licensed
Product.”
15. CVT Manufacturing Activities .
Section 3.4(a) of the Agreement is hereby amended to revise the
definition of CVT Manufacturing Activities to read as
follows:
“As used herein, “
CVT Manufacturing Activities ” shall mean: (i)
CVT’s activities in identifying, selecting, qualifying and
entering into definitive agreement(s) with Third Party(ies) to
manufacture clinical supplies of Licensed Compounds and Licensed
Products and to supply raw materials and components for clinical
supplies of Licensed Compounds and Licensed Products; and (ii)
CVT’s activities in support of FHI Manufacturing Activities,
including in connection with process development and scale up work,
preparation of primary stability lots and registration batches, the
Validation Package, and other CVT activities in support of FHI
Manufacturing Activities by FHI (on its own and with Third Parties
under FHI Manufacturing Contracts) under the
Agreement.”
16. FHI Manufacturing Activities .
Section 3.4(a) of the Agreement is hereby further amended to revise
the definition of FHI Manufacturing Activities to read as
follows:
“As used herein, “
FHI Manufacturing Activities ” shall mean FHI’s
activities up to and in connection with FDA approval of the first
NDA for the first Licensed Product hereunder, in accordance with
the timeline(s) and transition plan to be determined by the
Management Committee as provided above, to: (i) identify, select,
qualify and enter into definitive agreement(s) with Third
Party(ies) to contract manufacture commercial supplies of Licensed
Compounds and Licensed Products and to supply raw materials and
components for commercial supplies of Licensed Compounds and
Licensed Products; and (ii) to conduct process development and
scale up work to develop a commercial process for the manufacture
and supply of Licensed Compounds and Licensed Products, including,
without limitation, related analytical and stability work and the
Validation Package. For avoidance of doubt, FHI Manufacturing
Activities shall specifically include FHI’s activities in
securing additional sources for commercial supplies of Licensed
Compound and Licensed Products.”
17. CVT Reimbursement of FHI . Section
3.4 (c) of the Agreement respecting CVT’s responsibility to
reimburse FHI for a portion of FHI Development Costs is hereby
amended to become Section 3.4(c)(i), and to add the following new
Section 3.4(c)(ii) which reads as follows:
“(ii) Notwithstanding the
foregoing in Section 3.4(c)(i), financial responsibility for
FHI’s Development Costs related to manufacturing Validation
Batches (defined
below) shall be allocated as
follows: FHI shall be responsible for one hundred percent (100%) of
the Cost of Goods
