EXHIBIT 10.1
First Amendment to the Multi-Project Collaboration Agreement
dated May 13, 1997
This Amendment, dated September 29, 1997, is by and between the Procter
& Xxxxxx Company and its Affiliates ("P&G") and Regeneron Pharmaceuticals, Inc.,
and its Affiliates ("Regeneron").
The Parties entered into the Multi-Project Collaboration Agreement on
May 13, 1997, ("Collaboration Agreement"). AXOKINE (as defined herein) and CNTF
(as defined herein) were excluded from the scope of the Collaboration Agreement
as Regeneron Excluded Technology.
The Parties now desire to include AXOKINE and CNTF in the Collaboration
Agreement, to the extent set forth in this Amendment.
Defined terms shall be the same as the Collaboration Agreement, except
as specifically defined herein.
Accordingly, the Parties agree to amend the Collaboration Agreement as
follows:
Article I - Definitions
The following Sections shall be added:
1.50 "AXOKINE" means any CNTF (as defined herein) protein molecule
having one or more amino acid substitutions, deletions or additions, including,
but not limited to AxQ (as defined herein), unless designated otherwise by the
OC.
1.51 "CNTF" means ciliary neurotrophic factor, including but not limited
to rat, rabbit, or human CNTF. The full 200 amino acid sequence of human CNTF is
set forth in Attachment 1.51.
1.52 "AxQ" means any AXOKINE protein molecule claimed in U.S. Patent No.
5,349,056 and any continuations, continuations-in-parts, divisions, extensions
or foreign counterparts thereof.
1.53 "Proof of Concept Trial" means the first clinical trial in humans
that is conducted for the purpose of determining the safety and efficacy of
AXOKINE for weight reduction and glucose control in Type II diabetics (or as
otherwise modified by the OC) and that the OC specifically designates as such.
Attachment 1.13 (a) shall be modified as attached.
Article III - Research and Development
The following sections shall be added or modified (as applicable and
shown by redlined text):
3.3 (b) If the OC agrees that the Research Compound meets the Success
Criteria, then the Compound shall be designated a Development Compound.
Within *** (***) days after the designation of a Development Compound by
the OC, the OC shall approve a Product Plan for such Development
Compound. The Product Plan shall include general goals of the Parties
relating to the development and marketing of each Development Compound
and the timing, nature, and priority of resources to be applied and will
detail tasks and goals, personnel allocation, outside services and
costs, Success Criteria, Allowable Product Expenses, budgets, and such
other matters deemed necessary to implement the Product Plan. The
Product Plan will include a spending forecast through the end of
clinical trials for the Development Compound and a budget for the next
Fiscal Year that will be updated by the OC at least annually on a Fiscal
Year basis. Procter & Xxxxxx is responsible for taking the lead in
proposing such budget with significant and timely input from Regeneron.
The timing and calculations for the typical Product Plan budget is
contained in Attachment 3.1 as an example. The OC will have complete
authority to adopt all Product Plans. Notwithstanding the foregoing, the
OC shall approve the Product Plan for AXOKINE within *** (***) days of
signing this Amendment.
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3.3 (c) The Parties hereby designate AXOKINE as a Development Compound.
3.4 (a) Allowable Product Expenses. Allowable Product Expenses for
Development Compounds in the Muscle Field shall be shared equally.
Allowable Product Expenses to support an Investigational New Drug
application (IND) pursuant to 21 C.F.R. 312.1 et seq. for Development
Compounds other than those Development Compounds in the Muscle Field in
Fiscal Years 1 through 5 shall be paid by Procter & Xxxxxx; all other
Allowable Product Expenses for such Development Compounds shall be
shared equally. Notwithstanding the foregoing, Procter & Xxxxxx shall
pay for the Proof of Concept Trial. In addition, Procter & Xxxxxx shall
pay all other Allowable Product Expenses for AXOKINE until Regeneron's
receipt of all funding described in Section 3.9. All other Allowable
Product Expenses for AXOKINE shall be shared equally. Allowable Product
Expenses shall be payable quarterly in arrears, based on justification
of Allowable Product Expenses incurred over the quarter. Regeneron and
Procter & Xxxxxx shall submit reports to each other within thirty (30)
days of the end of each Fiscal Quarter detailing the number of FTEs
performing work pursuant to the Product Plan, Third Party costs and
other costs incurred in research, development and marketing activities,
as well as a detailed description of such work. Each Party shall review
and approve the other Party's reports within fifteen (15) days
thereafter, subject to the OC's approval, if necessary. Procter & Xxxxxx
will then calculate the amount that shall be paid by either Party to the
other Party to equalize funding and so advise Regeneron within seven (7)
days. The Party to whom funds are owed will issue an invoice for the
corresponding amount, payable within thirty (30) days. Costs incurred
and paid pursuant to this Section are subject to audit pursuant to
Section 6.5.
3.7. J-V Formation. Commencing at the end of the *** (***) Fiscal Year,
the Parties shall negotiate in good faith an agreement by the end of the
*** (***) Fiscal Year that contains all of the terms and conditions of
this Agreement, along with other terms and conditions as the Parties may
agree to develop and/or market Compounds, including without limitation
reasonable non-compete provisions ("J-V Agreement"). In the event that
the Parties cannot finalize such J-V Agreement prior to the end of the
*** (*** ) Fiscal Year the Parties may commence dispute resolution
pursuant to Section 2.5 or the Parties may terminate this Agreement
pursuant to Section 10.2, elect to continue to perform research,
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development and marketing activities pursuant to this Agreement until
its termination, or negotiate such other arrangement as the Parties may
agree. Notwithstanding the foregoing, the Parties shall use Commercially
Reasonable Efforts to execute a development agreement with respect to
AXOKINE, with terms consistent with this Agreement, such negotiations
commencing no later than *** ("AXOKINE Agreement"). The Parties shall
endeavor to draft such AXOKINE Agreement in a form such that it shall be
designated the J-V Agreement as described above.
3.9 Additional Funding - P&G shall pay Regeneron U.S. $2.5 million
promptly upon the execution of this Amendment. P&G shall pay Regeneron
U.S. *** million promptly upon the OC's agreement to the ***. P&G shall
pay Regeneron U.S. *** million promptly upon the *** . P&G shall pay
Regeneron *** million promptly upon *** after its *** the Proof of
Concept Trial results.
Article V - License Grants
The following Sections shall be modified (as shown by redlined text):
5.2. License Grants during Research Term.
(b) Regeneron hereby grants Procter & Xxxxxx a Sole License
under Regeneron Patents and Regeneron Know-how to make, have made, use,
import, and offer for sale and sell Regeneron Technology which (i) is
conceived or reduced to practice by Regeneron before the Term, (ii) is
acquired by Regeneron from a Third Party with the right to sublicense
prior to or during the Research Term, subject to Section 2.8, or (iii)
had been previously defined by the Parties as Regeneron Excluded
Technology, b had subsequently been removed from Regeneron Excluded
Technology as agreed in writing by both Parties. The license shall be
royalty free for uses which have actual or potential utility for the
identification, research or commercialization of products for the
prevention, diagnosis, or treatment of diseases or disorders in humans
or animals. For all other uses a reasonable royalty will be negotiated.
5.4 Rights on Termination if Milestones are Met. In the event a
Party terminates the Agreement pursuant to Section 10.2, and if ***
Research Compounds (excluding AXOKINE) have been determined by Procter &
Xxxxxx
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or the OC to meet their Success Criteria pursuant to a Research Project
Plan by the end of Fiscal Year 5, then:
(a) if Procter & Xxxxxx is the terminating party, then Procter &
Xxxxxx shall grant Regeneron an exclusive, royalty-free license in the
Territory under P&G Patents and P&G Know-how to make, have made, use,
import, offer for sale, and sell Lead Compounds and Validated Targets,
and a non-exclusive, royalty-free license in the Territory under P&G
Patents and P&G Know-how to make, have made, use, import, offer for
sale, and sell other Procter & Xxxxxx Technology; or
(b) if Regeneron is the terminating party, then Regeneron shall
xxxxx Xxxxxxx & Xxxxxx an exclusive, royalty-free license in the
Territory under Regeneron Patents and Regeneron Know-how to make, have
made, use, import, offer for sale, and sell Lead Compounds and Validated
Targets, and a non-exclusive, royalty-free license in the Territory
under Regeneron Patents and Regeneron Know-how to make, have made, use,
import, offer for sale, and sell other Regeneron Technology.
5.5. Rights in Technology upon Termination Pursuant to Section
10.3(b).
In the event that Procter & Xxxxxx terminates the Agreement pursuant to
Section 10.3(b) then the Parties shall grant the following licenses:
(a) If *** Research Compounds (excluding AXOKINE) have been
determined by Procter & Xxxxxx or the OC to have met their Success
Criteria pursuant to a Research Project Plan at the time of termination,
then Procter & Xxxxxx shall grant Regeneron an exclusive, royalty-free
license in the Territory under P&G Patents and P&G Know-how to make,
have made, use, import, offer for sale, and sell Lead Compounds and
Validated Targets, and a non-exclusive, royalty-free license in the
Territory unde Patents and P&G Know-how to make, have made, use, import,
offer for sale, and sell other Procter & Xxxxxx Technology; or.
(b) If Procter & Xxxxxx or the OC have not determined that ***
Compounds (excluding AXOKINE) have met their Success Criteria pursuant
to a Research Project Plan at the time of termination, then (i) Procter
& Xxxxxx shall xxxxx Regeneron a non-exclusive, royalty free license in
the Territory under P&G Patents and Know-how to Lead Compounds and
Procter & Xxxxxx Targets conceived and reduced to practice by Procter &
Xxxxxx, or acquired by Procter & Xxxxxx from a Third Party with the
right sublicense, during the Term to make,
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have made, use, import and offer for sale, and sell Lead Compounds and
Procter & Xxxxxx Targets; and (ii) Regeneron shall xxxxx Xxxxxxx &
Xxxxxx a non-exclusive license, royalty-free in the Territory under
Regeneron Patents and Regeneron Know-how to make, have made, use,
import, and offer for sale and sell Regeneron Technology which is
conceived and reduced to practice by Regeneron, or acquired by Regeneron
from a Third Party with the right to sublicense during the Term.
Article X - Term Termination, Change of Control
The following Section shall be modified accordingly (as shown by
redlined text):
10.2. Termination. Either Party may terminate the Research Term, and may
terminate the Agreement, provided there are no remaining royalty
obligations, at the end of Fiscal Year 5. Such termination may be made
following notice to the other Party delivered prior to the end of Fiscal
Year 4. Rights in technology shall be as set forth in Section 5.3.
However, if *** Research Compounds (excluding AXOKINE) have been
determined by Procter & Xxxxxx or the OC to meet their Success Criteria
pursuant to a Research Project Plan by the end of Fiscal Year 5, then
the terminating Party shall be granted rights pursuant to Section 5.4,
and any license that had been granted to the terminating Party pursuant
to Sections 5.6 or 5.7 shall be terminated.
10.3. Default.
(a) General Default. Failure by either Party (the "Defaulting
Party") to comply with any of the material obligations contained in this
Agreement, the Securities Purchase Agreement, the Registration Rights
Agreement, the Warrants Purchase Agreement or any J-V Agreement shall
entitle the other Party (the "Nondefaulting Party") to give to the
Defaulting Party notice specifying the nature of the default and
requiring it to cure such default. If the Defaulting Party disagrees
with the existence, extent or nature of the default, the Parties shall
use good faith efforts to resolve the dispute within thirty (30) days.
If (i) such default is not cured with such thirty (30) day period after
the receipt of such notice or (ii) the Parties have not otherwise
resolved the dispute during such thirty (30) day period, the
Nondefaulting Party shall be entitled to initiate arbitration under
Section 11.4 and at its sole discretion terminate this Agreement. In the
event of
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such termination, and in addition to any other remedies available to the
Nondefaulting Party, the Defaulting Party shall be deemed an Opting Out
Party with respect to any compounds pursuant to Section 5.7.
(b) Special Default. Regeneron shall promptly notify Procter &
Xxxxxx if any of its Key Executives leaves, or makes a decision to leave
the employment of Regeneron prior to the beginning of Fiscal Year 5. The
"Regeneron Key Executives" are listed in Attachment 10.3(b). Procter &
Xxxxxx may, after the end of a *** waiting period following such
notification, provide Regeneron with notice of termination, with the
termination to be effective *** after such notice of termination of the
Agreement. Rights in technology shall be as set forth in Section 5.5.
Notwithstanding the foregoing, this Section 10.3(b) shall not be
operative with respect to the Parties' rights and obligations under this
Agreement for AXOKINE.
The remaining Collaboration Agreement shall remain unchanged.
Accepted and agreed:
REGENERON PHARMACEUTICALS, INC.
_____________________________________
By Xxxxxxx X. Xxxxxxxxx, M.D., Ph.D.
President and Chief Executive Officer
Date ________
THE PROCTER & XXXXXX COMPANY Form ____________
Finance ____________
_____________________________________ Execution ____________
By Xxxxxx X. Xxxxxxx, Ph.D.
Vice President R&D, Pharmaceuticals, Health Care Products Worldwide
Date ________
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Attachment 1.13(a) Regeneron Excluded Technology
XXXX, XX-0, small molecule agonists or antagonists of neurotrophic factors as
defined in the Field in the Glaxo/Regeneron collaboration, small molecule
agonists and antagonists of cytokines and growth factors as defined in the Field
in the Pharmacopeia/Regeneron collaboration Agreement, and protein-based
cytokine agonists and antagonist of the compounds in the definition of the Field
in the Pharmacopeia/Regeneron collaboration, CNTF and AXOKINE to the extent set
forth in the Medtronic / Regeneron Collaborative Agreement (regardless of
whether such agreement is terminated), and CNTF and AXOKINE for direct
intraocular administration for the treatment of diseases of the eye.
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Attachment 9.1(b)
Third Party Agreements Relating to Excluded Technology
Technology Development Agreement dated as of March 20, 1989, between Sumitomo
Chemical Company, Limited and Regeneron Pharmaceuticals, Inc.
Collaboration Agreement dated as of August 31, 1990, between Amgen Inc., and
Regeneron Pharmaceuticals, Inc.
Collaboration Agreement dated as of July 22, 1993, between Glaxo Group Limited
and Regeneron Pharmaceuticals, Inc.
Research Development Agreement dated as of June 2, 1994, between Sumitomo
Pharmaceuticals Company, Ltd., and Regeneron Pharmaceuticals, Inc.
Collaboration Agreement dated as of October 9, 1996, between Pharmacopeia, Inc.,
and Regeneron Pharmaceuticals, Inc.
Collaborative Development Agreement dated as of June 27, 1996, between
Medtronic, Inc., and Regeneron Pharmaceuticals, Inc.
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