Collaborative Research and License Agreement [Amendment No. 2] - Merck & Co. Inc. and Cubist Pharmaceuticals Inc.
AMENDMENT NO. 2
TO
COLLABORATIVE RESEARCH AND LICENSE AGREEMENT
This Amendment No. 2 ("AMENDMENT NO. 2") is made this 30th day of
April, 1998, between Merck & Co., Inc., a New Jersey corporation ("MERCK")
and Cubist Pharmaceuticals, Inc., a Delaware corporation ("CUBIST"), and
amends a COLLABORATIVE RESEARCH AND LICENSE AGREEMENT between MERCK and
CUBIST dated as of June 13, 1996 (the "ORIGINAL AGREEMENT"), and AMENDMENT
NO. 1 TO COLLABORATIVE RESEARCH AND LICENSE AGREEMENT between MERCK and
CUBIST dated as of October 30, 1997, ("AMENDMENT NO. 1"). Terms not otherwise
defined in this AMENDMENT NO. 2 shall have the meanings ascribed to them in
the ORIGINAL AGREEMENT and AMENDMENT NO. 1.
WHEREAS, CUBIST possesses, CUBIST COMPOUNDS and desires, at its own
expense, to conduct a screening program for the purpose of determining the
enzyme inhibiting capability of certain of such CUBIST COMPOUNDS against the
PROGRAM tRNA SYNTHETASES (the "CUBIST SCREENING PROGRAM"), for the purpose of
identifying HITS and providing information regarding such HITS and rights to
such CUBIST COMPOUNDS to MERCK under the COLLABORATION on the terms specified
in the ORIGINAL AGREEMENT, as amended by AMENDMENT NO. 1 and this AMENDMENT
NO. 2 (collectively the "AMENDED AGREEMENT").
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WHEREAS, MERCK is willing to accept such information and rights to
such CUBIST COMPOUNDS on the terms specified in this AMENDMENT NO. 2;
NOW THEREFORE, it is agreed as follows:
1. DEFINITIONS
(a) The following defined terms shall have the indicated
meanings:
"CUBIST COMPOUND LIBRARY" or "CUBIST COMPOUNDS" shall mean those
chemical libraries or compounds owned or licensed by, or in the possession or
control of, CUBIST and comprised of natural products, combinatorial libraries
and synthetic sample collections.
"CUBIST DISCLOSURE PROGRAM" is defined in Paragraph 2 of this
AMENDMENT NO. 2.
"CUBIST LEAD COMPOUND" shall mean any CUBIST COMPOUND which is shown
to meet certain of the criteria for inhibitory activity against PROGRAM tRNA
SYNTHESES under the CUBIST SCREENING PROGRAM as such criteria are set forth
in the RESEARCH PLAN and which is disclosed to the RESEARCH COMMITTEE under
the CUBIST DISCLOSURE PROGRAM.
"LEAD CANDIDATE" shall mean any MERCK COMPOUND or CUBIST LEAD
COMPOUND targeted by the RESEARCH COMMITTEE for a LEAD CANDIDATE PRIMARY
SCREENING PROGRAM, a LEAD CANDIDATE
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SECONDARY SCREENING PROGRAM, a LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG
DISCOVERY PROGRAM and/or LEAD CANDIDATE DRUG DEVELOPMENT PROGRAM as a result
of the CUBIST DISCLOSURE PROGRAM. Any LEAD CANDIDATE shall be so designated
in writing by the RESEARCH COMMITTEE.
"LEAD CANDIDATE HIT" shall mean a LEAD CANDIDATE which, in the
course of the LEAD CANDIDATE PRIMARY SCREENING PROGRAM, is shown to meet the
criteria for inhibitory activity against a PROGRAM tRNA SYNTHETASES, as such
criteria is set forth in the RESEARCH PLAN.
"LEAD CANDIDATE PRIMARY SCREENING PROGRAM" shall mean a PRIMARY
SCREENING PROGRAM carried out under Paragraph 3 of this AMENDMENT NO. 2 with
respect to LEAD CANDIDATES .
"LEAD CANDIDATE SECONDARY SCREENING PROGRAM" shall mean a SECONDARY
SCREENING PROGRAM carried out under Paragraph 3 of this AMENDMENT NO. 2 with
respect to LEAD CANDIDATES.
"LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM"
shall mean a MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM carried out under
Paragraph 4 of this AMENDMENT NO. 2 with respect to LEAD CANDIDATES.
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"LEAD CANDIDATE DRUG DEVELOPMENT PROGRAM" shall mean a DRUG
DEVELOPMENT PROGRAM carried out under Paragraph 4 of this AMENDMENT NO. 2
with respect to LEAD CANDIDATES.
"ORIGINAL AMENDED AGREEMENT" shall mean the ORIGINAL AGREEMENT as
amended by AMENDMENT NO. 1.
"REVISED RESEARCH PLAN" means the Research Plan attached as Exhibit
A.
(b) The definitions contained in the ORIGINAL AMENDED AGREEMENT are
modified as follows:
"COLLABORATION" shall include the LEAD CANDIDATE PRIMARY SCREENING
PROGRAM, the LEAD CANDIDATE SECONDARY SCREENING PROGRAM, the LEAD CANDIDATE
MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM and the LEAD CANDIDATE DRUG
DEVELOPMENT PROGRAM carried out under Paragraph 4 of this AMENDMENT NO 2.
"COMPOUND" shall include any MERCK COMPOUND and any CUBIST LEAD
COMPOUND.
"CUBIST INTELLECTUAL PROPERTY" shall include CUBIST LEAD COMPOUNDS
and all information, research results and other KNOW-HOW
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disclosed by CUBIST to the RESEARCH COMMITTEE under the CUBIST DISCLOSURE
PROGRAM.
"DRUG DEVELOPMENT PROGRAM" shall include any LEAD CANDIDATE DRUG
DEVELOPMENT PROGRAM conducted under Paragraph 4 of this AMENDMENT NO. 2.
"HIT" shall include any LEAD CANDIDATE HIT.
"MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM" shall include any
LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM conducted under
Paragraph 4 of this AMENDMENT NO. 2.
"MERCK COMPOUND" shall include any MERCK COMPOUND which is
structurally modified under the COLLABORATION as a result of the CUBIST
DISCLOSURE PROGRAM.
"PRIMARY SCREENING PROGRAM" shall include the LEAD CANDIDATE PRIMARY
SCREENING PROGRAM conducted under Paragraph 3 of this AMENDMENT NO. 2 and the
REVISED RESEARCH PLAN.
"RESEARCH PLAN" shall include the REVISED RESEARCH PLAN.
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"SECONDARY SCREENING PROGRAM" shall include the LEAD CANDIDATE
SECONDARY SCREENING PROGRAM conducted under Paragraph 3 of this AMENDMENT NO.
2 and the REVISED RESEARCH PLAN.
2. CUBIST DISCLOSURE PROGRAM
During the term of the COLLABORATION, CUBIST may inform the RESEARCH
COMMITTEE of CUBIST LEAD COMPOUNDS identified under the CUBIST SCREENING
PROGRAM (the "CUBIST DISCLOSURE PROGRAM). Any such disclosures will be
accompanied by a full presentation of all information generated by CUBIST
under the CUBIST SCREENING PROGRAM regarding such CUBIST LEAD COMPOUNDS with
respect to (i) screening results using the PROGRAM tRNA SYNTHETASES under the
CUBIST SCREENING PROGRAM, (ii) chemical structures of such CUBIST LEAD
COMPOUNDS and (iii) such other information as the RESEARCH COMMITTEE may
request regarding such CUBIST LEAD COMPOUNDS and which is available to
CUBIST. The RESEARCH COMMITTEE may then determine, in its sole discretion, to
designate any such CUBIST LEAD COMPOUND as a LEAD CANDIDATE or to include
INTELLECTUAL PROPERTY received from CUBIST in connection with such CUBIST
LEAD COMPOUND under the CUBIST DISCLOSURE PROGRAM as part of the
COLLABORATION for potential incorporation into or any use in developing a
LEAD CANDIDATE. Any such election by the RESEARCH COMMITTEE shall be made in
writing. The initial CUBIST LEAD COMPOUNDS
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included in the COLLABORATION as LEAD CANDIDATES and/or with respect to which
INTELLECTUAL PROPERTY learned under the CUBIST DISCLOSURE PROGRAM may be
incorporated into or otherwise used in developing a LEAD CANDIDATE are
identified on Exhibit B to this AMENDMENT NO. 2.
3. LEAD CANDIDATE SCREENING PROGRAMS
The PRIMARY SCREENING PROGRAM and the SECONDARY SCREENING PROGRAM,
in so far as all LEAD CANDIDATES are concerned, shall proceed as follows:
(a) The PRIMARY SCREENING PROGRAM in Section 2.1.1(b)(i) of the
ORIGINAL AMENDED AGREEMENT is modified as follows:
(i) CUBIST shall employ the PRIMARY SCREENING MODULES in a
LEAD CANDIDATE PRIMARY SCREENING PROGRAM to screen the LEAD CANDIDATES
in a manner which, in the sole judgment of the RESEARCH COMMITTEE, is
suitable for such purpose. LEAD CANDIDATES which are MERCK COMPOUNDS
shall be provided to CUBIST in coded form. The LEAD CANDIDATE PRIMARY
SCREENING PROGRAM shall be carried out by CUBIST, at CUBIST's sole cost
and expense.
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(ii) Sections 2.1.1(b)(ii) and (iii) of the ORIGINAL AMENDED
AGREEMENT, as further amended by this AMENDMENT NO. 2, remain in effect
and shall apply to the LEAD CANDIDATE PRELIMINARY SCREENING PROGRAM.
(iii) Section 2.1.1(a) of the ORIGINAL AMENDED AGREEMENT, as
further amended by this AMENDMENT NO. 2, has been completed and no
further work thereunder shall be required as a part, of this AMENDMENT
NO. 2.
(b) The SECONDARY SCREENING PROGRAM in Section 2.1.1(c)(i) of the
ORIGINAL AMENDED AGREEMENT is modified as follows:
(i) Promptly following the identification of a LEAD CANDIDATE
HIT in the LEAD CANDIDATE PRIMARY SCREENING PROGRAM, CUBIST will begin
a LEAD CANDIDATE SECONDARY SCREENING PROGRAM with respect to each such
LEAD CANDIDATE HIT. Such LEAD CANDIDATE SECONDARY SCREENING PROGRAM
will be completed in a diligent manner and with respect to each LEAD
CANDIDATE HIT, and the results of such LEAD CANDIDATE SECONDARY
SCREENING PROGRAM will be promptly reported to MERCK. The LEAD
CANDIDATE SECONDARY SCREENING shall be carried out by CUBIST at
CUBIST's sole cost and expense.
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(ii) Section 2.1.1(c)(ii) and (iii) of the ORIGINAL AMENDMENT,
as further amended by this AMENDMENT NO. 2, remain in effect and shall
apply to the LEAD CANDIDATE SECONDARY SCREENING PROGRAM.
4. LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG DISCOVERY
PROGRAM; DRUG DEVELOPMENT PROGRAM
(a) The MEDICINAL CHEMISTRY DRUG DISCOVERY PROGRAM provisions in
Section 2.1.2 of the ORIGINAL AMENDED AGREEMENT are modified, insofar as all
LEAD CANDIDATE HITS are concerned, as follows:
(i) Promptly following receipt of the results of a LEAD
CANDIDATE SECONDARY SCREENING PROGRAM regarding a LEAD CANDIDATE HIT,
the RESEARCH COMMITTEE shall indicate whether it recommends such LEAD
CANDIDATE HIT for further evaluation as an ANTIINFECTIVE AGENT OR
AGENTS in a LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG DISCOVERY
PROGRAM, and shall notify CUBIST and MERCK of such designation (such
notice shall constitute a "MEDICINAL CHEMISTRY NOTICE"). Subject to
Sections 2.1.3(i) and 2.1.3(ii) of the ORIGINAL AMENDED AGREEMENT, as
applicable, CUBIST shall conduct the medicinal chemistry activities
during the course of the LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG
DISCOVERY PROGRAM. Subject to Section 2.1.3 of the ORIGINAL AMENDED
AGREEMENT and promptly following its receipt of the MEDICINAL CHEMISTRY
NOTICE, MERCK shall reveal to CUBIST the identity and
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chemical structure of the LEAD CANDIDATE HIT being developed (to the
extent not previously disclosed to or known by CUBIST), provided
however that MERCK shall not be obligated to make such disclosure if
CUBIST elects, pursuant to Section 2.1.3 of the ORIGINAL AMENDED
AGREEMENT, not to pursue the LEAD CANDIDATE MEDICINAL CHEMISTRY AND
DRUG DISCOVERY PROGRAM. Subject to Section 2.1.3(i) of the ORIGINAL
AMENDED AGREEMENT, CUBIST shall devote such FTEs to the LEAD CANDIDATE
MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM as are specified under
plans and budgets approved in advance by MERCK. MERCK will pay CUBIST
on an "FTE basis" (not to exceed [ ]* per FTE) for that number of FTEs
as have been committed to the LEAD CANDIDATE MEDICINAL CHEMISTRY DRUG
DISCOVERY PROGRAM and as have been approved by MERCK. Subject to
Sections 2.1.3(i) or (ii) of the ORIGINAL AMENDED AGREEMENT, as
applicable, during the LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG
DISCOVERY PROGRAM, MERCK will provide such other support as shall
reasonably be required by CUBIST. The goal of the LEAD CANDIDATE
MEDICINAL CHEMISTRY AND DRUG DISCOVERY PROGRAM is the identification of
a compound suitable for a DRUG DEVELOPMENT PROGRAM.
*Confidential treatment requested: Material has been
omitted and filed separately with the Commission.
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(ii) Section 2.1.3 of the ORIGINAL AMENDED AGREEMENT, as
further amended by this AMENDMENT NO. 2, remains in effect and shall
apply to the LEAD CANDIDATE MEDICINAL CHEMISTRY AND DRUG DISCOVERY
PROGRAM.
(b) The DRUG DEVELOPMENT PROGRAM provisions in Section 2.1.4 of the
ORIGINAL AMENDED AGREEMENT are modified, insofar as all LEAD CANDIDATE HITS
are concerned, to add the following:
CUBIST may be delegated the responsibility to perform preclinical
development work under a DRUG DEVELOPMENT PROGRAM relating to LEAD CANDIDATES
HITS and LICENSED PRODUCTS under a LEAD CANDIDATE DRUG DEVELOPMENT PROGRAM as
shall be determined by MERCK. All such work under LEAD CANDIDATE DRUG
DEVELOPMENT PROGRAM shall be accomplished pursuant to a work plan and budgets
approved in advance by MERCK. MERCK shall pay CUBIST on an "'FTE basis" (not
to exceed [ ]* per FTE) for the number of FTEs as have been committed to the
LEAD CANDIDATE DRUG DEVELOPMENT PROGRAM and as have been approved by MERCK.
CUBIST shall hold at least one meeting each calendar quarter to inform the
RESEARCH COMMITTEE regarding the progress of all work done in connection with
a LEAD CANDIDATE DRUG DEVELOPMENT PROGRAM.
*Confidential treatment requested: Material has been omitted
and filed separately with the Commission.
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MERCK may, at its discretion, discontinue or relocate any work delegated to
CUBIST in connection with a LEAD COMPOUND DRUG DEVELOPMENT PROGRAM at any
time upon three months prior written notice.
(c) CUBIST shall submit invoices to MERCK at the end of each
calendar quarter (January-March, April-June, July-September, and
October-December) for FTE's expended under the MEDICINAL CHEMISTRY DRUG
DISCOVERY and the DRUG DEVELOPMENT PROGRAM, including the LEAD CANDIDATE
MEDICINAL CHEMISTRY DRUG DISCOVERY PROGRAM and LEAD CANDIDATE DRUG
DEVELOPMENT PROGRAM, which amount shall be prorated on a daily basis for
partial calendar quarters. Invoices shall be payable by MERCK 30 days after
receipt. The conduct and cost and expense of all MEDICINAL CHEMISTRY AND DRUG
DISCOVERY PROGRAMS and all DRUG DEVELOPMENT PROGRAMS, other than the LEAD
CANDIDATE MEDICINAL CHEMISTRY DRUG DISCOVERY PROGRAM and LEAD CANDIDATE DRUG
DEVELOPMENT PROGRAM, shall continue to be as provided in Section 2.1.3 and
2.1.4 of the ORIGINAL AMENDED AGREEMENT.
5. NO ADDITIONAL PAYMENTS
It is agreed by CUBIST and MERCK that no additional payments shall
be due under Sections 3.1, 3.2 or 3.3 of the ORIGINAL AMENDED AGREEMENT
regarding the LEAD CANDIDATE PRIMARY SCREENING PROGRAM or the
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LEAD to CANDIDATE SECONDARY SCREENING PROGRAM, notwithstanding that
additional assays are to be conducted in connection therewith as provided in
Paragraph 2 of the AMENDMENT NO. 2 and additional INTELLECTUAL PROPERTY
rights may be provided by CUBIST.
6. MILESTONE CREDITS
In consideration of the entering into of this AMENDMENT NO. 2 by
CUBIST and the performance by CUBIST of its obligations hereunder, MERCK
agrees that the credit of BASE MILESTONE PAYMENTS against royalties under
Section 3.5(iii) of the ORIGINAL AMENDED AGREEMENT shall not apply to the
first two LICENSED PRODUCTS approved for marketing in any country. Similarly,
to the extent Section 3.6(ii) or 3.7(ii) of the ORIGINAL AMENDED AGREEMENT
would apply to either of such first two LICENSED PRODUCTS approved for
marketing in any country, the credit of BASE MILESTONE ROYALTY PAYMENTS
against royalties under such Sections 3.6(ii) or 3.7(ii) shall not apply to
such first LICENSED PRODUCTS.
7. TERMINATION OF CUBIST LEAD COMPOUND
In the event that (i) the RESEARCH COMMITTEE shall determine that a
LEAD CANDIDATE shall be discontinued from further research under a LEAD
CANDIDATE PRIMARY SCREENING PROGRAM, LEAD CANDIDATE SECONDARY SCREENING
PROGRAM, LEAD CANDIDATE MEDICINAL
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CHEMISTRY AND DRUG DISCOVERY PROGRAM, or a LEAD COMPOUND DRUG DEVELOPMENT
PROGRAM, or shall otherwise determine, to cease further research and
development efforts with respect to such LEAD COMPOUND and (ii) MERCK shall
have obtained marketing clearance in the United States for a LICENSED PRODUCT
under this COLLABORATION, then CUBIST may request and MERCK, in its sole
discretion, may extend to CUBIST, the opportunity to enter into good faith
negotiations to provide CUBIST the right to develop such LEAD COMPOUND
outside of the COLLABORATION by itself or with third parties.
8. ORIGINAL AGREEMENT IN EFFECT
Except as specifically modified or amended by this AMENDMENT NO. 2,
the ORIGINAL AMENDED AGREEMENT continues in full force and effect.
IN WITNESS WHEREOF, the parties have executed this AMENDMENT NO. 2
as of the date first written above.
CUBIST PHARMACEUTICALS, INC. MERCK & CO., INC.
By: /s/ Mark Carthy By: /s/
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Mark Carthy
Chief Business Officer
Cubist Pharmaceuticals, Inc.
21 - April -1998
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