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CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED
BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.
AMENDMENT TO COLLABORATION
AGREEMENT
This AMENDMENT
TO COLLABORATION AGREEMENT (the “Amendment”) by and
between ONYX PRARMACEUTICAIS, INC. , a California
corporation having its principal place of business in Richmond,
California (“Onyx”) and BAYER CORPORATION , an
Indiana corporation having its principal place of business in
Pittsburgh, Pennsylvania (“Bayer”), shall be effective
as of the date of last execution below. Each of Bayer and Onyx are
sometimes referred to herein as the “Party” or,
collectively, as the “Parties”.
WHEREAS ,
Onyx and Bayer (under the name Miles Inc., the prior name of Bayer)
entered into a Collaboration Agreement, dated April 22, 1994
(the “Collaboration Agreement”); and
WHEREAS ,
Onyx and Bayer desire to amend and modify the terms of the
Collaboration Agreement as set forth in this Amendment;
NOW,
THEREFORE , in consideration of the covenants and promises
contained in this Amendment, the Parties agree as
follows:
1. Capitalized terms used in this Amendment but not
defined herein shall have the same meanings as defined in the
Agreement, except as modified under the terms of this Amendment.
The term “Miles” in the Agreement is understood to mean
Bayer.
2. The
Agreement is amended by adding the following additional defined
terms to Article 1 “Defined Terms” in the
Agreement:
1.51
“Additional Cancer Targets” means specific
molecular entities that the JRDC decides to add, contingent upon
written approval by Onyx and Bayer, under the provisions of
Section 5.6, to the collaboration between the Parties as
targets for the discovery, research and development of compositions
of matter useful for cancer treatment, as listed on Exhibit E
attached hereto.
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1.52
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“Collaboration Cancer
Program” means a program of research and
development comprising a set of targets, or a research area to
discover targets, for the discovery, research and development of
compositions of matter useful for cancer treatment that the JRDC
decides to add, contingent upon written approval by Onyx and Bayer,
under the provisions of Section 5.6, to the collaboration
between the Parties, as listed on Exhibit E attached
hereto.
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[ *
] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS
BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES EXCHANGE ACT OF
1933, AS AMENDED.
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1.53
“Onyx Collaboration Manager” shall be a person
designated by Onyx. The initial designee for this position is
Dr. T. Evans. If his employment at Onyx is terminated for any
reason, or if he is incapacitated or unwilling to serve, or if for
any reason Onyx wishes to replace him, he may be replaced by a
person mutually acceptable to Onyx and Bayer.
1.54
“Bayer Collaboration Coordinator” shall be a person
designated by Bayer. The initial designee for this position is
Dr. M. Katz. If his employment at Bayer is terminated for any
reason, or if he is incapacitated or unwilling to serve, or if for
any reason Bayer wishes to replace him, he may be replaced by a
person mutually acceptable to Onyx and Bayer.
3. Section 1.9 of the Agreement is amended to
read in its entirety as follows:
1.9
“Collaboration Compound” means, except as provided
below, any composition of matter:
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(i)
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that is discovered, identified or
synthesized by or on behalf of Onyx or Miles or an Affiliate of
either of them, and is recognized as provided below for its
activity either (x) for inhibiting Ras Function, or (y) for
modulating the activity of an Additional Cancer Target or a target
selected by the JRDC from a Collaboration Cancer Program, prior to
[ * ] ; or
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(ii)
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as
to which Onyx or Miles or an Affiliate of either of them acquires
rights from a Third Party, on an absolute or contingent basis (such
as rights under an option), and which is recognized as provided
below for its activity either (x) for inhibiting Ras Function,
or (y) for modulating the activity of an Additional Cancer
Target or a target selected by the JRDC from a Collaboration Cancer
Program, prior to [ * ] .
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As used herein,
the activity of a composition of matter for inhibiting Ras Function
or for modulating the activity of an Additional Cancer Target or a
selected target in a Collaboration Cancer Program, as applicable,
will be “recognized” if it satisfies the standards for
specific activity set forth in Exhibit D, or such other
specific activity in the particular assay or assays within the
Field of Collaborative Research established by the JRDC from time
to time pursuant to Section 6.3 for the particular
targets.
Notwithstanding
the foregoing the term “Collaboration Compound” shall
not include:
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(a)
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any
composition of matter marketed by Miles or an Affiliate of Miles as
of the Effective Date or as to which Miles or an Affiliate of Miles
[ * ] (as determined by the appropriate committee of Miles
or an Affiliate of Miles), as of the Effective Date;
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(b)
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any
composition of matter owned by Miles or Onyx or an Affiliate of
either of them that would become subject to this Agreement by
reason of an expansion of the Field of Collaborative Research after
the Effective Date but as to which [ * ]
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[ *
] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS
BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES EXCHANGE ACT OF
1933, AS AMENDED.
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prior to such expansion;
or
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(c)
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any
composition of matter that is a Back-Up Compound after [ * ]
following the end of the Research Term.
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4. Section 1.23 of the Agreement is amended to
add, after the phrase “or Ras Function”, the following
phrase:
“or
Additional Cancer Targets, or targets in the Collaboration
Programs, but”
5. Section 1.24 of the Agreement is amended to
read in its entirety as follows:
1.24
“Field of Collaborative Research” means the
specific programs, targets, and assays that are selected by the
JRDC contingent upon written approval by Onyx and Bayer for
discovering either (a) inhibitors of Ras Pathway and Ras
Function, or (b) modulators of the activity of targets in the
Additional Cancer Targets or in the Collaborative Cancer Programs.
As of the Effective Date, the Field of Collaborative Research shall
be as described on the attached Exhibit B, which shall be
amended by the Parties as the specific programs, targets, and
assays within the Field of Collaborative Research are modified and
updated by the JRDC pursuant to Section 5.6 or 6.1. The Field
of Collaborative Research shall not include any molecular entities,
programs, targets, or assays that are not involved in the Ras
Pathway or Ras Function, or in the Additional Cancer Targets, or
targets in the Collaboration Cancer Programs.
6. Section 1.39 of the Agreement is amended to
add, in place of the phrase “as defined in Section
1.11,” which is deleted, the following phrase:
“or for
modulating the activity of an Additional Cancer Target or a
selected target in a Collaboration Cancer Program, as defined in
Section 1.9,”
7. Section 1.45 is amended to read as
follows:
1.45
“Research Term” means the period commencing on
February 1, 1994 and continuing until January 31, 1999,
unless extended under Section 5.5 or earlier terminated
pursuant to Section 24.2, 24.3 or 24.4.
8. The
Paragraph entitled “Overview of Collaboration” in
Chapter 2 of the Agreement is amended to read in its entirety
as follows:
OVERVIEW OF
COLLABORATION
Proteins and other
effectors in the Ras Pathway, and other biochemical pathways, are
directly involved in control of cell growth. Changes or mutations
to components in the such pathways have been shown to cause
abnormal cell growth, including certain cancers. Onyx has
technology, materials, and expertise relating to the modulation of
Ras Function and other biochemical pathways and to assays that can
identity compounds having activities useful in
[ *
] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS
BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES EXCHANGE ACT OF
1933, AS AMENDED.
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inhibiting Ras
Function or in modulating the activities of other targets
potentially useful in treating cancer. Bayer has an extensive
library of chemical substances and natural materials, and expertise
in the research, development, and commercialization of
pharmaceutical compounds. The Parties desire to establish a broad
collaboration in the Field to perform research towards identifying
and investigating substances that inhibit Ras Function or modulate
the activity of other targets selected by the Parties and to
develop and commercialize substances identified in such process as
pharmaceutical products for the treatment of cancer and other human
conditions and diseases. The Parties intend that this Agreement
shall establish such collaboration and determine the rights and
obligation of each Party in conducting all of the research,
development, and marketing of products, and all other related
activities, under the collaboration. Attached as Exhibit A is
a flowchart depicting in schematic form, the various activities of
the collaboration and the decision points in the progress of
identifying, researching, and developing Collaboration
Products.
9. The
first sentence of Section 4.2(a) is amended to read as
follows:
(a) Onyx hereby grants Miles and its Affiliates a worldwide,
fully-paid-up license, with the right to grant sublicenses, under
the Onyx Patents and Onyx Know-How to develop, make, have made,
use, have used, import and have imported, offer for sale, sell and
have sold Collaboration Products, subject to the terms and
conditions of this Agreement.
10. The first sentence of Section 4.2(b) is
amended to read as follows:
(b) Miles and its Affiliates hereby grant Onyx a fully
paid-up license in the United States, without the right to grant
sublicenses, under the Miles Patents and Miles Know-How to develop,
use, offer for sale, and sell Collaboration Products, subject to
the terms and conditions of this Agreement.
11.
Section 4.4 is amended to read in its entirety as
follows:
(a) Onyx hereby grants Miles and its Affiliates an
exclusive, royalty-bearing license, with the right to grant
sublicenses, under the Onyx Patents and the Onyx Know-How solely to
develop, make, have made, use, have used, import and have imported,
offer for sale, sell and have sold Royalty-Bearing Products of
Miles in such countries where such products are deemed hereunder to
be Royalty-Bearing Products, subject to the terms and conditions of
this Agreement.
(b) Miles hereby grants Onyx and its Affiliates an
exclusive, royalty-bearing license, with the right to grant
sublicenses, under the Miles Patents and Miles Know-How solely to
make, have made, use, have used, import, have imported, offer for
sale, sell, and have sold Royalty-Bearing Products of Onyx in such
countries where such products are deemed hereunder to be Royalty
Bearing Products, subject to the terms and conditions of this
Agreement.
12. Section 4.5 of the Agreement is amended to
add at the end of the Section the following phrase:
[ *
] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS
BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES EXCHANGE ACT OF
1933, AS AMENDED.
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“or to
the Additional Cancer Targets or the Collaboration Cancer
Programs.”
13. Section 4.6 is deleted and a new
Section 4.6 is added as follows:
4.6 Bayer
License Outside the Field. Notwithstanding any other provision
of this Agreement, Onyx hereby grants Bayer and its Affiliates a
worldwide, paid-up, royalty-free non-exclusive license outside the
Field (except within fields of use for which Onyx has already
granted exclusive rights to Warner-Lambert, Eli Lilly and Chiron as
of April 4, 1996), without the right to grant sublicenses,
under the Onyx Compound Patents and the Onyx Know-How, solely to
make and have made, use
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