EXHIBIT 10.24
[ * ] = 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 Act of 1933, as
amended.
COLLABORATION AND LICENSE
AGREEMENT
This COLLABORATION AND LICENSE
AGREEMENT (the “Agreement” ) is entered into
on February 13, 2006 (the “Effective Date”
) between AFFYMAX, INC. , a Delaware corporation, with its
principal place of business at 4001 Miranda Avenue, Palo Alto,
CA 94304, U.S.A. ( “Affymax” ), and
TAKEDA PHARMACEUTICAL COMPANY LIMITED, a company
incorporated under the laws of Japan, with a place of business at
1-1, Doshomachi 4-chome, Chuo-ku, Osaka, 540-8645, Japan (
“Collaborator” ). Affymax and Collaborator
are sometimes referred to herein individually as a
“Party” and collectively as the
“Parties”.
RECITALS
WHEREAS , Affymax is developing its proprietary
pegylated [ * ] drug candidate designated by Affymax as
Hematide™ for the treatment of anemia in patients with
chronic kidney disease and cancer;
WHEREAS , Collaborator possesses substantial resources
and expertise in the development, marketing, and commercialization
of pharmaceutical products in Japan;
WHEREAS , Collaborator desires to obtain exclusive
rights to develop further and commercialize Hematide in Japan, and
Affymax is willing to grant such rights on the terms and conditions
hereof.
NOW THEREFORE
, in consideration of the foregoing
premises and the mutual promises, covenants and conditions
contained in this Agreement, the Parties agree as
follows:
1
TABLE OF CONTENTS
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PAGE
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ARTICLE 1
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DEFINITIONS
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2
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1.1
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“Affiliate”
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2
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1.2
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“Affymax House Marks”
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2
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1.3
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“Affymax Know-How”
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2
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1.4
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“Affymax Patent”
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3
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1.5
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“Affymax Technology”
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3
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1.6
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“Affymax Territory”
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3
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1.7
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“Alternative ESA”
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3
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1.8
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“Backup Product”
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3
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1.9
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“Bulk Hematide”
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3
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1.10
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“Claims”
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3
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1.11
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“CTA”
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3
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1.12
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“Collaborator Know-How”
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4
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1.13
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“Collaborator Patent”
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4
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1.14
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“Collaborator Technology”
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4
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1.15
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“Commercialization”
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4
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1.16
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“Confidential
Information”
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4
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1.17
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“Control”
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4
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1.18
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“Develop” or
“Development”
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5
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1.19
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“Development Plan”
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5
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1.20
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“Diligent Efforts”
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5
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1.21
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“[ * ]”
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5
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1.22
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“Dollar”
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5
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1.23
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“EMEA”
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5
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1.24
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“ESA”
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6
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1.25
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“FDA”
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6
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1.26
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“FD&C Act”
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6
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1.27
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“Field”
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6
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1.28
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“Finished Manufacture”
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6
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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 Act of 1933, as
amended.
i
TABLE OF CONTENTS
(CONTINUED)
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PAGE
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1.29
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“Finished Product”
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6
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1.30
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“First Commercial Sale”
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6
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1.31
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“Formulation Technology”
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6
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1.32
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“Good Clinical Practices” or
“GCP”
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6
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1.33
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“Good Laboratory Practices” or
“GLP”
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7
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1.34
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“Good Manufacturing Practices” or
“GMP”
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7
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1.35
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“Governmental Authority”
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7
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1.36
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“Hematide”
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7
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1.37
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“IND”
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7
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1.38
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“Information”
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7
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1.39
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“Initial Indications”
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8
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1.40
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“Joint Committee”
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8
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1.41
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“Joint Inventions”
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8
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1.42
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“Joint Patent”
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8
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1.43
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“Laws”
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8
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1.44
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“Licensed Territory”
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8
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1.45
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“Manufacturing Costs”
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8
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1.46
|
“Marketing Authorization
Application” or “MAA”
|
10
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1.47
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“MHLW”
|
10
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1.48
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“Net Sales”
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10
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1.49
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“Oncology Indications”
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11
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1.50
|
“Patents”
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11
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1.51
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“Patent Term Extension”
|
12
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1.52
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“Peptide”
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12
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1.53
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“Phase I Clinical Trial”
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12
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1.54
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“Phase II Clinical Trial”
|
12
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1.56
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“Phase IIIB Clinical
Trial”
|
12
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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 Act of 1933, as
amended.
ii
TABLE OF CONTENTS
(CONTINUED)
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PAGE
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1.57
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“Phase IV Clinical Trial”
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12
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1.58
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“Pricing Approval”
|
13
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1.59
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“Product”
|
13
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1.60
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“Product Complaint”
|
13
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1.61
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“Product Infringement”
|
13
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1.63
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“Promotional Materials”
|
13
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1.64
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“Reagent”
|
13
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1.65
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“Regulatory Approvals”
|
14
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1.66
|
“Regulatory Authority”
|
14
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1.67
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“Regulatory Exclusivity”
|
14
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1.68
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“Regulatory Materials”
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14
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1.69
|
“Renal Indications”
|
14
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1.70
|
“Required Third Party
Data”
|
14
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1.72
|
“Stock Purchase
Agreement”
|
14
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1.73
|
“Term”
|
15
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1.74
|
“Territory”
|
15
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1.75
|
“Third Indication”
|
15
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1.76
|
“Third Party”
|
15
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1.77
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“Third Party Data”
|
15
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1.78
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“Third Party License
Agreements”
|
15
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1.79
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“Third Party Partner”
|
15
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1.80
|
“U.S.”
|
15
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1.81
|
“Valid Claim”
|
15
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1.82
|
“Yakka”
|
15
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ARTICLE 2
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MANAGEMENT
|
16
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2.1
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Joint Committee
|
16
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2.2
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Joint Committee Membership
|
17
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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 Act of 1933, as
amended.
iii
TABLE OF CONTENTS
(CONTINUED)
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PAGE
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2.3
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Joint Committee Meetings and Agendas
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18
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2.4
|
Joint Committee Decisions and Actions
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19
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2.5
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Project Coordinators
|
20
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2.6
|
Collaboration Guidelines
|
20
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ARTICLE 3
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PRODUCT DEVELOPMENT
|
20
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3.1
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Overview
|
20
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3.2
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Development Plan
|
21
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3.3
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Principles of Product Development
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22
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3.4
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Collaborator’s Performance
|
22
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3.5
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Records, Reports and Information
|
23
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3.6
|
Right of First Refusal to Backup Product
Developed in the Field
|
23
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ARTICLE 4
|
REGULATORY MATTERS
|
24
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4.1
|
Transfer of Data and Regulatory
Materials
|
24
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4.2
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Regulatory Filings and Approvals
|
29
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4.3
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Filings for Regulatory Exclusivity
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31
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4.4
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Regulatory Costs
|
31
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4.5
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Communications
|
31
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4.6
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Collaborator Regulatory Filings
|
32
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4.7
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No Harmful Actions
|
32
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4.8
|
Adverse Event Reporting and Safety Data
Exchange
|
33
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4.9
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Regulatory Authority Communications Received by
a Party
|
34
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4.10
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Regulatory Inspection or Audit
|
35
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4.11
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Recalls and Voluntary Withdrawals
|
36
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ARTICLE 5
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COMMERCIALIZATION
|
37
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5.1
|
Commercialization in the Licensed
Territory
|
37
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5.2
|
Pricing Approvals in the Licensed
Territory
|
37
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|
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5.3
|
Pricing of the Product in the Licensed
Territory
|
38
|
[ * ] = 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 Act of 1933, as
amended.
iv
TABLE OF CONTENTS
(CONTINUED)
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PAGE
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5.4
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Collaborator Performance
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38
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5.5
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Compliance
|
38
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5.6
|
Product Trademark and Affymax House
Marks
|
39
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ARTICLE 6
|
LICENSES AND EXCLUSIVITY
|
40
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|
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6.1
|
Licenses to Collaborator under Affymax
Technology
|
40
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|
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6.2
|
Limited License for Affymax House
Marks
|
40
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|
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6.3
|
License to Affymax under Collaborator
Technology
|
41
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|
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6.4
|
Negative Covenant
|
41
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|
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6.5
|
No Implied Licenses
|
41
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|
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6.6
|
Exclusivity
|
41
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|
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6.7
|
Third Party Licenses
|
42
|
|
ARTICLE 7
|
MANUFACTURE AND SUPPLY
|
42
|
|
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7.1
|
Roles of the Parties
|
42
|
|
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7.2
|
Preclinical and Clinical Supply of Bulk
Hematide
|
42
|
|
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7.3
|
Commercial Supply of Bulk Hematide
|
43
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|
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7.4
|
Finished Product
|
44
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|
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7.5
|
Comparator Drugs
|
44
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|
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7.6
|
Audit
|
44
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|
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7.7
|
Collaborator Audit Right of Bulk Hematide
Facility
|
45
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|
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7.8
|
Quality Agreement
|
46
|
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ARTICLE 8
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COMPENSATION
|
46
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|
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8.1
|
License Fee
|
46
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|
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8.2
|
Clinical Milestone Payments
|
47
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|
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8.3
|
Royalties
|
48
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|
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8.4
|
Existing and Future Third Party
Royalties
|
50
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|
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8.5
|
Taxes
|
51
|
|
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8.6
|
Foreign Exchange
|
52
|
[ * ] = 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 Act of 1933, as
amended.
v
TABLE OF CONTENTS
(CONTINUED)
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PAGE
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8.7
|
Late Payments
|
52
|
|
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8.8
|
Records; Audits
|
52
|
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ARTICLE 9
|
INTELLECTUAL PROPERTY MATTERS
|
53
|
|
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9.1
|
Ownership of Inventions
|
53
|
|
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9.2
|
Disclosure of Inventions
|
53
|
|
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9.3
|
Prosecution of Patents
|
54
|
|
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9.4
|
Patent Term Extensions in the Licensed
Territory
|
57
|
|
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9.5
|
Infringement of Patents by Third
Parties
|
58
|
|
|
9.6
|
Infringement of Third Party Rights in the
Licensed Territory
|
63
|
|
|
9.7
|
Patent Marking
|
64
|
|
|
9.8
|
Infringement of Trademarks by Third
Parties
|
64
|
|
|
9.9
|
Patent Oppositions and Other
Proceedings
|
64
|
|
|
9.10
|
Parties’ Patent Rights
|
65
|
|
|
9.11
|
Orange Book Listing, Compendial
Listing
|
66
|
|
|
9.12
|
Registration of Exclusive License
|
66
|
|
|
9.13
|
Certain Patent Matters
|
66
|
|
ARTICLE 10
|
REPRESENTATIONS AND WARRANTIES
|
66
|
|
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10.1
|
Mutual Representations and Warranties
|
66
|
|
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10.2
|
Additional Representations, Warranties and
Covenants of Affymax
|
67
|
|
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10.3
|
Disclaimer
|
69
|
|
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10.4
|
No Other Representations or
Warranties
|
70
|
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ARTICLE 11
|
INDEMNIFICATION
|
70
|
|
|
11.1
|
Indemnification by Affymax
|
70
|
|
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11.2
|
Indemnification by Collaborator
|
71
|
|
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11.3
|
Indemnification Procedures
|
71
|
|
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11.4
|
Limitation of Liability
|
72
|
|
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11.5
|
Insurance
|
72
|
[ * ] = 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 Act of 1933, as
amended.
vi
TABLE OF CONTENTS
(CONTINUED)
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PAGE
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ARTICLE 12
|
CONFIDENTIALITY
|
73
|
|
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12.1
|
Confidentiality
|
73
|
|
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12.2
|
Authorized Disclosure
|
74
|
|
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12.3
|
Publicity; Terms of Agreement
|
75
|
|
|
12.4
|
Publications
|
76
|
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ARTICLE 13
|
TERM AND TERMINATION
|
77
|
|
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13.1
|
Term
|
77
|
|
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13.2
|
Early Termination
|
77
|
|
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13.3
|
Effect of Termination of the
Agreement
|
79
|
|
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13.4
|
Other Remedies
|
80
|
|
|
13.5
|
Rights in Bankruptcy
|
81
|
|
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13.6
|
Survival
|
81
|
|
ARTICLE 14
|
DISPUTE RESOLUTION
|
81
|
|
|
14.1
|
English Language; Governing Law
|
81
|
|
|
14.2
|
Disputes
|
82
|
|
|
14.3
|
Patent and Trademark Dispute
Resolution
|
83
|
|
ARTICLE 15
|
MISCELLANEOUS
|
83
|
|
|
15.1
|
Entire Agreement; Amendment
|
83
|
|
|
15.2
|
Force Majeure
|
84
|
|
|
15.3
|
Notices
|
84
|
|
|
15.4
|
No Strict Construction; Headings
|
85
|
|
|
15.5
|
Assignment
|
85
|
|
|
15.6
|
Performance by Affiliates
|
86
|
|
|
15.7
|
Further Actions
|
86
|
|
|
15.8
|
Severability
|
86
|
|
|
15.9
|
No Waiver
|
86
|
|
|
15.10
|
Independent Contractors
|
87
|
[ * ] = 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 Act of 1933, as
amended.
vii
TABLE OF CONTENTS
(CONTINUED)
|
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PAGE
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|
|
|
|
|
15.11
|
Counterparts
|
87
|
[ * ] = 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 Act of 1933, as
amended.
viii
ARTICLE 1
DEFINITIONS
As used in this Agreement, the
following initially capitalized terms, whether used in the singular
or plural form, shall have the meanings set forth in this
Article 1. The terms in this Agreement with initial
letters capitalized, whether used in the singular or the plural,
shall have the meaning set forth below or, if not listed below, the
meaning designated in places throughout this Agreement.
1.1
“Affiliate” means, with respect to a particular Party, a
person, corporation, partnership, or other entity that controls, is
controlled by or is under common control with such Party. For
the purposes of this definition, the word “control”
(including, with correlative meaning, the terms “controlled
by” or “under the common control with”) means,
for the purpose of defining the Affiliate under this
Section 1.1, the actual power, either directly or indirectly
through one or more intermediaries, to direct or cause the
direction of the management and policies of such entity, whether by
the ownership of fifty percent (50%) or more of the voting stock of
such entity, or by contract or otherwise. Notwithstanding the
foregoing, (i) neither the government of Japan, nor any entity
controlled by the government of Japan, shall be deemed to be an
Affiliate of Collaborator, and (ii) TAP Pharmaceutical
Products Inc. shall not be deemed to be an Affiliate of
Collaborator.
1.2
“Affymax House
Marks” means the
Affymax names and logo as set forth in Exhibit A.
1.3
“Affymax
Know-How” means all
Information that is Controlled by Affymax or its Affiliates during
the Term and is necessary or useful for the Development,
manufacture and/or Commercialization of the Product. For
clarity, Affymax Know-How excludes the Affymax Patents.
[ * ] = 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 Act of 1933, as
amended.
2
1.4
“Affymax
Patent” means any
Patent, including any Joint Patent, that (a) is Controlled by
Affymax or its Affiliates at any time during the Term, and
(b) claims the Peptide, [ * ] , Hematide, Product or
their manufacture or use or any other invention that is otherwise
necessary or useful for the Development, Finished Manufacture
and/or Commercialization of the Product hereunder. The list of
Affymax Patent as of the Effective Date is attached hereto as
Exhibit B, and shall be from time to time amended during the
Term to incorporate the then current Affymax Patents.
1.5
“Affymax
Technology” means
the Affymax Patent and Affymax Know-How.
1.6
“Affymax
Territory” means
worldwide except Japan, its territories and possessions.
1.7
“Alternative
ESA” means any
peptide-based synthetic [ * ] ESA other than Hematide,
including any such ESA comprised of (i) the Peptide alone,
(ii) some peptide(s) other than the Peptide,
(iii) the Peptide linked to a chemical moiety other than the
Reagent(s) by any means, or (iv) some
peptide(s) other than the Peptide linked to any chemical
moiety(ies) by any means.
1.8
“Backup
Product” means any
product(s) Controlled by Affymax or its Affiliates, the active
therapeutic ingredient(s) of which are Alternative
ESAs.
1.9
“Bulk
Hematide” means the
active pharmaceutical ingredient (API) for Hematide, in bulk
form.
1.10
“Claims”
has the meaning set forth in
Section 11.1.
1.11
“CTA”
means an application for clinical
trial authorization filed with a Regulatory Authority in the
Licensed Territory to undertake clinical trials of an
investigational new drug, the filing of which is necessary to
commence or conduct clinical testing of a pharmaceutical product in
humans in the Licensed Territory.
[ * ] = 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 Act of 1933, as
amended.
3
1.12
“Collaborator
Know-How” means all
Information that is Controlled by Collaborator or its Affiliates
during the Term under this Agreement and is necessary or useful for
the Development, manufacture or Commercialization of the
Product. For clarity, Collaboration Know-How excludes
Collaborator Patents.
1.13
“Collaborator
Patent” means any
Patent, including any Joint Patent, that (a) is Controlled by
Collaborator or its Affiliates at any time during the Term under
this Agreement, and (b) claims the Peptide, [ * ] ,
Bulk Hematide and/or Product or any method or composition, or the
manufacture or use, of the Peptide, [ * ], Bulk Hematide and/or
Product.
1.14
“Collaborator
Technology” means
the Collaborator Patents and Collaborator Know-How.
1.15
“Commercialization”
, with a correlative meaning for
“Commercialize” , means all activities
undertaken before and after obtaining Regulatory Approval relating
specifically to the pre-launch, launch, promotion, marketing, sale,
and distribution of a pharmaceutical product, including:
(a) strategic marketing, sales force detailing, advertising,
medical education and liaison, and market and product support; and
(b) any Phase IV Clinical Trials, and (c) all customer
support and Product distribution, invoicing and sales
activities.
1.16
“Confidential
Information” means,
with respect to a Party, all confidential Information of such Party
that is disclosed to the other Party under this Agreement, which
may include specifications, know-how, trade secrets, legal
information, technical information, drawings, models, business
information, inventions, discoveries, methods, procedures,
formulae, protocols, techniques, data, and unpublished patent
applications, whether disclosed in oral, written, graphic, or
electronic form. All confidential Information disclosed by
either Party pursuant to the Mutual Confidential Disclosure
Agreement between the Parties dated September 30, 2005 shall
be deemed to be such Party’s Confidential Information
disclosed hereunder.
1.17
“Control”
means, with respect to any material,
Information, or intellectual property right, that a Party owns or
has a license to such material, Information, or intellectual
property right and has the ability to grant to the other Party
access, a license, or a sublicense (as
[ * ] = 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 Act of 1933, as
amended.
4
applicable) to such material, Information, or
intellectual property right on the terms and conditions set forth
herein without violating the terms of any agreement or other
arrangement with any Third Party existing at the time such Party
would be first required hereunder to grant to the other Party such
access, license, or sublicense.
1.18
“Develop” or
“Development” means all activities relating to preparing and
conducting preclinical testing, toxicology testing, human clinical
studies, regulatory affairs, formulation development, process
development for Finished Manufacture and associated validation,
quality assurance and quality control activities. Development
shall exclude all Phase IV Clinical Trials.
1.19
“Development
Plan” means the
plan for conducting Development of the Product to be Commercialized
by Collaborator in the Licensed Territory, as set forth in
Section 3.2.
1.20
“Diligent
Efforts” means,
with respect to a Party’s obligation under this Agreement to
Develop or Commercialize a Product, the level of efforts required
to carry out such obligation in a sustained manner consistent with
the efforts a similarly situated biopharmaceutical company (in the
case of Affymax) or pharmaceutical company (in the case of
Collaborator) devotes to a product of similar market potential,
profit potential or strategic value within its portfolio,
based on conditions then prevailing. Diligent Efforts
requires, with respect to such an obligation, that the Party:
(a) promptly assign responsibility for such obligation to
specific employee(s) who are held accountable for progress and
monitor such progress on an on-going basis, (b) set and
consistently seek to achieve specific, meaningful and measurable
objectives for carrying out such obligation, and
(c) consistently make and implement decisions and allocate
resources designed to advance progress with respect to such
objectives.
1.21
“ [ * ] ” means Affymax’s
proprietary ESA peptide [ * ] [ * ] with the chemical
structure attached hereto as Exhibit C.
1.22
“Dollar”
means a U.S. dollar, and
“$” shall be interpreted accordingly.
1.23
“EMEA”
means the European Agency for the
Evaluation of Medicinal Products, or any successor thereto, which
is responsible for coordinating the centralized system
for
[ * ] = 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 Act of 1933, as
amended.
5
Regulatory Approval of pharmaceutical products
in the European Union and the European Economic Area and
recommending to the European Commission (the
“EC” ) that the EC grant Regulatory Approval of
certain pharmaceutical products in the EU and EEA under such
centralized system.
1.24
“ESA”
means erythropoiesis stimulating
agent.
1.25
“FDA”
means the U.S. Food and Drug
Administration or its successor.
1.26
“FD&C
Act” means the U.S.
Federal Food, Drug and Cosmetic Act, as amended.
1.27
“Field”
means the prevention, treatment or
amelioration of anemia in humans, including the Renal Indications
and the Oncology Indications.
1.28
“Finished
Manufacture” means
the manufacture of Finished Product from Bulk Hematide.
1.29
“Finished
Product” means the
Product containing Hematide that has been filled into vials,
syringes or manufactured into other pharmaceutical presentations,
finished and labeled for use in clinical trials or for commercial
purposes in accordance with the applicable specifications and legal
requirements.
1.30
“First Commercial
Sale” means the
first sale to a Third Party of a Product in the Licensed Territory
after Regulatory Approval has been obtained in the Licensed
Territory.
1.31
“Formulation
Technology” means
any technology useful to facilitate delivery of therapeutic
compounds, or that is useful to optimize the absorption or
distribution of therapeutic compounds in the body, but that is not
itself a therapeutic compound; provided that Formulation Technology
shall exclude any technology that comprises a chemical modification
of the Peptide, [ * ] or Hematide.
1.32
“Good Clinical
Practices” or “GCP” means the then-current good clinical practice
standards, practices and procedures promulgated or endorsed by the
Regulatory
[ * ] = 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 Act of 1933, as
amended.
6
Authority in the Licensed Territory as set forth
in the guidelines including related regulatory requirements imposed
by such Regulatory Authority, as they may be updated from time to
time.
1.33
“Good Laboratory
Practices” or “GLP” means the then-current good laboratory practice
standards promulgated or endorsed by the Regulatory Authority in
the Licensed Territory, as they may be updated from time to
time.
1.34
“Good Manufacturing
Practices” or “GMP” means the then-current good manufacturing
practices required by the Regulatory Authority in the Licensed
Territory or, solely for purposes of Affymax’s obligations
under Sections 1.45 and 10.2(d), by the FDA and by the guideline
promulgated by the International Conference on Harmonization
designated ICH Q7A, entitled “Q7A Good Manufacturing Practice
Guidance for Active Pharmaceutical Ingredients” and the
regulations promulgated thereunder, at least until and unless
otherwise agreed by the Parties in the quality agreement entered
into pursuant to Section 7.8, for the manufacture and testing
of pharmaceutical materials, as they may be updated from time to
time.
1.35
“Governmental
Authority” means
any multi-national, federal, state, local, municipal or other
government authority of any nature (including any governmental
division, subdivision, department, agency, bureau, branch, office,
commission, council, court or other tribunal).
1.36
“Hematide”
means Affymax’s proprietary
pegylated ESA drug candidate referred to internally as [ * ]
, consisting of the [ * ] attached to the Reagent.
1.37
“IND”
means (a) an Investigational
New Drug Application as defined in the applicable regulations
promulgated by the Regulatory Authority in the Licensed Territory,
the filing of which is necessary to commence or conduct clinical
testing of a pharmaceutical product in humans in the Licensed
Territory.
1.38
“Information”
means any data, results, technology,
business information, and information of any type whatsoever, in
any tangible or intangible form, including, without limitation,
know-how, trade secrets, practices, techniques, methods, processes,
inventions, developments, specifications, formulations, formulae,
materials or compositions of matter of any
[ * ] = 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 Act of 1933, as
amended.
7
type or kind (patentable or otherwise),
software, algorithms, marketing reports, expertise, technology,
test data (including pharmacological, biological, chemical,
biochemical, toxicological, preclinical and clinical test data),
analytical and quality control data, stability data, other study
data and procedures.
1.39
“Initial
Indications” means
the Renal Indications and/or the Oncology Indications.
1.40
“Joint
Committee” means
the committee formed by the Parties as described in
Section 2.1(a).
1.41
“Joint
Inventions” has the
meaning set forth in Section 9.1.
1.42
“Joint
Patent” has the
meaning set forth in Section 9.3(c).
1.43
“Laws”
means all relevant laws, statutes,
rules, regulations, guidelines, ordinances and other pronouncements
having the effect of law of any federal, national, multinational,
state, provincial, county, city or other political subdivision,
domestic or foreign.
1.44
“Licensed
Territory” means
Japan, including its territories and possessions.
1.45
“Manufacturing
Costs” (“MC”) means:
(a)
With respect to Bulk Hematide
supplied to Affymax by its Third Party contract manufacturer(s),
Manufacturing Costs shall mean the sum of (i) all amounts of
all payments that Affymax makes to such Third Party contract
manufacturer(s) for supply and delivery to Collaborator
(either directly, or first to Affymax for subsequent delivery to
Collaborator) of such Bulk Hematide, plus all payments made to
third party contractors for release and batch stability testing
services for Bulk Hematide, and (ii) any Overhead Costs
incurred in, and reasonably allocable to, the procurement of Bulk
Hematide supplied to Affymax and supplied to Collaborator. As
used herein “Overhead Costs” means direct and indirect
logistics, quality control, quality assurance, support and
management costs incurred in support of the Third Party contract
manufacturer by Affymax and shall be subject to the
reasonable
[ * ] = 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 Act of 1933, as
amended.
8
approval of Collaborator. Further, such
methodology shall be consistent with U.S. Generally Accepted
Accounting Principles and Affymax’s methodology for other
products and shall be consistent from year-to-year ; and
(b)
With respect to Bulk Hematide
manufactured by Affymax and supplied to Collaborator , if any,
Manufacturing Costs shall mean Direct Expenses, Indirect Expenses
and Overhead Costs incurred in, and reasonably allocable to, the
manufacture of such Bulk Hematide. As used
herein:
(i)
“ Direct Expenses
” are those material and labor and services expenses captured
in time sheets, invoices, and the like which are specifically
attributable to manufacture of the Bulk Hematide supplied to
Collaborator, including costs of raw materials, manufacturing
supplies, solvents, containers, container components, packaging,
labels and other printed materials used in production. Direct
labor expenses include salaries and fringe benefits for personnel
directly involved in manufacturing Bulk Hematide in accordance with
cGMP requirements such as production, quality control, quality
assurance, microbiology, and other similar departments as needed
who participate directly in the production of Bulk Hematide and
components thereof. Direct services expenses include
reasonable out of pocket payments to Third Parties for services
related to the manufacture of Bulk Hematide or components
thereof.
(ii)
“ Indirect Expenses
” include production indirect costs such as a reasonable
allocation of expenses associated with Affymax personnel supporting
the direct manufacturing of Bulk Hematide in accordance with cGMP
requirements. Indirect Expenses can include labor for and
indirect costs of quality control, quality assurance, raw material
acquisition and acceptance, microbiology, document control,
calibration/validation, and non-R&D expenses for process
development and analytical methods development, and shall not
include any Direct Expenses.
(iii)
“ Overhead Costs
” are direct and indirect manufacturing costs that cannot be
identified in a practical manner with specific units of production
and, therefore, cannot be included in MC as Direct Expenses or
Indirect Expenses. The methodology to be used in making the
allocations for Overhead Costs shall be proposed by Affymax and
shall be subject to
[ * ] = 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 Act of 1933, as
amended.
9
the reasonable approval of Collaborator. Further
such methodology shall be consistent with U.S. Generally Accepted
Accounting Principles and Affymax’s methodology for other
products and shall be consistent from year-to-year.
For avoidance of doubt, any given
cost included in Manufacturing Costs shall not be included more
than once in any calculation described herein.
1.46
“Marketing Authorization
Application” or “MAA” means an application for Regulatory Approval
(but excluding Pricing Approval) in the Licensed
Territory.
1.47
“MHLW”
means the Ministry of Health, Labor
and Welfare, otherwise referred to as “Korosho”
or any successor thereto, which govern the scientific review of
human pharmaceutical products in Japan.
1.48
“Net
Sales” means, with
respect to a particular time period, the total amounts billed by
Collaborator, its Affiliates and their respective sublicensees for
sales of Finished Products made during such time period to
unaffiliated Third Parties, less the following deductions to the
extent actually allowed or incurred with respect to such
sales:
(a)
discounts, including cash and
quantity discounts, charge-back payments, and rebates actually
granted to trade customers, managed health care organizations,
federal, state, or local government and the agencies, purchasers
and reimbursers of managed health organizations or federal, state
or local government, including without limitation, any reasonable
inventory compensation due to Yakka revision, and contribution for
Drug Induced Suffering and Contribution for Measure for Drug Safety
(as required by Law or applicable Regulatory Authorities), in the
amount determined by the Pharmaceuticals and Medical Devices Agency
(so-called “KIKO”) in Japan, with the aggregate of such
discounts not to exceed [ * ] of the amounts billed;
provided, however, that if such limit is not sufficient or
appropriate for adequately maintaining the competitive position of
Products in the Licensed Territory, the Parties shall confer in
good faith regarding whether any increase in such limit is
appropriate under the circumstances;
[ * ] = 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 Act of 1933, as
amended.
10
(b)
credits or allowances actually
granted upon claims, damaged goods, rejections or returns of such
Finished Products, including in connection with recalls;
(c)
freight, postage, shipping,
transportation and insurance charges actually allowed or paid for
delivery of Finished Products, to the extent billed; and
(d)
taxes (other than income taxes),
duties, tariffs or other governmental charges levied on the sale of
such Products, including, without limitation, value-added taxes,
net of all reimbursements and allowances.
Notwithstanding the foregoing,
amounts billed by Collaborator, its Affiliates, or their respective
sublicensees for the sale of Finished Products among Collaborator,
its Affiliates or their respective sublicensees for resale shall
not be included in the computation of Net Sales hereunder.
Net Sales shall be accounted for in accordance with generally
accepted accounting principles as practiced internationally,
consistently applied. Net Sales shall exclude any samples of
Product transferred or disposed of at no cost for promotional or
educational purposes.
Further, the Parties agree to negotiate in good
faith for an equitable determination of the Net Sales of the
Product in the event Collaborator sells the Product in such a
manner that gross sales of the Product are not readily identifiable
(e.g., for Products to be sold as a combination product or bundling
with other products.)
1.49
“Oncology
Indications” means
use of the Product for the prevention, treatment or amelioration of
anemia in patients with cancer.
1.50
“Patents”
means (a) pending patent
applications, including provisional patents, issued patents,
utility models and designs; and (b) extensions, reissues,
substitutions, confirmations, registrations, validations,
re-examinations, additions, continuations, continued prosecution
applications, requests for continued examination,
continuations-in-part, or divisions of or to any patents, patent
applications, utility models or designs.
[ * ] = 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 Act of 1933, as
amended.
11
1.51
“Patent Term
Extension” means
any term extensions, supplementary protection certificates and
equivalents thereof offering patent protection beyond the initial
term with respect to any issued patents.
1.52
“Peptide”
means that certain peptide ESA known
as [ * ] , the chemical structure of which is attached
hereto as Exhibit D.
1.53
“Phase I Clinical
Trial” means a
small scale trial of a pharmaceutical product on subjects that
generally provides for the first introduction into humans of such
product with the primary purpose of determining safety, metabolism
and pharmacokinetic properties and clinical pharmacology of such
product.
1.54
“Phase II Clinical
Trial” means a
small scale clinical trial of a pharmaceutical product on patients,
including possibly pharmacokinetic studies, the principal purposes
of which are to make a preliminary determination that such product
is safe for its intended use and to obtain sufficient information
about such product’s efficacy to permit the design of further
clinical trials.
1.55
“Phase III Clinical
Trial” means one or
more clinical trials on sufficient numbers of patients, which
trial(s) are designed to (a) establish that a drug is
safe and efficacious for its intended use; (b) define
warnings, precautions and adverse reactions that are associated
with the drug in the dosage range to be prescribed; and
(c) support Regulatory Approval of such drug.
1.56
“Phase IIIB Clinical
Trial” means a
Phase III Clinical Trial, possibly including pharmacokinetic
studies, commenced prior to receipt of Regulatory Approval in the
jurisdiction for which such trials are being conducted, but which
is not required in order to obtain Regulatory Approval and which is
conducted primarily for the purpose of Product support (e.g.,
providing additional drug profile and safety data or supporting
expansion of the Product Labeling).
1.57
“Phase IV Clinical
Trial” means a
clinical trial of a Product conducted after Regulatory Approval of
such Product has been obtained from an appropriate Regulatory
Authority, which trial is (a) conducted voluntarily by a Party
to enhance marketing or scientific
[ * ] = 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 Act of 1933, as
amended.
12
knowledge of the Product (e.g., for expansion of
Product Labeling and dose optimization), or (b) conducted due
to a request or requirement of a Regulatory Authority.
1.58
“Pricing
Approval” means
such approval, agreement, determination or governmental decision
establishing prices (i.e., Yakka) for the Product that can be
charged to consumers and will be reimbursed by Governmental
Authorities in the Licensed Territory.
1.59
“Product”
means a pharmaceutical preparation
in any formulation that contains Hematide as an active
ingredient.
1.60
“Product
Complaint” means
any written, verbal or electronic expression of dissatisfaction
regarding the Product, including without limitation reports of
actual or suspected product tampering, contamination, mislabeling
or inclusion of improper ingredients.
1.61
“Product
Infringement” has
the meaning set forth in Section 9.5(b).
1.62
“Product
Labeling” means
(a) the full prescribing information for the Product approved
by the applicable Regulatory Authority, and (b) all labels and
other written, printed or graphic information included in or placed
upon any container, wrapper or package insert used with or for the
Product.
1.63
“Promotional
Materials” means
all sales representative training materials and all written,
printed, graphic, electronic, audio or video presentations of
information, including, without limitation, journal advertisements,
sales visual aids, formulary binders, reprints, direct mail,
direct-to-consumer advertising, internet postings, broadcast
advertisements and sales reminder aides (for example, note pads,
pens and other such items) intended for use or used by Collaborator
or its Affiliates, sublicensees or licensees in connection with any
promotion of a Product in the Licensed Territory (all to the extent
applicable for the Commercialization in the Licensed Territory),
but excluding Product Labeling.
1.64
“Reagent”
means the reagent described in
Exhibit E.
[ * ] = 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 Act of 1933, as
amended.
13
1.65
“Regulatory
Approvals” means
all approvals (including without limitation supplements,
amendments, and Price Approvals), licenses, registrations or
authorizations of any national, supra-national, regional, state or
local regulatory agency, department, bureau, commission, council or
other governmental entity, necessary for the manufacture,
distribution, use or sale of a pharmaceutical product in the
Licensed Territory.
1.66
“Regulatory
Authority” means,
in a particular country or jurisdiction, any applicable
Governmental Authority involved in granting Regulatory Approval in
such country or jurisdiction, including without limitation,
(a) in the U.S., the FDA and any other applicable Governmental
Authority in the U.S. having jurisdiction over the Product, and
(b) the MHLW.
1.67
“Regulatory
Exclusivity” means
any exclusive marketing rights or data exclusivity rights conferred
by any Governmental Authority with respect to the Product other
than a patent right in the Licensed Territory.
1.68
“Regulatory
Materials” means
regulatory applications, submissions, notifications, registrations,
Regulatory Approvals and/or other filings made to or with a
Regulatory Authority that are necessary or reasonably desirable in
order to develop, manufacture, market, sell or otherwise
commercialize Products in a particular country, territory or
possession. Regulatory Materials include, without limitation,
INDs, CTAs, MAAs, and applications for Pricing
Approvals.
1.69
“Renal
Indications” means
the use of the Product in the prevention, treatment or amelioration
of anemia in patients with chronic kidney disease, whether or not
on dialysis.
1.70
“Required Third Party
Data” has the
meaning set forth in Section 4.1(b).
1.71
“Sole
Inventions” has the
meaning set forth in Section 9.1.
1.72
“Stock Purchase
Agreement” shall
mean that certain Stock Purchase Agreement to be entered into by
and between Collaborator and Affymax pursuant to
Section 8.1(b), for the purchase by Collaborator of Preferred
Stock of Affymax.
[ * ] = 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 Act of 1933, as
amended.
14
1.73
“Term”
means the term of this Agreement, as
determined in accordance with Article 13.
1.74
“Territory” means the Affymax Territory or the Licensed
Territory, as applicable.
1.75
“Third
Indication” means
indications other than the Initial Indications.
1.76
“Third
Party” means any
entity other than Affymax or Collaborator or an Affiliate of either
of them.
1.77
“Third Party
Data” has the
meaning set forth in Section 4.1(a)(iv).
1.78
“Third Party License
Agreements” has the
meaning set forth in Section 6.7.
1.79
“Third Party
Partner” shall have
the definition ascribed thereto in
Section 4.1(a)(iv).
1.80
“U.S.”
means the United States of America
and its possessions and territories.
1.81
“Valid
Claim” means
(a) an unexpired claim of an issued Patent that has not been
disclaimed, revoked or held to be invalid or unenforceable by a
court or other authority of competent jurisdiction, from which
decision no appeal can be further taken; or (b) a claim of a
pending Patent application.
1.82
“Yakka”
means the approval by the MHLW of
the National Health Insurance System (NHI) reimbursable price for
the Product in the Licensed Territory.
1.83
“Yen”
means a Japanese unit of currency,
and “¥” shall be interpreted
accordingly.
[ * ] = 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 Act of 1933, as
amended.
15
ARTICLE 2
MANAGEMENT
2.1
Joint Committee
.
(a)
Formation and Role.
The Parties hereby establish
a Joint Committee that shall monitor and coordinate communication
regarding the Parties’ performance under this Agreement to
Develop and obtain Regulatory Approval for the Product in the Field
and in the Licensed Territory. Each Party shall have an equal
number of representatives on the Joint Committee, who initially
shall be the individuals set forth in Exhibit F. The
Joint Committee shall have the membership and authority, and shall
operate by the procedures, set forth for it in this
Section 2.1 and in Section 2.2. The role of the
Joint Committee shall be:
(i)
to review the overall strategy for
seeking Regulatory Approval in the Licensed Territory of the
Product for the Initial Indications and any other indications in
the Field Collaborator seeks to develop the Product for;
(ii)
to facilitate the exchange of
information between the Parties with respect to the activities
hereunder for the Licensed Territory and to establish procedures
for the efficient sharing of information and materials necessary
for Collaborator’s Development of Products hereunder,
consistent with this Agreement;
(iii)
to review, approve, and, if
necessary, amend the Development Plan;
(iv)
to seek to resolve any issues
arising under this Agreement;
(v)
to monitor the Parties’
performance against each then-current Development Plan;
(vi)
to provide a forum to evaluate
strategies for obtaining, maintaining and enforcing patent and
trademark protection for Products in the Licensed Territory;
and
(vii)
to perform such other functions as
appropriate to further the purposes of this Agreement, as
determined by the Parties.
[ * ] = 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 Act of 1933, as
amended.
16
The Joint Committee shall perform
its responsibilities under this Agreement based on the principles
of prompt and diligent Development of Products in the Licensed
Territory, consistent with good pharmaceutical practices and the
maximization of long-term profits derived from the sale of Products
in the Licensed Territory. The Joint Committee shall have
only the powers assigned expressly to it in this Article 2 and
elsewhere in this Agreement, and the Joint Committee shall not have
any power to amend, modify or waive compliance with this
Agreement.
2.2
Joint Committee
Membership
Affymax and Collaborator shall each designate
three (3) representatives to serve on the Joint Committee by
written notices to the other Party. Either Party may
designate substitutes for its representatives if one (1) or
more of such Party’s designated representatives are unable to
be present at a meeting. From time to time each Party may
replace its representatives by written notice to the other Party
specifying the prior representative(s) and their
replacement(s). Any such substitutes or replacements shall be
designated consistent with the following principles: one
(1) representative shall have appropriate expertise in the
clinical Development of pharmaceutical products, and one
(1) representative shall have appropriate expertise in
Commercialization of pharmaceutical products; provided that
the Joint Committee may vary the expertise required for Joint
Committee representatives of each Party as it deems appropriate as
the Parties gain experience with Products, but in any event at
least one (1) of such representatives on the Joint Committee
shall be at the [ * ] in each of the Party’s
organizations. Collaborator shall select one (1) of its
representatives as the initial chairperson of the Joint
Committee. On each anniversary of the Effective Date, the
Parties shall rotate designation of the chairperson for the
commencing year. The chairperson shall be responsible for
(i) calling meetings, and (ii) preparing and circulating
an agenda for the upcoming meeting pursuant to Section 2.3(b),
but shall have no special authority over the other members of the
Joint Committee, and shall have no additional voting rights.
One of Collaborator’s Joint Committee representatives shall
be responsible for preparing and issuing minutes of each such
meeting within thirty (30) days thereafter. Such minutes
shall not be finalized until Affymax reviews and
[ * ] = 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 Act of 1933, as
amended.
17
confirms with Collaborator the accuracy of such
minutes in writing, which review by Affymax shall be completed
within thirty (30) days after the receipt of the
minutes.
2.3
Joint Committee Meetings and
Agendas .
(a)
Meetings. The Joint Committee shall hold at least two
(2) meetings per year on such dates at such times each year as
it elects. Meetings of the Joint Committee shall be effective
only if at least [ * ] representatives of each Party are
present or participating. The Joint Committee may meet either
(i) in person at either Party’s facilities or at such
locations as the Parties may otherwise agree; or (ii) by audio
or video teleconference. With the prior consent of each
Party’s representatives, other representatives of each Party
or Third Parties involved with the Products may attend meetings as
nonvoting participants. Additional meetings of the Joint
Committee may also be held with the consent of each Party, or as
required under this Agreement, and neither Party shall unreasonably
withhold or delay its consent to hold such an additional
meeting. Each Party shall be responsible for all of its own
expenses incurred in connection with participating in the Joint
Committee.
(b)
Meeting Agendas
. The chairperson of the Joint
Committee shall prepare a draft agenda containing the topics (i.e.,
Development and/or manufacturing issues) for the upcoming
meeting. The chairperson shall disclose to the other members
of the Joint Committee (i) the draft agenda no later than ten
(10) business days in advance, and (ii) its final agenda
(along with appropriate related Information) at least five
(5) business days in advance, of each meeting of the Joint
Committee; provided that under exigent circumstances
requiring Joint Committee input, the chairperson may provide the
draft and final agenda to the other members of the Joint Committee
with a lesser period of time in advance of the meeting, or may
propose that there not be a specific agenda for a particular
meeting, so long as such other Joint Committee members consent to
such temporary changes to the general process for distributing the
agenda for Joint Committee meetings.
[ * ] = 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 Act of 1933, as
amended.
18
2.4
Joint Committee Decisions and
Actions .
(a)
Decision Making.
Except as expressly provided
in this Section 2.4, actions to be taken by the Joint
Committee shall be taken only following unanimous vote, with each
Party having one (1) vote. If the Joint Committee fails
to reach unanimous agreement on a matter before it for decision for
a period in excess of ten (10) business days from the
discussion at the Joint Committee and unless the Parties agree to
prolong such time period, the matter shall be referred to the
senior executive officers of the Parties pursuant to
Section 14.2, except as otherwise provided in
Section 2.4(b) or 2.4(c).
(b)
Dispute.
If the members of the Joint
Committee cannot reach a unanimous decision with respect to matters
involving the [ * ] , [ * ] or the approval of any
component of an amended or updated Development Plan (a “
Dispute ”) within the time period set forth in above
subsection (a), such matter shall not be referred to the senior
executive officers of the Parties; rather, the final decision on
such Dispute shall be made by Collaborator, as and to the extent
set forth in this subsection 2.4(b), except if such matter is an
Excepted Development Matter.
(c)
Excepted Development Matters.
For the purpose of this Section 2.4, “Excepted
Development Matters” means the following:
(i)
altering the [ * ] to provide
for the Development of [ * ] other than the [ *
] ; and
(ii)
[ * ] for the Product [ * ] in accordance with
its protocol, as a consequence of [ * ] that are likely to
affect the [ * ] the Product or [ * ] affect the [
* ] for such Product [ * ] , other than for purposes of
[ * ] or pursuant to a requirement imposed by the Regulatory
Authorities in the Licensed Territory or the external monitoring
board for such trial;
(iii)
altering the [ * ] or
otherwise proposing to conduct or conducting any Development
activities in a manner that would reasonably be expected to [ *
]] development or commercialization efforts for Products in the
[ * ] , other than for purposes of [ * ] or pursuant
to a requirement imposed by the Regulatory Authorities in the
Licensed Territory or the external monitoring board for such
trial.
[ * ] = 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 Act of 1933, as
amended.
19
If a matter in dispute is an Excepted
Development Matter, such matter shall be referred to the senior
executive officers of the Parties pursuant to Section 2.4(a),
and where such senior executive officers cannot resolve any such
Excepted Development Matter referred to them, then the status quo
shall prevail (i.e., Collaborator shall not have the right to have
such alteration or amendment implemented or a [ * ] shall
not be [ * ] ), and Collaborator shall proceed with
Development under the then-existing Development Plan, provided,
however, in case of subsection (iii) above, Collaborator shall
not have the right to so alter the [ * ] or conduct such
Development activities.
2.5
Project Coordinators
. Promptly following the
Effective Date, each Party shall designate on Exhibit F an
appropriate expert to facilitate communication and coordination of
the Parties’ activities under this Agreement relating to
Products and to provide support and guidance to the Joint Committee
(each, a “ Project Coordinator ”). Each
Project Coordinator shall be experienced in project management and
may also serve as one of the three (3) representatives of its
respective Party on the Joint Committee. From time to time each
Party may replace its Project Coordinator by written notice to the
other Party specifying the replacement.
2.6
Collaboration
Guidelines . In all
matters relating to this Agreement, each Party shall seek to comply
with good pharmaceutical and environmental practices consistent
with the Laws and its own existing practices. Subject to the
terms of this Agreement, the activities and resources of each Party
shall be managed by such Party, acting independently and in its
individual capacity. The relationship between Affymax and
Collaborator is that of independent contractors and neither Party
shall have the power to bind or obligate the other Party in any
manner, other than as expressly set forth in this
Agreement.
ARTICLE 3
PRODUCT
DEVELOPMENT
3.1
Overview . Collaborator shall Develop Products in
the Licensed Territory as provided in this Article 3 and in
accordance with the Development Plan, which shall set forth all
Development activities to be performed by Collaborator under this
Agreement, including without
[ * ] = 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 Act of 1933, as
amended.
20
limitation such activities as may be required by
the Regulatory Authorities in the Licensed Territory for Regulatory
Approval of Products for use in the Initial Indications in the
Licensed Territory, and any additional activities necessary for any
Product to meet the requirements of the Japanese Pharmacopoeia or
any other listings that are necessary or helpful for obtaining
Price Approval for such Product in the Initial Indications in the
Licensed Territory (such additional activities, “ Required
Studies ”). Affymax shall complete all [ * ]
regarding the Product that are listed on Exhibit G, at its own
cost, risk and responsibility and shall provide Collaborator the
data obtained therein as provided in Section 4.1(a).
Collaborator shall bear all of the costs and expenses incurred in
connection with any of the activities performed by the Collaborator
pursuant to the Development Plan.
3.2
Development Plan
. An initial
Development Plan has been agreed upon by the Parties and is
attached hereto as Exhibit H and incorporated herein by
reference. From time to time, either Party may submit to the
Joint Committee for discussion any proposed modifications to the
Development Plan, and the Joint Committee shall discuss such
proposed modifications at its next meeting, and any such
modification may be approved by the Joint Committee as provided in
Section 2.4. The Development Plan shall, at all times,
contain the following information for the Product for both of the
Initial Indications in the Licensed Territory:
(a)
scope and timelines for
Collaborator’s performance of all studies (including any
Required Studies) designed to support Regulatory Approval of the
Product in the Licensed Territory, including without limitation,
clinical trial protocols, additional preclinical tests (including
any and all carcinogenicity and toxicology studies), Finished
Product stability studies, enrollment numbers and filing submission
dates;
(b)
estimated dates of meetings with
Regulatory Authorities in the Licensed Territory for such
Product;
(c)
Collaborator’s forecasts of
its needs for preclinical or clinical supply of such Product and/or
Bulk Hematide; and
(d)
target dates for achieving
milestones in Developing such Product.
[ * ] = 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 Act of 1933, as
amended.
21
3.3
Principles of Product
Development. Collaborator’s Development of the Product
in the Initial Indications in the Licensed Territory shall be
conducted in a manner consistent with the following
principles:
(a)
using Diligent Efforts to seek a
Regulatory Approval that includes a label for such Product as broad
as reasonably possible;
(b)
using Diligent Efforts to seek a
product profile for such Product with maximum scope of recommended
usage and minimum scope of restrictions on use, in each case to the
extent reasonably possible;
(c)
using Diligent Efforts to obtain
Regulatory Approval for such Product consistent with (a) and
(b) in a timely manner; and
(d)
using Diligent Efforts not to
unreasonably adversely impact Affymax’s or its Third Party
Partner’s own Development or Commercialization efforts for
Products in the Affymax Territory, including without limitation,
and where reasonably practicable, using and filing in the Licensed
Territory regulatory filings that are equivalent to all MAAs and
related filings for Products that are provided by Affymax pursuant
to Section 4.2, to ensure that all Collaborator’s
filings and specifications for Products in the Licensed Territory
remain consistent, as far as reasonable, with those for the
relevant Products in the Affymax Territory.
3.4
Collaborator’s
Performance .
Collaborator shall devote Diligent Efforts to the Development of
the Product in the Field and in the Licensed Territory, consistent
with the then-agreed Development Plan, and in accordance with this
Agreement, including without limitation by using Diligent Efforts
to perform its obligations under the Development Plan and in
accordance with the regulations promulgated by the MHLW for the
manufacture, testing and Commercialization of pharmaceutical
products in the Licensed Territory. Collaborator shall
provide financial and other support for the Development of the
Product as necessary to carry out the Development Plan and to
achieve the objectives of this Agreement. Collaborator shall
conduct its activities under the Development Plan in good
scientific manner and in compliance in all material respects with
all applicable Laws, including without limitation applicable GCP,
GLP,
[ * ] = 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 Act of 1933, as
amended.
22
and GMP. Collaborator may not conduct any
material Development activities with respect to any Product that
are not set forth in the Development Plan or that are inconsistent
with this Agreement without Affymax’s prior written
consent.
3.5
Records, Reports and
Information .
Collaborator shall maintain complete, current and
accurate records of all work conducted by it under the Development
Plan and all data and other Information resulting from such
work. Such records shall fully and properly reflect all work
done and results achieved in the performance of the Development
Plan in sufficient detail and in good scientific manner appropriate
for patent and regulatory purposes. Affymax shall have the
right to review such records maintained by Collaborator at
reasonable times, upon written request. Collaborator shall
provide written reports in English to the Joint Committee on its
Development and regulatory activities with Products in the Licensed
Territory, including without limitation any significant formal or
informal meetings between Collaborator and the Regulatory Authority
in the Licensed Territory, on a quarterly basis at the end of each
calendar quarter, at a level of detail reasonably sufficient to
enable Affymax to determine Collaborator’s compliance with
its diligence obligation pursuant to Section 3.4.
3.6
Right of First Refusal to Backup
Product Developed in the Field. If, during the ten (10) year period
following the Effective Date, Affymax or its Third Party Partner
develops a potential Backup Product(s) in the Field,
Collaborator shall have a right of first refusal to develop and
commercialize such Backup Product(s) for the Licensed
Territory as provided in this Section 3.6. Upon the
initiation of the first Phase II Clinical Trial for such Backup
Product(s) in the Field, and before offering to any Third
Party rights to such potential Backup Product(s) in the
Licensed Territory, Affymax shall notify Collaborator in writing,
and shall include in such notification all material results and
data with respect to such potential Backup Product(s), for
Collaborator’s evaluation. Collaborator shall treat such
results and data as Affymax’s Confidential Information under
this Agreement, and shall respond to Affymax within thirty (30)
days of receiving such notification whether it desires to exercise
its right to negotiate exclusively for the rights to Develop and
Commercialize such Backup Product(s) in the Field, in the
Licensed Territory. If Collaborator notifies Affymax within
such thirty (30) day period of its desire to obtain such rights,
then Affymax and Collaborator shall negotiate in good faith
for
[ * ] = 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 Act of 1933, as
amended.
23
ninety (90) days the terms and conditions under
which Collaborator may obtain such rights. If Collaborator
and Affymax enter into an agreement under which Collaborator
obtains such rights with respect to certain Backup Product, then
such Backup Product(s) shall also be licensed to Collaborator
under such agreed terms and conditions. If Collaborator fails
to notify Affymax of its desire to obtain such rights within such
thirty (30) day period, or if the Parties, despite good faith
negotiation, do not enter into an agreement governing the terms and
conditions under which Collaborator may obtain such rights from
Affymax within such ninety (90) day period, then, unless the
Parties agree to prolong such period, Affymax shall have the right
to pursue such opportunity itself or with an Affiliate or Third
Party without any further obligation to Collaborator.
This Section 3.6 shall apply on a Backup Product by Backup
Product basis. For clarity, if and as far as a Backup Product
is developed outside the Field by Affymax and/or its Third Party
Partner, then Collaborator shall have no rights under this
Section 3.6 with respect to such Backup Product.
ARTICLE 4
REGULATORY MATTERS
4.1
Transfer of Data and Regulatory
Materials .
(a)
Data Generated by
Affymax.
(i)
Within thirty (30) days after the
Effective Date, Affymax shall provide Collaborator with copies of
IND and CTA filings made for the Product in the U.S. and Europe
prior to the Effective Date. With regard to all other
preclinical and non-clinical data (including [ * ]
above-mentioned IND and CTA filings, in the form then existing)
generated as of the Effective Date and Controlled by Affymax,
Affymax shall, if requested by Collaborator, provide Collaborator
with copies thereof within a reasonable time after such request to
the extent relevant to the Development of Product or
Collaborator’s seeking Regulatory Approval for the Product in
the Licensed Territory. Thereafter, from time to time but in
a timely manner compliant with the requirements of the Regulatory
Authority in the Licensed Territory, Affymax shall provide
Collaborator with copies of [ * ] preclinical and
non-clinical data generated from
[ * ] = 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 Act of 1933, as
amended.
24
[ * ] the Effective Date by Affymax and Controlled by
Affymax. Collaborator shall have the full right, without any
additional consideration, to use any and all such data and reports
supplied by Affymax under this Section 4.1(a)(i) in
connection with the Development of the Product in the Licensed
Territory, including the incorporation of such data or reports in
any MAA.
(ii)
Within thirty (30) days after the
Effective Date, Affymax shall provide Collaborator with copies of
all clinical data resulting from [ * ] completed or ongoing
(where available) as of the Effective Date and Controlled by
Affymax. Thereafter, following completion of any additional
[ * ] ] conducted by Affymax with or without [ * ] ,
Affymax shall, in a timely manner compliant with the requirements
of the Regulatory Authority in the Licensed Territory, provide
Collaborator with copies of all resulting data, to the extent such
data is Controlled by Affymax. Collaborator shall have the full
right to use any and all such data and reports supplied by Affymax
pursuant to this Section 4.1(a)(ii) in connection with
the Development of the Product in the Licensed Territory, including
the incorporation of such data or reports in any MAA.
(iii)
With respect to clinical data
Controlled by Affymax and resulting from [ * ] completed or
ongoing as of the Effective Date, Affymax shall provide
Collaborator with copies of all resulting data upon request of
Collaborator after completion of such trial. It is understood
and agreed, however, that Collaborator shall have the right to use
any and all such data and reports supplied by Affymax hereunder
only to the extent that the Regulatory Authorities in the Licensed
Territory require that such data and or reports be submitted to it
to substantiate the clinical data generated by or on behalf of
Collaborator in seeking Regulatory Approval for the Product in the
Licensed Territory, either as part of the MAA or otherwise.
In no event shall Collaborator have the right to utilize such [
* ] data in its MAA for the Product in the Licensed Territory
in lieu of additional [ * ] data generated by or on behalf
of Collaborator in the Licensed Territory, without the written
consent of Affymax, which consent may be withheld in its sole
discretion, and which consent if given, shall require [ * ]
to Affymax for such use of such data.
[ * ] = 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 Act of 1933, as
amended.
25
(iv)
Collaborator acknowledges and
understands that Affymax intends to license the Product to one or
more Third Party licensees for development and commercialization in
the Affymax Territory (each, a “ Third Party Partner
”). Pursuant to any agreements between Affymax and its
Third Party Partner, Affymax and/or such Third Party Partners will
generate, at the expense primarily of such Third Party Partner,
additional non-clinical, preclinical and clinical data and reports
(including in particular [ * ] and [ * ] with respect
to the Product for use in seeking Regulatory Approval for the
Product in the Affymax Territory (the “ Third Party
Data ”). With respect to any Third Party Data Controlled
by Affymax [ * ] , Affymax shall provide Collaborator with
copies of all such Third Party Data upon request of Collaborator
unless (X) Affymax [ * ] and/or (Y) [ * ]
Third Party Partner in connection therewith. For any Third Party
Data to which (X) and/or (Y) applies, Collaborator shall
have the rights set forth in Section 4.1(b)(ii).
It is understood and agreed, however, that Collaborator shall have
the right to use any and all such Third Party Data and reports
supplied by Affymax under this Section 4.1(a)(iv) only to
the extent that the Regulatory Authorities in the Licensed
Territory require that such data be submitted to it to substantiate
the non-clinical, preclinical or clinical data generated by or on
behalf of Collaborator in seeking Regulatory Approval for the
Product in the Licensed Territory, either as part of the MAA or
otherwise. In no event shall Collaborator have the right to
utilize such Third Party Data provided pursuant to this
Section 4.1(a)(iv) in its MAA for the Product in the
Licensed Territory in lieu of additional non-clinical, pre-clinical
or clinical data generated by or on behalf of Collaborator in the
Licensed Territory, without the written consent of Affymax, which
consent may be withheld in its sole discretion, and which consent
if given, shall require [ * ] for such use of such data.
For clarity, this Section 4.1(a)(iv) shall
not apply to any audited data that Affymax may provide to
Collaborator pursuant to Section 4.1(b)(i).
(v)
With respect to any data generated
pursuant to any [ * ] that is commenced [ * ] by
Affymax other than [ * ] , to the extent such data is
Controlled by Affymax, Affymax shall provide Collaborator with
copies of all data arising from such trial upon request of
Collaborator, provided that the Parties have first agreed upon a
mutually acceptable [ * ] for
[ * ] = 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 Act of 1933, as
amended.
26
such use of such data; provided that information
regarding adverse events and serious adverse events shall be
provided promptly as set forth in Section 4.8.
(vi)
For clarity, the foregoing shall not
be deemed to limit the Parties’ obligations with respect to
information to be provided pursuant to Section 4.8.
Additionally, except as expressly provided in subsections
(iii) and (iv), Collaborator shall not be obligated [ *
] for the information, data and reports to be provided pursuant
to this Section 4.1(a).
(b)
Audited Data Generated by Third
Parties on Behalf of Affymax; Requests for Additional Data by
Collaborator.
(i)
Affymax understands and acknowledges
Collaborator’s need to utilize and include copies of certain
[ * ] and certain summary and general information regarding
the [ * ] of the Product that has been a