1
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EXHIBIT 10.51
AMENDMENT NUMBER TWO (2)
TO COOPERATIVE RESEARCH AND DEVELOPMENT
AGREEMENT AI-0062
This Amendment Number Two (2) to Cooperative Research and Development Agreement
("CRADA") AI-0062 between Aviron ("Collaborator") and the National Institute of
Allergy and Infectious Diseases ("NIAID"), will be effective as of the date of
the last duly authorized signature below. The CRADA, which is entitled
"Development of a Live, Attenuated Cold-Adapted Influenza Vaccine," was executed
on June 12, 1995 for a term of five (5) Years and was first amended on August 3,
1999.
The purposes of this second Amendment are to add clinical trial-related
provisions to the CRADA, to modify the Research Plan and budget to allow for
[***], and to extend the term of the CRADA for an additional three (3) Years to
allow [***] described in the modified Research Plan.
This Amendment is being executed in duplicate. The Collaborator shall retain one
original, and one original shall be retained by NIAID.
Except as herein amended, all of the other terms and conditions of the CRADA
shall remain in full force and effect.
Pursuant to Article 14.6 of the CRADA, both Parties do hereby amend the CRADA as
follows:
I. Extension of CRADA Term
In order to continue the clinical research program described in Appendix
B (Research Plan) of the CRADA as modified below, the term of the CRADA
is extended by three (3) years. The new expiration date for the CRADA
will be June 12, 2003.
II. Modifications to Appendix B (Research Plan)
Appendix B is amended by changing or adding the following for CRADA
Years 4 through 8:
A. Background
As stated in the original Research Plan, dated May 19, 1995, the
CRADA has been, and continues to be, undertaken to advance the
live attenuated, cold-adapted (ca) influenza vaccine system
("CAIV-T") to an FDA-approved vaccine for use [***]. To
accomplish this goal, it was felt, in 1995, that the NIH and the
Collaborator would need to show that the vaccine could be
consistently
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PAGE 1 OF 16 CONFIDENTIAL
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manufactured and remain safe after transfer to a new producer,
and that [***] envisioned was efficacious in the target
populations.
Clinical trials conducted under the CRADA since 1995, include
[***]. The original goals of the CRADA, i.e. to show consistent
manufacture and safety after transfer to a new producer, and
efficacy in a target population, [***]
B. Description of the Revised Clinical Research Program
This Research Plan describes a clinical research program that
includes, or will include the following studies:
[***]
[***]
[***]
[***]
[***]
[***]
C. Respective Contributions of the Parties
Changes in each Party's contributions to the clinical studies for
CRADA Years 6, 7 and 8 are as follows:
Enrollment of Subjects by DMID Contractors [***]
and Grantees
Operations Manual, Case Report Forms [***]
IND preparation and filing [***]
Data reports for regulatory filings [***]
(related
to IND
sponsor)
Supply of all vaccine for [***]
investigator-proposed trials
Special requirements of [***]
investigator-proposed trials
Monitoring of Study sites:
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PAGE 2 OF 16 CONFIDENTIAL
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Study #1 [(***)] [***]
Study #2 [(***)] [***]
Study #3 [(***)] [***]
Study #4 [(***)] [***]
Study #5 [(***)] [***]
Note: NIH is not required to produce the live virus challenge lots as
described in the original Research Plan.
III. Modifications to Appendix C (Financial and Staffing Contributions of the
Parties)
Appendix C is amended by changing the following for CRADA Years 1
through 5:
Item E. ("Contract support"), including accompanying footnote 2, of
Section III. entitled "Annual Collaborator Contributions (internal)" is
hereby deleted in its entirety.
Appendix C is amended by changing or adding the following for CRADA
Years 6, 7 and 8:
I. Annual NIH Institute (DMID, NIAID) Contributions (internal):
A. Supply funds: [$***]
B. Equipment funds: [$***] (photocopier and/or computer
equipment)
C. Time requirements of NIAID personnel: [***] FTE
Professional
[***] FTE
Administrative
D. Contract and Grant/Cooperative Agreement support provided
to Study site institutions by NIAID:
CONTRACTS ANNUAL BUDGET
--------- -------------
[***] $ [***]
[***] $ [***]
[***] $ [***]
[***] $ [***]
[***] $ [***]
[***] $ [***]
Sub-Total $* [***]*
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PAGE 3 OF 16 CONFIDENTIAL
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*Exact amounts spent at any one Contract site may vary from Year to Year
but the annual total Contract expenditure is expected to remain constant
at approximately 2.0 million U.S.
dollars per year.
COOPERATIVE AGREEMENT ANNUAL BUDGET
[***] $ [***]
Sub-Total $ [***]
Total NIAID Support $ [***]
II. Funds to be Provided to NIH (DMID, NIAID) by the Collaborator Annually:
A. Supply funds: [$***]
B. Equipment funds: [$***]
C. Travel funds: [$***]
travel to contract and cooperative
agreement sites travel to scientific
meetings travel to DSMB
D. Personnel funds: [$***]
[***]
E. Contract support: [$***]
F. Overhead: [$***]
Total: [$***]
No full-time permanent NIH employees will be supported by funds provided
by the Collaborator to NIH under this CRADA.
CRADA payment schedule and instructions:
1. Funds for CRADA Year 6 are due at NIAID on [***], which is
the [***]
2. Funds for subsequent CRADA Years are due at NIAID [***]
3. The Collaborator shall make CRADA checks payable to
"National Institute of Allergy and Infectious Diseases,"
shall reference the CRADA
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PAGE 4 OF 16 CONFIDENTIAL
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number (AI-0062) and the NTH CAN number (if known) on the
checks, and send them to NIAID as follows:
Office of Technology Development
National Institute of Allergy and Infectious
Diseases
National Institutes of Health
00 Xxxxxx Xxxxx, XXX 0000
Building 31, Room 3B62
Xxxxxxxx, XX 00000-0000
Attn: Director
4. The Collaborator authorizes NIAID to redistribute these
funds between categories to support the objectives of this
CRADA.
III. Annual Collaborator Contributions (internal): (All U.S. Dollars in
Thousands ($000))
Year 6 Year 7 Year 8
------ ------ ------
A. Supply funds: [$ *** *** ***
B. Equipment funds(1): $ *** *** ***
C. Travel funds: $*** *** ***
D. Time requirements of Company *** *** ***
personnel (approximate FTE
Requirements)
E. Monitoring Costs: $ *** *** ***]
Notes:
Internal contributions shown are estimated costs, dependent upon
trial scheduling, and not including costs relating to study drugs
provided by Collaborator.
IV. Modifications to the CRADA (Appendix D)
The Agreement is modified as follows:
A. The following twelve new provisions are added to Article 2:
--------
(1) Collaborator will provide sufficient support to fulfill its obligations
under the Research Plan.
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PAGE 5 OF 16 CONFIDENTIAL
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2.9 "ADVERSE DRUG EXPERIENCE" means an adverse clinical
experience as defined under 21 C.F.R. Section 310.305 or
Section 312.32 as applicable.
2.10 "ANNUAL REPORT" means the brief report of the progress of
an IND associated investigation that the IND sponsor is
required to submit to the FDA within sixty (60) days of
the anniversary date on which the IND went into effect
(pursuant to 21 C.F.R. Section 312.33).
2.11 "CLINICAL DATA AND RESEARCH RESULTS IN NIH'S POSSESSION
AND CONTROL" means all data obtained by NIH under
Contract(s) with Extramural Investigator(s) for completion
of Studies within the scope of the Protocol(s), and all
information and data in the NIH-sponsored INDs for the
Study Drug.
2.12 "CONTRACT" means a written funding agreement between the
Government and an eligible party ("the Contractor"), which
is subject to the Federal Acquisition Regulations, Title
48 CFR. For purposes of this CRADA, the term "Contract"
includes research and development Contracts, under which
the Contractor performs research and development work for
the Government with an expectation of the delivery to the
Government of a report, data, material(s) and/or other
product(s) resulting from the research and development
work.
2.13 "EXTRAMURAL INVESTIGATOR(s)" means the principal
investigator(s) who conduct(s) research under an
NIH-funded Contract, Grant or Cooperative Agreement.
2.14 "GRANT" means a financial assistance mechanism through
which the Government provides money, property, or both to
an eligible party to carry out a Government-approved
project or activity. A "Cooperative Agreement" is a type
of Grant in which there is substantial programmatic
involvement of the Government funding agency in the
project or activity.
2.15 "IND" means an Investigational New Drug Application
submitted to the FDA to receive approval to conduct
experimental clinical trials.
2.16 "INFLUENZA PROGRAM OFFICER" means the individual within
DMID who has primary responsibility for the research
activities of the DMID Influenza Program and all
administrative responsibility for that program's Grants
and Cooperative Agreements, and who serves as the liaison
between the Collaborator and the Project Officer and/or
the Extramural Investigator(s).
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PAGE 6 OF 16 CONFIDENTIAL
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2.17 "PROJECT OFFICER" means the individual within DMID whose
responsibilities include oversight of the Contract(s)
relevant to the research to be conducted under this CRADA.
2.18 "PROTOCOL(s)" means the Study protocols that are described
briefly in the Research Plan (Appendix B) and that are
incorporated herein by reference.
2.19 "STUDY(ies)" means the work performed by the Principal
Investigators and the Extramural Investigator(s) in
connection with the Protocol(s).
2.20 "STUDY DRUG" means [***]. The term also includes a
finished dosage form that does not contain an agent but is
intended to be used as a placebo, as stated in the
definition of "Drug product" at 21 C.F.R. Section
210.3(a)(4).
B. Article 3.5 is deleted in its entirety and replaced by the
following:
3.5 INVESTIGATIONAL NEW DRUG APPLICATIONS (INDS). The Parties
expect that either NIH or the Collaborator will submit an
IND that may cross-reference an IND sponsored by the
other. The Collaborator will supply all manufacturing
information required by the FDA in support of the INDs.
a. The Collaborator owns IND numbers [***] ("Aviron
INDs"). [***] The Collaborator shall allow NIH to
review, cross-reference or, as appropriate,
otherwise use those INDs for the conduct of
clinical trials involving the technology that is
the subject of this CRADA.
b. [***] NIH shall allow the Collaborator and those
corporate entities that Collaborator may from time
to time designate in writing to review, cross
reference or, as appropriate, otherwise use those
INDs for the conduct of clinical trials involving
the technology that is the subject of this CRADA,
and to fulfill all the requirements necessary to
obtain regulatory approval to market products that
incorporate the technology that is the subject of
this CRADA and to use in patent applications
covering the technology. Subject to Article 9.8 and
to the extent permitted by law, NIH shall make
available [***]
c. Both Parties shall keep the information in these
INDs confidential in accordance with Article 9.
However, nothing in this Agreement shall prohibit
NIH or the Extramural Investigator(s) from
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PAGE 7 OF 16 CONFIDENTIAL
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publishing in accordance with NIH policy or submitting to
the U.S. or international patent offices [***]
C. The following five new provisions are added to Article 3:
3.6 PROTOCOL MODIFICATION. The Studies will be conducted in
strict accordance with the Protocol(s) and no changes in
the finalized Protocol(s) will be made unless mutually
agreed upon in advance by both Parties. If the appropriate
Institutional Review Board (IRB) [***] the Protocol(s) or
the informed consent form(s), both Parties agree to [***]
the Protocol(s) and/or informed consent form(s) as
appropriate.
3.7 DRUG INFORMATION AND SUPPLY. The Collaborator agrees to
provide to the Extramural Investigators, at time and in
quantities that are commercially reasonable, [***] in
sufficient quantity to complete the clinical trial
Protocol(s) funded by NIH. The Collaborator will provide
lot release documents to NIH for each lot of finished
Study Drug provided for clinical trials.
3.8 DRUG DELIVERY AND USAGE. The Collaborator shall ship the
Study Drug to the Study sites in appropriately marked
containers in accordance with the Code of Federal
Regulations.
3.9 PROTECTION OF HUMAN SUBJECTS. All human clinical trials
performed under this CRADA shall conform to the
appropriate federal laws including, but not limited to,
all applicable FDA regulations and DHHS regulations
relating to the protection of human subjects (see 45
C.F.R. Part 46). Additional information is available from
the NIH Office for Protection from Research Risks,
Telephone, 000-000 0000.
3.10 MONITORING. For each Study, responsibility for clinical
site monitoring and the quality assurance of all data will
be established prior to the start of the Study. Monitoring
shall be done in compliance with FDA Good Clinical
Practices Guidelines.
D. The following two sentences are added to the end of Article 4.1:
Copies of the Annual Reports and other pertinent IND data
(including, but not limited to, clinical brochure data, and
formulation and preclinical data, including toxicology findings)
will be exchanged by the Parties as they become available.
Exchange of copies of the Annual Reports will fulfill the
Parties' reporting requirements under this Article 4.1.
Article 4.1 now reads as follows:
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4.1 INTERIM REPORTS. The Parties shall exchange formal written
interim progress reports on a schedule agreed to by the
PIs, but at least within six (6) months after this CRADA
becomes effective and at least within every six (6) months
thereafter. Such reports shall set forth the technical
progress made, identifying such problems as may have been
encountered and establishing goals and objectives
requiring further effort. Copies of the Annual Reports and
other pertinent IND data (including, but not limited to,
clinical brochure data, and formulation and preclinical
data, including toxicology findings) will be exchanged by
the Parties as they become available. Exchange of copies
of the Annual Reports will fulfill the Parties' reporting
requirements under this Article 4.1.
E. The following new provision is added to Article 4:
4.3 ADVERSE DRUG EXPERIENCE REPORTING. In accordance with FDA
requirements, the Party that sponsors the IND (hereinafter
referred to as the "IND Sponsor"), shall establish and
maintain records and make reports to the FDA as required
by 21 C.F.R. Section 310.305 and 21 C.F.R. Section 312.32
as applicable. In the conduct of research under this
CRADA, the Parties also agree to adhere to specific NIH
and NIAID guidelines and policies for reporting Adverse
Drug Reporting, as specified in each Protocol. The IND
Sponsor agrees to provide to the other Party copies of all
Adverse Drug Experience reports concurrently with their
submission to the FDA, including copies of any warning
letters or other information affecting the safety and/or
well-being of human subjects in research conducted under
this CRADA.
F. Article 9.1 is deleted in its entirety and replaced by the
following:
9.1 RIGHT OF ACCESS. NIH and the Collaborator agree to
exchange all Clinical Data and Research Results, and Raw
Data produced in the course of research under this CRADA,
whether developed solely by NIH, jointly with the
Collaborator, or solely by the Collaborator. Tangible
research products developed under the CRADA will be shared
equally by the Parties to the CRADA unless other
disposition is agreed to by the Principal Investigators.
The Parties to the CRADA will be free to utilize Clinical
Data and Research Results and Raw Data for their own
purposes, consistent with their obligations under this
CRADA.
[***]
G. Article 9.2 is deleted in its entirety and replaced by the
following:
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9.2 OWNERSHIP OF AND ACCESS TO CLINICAL DATA AND RESEARCH
RESULTS. Subject to the requirements of Article 3.5 and
Article 9.1, the [***] The Collaborator's right of access
to data produced by Extramural Investigator(s) is set
forth in Article 9.8.
H. The seventh sentence of Article 9.3 is amended as follows:
Unless disclosure is otherwise mutually agreed upon, the Parties
to this CRADA agree to keep Clinical Data and Research Results in
NIH's Possession and Control, and Raw Data received by NIH
confidential, to the extent permitted by law, until published or
reasonable opportunity has been provided for publication, or
filing or publication of corresponding IP applications. (The
Parties mutually agree that Collaborator may share, Clinical Data
and Research Results, and Raw Data with regulatory agencies and,
under appropriate confidentiality agreements, its commercial
partners, advisory bodies and otherwise as necessary to exercise
its rights under Article 9.2, but shall not publish such
information in academic journals.)
Article 9.3 now reads as follows:
9.3 CONFIDENTIAL INFORMATION. Each Party agrees to limit its
disclosure of Confidential Information to [***], and shall
place a confidentiality notice on all such information.
Materials required for the RP may also be designated as
Confidential Information from the party receiving
Confidential Information. Each party receiving
Confidential Information from the other Party agrees that
any information so designated shall be used by it [***].
Any party may object to the designation of information as
Confidential Information by another Party and may decline
to accept such information. In addition to all other
information identified as Confidential Information as set
forth in Section 2.2 above, [***] may be designated as
Confidential Information when they are [***], and advance
designation of such data and product categories is set
forth in the Research Plan. The exchange of confidential
information, e.g., [***] should be similarly limited and
treated. Unless disclosure is otherwise mutually agreed
upon, the Parties to this CRADA agree to keep [***], to
the extent permitted by law, [***]. (The Parties
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mutually agree that Collaborator may [***] The use of
Confidential Information shall be governed by Sections 9.4
and 9.6 below. However, nothing contained herein shall be
deemed to [***] consistent with NIH policy. Information
provided to one or more third parties pursuant to
Confidential Disclosure Agreements in connection with
their determination of the desirability of entering into a
CRADA for [***] shall be maintained as Confidential
Information.
I. The following new provisions are added to Article 9:
9.8 EXTRAMURAL RESEARCH AND DATA. In pursuing the development
of the Study Drug under this CRADA, NIH may utilize
Extramural Investigator(s) for part or all of the
completion of the Protocol(s) through either Grants,
including Cooperative Agreements, or Contracts. However,
those Extramural Investigator(s) are not parties to this
CRADA, and this CRADA does [***],
a. To the extent permitted by law and subject to the
other provisions of Article 9 of this CRADA, NIH
shall [***] all Clinical Data and Research Results
[***] as Confidential Information, and make them
available [***] to the Collaborator for [***] and
for [***].
b. In the case of an Extramural Investigator(s) being
funded under a Contract, NIH shall [***] a Contract
for preclinical studies or clinical trials for the
development of the Study Drug unless the Extramural
Investigator(s) agree(s) to [***] and agrees to
[***] in accordance with Article 9.8(a) for [***]
and for [***].
c. In the case of an Extramural Investigator(s) being
funded under a Grant or Cooperative Agreement, NIH
shall [***] all Extramural
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PAGE 11 OF 16 CONFIDENTIAL
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Investigator(s) participating in the Studies
sponsored by NIH and using the Study Drug to [***]
with the Collaborator in providing [***]. However,
NIH's [***] will not constitute a [***] a Grant
award to the Extramural Investigator(s).
d. Collaborator acknowledges that NIH is [***] for
management of clinical trials at the Study site of
each Extramural Investigator, and NIH acknowledges
the [***] by Collaborator to [***] and agrees to
[***] Extramural Investigators to [***] to the
Collaborator as described in Article 9.8(c).
e. In seeking direct access to Raw Data, Clinical Data
and Research Results or any other information that
is in the possession of Extramural Investigator(s)
working with the Study Drug under the sponsorship
of NIH, the Collaborator shall first contact the
Influenza Program Officer, who currently is [***].
For efficiency, direct contact between Collaborator
and Extramural Investigators for certain types of
discussions may be arranged by the NIAID Influenza
Program Officer and Collaborator on a study by
study basis. Subsequent to authorization by DMID,
the Collaborator may directly contact the
Extramural Investigator(s). Costs associated with
providing Raw Data, Clinical Data and Research
Results or any other information to the
Collaborator in customized formats shall be borne
by the Collaborator.
f. The Collaborator's exclusive access under
subsection (a) above to Clinical Data and Research
Results in NIH's Possession and Control is
dependent, however, upon [***]. If the Collaborator
[***] without the transfer of its [***] to another
party within [***], NIH retains the right to make
the Clinical Data and Research Results in NIH's
Possession and Control available to another party.
9.9 MATERIAL TRANSFER AGREEMENTS BETWEEN COLLABORATOR AND
STUDY SITE INSTITUTIONS. The Parties acknowledge that
Collaborator requires that an appropriate Materials
Transfer Agreement (MTA) be in place and maintained with
each Study site institution for each shipment of Study
Drug provided as a condition of receipt and use by the
Extramural Investigator (to manage and protect, among
other matters, the intellectual
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and physical property rights of Collaborator in the Study
Drug). With respect to MTAs, the Parties agree as follows:
a. Collaborator acknowledges that NIH funds the Study
site institutions under Contracts or Cooperative
Agreements and is the IND Sponsor for certain of
the Protocols, and therefore the Study site
institutions have certain preexisting contractual
or other legal obligations to the NIH. NIH
acknowledges that Collaborator entered into certain
MTAs with Study site institutions. The Parties
collectively acknowledge that these agreements
[***]. Accordingly, in order to ensure that [***]
do not impede the progress of the Studies, [***].
As an example of the foregoing, [***]
b. For further shipments of Study Drug for which
Collaborator requires new MTAs, Collaborator shall
[***]
J. Article 11.2 is deleted in its entirety and replaced by the
following:
11.2 UNILATERAL TERMINATION. Either NIH or the Collaborator may
unilaterally terminate this entire CRADA at any time by
giving written notice at least six (6) months prior to the
desired termination date, and any rights accrued in
property, patents or other IP rights shall be disposed of
as provided in Article 11.1.
K. The following new provision is added to Article 11:
11.6 ALTERNATIVE SOURCES OF SUPPLY AND RESEARCH LICENSE IN THE
EVENT THE COLLABORATOR TERMINATES DEVELOPMENT OF THE STUDY
DRUG
a. If the Collaborator elects to terminate its
development of the Study Drug without the transfer
of its development efforts and obligations under
this CRADA to another party acceptable to NIH
within [***] of discontinuation, and NIH wishes to
continue its development of the Study Drug, then
the Collaborator shall:
(i) [***]; or
(ii) [***]
b. In the event that Collaborator provides written
notification that Collaborator is terminating
development of Study Drug, and only to the extent
permitted by the Materials Transfer and
Intellectual Property Agreement between Aviron and
the University of
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PAGE 13 OF 16 CONFIDENTIAL
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Michigan effective February 24, 1995 (redacted version
attached hereto as Exhibit I), the Collaborator [***]
L. The following three new provisions are added to Article 14:
14.13 FDA MEETINGS. All meetings with the FDA concerning
clinical studies for the development of the Study Drug
within the scope of the CRADA Research Plan will be
discussed by the Collaborator and NIH in advance and will
be held on mutually agreed upon dates. The Collaborator
reserves the right to set jointly with NIH the agenda for
any such meeting.
14.14 CONFLICTS. In the event of a conflict between the
Protocol(s) incorporated herein by reference and the other
provisions of this Agreement, the other provisions of this
Agreement shall prevail.
14.15 STATUTORY COMPLIANCE. NIH and the Collaborator agree to
conduct the Studies in accordance with the applicable
portions of the Federal Food, Drug, and Cosmetic Act, 21
U.S.C. Section 301 et. seq., and its implementing
regulations including FDA good clinical practices
guidelines and other applicable federal statutes and
regulations.
M. Article 15.2 is deleted in its entirety and replaced by the
following:
15.2 SURVIVABILITY. The provisions of Articles 3.5, 3.7, 4.2,
4.3, Articles 5-9, 11.3, 11.4, 11.5, 11.6, 12.1, 13.2,
13.3, 13.4, 14.1, 14.10 and 15.2 shall survive expiration
or earlier termination of this CRADA.
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SIGNATURES BEGIN ON NEXT PAGE
CONFIDENTIAL TREATMENT REQUESTED BY AVIRON
[***] - CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
[***], IS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES ACT OF 1934, AS AMENDED.
PAGE 15 OF 16 CONFIDENTIAL
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AMENDMENT NUMBER TWO (2) TO CRADA AI-0062
SIGNATURE PAGE
FOR NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES:
/s/ Xxxx X. XxXxxxxxxx, Ph.D. 6/12/00
-----------------------------------
Xxxx X. XxXxxxxxxx, Ph.D. Date
Deputy Director
Mailing Address for Notices:
Office of Technology Development
National Institute of Allergy and Infections Diseases
National Institutes of Health
Xxxxxxxx 00, Xxxx 0X00
00 Xxxxxx Xxxxx, XXX 0000
Xxxxxxxx, XX 00000-0000
(000) 000-0000/tel.
(000) 000-0000/fax
Attn: Director
FOR AVIRON:
/s/ X. Xxxx Xxxxxx Xxxx 6, 2000
-----------------------------------
C. Xxxx Xxxxxx Date
President and CEO
Mailing Address for Notices:
Aviron
000 Xxxxx Xxxxxxx Xxxxxx
Xxxxxxxx Xxxx, XX 00000
(000) 000-0000/tel.
(000) 000-0000/fax
CONFIDENTIAL TREATMENT REQUESTED BY AVIRON
[***] - CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
[***], IS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES ACT OF 1934, AS AMENDED.
PAGE 16 OF 16 CONFIDENTIAL
