EXHIBIT 10.62
Confidential Treatment Requested
Cooperative Research and
Development Agreement
(CRADA 02177)
Cooperative and Research Development Agreement for the
Development of Introgen Proprietary Vectors and
Recombinants for the Treatment of Cancer
Steven A. Rosenberg, M.D., Ph.D.
Surgery Branch
Center for Cancer Research
National Cancer Institute
Robert E. Sobol, M.D.
Introgen Therapeutics, Inc.
Prepared by
Technology Transfer Branch
National Cancer Institute

 

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PUBLIC HEALTH SERVICE
COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT
FOR INTRAMURAL-PHS CLINICAL RESEARCH
This Agreement is based on the model Cooperative Research and Development
Agreement (“CRADA”) adopted by the U.S. Public Health Service (“PHS”) Technology
Transfer Policy Board for use by components of the National Institutes of Health
(“NIH”), the Centers for Disease Control and Prevention (“CDC”), and the Food
and Drug Administration (“FDA”), which are agencies of the PHS within the
Department of Health and Human Services (“HHS”).
This Cover Page identifies the Parties to this CRADA:
The U.S. Department of Health and Human Services, as represented by
the National Cancer Institute
an Institute, Center, or Division (hereinafter referred to as the “ICD”) of the
National Institutes of Health
and
Introgen Therapeutics, Inc.,
hereinafter referred to as the “Collaborator”,
having offices at 2250 Holcombe Blvd. Houston, Texas 77030,
created and operating under the laws of Delaware.

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COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT
FOR INTRAMURAL-PHS CLINICAL RESEARCH
Article 1. Introduction
This CRADA between ICD and Collaborator will be effective when signed by the
Parties, which are identified on both the Cover Page and the Signature Page
(page 18). The official contacts for the Parties are identified on the Contacts
Information Page (page 19). Publicly available information regarding this CRADA
appears on the Summary Page (page 20). The research and development activities
that will be undertaken by ICD and Collaborator in the course of this CRADA are
detailed in the Research Plan, attached as Appendix A. The staffing, funding,
and materials contributions of the Parties are set forth in Appendix B. Any
changes to the model CRADA are set forth in Appendix C.
Article 2. Definitions
The terms listed in this Article will carry the meanings indicated throughout
the CRADA. To the extent a definition of a term as provided in this Article is
inconsistent with a corresponding definition in the applicable sections of
either the United States Code (U.S.C.) or the Code of Federal Regulations
(C.F.R.), the definition in the U.S.C. or C.F.R. will control.
“Adverse Drug Experience” or “ADE” means an Adverse Event associated with the
use of the Test Article, that is, an event where there is a reasonable
possibility that the Test Article may have caused the event (a relationship
between the Test Article and the event cannot be ruled out), in accordance with
the definitions of 21 C.F.R. Part 310, 305, or 312, or other applicable
regulations.
“Adverse Event” or “AE” means any untoward medical occurrence in a Human Subject
administered Test Article. An AE does not necessarily have a causal relationship
with the Test Article, that is, it can be any unfavorable and unintended sign
(including an abnormal laboratory finding), symptom, or disease temporally
associated with the use of the Test Article, whether or not it is related to it.
See FDA Good Clinical Practice Guideline (FDA GCP, from International Conference
on Harmonisation (ICH) E6: “Good Clinical Practice: Consolidated Guidance, 62
Federal Register 25, 691 (1997)).
“Affiliate” means any corporation or other business entity controlled by,
controlling, or under common control with Collaborator at any time during the
term of the CRADA. For this purpose, “control” means direct or indirect
beneficial ownership of at least fifty percent (50%) of the voting stock or at
least fifty percent (50%) interest in the income of the corporation or other
business entity.
“Annual Report” means the report of progress of an IND-associated investigation
that ICD, as the IND Sponsor, must submit to the FDA within sixty (60) days of
the anniversary of the effective date of the IND (pursuant to 21 C.F.R. §
312.33).
“Background Invention” means an Invention conceived and first actually reduced
to practice before the Effective Date.
“Clinical Investigator” means, in accordance with 21 C.F.R. § 312.3, an
individual who actually conducts a clinical investigation, that is, who directs
the administration or dispensation of Test Article to a subject, and who assumes
responsibility for studying Human Subjects, for recording

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and ensuring the integrity of research data, and for protecting the welfare and
safety of Human Subjects.
“Collaborator Materials” means all tangible materials not first produced in the
performance of this CRADA that are owned or controlled by Collaborator and used
in the performance of the Research Plan. The term “Collaborator Materials” does
not include “Test Article” (defined below).
“Confidential Information” means confidential scientific, business, or financial
information provided that the information does not include:

  (a)   information that is publicly known or that is available from public
sources;     (b)   information that has been made available by its owner to
others without a confidentiality obligation;     (c)   information that is
already known by the receiving Party, or information that is independently
created or compiled by the receiving Party without reference to or use of the
provided information; or     (d)   information that relates to potential hazards
or cautionary warnings associated with the production, handling, or use of the
subject matter of the Research Plan.

“Cooperative Research and Development Agreement” or “CRADA” means this
Agreement, entered into pursuant to the Federal Technology Transfer Act of 1986,
as amended (15 U.S.C. § 3710a et seq.), and Executive Order 12591 of April 10,
1987.
“CRADA Data” means all recorded information first produced in the performance of
the Research Plan.
“CRADA Materials” means all tangible materials first produced in the performance
of the Research Plan other than CRADA Data.
“CRADA Principal Investigator(s)” or “CRADA PI(s)” means the person(s)
designated by the Parties who will be responsible for the scientific and
technical conduct of the Research Plan.
      The CRADA PI may also be a Clinical Investigator.
“CRADA Subject Invention” means any Invention of either or both Parties,
conceived or first actually reduced to practice in the performance of the
Research Plan.
“Drug Master File” or “DMF” is described in 21 C.F.R. Part 314.420. A DMF is a
submission to the FDA that may be used to provide confidential detailed
information about facilities, processes, or articles used in the manufacturing,
processing, packaging, and storing of one or more human drugs.
“Effective Date” means the date of the last signature of the Parties executing
this Agreement.
“Government” means the Government of the United States of America.
“Human Subject” means, in accordance with the definition in 45 C.F.R. §
46.102(f), a living individual about whom an investigator conducting research
obtains:

  (a)   data through intervention or interaction with the individual; or     (b)
  Identifiable Private Information.

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“ICD Materials” means all tangible materials not first produced in the
performance of this CRADA that are owned or controlled by ICD and used in the
performance of the Research Plan.
“IND” means an “Investigational New Drug Application”, filed in accordance with
21 C.F.R. Part 312 under which clinical investigation of an experimental drug or
biologic (Test Article) is performed in Human Subjects in the United States or
intended to support a United States licensing action.
“Identifiable Private Information” or “IPI” about a Human Subject means private
information from which the identity of the subject is or may readily be
ascertained. Regulations defining and governing this information include 45
C.F.R. Part 46 and 21 C.F.R. Part 50.
“Institutional Review Board” or “IRB” means, in accordance with 45 C.F.R.
Part 46, 21 C.F.R. part 56, and other applicable regulations, an independent
body comprising medical, scientific, and nonscientific members, whose
responsibility is to ensure the protection of the rights, safety, and well-being
of the Human Subjects involved in a study.
“Invention” means any invention or discovery that is or may be patentable or
otherwise protected under Title 35 of the United States Code, or any novel
variety of plant which is or may be protectable under the Plant Variety
Protection Act, 7 U.S.C. §§ 2321 et seq.
“Investigator’s Brochure” means, in accordance with the definition in 21 C.F.R.
§ 312.23(a)(5), a document containing information about the Test Article,
including animal screening, preclinical toxicology, and detailed pharmaceutical
data, including a description of possible risks and side effects to be
anticipated on the basis of prior experience with the drug or related drugs, and
precautions, such as additional monitoring, to be taken as part of the
investigational use of the drug.
“Patent Application” means an application for patent protection for a CRADA
Subject Invention with the United States Patent and Trademark Office
(“U.S.P.T.O.”) or the corresponding patent issuing authority of another nation.
“Patent” means any issued United States patent, any international
counterpart(s), and any corresponding grant(s) by a non-U.S. government in place
of a patent.
“Placebo” means an inactive substance identical in appearance to the material
being tested that is used to distinguish between drug action and suggestive
effect of the material under study.
“Protocol” means the formal, detailed description of a study to be performed as
provided for in the Research Plan. It describes the objective(s), design,
methodology, statistical considerations, and organization of a trial. For the
purposes of this CRADA, the term, Protocol, for clinical research involving
Human Subjects, includes any and all associated documents, including informed
consent forms, to be provided to Human Subjects and potential participants in
the study.
“Raw Data” means the primary quantitative and empirical data first collected
from experiments and clinical trials conducted within the scope of this CRADA.
“Research Plan” means the statement in Appendix A of the respective research and
development commitments of the Parties. The Research Plan should describe the
provisions for sponsoring the IND, clinical and safety monitoring, and data
management.

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“Sponsor” means, in accordance with the definition in 21 C.F.R. § 312.3, an
organization or individual who assumes legal responsibility for supervising or
overseeing clinical trials with Test Articles, and is sometimes referred to as
the IND holder.
“Steering Committee” means the research and development team whose composition
and responsibilities with regard to the research performed under this CRADA are
described in Appendix A.
“Summary Data” means any extract or summary of the Raw Data, generated by, or on
behalf of, ICD or by, or on behalf of, Collaborator. Summary Data will not
include extracts or summaries that incorporate IPI.
“Test Article” means, in accordance with 21 C.F.R. 50.3 (j), any drug (including
a biological product), medical device, food additive, color additive, electronic
product, or any other Article subject to regulation under the Federal Food,
Drug, and Cosmetic Act that is intended for administration to humans or animals,
including a drug or biologic as identified in the Research Plan and Appendix B,
that is used within the scope of the Research Plan. The Test Article may also be
referred to as Investigational Agent, Study Material, or Study Product.
Article 3. Cooperative Research and Development
3.1 Performance of Research and Development. The research and development
activities to be carried out under this CRADA will be performed solely by the
Parties identified on the Cover Page, unless specifically stated elsewhere in
the Agreement. The CRADA PIs will be responsible for coordinating the scientific
and technical conduct of this project on behalf of their employers. Any
Collaborator employees who will work at ICD facilities will be required to sign
a Guest Researcher or Special Volunteer Agreement appropriately modified in view
of the terms of this CRADA.
3.2 Research Plan. The Parties recognize that the Research Plan describes the
collaborative research and development activities they will undertake and that
interim research goals set forth in the Research Plan are good faith guidelines.
Should events occur that require modification of these goals, then by mutual
agreement the Parties can modify them through an amendment, according to
Paragraph 13.6.
3.3 Use and Disposition of Collaborator Materials and ICD Materials. The Parties
agree to use Collaborator Materials and ICD Materials only in accordance with
the Research Plan and Protocol(s), not to transfer these materials to third
parties except in accordance with the Research Plan and Protocol(s) or as
approved by the owning or providing Party, and, upon expiration or termination
of the CRADA, to dispose of these materials as directed by the owning or
providing Party.
3.4 Third Party Rights in Collaborator’s CRADA Subject Inventions. If
Collaborator has received (or will receive) support of any kind from a third
party in exchange for rights in any of Collaborator’s CRADA Subject Inventions,
Collaborator agrees to ensure that its obligations to the third party are both
consistent with Articles 6-8 and subordinate to Article 7 of this CRADA.
3.5 Disclosures to ICD. Prior to execution of this CRADA, Collaborator agrees to
disclose to ICD all instances in which outstanding royalties are due under a PHS
license agreement and in which Collaborator had a PHS license terminated in
accordance with 37 C.F.R. § 404.9. These

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disclosures will be treated as Confidential Information upon request by
Collaborator in accordance with Paragraphs 2.4, 8.3, and 8.4.
3.6 Clinical Investigator Responsibilities. The Clinical Investigator will be
required to submit, or to arrange for submission of, each Protocol associated
with this CRADA to the IRB. In addition to the Protocol all associated
documents, including informational documents and advertisements, must be
reviewed and approved by the IRB before starting the research. The research will
be done in strict accordance with the Protocol(s) and no substantive changes in
a finalized Protocol will be made unless mutually agreed upon by the Parties.
Research will not commence (or will continue unchanged, if already in progress)
until each substantive change to a Protocol, including those required by either
the FDA or the IRB, has been integrated in a way acceptable to the Parties,
submitted to the FDA and approved by the IRB.
3.7 Investigational Applications.
3.7.1 If an IND is required, ICD will be the IND Sponsor and will submit an IND.
All Clinical Investigators must have completed registration documents on file
(1572 forms).
3.7.2 When ICD files the IND, Collaborator agrees to provide ICD background data
and information necessary to support the IND. Collaborator further agrees to
provide a letter of cross-reference to all pertinent regulatory filings
sponsored by Collaborator. Collaborator’s employees will be reasonably available
to respond to inquiries from the FDA regarding information and data contained in
the Collaborator’s IND, DMF, other filings, or other information and data
provided to ICD by the Collaborator pursuant to this Article 3.
3.7.3 If Collaborator supplies Confidential Information to ICD in support of an
IND filed by ICD, this information will be protected in accordance with the
corresponding confidentiality provisions of Article 8.
3.7.4 Collaborator may sponsor its own clinical trials and hold its own IND for
studies performed outside the scope of this CRADA. These studies, however,
should not adversely affect the ability to accomplish the goal of the Research
Plan, for example, by competing for the same study population. All data from
those clinical trials are proprietary to Collaborator for purposes of this
CRADA.
3.8 Test Article Information and Supply. Collaborator agrees to provide ICD
without charge and on a schedule that will ensure adequate and timely
performance of the research, a sufficient quantity of formulated and acceptably
labeled, clinical-grade Test Article (and, as required by the Protocol(s),
Placebo) to complete the clinical trial(s) agreed to and approved under this
CRADA. Collaborator will provide a Certificate of Analysis to ICD for each lot
of the Test Article provided.
3.9 Test Article Delivery and Usage. Collaborator will ship the Test Article
and, if required, Placebo to ICD in containers marked in accordance with 21
C.F.R. § 312.6. ICD agrees that the Clinical Investigators will keep appropriate
records and take reasonable steps to ensure that the Test Article is used in
accordance with the Protocol(s) and applicable FDA regulations. In addition, ICD
agrees that the Test Article (and all Confidential Information supplied by
Collaborator relating to the Test Article) will be used solely for the conduct
of the CRADA research and development activities. Furthermore, ICD agrees that
no analysis or modification of the Test Article will be performed without
Collaborator’s prior written consent. At the completion of the Research Plan,
any unused quantity of Test Article will be returned to Collaborator or disposed
as directed by Collaborator. Pharmacy contacts at ICD will be determined by ICD
and communicated to Collaborator.

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3.10 Monitoring. Subject to the restrictions in Article 8 concerning IPI, and
with reasonable advance notice and at reasonable times, ICD will permit
Collaborator or its designee(s) to monitor the conduct of the research, as well
as to audit source documents containing Raw Data, to the extent necessary to
verify compliance with FDA Good Clinical Practice (International Conference on
Harmonisation (ICH) E6: A Good Clinical Practice: Consolidated Guidance; 62
Federal Register 25, 691 (1997)) and the Protocol(s).
3.11 FDA Meetings/Communications. All meetings with the FDA concerning any
clinical trial within the scope of the Research Plan will be discussed by
Collaborator and ICD in advance. Each Party reserves the right to take part in
setting the agenda for, to attend, and to participate in these meetings. ICD
will provide Collaborator with copies of FDA meeting minutes, all transmittal
letters for IND submissions, IND safety reports, formal questions and responses
that have been submitted to the FDA, Annual Reports, and official FDA
correspondence, pertaining either to the INDs under this CRADA or to the
Clinical Investigators on Protocols performed in accordance with the Research
Plan, except to the extent that those documents contain the proprietary
information of a third party or dissemination is prohibited by law.
Article 4. Reports
4.1 Interim Research and Development Reports. The CRADA PIs should exchange
information regularly, in writing. This exchange may be accomplished through
meeting minutes, detailed correspondence, circulation of draft manuscripts,
Steering Committee reports, copies of Annual Reports and any other reports
updating the progress of the CRADA research. However, the Parties must exchange
updated Investigator’s Brochure, formulation and preclinical data, and
toxicology findings, as they become available.
4.2 Final Research and Development Reports. The Parties will exchange final
reports of their results within [*] after the expiration or termination of this
CRADA. These reports will set forth the technical progress made; any
publications arising from the research; and the existence of invention
disclosures of potential CRADA Subject Inventions and/or any corresponding
Patent Applications.
4.3 Fiscal Reports. If Collaborator has agreed to provide funding to ICD under
this CRADA and upon the request of Collaborator, then concurrent with the
exchange of final research and development reports according to Paragraph 4.2,
ICD will submit to Collaborator a statement of all costs incurred by ICD for the
CRADA. If the CRADA has been terminated, ICD will specify any costs incurred
before the date of termination for which ICD has not received funds from
Collaborator, as well as for all reasonable termination costs including the cost
of returning Collaborator property or removal of abandoned Collaborator
property, for which Collaborator will be responsible.
4.4 Safety Reports. In accordance with FDA requirements ICD, as the IND Sponsor,
will establish and maintain records and submit safety reports to the FDA, as
required by 21 C.F.R. § 312.32 and 21 C.F.R. 812.150(b)(1), or other applicable
regulations. In the conduct of research under this CRADA, the Parties will
comply with specific ICD guidelines and policies for reporting ADEs and AEs, as
well as procedures specified in the Protocol(s). ICD must provide Collaborator
with copies of all Safety Reports concurrently with their submission to the FDA,
and with any other information affecting the safety of Human Subjects in
research conducted under this CRADA.
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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4.5 Annual Reports. ICD will provide Collaborator a copy of the Annual Report
concurrently with the submission of the Annual Report to the FDA. Annual Reports
will be kept confidential in accordance with Article 8.
Article 5. Staffing, Financial, and Materials Obligations
5.1 ICD and Collaborator Contributions. The contributions of any staff, funds,
materials, and equipment by the Parties are set forth in Appendix B. The Federal
Technology Transfer Act of 1986, 15 U.S.C. § 3710a(d)(1) prohibits ICD from
providing funds to Collaborator for any research and development activities
under this CRADA.
5.2 ICD Staffing. No ICD employees will devote 100% of their effort or time to
the research and development activities under this CRADA. ICD will not use funds
provided by Collaborator under this CRADA for ICD personnel to pay the salary of
any permanent ICD employee. Although personnel hired by ICD using CRADA funds
will focus principally on CRADA research and development activities,
Collaborator acknowledges that these personnel may nonetheless make
contributions to other research and development activities, and the activities
will be outside the scope of this CRADA.
5.3 Collaborator Funding. Collaborator acknowledges that Government funds
received by Collaborator from an agency of the Department of Health and Human
Services may not be used to fund ICD under this CRADA. If Collaborator has
agreed to provide funds to ICD then the payment schedule appears in Appendix B
and Collaborator will make payments according to that schedule. If Collaborator
fails to make any scheduled payment, ICD will not be obligated to perform any of
the research and development activities specified herein or to take any other
action required by this CRADA until the funds are received. ICD will use these
funds exclusively for the purposes of this CRADA. Each Party will maintain
separate and distinct current accounts, records, and other evidence supporting
its financial obligations under this CRADA and, upon written request, will
provide the other Party a Fiscal Report according to Paragraph 4.3, which
delineates all payments made and all obligated expenses, along with the Final
Research Report described in Paragraph 4.2.
5.4 Capital Equipment. Collaborator’s commitment, if any, to provide ICD with
capital equipment to enable the research and development activities under the
Research Plan appears in Appendix B. If Collaborator transfers to ICD the
capital equipment or provides funds for ICD to purchase it, then ICD will own
the equipment. If Collaborator loans capital equipment to ICD for use during the
CRADA, Collaborator will be responsible for paying all costs and fees associated
with the transport, installation, maintenance, repair, removal, or disposal of
the equipment, and ICD will not be liable for any damage to the equipment.
Article 6. Intellectual Property
6.1 Ownership of CRADA Subject Inventions, CRADA Data, and CRADA Materials.
Subject to the Government license described in Paragraph 7.5, the sharing
requirements of Paragraph 8.1 and the regulatory filing requirements of
Paragraph 8.2, the producing Party will retain sole ownership of and title to
all CRADA Subject Inventions, all copies of CRADA Data, and all CRADA Materials
produced solely by its employee(s). The Parties will own jointly all CRADA
Subject Inventions invented jointly and all CRADA Materials developed jointly.
6.2 Reporting. The Parties will promptly report to each other in writing each
CRADA Subject Invention reported by their respective personnel, and any Patent
Applications filed thereon, resulting from the research and development
activities conducted under this CRADA. Each Party will report all CRADA Subject
Inventions to the other Party in sufficient detail to determine inventorship,
which will be determined in accordance with U.S. patent law. These reports will
be treated as Confidential Information in accordance with

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Article 8. Formal reports will be made by and to the Patenting and Licensing
Offices identified on the Contacts Information Page herein.
6.3 Filing of Patent Applications. Each Party will make timely decisions
regarding the filing of Patent Applications on the CRADA Subject Inventions made
solely by its employee(s). Collaborator will have the first opportunity to file
a Patent Application on joint CRADA Subject Inventions and will notify PHS of
its decision within [*] of an Invention being reported or at least [*] before
any patent filing deadline, whichever occurs sooner. If Collaborator fails to
notify PHS of its decision within that time period or notifies PHS of its
decision not to file a Patent Application, then PHS has the right to file a
Patent Application on the joint CRADA Subject Invention. Neither Party will be
obligated to file a Patent Application. Collaborator will place the following
statement in any Patent Application it files on a CRADA Subject Invention: “This
invention was created in the performance of a Cooperative Research and
Development Agreement with the [INSERT into Agency’s model as appropriate:
National Institutes of Health, Food and Drug Administration, Center for Disease
Control and Prevention], an Agency of the Department of Health and Human
Services. The Government of the United States has certain rights in this
invention.” If either Party files a Patent Application on a joint CRADA Subject
Invention, then the filing Party will include a statement within the Patent
Application that clearly identifies the Parties and states that the joint CRADA
Subject Invention was made under this CRADA.
6.4 Patent Expenses. Unless agreed otherwise, the Party filing a Patent
Application will pay all preparation and filing expenses, prosecution fees,
issuance fees, post issuance fees, patent maintenance fees, annuities,
interference expenses, and attorneys’ fees for that Patent Application and any
resulting Patent(s). If a license to any CRADA Subject Invention is granted to
Collaborator, then Collaborator will be responsible for all expenses and fees,
past and future, in connection with the preparation, filing, prosecution, and
maintenance of any Patent Applications and Patents claiming exclusively licensed
CRADA Subject Inventions and will be responsible for a pro-rated share, divided
equally among all licensees, of those expenses and fees for non-exclusively
licensed CRADA Subject Inventions. Collaborator may waive its exclusive option
rights at any time, and incur no subsequent financial obligation for those
Patent Application(s) or Patent(s).
6.5 Prosecution of Patent Applications. The Party filing a Patent Application
will provide the non-filing Party with a copy of any official communication
relating to prosecution of the Patent Application within [*] of transmission of
the communication. Each Party will also provide the other Party with the power
to inspect and make copies of all documents retained in the applicable Patent
Application or Patent file. With respect to joint CRADA Subject Inventions and
sole ICD CRADA Subject Inventions for which Collaborator has exercised its
licensing option in accordance with Paragraph 7.2, the Parties agree to consult
with each other regarding the prosecution of Patent Applications. If
Collaborator elects to file and prosecute Patent Applications on joint CRADA
Subject Inventions, then Collaborator agrees to use the U.S.P.T.O. Customer
Number Practice and/or grant PHS a power(s) of attorney (or equivalent)
necessary to assure PHS access to its intellectual property rights in these
Patent Applications. PHS and Collaborator will cooperate with each other to
obtain necessary signatures on Patent Applications, assignments, or other
documents.
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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Article 7. Licensing
7.1 Background Inventions. Other than as specifically stated in this Article 7,
nothing in this CRADA will be construed to grant any rights in one Party’s
Background Invention(s) to the other Party, except to the extent necessary for
the Parties to conduct the research and development activities described in the
Research Plan.
7.2 Collaborator’s Option for Commercialization License. With respect to
Government rights to any CRADA Subject Invention made solely by an ICD
employee(s) or made jointly by an ICD employee(s) and a Collaborator employee(s)
for which a Patent Application was filed, PHS hereby grants to Collaborator an
exclusive option to elect an exclusive or nonexclusive commercialization
license. The license will be substantially in the form of the appropriate model
PHS license agreement and will fairly reflect the nature of the CRADA Subject
Invention, the relative contributions of the Parties to the CRADA Subject
Invention and the CRADA, a plan for the development and marketing of the CRADA
Subject Invention, the risks incurred by Collaborator, and the costs of
subsequent research and development needed to bring the CRADA Subject Invention
to the marketplace. The field of use of the license will not exceed the scope of
the Research Plan.
7.3 Exercise of Collaborator’s License Option. To exercise the option of
Paragraph 7.2 Collaborator must submit a written notice to the PHS Patenting and
Licensing Contact identified on the Contacts Information Page (and provide a
copy to the ICD Contact for CRADA Notices) within [*] after either
(i) Collaborator receives written notice from PHS that the Patent Application
has been filed or (ii) the date on which Collaborator files the Patent
Application. The written notice exercising this option will include a completed
“Application for License to Public Health Service Inventions” and will initiate
a negotiation period that expires [*] after the exercise of the option. If PHS
has not responded in writing to the last proposal by Collaborator within this
[*] period, the negotiation period will be extended to expire [*] after PHS so
responds, during which [*] Collaborator may accept in writing the final license
proposal of PHS. In the absence of Collaborator’s exercise of the option, or
upon election of a nonexclusive license, PHS will be free to license the CRADA
Subject Invention to others. These time periods may be extended at the sole
discretion of PHS upon good cause shown in writing by Collaborator.
7.4 Government License in ICD Sole CRADA Subject Inventions and Joint CRADA
Subject Inventions. Pursuant to 15 U.S.C. § 3710a(b)(1)(A), for CRADA Subject
Inventions owned solely by ICD or jointly by ICD and Collaborator, and licensed
pursuant to the option of Paragraph 7.2, Collaborator grants to the Government a
nonexclusive, nontransferable, irrevocable, paid-up license to practice the
CRADA Subject Invention or have the CRADA Subject Invention practiced throughout
the world by or on behalf of the Government. In the exercise of this license,
the Government will not publicly disclose trade secrets or commercial or
financial information that is privileged or confidential within the meaning of 5
U.S.C. § 552(b)(4) or which would be considered privileged or confidential if it
had been obtained from a non-federal party.
7.5 Government License in Collaborator Sole CRADA Subject Inventions. Pursuant
to 15 U.S.C. § 3710a(b)(2), for CRADA Subject Inventions made solely by an
employee of Collaborator, Collaborator grants to the Government a nonexclusive,
nontransferable, irrevocable, paid-up license to practice the CRADA
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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Subject Invention or have the CRADA Subject Invention practiced throughout the
world by or on behalf of the Government for research or other Government
purposes.
7.6 Third Party License. Pursuant to 15 U.S.C. § 3710a(b)(1)(B), if PHS grants
an exclusive license to a CRADA Subject Invention made solely by an ICD employee
or jointly with a Collaborator employee, the Government will retain the right to
require Collaborator to grant to a responsible applicant a nonexclusive,
partially exclusive, or exclusive sublicense to use the CRADA Subject Invention
in Collaborator’s licensed field of use on terms that are reasonable under the
circumstances; or if Collaborator fails to grant a license, to grant a license
itself. The exercise of these rights by the Government will only be in
exceptional circumstances and only if the Government determines (i) the action
is necessary to meet health or safety needs that are not reasonably satisfied by
Collaborator, (ii) the action is necessary to meet requirements for public use
specified by federal regulations, and such requirements are not reasonably
satisfied by Collaborator; or (iii) Collaborator has failed to comply with an
agreement containing provisions described in 15 U.S.C. § 3710a(c)(4)(B). The
determination made by the Government under this Paragraph is subject to
administrative appeal and judicial review under 35 U.S.C. § 203(2).
7.7 Third-Party Rights In ICD Sole CRADA Subject Inventions. For a CRADA Subject
Invention conceived prior to the Effective Date solely by an ICD employee that
is first actually reduced to practice after the Effective Date in the
performance of the Research Plan, the option offered to Collaborator in
Paragraph 7.2 may be restricted if, prior to the Effective Date, PHS had filed a
Patent Application and has either offered or granted a license in the CRADA
Subject Invention to a third party. Collaborator nonetheless retains the right
to apply for a license to any such CRADA Subject Invention in accordance with
the terms and procedures of 35 U.S.C. § 209 and 37 C.F.R. Part 404.
7.8 Joint CRADA Subject Inventions Not Exclusively Licensed by Collaborator. If
Collaborator does not acquire an exclusive commercialization license in a joint
CRADA Subject Invention in all fields of use then, for those fields of use not
exclusively licensed to Collaborator, each Party will have the right to use the
joint CRADA Subject Invention and to license its use to others, and each Party
will cooperate with the other, as necessary, to fulfill international licensing
requirements. The Parties may agree to a joint licensing approach for any
remaining fields of use.
Article 8. Rights of Access and Publication
8.1 Right of Access to CRADA Data and CRADA Materials. ICD and Collaborator
agree to exchange all CRADA Data and to share all CRADA Materials. If the CRADA
is terminated, both Parties agree to provide CRADA Materials in quantities
needed to complete the Research Plan. Such provision will occur before the
termination date of the CRADA or sooner, if required by the Research Plan. If
Collaborator possesses any human biological specimens from clinical trials under
the CRADA, the specimens must be handled as described in the Protocol or as
otherwise directed by ICD before the termination date of the CRADA.
8.2 Use of CRADA Data and CRADA Materials. The Parties will be free to utilize
CRADA Data and CRADA Materials internally for their own purposes, consistent
with their obligations under this CRADA. The Parties may share CRADA Data or
CRADA Materials with their Affiliates, agents or contractors provided the
obligations of this Article 8.2 are simultaneously conveyed.
8.2.1 CRADA Data.
Collaborator and ICD will use reasonable efforts to keep CRADA Data confidential
until published or until corresponding Patent Applications are filed. To the
extent permitted by law, each Party will have the right to use any and all CRADA
Data in and for any regulatory filing by or on behalf of the Party.

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8.2.2 CRADA Materials.
Collaborator and ICD will use reasonable efforts to keep descriptions of CRADA
Materials confidential until published or until corresponding Patent
Applications are filed. Collaborator acknowledges that the basic research
mission of PHS includes sharing with third parties for further research those
research resources made in whole or in part with NIH funding. Consistent with
this mission and the tenets articulated in “Sharing of Biomedical Research
Resources: Principles and Guidelines for Recipients of NIH Research Grants and
Contracts”, December 1999, available at
http://ott.od.nih.gov/NewPages/RTguide_final.html, following publication either
Party may make available to third parties for further research those CRADA
Materials made jointly by both PHS and Collaborator. Notwithstanding the above,
if those joint CRADA Materials are the subject of a pending Patent Application
or a Patent, or were created using a patent-pending or patented material or
technology, the Parties may agree to restrict distribution or freely distribute
them. Either Party may distribute those CRADA Materials made solely by the other
Party only upon written consent from that other Party or that other Party’s
designee.
8.3 Confidential Information. Each Party agrees to limit its disclosure of
Confidential Information to the amount necessary to carry out the Research Plan,
and will place a confidentiality notice on all this information. A Party orally
disclosing Confidential Information to the other Party will reduce the
disclosure to writing within fifteen (15) days of the disclosure. Each Party
receiving Confidential Information agrees to use it only for the purposes
described in the Research Plan. Either Party may object to the designation of
information as Confidential Information by the other Party.
8.4 Protection of Confidential Information. Confidential Information will not be
disclosed, copied, reproduced or otherwise made available to any other person or
entity without the consent of the owning or providing Party except as required
by a court or administrative body of competent jurisdiction, or federal law or
regulation. Each Party agrees to use reasonable efforts to maintain the
confidentiality of Confidential Information, which will in no instance be less
effort than the Party uses to protect its own Confidential Information. Each
Party agrees that a Party receiving Confidential Information will not be liable
for the disclosure of that portion of the Confidential Information which, after
notice to and consultation with the disclosing Party, the receiving Party
determines may not be lawfully withheld, provided the disclosing Party has been
given a reasonable opportunity to seek a court order to enjoin disclosure.
8.5 Human Subject Protection. The research to be conducted under this CRADA
involves Human Subjects or human tissues within the meaning of 45 C.F.R.
Part 46, and all research to be performed under this CRADA will conform to
applicable federal laws and regulations. Additional information is available
from the HHS Office for Human Research Protections (http://www.hhs.gov/ohrp/).
8.6 Duration of Confidentiality Obligation. The obligation to maintain the
confidentiality of Confidential Information will expire at the earlier of the
date when the information is no longer Confidential Information as defined in
Paragraph 2.4 or [*] after the expiration or termination date of this CRADA.
Collaborator may request an extension to this term when necessary to protect
Confidential Information relating to products not yet commercialized.
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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8.7 Publication. The Parties are encouraged to make publicly available the
results of their research and development activities. Before either Party
submits a paper or abstract for publication or otherwise intends to publicly
disclose information about a CRADA Subject Invention, CRADA Data, or CRADA
Materials, the other Party will have [*] to review proposed manuscripts and [*]
to review proposed abstracts to assure that Confidential Information is
protected. Either Party may request in writing that the proposed publication or
other disclosure be delayed for up to [*] as necessary to file a Patent
Application.
Article 9. Representations and Warranties
9.1 Representations of ICD. ICD hereby represents to Collaborator that:
9.1.1 ICD has the requisite power and authority to enter into this CRADA and to
perform according to its terms, and that ICD’s official signing this CRADA has
authority to do so.
9.1.2 To the best of its knowledge and belief, neither ICD nor any of its
personnel involved in this CRADA is presently subject to debarment or suspension
by any agency of the Government which would directly affect its performance of
the CRADA. Should ICD or any of its personnel involved in this CRADA be debarred
or suspended during the term of this CRADA, ICD will notify Collaborator within
thirty (30) days of receipt of final notice.
9.2 Representations and Warranties of Collaborator. Collaborator hereby
represents and warrants to ICD that:
9.2.1 Collaborator has the requisite power and authority to enter into this
CRADA and to perform according to its terms, and that Collaborator’s official
signing this CRADA has authority to do so.
9.2.2 Neither Collaborator nor any of its personnel involved in this CRADA,
including Affiliates, agents, and contractors are presently subject to debarment
or suspension by any agency of the Government. Should Collaborator or any of its
personnel involved in this CRADA be debarred or suspended during the term of
this CRADA, Collaborator will notify ICD within thirty (30) days of receipt of
final notice.
9.2.3 Subject to Paragraph 12.3, and if and to the extent Collaborator has
agreed to provide funding under Appendix B, Collaborator is financially able to
satisfy these obligations in a timely manner.
9.2.4 The Test Article provided has been produced in accordance with the FDA’s
current Good Manufacturing Practice set out in 21 C.F.R. § 210-211 and ICH QA7,
and meets the specifications cited in the Certificate of Analysis and
Investigator’s Brochure provided.
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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Article 10. Expiration and Termination
10.1 Expiration. This CRADA will expire on the last date of the term set forth
on the Summary Page. In no case will the term of this CRADA extend beyond the
term indicated on the Summary Page unless it is extended in writing in
accordance with Paragraph 13.6.
10.2 Termination by Mutual Consent. ICD and Collaborator may terminate this
CRADA at any time by mutual written consent.
10.3 Unilateral Termination. Either ICD or Collaborator may unilaterally
terminate this CRADA at any time by providing written notice at least sixty
(60) days before the desired termination date. ICD may, at its option, retain
funds transferred to ICD before unilateral termination by Collaborator for use
in completing the Research Plan. If Collaborator terminates this Agreement
before the completion of all approved or active Protocol(s), then Collaborator
will supply enough Test Article (and Placebo, if applicable) to complete these
Protocol(s) unless termination is for safety concerns.
10.4 Funding for ICD Personnel. If Collaborator has agreed to provide funding
for ICD personnel and this CRADA is mutually or unilaterally terminated by
Collaborator before its expiration, then Collaborator agrees that funds for that
purpose will be available to ICD for a period of [*] after the termination date
or until the expiration date of the CRADA, whichever occurs sooner. If there are
insufficient funds to cover this expense, Collaborator agrees to pay the
difference.
10.5 New Commitments. Neither Party will incur new expenses related to this
CRADA after expiration, mutual termination, or a notice of a unilateral
termination and will, to the extent feasible, cancel all outstanding commitments
and contracts by the termination date. Collaborator acknowledges that ICD will
have the authority to retain and expend any funds for up to [*] subsequent to
the expiration or termination date to cover any unpaid costs obligated during
the term of the CRADA in undertaking the research and development activities set
forth in the Research Plan.
10.6 Collaborator Failure to Continue Development. If Collaborator suspends
development of the Test Article without the transfer of its active development
efforts, assets, and obligations to a third party within [*] of discontinuation,
Collaborator agrees that ICD may continue developing the Test Article. In that
event, the following will apply:
10.6.1 Collaborator agrees to transfer to ICD all information necessary to
enable ICD to contract for the manufacture of the Test Article and, unless
abandoned for reasons relating to safety as determined by the data safety
monitoring board, to provide the Test Article (and Placebo, if any) in
Collaborator’s inventory to ICD.
10.6.2 Further, Collaborator hereby grants to ICD a nonexclusive, irrevocable,
world-wide, paid-up license to practice, or have practiced for or on behalf of
the Government, any Background Invention that Collaborator may currently have or
will obtain on the Test Article, its manufacture, or on any
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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method of using the Test Article for the indication(s) described in the Research
Plan, including the right to sublicense to third parties.
Article 11. Disputes
11.1 Settlement. Any dispute arising under this CRADA which is not disposed of
by agreement of the CRADA Principal Investigators will be submitted jointly to
the signatories of this CRADA. If the signatories, or their designees, are
unable to jointly resolve the dispute within thirty (30) days after notification
thereof, the Assistant Secretary for Health (or his/her designee or successor)
will propose a resolution. Nothing in this Paragraph will prevent any Party from
pursuing any additional administrative remedies that may be available and, after
exhaustion of such administrative remedies, pursuing all available judicial
remedies.
11.2 Continuation of Work. Pending the resolution of any dispute or claim
pursuant to this Article 11, the Parties agree that performance of all
obligations will be pursued diligently.
Article 12. Liability
12.1 NO WARRANTIES. EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES MAKE
NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER, INCLUDING THE
CONDITIONS OF THE RESEARCH OR ANY INVENTION OR MATERIAL, WHETHER TANGIBLE OR
INTANGIBLE, MADE OR DEVELOPED UNDER OR OUTSIDE THE SCOPE OF THIS CRADA, OR THE
OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF THE RESEARCH
OR ANY INVENTION OR MATERIAL, OR THAT A TECHNOLOGY UTILIZED BY A PARTY IN THE
PERFORMANCE OF THE RESEARCH PLAN DOES NOT INFRINGE ANY THIRD-PARTY PATENT
RIGHTS.
12.2 Indemnification and Liability. Collaborator agrees to hold the Government
harmless and to indemnify the Government for all liabilities, demands, damages,
expenses and losses arising out of the use by Collaborator for any purpose of
the CRADA Data, CRADA Materials or CRADA Subject Inventions produced in whole or
part by ICD employees under this CRADA, unless due to the negligence or willful
misconduct of ICD, its employees, or agents. The Government has no statutory
authority to indemnify Collaborator. Each Party otherwise will be liable for any
claims or damages it incurs in connection with this CRADA, except that ICD, as
an agency of the Government, assumes liability only to the extent provided under
the Federal Tort Claims Act, 28 U.S.C. Chapter 171.
12.3 Force Majeure. Neither Party will be liable for any unforeseeable event
beyond its reasonable control and not caused by its own fault or negligence,
which causes the Party to be unable to perform its obligations under this CRADA,
and which it has been unable to overcome by the exercise of due diligence. If a
force majeure event occurs, the Party unable to perform will promptly notify the
other Party. It will use its best efforts to resume performance as quickly as
possible and will suspend performance only for such period of time as is
necessary as a result of the force majeure event.
Article 13. Miscellaneous
13.1 Governing Law. The construction, validity, performance and effect of this
CRADA will be governed by U.S. federal law, as applied by the federal courts in
the District of Columbia. If any provision in this CRADA conflicts with or is
inconsistent with any U.S. federal law or regulation, then the U.S. federal law
or regulation will preempt that provision.

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13.2 Compliance with Law. ICD and Collaborator agree that they, and advise their
contractors and agents to comply with, will comply with all applicable statutes,
Executive Orders, and HHS regulations relating to research on human subjects (45
C.F.R. Part 46, 21 C.F.R. Parts 50 and 56) and relating to the appropriate care
and use of laboratory animals (7 U.S.C. §§ 2131 et seq.; 9 C.F.R. Part 1,
Subchapter A). ICD will advise all contractors or grantees conducting clinical
trials that they must comply with all applicable federal regulations for the
protection of Human Subjects, which may include the Standards for Privacy of
Individually Identifiable Health Information set forth in 45 C.F.R. Part 164.
Collaborator agrees to ensure that employees, contractors, and agents of
Collaborator who might have access to a “select agent or toxin” (as that term is
defined in 42 C.F.R. §§ 73.4-73.5) transferred from ICD is properly licensed to
receive the “select agent or toxin”.
13.3 Waivers. None of the provisions of this CRADA will be considered waived by
any Party unless a waiver is given in writing to the other Party. The failure of
a Party to insist upon strict performance of any of the terms and conditions
hereof, or failure or delay to exercise any rights provided herein or by law,
will not be deemed a waiver of any rights of any Party.
13.4 Headings. Titles and headings of the articles and paragraphs of this CRADA
are for convenient reference only, do not form a part of this CRADA, and will in
no way affect its interpretation.
13.5 Severability. The illegality or invalidity of any provisions of this CRADA
will not impair, affect, or invalidate the other provisions of this CRADA.
13.6 Amendments. Minor modifications to the Research Plan may be made by the
mutual written consent of the Principal Investigators. Substantial changes to
the CRADA, extensions of the term, or any changes to Appendix C will become
effective only upon a written amendment signed by the signatories to this CRADA
or by their representatives duly authorized to execute an amendment. A change
will be considered substantial if it directly expands the range of the potential
CRADA Subject Inventions, alters the scope or field of any license option
governed by Article 7, or requires a significant increase in the contribution of
resources by either Party.
13.7 Assignment. Neither this CRADA nor any rights or obligations of any Party
hereunder will be assigned or otherwise transferred by either Party without the
prior written consent of the other Party. This CRADA will be binding upon and
inure to the benefit of the Parties and their respective successors and
permitted assigns.
13.8 Notices. All notices pertaining to or required by this CRADA will be in
writing, signed by an authorized representative of the notifying Party, and
delivered by first class, registered, or certified mail, or by an
express/overnight commercial delivery service, prepaid and properly addressed to
the other Party at the address designated on the Contacts Information Page, or
to any other address designated in writing by the other Party. Notices will be
considered timely if received on or before the established deadline date or sent
on or before the deadline date as verifiable by U.S. Postal Service postmark or
dated receipt from a commercial carrier. Notices regarding the exercise of
license options will be made pursuant to Paragraph 7.3. Either Party may change
its address by notice given to the other Party in the manner set forth above.
13.9 Independent Contractors. The relationship of the Parties to this CRADA is
that of independent contractors and not agents of each other or joint venturers
or partners. Each Party will maintain sole and exclusive control over its
personnel and operations.
13.10 Use of Name; Press Releases. By entering into this CRADA, the Government
does not directly or indirectly endorse any product or service that is or will
be provided, whether directly or indirectly related to either this CRADA or to
any patent or other intellectual-property license or agreement that implements
this CRADA by Collaborator, its successors, assignees, or licensees.
Collaborator will not in any way state or

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imply that the Government or any of its organizational units or employees
endorses any product or services. Each Party agrees to provide proposed press
releases that reference or rely upon the work under this CRADA to the other
Party for review and comment at least five (5) business days before publication.
Either Party may disclose the Title and Abstract of the CRADA to the public
without the approval of the other Party.
13.11 Reasonable Consent. Whenever a Party’s consent or permission is required
under this CRADA, its consent or permission will not be unreasonably withheld.
13.12 Export Controls. Collaborator agrees to comply with U.S. export law and
regulations. If Collaborator has a need to transfer any CRADA Materials made in
whole or in part by ICD, or ICD Materials, or ICD’s Confidential Information to
a person located in a country other than the United States, to an Affiliate
organized under the laws of a country other than the United States, or to an
employee of Collaborator in the United States who is not a citizen or permanent
resident of the United States, Collaborator will acquire any and all necessary
export licenses and other appropriate authorizations, if necessary.
13.13 Entire Agreement. This CRADA constitutes the entire agreement between the
Parties concerning the subject matter of this CRADA and supersedes any prior
understanding or written or oral agreement.
13.14 Survivability. The provisions of Paragraphs 3.3, 3.4, 3.8, 4.2, 4.3, 5.3,
5.4, 6.1-9.2, 10.3-10.6, 11.1, 11.2, 12.1-12.3, 13.1-13.3, 13.7, 13.10 and 13.14
will survive the expiration or early termination of this CRADA.
SIGNATURES BEGIN ON THE NEXT PAGE

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SIGNATURE PAGE
ACCEPTED AND AGREED
By executing this agreement, each party represents that all statements made
herein are true, complete, and accurate to the best of its knowledge.
Collaborator acknowledges that it may be subject to criminal, civil, or
administrative penalties for knowingly making a false, fictitious, or fraudulent
statement or claim.
FOR ICD:

     
/s/ Anna D. Barker
  03/01/07
 
   
Signature
  Date
 
   
Anna D. Barker, Ph.D.
   
Typed Name
   
 
   
Deputy Director, NCI
   
Title
   
 
   
FOR COLLABORATOR:
   
 
   
/s/ David L. Parker
  3/22/07
 
   
Signature
  Date
 
   
David L. Parker
   
Typed Name
   
 
   
Senior V.P. — I.P.
   
Title
   

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CONTACTS INFORMATION PAGE
CRADA Notices

     
For ICD:
  For Collaborator:
 
   
Technology Transfer Branch, NCI
  David L. Parker, Ph.D., J.D.
6120 Executive Blvd., Suite 450
  Introgen Therapeutics, Inc.
Rockville, MD 20852
  301 Congress Avenue, Suite 1850
 
  Austin, Texas 78701

Patenting and Licensing

     
For ICD:
  For Collaborator (if separate from above):
 
   
Division Director, Division of Technology
   
 
   
and Transfer
   
 
     
NIH Office of Technology Transfer
   
 
   
6011 Executive Blvd., Suite 325
   
 
   
Rockville, Maryland 20852-3804
   
 
   
Tel: 301-396-7057
   
Fax: 301-402-0220
   

Delivery of Materials Identified In Appendix B (if any)

     
For ICD:
  For Collaborator:
 
   
Steven A. Rosenberg, M.D., Ph.D.
  Robert E. Sobol, M.D.
Surgery Branch, NCI
  Introgen Therapeutics, Inc.
10 Center Drive, MSC 120
  2250 Holcombe Blvd.
Bldg. 10, CRC Room 3-3940
  Houston, TX 77030
Bethesda, MD 20892-1201
   

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SUMMARY PAGE
Either party may, without further consultation or permission,
release this summary page to the public.
TITLE OF CRADA: Cooperative and Research Development Agreement for the
Development of Introgen Proprietary Vectors and Recombinants for the Treatment
of Cancer

     
ICD Component:
  National Cancer Institute, Surgery Branch
 
   
ICD Principal Investigator:
  Steven A. Rosenberg, M.D., Ph.D.
 
   
Collaborator:
  Introgen Therapeutics, Inc.
 
   
Collaborator Principal Investigator:
  Robert E. Sobol, M.D.
 
   
TERM OF CRADA:
  Five (5) years from the Effective Date.

ABSTRACT OF THE RESEARCH PLAN:
The principal goals of this CRADA between the National Cancer Institute and
Introgen Therapeutics, Inc. are to develop Introgen’s proprietary cancer
immunotherapies utilizing immunization with adenoviruses expressing p53
utilizing immunization either alone or in dendritic cells and/or in conjunction
with adoptive transfer of anti-p53 lymphocytes.

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CRADA #02177
APPENDIX A
RESEARCH PLAN
TITLE OF CRADA: Cooperative and Research Development Agreement for the
Development of Introgen
Proprietary Vectors and Recombinants for the Treatment of Cancer

     
NIH PRINCIPAL INVESTIGATOR:
  Steven A. Rosenberg
and his/her laboratory:
  Surgery Branch

COLLABORATOR PRINCIPAL INVESTIGATOR: Robert E. Sobol

     
 
  Senior Vice President, Medical and Scientific Affairs
 
  Introgen Therapeutics, Inc.

TERM OF CRADA: (5) years.
The Research Plan which follows this page should be concise but of sufficient
detail to permit reviewers of this CRADA to evaluate the scientific merit of the
proposed collaboration. The RP should explain the scientific importance of the
collaboration and the research goals of PHS and the Collaborator. The respective
contributions in terms of expertise and/or research materials of PHS and
Collaborator should be summarized. Initial and subsequent projects contemplated
under the RP, and the time periods estimated for their completion, should be
described, and pertinent methodological considerations summarized. Pertinent
literature references may be cited and additional relevant information included.

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APPENDIX A
RESEARCH PLAN
Title of CRADA
Cooperative Research and Development Agreement for the Development of Introgen
Proprietary Vectors and
Recombinants for the Treatment of Cancer
NCI Principal Investigator:
Steven A. Rosenberg, M.D., Ph.D.
Surgery Branch, CCR, NCI
Collaborator Principal Investigators
Robert E. Sobol, M.D.
Senior Vice President, Medical and Scientific Affairs
Introgen Therapeutics, Inc.
Term of CRADA
Five (5) years from the date of the final CRADA signature.
Goals of this CRADA
[*]
 

[*]   Certain information on this page has been omitted and filed separately
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the omitted portion.

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[*]
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

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with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

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with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

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with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

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with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

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with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

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the omitted portion.

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CACR-02177
APPENDIX B
FINANCIAL AND STAFFING CONTRIBUTIONS OF THE PARTIES
[Insert the Financial and Staffing Contributions as Appendix B behind this
page.]

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Public Health Service
Cooperative Research and Development Agreement
APPENDIX B
STAFFING, FUNDING AND MATERIALS/EQUIPMENT CONTRIBUTIONS
OF THE PARTIES
[*]
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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[*]
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
the omitted portion.

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CACR-02177
APPENDIX C
EXCEPTIONS OR MODIFICATIONS TO THIS CRADA

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Public Health Service
Cooperative Research and Development Agreement
APPENDIX C
MODIFICATIONS TO THE MODEL CRADA
(Additions are indicated by underline, deletions by strike-out)
Amend Section 4.4 as follows:
4.4 Safety Reports. In accordance with FDA requirements ICD, as the IND Sponsor,
will establish and maintain records and submit safety reports to the FDA, as
required by 21 C.F.R. § 312.32 and 21 C.F.R. 812.150(b)(1), or other applicable
regulations. In the conduct of research under this CRADA, the Parties will
comply with specific Collaborator and ICD guidelines and policies for reporting
ADEs and AEs, as well as procedures specified in the Protocol(s). ICD must
provide Collaborator with copies of all Safety Reports concurrently with their
submission to the FDA, and with any other information affecting the safety of
Human Subjects in research conducted under this CRADA.
Amend Section 8.3 to read as follows:
8.3 Confidential Information. Each Party agrees to limit its disclosure of
Confidential Information to the amount necessary to carry out the Research Plan,
and will place a confidentiality notice on all this information. A Party orally
disclosing Confidential Information to the other Party will reduce the
disclosure to writing within fifteen (15) days of the disclosure. Each Party
receiving Confidential Information agrees to use it only for the purposes
described in the Research Plan. Either Party may object to the designation of
information as Confidential Information by the other Party. Although certain
information provided under this Agreement is CONFIDENTIAL and will be so
stamped, Collaborator recognizes that the NIH PI may need to disclose certain
information concerning Confidential Information to patients (or to physicians or
scientists where such disclosure is made in order to directly facilitate the
ongoing treatment of a patient, or the development of a treatment for a
patient). Collaborator hereby authorizes such limited disclosures and the NIH PI
agrees to promptly acknowledge to Collaborator the making of any such
disclosure.
Amend Section 8.4 to read as follows:
8.4 Protection of Confidential Information. Subject to Paragraph 8.3,
Confidential Information will not be disclosed, copied, reproduced or otherwise
made available to any other person or entity without the consent of the owning
or providing Party except as required by a court

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or administrative body of competent jurisdiction, or federal law or regulation.
Each Party agrees to use reasonable efforts to maintain the confidentiality of
Confidential Information, which will in no instance be less effort than the
Party uses to protect its own Confidential Information. Each Party agrees that a
Party receiving Confidential Information will not be liable for the disclosure
of that portion of the Confidential Information which, after notice to and
consultation with the disclosing Party, the receiving Party determines may not
be lawfully withheld, provided the disclosing Party has been given a reasonable
opportunity to seek a court order to enjoin disclosure.
Amend Section 8.6 to read as follows:
8.6 Duration of Confidentiality Obligation. The obligation to maintain the
confidentiality of Confidential Information as described in Paragraph 8.3, will
expire at the earlier of the date when the information is no longer Confidential
Information as defined in Paragraph 2.4 or [*] after the expiration or
termination date of this CRADA. Collaborator may request an extension to this
term when necessary to protect Confidential Information relating to products not
yet commercialized.
Amend Section 10.3 to read as follows:
10.3 Unilateral Termination. Either ICD or Collaborator may unilaterally
terminate this CRADA at any time by providing written notice at least ninety
(90) days before the desired termination date. If Collaborator terminates this
Agreement before the completion of all approved or active Protocol(s), then
Collaborator will supply enough Test Article (and Placebo, if applicable) to
complete these Protocol(s) unless termination is for safety concerns.
Amend Section 10.6 to read as follows:
10.6 Collaborator Failure to Continue Development. If Collaborator elects to
suspend development of the Test Article without the transfer of its active
development efforts, assets, and obligations to a third party within [*] of
discontinuation, Collaborator agrees that ICD may continue developing the Test
Article. In that event, the following will apply:
10.6.1 Collaborator agrees to transfer to ICD all information necessary to
enable ICD to contract for the manufacture of the Test Article and, unless
abandoned for reasons relating to safety as determined by the data safety
monitoring board, to provide the Test Article (and Placebo, if any) in
Collaborator’s inventory to ICD.
 

[*]   Certain information on this page has been omitted and filed separately
with the Commission. Confidential treatment has been requested with respect to
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10.6.2 Further, Collaborator hereby grants to ICD a nonexclusive, irrevocable,
world-wide, paid-up license to practice, or have practiced for or on behalf of
the Government, any Background Invention that Collaborator may currently have or
will obtain on the Test Article, its manufacture, or on any method of using the
Test Article for the indication(s) described in the Research Plan, including the
right to sublicense to third parties.
Amend Section 13.13 to read as follows:
13.13 Entire Agreement. This CRADA constitutes the entire agreement between the
Parties concerning the subject matter of this CRADA and supersedes any prior
understanding or written or oral agreement. In furtherance, but not in
limitation of the foregoing, the Parties agree that all activities relating to
Introgen’s proprietary Adenovirus p53 pursuant to the Material Transfer
Agreement No. 2-21011-06 executed on March 8, 2006 are hereby terminated as of
the execution date of this CRADA, and shall, as of the CRADA execution date, be
conducted solely pursuant to, and subject to, the terms and conditions of this
CRADA.

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