EXHIBIT 10.13 CLINICAL TRIALS AGREEMENT
between Vion Pharmaceuticals, Inc. and the
Division of Cancer Treatment and Diagnosis, NCI
for the Clinical Development of
3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine'r')
INTRODUCTION
The Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute
(NCI), recognizes the importance of the pharmaceutical industry in the clinical
development of new anti-cancer agents. DCTD wishes to xxxxxx collaboration with
industry whenever possible. As part of its mission to improve cancer care, DCTD
shares with industry the important goal of defining the contribution of a new
drug or biologic in the treatment of cancer. DCTD therefore recognizes and
supports the need of a private sponsor to focus at the appropriate time on
clinical trials which lead to a New Drug Application (NDA) or a Biologics
License Application (BLA) since an NDA and a BLA, once approved, are the
vehicles through which new anti-cancer therapies become widely available to
cancer patients. Thus DCTD considers it appropriate for the investigators
sponsored by DCTD to do clinical trials of interest to, and partially supported
by a pharmaceutical firm, provided that the trials have scientific merit and are
consistent with the overall goals of the investigators and DCTD.
Inasmuch as DCTD coordinates a large volume of clinical research with new
anti-cancer agents, industry recognizes DCTD's need to be aware of industry's
plans for the clinical development of new agents of mutual interest,
particularly if a pharmaceutical firm wishes to utilize the resources of the
DCTD-supported clinical trials mechanism. Industry also recognizes the necessity
of preserving the spirit of free and open inquiry among clinical investigators.
AGREEMENT
The following statement serves as the basis for the co-development of
3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine'r') by
Collaborator and DCTD.
Article 1. Definitions
"Adverse Event" means an adverse clinical event as defined under 21 CFR 312.32
IND Safety Reports and other applicable Federal Regulations. NCI shall establish
and maintain records and make reports to the FDA for the following Adverse
Events: (1) all serious, unexpected adverse events, (2) any significant increase
in the frequency of serious expected adverse events, and (3) any significant
increase in the frequency of therapeutic failures. Specific NIH and NCI
guidelines and policies for reporting Adverse Drug Experience, as well as common
toxicity criteria, have been developed. These guidelines and policies appear in
the "Investigator's Handbook: A Manual for Participants in Clinical Trials of
Investigational Agents Sponsored by the Division of Cancer Treatment, and
Diagnosis, National Cancer Institute."
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"Affiliates" means any corporation or other business entity controlled by,
controlling, or under common control with Collaborator (see "Collaborator"). For
this purpose, "control" means direct or indirect beneficial ownership of at
least fifty (50) percent of the voting stock, or at least fifty (50) percent
interest in the income of such corporation or other business.
"Agent" means 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP,
Triapine'r'), an investigational agent of Vion Pharmaceuticals, Inc.
"Amendment" means any formal change to this Agreement that is made after its
effectiveness in accordance with Article 23 of this Agreement.
"Annual Report" means a brief report of the progress of an IND-associated
investigation which the IND sponsor is required to submit to the FDA within 60
days of the anniversary date that the IND went into effect (pursuant to 21 CFR
312.33). NCI shall provide Collaborator a copy of the Annual Report
simultaneously with the submission of the Annual Report to the FDA. Collaborator
will then have thirty (30) days to review the Annual Report and to provide
comments.
"BLA" means a Biologics License Application. The BLA is a formal process by
which the FDA approves a biologic for commercial distribution.
"Biological Product" means any virus, therapeutic serum, toxin, antitoxin, or
analogous product applicable to the prevention, treatment or cure of diseases or
injuries of man, as further defined at 21 CFR 600.3(h).
"Clinical Brochure" means a document containing all the relevant information
about the drug, including preclinical pharmacology, preclinical toxicology, and
detailed pharmaceutical data. Also included, if available, is a summary of
current knowledge about pharmacology and mechanism of action and a full
description of the clinical toxicities.
"Clinical Data and Results" means all information, data, and results developed
or obtained in connection with clinical trials conducted within the scope of
this Agreement whether by intramural research scientists or extramural grantee
or contract investigators.
"Clinical Trials Monitoring Service" or "CTMS" means a non-governmental
organization contracted by CTEP to receive, review, and perform data management
tasks on individual patient case report forms for Phase 1 and selected Phase 2
NCI investigational drug studies. On-site audits are performed by the CTMS to
assess data validity, protocol compliance, and adherence to regulatory
requirements.
"Clinical Trials Monitoring Service Contract" or "CTMS Contract" means the
contract which defines the obligations and the services that the
non-governmental organization CTMS (as defined supra) has agreed to provide to
DCTD. This organization is chosen by DCTD through a
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competitive acquisition process in accordance with the Federal Acquisition
Regulations and all applicable DHHS, NIH and NCI policies and procedures.
"Collaborator" means Vion Pharmaceuticals, Inc., a corporation organized and
existing under the laws of the State of Delaware, having a place of business at
Four Science Park, New Haven, Connecticut 06511, and its Affiliates.
"Contract" means a Funding Agreement that is a research and development contract
that provides that the contractor perform for the benefit of the Government,
with an expectation of completion of the stated research goals and the delivery
of a report, data, materials or other product. Generally, Government contracts
are administered under the Federal Acquisition Regulations (FAR), codified at
Title 48 Code of Federal Regulations, Chapter 1.
"Cooperative Agreement" means a Funding Agreement that is a grant, whereby the
funding Federal agency intends to be substantially involved in carrying out the
research program. Cooperative Agreements may be used where the Federal agency
intends for its scientists to directly collaborate with the researchers of the
funded institution on a joint research project. The Federal agency may then pay
for the research of both its employees and those of the funded institution (see
45 CFR Part 74).
"Cooperative Group" means the cancer cooperative group composed of investigators
who join together to develop and implement common protocols, which have been
approved by the Steering Committee (see "Steering Committee"), and mutually
agreed to by DCTD and Collaborator. The distinguishing characteristic of
cooperative groups is the central operations and statistical offices which
support the administrative requirements of the research and perform central data
collection and analysis. Protocol compliance of cooperative groups is verified
by each group through its own quality assurance program and through site visit
auditing coordinated by CTMS. The Cancer Therapy Evaluation Program of the DCTD
has established guidelines, "The NCI-Cooperative Group-Industry Relationship
Guidelines", to explain the policies and procedures of the NCI with respect to
the Clinical Trials Cooperative Groups and Industry. Some of these policies
reflect DHHS's requirements for Federally funded clinical research while others
are the result of a consensus among NCI staff and qualified extramural clinical
investigators.
"CTA" means Clinical Trials Agreement.
"CTEP" means the Cancer Therapy Evaluation Program, DCTD, NCI.
"CTMS Monitored Studies" means Phase 1 and selected Phase 2 studies that are
monitored by CTMS under the CTMS Contract for the purpose of assuring patient
safety and prompt toxicity reporting. Data are submitted to CTMS on a biweekly
basis. On-site data audits are performed thrice yearly. Data are reviewed by NCI
staff on a monthly basis.
"DCTD" means the Division of Cancer Treatment and Diagnosis, NCI.
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"DHHS" means the Department of Health and Human Services.
"Drug Master Files" or "DMFs" means reference files submitted to FDA that are
used in the review of investigational and marketing applications for human
agents. Drug Master Files allow another party to reference this material without
disclosing to that party the contents of the file.
"Extramural Principal Investigator" means a Principal Investigator, who is a not
a government employee, whose clinical trials are funded by NCI under a Grant,
Contract or Cooperative Agreement.
"FAR" means Federal Acquisition Regulations.
"FDA" means the Food and Drug Administration, DHHS.
"Funding Agreement" means a Contract, Grant, or Cooperative Agreement entered
into between a Federal agency and another party for the performance of
experimental, developmental, or research work funded in whole or in part by the
Federal Government.
"Government" means the U.S. Government and any of its agencies.
"Grant" means a Funding Agreement that is an award of financial assistance which
may be provided for support of basic research in a specific field of interest to
the funding Federal agency (See 45 CFR Part 74, for grants from the U.S. Public
Health Service.) While no specific product is anticipated, the funding agency
may review the progress and direction of the funded research.
"Group C Drugs" means those drugs supported by evidence of reproducible relative
efficacy in patients with a specific tumor type, which alter the pattern of care
of the disease, and which are safely administered by properly trained physicians
without requiring specialized supportive care facilities as judged by available
abstracts, papers, and reports in the IND.
"HSAR" or "Health Services Acquisition Regulations" means the acquisition
regulations which, in addition to the FAR, govern the Department of Health and
Human Services contracts which are codified at Title 48 Code of Federal
Regulations, Chapter 3.
"Human Subjects" means individuals whose physiologic or behavioral
characteristics and responses are the objects of study in a research project.
Under the Federal regulations for the protection of human subjects, human
subjects are defined as living individuals about whom an investigator conducting
research obtains: (1) data through intervention or interaction with the
individual; or (2) identifiable private information (45 CFR 46.102(f)).
"Identifiable Private Information" means patient-identifying data from medical
records or attached to patient specimens, to be obtained prospectively or from
stored medical records or specimens, that can be linked to individual human
subjects, either directly or indirectly through codes.
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"IND" means an Investigational New Drug Application. The IND is the legal
mechanism under which experimental drug research is performed in the United
States. An IND is submitted to the Food and Drug Administration in order to
conduct experimental clinical trials. The FDA regulations require continual
updates to the IND including, but not limited to, Annual Reports, adverse drug
experience reports, new protocols, protocol amendments and pharmaceutical data.
"Investigator" means any physician who assumes full responsibility for the
treatment and evaluation of patients on research protocols as well as the
integrity of the research data.
"Letter of Intent" or "LOI" means an investigator's declaration of interest in
conducting a Phase 1, Phase 2 or Phase 3 trial with a specific investigational
agent in a particular disease. Approval of the LOI by CTEP commits an
investigator to submit a protocol within a specified time frame.
"Multi-Party Data" means clinical data which is collected from clinical studies
sponsored by NCI for combinations of proprietary investigational agents supplied
by more than one Collaborator.
"NCI" means the National Cancer Institute, NIH, DHHS.
"NDA" means a New Drug Application. The NDA is the formal process by which the
FDA approves a drug for commercial distribution.
"NIH" means the National Institutes of Health, PHS, DHHS.
"Parties" means Collaborator and NCI.
"PHS" means the Public Health Service, DHHS.
"PRC" means the CTEP Protocol Review Committee which reviews all studies
involving NCI investigational agents and/or activities supported by NCI.
"Principal Investigator" means a physician who has organizational and fiscal
responsibility for the use of Federal funds to conduct a plan of research which
frequently includes several clinical trials, e.g., Contract Principal
Investigator or Grant Principal Investigator.
"Project Officer" means the individual whose responsibilities include oversight
of the activities of a government contract.
"Proprietary Data" means confidential scientific, business or financial data,
provided that such data:
are not publicly known or available from other sources who are not under a
confidentiality obligation to the source of the information;
have not been made available by its owners to others without a confidentiality
obligation;
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are not already known by or available to the receiving Party without a
confidentiality obligation;
do not relate to potential hazards or warnings associated with the production,
handling or use of the subject matter of this Agreement; and
If any one or more of the above provisions of this definition are not met, the
relevant information shall no longer be considered proprietary.
"Raw Data" means the primary quantitative and empirical data first collected by
the intramural and extramural investigators from experiments and clinical trials
conducted under the scope of this Agreement.
"Regulatory Affairs Branch" means the Regulatory Affairs Branch, CTEP, DCTD,
NCI.
"Sponsor" means an organization or individual who assumes legal responsibility
for overseeing clinical trials with investigational drugs.
"Steering Committee" means a team, whose members will include the principal NCI
and Collaborator scientists responsible for the cooperative development of
Agent, which will coordinate the clinical development of Agent under this
Agreement. Such development will be a collaborative undertaking by Collaborator
and NCI. Details of this development will be formulated or discussed in Steering
Committee meeting(s) before implementation of large-scale or resource intensive
studies. The clinical development plans formulated by the Steering Committee
will be implemented either intramurally at the NCI or extramurally under
NCI-sponsored funding agreements.
"Summary Data" means a summary of the Raw Data which will be made available to
DCTD, which summary is used by DCTD to prepare an Annual Report to the FDA.
Article 2. Planning of Clinical Trials with Agent
The overall plan for the clinical development of Agent will be a collaborative
undertaking by Collaborator and DCTD. Such a plan will be formulated or
discussed in (a) meeting(s) of the Steering Committee before implementation of
large-scale clinical testing. In addition to areas of mutual interest,
Collaborator may independently pursue clinical studies of particular interest to
Collaborator; DCTD may independently pursue clinical studies of particular
interest to DCTD. Because studies independently sponsored by DCTD have
implications for commitment of resources by both DCTD and Collaborator, such
studies will also be the subject of joint discussion and planning between DCTD
and Collaborator. There should be frequent and full interchange between
Collaborator and staff members of the DCTD Cancer Therapy Evaluation Program,
Developmental Therapeutics Program and Biological Resources Branch. Furthermore,
whenever possible, the planning of a particular trial, particularly large-scale
studies and/or trials of pivotal importance, should be a joint effort of the
investigators, Collaborator, and DCTD. All studies sponsored by DCTD using
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Agent will be mutually agreeable to Collaborator and DCTD, in as much as
Collaborator will have final authority over the provision of Agent to DCTD.
Article 3. INDs
Generally the needs of both DCTD and Collaborator are best served when each
sponsors an IND. It is expected, therefore, that either DCTD or Collaborator
will submit an IND which may cross-reference an IND or Drug Master File held by
the other. All information in IND(s) will be fully shared between DCTD and
Collaborator. However, certain information pertaining to manufacturing processes
may be held in confidence by Collaborator (see Article 9 below).
In the event that Canadian institutions are participating on NCI-sponsored
trials, Collaborator will need to assist in the submission of the regulatory
documents to the Canadian Health Products and Food Branch to allow for such
participation. This may include a letter of cross reference to an existing
Clinical Trials Application (CTA) or Drug Master File, including supporting
documentation on the production of the product. The forms and procedures for
preparing Canadian CTAs are available at xxxx://xxx.xxxx.xx/xxx/xxxxx.
Article 4. Protocols
A. A general plan for the clinical development of Agent will be established by
both parties through the Steering Committee. Based on this plan, protocol XXXx
will be solicited from investigators. Each clinical research protocol received
by DCTD will be forwarded to Collaborator for review and comment approximately
two weeks before it is reviewed by the Protocol Review Committee (PRC) of CTEP.
Comments from Collaborator received by CTEP before the PRC meeting will be
discussed by the PRC, will be given due consideration, and will be incorporated
into the protocol, absent good cause. Comments from either Collaborator or the
CTEP staff that are agreed upon in the PRC meeting will be formatted as a
consensus review, which is returned to the investigator for necessary and/or
suggested changes before the protocol can be given final approval and submitted
to the FDA. A copy of the final approved protocol will be forwarded to
Collaborator at the same time it is submitted to the FDA. In summary,
Collaborator will co-develop with DCTD a clinical plan for the overall
development of Agent and receive copies of all DCTD-sponsored protocols both
before review and after approval. Subject to the terms of Article 6, all
protocols sponsored by DCTD using Agent must be mutually agreeable to
Collaborator and DCTD, in as much as Collaborator will have final authority over
the provision of its agent to DCTD.
B. For clinical protocol(s) where Agent is used in combination with another
proprietary investigational agent which is the subject of another Clinical
Trials Agreement or Cooperative Research and Development Agreement, the access
to and use of data by Collaborator and party
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supplying other agent (hereinafter referred to as "Other Party") shall be as
follows (data pertaining to such combination use shall hereinafter be referred
to as "Multi-Party Data."):
i. NCI must provide all parties with written notice regarding the existence and
nature of any agreements governing their collaboration with NIH, the design of
proposed combination protocol(s), and the existence of any obligations which
would tend to restrict NCI's participation in proposed combination protocols.
ii. Collaborator shall agree to permit use of the Multi-Party Data from these
clinical trials by Other Party to the extent necessary to allow Other Party to
develop, obtain regulatory approval of, or commercialize its own proprietary
investigational agent, provided Other Party permits Collaborator similar,
reciprocal rights to use Multi-Party Data.
iii. Any party having the right to use the Multi-Party Data from these trials
must agree in writing prior to the commencement of the trials that it will use
the Multi-Party Data solely for development, regulatory approval, and
commercialization of its own proprietary investigational agent(s).
Article 5. Adverse Events, Annual Reports and Other IND Data
DCTD shall report all serious and/or unexpected adverse events to FDA in
accordance with the reporting obligations of 21 CFR 312.32 and will,
concurrently, forward all such reports to Collaborator. All other adverse event
reports received by DCTD shall be reported to the FDA consistent with 21 CFR
'SS' 312.32 and 312.33. In addition, copies of the Annual Reports and other
pertinent IND data (including, but not limited to, Investigator's Brochure data,
formulation and preclinical data, including toxicology findings) will be
provided to Collaborator as they become available.
In the event that Collaborator informs the FDA of any serious or unexpected
adverse events, Collaborator must notify the NCI at the same time. NCI will then
notify the investigator(s) conducting studies under NCI-sponsored protocols.
Article 6. Drug Information and Supply
Collaborator agrees to provide to DCTD, without charge, formulated and
acceptably labeled clinical-grade Agent in sufficient quantity to complete the
protocol(s) sponsored by DCTD, that have been mutually agreed upon by
Collaborator and DCTD; it being understood that PHS shall take responsibility
for and reasonable steps to maintain appropriate records and assure appropriate
supply, handling, storage, distribution and usage of these materials in
accordance with the terms of this Agreement, the protocol(s) and any applicable
laws and regulations relating thereto. The contact person for DCTD will be Xx.
Xxxx Xxxxxxx, Acting Chief, Pharmaceutical Management Branch (Telephone Number
000-000-0000) and the Collaborator contact will be Xxxxx Xxxxxxx, Senior
Clinical Research Associate (Telephone Number 000-000-0000). Collaborator will
provide Certificates of Analysis to DCTD for each lot of finished product
provided. Collaborator further agrees to provide draft Agent labels to the
Pharmaceutical
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Management Branch (PMB) for review and agree to reasonable labeling revisions to
comply with DCTD label guidelines. Collaborator agrees to supply sufficient
inventory to ensure adequate and timely supply of Agent for mutually agreed upon
protocol(s). PMB and Collaborator will negotiate the inventory requirements and
Agent shipments sufficient to meet DCTD's requirements for approved protocol(s).
Furthermore, Collaborator agrees to permit DCTD to provide Agent, or
unformulated analytical grade Agent or metabolites, if available, to DCTD
extramural investigators for the development of analytical assays or ancillary
correlative studies conducted in conjunction with protocols approved by DCTD and
agreeable to Collaborator in accordance with the provisions of Articles 2 and 4.
All protocols sponsored by DCTD using Agent must be mutually agreeable to
Collaborator and DCTD, in as much as Collaborator will have final authority over
the provision of its agent to DCTD.
Collaborator agrees to allow Agent to be distributed for mutually agreeable
preclinical studies designed to enhance the basic understanding and development
of the agent. These will include preclinical studies designed to support
clinical trials in pediatric patients; preclinical combination studies to
provide data in support of a clinical trial and other pertinent requests. All
NCI intramural investigators will sign appropriate NCI Intramural MTAs. Requests
from NCI extramural investigators will sign either a Collaborator MTA for the
agent Agent will be considered by Collaborator and DCTD on a case by case basis.
At the discretion of the Collaborator, DCTD will have extramural investigators
xxxxxx the appropriate NCI MTAs for single agent preclinical studies, that
acknowledge the proprietary nature of the Agent to Collaborator and include
intellectual property and publication provisions consistent with those in this
agreement and for clinical trials. The appropriate MTA will be discussed on a
case by case basis with Collaborator and DCTD.
Article 7. Data Rights
The data generated under this Agreement are considered the property of the party
that generates the data. Generally, data generated in trials sponsored by DCTD
with funding through Grants or Cooperative Agreements are considered the
property of the Extramural Principal Investigator or the Cooperative Groups,
respectively. Generally, the data generated in trials sponsored by DCTD with
funding through Contracts are the property of DCTD. The data generated by NCI
intramural principal investigators are the property of NCI. It is the intention
of the NCI that except as may be required by the Freedom of Information Act or
other applicable law or court order that Collaborator shall have complete and
exclusive access to all the data and results generated under this Agreement that
are in the possession and control of DCTD. This includes all data received from
DCTD-sponsored extramural clinical trials, which are generally made available to
DCTD in summary form (Summary Data), compilations of which are included in the
Annual Report to FDA. All the data and results generated under this Agreement
that are in the possession and control of DCTD will be made fully and
exclusively available to Collaborator for its own analyses and for its
application for FDA approval. If there are additional costs to the investigator
for providing such data, the investigator shall be reimbursed for the reasonable
additional costs by Collaborator in a manner to be negotiated by investigator
and Collaborator, after discussing the data required with the CTEP contact (Xx.
Xxxxxx Xxxxxx, Regulatory Affairs Branch,
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Telephone Number 000-000-0000). As described in the Intellectual Property Option
to Collaborator and the NCI Standard Protocol Language, Clinical Data and
Results and Raw Data will be provided exclusively to the NCI, the Collaborator
and the FDA, as appropriate. In accordance with the HHS Office of Human Research
Protection guidelines, Collaborator access to and review of Identifiable Private
Information shall be only for on-site quality auditing. Collaborator will
receive Identifiable Private Information only for purposes of satisfying FDA or
other health authorities' reporting requirements, and for internal research
purposes, directly related to obtaining regulatory approval of Agent.
Collaborator is prohibited from access, review, receipt, or use of such
information for other purposes.
Article 8. FDA Meetings
All meetings with FDA concerning Agent will be discussed by Collaborator and
DCTD in advance and will be held on mutually agreed upon dates. Collaborator
will have the option to set the agenda for such a meeting. One of the missions
of DCTD is to ensure that active investigational therapies are approved and made
widely available in a timely fashion. Therefore, DCTD feels it is important to
participate in the development plan for Agent and in discussions with the FDA
regarding the design and endpoints of the pivotal trials. In addition, DCTD
expects that Collaborator will actively pursue approval of Agent by the FDA and
will take the initiative in arranging meetings with the FDA.
Article 9. Proprietary Data
Any preclinical or formulation data considered proprietary by Collaborator will
be treated as such by DCTD. Collaborator should state in advance what
information it considers proprietary and DCTD can accept, or decline to accept,
information so designated. DCTD shall treat in confidence any of Collaborator's
written information about the study that is stamped "CONFIDENTIAL" for a period
of three (3) years from the date of disclosure, unless Collaborator informs DCTD
that the Confidential Information is still secret and confidential, and DCTD
concurs, in which case the obligations hereof shall extend for a further period
of two (2) years. Any proprietary information which is orally disclosed must be
reduced to writing and marked "CONFIDENTIAL" within thirty (30) days of such
disclosure. Such Proprietary Data shall not include information or data exempted
from the definition of "Proprietary Data" under Article 1. Primary data relating
to sensitive laboratory studies will, upon request by Collaborator, be returned
to Collaborator by DCTD. However, summaries of all such studies will be retained
in the DCTD files. It is the intention of the NCI that except as may be required
by the Freedom of Information Act or other applicable law or court order that
all data derived from clinical trials at a DCTD-sponsored institution will be
made fully, and exclusively available for use by Collaborator in obtaining
regulatory approval. The data will be made available to DCTD in summary form
(Summary Data).
Article 10. Data Exchange
DCTD will supply Collaborator with all information submitted to its IND as
outlined above and subject to the limitations set forth in this Agreement. DCTD
will receive information from the
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Collaborator's IND including, but not limited to, Annual Reports, Clinical
Brochures, adverse drug experiences, and formulation and preclinical data,
including toxicology findings.
Article 11. Monitoring
In conjunction with the DCTD Project Officer for the CTMS Contract, Collaborator
can make arrangements to receive copies of data from CTMS Monitored Studies in
the format it desires. CTMS will be reimbursed by Collaborator for the cost of
reformatting (if any) and reproduction of the data. Copies of annual data
summaries submitted to DCTD for non-CTMS Monitored Studies will be available to
Collaborator upon request. More frequent monitoring of any non-CTMS Monitored
Study can be arranged. Collaborator, at the time of protocol review, should
indicate which protocol(s) it wishes to monitor more frequently. A section will
be added to the protocol(s) to document the arrangements. Any arrangement which
involves the collection of more than summarized data provided annually will be
at the expense of Collaborator. For instance, Collaborator may, independently of
this Agreement, enter into a separate agreement with a third party, mutually
agreed upon between DCTD and Collaborator, where under Collaborator will pay for
the services of data management personnel to assist the DCTD Principal
Investigator with data entry and other data-related activities involved in the
performance of the Study. Should DCTD conduct an audit to confirm the anti-tumor
activity of a treatment regimen using Agent, Collaborator is encouraged to
attend and participate in the data review. Since data will be collected under
the NCI IND, should Collaborator choose to contact an investigator to collect or
review data, Collaborator must first contact the Regulatory Affairs Branch, DCTD
for prior approval. The Regulatory Affairs Branch will then notify the
investigator(s) of Collaborator's request and encourage the investigator(s) to
provide full access to the requested data. Collaborator will reimburse the
investigator(s) for any and all costs associated with fulfilling Collaborator's
request.
Article 12. Publications and Commercialization
The DCTD investigators maintain the full right to present and publish the data
at such time and place as they see fit. Manuscripts from all clinical trials
involving Agent or those to which Collaborator has specifically committed
financial resources should have advisory review and comment to assure that
Proprietary Data is protected prior to submission for publication. Collaborator,
at the time of protocol review, should indicate for which protocol(s) it wishes
to review manuscripts prior to submission. The amount of time required for the
review shall not exceed thirty (30) days. The publication or other disclosure
shall be delayed for up to an additional thirty (30) days upon written request
by either Party to this Agreement as necessary to preserve U.S. or foreign
patent or other intellectual property rights.
Abstracts presented by NCI investigators will be sent to NCI's Regulatory
Affairs Branch for forwarding to Collaborator as soon as they are received,
preferably prior to submission, but prior to presentation or publication for
courtesy notification.
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Article 13. Use of Name
Collaborator may use, refer to and disseminate reprints of scientific, medical
and other published articles which disclose the name of DCTD or NCI consistent
with U.S. copyright laws, provided such use does not constitute an endorsement
of any commercial product or service by DCTD or NCI. Collaborator shall take
every step possible to ensure that references to the articles are accurate, and
shall explicitly state that any such reference does not claim, infer or imply an
endorsement or recommendation of the product by the Investigator or the NCI,
NIH, PHS or DHHS. Collaborator shall not use the name of DCTD or NCI or any of
the foregoing in any advertising, packaging, or promotional material in
connection with Agent except with the written permission of DCTD or NCI or as
may be required by law. Collaborator-issued press releases that reference or
rely upon the work of NCI under this Agreement shall be made available to CTEP
at least seven days prior to publication for review and comment. They should be
sent to Xx. Xxxxxx Xxxxxx, Regulatory Affairs Branch (fax 000-000-0000; email
xxxxxxx@xxxx.xxx.xxx.xxx).
Article 14. Patents
Generally, the rights of ownership of inventions, discovered or made solely in
connection with work covered by this Agreement, are retained by the organization
that is the employer of the inventor. Both Collaborator and DCTD recognize that
these rights will be determined under patent law. However, pursuant to 35 U.S.C.
201(c) and 35 U.S.C. 202(c)(4), when an individual who is not a Government
employee, but who is under a Government Funding Agreement, is the sole inventor,
the U.S. Government retains a nonexclusive, irrevocable, paid-up license to
practice the invention or to have the invention practiced throughout the world
by or on behalf of the U.S. Government. DCTD will notify Collaborator upon
filing a patent application on any invention NCI employees make while using the
Agent furnished to DCTD under this Agreement. Such notification of an invention
report or patent application filing shall not constitute a grant to Collaborator
of an option to a license in advance, nor shall it guarantee the exclusivity of
any license which may subsequently be negotiated. DCTD will seriously consider
Xxxxxxxxxxxx's request for a nonexclusive, partially exclusive or exclusive
royalty-bearing license to make, use and/or sell products embodying the
invention as claimed in the filed patent application, subject to the terms of 35
U.S.C. 207, 208, and 209, under 37 CFR Part 404 to any invention made by DCTD
investigators during this study when a U.S. Government employee is the sole
inventor. NCI will cooperate with Collaborator by ensuring that all
investigators conducting clinical trials with Agent have the Intellectual
Property Option to Collaborator on file with their institutions.
Collaborator warrants, to the best of its knowledge, that DCTD's use of Agent in
this Clinical Trials Agreement and Collaborator's commercialization of Agent
does not infringe any U.S. Letters Patent (except U.S. Letters Patent issued
upon an application which is now or may hereafter be kept secret or otherwise
withheld from issue).
The Collaborator shall promptly report to DCTD each notice or claim of patent or
copyright infringement based on the performance of this CTA of which the
Collaborator has knowledge.
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Article 15. Travel and Other Interactions
In order to xxxxxx development of Agent, the participation of DCTD staff will
likely be required at selected scientific or development meetings. As part of
this Agreement, it is agreed that Collaborator will provide for the
transportation and associated costs for attendance of DCTD staff in such
activities. Selection of participating DCTD staff must be based on choices
mutually acceptable to both Collaborator and DCTD. Both Collaborator and DCTD
must agree that the activities would be appropriate under this Agreement, and
acceptance of Collaborator's support of DCTD's participation in the activities
will be contingent upon appropriate DCTD approval. Other interactions which
materially assist the development of potentially important new therapies will
also be possible. Again, mutual agreement and appropriate DCTD approval will be
necessary, according to the terms of this Agreement. However, notwithstanding
anything to the contrary, this Agreement does not represent a Cooperative
Research and Development Agreement (CRADA, under the Federal Technology Transfer
Act, 15 U.S.C. 3701 et seq.) Travel costs are limited by the Federal Travel
Rules and Regulations for all government staff whether paid for by government
funds or private Collaborators.
Article 16. Liability
No indemnification for any loss, claim, damage, or liability is intended or
provided by either Party under this Agreement. Each Party shall be liable for
any loss, claim, damage, or liability that said Party incurs as a result of said
Party's activities under this Agreement, except that DCTD, as an agency of the
United States, assumes liability only to the extent as provided under the
Federal Tort Claims Act (28 U.S.C. Chapter 171 Sections 2671-2680).
Article 17. Governing Law
This Agreement shall be governed by and construed in accordance with Federal law
as construed by the Federal Courts of the District of Columbia.
Article 18. Severability
The terms of this Agreement are severable. If any item or provision of this
Agreement shall to any extent be invalid or unenforceable, the remainder of this
Agreement shall not be affected, and each remaining item and provision of this
Agreement shall be valid and shall be enforceable to the fullest extent
permitted by law.
Article 19. Survivability
The provisions of this Agreement as they relate to confidentiality and drug
supply shall survive the expiration or earlier termination of this Agreement.
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Article 20. Compliance with DHHS Regulations
DCTD and Collaborator agree to comply with all Department of Health and Human
Services regulations relating to Human Subject use, and all Public Health
Service policies relating to the use and care of laboratory animals.
Article 21. Termination
A. This Agreement expires on the earlier to occur of the completion of the
research or three (3) years from the date of execution of this Agreement. Said
expiration date may be changed by mutual agreement and written amendment of this
Agreement.
B. This Agreement may be terminated at any time by the mutual written consent of
the Parties.
C. Either Party may unilaterally terminate the Agreement at any time by giving
written notice to the other Party at least sixty (60) days prior to the desired
termination date.
D. On expiration or earlier termination of this Agreement, Collaborator will
supply enough Agent to complete the clinical studies as are then ongoing or
approved, pursuant to the provisions of Article 6.
E. If Collaborator unilaterally terminates this Agreement, but DCTD elects to
continue its development of Agent, and if Collaborator elects to sublicense
Agent to a third party, the third party will be mutually agreeable to the NCI
and will agree to enter into a collaborative clinical development agreement
(Clinical Trials Agreement or Cooperative Research and Development Agreement) to
ensure the continued development of Agent. Finally, the IND, the Raw Data, and
Clinical Data and Results generated by the clinical trials are being provided
under this Agreement exclusively to Collaborator for use in Agent's anticipated
commercialization and, therefore, shall not be shared or transferable to any
third party without the written permission of the NCI.
Article 22. Clinical Trial Agreement Amendments
Upon mutual agreement of both parties, this Agreement may be amended as
necessary to ensure the Agreement accurately reflects the terms and scope of the
collaborative research project. The Amendment shall be in writing signed by both
the authorized representative of Collaborator and the Director of the DCTD.
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SIGNATURES
This Agreement, and any Amendments hereto, provides the basis for mutually
satisfactory co-development of Agent as an anti-cancer agent.
By executing this Agreement, each of the undersigned represents and confirms
that he or she is fully authorized to bind the identified entity to its terms.
Each of the undersigned expressly certifies or affirms that the contents of any
statement made or reflected in this document are truthful and accurate.
AGREED TO AND ACCEPTED BY:
For the National Cancer Institute:
/s/ Xxxxx Xxxxxx 1/6/2003
------------------------------ ---------------------
Xxxxx Xxxxxx, M.D. Date
Acting Director, Division of Cancer Treatment and Diagnosis
Address correspondence related to this Agreement to:
Xxxxx Xxxxxxx
Senior Specialist, Research & Development Agreements
Regulatory Affairs Branch
Cancer Therapy Evaluation Program, DCTD
National Cancer Institute, NIH
0000 Xxxxxxxxx Xxxxxxxxx, Xxxxx 0000
Xxxxxxxxx, XX 00000
Telephone: 000-000-0000
Fax: 000-000-0000
For the Collaborator:
/s/ Xxxxx Xxxxx, M.D. 1/9/2003
------------------------------ ---------------------
Xxxxx Xxxxx, M.D. Date
Vice President, Clinical Affairs
Address correspondence related to this Agreement to:
Xxxxx XxXxxx
Associate Director, Project Management
Vion Pharmaceuticals, Inc.
Four Science Park
New Haven, Connecticut 06511
Telephone: 000-000-0000, ext. 552
Fax: 000-000-0000
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