[Federal Register Volume 61, Number 227 (Friday, November 22, 1996)]
[Notices]
[Pages 59452-59453]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-29892]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Cancer Institute and the Food and Drug Administration
Opportunity for a Cooperative Research and Development Agreement
(CRADA) for the Scientific and Commercial Development of Soluble Tat
Peptide Analogs for the Inhibition of HIV Transcription and Viral
Replication.
AGENCY: National Institutes of Health and the Food and Drug
Administration, PHS, DHHS.
ACTION: Notice.
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SUMMARY: The National Cancer Institute (NCI) and the Food and Drug
Administration (FDA), wherein the participation of the FDA is
contingent on resolution of any apparent conflict of interest issues,
seek a company that can collaboratively pursue the pre-clinical and
clinical development of Soluble Tat Peptide Analogs for the Inhibition
of HIV Transcription and Viral Replication. The National Cancer
Institute, Laboratory of Molecular Virology (LMV) and the Food and Drug
Administration, Center for Biologics, Laboratory of Immunochemistry,
have established that particular Soluble Tat Peptide Analogs can
inhibit the transcription and replication of the Human Immunodeficiency
Virus in vitro. The selected sponsor will be selected as a CRADA
partner for the co-development of this agent with the National Cancer
Institute and the Food and Drug Administration for the co-development
of this agent with the NCI and with the FDA, wherein the participation
of the FDA is contingent on resolution of any apparent conflict of
interest issues.
ADDRESSES: Questions about this opportunity may be addressed to Jeremy
A. Cubert, M.S., J.D., Office of Technology Development, NCI, 6120
Executive Blvd. MSC 7182, Bethesda, MD 20892-7182, Phone: (301) 496-
0477, Facsimile: (301) 402-2117, from whom further information may be
obtained. The Government has filed a patent application related to this
CRADA opportunity. For further information on licensing this patent
application (DHHS ref. no. E-059-96/0) contact Cindy Fuchs, J.D., NIH
Office of Technology Transfer, 6011 Executive Blvd., Suite 325,
Rockville, MD 20852, Phone: (301) 496-7735 (ext. 232); Facsimile: (301)
40002-0220.
DATES: In view of the important priority of developing new agents for
the treatment of infectious disease and related malignancies,
interested parties should notify this office in writing no later than
January 21, 1997. Respondents will then be provided an additional 30
days for the filing of formal proposals.
SUPPLEMENTARY INFORMATION: ``Cooperative Research and Development
Agreement'' or ``CRADA'' means the anticipated joint agreement to be
entered into by NCI pursuant to the Federal Technology Transfer Act of
1986 and amendments (including 104 Pub. L. 133) and Executive Order
12591 of October 10, 1987 to collaborate on the specific research
project described below.
The Government is seeking a pharmaceutical company which, in
accordance with the requirements of the regulations governing the
transfer of agents in which the Government has taken an active role in
developing (37 CFR 404.8), can further develop the subject compounds
through Federal Food and Drug Administration approval and to a
commercially available status to meet the needs of the public and with
the best terms for the Government. The government has applied for a
patent application directed to Inhibition of HIV Transcription and
Viral Replication Using Soluble Tat Peptide Analogs. Licenses to
intellectual property rights related to this opportunity are available
from the National Institutes of Health, Office of Technology Transfer
and may be necessary to continue development of the technology.
The tat gene encodes an 86 amino acid protein with a number of
identified domains including an N-terminus, a cysteine rich, a core
domain and a basic domain. Tat, through the core region, has been shown
to interact with and stabilize the TFIID basal transcription factor and
TFIIA preinitiation complex. Mutations within the core domain of Tat
significantly decrease both gene expression and viral replication.
National Cancer Institute (``NCI'') and Food and Drug Administration
(``FDA'') studies have been directed at synthesis of Tat peptide
analogs to compete with wild-type Tat in vivo. The NCI and FDA
synthesized soluble peptide analogs of the HIV-1 Tat protein. These
peptide analogs inhibit transactivation of HIV, viral replication and
formation of viral particles. The peptide analogs compete with Tat in
down-regulating Tat transactivation and induce a ninety percent
reduction of viral particles from infected cells in vitro. The
inhibitory peptide analogs are not toxic in vitro.
The Laboratory of Molecular Virology, Division of Basic Sciences,
NCI and the Laboratory of Immunochemistry, Division of Transfusion and
Transmitted Diseases, FDA are interested in establishing a CRADA with a
company to assist in the continuing development of these peptide
analogs, wherein the participation of the FDA is contingent on
resolution of any apparent conflict of interest issues. The Government
will provide all available expertise and information to date and will
jointly pursue pre-clinical and clinical studies as required, giving
the company full access to existing data and data developed pursuant to
the CRADA. The successful company will provide the necessary
scientific, financial and organizational support to establish clinical
efficacy and possible commercial status of the subject compounds.
The expected duration of the CRADA will be two (2) to five (5)
years.
The role of the National Cancer Institute and Food and Drug
Administration, wherein the participation of the FDA is contingent on
resolution of any apparent conflict of interest issues, includes the
following:
1. Determine the stability, half-life, and distribution of the Tat
peptides upon delivery into cells.
2. Determine the mechanism of the Tat peptide inhibition.
3. Determine the inhibitory effect of peptides on human ``primary''
T-lymphocytic and monocytic cells infected with various HIV-1 clades
(subtypes A, G, O, M).
4. Determine the inhibitory effect of peptide derivatives on
Kaposi's sarcoma primary cells.
5. Determine the effective dose of Tat Peptide analogs in
combination with other anti-retroviral drugs.
6. Conduct in vivo testing of appropriate compounds and/or peptide
analogs.
7. Evaluate in vivo test results.
8. Prepare manuscripts for publication.
The role of the collaborator, includes the following:
1. Synthesize soluble organic compounds using peptide mimetics to
[[Page 59453]]
mimic the inhibitory activity of the soluble peptide analogs.
2. Determine the mechanism of the Tat peptide inhibition.
3. Establish a suitable non-invasive peptide delivery system for
the preclinical and animal model studies.
4. Determine the effective dose of Tat peptide analogs in
combination with other anti-retroviral drugs.
5. Determine the stability, half-life, and distribution of the Tat
peptides upon delivery into cells.
6. Conduct in vivo testing of appropriate compounds and/or peptide
analogs.
7. Evaluate in vivo test results.
8. Develop vehicle for delivery of compounds to patients.
9. Conduct pre-clinical and clinical trials of appropriate
candidate compounds and/or peptide analogs.
10. Prepare manuscripts for publication.
Criteria for choosing the collaborator include its demonstrated
experience and commitment to the following:
1. The aggressiveness of the development plan, including the
appropriateness of milestones and deadlines for preclinical and
clinical development.
2. Scientific expertise in and demonstrated commitment to the
development of drug delivery systems.
3. Experience in preclinical and clinical drug development.
4. Experience and ability to produce, package, market and
distribute pharmaceutical products.
5. Experience in the monitoring, evaluation and interpretation of
the data from investigational agent clinical studies under an IND.
6. A willingness to cooperate with the NCI and FDA in the
collection, evaluation, publication and maintaining of data from pre-
clinical studies and clinical trials regarding the subject compounds.
7. Provision of defined financial and personnel support for the
CRADA to be mutually agreed upon.
8. An agreement to be bound by the DHHS rules involving human and
animal subjects.
9. Scientific expertise in and demonstrated commitment to the
treatment of HIV infection and related disorders.
10. Provisions for equitable distribution of patent rights to any
CRADA inventions. Generally the rights of ownership are retained by the
organization which is the employer of the inventor, with (1) an
irrevocable, nonexclusive, royalty-free license to the Government and
(2) an option for the collaborator to elect an exclusive or
nonexclusive license to Government owned rights under terms that comply
with the appropriate licensing statutes and regulations.
Dated: November 12, 1996.
Kathleen Sybert,
Deputy Director, Office of Technology Development, OD, NCI.
[FR Doc. 96-29892 Filed 11-21-96; 8:45 am]
BILLING CODE 4140-01-M