[Federal Register Volume 62, Number 38 (Wednesday, February 26, 1997)]
[Notices]
[Pages 8745-8746]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-4742]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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) 
402-0220.

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 
April 28, 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 P.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 
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

[[Page 8746]]

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 
mimic the inhibitory activity of the soluble 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: February 7, 1997.
Thomas D. Mays,
Director, Office of Technology Development, OD, NCI.
[FR Doc. 97-4742 Filed 2-25-97; 8:45 am]
BILLING CODE 4140-01-M