[Federal Register Volume 60, Number 154 (Thursday, August 10, 1995)]
[Notices]
[Pages 40844-40846]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-19733]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Cancer Institute: Opportunity for a Cooperative Research 
and Development Agreement (CRADA) for the Development of New Types of 
Therapeutic Compounds for Acquired Immunodeficiency Syndrome (AIDS) and 
Other Human and Animal Diseases of Retroviral Etiology Identified Using 
Novel Screening Assays

AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: Pursuant to the Federal Technology Transfer Act of 1986 (FTTA, 
15 U.S.C. Sec. 3710; Executive Order 12591 of April 10, 1987), the 
National Cancer Institute (NCI) of the National Institutes 

[[Page 40845]]
of Health (NIH) of the Public Health Service (PHS) of the Department of 
Health and Human Services (DHHS) seeks a Cooperative Research and 
Development Agreement (CRADA) with a pharmaceutical or biotechnology 
company to develop novel therapeutics for AIDS and other human and 
animal diseases of retroviral etiology based upon a newly identified 
highly conserved HIV target protein. Any CRADA for the biomedical use 
of this technology will be considered. The CRADA would have an expected 
duration of one (1) to five (5) years. The goals of the CRADA include 
the rapid publication of research results and their timely 
commercialization. The CRADA Collaborator will have an option to 
negotiate the terms of an exclusive or nonexclusive commercialization 
license to subject inventions arising under the CRADA.

ADDRESSES: Proposals and questions about this CRADA opportunity may be 
addressed to Cindy K. Fuchs, J.D., Office of Technology Development, 
National Cancer Institute-Frederick Cancer Research and Development 
Center, P.O. Box B, Frederick, MD 21702-1201, Telephone: (301) 846-
5465, Facsimile: (301) 846-6820. Background information, including 
abstracts and reprints, is available. In addition, pertinent 
information not yet publicly disclosed may be obtained under a 
confidential disclosure agreement.
    Requests for copies of the patent applications, license application 
form, or other questions and comments concerning the licensing of this 
technology should be directed to Steven M. Ferguson, Acting Chief, 
Infectious Disease Branch, Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
MD 20852-3804, Telephone: (301) 496-7735 ext. 266, Facsimile: (301) 
402-0220. A signed confidentiality agreement will be required to 
receive copies of the patent applications.

EFFECTIVE DATE: In view of the high priority for developing new drugs 
for the treatment of HIV infection, interested parties should notify 
the NCI Office of Technology Development in writing no later than sixty 
(60) days from the date of this announcement. Respondents will then be 
provided an additional ninety (90) days for submitting formal CRADA 
proposals.

SUPPLEMENTARY INFORMATION: Current antivirals are ineffective against 
HIV-1 largely due to the emergence of drug resistant viral mutants. 
HIV-1 contains regions known as CCHC zinc fingers in the retroviral 
nucleocapsid protein. These CCHC zinc fingers are highly conserved 
throughout nearly all retroviruses. The CCHC zinc fingers are sequences 
of 14 amino acids with four invariant residues, 
Cys(X)2Cys(X)4His(X)4Cys, that chelate zinc and perform 
essential functions in viral infectivity. Mutations in the CCHC zinc 
fingers render HIV-1 non-infectious. Many compounds that disrupt the 
CCHC zinc fingers also inactivate the HIV-1 virus. HIV-1 has two zinc 
fingers, both of which are necessary for infectivity. The invariant 
nature of the retroviral zinc fingers and the requirement of both 
fingers would make the development of drug resistant viral mutants 
unlikely. HIV-1 CCHC zinc fingers exhibit a previously unrecognized 
susceptibility to attack by certain types of compounds. Compounds with 
this activity may be useful for developing new types of anti-retroviral 
drugs.
    The AIDS Vaccine Program at the National Cancer Institute-Frederick 
Cancer Research and Development Center (NCI-FCRDC) has developed novel 
screening assays for identifying compounds capable of inactivating 
retroviruses, including HIV-1. The screening assays are based on the 
ability of a compound to disrupt the CCHC zinc fingers. Retroviral CCHC 
zinc fingers complex with two zinc ions, each with a formal charge of 
+2. Compounds that react with the CCHC zinc fingers and remove the zinc 
ions cause a change in the conformation and charge of the nucleocapsid 
protein, which can be detected as a change in its electrophoretic 
mobility using capillary zone electrophoresis (CZE). Purified CCHC zinc 
fingers may be reconstituted with radioactive zinc\65\. By monitoring 
the release of radioactive zinc\65\ caused by the reaction of a test 
compound with a retroviral CCHC zinc finger, it is possible to 
determine the reactivity of the test compound. Changes in the intrinsic 
fluorescence, fluorescence of artificial probes, or fluorescent zinc 
chelators can be used to monitor the loss of zinc from the HIV-1 CCHC 
zinc fingers. Reverse phase high performance liquid chromatography 
(HPLC) can be used to separate CCHC zinc fingers that have been reacted 
with compounds resulting in covalent changes in these proteins. Nuclear 
magnetic resonance (NMR) can be used to monitor the loss of zinc from 
retroviral CCHC zinc fingers. Because these assays do not utilize live 
virus, special containment facilities are not required for the 
screening procedures. Several of these assays are adaptable for high 
through-put screening. Gel mobility shift assays also can be used to 
identify and study compounds which are able to penetrate intact virus 
and to induce conformational changes in the CCHC zinc fingers. These 
assays can utilize HIV-1 or retroviruses that are not pathogenic for 
humans. Since CCHC zinc fingers are highly conserved among nearly all 
retroviruses, assays based upon these structures are suitable for 
screening for drugs that would be effective against viruses for adult 
T-cell leukemia, tropical spastic paraparesis caused by Human T-Cell 
Leukemia Virus-I and -II (HTLV-I and HTLV-II) as well as retroviral 
infections in animals such as feline leukemia virus and feline 
immunodeficiency virus in cats, equine infectious virus in horses, and 
lentivirus isolated from sheep, goats and cattle.
    The patent portfolio for this technology includes the following 
pending patent applications:

Serial Numbers: 08/312,331 and 08/379,420
Title: ``A Method for Identifying and Using Compounds that Inactivate 
HIV-1 and Other Retroviruses by Attacking Highly Conserved Zinc Fingers 
in the Viral Nucleocapsid Protein''
Inventors: Dr. Louis E. Henderson, Dr. Larry O. Arthur, and Dr. William 
G. Rice.

    The patent rights in these inventions have been assigned to the 
United States of America. Parties interested in submitting a CRADA 
proposal should be aware that it may be necessary to secure a license 
to the foregoing patent applications in order to commercialize products 
arising from the CRADA.
    The role of the National Cancer Institute in this CRADA will 
include but not be limited to:

1. Providing intellectual, scientific, and technical expertise and 
experience to the research project.
2. Planning research studies and interpreting research results.
3. Providing screening assay reagent(s) to the CRADA Collaborator in 
``start-up'' quantities.
4. Contracting, as needed, support services at the NCI-FCRDC such as 
antigen and antibody production.
5. Screening candidate therapeutic compounds using the novel assays 
described above.
6. Screening promising candidates in HIV viral infectivity assays.
7. Publishing research results.

    The role of the CRADA Collaborator may include but not be limited 
to:

1. Providing significant intellectual, scientific, and technical 
expertise or experience to the research project.
2. Planning research studies and interpreting research results. 

[[Page 40846]]

3. Providing support for ongoing CRADA-related research in the 
development of candidate therapeutic compounds:
    (a) financial support to facilitate scientific goals;
    (b) technical or financial support for further design of candidate 
therapeutic compounds; and
    (c) financial and logistical support for clinical trials Phases I-
III.
4. Providing and implementing plans to independently secure future 
continuing supplies of candidate therapeutic compounds to assure 
continued preclinical and clinical development.
5. Providing plans and supporting clinical development leading to FDA 
approval of candidate therapeutic compounds.
6. Producing, packaging, marketing, and distributing successful 
therapeutic compounds.
7. Using the proposed technology for other novel biopharmaceutical and/
or veterinary applications.
8. Publishing research results.

    Selection criteria for choosing the CRADA Collaborator may include 
but not be limited to:
    1. The ability to collaborate with NCI on further research and 
development of this technology. This ability can be demonstrated 
through experience and expertise in this or related areas of technology 
indicating the ability to contribute intellectually to ongoing research 
and development.
    2. The demonstration of adequate resources to perform the research, 
development and commercialization of this technology (e.g. facilities, 
personnel and expertise) and accomplish objectives according to an 
appropriate timetable to be outlined in the CRADA Collaborator's 
proposal.
    3. The ability to perform clinical testing or trials, and obtain 
IND, NDA and FDA approval for a new drug or treatment modality.
    4. The willingness to commit best effort and demonstrated resources 
to the research, development and commercialization of this technology.
    5. The demonstration of expertise in the commercial development, 
production, marketing and sales of products related to this area of 
technology.
    6. The level of financial support the CRADA Collaborator will 
provide for CRADA-related Government activities.
    7. The willingness to cooperate with the National Cancer Institute 
in the timely publication of research results.
    8. The agreement to be bound by the appropriate DHHS regulations 
relating to human subjects, and all PHS policies relating to the use 
and care of laboratory animals.
    9. The willingness to accept the legal provisions and language of 
the CRADA with only minor modifications, if any. These provisions 
govern the equitable distribution of patent rights to CRADA inventions. 
Generally, the rights of ownership are retained by the organization 
which is the employer of the inventor, with (1) the grant of a research 
license to the Government when the CRADA Collaborator's employee is the 
sole inventor, or (2) the grant of an option to negotiate for an 
exclusive or nonexclusive license to the CRADA Collaborator when the 
Government employee is the sole inventor.

    Dated July 28, 1995.
Thomas D. Mays,
Director, Office of Technology Development, National Cancer Institute, 
National Institutes of Health.
[FR Doc. 95-19733 Filed 8-9-95; 8:45 am]
BILLING CODE 4140-01-P