[Federal Register Volume 61, Number 57 (Friday, March 22, 1996)]
[Notices]
[Pages 11852-11853]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-7015]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institute of Environmental Health Sciences: Opportunity 
for a Cooperative Research and Development Agreement (CRADA) for the 
Application of Highly Potent and Ultraselective  Opioidmimetic 
Peptide Antagonists for Biochemical, Pharmacological, Clinical and 
Therapeutic Studies

AGENCY: National Institute of Environmental Health Sciences, National 
Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The National Institutes of Health (NIH) seeks an agreement 
with a company(s) which can pursue commercial development of highly 
selective  opioid dipeptide antagonists (U.S. Patent 
Application Serial No. 08/347,531). The National Institute of 
Environmental Health Sciences has also determined that the developed 
technology can be utilized in several scientific areas, including 
development of a radiochemically labelled ligand, production of gram 
quantities of the dipeptide, application in the treatment of many 
clinical syndromes with therapeutic application to numerous health 
problems. A CRADA for the application of these compounds will be 
granted to the awardee(s).

ADDRESSES: Proposals and questions about this opportunity may be 
addressed to Dr. Lawrence H. Lazarus, NIEHS, Mail Drop C3-04, P.O. Box 
12233, Research Triangle Park, NC 27709; Telephone 919/541-3238; Fax 
919/541-0626; Email L[email protected]
    Requests to view the patent application and questions related to 
licensing this technology should be addressed to Leopold J. Luberecki, 
Jr., J.D., Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804 
(Telephone: 301/496-7735 ext. 223; Fax: 301/402-0220).
    Respondees interested in submitting a CRADA proposal should be 
aware that it may be necessary to secure a license to the above patent 
rights in order to commercialize products arising from a CRADA 
agreement.

DATES: Capability statements must be received by NIH on, or before May 
21, 1996.

SUPPLEMENTARY INFORMATION: The National Institute of Environmental 
Health Sciences has determined the specific chemical structure, high 
potency and selectivity of a series of unique opiod di- and tripeptide 
antagonists. The most active dipeptide exhibited an affinity for the 
 opioid receptor of 0.022 nM and a  selectivity of 
150,000 (relative to the  receptor); affinity toward  
receptors was negligible (> 20 M). the tripeptide had 
 selectivity of 20,000 and was similarly without effect on 
 receptors (> 50 M). Pharmacological functional 
bioassays in vitro indicated antagonistic activity at  
receptors without activity toward  receptors (> 10 
M), which makes these compounds more utilitarian than the 
commonly employed  antagonist naltrindole. Similarly, in vivo 
data in mice confirmed the antagonistic behavior of these peptides. 
Furthermore, the molecular model of the low energy conformer indicated 
a unique solution topography of a universal antagonist.
    The commercial advantage of these substances is manifold:
    1. The preparation of radiolabelled ligands for the biochemical 
characterization of the  opioid receptor, localization of this 
receptor in animal tissues by various immunohistochemical methods, and 
body distribution/compartmentalization kinetics, such as in determining 
the extend of transit across the blood-brain barrier. Current 
radioactive opioid ligands generally have lower affinities and are 
considerably less selective by orders of magnitude than our opioid 
dipeptide.
    2. The preparation of large quantities of highly pure peptide for 
pharmacological and physiological studies in the laboratory, and their 
availability for animal and clinical trials, and eventually for 
therapeutic applications in medical orientated facilities. For example, 
the potential for treatment of alcohol dependency and narcotic 
addition, obesity, and suppression of the immune response in organ 
transplants, in addition to other numerous clinical situations. These 
proposed studies would eventually necessitate multigram quantities of 
the dipeptide in spite of its high affinity and selectivity.
    3. Production of monoclonal antibodies to these peptides would 
provide science with high affinity substances that could be effectively 
used in both the laboratory and clinical settings.
    The CRADA awardees will have an option to negotiate for an 
exclusive license to market and commercialize any new technology 
developed within the scope of the research plan for the ultraselective 
 opioid dipeptide antagonists. This CRADA may be directed 
toward the preparation of radioligands, synthesis of gram quantities of 
peptide, its application in

[[Page 11853]]
animal model studies, as well as in clinical and therapeutic 
situations, and in the formation of monoclonal antibodies.

Roles of NIEHS

    1. Provide design and specifications of synthesizing the opioid 
dipeptide and assist in beta testing both the labeled and unlabled 
ligands, and monoclonal antibodies.
    2. Work cooperatively with the company(s) to determine the market 
potential for these opioidmimetic peptides.

Roles of the CRADA Partner

    1. Provide expertise in application and commercial-oriented 
production of large quantities of opioid peptides.
    2. Provide knowledge on the formation, purification, and 
stabilization of radioactive substances.
    3. Provide the expertise for the production of high affinity, high 
specific monoclonal antibodies.
    4. Develop a plan for the production, testing and commercialization 
of the dipeptide, radiolabeled compounds and monoclonal antibodies.
    Selection criteria for choosing the CRADA partner(s) will include, 
but will not be limited to the following:
    1. Experience in peptide synthesis.
    2. Capability to produce stable radiolabeled peptides with high 
specific activity.
    3. Ability to develop, implement and manage the product 
commercialization so as to ensure the dissemination of the substances 
of research or health care services.
    4. Capacity to test labeled peptides and monoclonal antibodies.

    Dated: March 13, 1996.

Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-7015 Filed 3-21-96; 8:45 am]
BILLING CODE 4140-01-M