[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] ----------------------------------------------------------------------- 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 UltraselectiveOpioidmimetic Peptide Antagonists for Biochemical, Pharmacological, Clinical and Therapeutic Studies AGENCY: National Institute of Environmental Health Sciences, National Institutes of Health, PHS, DHHS. ACTION: Notice. ----------------------------------------------------------------------- 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