[Federal Register Volume 62, Number 101 (Tuesday, May 27, 1997)]
[Notices]
[Pages 28720-28721]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-13832]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Opportunity for a Cooperative Research and Development Agreement 
(CRADA) and Licensing Opportunity for Testosterone Bucyclate

AGENCY: National Institute of Child Health and Human Development, 
National Institutes of Health, Public Health Service, DHHS; and UNDP/
UNFPA/WHO/World Bank Special Programme of Research, Development and 
Research Training in Human Reproduction (WHO/HRP).

ACTION: Notice.

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SUMMARY: The National Institutes of Health and the World Health 
Organization are seeking (a) partner(s) for the further development, 
evaluation and commercialization of testosterone bucyclate and 
pharmaceutical compositions thereof. The invention claimed in the 
issued U.S. patent referenced below is available for either exclusive 
or non-exclusive licensing. Licensing by NIH is subject to 35 U.S.C. 
207 and 37 CFR part 404.

Long-Acting Androgenic Compounds and Pharmaceutical Compositions 
Thereof

    Inventors: Sydney Archer, Gabriel Bialy, Richard P. Blye, Pierre 
Crabbe, Egon R. Diczfalusy, Carl Djerassi, Josef Fried and Hyun K. Kim.
    Assignees: National Institutes of Health and the World Health 
Organization.
    Issued: August 14, 1990.
    Patent Number: 4,948,790.
    To expedite the research, development and commercialization of 
testosterone bucyclate, the National Institutes of Health and the World 
Health Organization are seeking one or more CRADA and/or license 
agreements with pharmaceutical or biotechnology companies in accordance 
with the regulations governing the transfer of Government-developed 
agents and WHO's public sector objectives, as outlined below. Any 
proposal to use or develop these drugs will be considered.

SUPPLEMENTARY INFORMATION: Androgens are principally employed in 
therapeutic medicine for replacement or supplementation in androgen 
deficiency states but also find use in hypopituitarism, menstrual 
disorders, anemia, promotion of anabolism, suppression of lactation and 
as a palliative measure in recurrent and metastatic carcinoma of the 
breast. NIH's and WHO's interest is to develop testosterone bucyclate 
for use in a hormonal method of male contraception and for androgen 
replacement in other methods of male contraception which usually 
compromise the endocrine as well as the gametogenic function of the 
testis. Long-term androgen therapy is complicated by the side effectes 
and/or poor bioavailability of oral preparations and the need for 
frequent injections of parenteral products. Two of the most commonly 
used injectable androgens, testosterone enanthate and testosterone 
cypionate, must be administered about every two weeks. There is thus a 
crucial need for longer-acting injectable androgens.
    Testosterone bucyclate emanated, in 1980, from a joint NIH-WHO-
sponsored steroid synthesis program in which the preparation of 
selected steroid esters was contracted by WHO and the resulting 
compounds screened by the Contraceptive Development Branch (CDB) of the 
National Institute for Child Health and Human Development at its 
Biological Testing Facility. Chemically, testosterone bucyclate is 
Testosterone 17-(trans-4n-butyl) cyclohexyl carboxylate. This 
ester of the natural hormone, testosterone, exhibits prolonged activity 
when administered intramuscularly as an aqueous crystalline suspension 
in all species studied, including man. The drug was evaluated, 
including pharmacokinetics and metabolic studies in both rodents and 
primates, by CDB. WHO supported studies in primates as well as the 
first clinical studies in hypogonadal and normal men. The patent is 
jointly held by NIH and WHO. NIH and WHO intend to continue joint 
development of testosterone bucyclate.
    Although each patentee may proceed with granting a non-exclusive 
license independently, joint licensing is envisaged. Licensing will 
include use of testosterone bucyclate as a hormonal method of male 
contraception, use for androgen replacement in other methods of male 
contraception, which usually compromise the endocrine as well as the 
gametogenic function of the testis and use as a therapeutic androgen 
for patients with androgen deficiency syndromes. A ``Notice of Claimed 
Investigational Exemption For A New Drug'' (IND) was filed with the FDA 
in October, 1996.
    The National Institute of Child Health and Human Development and 
the World Health Organization seeks partners for the further 
development and commercialization of testosterone bucyclate.
    The role of the National Institute of Child Health and Human 
Development and the World Health Organization is expected to be as 
follows:
    1. Provide the commercial partner with all biological data on 
testosterone bucyclate covered by the agreement.
    2. Provide samples of the drug and, upon successful completion of 
ongoing formulation studies, clinical dosage forms.
    3. Provide, upon successful completion of ongoing studies, chemical 
data on testosterone bucyclate, including routes of synthesis, 
analytical methods employed, purity, stability and formulation.
    4. Provide reports of all safety studies of the drug.
    5. Continue studies on the pharmacokinetics and biological activity 
of testosterone bucyclate and formulations thereof.
    6. Conduct appropriate studies to optimize formulations of 
testosterone bucyclate.

[[Page 28721]]

    7. Participate in meetings with the Food and Drug Administration 
for establishment of the protocols for Phase I, II and III clinical 
investigations and provide liaison with the FDA.
    The role of the commercial partner is expected to be as follows:
    1. Obtain a commercialization license from the NIH and the WHO.
    2. Assume responsibility for regulatory affairs including amending 
the IND as necessary.
    3. Assume responsibility for preparation and formulation of the 
drug for all pre-Phase III safety studies and clinical trials.
    4. Undertake such additional safety studies as may be required for 
Phase III clinical trials and for NDA submission.
    5. Undertake an orderly sequence of clinical investigations of 
testosterone bucyclate as a hormonal methods of male contraception and 
for androgen replacement in other methods of male contraception.
    6. Assume responsibility for preparation and filing of the NDA.
    7. Assume responsibility for commercial manufacture and 
distribution of the final products.
    8. Ensure availability of the final products to the public sector 
of developing countries in sufficient quantities, at a preferential 
price, in accordance with WHO's public sector objectives.
    Selection criteria for choosing commercial partners will 
furthermore include, but will not be limited to the following:
    1. The proposal must contain a clear statement of capabilities and 
experience with respect to the tasks to be undertaken. This would 
include experience in drug development, regulatory affairs and 
marketing.
    2. The proposal must contain a clear and concise outline of the 
work to be undertaken, a schedule of significant events, an outline of 
objectives to be accomplished with individual and overall times frames, 
and details of experimental procedures and techniques to be employed.
    3. The proposal must contain the level of financial support which 
will be supplied for the development of testosterone bucyclate.
    4. Agreement to be bound by DHHS and WHO rules and regulations 
regarding patent rights, the ethical treatment of animals, the 
involvement of human subjects in clinical investigations and the 
conduct of randomized clinical trials.
    5. Agreement with provisions for equitable distribution of patent 
rights to any inventions developed under the CRADA and license 
agreements.

DATES: In view of the high priority for developing and commercializing 
testosterone bucyclate, all proposals must be received no later than 
June 26, 1997 for priority consideration.

ADDRESSES: CRADA proposals and questions should be addressed to Dr. 
Diana Blithe, Contraceptive Development Branch, Center for Population 
Research, National Institutes of Child Health and Human Development, 
Room 8B 13, 6100 Executive Boulevard, Rockville, Maryland 20892 
(Telephone: 301/496-1661); with a copy to Director, UNDP/UNFPA/WHO/
World Bank Special Programme of Research, Development and Research 
Training in Human Reproduction, World Health Organization, 20, Avenue 
Appia, CH-1211 Geneva 27, Switzerland. Responders interested in 
submitting a CRADA proposal should simultaneously submit a license 
application concerning the above-mentioned patent rights to NIH and WHO 
for commercialization of products arising from the CRADA.
    Requests for copies of the U.S. patent, license application forms, 
or questions about the licensing opportunity should be addressed to Ms. 
Carol Lavrich, Technology Licensing Specialist, Office of Technology 
Transfer, National Institutes of Health, 6011 Executive Boulevard, 
Suite 325, Rockville, Maryland 20852-3804 (Telephone: 301/496-7735 ext. 
287), with a copy to Office of the Legal Counsel, World Health 
Organization, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland 
(Telephone: 00-41-22 7912685). Completed license applications should be 
submitted to the same addresses.
    Pertinent information not yet publicly described can be obtained 
under a Confidential Disclosure Agreement with the appropriate agency.

    Dated: May 16, 1997.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 97-13832 Filed 5-23-97; 8:45 am]
BILLING CODE 4140-01-M