[Federal Register Volume 60, Number 108 (Tuesday, June 6, 1995)]
[Notices]
[Pages 29856-29857]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-13711]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

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

AGENCIES: 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 as 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 effects 
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 
[[Page 29857]] 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-4-n-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) is currently being 
prepared.
    The National Institute of Child Health and Human Development and 
the World Health Organization seek 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 clinical dosage forms.
    3. Provide 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.
    7. Prepare the IND.
    8. 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 NIH and the WHO.
    2. Participate in the development of the IND.
    3. Assume responsibility for regulatory affairs.
    4. Assume responsibility for preparation and formulation of the 
drug for pre-Phase III safety studies and Phase III clinical trials.
    5. Undertake such additional safety studies as may be required for 
Phase III clinical trials and for NDA submission.
    6. Undertake an orderly sequence of clinical investigations of 
testosterone bucyclate as a hormonal method of male contraception and 
for androgen replacement in other methods of male contraception.
    7. Assume responsibility for preparation and filing of the NDA.
    8. Assume responsibility for commercial manufacture and 
distribution of the final products.
    9. 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.

EFFECTIVE DATE: In view of the high priority for developing and 
commercializing testosterone bucyclate, all proposals must be received 
no later than September 5, 1995 for priority consideration.

ADDRESSES: CRADA proposals and questions should be addressed to Dr. 
Gordon Guroff, Deputy Scientific Director, National Institutes of Child 
Health and Human Development, Building 49, Room 5A64, Bethesda, 
Maryland 20892 (Telephone: 301/496-4751); 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 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 24, 1995.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 95-13711 Filed 6-5-95; 8:45 am]
BILLING CODE 4140-01-P