[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