DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health

National Cancer Institute: Opportunity for a Cooperative Research Agreement
(CRADA) for the Scientific and Commercial Development of Diagnostic and/or
Therapeutic Agents for Hyperpigmentary Lesions

AGENCY: National Institutes of Health, PHS, DHHS

ACTION: Notice

SUMMARY: The National Cancer Institute (NCI), seeks a pharmaceutical or
cosmetic company that can effectively pursue the scientific and commercial
generation and development of agents inhibiting pigmentation. The project is
of scientific importance since it will characterize mechanisms whereby
melanocyte function is compromised to produce hyperpigmented lesions. As
such, this research will seek to provide insights into mechanisms responsible
for clinically abnormal hyperpigmentation such as occurs in postinflammatory
hyperpigmentation and other pigmentary diseases. NCI has successfully
characterized the melanogenetic functions of several pigmentary genes that are
important to the regulation of mammalian pigmentation. The NCI has produced a
number of specific antibodies which recognize those gene products as well as a
number of oligonucleotides and cDNAs whereby expression of their encoding
genes can be quantitated. The selected sponsor will collaborate in a project
aimed at using those probes to characterize melanocyte function in
hyperpigmentary conditions and to develop agents useful commercially to down
regulate melanogenic function.

ADDRESS: Inquiries and proposals regarding this opportunity should be
addressed to Mark Noel or Bert Zbar (Telephone 301/496-0477, Facsimile
301/402-2117), Office of Technology Development, National Cancer Institute,
Bldg 31, Room 4A49, National Institutes of Health, 9000 Rockville Pike,
Bethesda MD 20892.

DATES: Proposals must be received at the above address by no later than [FR:
insert date 60 days after date of publication].

SUPPLEMENTARY INFORMATION: "Cooperative Research and Development Agreement"
or "CRADA" means the anticipated joint agreement to be entered into by NCI
pursuant to the Federal Technology Transfer Act of 1986 and Executive Order
12591 of October 10, 1987 to collaborate on the specific research project
described below.

The NCI is seeking a pharmaceutical or cosmetic company which can lend
resources and scientific expertise to a project aimed at identifying
mechanisms responsible for abnormal melanocyte function in clinical
hyperpigmentary conditions. Little is known about the level of abnormal
function of melanocytes in a number of clinical conditions of
hyperpigmentation, such as occurs in postinflammation, wound healing and/or
photodamaged/age pigmented lesions. This proposed study will employ a number
of antibodies specific for melanogenic proteins to examine melanocyte
function, and thus levels of melanogenic protein expression, in such lesions.
DNA probes specific for the encoding genes will be used to characterize the
level of abnormal regulation of any gene products so identified. Approaches
will be designed to attempt to correct abnormal expression of such genes, or
the function of their encoded proteins and thus down-regulate pigmentation
in vitro, with the ultimate goal of developing commercially useful therapeutic
agents to treat conditions of epidermal hyperpigmentation. Since pigment
production is inherently associated with photoprotection against UV-induced
carcinogenesis, further benefit of these studies towards photoprotection may
evolve. The CRADA will allow the selected partner to provide expertise and
resources, in collaboration with NCI, for the preclinical development of
agents useful in the treatment of epidermal hyperpigmentary conditions.
Further clinical development of such agents may also be made subject to this
agreement, or a separate agreement at a later date, and upon mutual agreement
of the parties.

The expected duration of the CRADA will be three (3) to five (5) years.

The role of the National Cancer Institute, the Division of Cancer Biology,
Diagnosis and Centers includes:

1. NCI will provide specific antibodies and probes useful to examine
expression of pigmentary genes in hyperpigmented tissues.

2. NCI will perform enzymatic assays that measure melanogenic protein
function in hyperpigmented tissues.

3. NCI will examine melanocyte function via expression of pigmentary genes
in hyperpigmentary lesions.

4. NCI will screen potential inhibitors or down-regulators of melanogenic
activity using in vitro techniques with melanocytes in culture.

5. NCI will collaborate with the corporate partner on the design of
experiments and evaluation of results.

The role of the successful corporate partner will include:

1. Supply expertise in melanocyte function in hyperpigmentary disorders.

2. Supply potential melanogenic inhibitors or down-regulators of
melanogenic activity for testing.

3. Provide funds to support a postdoctoral fellow and associated expenses
of the study.

4. The corporate partner will collaborate with the NCI on the design of
experiments and the evaluation of results.

Criteria for choosing the collaborating company will include:

1. Experience in the study of hyperpigmentary disorders.

2. Ability to provide adequate amounts of potential melanogenic inhibitors
or down regulators of melanogenic activity for the preclinical studies
which are subject to the research plan.

3. Experience and ability to produce, package, market and distribute
pharmaceutical and/or cosmetic products, including experience with the
regulatory approval process and with the FDA.

4. Willingness to cooperate with the NCI in the collection, evaluation,
maintenance and publication of data from the investigation.

5. Willingness to share costs of the laboratory studies.

6. An agreement to be bound by DHHS rules involving the use of human and
animal subjects, and human tissue.

7. Provisions for equitable distribution of patent rights to any
inventions. Generally the rights of ownership are retained by the
organization which is the employer of the inventor, with (1) an
irrevocable, nonexclusive, royalty-free license to the Government (when
a company employee is the sole inventor) or (2) an option to negotiate
an exclusive or nonexclusive license to the company on terms that are
appropriate (when the Government employee is the sole inventor or where
a joint invention arises).