SCIENTIFIC AND COMMERCIAL DEVELOPMENT OF A NOVEL DRUG TARGETING MELANIN PRODUCING CELLS
Commerce Business Daily
SCIENTIFIC AND COMMERCIAL DEVELOPMENT OF A NOVEL DRUG TARGETING MELANIN
PRODUCING CELLS
National Cancer Institute Technology Transfer Branch CRADA Opportunity
Announcement Summary: The National Cancer Institute (NCI) is currently
seeking a Collaborator for a Cooperative Research and Development
Agreement (CRADA) to work with investigators in the Center for Cancer
Research (CCR) to develop a novel drug that targets melanin producing
cells for clinical use. Development will include formulation for topical
application, and subsequently for systemic administration, if this
latter route is deemed safe and effective. Background: The incidence of
malignant melanoma has increased during the past decade at a rate faster
than that of any other cancer, with the exception of lung cancer in
women. While a diagnosis is made early in the disease's clinical course
in the majority of patients, advanced disease occurs in a substantial
percentage of patients, and it is estimated that more than 7000 patients
will die of disseminated disease in 2001. Surgical management remains
the cornerstone of therapy, although significant advances have been made
in the immunotherapy of this disease in the past decade. Unfortunately,
chemotherapy has failed to contribute significantly to survival. A
majority of melanomas are pigmented at presentation and remain so during
their clinical history. The synthesis of melanin begins with the
hydroxylation of tyrosine, and following several steps leading to the
formation of DOPAchrome (3,4-dihydroxyphenylalanine), proceeds through a
spontaneous decarboxylation that leads to the production of DHI
(5,6-dihydroxyindole) and in turn Eumelanin. This CRADA proposes to
exploit this specific and highly active pathway using a newly synthesized
agent developed by NCI that would release free CN only in melanin
producing cells resulting in cancer cell death. In vitro studies
performed by NCI have shown that this agent is an excellent substrate for
tyrosinase, and that tyrosinase can convert the agent to melanin with the
release of free cyanide. Preliminary in vivo studies have demonstrated
that the agent is well tolerated in mice, with an LD50 exceeding 100
mg/kg. In addition to its use in the therapy of malignant melanoma, this
agent may have useful local applications in patients with the dysplastic
nevus syndrome as well as other cosmetic uses. Proposed NCI Contribution:
The role of the NCI in the CRADA will include, but not be limited to, the
following: -- Synthesize the initial lot of agent. -- Conduct preliminary
preclinical testing to determine the toxicity of the topically formulated
agent, and it activity as a specific toxin to melanin producing cells. --
As appropriate, NCI will initiate collaborative phase I clinical trials
for topical administration under its intramural or extramural clinical
trials network. Trials examining the systemic administration of the same
or another compound will also be considered depending on the available
data. Proposed CRADA Collaborator Contribution: The role of the CRADA
Collaborator will include, but not be limited to, the following: --
Formulate the initial lot of agent for topical administration.
Encapsulation in liposomes is desirable. -- Manufacture the topical
formulation of agent in sufficient quantities for use in clinical trials.
-- Collaborate in the planning and support clinical development leading
to FDA approval and marketing. Proposed Joint Contribution: NCI and the
CRADA collaborator will: -- NCI and the Collaborator will jointly design
a CRADA research plan and will jointly interpret the data generated
under the research plan. -- Provided the preliminary preclinical testing
is encouraging, conduct more extensive preclinical testing to determine
the toxicity of the topically formulated agent, and its activity as a
specific toxin to melanin producing cells. -- Publish these results and
share all data as soon as they become available. Selection Criteria for
Choosing the CRADA Collaborator May Include: 1. A demonstrated background
and expertise in conducting clinical trials, and in the topical
formulation of drugs. 2. The demonstration of adequate resources to
perform the research and development necessary for commercialization of
the technology and any inventions. 3. A demonstrated record of success in
the commercial development and production of products related to this
area of technology. 4. The level of financial and staffing support the
CRADA collaborator will provide for CRADA-related activities. 5. The
willingness to cooperate with the NCI in the collection, evaluation, and
maintenance of data from preclinical and clinical trials of
investigational agents; and in the timely publication of research
results. 6. The agreement to be bound by the Department of Health and
Human Services (DHHS) regulations involving the use of human and animal
subjects, and human tissue. 7. The willingness to accept the legal
provisions and language of the CRADA. These provisions govern the
distribution of future patent rights to CRADA inventions. Generally, the
rights of ownership are retained by the organization which is the
employer of the inventor, with (a) the grant of a license for research
and other Government purposes to the Government when the CRADA
collaborator's employee is the sole inventor, or (b) the grant of an
option to elect an exclusive or non-exclusive license to the CRADA
collaborator when the Government employee is the sole inventor. Response
Procedure: Interested parties should notify the Technology Transfer
Branch of the NCI in writing of their interest in the CRADA collaboration
no later than November 28, 2001. The written notice should briefly
address the selection criteria listed above. Contact Information: CRADA
Contact: Suzanne M. Frisbie, Ph.D. 6120 Executive Boulevard, Suite 450
Rockville, Maryland 20852 Phone: 301-496-0477; Fax: 301-402-2117 E-mail:
Fris...@otd.nci.nih.gov WEB: Click here to view the standard NIH CRADA
document., http://ttb.nci.nih.gov/forms.html. E-MAIL: Click here to send
a message to the CRADA point of, Fris...@otd.nci.nih.gov. Posted
11/02/01 (W-SN5121O5).