SCIENTIFIC AND COMMERCIAL DEVELOPMENT OF A NOVEL DRUG TARGETING MELANIN PRODUCING CELLS

Notice Date

October 18, 2001

Contracting Office

NIH/TDCB, 6120 Executive Blvd., Suite 450, Rockville, MD 20852

ZIP Code

20852

E-Mail Address

Click here to send a message to the CRADA point of (FrisbieS@otd.nci.nih.gov)

Description

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: FrisbieS@otd.nci.nih.gov

Web Link

Click here to view the standard NIH CRADA document. (http://ttb.nci.nih.gov/forms.html)

Record

Loren Data Corp. 20011022/SPMSC001.HTM (W-291 SN5109L3)