SPECIAL NOTICE
A -- Development of anti-CD 30 immunotoxins for the treatment of cancer
- Notice Date
- 12/5/2002
- Notice Type
- Special Notice
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bldg 427 Room 12, Frederick, MD, 21702
- ZIP Code
- 21702
- Solicitation Number
- Reference-Number-PT01
- Archive Date
- 1/31/2003
- Point of Contact
- Patrick Twomey, Senior Technology Transfer Specialist, Phone (301) 496-0477, Fax (301) 402-2117, - Bonnie Chamberlain, Marketing Coordinator, Phone (301)435-3134, Fax (301)402-2117,
- E-Mail Address
-
twomeyp@otd.nci.nih.gov, chamberbo@mail.nih.gov
- Description
- To develop a novel therapeutic agent to treat Hodgkin's disease and anaplastic large cell lymphoma, NCI has made a panel of recombinant immunotoxins specific for CD30 using Fvs of newly produced anti-CD30 monoclonal antibodies (MAbs) and a truncated mutant of Pseudomonas exotoxin. CD30 is highly expressed on both Hodgkin's disease and anaplastic large cell lymphoma. NCI is currently seeking cooperative partners to work with the Laboratory of Molecular Biology in the development and clinical application of immunotoxins directed against CD 30 epitopes found on cells in Hodgkin's Lymphoma and anaplastic large cell lymphoma. Potential Areas of Application: ? Treatment of Hodgkin's Lymphoma ? Treatment of anaplastic large cell lymphoma Main Advantages of Technology/Invention Recombinant immunotoxins are chimeric proteins in which a truncated toxin is fused to the Fv portion of an antibody. The binding activity of the Fv moiety targets the immunotoxins to antigen-positive cells, which are killed by the cytotoxic activity of the toxin moiety. For cancer therapy NCI has produced many different recombinant immunotoxins using PE383 that lacks its cell binding domain and Fvs that bind to tumor-related antigens or to differentiation antigens such as CD22 and CD25. NCI has also improved the therapeutic potency of several immunotoxins by protein engineering and chemical modification. These efforts have been directed at making immunotoxins that are smaller for better tumor penetration, that are less immunogenic and less toxic to animals, that bind antigen with higher affinity, that are more stable, and that are suitable for large-scale production. One of the important advances is the development of dsFvs in which one of the immunoglobulin variable chains genetically fused with PE38 is linked with the other chain by a disulfide bond between two cysteine residues engineered in the framework region of each chain. These immunotoxins showed greater stability in vivo and in vitro than the widely used scFv forms. Recent clinical trials indicate that targeted therapy by recombinant immunotoxins shows great promise especially for some types of hematologic malignancies. The anti-CD25 scFv immunotoxin, LMB-2, produced major clinical responses in various types of leukemia and lymphoma, and the anti-CD22 immunotoxin, RFB4(dsFv)-PE38, gave a remarkable high rate of complete remissions in patients with drug resistant Hairy cell leukemia. Current State of Development ? In vitro demonstration of toxicity. Further R&D Required ? To identify modifications to the immunotoxin molecule to increase anti-tumor activity and to decrease immunogenicity. ? To conduct in vivo tests of anti-tumor activity. ? to conduct preclinical toxicology and pharmacology studies preparatory to FDA IND filing. The role of the NCI in the CRADA may include, but not be limited to: 1. Providing intellectual, scientific, and technical expertise and experience to the research project. 2. Providing the CRADA collaborator with information and data relating to the anti-CD 30 immunotoxins. 3. Planning research studies and interpreting research results. 4. Carrying out research to validate the use of anti-CD 30 immunotoxins in preclinical, diagnostic and clinical settings. 5. Carrying out research to increase the potency of the immunotoxins against CD30. 6. Carrying out clinical trials with the immunotoxin against CD30. The NCI seeks a collaborator with experience in conducting preclinical studies with drugs used to treat cancer . The collaborator should have demonstrated capability to scale up production of therapeutic proteins for pre-clinical studies. The role of the CRADA Collaborator may include, but not be limited to: 1. Providing significant intellectual, scientific, and technical expertise or experience to the research project. 2. Providing technical and/or financial support to facilitate scientific goals and for further design of applications of the technology outlined in the agreement. 3.Carrying out pre-clinical studies needed to obtain an IND. 4. Supply immunotoxin to NCI for clinical trials. Terms/Licensing Potential/Patent Status ? Term of the CRADA will be up to five (5) years ? No funding from the Government is available to Collaborator under a CRADA. ? U.S. patent application has been filed June 7, 2002. ? Non-exclusive license option available for background rights. Exclusive license rights may be available in a specified field of use. Selection Criteria: 1. The ability to collaborate with NCI on further research and development of this technology. This ability can be demonstrated through experience and expertise in the production and testing of therapeutic proteins or related areas of technology indicating the ability to contribute intellectually to ongoing research and development. 2. The demonstration of adequate resources to perform the research, development and commercialization of this technology (e.g., facilities, personnel and expertise) and accomplish objectives according to an appropriate timetable to be outlined in the CRADA Collaborator's proposal. 3. The willingness to commit best effort and demonstrated resources to the research, development and commercialization of this technology. 4. The demonstration of expertise in the commercial development, production, marketing and sales of products related to this area of technology. 5. The level of financial support the CRADA Collaborator will provide for CRADA-related Government activities. 6. The willingness to cooperate with the NCI in the timely publication of research results. 7. The agreement to be bound by the appropriate DHHS regulations relating to human subjects, and all PHS policies relating to the use and care of laboratory animals. 8. The willingness to accept the legal provisions and language of the CRADA with only minor modifications, if any. These provisions govern the equitable distribution of patent rights to CRADA inventions. Generally, the rights of ownership are retained by the organization that is the employer of the inventor, with (1) the grant of license for research and other Government purposes to the Government when the CRADA Collaborator's employee is the sole inventor, or (2) the grant of an option to elect an exclusive or nonexclusive license to the CRADA Collaborator when the Government employee is the sole inventor. Pertinent References: ? Nagata, S., Onda, M., Numata, Y., Santora, K., Beers, R., Kreitman, R., and Pastan, I. Clinical Cancer Research 2002, Vol. 8 (July), 2345-2355. Submission Dates: ? Date by which a written statement of interest must be submitted: 1/03/03. ? Date by which a formal proposal must be submitted: 1/17/02. Contact Information: ? Patrick Twomey, Ph.D. ? Technology Transfer Branch, National Cancer Institute, 6120 Executive Blvd., Suite 450, Rockville, MD 20852 ? Jonathan Dixon, Ph.D., Office of Technology Transfer, National Institutes of Health, 6011 Executive Blvd., Room 325, Rockville, MD 20852
- Record
- SN00217432-W 20021207/021205213340 (fbodaily.com)
- Source
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