[Federal Register: July 7, 1999 (Volume 64, Number 129)] [Notices] [Page 36701-36702] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr07jy99-93] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental and Craniofacial Research: Opportunity for a Cooperative Research and Development Agreement (CRADA) for the Development of Either Diagnostics or Therapeutics for Bone Metastasizing Cancers Including Breast and Prostate Cancer AGENCY: National Institutes of Health (NIH), PHS, DHHS. ACTION: Notice of an opportunity for a Cooperative Research and Development Agreement. ----------------------------------------------------------------------- SUMMARY: The National Institute of Dental and Craniofacial Research (NIDCR), Craniofacial Developmental Biology and Regeneration Branch, has developed technology in the area of the metastasis of breast and prostate cancer to bone and wishes to further develop that technology. Therefore, the NIDCR seeks an agreement with a pharmaceutical or biotechnology company to develop diagnostics and therapeutics related to osteonectin and/or its receptor on metastatic cancer cells. The spread of tumor cells (metastasis) to distant organs is the leading cause of morbidity and death in cancer. In order to spread, tumor cells must detach from the primary tumor, enter the circulation, and attach to organs able to support their further growth. To enter and exit the circulation, tumor cells must degrade tissue and matrix barriers, but the underlying mechanism for the organ specific metastasis of prostate and breast cancer to bone is not understood. For instance, it is not clear whether these calls only invade and grow in bone, or whether they invade many tissues but survive mainly in bone. NIDCR scientists have found that chemoinvasion of different prostate and breast cancer cell lines through basement membrane is several fold greater in response to bone extracts than to extracts from other tissues. Control studies showed that invasion of melanoma and fibrosarcoma cells is not stimulated by bone extracts. The bone extracts and partially purified materials had no effect on prostate cancer cell growth (in-vitro or in-vivo). The active factor from bone which promoted prostate cell invasion was purified and shown to be a glycosylated derivative of osteonectin. Moreover, osteonectin was found to specifically induce matrix metalloprotease activity in both breast and prostate cancer cells, which both invade bone. No induction was observed with three non bone metastasizing cell lines (3T3, HT1080 and B16F10). More recently, a cellular receptor for osteonectin, which is elevated on breast and prostate cancer cells but not on melanoma or 3T3 cells, has been identified. Experiments with subcutaneously implanted minipumps containing osteonectin have demonstrated that prostate cancer cells preferentially metastasize to the site of the implant and form tumors, whereas control pumps containing saline or a non active bone fraction did not show this activity. These data suggest that invasion of bone by prostate cancer cells is mediated by osteonectin. A CRADA partner is sought to participate in the development of antibodies or diagnostic tools to quantitate the osteonectin receptor, as it may be a marker for tumors that are metastasic to bone. If the receptor is elevated on metastatic cells, then antagonists can be developed to block its occupancy and inhibit metastasis to bone. The collaboration could also explore whether serum levels of osteonectin may provide a new and early diagnostic tool to detect metastasis of breast and prostate cancer cells. Improvement in the understanding of the mechanisms by which breast and prostate cancer cell metastasize to bone could provide an opportunity to develop diagnostic and therapeutic reagents. The proposed duration of the CRADA is two (2) years. ADDRESSES: Proposals and questions about this opportunity may be addressed to Jacob A. Donkersloot, Sc.D., Technology Development Coordinator, NIDCR, tel: (301) 496-4216, fax: (301) 402-0396 or David A. Steffes, J.D., Technology Development and Commercialization Branch, National Cancer Institute, tel: (301) 496-0477, fax: (301) 402-2117. DATES: Interested parties should submit a one page statement of interest addressing the collaborator's ability to fulfill its collaborative responsibilities. The statement of interest should be submitted in writing on or before September 7, 1999. SUPPLEMENTARY INFORMATION: A ``Cooperative Research and Development Agreement'' or ``CRADA'' is the anticipated joint agreement to be entered into by the NIDCR pursuant to the Federal Technology Transfer Act of 1986 as amended by the National Technology Transfer and Advancement Act of 1995 (Pub. L. 104-113 (Mar. 7, 1996)) and by Executive Order 12591 of October 10, 1987. The CRADA objective is the rapid publication of research results and the timely commercialization of improved diagnostics and/or therapeutics in the areas of breast and prostate cancer metastasis to bone. Under a CRADA, the NIDCR can contribute facilities, staff, materials, and expertise to the effort. The NIDCR cannot contribute funding. The CRADA collaborator receives an exclusive option to negotiate an exclusive or non-exclusive license to Government intellectual property rights arising under the CRADA in a pre- determined field of use and may qualify as a co-inventor of new technology developed under the CRADA. Background information, including reprints of this announcement and issued patents, is available from the above-referenced address. Patent applications and pertinent information not yet publicly described can be obtained under a Confidential Disclosure Agreement. CRADA proposals will be evaluated under the following criteria: --Corporate research and development competencies --Demonstrated abilities to productively collaborate in research programs [[Page 36702]] --The nature of resources to be contributed to the collaboration --Key staff expertise, qualifications and relevant experience --Willingness to assign technical staff to on-site collaborative efforts --Ability to effectively commercialize new discoveries The roles of the Craniofacial Developmental Biology and Regeneration Branch for the proposed CRADA are as follows: 1. Provide project coordination for the overall development and testing. 2. Further develop and refine animal models to study bone metastasis and the role of osteonectin for testing of the therapeutics. 3. Provide further characterization of the cellular receptor for osteonectin. 4. Provide in-vitro testing of biological activity of possible therapeutics with various cell lines. 5. Provide in-vitro testing of receptor-based diagnostics. 6. Jointly publish research results. The roles of the Collaborator under the proposed CRADA are as follows: 1. Provide project coordination for the overdevelopment and testing. 2. Develop and provide antibodies or other tools for diagnostic purposes based on the cellular receptor. This may also include peptide mimetics or other reagents based on the binding site on osteonectin for its cellular receptor. 3. Determine if the level of osteonectin in serum is a possible diagnostic tool and develop an easy and reliable assay for osteonectin. 4. Develop therapeutics for cancer metastasis based either on matrix metalloprotease activity, receptor antagonists or other acceptable treatments for patients. 5. Jointly publish research results. Dated: June 25, 1999. Kathleen Sybert, Chief, Technology Development and Commercialization Branch, NCI. [FR Doc. 99-17120 Filed 7-6-99; 8:45 am] BILLING CODE 4140-01-M