[Federal Register Volume 64, Number 129 (Wednesday, July 7, 1999)]
[Notices]
[Pages 36701-36702]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-17120]


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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.

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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