National Institutes of Health, Public Health Service, HHS.
The inventions listed below are owned by agencies of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.
Licensing information and copies of the U.S. patent applications listed below may be obtained by contacting Kai Chen, Ph.D., M.B.A., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057 ext. 247; fax: 301/402-0220; e-mail: ChenK@od.nih.gov. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.
Antiproliferative Actions of Human IGF Binding Protein-3 Mutants That Do Not Bind IGF-I or IGF-II
M.M. Rechler (NIDDK)
Recent epidemiological studies indicate that increased serum insulin-like growth factor binding protein-3 (IGFBP-3) is associated with decreased Start Printed Page 11351risk of prostate, breast, lung and colorectal cancers, and childhood leukemia. IGFBP-3 can inhibit cell growth and stimulate death through formation of complexes with IGF-I and IGF-II that prevent activation of the IGF-I receptor to stimulate proliferation and survival.
The current invention embodies a novel mechanism of action for IGFBP-3: direct inhibition of cell growth and stimulation of cell death through a mechanism that is independent of IGF-I, IGF-II and the IGF-I receptor. In the current invention, human IGFBP-3 has been genetically modified so that its affinity for IGF-I and IGF-II is greatly reduced, and it can act only through this novel direct mechanism. These human IGFBP-3 mutants still can inhibit DNA synthesis and stimulate apoptosis, and have been shown to induce apoptosis in human prostate cancer cells. The current invention could selectively exert antiproliferative action without interfering with IGF actions, and may have therapeutic uses as an antitumor agent.
A Novel DNA Methyltransferase Assay System With High Throughput/Automation Potential
K. Robertson, T. Yokochi (NCI)
It is now believed that unregulated cell growth is due to aberrant gene expression in cells caused by deletion, mutation, or silencing of one or more critical growth regulatory proteins. The latter method, gene silencing, is mediated by DNA methylation, or the addition of methyl groups to cytosine residues at critical gene expression control regions.
The current invention embodies a novel and highly sensitive assay for detecting DNA methyltransferase activity, which catalyzes the addition of methyl groups to DNA. Treatment with DNA methyltransferase inhibitors in a clinical setting might lead to expression of silenced gene(s) and restoration of controlled cell growth. Huge numbers of compounds must be screened to identify ones that are active against DNA methyltransferases. The assay embodied in the current invention represents the first such assay adaptable for high-throughput and/or automated screening of potential DNA methyltransferase inhibitors. This assay also is fast, easy, reproducible, and highly sensitive.
Generation and Use of Tc1 and Tc2 Cells
D. Fowler (NCI), U. Jung (NCI), J. Medin (NINDS), R. Gress (NCI), A. Erdmann (NCI), B. Levine, and C. June
Allogeneic stem cell transplantation represents a potentially curative treatment option for patients with both hematologic and solid cancers, and for patients with other non-malignant conditions. However, the clinical application of allogeneic stem cell transplantation is limited by T cell immune reactions.
The current invention embodies a method for enrichment of donor T cells of Tc1 and Tc2 phenotypes by in vitro culture. This method represents a significant advance in terms of T cell numbers produced, level of cytokine polarization, and efficacy of in vivo effects. In murine transplantation models, this method greatly reduces graft-versus-host disease (GVHD) associated with donor CD8 cell administration. Murine Tc2 cells generated by this method are particularly potent in abrogating graft rejection by a mechanism that does not involve GVHD. In addition, this method can generate Tc1 and Tc2 cells that mediate graft-versus-tumor (GVT) effects against murine breast cancer and murine leukemia. The Tc1 and Tc2 cells produced by this method are also amenable to insertion of a suicide gene, which represents a potential strategy for mediating potent allogeneic GVT effects, with subsequent reversal of T cell mediated GVHD. Allogeneic transplantation using Tc1 and Tc2 cells generated via this method may therefore represent an approach to increase the anti-tumor efficacy and reduce the GVHD-toxicity of allogeneic stem cell transplantation, and to extend allogeneic transplantation to those patients lacking an HLA-matched sibling.Start Signature
Dated: March 7, 2002.
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 02-6062 Filed 3-12-02; 8:45 am]
BILLING CODE 4140-01-P