[Federal Register Volume 67, Number 49 (Wednesday, March 13, 2002)]
[Notices]
[Pages 11350-11351]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-6062]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: 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.

ADDRESSES: 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: [email protected]. 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)

[DHHS Reference No. E-048-02/0 filed 17 Dec 2001]

    Recent epidemiological studies indicate that increased serum 
insulin-like growth factor binding protein-3 (IGFBP-3) is associated 
with decreased

[[Page 11351]]

risk 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)

[DHHS Reference No. E-030-02/0 filed 14 Jan 2002]

    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

[U.S. Provisional Patent Application 60/336,473 filed 31 Oct 2001]

    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.

    Dated: March 7, 2002.
Jack Spiegel,
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