Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by an agency 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 writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Maleiimide Anti-Tumor Phosphatase Inhibitors

Christophe Michejda et al. (NCI).

U.S. Provisional Application No. 60/546,841 filed 22 Feb 2004 (DHHS Reference No. E-110-2004/0-US-01).

Licensing Contact: George Pipia; 301/435-5560; pipiag@mail.nih.gov.

The present invention describes novel phosphatase inhibitors that appear to target the CDC25 family of phosphatases. The new compounds have potent activity against human liver cancer cells in vitro and in vivo against an orthotopic liver cancer in rats. In tumor cells, these new inhibitors appear to target the phosphorylation status of several cell cycle proteins that are important for cell survival and thus could represent a novel class of chemotherapeutic agents targeting cancer cells.

New Building Blocks for DNA Binding Agents

Zoltan Szekely, Christophe Michejda (NCI).

U.S. Provisional Application No. 60/508,543 filed 03 Oct 2003 (DHHS Reference No. E-291-2003/0-US-01).

Licensing Contact: George Pipia; 301/435-5560; pipiag@mail.nih.gov.

There remains a need for therapeutic conjugates that have improved antitumor selectivity and nucleic acid sequence-binding specificity. Ideally such conjugates will have fewer side effects and lower cytotoxicity to healthy cells and tissues. The knowledge of the geometry of conjugates allows for a rational design of therapeutic conjugates, ones that have increased specificity of binding to a minor groove of the DNA, while maintaining maximum activity of the alkylating subgroup of the conjugates. The present invention provides such conjugates. The conjugates of the present invention bind to the minor grove of DNA in a sequence-specific manner and deliver an alkylating moiety to a specific site on the DNA. The present invention provides a pharmaceutical composition comprising a pharmaceutically or pharmacologically acceptable carrier and compounds of the present invention. The present invention also provides a method of preventing or treating a disease or condition by the use of the compound. The NIH inventors currently are testing the conjugates in in vitro assay and are starting pre-clinical studies of the conjugates using animal cancer models.

Use of Cripto-1 as a Biomarker for Neurodegenerative Disease and Method of Inhibiting Progression Thereof

David S. Salomon (NCI), Berman Nancy (EM), Edward B. Stephens (EM).

U.S. Provisional Application No. 60/508,750 filed 03 Oct 2003 (DHHS Reference No. E-075-2003/0-US-01).

Licensing Contact: Brenda Hefti; 301/435-4632; heftib@mail.nih.gov.

Cripto-1 is a gene that is currently thought to play an important role in several cancers, and is being developed in clinical trials as a cancer therapeutic.

The current invention relates to another use of Cripto-1 as a biomarker and possible therapeutic target for a variety of neurodegenerative diseases, including NeuroAids, Alzheimer's disease, MS, ALS, Parkinson's disease and encephalitis. Cripto-1 appears to be overexpressed by 20-fold or more in NeuroAids and as such may be enhanced in other inflammatory neurological diseases, and thus assist in the early detection of neurological changes associated with these diseases, as well as a possible therapeutic target for slowing progression.

Antibodies That Bind POTE and Uses Thereof

Ira H. Pastan, Tapan Y. Bera, and Byungkook Lee (NCI).

U.S. Provisional Application No. 60/546,058 filed 18 Feb 2004 (DHHS Reference No. E-325-2002/0-US-01).

Licensing Contact: Brenda Hefti; 301/435-4632; heftib@mail.nih.gov.

The current invention describes a family of genes, termed Prostate, Ovary, Testis and Prostate cancer genes (POTE). POTE is highly expressed in prostate cancer and ovarian cancer, but not in essential normal tissues. Antibodies to POTE and immunotoxins that selectively bind POTE are also described.

POTE appears to be a membrane protein with at least one extracellular domain, and is therefore a desirable target for antibody or immunoconjugate therapies.

Immunogenic peptide fragments might be used to generate an immune response in a patient. This invention might also be useful as an antibody-based or immunoconjugate therapeutic to treat prostate and ovarian cancers.

DNA Encoding CAI Resistance Proteins and Uses Thereof

Elise Kohn et al. (NCI).

U.S. Patent 5,652,223 issued 29 Jul 1997 (DHHS Reference No. E-112-1994/0-US-01); U.S. Patent 5,981,712 issued 09 Nov 1999 (DHHS Reference No. E-112-1994/0-US-02); Serial No. 09/436,469 filed 08 Nov 1999 (DHHS Reference No. 112-1994/0-US-03).

Licensing Contact: Jesse S. Kindra; 301/435-5559; kindraj@mail.nih.gov.

Novel targets for therapeutic intervention in cancer proliferation and invasion are needed. Calcium influx has been shown to be required for invasion. Carboxyamid-triazole (CAI), a synthetic blocker of calcium influx in nonexcitable cells, inhibits tumor and endothelial cell motility and decreases the expression of matrix metalloproteinases involved in invasion and angiogenesis. Thus, CAI plays a role in the inhibition of malignant proliferation, invasion, and metastasis of cancer cells. The effectiveness of CAI as a cancer therapeutic agent is currently being tested in clinical trials.

The technology which is available for licensing relates to the CAI resistance (CAIR-1) gene that encodes a protein identified in CAI conditioned cells. The CAIR-1 gene provides a potential source of information about the mechanism of drug conditioning and could also be useful as a marker for detecting the acquisition of a drug conditioned phenotype and/or as a target for intervention.

In addition, CAIR was also independently identified as BAG-3 and Bis. CAIR/BAG-3/Bis has been shown to play a role in protein folding inside the cell and to modulate programmed cell death (apoptosis). Thus, the CAIR/BAG-3/Bis protein serves as an important link between pathways regulating calcium influx, protein folding, and apoptosis and may be a valuable drug discovery target for therapeutic intervention in cancer proliferation and invasion.

Circularly Permuted Ligands and Circularly Permuted Fusion Proteins

Ira H. Pastan, Robert J. Kreitman, Raj K. Puri (NCI).

U.S. Patent 5,635,599 issued 03 Jun 1997 (DHHS Reference No. E-047-1994/0-US-01). U.S. Patent 6,011,002 issued 04 Jan 2000 (DHHS Reference No. E-047-1994/1-US-01).

Licensing Contact: Brenda Hefti; 301/435-4632; heftib@mail.nih.gov.

Circularly permuted proteins are ligands wherein the amino and carboxy ends have been joined together and new amino and carboxy ends are formed at a different location in the ligand. The modified ligands are as fully active as the original. The circularly permuted ligands are especially useful when employed as a component in a fusion protein of interest. Fusion proteins are polypeptide chains of two or more proteins fused together in a single polypeptide chain. A fusion protein may act as a potent cell-killing agent or as a linker to bind and enhance the interaction between cells or cellular components to which the protein binds, depending on the nature of the proteins being fused. Therefore, fusion proteins have functional utility as a specific targeting moiety to either kill or direct an immune response to cancer cells. While some targeting moieties have shown lower specificity and affinity for their targets when incorporated into fusion proteins, the use of circularly permuted ligands improves the binding affinity of certain fusion proteins. This invention provides novel ligands and ligand fusion proteins that have a binding specificity and affinity comparable to or greater than native ligand fusion proteins.