[Federal Register Volume 69, Number 125 (Wednesday, June 30, 2004)]
[Notices]
[Pages 39489-39491]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-14778]


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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, DHHS.

ACTION: Notice.

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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).

[[Page 39490]]

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; [email protected].

    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; [email protected].

    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; [email protected].

    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; [email protected].

    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; [email protected].

    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; [email protected].

    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

[[Page 39491]]

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.

    Dated: June 22, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-14778 Filed 6-29-04; 8:45 am]
BILLING CODE 4140-01-P