[Federal Register Volume 72, Number 89 (Wednesday, May 9, 2007)]
[Notices]
[Pages 26402-26404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-8893]



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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 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.

Selenocysteine Mediated Hybrid Antibody Molecules

    Description of Technology: Available for licensing is a new class 
of hybrid molecules composed of an antibody, or antibody fragment, and 
a small synthetic molecule (such as a small molecule inhibitor, or 
cytotoxic compound). These biological and chemical components are 
covalently linked at an engineered selenocysteine near the C-terminus 
of the antibody, or antibody fragment. Through this covalent linkage, 
the chemical and the biological component can acquire properties of one 
another. For example, the synthetic molecule acquires antibody 
properties such as circulatory half-life, effector functions, and 
ability to interfere with protein interactions whereas the antibody, or 
antibody fragment, acquires properties of the small synthetic molecule 
such as specificity, affinity, and stability to bind to targets that 
are sterically inaccessible to immunoglobulins. The technology can also 
be used to equip an antibody, or antibody fragment, with a small 
synthetic molecule that enhances target destruction or imaging 
capabilities through site-selective biotinylation, PEGylation, addition 
of an imaging agent, or addition of a cytotoxic agent such as a 
chemotherapeutic drug or a chelate for radioisotope labeling. The 
hybrid antibody molecules can be engineered with a variety of small 
synthetic molecules, and the combination of immunogenic properties and 
those of the small synthetic molecules results in compounds with 
powerful target destruction or imaging capabilities. This technology 
could be applied towards the targeted delivery of small synthetic 
molecules to various cell surface receptors, and may have applicability 
as a prevention, diagnosis, or therapy for numerous disease states.
    Applications: Potent novel compositions that retains immunogenic 
properties and those of small synthetic molecules that can be produced 
at a large scale; Method to prevent, diagnose, and treat cancer, 
infectious diseases and autoimmune diseases.
    Market: Monoclonal antibody market is projected to exceed $30 
billion by 2010; Revenue from antibodies for therapeutics and 
diagnostic uses are expected to grow at an average annual growth rate 
of 11.5%.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Christoph Rader et al. (NCI).
    Patent Status: U.S. Provisional Application No. 60/909,665 filed 02 
Apr 2007 (HHS Reference No. E-146-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Experimental Transplantation and Immunology 
Branch, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize Selenocysteine Mediated Hybrid Antibody Molecules. Please 
contact Dr. Christoph Rader at (301) 451-2235 or [email protected] 
for more information.

Mutant Alleles of Hsp90 that Modulates the Lifespan of Yeast

    Description of Technology: Heat shock protein 90 (Hsp90) are a 
class of chaperone proteins that are up-regulated in response to 
elevated temperature and other environmental stresses. They act as 
chaperones to other cellular proteins and facilitate their proper 
folding and repair, and aid in the refolding of misfolded client 
proteins.
    This invention identifies Hsp90 mutant residues that affect the 
chronological lifespan of yeast. These mutations in addition to a 
deletion in the sch9 allele, the yeast homolog to human kinase AKT, can 
increase yeast lifespan from 45 to 57 days, approximately 20% longer 
than the wildtype strain. These genetically engineered yeast strains 
may have the longest chronological lifespan reported to date.
    Applications: Model to study aging and longevity factors; Model to 
screen compounds that affect lifespan; A long-lived yeast strain could 
be used to ferment alcohol in a more efficient and cost effective as an 
alternative fuel source; Method to extend lifespan of transgenic farm 
animals.
    Market: Anti-aging and alternative fuel industries are worth 
billions of dollars.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Bradley T. Scroggins (NCI) et al.
    Related Publication: BT Scroggins et al. An acetylation site in the 
middle domain of Hsp90 regulates chaperone function. Mol Cell. 2007 Jan 
12;25(1):151-159.
    Patent Status: U.S. Provisional Application No. 60/848,346 filed 09 
Sep 2006 (HHS Reference No. E-319-2006/0-US-01).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Urologic Oncology Branch is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize models to study aging and longevity 
factors. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Inhibitors of Ubiquitin E1

    Description of Technology: The present invention discloses novel 
pyrazolidinyl compounds that inhibit undesired cell proliferation. The 
compounds inhibit ubiquitin E1 and can be useful for regulating protein 
ubiquitination. Specifically, the novel pyrazolidinyl compounds can 
stabilize p53 and induce apoptosis in mammalian cells through selective 
inhibition of ubiquitin E1.
    Ubiquitin-mediated proteolysis is an important pathway of non-
lysosomal protein degradation that controls the timed destruction of a 
number of cellular regulatory proteins including p53. The ubiquitin 
pathway leads to the

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covalent attachment of poly-ubiquitin chains to target substrates which 
are then degraded by a multi-catalytic proteosome complex.
    The compounds can be useful in the treatment of solid and 
disseminated cancers or other undesired cell proliferation disease or 
retroviral infections such as HIV.
    Applications and Modality: Treatment of disorders related to 
ubiquitin E1, such as HIV and viral infections; Compounds are the first 
general inhibitors of Ubiquitin E1 with broader biological effects than 
existing proteosome inhibitors; The compounds can serve as a probe to 
understand the ubiquitin system.
    Market: Bortezomib (marketed as VelcadeTM by Millennium 
Pharmaceuticals) is the first therapeutic proteasome inhibitor approved 
by the FDA. Severe side effects such as peripheral neuropathy occur in 
30% of patients treated with Bortezomib. New drugs targeting proteins 
in ubiquitination pathway are needed that will have broader efficacy 
and reduced side effects.
    Development Status: The technology is in the pre-clinical stage of 
development.
    Inventors: Allan M. Weissman et al. (NCI).
    Related Publications:
    1. A manuscript related to this technology will be available as 
soon as it is accepted for publication.
    2. Y Yang et al. Small molecule inhibitors of HDM2 ubiquitin ligase 
activity stabilize and activate p53 in cells. Cancer Cell. 2005 
Jun;7(6):547-559.
    Patent Status: U.S. Provisional Application No. 60/738,242 filed 19 
Nov 2005, entitled ``Inhibitors of Ubiquitin E1'' (HHS Reference No. E-
070-2005/0-US-01); International Patent Application No. PCT/US2006/
0045032 filed 20 Nov 2006, entitled ``Inhibitors of Ubiquitin E1'' (HHS 
Reference No. E-070-2005/0-PCT-02)
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Thomas P. Clouse; 301/435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Laboratory of Protein Dynamics and Signaling is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize inhibitors of 
ubiquitin E1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Biomarkers for Tissue Status

    Description of Technology: Tissue regeneration and tumorigenesis 
are complex, adaptive processes controlled by cues from the tissue 
microenvironment. There are complex processes both characterized by 
cell proliferation, migration, and angiogenesis suggesting that wounds 
and cancer share a number of phenotypic similarities including cellular 
behavior, signaling molecules, and gene expression.
    Utilizing the kidneys as a model to compare renal regeneration and 
repair (RRR) from ischemically-injured tissues and renal cellular 
carcinoma (RCC), the inventors have identified biomarkers which are 
differentially expressed. The invention relates to methods of quickly 
and accurately diagnosing RCC and monitoring renal tissue health as 
well as RCC treatment.
    Applications: Method to accurately diagnose RCC; RCC biomarker 
inhibitors such siRNA; Method to treat RCC; Method to determine and 
monitor renal tissue health status; Method for improving renal ischemia 
recovery without promoting RCC; Biomarkers for immunotherapy, drug 
targeting and drug screening, for targeting tumors and not normal 
regenerating tissue; Biomarkers for immunotherapy, drug targeting and 
drug screening, for targeting ischemic tissue and not tumors.
    Market: Kidney cancer is one of the top ten most prevalent cancers 
in the U.S. and it accounts for 12,200 deaths annually; Approximately 
35,000 new cases of kidney cancer are diagnosed annually; 50% survival 
rate after five years of diagnosis; Renal cancer accounts for 3% of all 
adult male malignancies.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Joseph Riss (NCI) et al.
    Publications:
    1. Journal of Urology, May 2007, Vol. 177 No. 5, in press.
    2. J Riss et al. Cancers as wounds that do not heal: differences 
and similarities between renal regeneration/repair and renal cell 
carcinoma. Cancer Res. 2006 July 15;66(14):7216-7224.
    Patent Status: U.S. Provisional Application No. 60/649,208 filed 01 
Feb 2005 (HHS Reference No. E-064-2005/0-US-01); PCT Application No. 
PCT/US2006/003611 filed 01 Feb 2006 (HHS Reference No. E-064-2005/0-
PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Cancer Biology and Genetics, 
Wound Healing and Oncogenesis (NCI/CCR/LCBG), is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize topics of 
invention or related to cancer biology, metastasis, wound healing, 
bioinformatics, pharmacogenomics and therapeutic. Please contact John 
D. Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

New Maleiimide Anti-Phosphatase Inhibitors

    Description of Technology: The present invention describes novel 
phenyl maleiimide phosphatase inhibitors that appear to target the 
Cdc25 family of phosphatases. The new compounds are inhibitors of 
several human tumor cell lines. The 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.
    Applications and Modality: Compound targets Cdc25 family of 
phosphatases and inhibit growth of several human tumor cell lines; 
Potent activity in vitro against human liver cancer cells and in vivo 
against orthotopic liver cancer in rats; Targets phosphorylation of 
cell cycle proteins important for cell survival.
    Market: 600,000 deaths from cancer related diseases were estimated 
in 2006; In 2006, cancer drug sales were estimated to be $25 billion.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Christopher Michejda (NCI) et al.
    Relevant Publication: S Kar, M Wang, W Yao, CJ Michejda, BI Carr. 
PM-20, A novel inhibitor of Cdc25A, induces extracellular signal-
regulated kinase 1/2 phosphorylation and inhibits hepatocellular 
carcinoma growth in vitro and in vivo. Mol Cancer Ther. 2006 
Jun;5(6):1511-1519.
    Patent Status: PCT Patent Application No. PCT/US2005/05742 filed 22 
Feb 2005, which published as WO 2005/081972 on 09 Sep 2005 (HHS 
Reference No. E-110-2004/0-PCT-02); U.S. Patent Application No. 11/
508,605 filed 22

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Aug 2006 (HHS Ref. No. E-110-2004/0-US-06).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560; 
[email protected].

Leu574 of HIF-1alpha as a Molecular Basis for Therapeutic Application

    Description of Technology: The hypoxia-inducible factor 1 (HIF-1) 
is a transcription factor that plays a pivotal role in cellular 
adaptation to oxygen availability. HIF-1alpha protein is a subunit of 
HIF-1. Although the gene for HIF-1alpha is constitutively expressed, it 
is an extremely short-lived protein under normoxic conditions and is 
targeted for destruction via the proteosome pathway by an E3 ubiquitin 
ligase involving the VHL protein.
    The invention relates to the discovery that mutations or deletions 
of Leu574 result in a more stable and more active form of HIF-1alpha. 
Therefore, the invention relates to methods and compositions for 
modulating oxygen homeostasis for therapeutic application. In one 
aspect, the inventors contemplate the use of a more stable form of HIF-
1alpha protein for therapeutic angiogenesis purposes such as may be 
useful in ischemic vascular disease. In another aspect, the inventors 
contemplate the use of this particular site in a screen for targeted 
drugs that modulates HIF-1alpha activity. The inventors also suggest 
that Leu574 could be used for developing drugs targeted to HIF 
hydroxylase binding, thereby altering HIF-1alpha stability.
    Inventor: L. Eric Huang (NCI).
    Patent Status: U.S. Patent No. 7,193,053 issued 20 Mar 2007 (HHS 
Reference No. E-281-2002/0-US-02).
    Licensing Status: This technology is available for licensing on an 
exclusive or a non-exclusive basis.
    Licensing Contact: Jesse S. Kindra, J.D.; 301/435-5559; 
[email protected].

    Dated: April 30, 3007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer,Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-8893 Filed 5-8-07; 8:45 am]
BILLING CODE 4140-01-P