[Federal Register Volume 71, Number 240 (Thursday, December 14, 2006)]
[Notices]
[Pages 75258-75260]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-21301]


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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.

Peptide and Peptidomimetic Inhibitors of Smoothened Protein as Anti-
neoplastic Agents

    Description of Technology: Cancer is caused by the improper 
regulation of certain signaling proteins in the cell.

[[Page 75259]]

One of these pathways is the Hedgehog/Patched (HH/PTCH) pathway. 
Hedgehog is a secreted protein involved in the growth and development 
of embryonic cells. Patched is the receptor for hedgehog proteins and 
regulates a membrane protein called Smoothened (SMO). This pathway is 
activated in many tumor cells, including those in prostate, pancreas, 
stomach, and small cell cancer.
    The technology is directed towards several synthetic peptides 
(including all-D analogs) corresponding to specific region of the SMO 
protein. Experiments in vitro demonstrate that they potentially 
suppress the growth of cancer cells and inhibit the expression of the 
HH/PTCH pathway genes. These novel SMO inhibitors are much more 
effective in inhibiting cell growth than currently available 
cyclopamine and cyclopamine derivatives. These novel peptides and their 
metabolically more stable analogs have a high potential for cancer 
therapy. Due to their high hydrophobic properties, these can be easily 
formulated for specific intratumor delivery or topical creams for skin 
disorders.
    Applications and Modality: (1) A potent, highly soluble cancer 
therapeutic; (2) Novel compounds that inhibit HH/PTCH pathway genes; 
(3) Skin permeable compounds that can be formulated into topical creams 
for skin malignancies treatment and prevention and treatment of 
psoriasis.
    Market: (1) 600,000 deaths from cancer related diseases estimated 
in 2006; (2) This technology involving therapeutics for the treatment 
of several cancers has a potential market of several billion U.S. 
dollars; (3) Psoriasis affects an estimated 2-3 percent of the world's 
population; (4) Dermatologic diseases affect an estimated 50 million 
Americans; (5) Skin therapeutic market is worth over $2 billion in 
annual sales of prescription medications with an estimated yearly 
growth rate of 5%;
    (6) The overall annual cost of psoriasis treatment has been 
estimated to be from $650 million to $2 billion in the United States.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Nadia Tarasova, Michael Dean, and Lou Hong (NCI).
    Related Publication: L Covic et al. Activation and inhibition of G 
protein-coupled receptors by cell-penetrating membrane-tethered 
peptides. Proc Natl Acad Sci USA. 2002 Jan 22; 99(2):643-648.
    Patent Status: U.S. Provisional Application No. 60/855,422 filed 31 
Oct 2006 (HHS Reference No. E-014-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The NCI-Frederick Structural 
Biophysics Laboratory is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize Peptide and Peptidomimetic Inhibitors of 
Smoothened Protein as Anti-neoplastic Agents. Please contact Betty 
Tong, Ph.D. at 301-594-4263 for more information.

Extracellular Matrix/Metastasis Modifier Genes as a Method for 
Characterization and Prevention of Metastatic Tumor

    Description of Technology: To a large extent cancer mortality is 
due to metastatic disease than a primary tumor. Recent evidence 
suggests that metastatic disease can be an early event and in majority 
of patients metastasis starts by the time the disease is diagnosed. 
Thus there is a need for methods of characterizing the early metastatic 
process for better treatment of cancer.
    This invention provides methods of characterizing the metastatic 
capacity of a tumor as well as inhibiting metastasis of a cancer cell. 
More specifically, this invention discloses an extracellular matrix 
(ECM) modifier protein named Anakin, detection of the Anakin protein as 
a marker for metastatic disease and use of Anakin as potential 
therapeutic target.
    Applications and Modality: (1) Method of diagnosis for early 
metastasis and therapeutic inhibition of metastasis; (2) Nucleic acid 
sequence of Anakin protein, an extracellular matrix (ECM) modifier 
gene; (3) SiRNA sequences that inhibit Anakin expression as 
therapeutics; (4) Purified antibodies that recognize Anakin protein as 
a research reagent and in diagnostics related products.
    Market: 600,000 deaths from cancer related diseases estimated in 
2006.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Kent W. Hunter (NCI) et al.
    Patent Status: U.S. Provisional Application No. 60/778,463 filed 31 
Mar 2006 (HHS Reference No. E-125-2006/1-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Mojdeh Bahar, J.D.; 301/435-2950; 
[email protected].
    Collaborative Research Opportunity: The NCI Laboratory of 
Population Genetics is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of Anakin as a prognostic tool for 
diagnosing breast cancer outcome. Please contact Betty Tong, Ph.D. at 
301-594-4263 for more information.

Novel Treatments for Autoimmune Neuroinflammatory Diseases Including 
Multiple Sclerosis

    Description of Technology: Multiple sclerosis is caused when T 
cells mistakenly attack myelin, the protective fatty layer surrounding 
neurons in the brain and spinal cord, to initiate autoimmune responses 
and inflammation of the central nervous system (CNS). An increase in T 
cell-endothelial cell interactions and/or increased infiltration of 
immune cells to the CNS may play a role in the onset and/or progression 
of this disease.
    Researchers at the NIH previously reported that extracellular 
adherence protein (Eap) produced by Staphylococcus aureus interacts 
with intercellular adhesion molecule 1 to prevent beta2-integrin-
dependent inflammatory cell recruitment. They have now shown that Eap 
administration to mice with experimental autoimmune encephalomyelitis, 
a condition thought to be a model for human multiple sclerosis, blocks 
T cell recruitment to the brains of the EAE affected mice, inhibits the 
onset of this disease, and reverses paralysis. Eap also reduces 
delayed-type hypersensitivity in affected mice by inhibiting T cell 
infiltration and plasma leakage.
    Available for licensing are methods for administering an Eap agent 
in an amount that will treat or prevent autoimmune neuroinflammatory 
diseases such as multiple sclerosis, decrease the infiltration of 
immune cells to the central nervous system, and inhibit T cell-
endothelial cell interactions.
    Applications: (1) Potential non-toxic treatment for autoimmune 
neuroinflammatory diseases, such as multiple sclerosis; (2) Potential 
therapy for alleviating symptoms associated with multiple sclerosis 
such as paralysis.
    Market: (1) In the United States, approximately 400,000 people are 
living with multiple sclerosis, and about 200 people are diagnosed with 
multiple sclerosis each week; (2) The average annual direct and 
indirect cost of multiple sclerosis in the United States is $23 
billion.

[[Page 75260]]

    Development Status: Animal data is available.
    Inventors: Triantafyllos Chavakis (NCI) et al.
    Publications:
    (1) T Chavakis et al. Staphylococcus aureus extracellular adherence 
protein serves as anti-inflammatory by inhibiting the recruitment of 
host leukocytes. Nat Med. 2002 Jul;8(7):687-693.
    (2) C Xie et al. Suppression of experimental autoimmune 
encephalomyelitis by extracellular adherence protein of Staphylococcus 
aureus. J Exp Med. 2006 Apr 17;203(4):985-994.
    Patent Status: U.S. Provisional Application No. 60/771,884 filed 10 
Feb 2006 (HHS Reference No. E-295-2005/0-US-01).
    Availability: Available for exclusive and non-exclusive licensing.
    Licensing Contact: Norbert Pontzer, Ph.D., J.D.; 301/435-5502; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Experimental Immunology Branch is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize Novel Treatments for Autoimmune 
Neuroinflammatory Diseases including Multiple Sclerosis. Please contact 
Betty Tong, Ph.D. at 301-594-4263 for more information.

Gene Cassette for Enhancement of Protein Production

    Description of Technology: There is a continuing market need for 
expression systems that improve recombinant protein production for 
disease therapeutics or research materials. The present invention 
describes a ``gene cassette'' containing the aadA1 (aminoglycoside 
adenylyltransferase) gene that increases protein expression levels when 
incorporated into a bacterial or eukaryotic host genome. In bacterial 
systems, the inventors have shown that this gene cassette induces 
enhancement of protein production and accumulation. This inducement is 
not restricted by the nature of the vector, induction system or nature 
of protein. In particular, this invention has yielded 3-fold 
upregulation of anti-HIV peptide expression levels in a microbial 
microbicide (see reference below). This technology offers an effective 
mechanism for increased product yield that can be utilized for 
pharmaceutical or biotechnological applications.
    Applications: (1) Affordable gene cassette that increases 
production of recombinant or native proteins with reduced culture 
volume and faster processing time; (2) Increases efficacy and potency 
of cell-based therapeutics that overexpress endogenous or heterologous 
proteins.
    Market: (1) Producers of protein, peptide, or cell-based 
therapeutics who would benefit from enhanced protein expression; (2) 
Researchers worldwide who utilize expression systems for protein 
synthesis.
    Development Status: System validated in bacterial cells. 
Development underway for use in eukaryotic expression systems.
    Inventors: Shankar Adhya and Sudeshna Kar (NCI).
    Publication: S Rao, S Hu, L McHugh, K Lueders, K Henry, Q Zhao, RA 
Fekete, S Kar, S Adhya, DH Hamer. Toward a live microbial microbicide 
for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. 
Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):11993-8. Epub 2005 Jul 
22, doi 10.1073/pnas.0504881102.
    Patent Status: U.S. Provisional Application No. 60/571,943 filed 18 
May 2004 (HHS Reference No. E-261-2003/0-US-01); PCT Application No. 
PCT/US2005/17001 filed 17 May 2005, which published as WO 2005/116222 
on 08 Dec 2005 (HHS Reference No. E-261-2003/0-PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Tara L. Kirby, Ph.D.; 301/435-4426; 
[email protected].

    Dated: December 6, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E6-21301 Filed 12-13-06; 8:45 am]
BILLING CODE 4140-01-P