[Federal Register Volume 74, Number 85 (Tuesday, May 5, 2009)]
[Notices]
[Pages 20710-20711]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-10300]


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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.

Ratio Based Biomarkers for the Prediction of Cancer Survival

    Description of Technology: The AKT pathway plays a key role in the 
regulation of cellular survival, apoptosis, and protein translation and 
has been shown to have prognostic significance in a number of cancers. 
Recently, the inventors have identified several functions of the AKT 
pathway in certain cancers, such as extrahepatic cholangiocarcinoma 
(EHCC).
    This technology describes compositions, methods and kits for 
identifying, characterizing biomolecules expressed in a sample that are 
associated with the presence, the development, or progression of 
cancer. Utilizing multiplex tissue immunoblotting, the inventors have 
demonstrated that PTEN expression, PTEN/p-AKT ratios, and PTEN/p-mTOR 
ratios can predict the survival of cancer patients. These biomarkers 
may provide useful diagnostic information for cancer patients as well 
as identify patients appropriate for mTOR analog-based chemotherapy or 
agents directed against AKT.

Applications

     Diagnostic and Prognostic tool to detect the presence of 
cancer and predict the relative cancer survival rate for a subject with 
cancer.
     Method of identifying patients appropriate for therapies 
targeted to the AKT pathway.
     A kit for detecting cancer associated proteins in a 
sample.
    Development Status: Pre-clinical stage of development.
    Market: Extrahepatic cholangiocarcinoma (EHCC) is a malignant 
neoplasm of biliary tract epithelia, and constitutes approximately 80-
90% of all cholangiocarcinomas. Surgical resection is the mainstay of 
treatment, but results in only an approximately 20% 5-year survival 
rate. Neoadjuvant therapies, including chemotherapy, radiation therapy, 
and photodynamic therapy have also failed to show significant survival 
benefit, thus emphasizing the need for prognostic and predictive 
biomarkers.
    Inventors: Stephen M. Hewitt and Joon-Yong Chung (NCI).

Publications

    1. JY Chung et al. The expression of phospho-AKT, phospho-mTOR, and 
PTEN in extrahepatic cholangiocarcinoma. Clin Cancer Res. 2009 Jan 
15;15(2):660-667.
    2. JY Chung et al. Transfer and multiplex immunoblotting of a 
paraffin embedded tissue. Proteomics 2006 Feb;6(3):767-774.
    3. JY Chung et al. A multiplex tissue immunoblotting assay for 
proteomic profiling: a pilot study of the normal to tumor transition of 
esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 
2006 Jul;15(7):1403-1408.
    Patent Status: U.S. Provisional Application No. 61/114,501 filed 
January 14, 2009 (HHS Reference No. E-025-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].

Modulating Expression of the Metastasis Suppressor MxA

    Description of Technology: The invention discloses compounds that 
could be used to inhibit metastases. The compounds of the current 
invention were discovered by high-throughput screening of a novel cell 
line engineered with a MxA reporter. The compounds could be used to 
treat metastatic cancers including prostate and melanomas by increasing 
MxA expression.
    MxA expression reduces cell motility and metastases in a mouse 
model. Cells expressing MxA produced smaller tumors in engrafted mice 
compared to controls. When injected into mouse spleens, cells 
expressing MxA showed a significantly delayed metastasis, and the mice 
survived significantly longer than controls. Expression of MxA reduced 
cellular motility of prostate cancer cell lines in vitro and reduced 
cellular motility and invasiveness of the highly metastatic melanoma 
cell line LOX. In addition to the use of the instant MxA compounds as 
antimetastatic agents, MxA is a known effective anti-viral agent and 
the MxA-inducing compounds could be used to treat infections sensitive 
to the antiviral activity of MxA, which potentially include myxovirus-
associated disease.

Applications

     Treatment or prevention of cancers using MxA-targeted 
small molecule therapeutics.
     MxA diagnostic to identify metastatic potential in tumor 
biopsies.
     Treatment or prevention of a myxovirus-associated 
infection, including seasonal and avian flu, using MxA-inducing small 
molecule therapeutics.
    Development Status: Identifying lead compounds for clinical 
development using structure-activity relationship (SAR) analysis.
    Inventors: Jane B. Trepel et al. (NCI).

Publications

    1. JF Mushinski, P Nguyen, LM Stevens, C Khanna, S Lee, EJ Chung, 
MJ Lee, YS Kim, WM Linehan, MA Horisberger, JB Trepel. Inhibition of 
tumor cell motility by the interferon-inducible GTPase MxA. J Biol 
Chem. 2009 Mar 18; online publication ahead of print.

[[Page 20711]]

    2. G Athauda, A Giubellino, JA Coleman, C Horak, PS Steeg, MJ Lee, 
J Trepel, J Wimberly, J Sun, A Coxon, TL Burgess, DP Bottaro. c-Met 
ectodomain shedding rate correlates with malignant potential. Clin 
Cancer Res. 2006 Jul 15;12(14 Pt 1):4154-4162.
    Patent Status: U.S. Patent Application No. 11/663,936 filed March 
27, 2007 (HHS Reference No. E-257-2004/0-US-06) and foreign 
counterparts.
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Medical Oncology Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
John D. Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

Targeted Recombinant Adenoviral Vectors

    Description of Technology: The current invention embodies 
recombinant adenoviral vectors for use in targeted gene transfer. The 
method by which these vectors are generated involves no molecular 
modifications to the adenovirus genome, and allows for the production 
of vectors targeted specifically to virtually any cell line of choice. 
Specifically, the vectors are generated by directly linking biotin to 
the capsid of adenovirus particles. The particles are then treated with 
streptavidin and subsequently incubated with a biotinylated targeting 
moiety which is capable of recognizing a specific marker which is 
expressed on the surface of selected cells. The resulting adenoviral 
vectors are useful for gene transfer, and can be targeted to virtually 
any cell type of interest via incubation with a specific targeting 
moiety.
    To date, the inventors have demonstrated that these vectors can be 
specifically directed to target and infect hematopoietic cell lines 
which display the c-kit receptor, and are capable of achieving high 
levels of gene expression in these cell lines. Also, these vectors can 
be specifically directed to cell surface markers such as CD34, CD44 and 
others through antibodies directly attached to the biotynilated 
adenoviral vectors. Such gene transfer represents a gene therapy 
approach upon which the development of specific therapies against a 
broad range of diseases may be based, including immunodeficiency 
diseases, blood cell disorders, and various cancers.

Applications

     Adenovirus with gene plus Biotinylation kit with 
strepavidin with ligand or antibody for gene of interest
     Biotin linking kits with methods for use
    Development Status: Delivery of the biotinylated recombinant 
adenoviral vector in vitro for use in targeted gene transfer.
    Inventors: Jonathan Keller et al. (NCI).

Publications

    1. JS Smith, JR Keller, NC Lohrey, CS McCauslin, M Ortiz, K Cowan, 
SE Spence. Redirected infection of directly biotinylated recombinant 
adenovirus vectors through cell surface receptors and antigens. Proc 
Natl Acad Sci U S A. 1999 Aug 3;96(16):8855-8860.
    2. S Ponnazhagan, G Mahendra, S Kumar, JA Thompson, M Castillas Jr. 
Conjugate-based targeting of recombinant adeno-associated virus type 2 
vectors by using avidin-linked ligands. J Virol. 2002 Dec;76(24):12900-
12907.
    3. M Brandon Parrott, KE Adams, GT Mercier, H Mok, SK Campos, MA 
Barry. Metabolically biotinylated adenovirus for cell targeting, ligand 
screening, and vector purification. Mol Ther. 2003 Oct;8(4):688-700.

Patent Status

     U.S. Patent 6,555,367 issued April 29, 2003 (HHS Reference 
No. E-193-1997/0-US-03).
     U.S. Patent Application Publication No. US2003/0175973, 
published September 18, 2003 (HHS Reference No. E-193-1997/0-US-04).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].

    Dated: April 27, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-10300 Filed 5-4-09; 8:45 am]
BILLING CODE 4140-01-P