[Federal Register Volume 75, Number 207 (Wednesday, October 27, 2010)]
[Notices]
[Pages 66108-66110]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-27177]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

Photosensitizing Antibody-Fluorophore Conjugate for Photo-Immunotherapy

    Description of Invention: A major goal of targeted cancer therapy 
is to improve the sensitivity and specificity of the therapy so that 
cancer cells can be detected and targeted for elimination, while normal 
cells in the surrounding area remain largely intact. Photodynamic 
therapy (PDT) is a treatment for cancer and non-cancerous lesions 
involving light and a photosensitizer. The photosensitizer can be 
targeted to a specific cell using antibodies specific for proteins 
expressed on the target cell surface, the target cells will then be 
destroyed after being exposed to light at appropriate wavelength.
    The NIH technology describes a method of photosensitizing cancerous 
cells by irradiating an antibody fluorophore conjugate. The NIH 
investigators have conducted in vitro studies using a proprietary IRDye 
700DX NHS Ester. The IR700 dye was conjugated to a proprietary 
humanized anti-HER1 or anti-HER2 or anti-PSMA antibody, Panitumumab or 
Trastuzumab or huJ591. Subsequent irradiation of non-ionizing near 
infrared light showed rapid cell death of tumor cells, while normal 
cells were not noticeably killed. The studies were repeated in mice 
with similar results.
    Applications and Market:
     Photodynamic therapy for cancer by selective targeting and 
killing of cells without suffering normal tissue side effects.
     Cancer was responsible for about 13% of all human deaths 
in 2007. There remains a need for therapies that effectively kill the 
tumor cells while not harming non-cancerous cells.
    Development Status: Both in vitro and in vivo data available.
    Inventors: Hisataka Kobayashi, Peter L. Choyke, Makoto Mitsunaga 
(NCI)
    Publications: Manuscript in submission.
    Patent Status: U.S. Provisional Patent Application No. 61/363,079, 
filed July 9, 2010 (HHS Reference No. E-205-2010/0-US-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, PhD; 301-594-6565; 
[email protected].

Soluble Glypican-3 Protein for Treatment of Cancer

    Description of Technology: Hepatocellular carcinoma (HCC) is a form 
of liver cancer that is among the more deadly cancers in the world. HCC 
is typically only detected at the later stages of cancer development, 
which is always associated with poor prognosis. Because HCC is often 
associated with liver disease, traditional chemotherapy is not an 
option, making surgery the most common form of treatment. As a result, 
there is a need for new treatments.
    Glypican-3 (GPC3) is a cell surface protein that is normally 
involved in cell growth and differentiation. GPC3 has been shown to act 
through the Wnt-signaling pathway, a pathway that is often activated in 
a number of different cancer cell types. Significantly, the ability of 
GPC3 to activate signaling through Wnt requires that GPC3 be bound to 
the cell membrane. GPC3 is also preferentially expressed on HCC cells, 
suggesting it could play a particularly important role in tumorigenesis 
in HCC.
    This invention concerns a soluble form of GPC3 that lacks its cell 
membrane anchoring domain. This soluble form of GPC3 maintains its 
ability to interact with the Wnt signaling pathway, but cannot induce 
the activation of the pathway because it is not bound to the cell 
membrane. By competing with fully functional GPC3, the soluble GPC3 is 
able to inhibit the growth of HCC cells, thereby decreasing the ability 
of tumors to grow and metastasize. This suggests that soluble GPC3 
represents a possible therapeutic for HCC.
    Applications:
     Soluble GPC3 represents a potential therapeutic for 
patients with cancer with hyperactivated Wnt-signaling pathways.
     Specific cancers include hepatocellular cancer (HCC), 
melanoma, thyroid cancer, lung squamous cell carcinoma, Wilms' tumor, 
neuroblastoma, hepatoblastoma, and testicular germ-cell tumors.
    Advantages:
     Removal of the glycosyl-phosphatidylinositol (GPI) anchor 
results in a soluble form of GPC3 that can interrupt Wnt-signaling.
     Soluble GPC3 maintains the ability to compete with fully 
functional GPC3 despite its inability to activate signaling.
     For treatment of HCC, offers a non-invasive, potentially 
non-liver toxic alternative to current strategies.
    Development Status: Preclinical stage of development; cell culture 
data with HCC cells
    Inventors: Ho (NCI) et al.
    For more information, see:
     ``Recombinant soluble glypican 3 protein inhibits the 
growth of hepatocellular carcinoma in vitro'' Feng et al. Int. J. 
Cancer: E-pub (8 July 2010).
     ``Soluble Glypican 3 inhibits the growth of Hepatocellular 
Carcinoma in vitro and in vivo'' Zitterman et al. Int. J. Cancer: 126, 
1291-1301 (2010).
    Patent Status: U.S. provisional applications 61/334,135 (E-176-
2010/0-US-01) and 61/350,722 (E-176-2010/1-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Molecular Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
John Hewes,

[[Page 66109]]

PhD, at 301-435-3121 or [email protected] for more information.

Drug Combination of DNA Topoisomerase I (TOP1) Inhibitors and 
Extracellular ATP Produces a Significant Increase in Beneficial Anti-
Carcinoma Cytotoxicity

    Description of Invention: DNA Topoisomerase inhibitors are a 
category of drugs used for cancer therapy. DNA topoisomerase 1 (TOP1) 
inhibitors, such as Camptothecin (CPT) and its structurally related 
analogues, bind to the TOP1 complex and prevent the religation of the 
single strand DNA molecules, ultimately leading to cell death. CPT and 
close analogues show anticancer activity in clinical trials treating 
ovarian, small-cell lung, and colorectal cancers, but also adverse drug 
reaction. By reducing the cytotoxic dose in the thousands of folds, the 
NIH scientists are able to target the tumor and reduce the cytotoxicity 
to normal cells. The instant invention discloses that the drug 
combination of DNA topoisomerase 1 (TOP1) inhibitors, such as the anti-
cancer drug Camptothecin (CPT), and extracellular ATP produces a 
significant increase in beneficial anti-carcinoma cytotoxicity.
    Applications and Market:
     This invention may provide a new combination of drug with 
extracellular ATP to target various cancers for treatment.
     Cancer is the second leading cause of death in the U.S. 
The National Cancer Institute estimate the overall annual costs for 
cancer in the U.S. at $107 billion; development of more effective 
therapies with less adverse drug reaction is always in high demand.
    Development Status: Pre-clinical stage of development.
    Inventors: Joseph Riss, Glenn Merlino, J. Carl Barrett (NCI).
    Publications: Manuscript in preparation.
    Patent Status: U.S. Provisional Application No. 61/350,660 filed 02 
Jun 2010 (HHS Reference No. E-098-2010/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, PhD; 301-594-6565; 
[email protected].

Novel Prognostic and Therapeutic Biomarker for Cancer and Inflammatory 
Diseases

    Description of Invention: There remains a significant unmet need 
for diagnostics, prognostics, and therapeutics for conditions that 
involve inflammation and the formation of blood clots such as bleeding 
disorders, trauma, and diseases such as sepsis, cardiovascular disease, 
stroke, and cancer. The global market for such products is varied and 
competitive, and is forecast to be over $40 billion by 2010.
    Researchers at the National Cancer Institute (NCI) have identified 
that levels of a novel soluble protein involved in the repair mechanism 
for damaged blood vessels correlate with outcome in sepsis and with the 
diagnosis of disseminated intravascular coagulation, a contributing 
factor to the morbidity and mortality associated with sepsis.
    Further, the NCI researchers have demonstrated that a recombinant 
version of this novel protein facilitates the clotting of blood, 
suggesting a potentially significant therapeutic benefit for the 
treatment of bleeding disorders or trauma.
    Applications:
     Diagnostic and prognostic biomarker for diseases that 
involve inflammation and blood clot formation (i.e., sepsis, 
cardiovascular disease, stroke, cancer).
     Treatment of bleeding disorders or trauma.
     Treatment of cerebral bleeding associated with aneurism or 
stroke.
     Therapy for patients with low platelet counts.
     Therapy for women suffering from preeclampsia or 
thrombotic episodes.
    Advantages:
     High specificity.
     Protein levels correlate with disease state/outcome.
     Administration of recombinant protein accelerates the 
formation of blood clots.
    Development Status: Pre-clinical.
    Inventors: Daniel McVicar et al. (NCI).
    Relevant Publications:
    1. Washington AV et al. TREM-like transcript-1 protects against 
inflammation-associated hemorrhage by facilitating platelet aggregation 
in mice and humans. J Clin Invest. 2009 Jun;119(6):1489-1501. [PubMed: 
19436112].
    2. Ford JW, McVicar DW. TREM and TREM-like receptors in 
inflammation and disease. Curr Opin Immunol. 2009 Feb;21(1):38-46. 
[PubMed: 19230638].
    Patent Status:
     U.S. Provisional Application No. 61/177,242 filed 11 May 
2009 (HHS Reference No. E-197-2009/0-US-01).
     PCT Application No. PCT/US10/34263 filed 10 May 2010 (HHS 
Reference No. E-197-2009/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Patrick P. McCue, PhD; 301-435-5560; 
[email protected].

Treatment and Prevention of Inflammatory Bowel Disease (IBD) Using 
Mutant and Chimeric IL-13 Molecules

    Description of Invention: Ulcerative colitis (UC) is a chronic 
inflammatory disease of the colorectum and affects approximately 
400,000 people in the United States. The cause of UC is not known, 
although an abnormal immunological response to bacterial antigens in 
the gut microflora is thought to be involved. Present treatments for UC 
include anti-inflammatory therapy using aminosalicylates or 
corticosteroids, as well as immunomodulators and diet. However, 25-40% 
of ulcerative colitis patients must eventually have their colons 
removed due to massive bleeding, severe illness, rupture of the colon, 
risk of cancer or due to side effects of corticosteroids and novel 
treatments are still actively being sought. NIH scientists and their 
collaborators have used a mouse model of experimental colitis 
(oxazolone colitis, OC) to show that IL-13, a Th2 cytokine, is a 
significant pathologic factor in OC and that neutralizing IL-13 in 
these animals effectively prevents colitis.
    OC is a colitis induced by intrarectal administration of a 
relatively low dose of the haptenating agent oxazolone subsequent to 
skin sensitization with oxazolone. A highly reproducible and chronic 
colonic inflammation is obtained that is histologically similar to 
human ulcerative colitis. Studies show that Natural Killer T (NKT) 
cells, rather than conventional CD4+T cells, mediate oxazolone colitis 
and are the source of IL-13 as well as being activated by CD1- 
expressing intestinal epithelial cells. Tissue removed from ulcerative 
colitis patients were also shown to contain increased numbers of 
nonclassical NKT cells that produce markedly increased amounts of IL-13 
and that in keeping with epithelial damage being a key factor in UC, 
these NKT cells are cytotoxic for epithelial cells. Building on their 
previous work, scientists at NIAID and FDA have shown that an Il-13 
chimeric fusion protein linked to an effector molecule was able to 
prevent colitis in a mouse model of ulcerative colitis.
    Available for licensing are methods for treating or preventing the 
inflammatory response of IBD by inhibiting the binding of IL-13 to IL-
13 receptors on NKT cells. Additionally, these mutant and chimeric Il-
13 molecules are able to block the chronic

[[Page 66110]]

inflammatory response that results in fibrosis as seen in Crohn's 
disease. Preventing the inflammatory response of colitis by either 
modulating or blocking IL-13 and NKT cell activity continues to be an 
effective therapeutic approach in animal models of colitis with 
implications for the treatment of human ulcerative colitis and for the 
treatment of fibrosis associated with Crohn's disease.
    Inventors: Warren Strober (NIAID), Ivan J. Fuss (NIAID), Peter 
Mannon (NIAID), Jan Preiss (NIAID), Raj Puri (FDA), Koji Kawakami 
(FDA), Stefan Fichtner-Feigl (NIAID), Atsushi Kitani (NIAID).
    Related Publications:
    1. F Heller, IJ Fuss, EW Nieuwenhuis, RS Blumberg, W Strober. 
Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, 
is mediated by IL-13-producing NK-T cells. Immunity 2002 Nov;17(5):629-
628. [PubMed: 12433369].
    2. IJ Fuss, F Heller, M Boirivant, F Leon, M Yoshida, S Fichtner-
Feigl, Z Yang, M Exley, A Kitani, RS Blumberg, P Mannon, W Strober. 
Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize 
an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004 May 
15;113(10):1490-1497. [PubMed: 15146247].
    Patent Status: U.S. Patent Application No. 11/918,711 filed 14 Apr 
2006 (HHS Reference No. E-003-2005/0-US-03) and related international 
filings.
    Related Technologies:
     IL-13 modulators and inhibitors--U.S. Patent No. 7,666,411 
issued 23 Feb 2010 (HHS Reference No. 131-2002/0-US-02), U.S. Patent 
Application No. 12/709,029 filed 19 Feb 2010 (HHS Reference No. E-131-
2002/0-US-10), and related international filings.
     NF-kappa B decoy oligonucleotides--U.S. Patent Application 
No. 11/920,214 filed 09 Nov 2007 (HHS Reference No. E-108-2005/0-US-
03).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].

    Dated: October 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-27177 Filed 10-26-10; 8:45 am]
BILLING CODE 4140-01-P