[Federal Register Volume 76, Number 54 (Monday, March 21, 2011)]
[Notices]
[Pages 15324-15326]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-6570]


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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.

UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell 
Carcinoma

    Description of Technology: Hereditary Leiomyomatosis and Renal Cell 
Carcinoma (HLRCC) is an extremely aggressive cancer syndrome with no 
effective treatment regimen and currently no cure. The progress of 
identifying HLRCC treatments and cures has likely been hindered due to 
the lack of an HLRCC model for studying the cancer syndrome and for 
screening therapeutic drug candidates.
    This technology describes the UOK 268 cell line, a spontaneously 
immortalized renal tumor cell line that may be of great interest to 
industry for studying HLRCC, drug screening, and searching for tumor 
markers related to diagnosis, prognosis, and drug resistance. This cell 
line is only the second spontaneously immortalized cancer cell line of 
its kind in the world and is unique in that it is a primary tumor cell 
model (the other cell line, UOK 262, is from a metastasis cell model). 
The UOK 268 cell line is an established, clonal, immortalized renal 
cancer cell line derived from the long-term culture of aggressive tumor 
tissues of HLRCC in a specially designed culture medium under strict 
culture conditions. The UOK 268 exhibits an array of HLRCC kidney 
cancer characteristics that can promote protein and fatty acid 
biosynthesis and modulate HIF activities in a manner conducive to 
cancer cell proliferation.
    Benefits:
     This is only one of two immortalized HLRCC cell lines, and 
is unique in that it is from a primary tumor cell model.
     Developing a diagnostic to search for tumor targets and 
screen for HLRCC and related cancers drug candidates will have 
significant benefits, including early detection and treatment.
    Applications:
     In vitro and in vivo cell model for understanding the 
biology of HLRCC and related cancers, including growth, motility, 
invasion, and metabolite production.
     High throughput screening to test for drug candidates that 
could be used to treat particular cancers, such as HLRCC.
     Diagnostic tool for the diagnosis, prognosis, and drug 
resistance of tumor markers.
    Advantages:
     Cell line is derived from a HLRCC patient: This cell line 
is anticipated to retain many features of primary HLRCC samples and 
novel HLRCC antigens identified from this cell line are likely to 
correlate with antigens expressed on human HLRCC tumors. Studies 
performed using this cell lines may have a direct correlation to the 
initiation, progression, treatment, and prevention of HLRCC in humans.
     Molecular and genetic features are well characterized: The 
inventors have elucidated many physical characteristics of the cell 
lines and their data reveals previously unrecognized coordination 
between mammalian glucose and iron metabolisms through AMPK signaling, 
and a novel mechanism for modulating HIF activities in renal cancers.
    Inventors: W. Marston Linehan and Youfeng Yang (NCI)
    Publications:
    1. Youfeng Yang et al. Distinct Mito-transcriptome Profiling in 
Fumarate Hydratase-deficient Novel Primary Tumor Cell Line UOK268 Leads 
to Better Understanding of Early Human HLRCC-associated Cancer with 
Multiple Dysregulated Molecular Events and Metabolic Shunts. Under 
submission.
    2. Wing-Hang Tong et al. Hypoactivation of AMPK pathway and 
remodeling of iron metabolism in hereditary leiomyomatosis and renal 
cell carcinoma tumorigenesis. Under resubmission.
    Patent Status: HHS Reference No. E-254-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Urologic Oncology Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize UOK268 as human HLRCC primary cell 
line model to comparing previously established UOK262, which was from 
metastasis lympho node. UOK 268 is a unique cell model for studying the 
underlying molecular derangements associated with impaired oxidative 
phosphorylation in cancer and for evaluating novel therapeutic 
approaches for this HLRCC-associated kidney cancer. Please contact John 
Hewes, PhD at 301-435-3121 or [email protected] for more information.

Agonistic Human Monoclonal Antibodies Against DR4

    Description of Technology: The tumor necrosis factor (TNF)-related 
apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and 
DR5, have been recognized as promising targets for cancer treatment. 
Therapeutics targeting TRAIL and its receptors are not only effective 
in killing many types of tumors but they also synergize with 
traditional therapies, and show efficacy against tumors that are 
otherwise resistant to conventional treatments.
    The researchers at the NIH have developed two human monoclonal 
antibodies (mAbs) that bind to death receptor 4 (``DR4''). One of the 
mAbs is agonistic and inhibits the growth of ST486 cells with IC50 of 
about 10nM. The two mAbs were selected from a human phage-displayed Fab 
library by panning against a recombinant DR4

[[Page 15325]]

extracellular domain. Therefore the two mAbs are fully human. These 
antibodies could have considerable potential as cancer therapeutics 
alone or in combination with other drugs. Further, these antibodies 
could be used as a research tool for the study of DR4.
    Applications:
     The DR4 antibodies could be promising candidate cancer 
therapeutics. Ongoing phase I and II clinical trials with mostly DR5-
targeting agonistic antibodies have indicated that they are safe and 
could be efficacious for certain indications.
     DR4 is expressed in a broad range of solid tumors and 
malignancies and therefore antibodies to DR4 would be also useful 
reagents to study this expression.
    Development Status: Pre-clinical proof of principle
    Inventors: Dimiter S. Dimitrov (NCI) et al.
    Publication: Feng Y, Xiao X, Zhu Z, Dimitrov D. Identification and 
characterization of a novel agonistic anti-DR4 human monoclonal 
antibody. MAbs. 2010 Sep-Oct;2(5):565-570. [PubMed: 20581445]
    Patent Status: U.S. Provisional Application No. 61/355,449 filed 16 
Jun 2010 (HHS Reference No. E-158-2010/0-US-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Membrane Structure and Function Section, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize topic of 
invention or related laboratory interests. Please contact John Hewes, 
PhD at 301-435-3121 or [email protected] for more information.

Gene Signature for Predicting Solid Tumors Patient Prognosis

    Description of Technology: A progressive sequence of somatic 
mutations and epigenetic changes of oncogenes or tumor suppressor genes 
are believed to cause tumor development. However, high genomic 
instability in tumors causes the accumulation of genomic aberrations 
that do not contribute to tumor progression. Therefore it is important 
to distinguish between `driver' mutations which are functionally 
important and `passenger' mutations which do not provide a selective 
advantage to the tumor cells.
    The current invention describes a driver gene signature for 
predicting survival in patients with solid malignancies including 
hepatocellular carcinoma (HCC) and breast cancer. The gene signature 
includes ten cancer-associated genes, and the NIH researchers further 
discovered that a decrease in DNA copy number or mRNA expression of 
some genes is associated with poor prognosis in HCC tumors and breast 
cancer, while a decrease in DNA copy number or mRNA expression of a few 
other genes is associated with good prognosis. They have also 
demonstrated that at least four of these cancer-associated genes are 
functional tumor suppressor genes. Thus, these genes may be potential 
molecular targets of HCC and breast cancer.
    Available for licensing is a method of predicting the prognosis of 
a patient diagnosed with HCC or breast cancer by detecting expression 
of one or more cancer-associated genes, and a method of identifying an 
agent for use in treating HCC.
    Applications:
     Prognosis for hepatocellular carcinoma (HCC) and breast 
cancer patient survival.
     Potential new method to identify therapeutic treatment for 
HCC and breast cancer patients.
    Development Status: Early-stage development.
    Market:
     Hepatocellular carcinoma (HCC) is the most frequent 
malignant tumor in the liver and the third leading cause of cancer 
death worldwide. Systemic chemotherapy has been shown to be ineffective 
and tumor recurrence rate after surgical resection is high due to 
relapse and metastasis. Therefore, the development of new drugs will be 
crucial to prevent relapse and to prolong patient survival.
     Breast cancer
    Inventors: Dr. Xin Wei Wang and Dr. Stephanie Roessler (NCI)
    Patent Status:
     U.S. Provisional Application No. 61/198,813 filed 10 Nov 
2008 (HHS Reference No. E-024-2009/0-US-01)
     PCT Application No. PCT/US2009/063883 filed 10 Nov 2009, 
which published as WO 2010/054379 on 14 May 2010 (HHS Reference No. E-
024-2009/0-PCT-02)
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, PhD; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Human Carcinogenesis, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this Gene Signature for Predicting Hepatocellular Carcinoma Patient 
Prognosis. Please contact John Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Prevention of Head and Neck Cancer Using Rapamycin and Its Analogs

    Description of Technology: It is frequently observed in head and 
neck squamous cell carcinoma (HNSCC), a cancer occurring mostly in the 
mouth, that the Akt/mTOR pathway is abnormally activated. Therefore, 
inhibiting this signaling pathway may help in treating this disease. 
Rapamycin and its analogs are known to inhibit the activity of mTOR so 
in principle they could serve as therapeutics for treating HNSCC.
    Researchers at the NIH have developed a method of potentially 
preventing or treating HNSCC through the inhibition of mTOR activity. 
The proof of this principle was demonstrated by rapid regression of 
mouth tumors in mice afflicted with Cowden syndrome with the 
administration of rapamycin. Like HNSCC, development of this disease is 
linked to over activation of the Akt/mTOR pathway. Furthermore, the 
therapeutic potential of rapamycin was demonstrated using mice in 
experiments that model chronic exposure to tobacco, which promotes the 
development of HNSCC. Therefore, inhibitors of mTOR have considerable 
potential in the prevention and treatment of HNSCC.
    Applications: Preventing the development of oral cancer using mTOR 
inhibitors to halt progression of pre-cancerous lesions.
    Development Status: Pre-clinical proof of principle.
    Market:
     Approximately 500,000 new cases of squamous cell 
carcinomas of the head and neck arise every year making it the 6th most 
common cancer in the world.
     Frequently, prognosis is poor due to late detection of 
cancer.
    Inventors: J. Silvio Gutkind et al. (NIDCR)
    Publications:
    1. Squarize CH, Castilho RM, Gutkind JS. Chemoprevention and 
treatment of experimental Cowden's disease by mTOR inhibition with 
rapamycin. Cancer Res. 2008 Sep 1;68(17):7066-7072. [PubMed: 18757421]
    2. Czerninski R, Amornphimoltham P, Patel V, Molinolo AA, Gutkind 
JS. Targeting mTOR by rapamycin prevents

[[Page 15326]]

tumor progression in an oral-specific chemical carcinogenesis model. 
Cancer Prevention Res. 2009 Jan;2(1):27-36. [PubMed: 19139015]
    3. Raimondi AR, Molinolo A, Gutkind JS. Rapamycin prevents early 
onset of tumorigenesis in an oral-specific K-ras and p53 two-hit 
carcinogenesis model. Cancer Res. 2009 May 15;69(10):4159-4166. 
[PubMed: 19435901]
    Patent Status: U.S. Patent Application No. 13/059,335 filed August 
20, 2009 (HHS Reference No. E-302-2008/0-US-05) and related 
international filings
    Related Technology: International Application No. PCT/IL2010/000694 
filed August 25, 2010 (HHS Reference No. E-282-2009/0-PCT-02), entitled 
``Prevention and Treatment of Oral and Lips Diseases Using Sirolimus 
and Derivatives Sustained Release Delivery Systems for Local 
Application to the Oral Cavity and Lips''
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected]
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research, Oral and Pharyngeal Cancer Branch, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact David W. Bradley, PhD at 
[email protected] for more information.

Three-Dimensional Co-Culture Assay System for Angiogenesis and 
Metastasis

    Description of Technology: This technology features an assay for 
the detection and measurement of angiogenesis (formation of new blood 
vessels) and metastasis (spread of cancer). The inventors have 
developed a three-dimensional co-culture system that closely mimics the 
in vivo environment in which angiogenesis and metastatic tumors 
develop. The co-culture system consists of cancerous cells (tumor 
spheroid or biopsy), endothelial cells, and a combination of other 
mammalian cells (mast cells, adipocytes, fibroblasts, macrophages, 
etc.). The cancerous cells can be obtained from cell lines or biopsied 
tumors from various cancers, such as melanoma, ovarian cancer, 
hepatocellular cancer, or colon cancer. Cells in the three-dimensional 
co-culture system express a fluorescent protein having a different 
emission spectrum. Consequently, the co-culture systems can be used to 
identify, monitor, and measure changes in morphology, migration, 
proliferation and apoptosis of cells involved in angiogenesis and/or 
metastasis. The co-cultures are developed in 96-well plates to allow 
rapid and efficient screening for whether a drug impacts multiple cell 
types, modulates angiogenesis and/or has a therapeutic impact on 
metastasis. This technology not only represents an important tool for 
angiogenesis and cancer research, but also may be developed into a 
diagnostic test that allows the development of personalized therapies 
for cancer and other angiogenesis-mediated disease.
    Applications:
     Personalized therapies for cancer and other angiogenesis-
mediated diseases
     Screening for cytotoxic compounds, modulators of 
angiogenesis, and anti-metastatic compounds
     Basic research applications, such as fluorescence-
activated cell sorting (FACS), time-lapse cinematography, and confocal 
microscopy
    Advantages:
     Closely mimics tumor microenvironment
     Efficient screening method for basic research, drug 
discovery and for clinical use
    Development Status: Experimental data available; inventors have 
also developed a high-throughput screening assay based on this 
technology
    Inventors: Changge Fang, Enrique Zudaire, Frank Cuttitta (NCI)
    Patent Status:
     U.S. Provisional Application No. 60/976,732 filed 01 Oct 
2007 (HHS Reference No. E-281-2007/0-US-01)
     U.S. Application No. 12/802,666 filed 10 Jun 2010 (HHS 
Reference No. E-281-2007/1-US-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Tara L. Kirby, PhD; 301.435.4426; 
[email protected].
    Collaborative Research Opportunity: We are very interested in 
setting up collaborations with pharmaceutical, biomedical, or academic 
investigators to use our technology in the form of a CRADA or joint 
grant submission (e.g. DOD). These studies could include expanding the 
complexity of a 3D co-culture by increasing the partner cell number--
paralleling the current model of in vivo angiogenesis. Our existing co-
culture assay incorporates both immortalized tumor and endothelial 
cells. However, other anatomically distinct cells could be added (e.g. 
pericytes, inflammatory cells [mast cell or macrophages], or 
fibroblasts) to more accurately mimic the in vivo setting. In addition, 
a more thorough analysis of our prior xenograft biopsy studies for 
assessing drug sensitivity could be done using a variety of human tumor 
cell lines that include lung, colon, breast, prostate, and ovarian 
cancer. Finally, this collaboration would segue into clinical studies 
taking biopsy material from cancer patients (following approved IRB 
protocols) to evaluate anti-angiogenic drug sensitivities to determine 
the most appropriate FDA reviewed/certified anti-cancer drugs.
    The National Cancer Institute, Radiation Oncology Branch, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology as noted above. Please contact John Hewes, PhD at 301-
435-3121 or [email protected] for more information.

    Dated: March 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-6570 Filed 3-18-11; 8:45 am]
BILLING CODE 4140-01-P