15324 Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 

the docket number found in brackets in 

the heading of this document. 

Comments and petitions that have not 

been made publicly available on 

http://www.regulations.gov may be 

viewed in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

Dated: February 14, 2011. 

Jane A. Axelrad, 

Associate Director for Policy, Center for Drug 

Evaluation and Research. 

[FR Doc. 2011–6509 Filed 3–18–11; 8:45 am] 

BILLING CODE P 

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. 

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 longterm 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 Mitotranscriptome 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; hastingw@mail.nih.gov. 

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 HLRCCassociated kidney cancer. Please contact 

John Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Agonistic Human Monoclonal 

Antibodies Against DR4 

Description of Technology: The tumor 

necrosis factor (TNF)-related apoptosisinducing 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 

mstockstill on DSKH9S0YB1PROD with NOTICES

Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 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; hastingw@mail.nih.gov. 

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 hewesj@mail.nih.gov 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 cancerassociated 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 cancerassociated 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; 

tongb@mail.nih.gov. 

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 

hewesj@mail.nih.gov 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 precancerous 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 

mstockstill on DSKH9S0YB1PROD with NOTICES

15326 Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 

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; hastingw@mail.nih.gov 

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 

bradleyda@nidcr.nih.gov 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 coculture 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 coculture 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 cocultures 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 antimetastatic 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; kirbyt@mail.nih.gov. 

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 coculture by increasing the partner cell 

number—paralleling the current model 

of in vivo angiogenesis. Our existing coculture 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 

hewesj@mail.nih.gov 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 

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. 

Synthetic Peptide Inhibitors of the Wnt 

Pathway 

Description of Technology: Available 

for licensing are peptide inhibitors of 

mstockstill on DSKH9S0YB1PROD with NOTICES