[Federal Register Volume 75, Number 102 (Thursday, May 27, 2010)]
[Notices]
[Pages 29766-29768]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-12790]


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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 257, the First BHD Tumor Cell Line, and UOK257-2 Wild Type FLCN-
Restored Renal Cell Line as In Vitro and In Vivo Models of Energy/
Nutrient Sensing Through the AMPK and mTOR Signaling Pathways

    Description of Invention: Scientists at the National Institutes of 
Health (NIH) have developed a novel renal cell carcinoma (RCC) cell 
line designated UOK257, which was derived from the surgical kidney 
tissue of a patient with hereditary Birt-Hogg-Dube' (BHD) syndrome and 
companion cell line UOK257-2 in which FLCN expression has been restored 
by lentivirus infection. These cell lines harbors a germline mutation 
of FLCN gene (alias BHD) and displays loss of heterozygosity, can grow 
as xenograft in nude mice. Patients affected with BHD develop skin 
papules (fibrofolliculomas), lung cysts, spontaneous pneumothorax and 
an increased risk for bilateral multifocal renal tumors. Loss of both 
copies of the FLCN gene has been documented in BHD renal tumors; 
however, the molecular mechanisms by which inactivation of the encoded 
protein, folliculin, leads to the BHD phenotype are currently unknown. 
They have developed an important research tool for in vitro folliculin 
functional studies. The companion cell line will be extremely useful 
for comparative biochemical analyses of cell culture systems in which 
the FLCN gene is either expressed or inactivated, including 
identification of renal tumor biomarkers, alteration of biochemical 
pathways resulting from loss of FLCN

[[Page 29767]]

function, tumorigenicity of FLCN null versus FLCN restored cells, 
preclinical therapeutic drug testing in xenograft animal models 
produced from injection of these cell lines, etc. UOK 257 and UOK257-2 
are thus useful cell models for studying the underlying molecular 
derangements associated with mTOR pathways and other biogenesis 
pathways in human kidney cancer and for evaluating novel therapeutic 
approaches for this disease. UOK257 is also one of the 40-member renal 
cancer cell lines in the Tumor Cell Line Repository of the Urologic 
Oncology Branch (UOB), National Cancer Institute (NCI).

Applications

    <bullet> In vitro and in vivo cell model for BHD cancer syndrome. 
Research tool for investigating the underlying molecular mechanisms 
contributing to advanced BHD, including the identification of new BHD 
tumor antigens for immunotherapy.
    <bullet> Research tool for studying genes transcription status of 
genes involved in BHD to reveal the genetic processes occurring in BHD 
tissues that may contribute to advanced disease.
    <bullet> Positive control cell line for FLCN gene expression and 
function studies, including cytogenetics, gene mutation research, and 
examination abnormalities of interaction with other proteins that may 
contribute to BHD.
    <bullet> Research tools for testing the activity of potential anti-
cancer drugs against BHD, a disease which has no effective treatment 
options; tool for searching tumor markers for diagnosis, prognosis and 
drug resistance.
    <bullet> Therapeutic drug testing for targeting BHD renal tumors, 
possible starting material for developing a cancer vaccine against BHD.

Advantages

    <bullet> Cell line is derived from a BHD patient: These cell lines 
are anticipated to retain many features of primary BHD samples and 
novel BHD antigens identified from this cell line are likely to 
correlate with antigens expressed on human BHD type of RCC tumors. 
Studies performed using these cell lines may have a direct correlation 
to the initiation, progression, treatment, and prevention of BHD type 
of RCC in humans.
    <bullet> Molecular and genetic features are well characterized: 
This cell line is part of NCI Urologic Oncology Branch's Tumor Cell 
Line Repository. The inventor has elucidated many physical 
characteristics of the cell lines, including chromosomal attributes and 
valuable studies on functions of BHD gene, their data suggest that 
FLCN, mutated in the BHD syndrome, and its novel interacting partner, 
folliculin-interacting protein (FNIP1), may be involved in energy and/
or nutrient sensing through the AMPK and mTOR signaling pathways.
    Inventor: W. Marston Linehan (NCI).

Related Publications

    1. Yang Y, Padilla-Nash HM, Vira MA, Abu-Asab MS, Val D, Worrell R, 
Tsokos M, Merino MJ, Pavlovich CP, Ried T, Linehan WM, Vocke CD. The 
UOK 257 cell line: a novel model for studies of the human Birt-Hogg-
Dub[eacute] gene pathway. Cancer Genet Cytogenet. 2008 Jan 
15;180(2):100-109. [PubMed: 18206534.]
    2. Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, 
Esposito D, Gillette WK, Hopkins RF 3rd, Hartley JL, Furihata M, Oishi 
S, Zhen W, Burke TR Jr, Linehan WM, Schmidt LS, Zbar B. Folliculin 
encoded by the BHD gene interacts with a binding protein, FNIP1, and 
AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci 
USA. 2006 Oct 17;103(42):15552-15557. [PubMed: 17028174.]
    Patent Status: HHS Reference No. E-131-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a Biological 
Materials License Agreement.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
<a href="/cdn-cgi/l/email-protection#43372c2d2421032e222a2f6d2d2a2b6d242c35"><span class="__cf_email__" data-cfemail="05716a6b62674568646c692b6b6c6d2b626a73">[email protected]</span></a>.
    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 kidney cancer tumor cell lines as 
described in above abstract through MTA, CRADAs, CTAs, BML, etc.:
    <bullet> For laboratory interests in the basis of metazoan tumor 
cell survival, including growth factor-regulated nutrient uptake; 
glucose or glutamine metabolism and epigenetic gene control; tumor cell 
bioenergetics and cell growth through AMPK and mTOR signaling pathways.
    <bullet> In vitro and in vivo cell model for BHD cancer syndrome. 
It is a valuable research tool for a laboratory interested in 
identification of new BHD tumor antigens for immunotherapy.
    <bullet> These paired cell lines for FLCN gene expression and 
function studies, including gene therapy, cytogenetics, gene mutation 
research, and examination of abnormalities of interaction with other 
proteins that may contribute to BHD.
    <bullet> The excellent in vivo model for preclinical xenograft 
imaging, including stable transfection. Cells could be labeled with 
reagents for PET, Luciferase, Fluorescence, for transgenic mice, 
optical molecular imaging, etc., and provides a useful platform for 
preclinical drug evaluations.
    Please contact John Hewes, Ph.D. at 301-435-3131 or 
<a href="/cdn-cgi/l/email-protection#7119140614021b311c10181d5f1f18195f161e07"><span class="__cf_email__" data-cfemail="741c110311071e3419151d185a1a1d1c5a131b02">[email protected]</span></a> for more information.

Highly Sensitive microRNA 31 in situ Hybridization Assay To Detect 
Endometrial Cancer

    Description of Invention: Investigators at the National Cancer 
Institute have developed a sensitive, specific and robust human 
microRNA in situ hybridization (ISH) assay that can detect, quantify, 
and identify cancer biomarkers. Currently available microRNA (miRNA) 
markers can be detected by microarray, Northern Blot, real time RT-PCR, 
and sequencing analysis. However, these assays cannot specify tissue 
and cell types that contain miRNAs without laser microdissection (LMD). 
LMD has severe limitations as it requires expensive equipment and its 
miRNA yields are too low to be detected by the aforementioned 
techniques.
    Available for licensing is an optimized an ISH assay to detect 
miRNAs. ISH represents an efficient and specific assay to detect miRNA 
of interest due to direct interaction with specific tissue and cell 
types. This ISH assay utilized fresh cell lines and it can be adapted 
to frozen cells and tissue samples. Utilizing the assay, the 
investigators have found that miRNA-31 is decreased in cancerous 
endometrial cells in comparison to controls. This ISH assay provides 
for a less expensive, more efficient and highly sensitive assay to 
detect and quantify microRNAs.

Applications

    <bullet> Method to detect and quantify miRNAs.
    <bullet> Method and kits to diagnose endometrial cancer.
    Advantages: Cost effective, highly sensitive assay to detect 
miRNAs.
    Development Status: The technology is currently in the pre-clinical 
stage of development.

Market

    <bullet> U.S. microRNA revenues were $20 million in 2008 will 
increase to more than an estimated $98 million in 2015.
    <bullet> Global cancer market is worth more than eight percent of 
total global pharmaceutical sales.

[[Page 29768]]

    <bullet> Cancer industry is predicted to expand to $85.3 billion by 
2010.
    Inventors: Hui Han and John E. Niederhuber (NCI).
    Patent Status: U.S. Provisional Application No. 61/253,617 filed 21 
Oct 2009 (HHS Reference No. E-303-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
<a href="/cdn-cgi/l/email-protection#25524a4b424f406548444c490b4b4c4d0b424a53"><span class="__cf_email__" data-cfemail="98eff7f6fff2fdd8f5f9f1f4b6f6f1f0b6fff7ee">[email protected]</span></a>.

    Dated: May 20, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-12790 Filed 5-26-10; 8:45 am]
BILLING CODE 4140-01-P


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