National Institutes of Health, Public Health Service, HHS.
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.
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 Start Printed Page 29767function, 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).
- 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.
- 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.
- 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.
- 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.
- Therapeutic drug testing for targeting BHD renal tumors, possible starting material for developing a cancer vaccine against BHD.
- 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.
- 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, f olliculi n-i nteracting p rotein (FNIP1), may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways.
Inventor: W. Marston Linehan (NCI).
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-Dubé 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; firstname.lastname@example.org.
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.:
- 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.
- 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.
- 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.
- 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 email@example.com 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.
- Method to detect and quantify miRNAs.
- 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.
- U.S. microRNA revenues were $20 million in 2008 will increase to more than an estimated $98 million in 2015.
- Global cancer market is worth more than eight percent of total global pharmaceutical sales.Start Printed Page 29768
- 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; firstname.lastname@example.org.Start Signature
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