Federal Inventions for August 24, 2000 --- SSTI Weekly Digest

Federal Tech Transfer Opportunities

During the past week, the following agencies have listed inventions available for licensing.

Department of Energy (1 invention)
Department of Health & Human Services
- Office of Technology Transfer, National Institutes of Health (3 inventions)

This is a special notice issued by Westinghouse Savannah River Company (WSRC), management and operating contractor for the U.S. Department of Energy's Savannah River Site near Aiken, South Carolina. WSRC wishes to determine public interest in licensing for commercial resale the Ball Valve Extractor, a simple, sliding impact tool for quickly and easily removing a ball valve from a process line. Using conventional hand tools, such as pliers or a bar, or a specialized clamp-on tool, to pry valve parts loose for maintenance or repair is cumbersome, time consuming, and can damage the outer surface of the ball valve. Reuse of surface-damaged valves deteriorates the sealing gaskets, requiring more frequent repair and replacement. The new Ball Valve Extractor allows the worker to unseat and remove the ball valve in seconds without damage to the outer surface of the valve. The tool is equally useful with ball valve assemblies that are covered with process residue, which can make conventional removal of ball valves even more difficult. The tool can be used in any position or angle from vertical to horizontal. Interchangeable tips enable the tool to be used with different valve stem hole configurations and with valves sized for various inner flow diameter openings.

For more information on the Ball Valve Extractor and licensing opportunities, contact Dale K. Haas via telephone at (803) 725-4185 or (800) 228-4988; via Fax at (803) 725-4988; via email at dale.haas@srs.gov; or via regular mail at Westinghouse Savannah River Company, ATTN: Dale K. Haas, Building 773-41A #238, Aiken, SC 29808. Responses to this notice should be received by September 20, 2001. This is not a request for a formal subcontract; it is a request for interested parties and licensing opportunities only.

Department of Health & Human Services

Office of Technology Transfer, National Institutes of Health

SUMMARY: The inventions listed below are owned by agencies 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.

Single-Chain Antibody Fragment Protein Binding to HIV-1 Integrase
Eugene Barsov and Stephen Hughes (NCI), DHHS Reference No. E-193-01/0
Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: hus@od.nih.gov
Integration of the viral DNA into the host genome is a prerequisite for efficient viral transcription and establishment of productive HIV-1 infection in humans. This function is mediated by the viral protein integrase. The invention discloses a single-chain Fab fragment of a murine monoclonal antibody (scFv35) that is able to inhibit the viral integrase. The antibody fragment can be recombinantly expressed. The Fab fragment is further described in the Journal of Virology 70 (7), pp 4484-4495, 1996. It is available for licensing through a Biological Materials License Agreement as no patent application has been filed.

Plasmid Based Assay for the in vitro Repair of Oxidatively Induced DNA Double Strand Breaks
Thomas A. Winters, Elzbeitz Pastwa, and Ronald D. Neumann (CC), DHHS Reference No. E-319-00/0 filed 06 Oct 2000
Licensing Contact: Wendy Sanhai; 301/496-7736 ext. 244; e-mail: sanhaiw@od.nih.gov
We describe a new non-radioactive, high throughput in vitro assay for the repair of oxidatively induced DNA double-strand breaks by HeLa cell nuclear extracts. The assay measures non-homologous end joining (NHEJ) repair by employing linear plasmid DNA containing DNA double-strand breaks (DSBs) produced by either the radiomimetic drug bleomycin or StuI restriction endonuclease. The complex structure of the bleomycin-induced DSB more closely models naturally occurring DSBs than restriction enzyme induced DSBs. Although initial optimization reactions were conducted with these DNA molecules, any double-strand-break-inducing agent may be employed to create the linear DNA substrates used in the assay. Cellular extraction and initial end-joining reaction conditions were optimized with restriction enzyme cleaved DNA to maximize ligation activity. Several parameters affecting ligation were examined including extract protein concentration, substrate concentration, ATP utilization, reaction time, temperature, and effect of ionic strength. Similar reactions were performed with the bleomycin-linearized substrate. In all cases, end-joined molecules ranging from dimers to higher molecular weight forms were produced and observed directly in agarose gels stained with Vistra Green and imaged with a FluorImager 595. This method permits detection of less than or equal to 0.25 ng double-stranded DNA per band directly in post-electrophoretically stained agarose gels. Therefore, the optimized end joining reactions required only 100 ng or less of substrate DNA, and up to 50% conversion of substrate to product was achieved. The DSB end structure was shown to directly affect repair of the strand break. Bleomycin-induced DSBs were repaired at a 6-fold lower rate than blunt-ended DNA, and initiation of the reaction lagged behind that of the blunt-end rejoining reaction. Recent experiments have shown repair of DSBs produced by -rays to be 15-fold less efficient than for DSBs produced by restriction enzyme. While repair of the high-LET-like DSB produced by 125I was near the lower limit of detection. Thus, as the cytotoxicity of the DNA damaging agent increases, the DSB created by the agent is less efficiently repaired. Repair efficiency is also dependent upon the repair capacity of the cellular extract employed as a source of repair enzymes. These repair activities are known to vary from tissue to tissue, and person to person. Therefore, by using patient samples as a source of enzyme activities, our method might be employed clinically as a predictive assay for patient sensitivity to DNA damaging agents. Knowledge of a patient's sensitivity to DNA damaging agents may permit more effective choices to be made when selecting treatment options in cases of cancer, and other diseases where DNA damaging agents are commonly used.

Sensitization of Cancer Cells to Immunoconjugate-Induced Cell Death by Transfection With Interleukin-13 Receptor Alpha-Chain
R. Puri (FDA), DHHS Reference No. E-032-00/1 filed 31 August 2000
Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail: rodrigur@od.nih.gov
The claimed technology relates to the use of gene transfer techniques to sensitize cancer cells to IL-13 Receptor-mediated immunotoxin induced cell death. Specifically, the inventor has shown that stable gene transfer of the IL-13R2 chain, of the IL-13 receptor, significantly sensitizes cancer cells to the effects of IL-13 toxin by approximately 520-1000-fold. Since many cancers, e.g., brain, breast, lung, head and neck, pancreatic, prostate or liver, can be inoperable, direct intratumoral administration of treatment-agents may become necessary. As such, the claimed invention shows that a combination approach, utilizing both gene transfer and systemic or locoregional cytotoxin therapy, may be available as a new potent treatment regimen for intractable or refractory cancers.

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