E6-21665. 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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Production, Recovery and Purification Process for Plasmid DNA Clinical Manufacturing

Description of Technology: Available for licensing from NIH is a method for large scale production, recovery, and purification process for plasmid DNA manufacturing meeting human clinical trial requirements. DNA plasmid recovery and purification methods can separate plasmid from contamination from a variety of sources including cellular debris and proteins as well as genomic DNA and RNA. Traditionally, DNA plasmid recovery methods utilizing column chromatography have had poor results such as product elutes with broad smears rather than sharp peaks, product elutes appearing in the flow through thereby preventing isolation from lysate components, and monomeric supercoiled plasmids are not separated from other forms of plasmids. To overcome these shortcomings, a fermentation, recovery, purification, and formulation process for the production of plasmid has been developed. The overall recovery of this process is greater than 400 mg of formulated final product per kilogram (wet weight) of E. coli cell paste.

Applications: (1) Produce clinical grade plasmid DNA for clinical trials; (2) Therapeutic reagents.

Market: This technology has potential uses in drug manufacturing and clinical studies. In the United States alone, there were approximately over 40,000 clinical trials conducted. The potential market is worth several billion dollars.

Inventors: Yueqing Xie et al. (NCI/SAIC).

Related Publications:

1. N Horn et al. U.S. Patent No. 5,707,812, Purification of plasmid DNA during column chromatography.

2. R Lemmens et al. Supercoiled plasmid DNA: selective purification by thiophilic/aromatic adsorption. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Feb 5;784(2):291-300.

3. J Urthaler et al. Application of monoliths for plasmid DNA purification development and transfer to production. J Chromatogr A 2005 Feb 11;1065(1):93-106.

Patent Status: HHS Reference No. E-033-2007/0—Research Tool.

Licensing Status: This technology is available as a non-exclusive license.

Licensing Contact: Jennifer Wong; 301/435-4633; [e-mail].

Collaborative Research Opportunity: The National Cancer Institute—Frederick is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize A Production, Recovery and Purification Process for Plasmid DNA Clinical Manufacturing. Please contact Betty Tong, PhD at [e-mail] for more information.

Chitosan as a Universal Vaccine Adjuvant, Antigen Depot and Cytokine Depot

Description of Technology: This technology describes the use of chitosan depots with appropriate antigens and/or cytokines for generating an immune response in a subject. Such depots are made by mixing one or more antigens and/or cytokines with chitosan or a chitosan derivative. Similar compositions are described wherein chitosan or a derivative forms a micro-or nanoparticle, which have resulted in a more immunogenic presentation of antigen compared to antigen in solution. Using a representative antigen, the inventors showed that mice vaccinated with the subject depots had increased humoral and cellular immune responses compared to mice vaccinated with antigen alone.¹ Furthermore, comparative mouse studies showed the antigen-specific immune response generated with chitosan depots of this invention to be equipotent to incomplete Freund's adjuvant (IFA) and superior to aluminum hydroxide, a widely used adjuvant for licensed and routinely administered vaccines.¹ Thus, this technology improves upon commonly used adjuvant technology and is widely applicable. This technology is the first to show that subcutaneous administrations of chitosan and an appropriate antigen, with no other component, can be used for enhancing immune responses. In additional studies, the inventors showed that chitosan is able to maintain a depot of recombinant cytokine. A single subcutaneous injection of chitosan-cytokine outperforms daily injections of recombinant cytokine in both the expansion of draining lymph nodes and in the antigen presenting ability of lymph node cells. This technology is the first to show that chitosan can maintain a depot of cytokine which results in a significant enhancement of the functional effects of a cytokine. This technology can be used for vaccines and immunotherapies against various infectious agents and cancer.

Applications: Vaccine adjuvant; Immunogenic depots, including vaccine and cytokine.

Development Status: Animal (mouse) data available.

Inventor: Jeffrey Schlom et al. (NCI).

Reference:¹ DA Zaharoff, CJ Rogers, KW Hance, J Schlom, JW Greiner. Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination. Vaccine (accepted November 2006).

Patent Status: U.S. Provisional Application No. 60/846,481 filed 22 Sep 2006 (HHS Reference No. E-311-2006/0-US-01).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Susan Ano, PhD; 301/435-5515; [e-mail]

Collaborative Research Opportunity: The NCI Laboratory of Tumor Immunology and Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize chitosan-mediated immunopotentiation of vaccines and immunotherapies. Please contact Betty Tong, PhD at 301-594-4263 or [e-mail] for more information.

Preparative Two Dimensional Gel Electrophoresis System

Description of Technology: The National Institute of Environmental Health Sciences has developed procedures and a prototype device for isolation of proteins from complex mixtures for protein identification. The system serves as a one-step purification method for isolation of biologically relevant proteins affected by disease or experimental treatment and has been described in Electrophoresis 15, 735-745, 1994. The system includes a preparative isoelectric focusing device for separation of proteins by charge, a glass mold for preparative polyacrylamide gel separation by mass and a protocol for use.

The commercial advantage of the Preparative Two Dimensional Gel Electrophoresis system is to separate and isolate sufficient amounts of individual protein for sequencing in a powerful one-step purification method. The Preparative Two Dimensional Gel Electrophoresis system can resolve individual proteins by charge and mass from up to 1 to 2 mg of unpurified starting material from protein mixtures. Current devices for two dimensional gel electrophoresis are generally for analytical scale work and are not physically or procedurally adapted to accommodate preparative sample loads. Although other preparative electrophoresis devices do exist, they separate by either mass or charge alone and function as stand-alone units without ready integration into additional systems for resolution of individual proteins.

Applications: Protein sequencing, protein immunization for antibody production, immunostaining and other modes of protein characterization.

Development Status: The system has been tested and is operational; however some refinements in protein resolution are still possible which may involve procedural, reagent or equipment modifications.

Inventors: B. Alex Merrick (NIEHS), Rachel Patterson (NIEHS), Robert Hall (NIEHS), Chaoying He (NIEHS), James Selkirk (NIEHS).

Publication: BA Merrick, RM Patterson, LL Witcher, C He, JK Selkirk. Separation and sequencing of familiar and novel murine proteins using preparative two-dimensional gel electrophoresis. Electrophoresis. 1994 May;15(5):735-745.

Patent Status: U.S. Patent No. 5,534,121 issued 09 July 1996, claiming priority to 16 May 1994 (HHS Reference No. E-066-1994/0-US-01).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Michael A. Shmilovich; 301/435-5019; [e-mail].

Collaborative Research Opportunity: The NIEHS National Center for Toxicogenomics, Proteomics Group, may consider statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this preparative two-dimensional gel electrophoresis system. Please contact John Penta, NIEHS Office of Translational Research, at 919/541-3696 or [e-mail] for additional information.

Dated: December 8, 2006.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.