E7-16644. 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.

Methods for Prevention and Treatment of Polyomavirus Infection or Reactivation

Description of Technology: Available for licensing and commercial development are methods of using Tranilast [N-(3',4'-dimethoxycinnamoyl)anthranilic acid] in the prevention and treatment of human polyomavirus infection. Treatment with Tranilast decreases viral protein expression for two human polyomavirus species, JC virus (JCV) and BK virus (BKV). Furthermore, the increase in JCV/BKV protein production observed upon the addition of TGF-β could also be effectively abolished by Tranilast co-treatment. This is of relevance because TGF-β has previously been demonstrated to increase during immunosuppressive conditions, including HIV infection and kidney transplantation.

JCV is responsible for demyelization of the central nervous system, which is observed in cases of progressive multifocal leukoencephalopathy (PML). PML is most frequently seen in patients with HIV/AIDS, but is also a contributing factor in fatalities in patients with leukemia, lymphoma, and connective tissue diseases, in addition to individuals receiving immunosuppressive therapy for autoimmune disorders or prevention of transplant rejection. BKV is associated with serious clinical syndromes such as viruria and viremia, ureteral ulceration and stenosis, and hemorrhagic cystitis and has a causative role in polyomavirus-associated nephrophathy in as many as 10% of all renal transplant recipients. Currently, there are no effective antiviral agents available to treat these opportunistic infections. In all observed cases, activation of either JCV or BKV in immunosuppressed patients has resulted in fatalities.

Applications: Use in treatment and prevention of polyomavirus infection in immunocompromised patients. Specific target is the prevention of PML in treatment therapies for MS patients.

Development Status: In vitro data is currently available and inventors are actively developing the technology.

Inventors: Veersamy Ravichandran (NINDS), Jeffrey B. Kopp (NIDDK), and Eugene O. Major (NINDS)

Patent Status: U.S. Provisional Application No. 60/948,426 filed 06 Jul 2007, entitled “Compositions and Methods for Preventing or Treating Disease Caused by Polyomavirus Infection or Reactivation in a Mammalian Subject” (HHS Reference No. E-179-2007/0-US-01).

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

Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301/435-4507; [e-mail].

Collaborative Research Opportunity: The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize treatment and prevention of polyomavirus infections in immunocompromised patients, with particular interest in JCV and demyelination. Please contact Melissa Maderia, Ph.D., at [e-mail] for more information.

Measles Virus Strain for Diagnostic Applications

Description of Technology: This technology describes a low passage Edmonston strain of measles virus that is more sensitive to neutralization by serum antibodies than the same virus that has been passaged more. This strain can be used to detect lower levels of measles neutralizing antibody than other measles virus strains. This material could also be used to assess effectiveness of anti-measles therapeutics or vaccines.

Application: Measles diagnostic.

Inventors: Paul Albrecht, Judy Beeler, Susette Audet, Dorothy Farrell, G. Richard Burns (CBER/FDA).

Publication: P Albrect et al. Role of virus strain in conventional and enhanced measles plaque neutralization test. J Virol Methods. 1981 Dec;3(5):251-260.

Patent Status: HHS Reference No. E-125-2007/0—Research Tool. Patent protection is not being sought for this technology.

Licensing Status: Available for non-exclusive licensing.

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

Recombinant Baculoviruses Containing Inserts of the Major Structural Genes (vp1) of the Human Polyomaviruses JCV and BKV

Description of Invention: The development of sensitive and specific tests for JC virus and BK virus activity may provide tools essential in the steps required to find a treatment for these fatal infections. This invention describes a Recombinant Vp1 protein (rVp1) that can be used (1) as an antigen source for ELISA assays (2) for studies of viral proteins in cells and (3) for the self assembly of icosahedral particles encapsidating DNA [gene expression of choice in range of up to 5.1kb size gene].

rVp1 can be utilized in ELISA assays to detect both JCV and BKV antibodies. The JCV and BKV rVp1 proteins may serve as antigens for the production of useful anti-sera and monoclonal-antibodies for polyomavirus research, as well as for the detection of existing and/or changing levels of antibodies in human sera by way of ELISA assays. Such ELISA studies allow for tracking of the spread and/or reactivation of polyomavirus infections in the human population, of special importance for individuals at high risk of polyomavirus associated pathologies. The rVp1s eliminate the need to produce infectious, native polyomavirus virions as antigens for such work.

The rVp1 proteins may also be utilized as vector delivery systems. The rVp1 proteins self-assemble into Virus-Like Particles (VLPs) which can be dissociated, reconstituted in the presence of exogenous DNA (that is non-specifically encapsidated), and then internalized through cell membranes that native virions normally cross.

Applications: JCV or BKV antigens useful for polyomavirus research; ELISA studies for individuals at high risk of polyomavirus associated pathologies; Vector Delivery systems.

Developmental Status: ELISA is fully developed and materials are available for licensing.

Inventors: Eugene Major and Peter Jensen (NINDS).

Publications:

1. C Goldmann et al. Molecular cloning and expression of major structural protein VP1 of the human polyomavirus JC virus: Formation of virus-like particles useful for immunological and therapeutic studies. J Virol 1999 May;73(5):4465-4469.

2. RS Hamilton et al. Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus. J Clin Microbiol. 2000 Jan;38(1):105-109.

3. P Lenz et al. Papillomavirus-like particles induce acute activation of dendritic cells. J Immunol. 2001 May 1;166(9):5346-5355.

4. DL Bohl et al. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant. 2005 Sep;5(9):2213-2221.

5. EO Major and P Matsumura. Human embryonic kidney cells: stable transformation with an origin-defective simian virus 40 DNA and use as hosts for human papovavirus replication. Mol Cell Biol. 1984 Feb;4(2):379-382.

6. EO Major et al. Establishment of a line of human fetal glial cells that supports JC virus multiplication. Proc Natl Acad Sci USA. 1985 Feb;82(4):1257-1261.

Patent Status: HHS Reference No. E-216-2006/0—Research Material. Patent protection is not being sought for this technology.

Licensing Status: Available for non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; [e-mail].

Collaborative Research Opportunity: The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize treatment and prevention of polyomavirus infections in immunocompromised patients. Please contact Melissa Maderia, Ph.D., at [e-mail] for more information.

Probe Set Global Optimization

Description of Technology: Available for licensing and commercial development are methods to optimize sequence-based assays such as microarrays, multiplexed PCR or multiplexed antibody methods. This computational method uses numerical optimization to identify an optimal probe set to be used in an assay for the measurement of a specified set of targets. The method incorporates the sequence information of the target (protein, DNA, RNA or other polymer), the assay characteristics, limits on probe set size and assay probe length in its optimization. The method selectively optimizes the total information provided by the assay within constraints of individual probe performance and coverage of all targets in the target set. For example, the target set of sequences could represent known viral or bacterial pathogens, or splice variants of a single gene. The method selectively identifies sequences within each target sequence with the best individual probe performance and providing the most information. An individual probe may be selected because it provides specific information about a single target (specificity) or because it increases (sensitivity) by providing replicate measurements of a sequence common to several targets.

The method's software design allows for large (>10,000) target sets and large probe set sizes (2->1,000,000). While current selection criteria involve a time consuming iterative and manual process, the present invention allows for the identification of a quantitatively optimized probe set which balances probe performance criteria and simultaneously optimizes the sensitivity and specificity of the assay for a given set of targets.

Applications: The invention has applications in the design of various important assays, such as those based on microarrays, multiplexed PCR and SPR, targeted protein fragment detection, or any sequence-specific binding and detection. It has application where the number of probes to be used in an assay is too large for manual design and review.

Inventors: Eric Billings and Kevin E. Brown (NHLBI).

Patent Status: U.S. Provisional Application No. 60/871,447 filed 21 Dec 2006, entitled “Probe Set Global Optimization” (HHS Reference E-332-2005/0-US-01).

Development Status: The technology is ready to be applied and validated in many different areas for research and diagnostic purposes.

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

Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301/435-4507; [e-mail].

Collaborative Research Opportunity: The National Heart, Lung and Blood Institute, Computational Biophysics Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, utilize or commercialize a method for optimizing sequence-based assays. Please contact Dr. Eric Billings, at [phone] or via e-mail at [e-mail] for more information.

Dated: August 16, 2007.

Steven M. Ferguson,

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