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Government-Owned Inventions; Availability for Licensing

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AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

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.

Methods for Using Modulators of Extracellular Adenosine or an Adenosine Receptor to Enhance Immune Response and Inflammation

Michail V. Sitkovsky, Akio Ohta (NIAID),

DHHS Reference No. E-051-02/1 filed 19 Dec 2001,

Licensing Contact: Cristina Thalhammer-Reyero; 301/496-7736 ext. 263; e-mail: thalhamc@od.nih.gov.

Local inflammation processes are crucially important in the host defense against pathogens and for successful immunization because pro-inflammatory cytokines are necessary for initiation and propagation of an immune response. However, normal inflammatory responses are eventually terminated by physiological termination mechanisms, thereby limiting the strength and duration of immune responses, especially to weak antigens. The inventors have shown that adenosine receptors play a critical and non-redundant role in down-regulation of inflammation in vivo by acting as the physiological termination mechanism that can limit the immune response. The adenosine A2a and A3a receptors have been identified as playing a critical role in down-regulation of the immune response during inflammation.

This invention claims methods for inhibiting signaling through the adenosine receptor to prolong and intensify the immune response. The method involves administering either an adenosine-degrading drug or an adenosine receptor agonist. Also claimed in the invention is use of adenosine receptor agonists or adenosine-degrading drugs as vaccine adjuvants and methods for accomplishing targeted tissue damage such as for tumor destruction. This invention is further described in Ohta A et al., “Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage,” Nature 2001 Dec 20-27;414(6866):916-20.

Novel Spore Wall Proteins and Genes From Microsporidia

J. Russell Hayman, John T. Conrad, Theodore Nash (NIAID),

DHHS Reference No. E-125-01/0 filed 04 Dec 2001,

Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; e-mail: soukasp@od.nih.gov.

Microsporidia are obligate intracellular organisms that infect a wide variety of animals ranging from insects and fish to mammals, including humans. Of over 1000 microsporidial species identified, at least thirteen are known to infect humans. The species most commonly identified in humans are members of the families Encephalitozoonidae and Enterocytozoonidae. In humans, microsporidiosis is most often found in HIV/AIDS patients and commonly results in severe diarrhea and wasting. However, microsporidiosis also occurs in immunocompetent individuals and common farm animals. The disease is Start Printed Page 18233transmitted via environmentally resistant spores.

This invention claims two spore wall constituents (SWP1 and SWP2) from the microsporidian Encephalitozoon intestinalis and the genes from which these two proteins are derived. Further claimed are methods of diagnosing and treating microsporidiosis in a subject. Also claimed are methods for producing an immunoprotective response in a subject. SWP1 is expressed on the surfaces of developing sporonts and SWP2 is expressed on the surfaces of fully formed sporonts. Therefore, they should be exposed to the host cell environment. Based on this theory, antibody responses to SWP1 and SWP2 were addressed in an in vivo mouse model. Immunoprecipitation and Western blot analyses indicated that SWP1 and SWP2 are immunogenic in mouse infections.

This invention is further described in Hayman et al., “Developmental expression of two spore wall proteins during maturation of the microsporidian Encephalitozoon intestinalis,Infect. Immun. 2001 Nov;69(11):7057-66.

Activated Dual Specificity Lymphocytes and Their Methods of Use

P. Hwu, M.H. Kershaw, and S.A. Rosenberg (NCI),

U.S. Utility Patent Application 09/803,578 filed 09 Mar 2001,

Licensing Contact: Jonathan Dixon; 301/496-7735 ext. 270; e-mail: dixonj@od.nih.gov.

While T-cell therapies can work in some patients, the use of these cells to treat cancer and viral diseases is often limited by the poor survival and proliferation of these cells in vivo. Cancer clinical trials have demonstrated that the transferred lymphocytes can recognize tumors in vitro, but human subjects often do not respond to infusion. Gene marking studies have demonstrated that the transferred cells often survive for only short periods of time in vivo, thus limiting their effectiveness.

The current invention relates to a method that using genetic modification to generate leukocytes with multiple specificities. To improve proliferation and activation of the transduced T cells, cell transfer is combined with stimulation using a second antigen. Thus T cells are stimulated through their native T cell receptor, using a powerful immunogen, which facilitates expansion and activation. In experiments, mice receiving alloantigen stimulated cells rejected tumors while mice receiving the unstimulated cells did not reject the tumor cells.

This technology represents a potential therapy for a wide variety of malignancies, and because of the genetic modification used, this therapy will be applicable to patients of any MHC type.

Effect of COMT Genotype on Frontal Lobe Function

Daniel R. Weinberger (NIMH), Michael F. Egan (NIMH), Terry E. Goldberg (NIMH), David Goldman (NIAAA), Joseph H. Callicott (NIMH),

DHHS Reference No. E-174-00/0 filed 11 May 2001,

Licensing Contact: Norbert Pontzer; 301/496-7736, ext. 284; e-mail: np59n@nih.gov.

Abnormalities of prefrontal cortical function are prominent features of schizophrenia and have been associated with genetic risk, suggesting that susceptibility genes for schizophrenia may impact on the molecular mechanisms of prefrontal function. A potential susceptibility mechanism involves regulation of prefrontal dopamine, which modulates the response of prefrontal neurons during working memory. The Catechol-o-methyltranferase (COMT) gene contains a G to A mutation which causes a substitution of methionine for valine at codon 158. The met allele has a four fold reduction in enzyme activity which leads to an increase in prefrontal cortical dopamine levels. NIH investigators observed that the functional polymorphism in the gene encoding COMT is associated with variations in executive function and efficiency of working memory in normal controls and schizophrenic patients.

The invention provides a method of detecting impaired prefrontal cognitive function in a subject individual comprising determining the individual's COMT genotype and associating a high activity val allele with impaired prefrontal cognitive function and a low activity met allele with enhanced prefrontal cognitive function. The COMT genotype can be determined using a relatively simple restriction fragment length polymorphism analysis after PCR amplification of the polymorphic region of exon four since the met substitution introduces a NlaIII restriction site into the allele. Clinical medical tests to determine prognosis in schizophrenia and other conditions associated with the polymorphism would thus be possible. The invention also provides for treating patients with COMT inhibitors after tests that predict the response of a patient with schizophrenia, other neurological disorders or aging related declines in cognition to administration of a COMT inhibitor.

Identification of a Transforming Fragment of Herpes Simplex Type 2 and Detection thereof in Clinical Specimen

Joseph A. DiPaolo (NCI), Allegria Dessous-Elbaz, Francois Coutlee,

U.S. Provisional Application SN 60/020,957 filed 01 Jul 1996; PCT Application No. PCT/CA97/00470 filed 30 Jun 1997; U.S. Patent Application SN 09/202,918 filed 23 Dec 1998; Canadian Patent Application SN 2,259,657 filed 23 Dec 1998,

Licensing Contact: Uri Reichman; 301/496-7736 ext. 240; e-mail: reichmau@od.nih.gov.

The present invention relates to novel diagnostic and therapeutic methods for Herpes Simplex Virus Type 2 (HSV-2). HSV-2 infects approximately one fifth of adults in the United States and is the most common cause of genital ulceration. The invention relates to the detection of HSV-2 based on a transforming nucleic acid sequence and its protein product. This DNA sequence harbors the potential to induce the tumorigenic transformation of normal cells in in vitro and in vivo assays and thus will be useful as a means of prognostic evaluation in predicting the development of genital or cervical cancer. Current HSV-2 diagnostic tests relying on tedious viral culture and/or immunoassays do not have the sensitivity and the specificity essential for diagnosis. Using PCR, the current invention will provide a superior method for viral detection and subtyping. In addition the in vivo administration of the antisense primers corresponding to the transforming DNA sequence and the use of antibodies against the protein product can be powerful therapeutic treatments against HSV-2.

Mitochondrial Topoisomerase I

Yves Pommier and Hong-Liang Zhang (NCI),

DHHS Reference No. E-099-01/0 filed 16 Feb 2001,

Licensing Contact: Matthew Kiser; 301/496-7056 ext. 223; e-mail: kiserm@od.nih.gov.

This invention describes a gene that codes for a human topoisomerase that exclusively acts on mitochondrial DNA, and is the first described mitochondrial topoisomerase. Since a number of diseases are caused by mitochondrial malfunction, this gene could form the basis of a number of different therapies. For instance, mitochondrial malfunctions could lead to disturbances in energy metabolism and programmed cell death (apoptosis). This Start Printed Page 18234mitochondrial gene product could thus lead to new diagnoses and therapies centered on apoptosis, which is a critical event in cancer and autoimmune disorders.

In addition to the gene sequence, the patent application covers the encoded protein, protein fragments, monoclonal and polyclonal antibodies, and methods to alter the level of this gene's expression. Also included in the claims are methods to identify activators or inhibitors of the topoisomerase enzyme. NIH invites commercial partners to apply for either an exclusive or non-exclusive license to this technology. We also invite companies who may be interested in commercializing the topoisomerase or the antibodies for research reagent use.

This abstract replaces one published in the Federal Register on January 28, 2002 (67 FR 3905).

Start Signature

Dated: April 3, 2002.

Jack Spiegel,

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

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[FR Doc. 02-9094 Filed 4-12-02; 8:45 am]

BILLING CODE 4140-01-P