[Federal Register Volume 67, Number 72 (Monday, April 15, 2002)]
[Notices]
[Pages 18232-18234]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-9094]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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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: [email protected].
    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: 
[email protected].
    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

[[Page 18233]]

transmitted 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: 
[email protected].
    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: 
[email protected].
    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: 
[email protected].
    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: 
[email protected].
    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

[[Page 18234]]

mitochondrial 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).

    Dated: April 3, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-9094 Filed 4-12-02; 8:45 am]
BILLING CODE 4140-01-P