[Federal Register Volume 65, Number 163 (Tuesday, August 22, 2000)]
[Notices]
[Pages 51000-51002]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-21367]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

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

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.

Identification of a Novel Renal NADPH Oxidase

Thomas L. Leto, Miklos Geiszt (NIAID)
DHHS Reference No. E-116-00/0
Filed 12 Apr 2000
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    The NIH announces the identification of a renal NAD(P)H oxidase 
termed RenOX, produced by the proximal convoluted tubule cells of the 
kidney, which is proposed to be an oxygen sensor in the kidney involved 
in regulation of production of erythropoietin. As a source of 
superoxide and other reactive oxygen species in the kidney, RenOX is 
thought to have a direct role in the oxidative down-regulation of 
erythropoietin and other hypoxia-responsive genes in response to oxygen 
levels detected in the kidney.
    Because the inhibition of RenOX may lead to an increase in the 
production of erythropoietin, it has been suggested that it can be used 
as a screening tool for the development of therapies against diseases 
which currently use recombinant erythropoietin as a treatment. These 
include anemia associated with chronic renal failure, HIV infection and 
antiretroviral therapy, cancer, cancer chemotherapy, and chronic 
inflammatory conditions (rheumatoid arthritis, inflammatory bowel 
disease). Because recombinant erythropoietin is considered a costly 
therapy, it may be that an inhibitor of RenOX may prove to be a less 
expensive alternative.
    It is also possible that drugs determined to affect RenOX activity 
may be used to treat hypertension in patients, since RenOX may also 
affect proton transport and sodium reabsorption by kidney tubule cells. 
Because expression of recombinant RenOX was shown to induce cellular 
senescence, other uses of RenOX, by way of gene therapy, may include 
limiting the growth of tumors either by inducing tumor cell senescence 
or inhibiting angiogenesis.
    Because RenOX is proposed to be a key component of oxygen sensing 
in the kidney, the NIH believes it to be a valuable means by which new 
drugs and therapies can be developed and benefit the public health.
    This research has been published in Geiszt et al., ``Identification 
of RenOX, an NAD(P)H Oxidase in Kidney,'' Proc. Nat. Acad.Sci., U.S.A., 
vol 97, pp 8010-8014 (July 5, 2000).

Amyloid  Is a Ligand for FPR Class Receptors

Ji Ming Wang et al. (NCI)
Serial No. 60/186,144
Filed 01 Mar 2000
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    Alzheimer's disease is the most important dementing illness in the 
United States because of its high prevalence. 5 to 10% of the United 
States population 65 years and older are afflicted with the disease. In 
1990 there were approximately 4 million individuals with Alzheimer's, 
and this number is expected to reach 14 million by the year 2050. It is 
the fourth leading cause of death for adults, resulting in more than 
100,000 deaths annually.
    Amyloid beta (A) has been identified as playing an 
important role in the neurodegeneration of Alzheimer's disease. However 
the mechanism used is unknown and has been postulated to be either 
direct or indirect through an induction of inflammatory responses.
    The NIH announces a new early stage technology, that identifies the 
7-transmembrane, G-protein-coupled receptor, FPRL-1, as a functional 
receptor for A peptides. The A peptides use the FPRL-
1 receptor to attract and activate human monocytes, and have been 
identified as a principal component of the amyloid plaques associated 
with Alzheimer's disease. In addition, astrocytes stimulated with 
ligands of FPRL1 produce a proinflammatory cytokine interleukin 6. 
Because amyloid  peptides interact with the FPRL1 receptor, a 
direct link is created between A and the inflammation observed 
during the course of Alzheimer's disease.
    This technology provides a target in which to direct the 
development of preventative or therapeutic agents for Alzheimer's 
disease. Newly discovered A-FPR class receptor complexes can 
be used to modulate the A-induced inflammation response by 
administering polynucleotides, chemical compounds, or polypeptides that 
interact with either A or the FPR class receptor(s), or 
inhibit complex formation altogether. Although this technology is in 
the early stages of drug development, the potential to find new drugs 
to Alzheimer's and other neurodegenerative diseases is a real 
possibility, through its use, to those working in this field.

Constitutively Open Voltage-Gated K+ Channels and Methods for 
Discovering Modulators Thereof

Drs. Kenton J. Swartz, David H. Hackos (NINDS)
DHHS Reference Number E-286-99/0
    Filed 10 Feb 2000
Licensing Contact: John Rambosek, Ph.D.; 301/496-7056 ext. 270; e-mail: 
[email protected]


[[Page 51001]]


    This technology relates to materials and methods for developing 
high throughput strategies for discovery of both inhibitors and 
activators of voltage-gated potassium channels. Voltage gated potassium 
channels are important regulators of electrical excitability throughout 
the nervous system, vascular and cardiac smooth muscle, and various 
secretory tissues such as the pancreas. Drugs that modulate the 
activity of these receptors could have applications in a variety of 
therapeutic areas involving abnormal electrical activity, including 
epilepsy, stroke, cardiac arrhythmia, hypertension, and diabetes.
    The technology described here involves the identification of 
mutations in voltage-gated potassium channels that effectively lock the 
pore open at all membrane potentials. Previously, it has not been 
possible to develop yeast-based high throughput screens using voltage-
gated potassium channels because these channels are normally closed at 
the negative membrane potentials associated with yeast.
    In addition, other types of high-throughput screens for K channel 
inhibitors and activators use voltage-sensitive dyes or indicators as 
reporters of K channel activity. Mutations that lock voltage-gated K 
channels open at negative voltages could significantly improved the 
sensitivity of these voltage-sensitive screens. The strategy employed 
to lock open voltage-gated potassium channels involves alterations in 
an area of the protein that is conserved in all voltage-gated potassium 
channels, and should therefore be applicable to all such potassium 
channels. This will allow generally for the development of high-
throughput screens for activators and inhibitors of all voltage-gated 
potassium channels.
    A Provisional Patent Application Serial Number 60/081,692 has been 
filed for this technology. It is available for licensing through a DHHS 
Patent license.

Equilibrium Thermodynamics-Based Ligand Binding Assays for 
Macromolecules

Dong Xie, John W. Erickson (NCI)
DHHS Reference No. E-076-00/0
    Filed 01 Feb 2000
Licensing Contact: J.P. Kim; 301/496-7056 ext. 264; e-mail: 
[email protected]

    High affinity binding is observed in many biological processes and 
is assayed in the design and development of compounds as therapeutic 
agents for specific biological targets. The accurate determination of 
binding affinities for HIV protease inhibitors is important for the 
determination of the biochemical fitness of drug-resistant HIV variants 
that contain mutations in the protease gene.
    There remains a need for a highly sensitive, accurate, and widely 
applicable method for determining the binding affinity of a ligand for 
a folded macromolecule. Accordingly, the present invention provides 
methods for determining the binding affinity of a ligand for a 
macromolecule and methods for determining whether or not a compound is 
a reversible ligand for a macromolecule, e.g., in the development of 
HIV therapeutics.

Delivery of Proteins Across Polar Epithelial Cell Layers

David Fitzgerald et al. (NCI)
DHHS Reference No. E-277-98/0
    Filed 22 Oct 1999
Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected]

    Many pharmaceutical proteins which need to gain systemic access 
cannot be administered enterally because the enzymes of the digestive 
system degrade the proteins before they gain access. Therefore, 
pharmaceutical proteins generally are administered by injection. 
Diseases that require repeated administration of a protein over long 
period of time, such as diabetes, can require daily injection. Of 
course, frequent injections are not pleasant for the patient and means 
to deliver proteins without injection would be advantageous.
    This invention provides methods for parenteral administration of a 
protein by transmucosal delivery and without injection. Molecules that 
bind 2 macroglobulin receptor, when applied to the apical 
surface of a polarized epithelial cell layer, are able to traverse 
through the basal side of the cell and released into the sub-epithelial 
space. This invention takes advantage of that fact by using Pseudomonas 
exotoxin and derivatives as carriers to deliver proteins and molecules 
bound to them across the epithelial surface without resorting to 
injection of the protein.

Nucleic Acid Molecules Encoding Hepatitis C Virus, Chimeric 
Hepatitis C Virus or Hepatitis C Virus Envelope Two Protein Which 
Lacks All or Part of Hypervariable Region One of the Envelope Two 
Protein and Uses Thereof

Xavier Forns, Jens Bukh, Suzanne U. Emerson, Robert H. Purcell (NIAID)
DHHS Reference No. E-287-99/0
Filed 23 Sep 1999
Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected]

    HCV is an enveloped, single stranded RNA virus, approximately 50 nm 
in diameter, that has been classified as a separate genus in the 
Flaviviridae family. The ability of HCV to undergo rapid mutation in a 
hypervariable region(s) of the genome coding for envelope protein may 
allow it to escape immune surveillance by the host; thus, most persons 
infected with HCV develop chronic infection. These chronically infected 
individuals have a relatively high risk of developing chronic 
hepatitis, liver cirrhosis and hepatocellular carcinoma.
    This invention relates to nucleic acid molecules which encode a 
hepatitis C virus envelope two protein which lacks all or part of the 
hypervariable region one (HVR1) of the envelope two (E2) protein. RNA 
transcripts from a full-length HCV cDNA clone from which the HVR1 was 
removed were able to replicate when transfected into the liver of a 
chimpanzee. The fact that the HVR1 is not essential for virus 
replication is relevant because the partial or complete deletion of 
this region might change the immune response to a more effective one. 
Attenuated viruses could be generated and used as vaccine candidates. 
In addition, DNA constructs or proteins lacking this region could be 
used as vaccine candidates.

Agonist and Antagonist Peptides of CEA

Jeffrey Schlom, Elena Barzaga, Sam Zaremba (NCI)
Serial No. 60/061,589 filed 10 Oct 1997; PCT/US98/19794 filed 22 Sep 
1998; DHHS Reference No. E-099-96/3 filed 06 Apr 2000
Licensing Contact: Elaine White; 301/496-7056 ext. 282; e-mail: 
[email protected]

    The current invention embodies the identification of an enhancer 
agonist peptide variant of a nine amino acid sequence (designated CAP-
1) contained in the human carcinoembryonic antigen (CEA) gene. CEA is 
an antigen which is overexpressed on a variety of human tumor types 
including the following carcinomas: colorectal, breast, non-small cell 
lung, pancreatic and head and neck. Studies have shown that the CAP-1 
peptide is an immunodominant epitope of CEA. Moreover, recent studies 
have shown that the modification of a single amino acid in the CAP-1 
sequence results in the generation of a enhancer agonist peptide, 
designated CAP1-6D. The CAP1-6D peptide is capable of stimulating human 
T-cells to far greater levels than that of CAP1. These T-cells, 
moreover, have been shown to lyse human tumor cells expressing native 
CEA. Thus the CAP1-6D enhancer

[[Page 51002]]

agonist peptide represents a potential immunogen for use as therapeutic 
vaccine against a wide range of human cancers which express CEA and may 
also have potential use as a vaccine to prevent preneoplastic lesions 
or cancers expressing CEA.

    Dated: August 14, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-21367 Filed 8-21-00; 8:45 am]
BILLING CODE 4140-01-P