[Federal Register Volume 66, Number 64 (Tuesday, April 3, 2001)]
[Notices]
[Pages 17720-17721]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-8086]


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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, DHHS.

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 and Compositions for Analysis of M3 Muscarinic 
Acetylcholine Receptors

Jurgen Wess, Masahisa Yamada (NIDDK), DHHS Reference No. E-291-00/0 
filed 30 Oct 2000, Licensing Contact: John Rambosek; 301/496-7056 ext. 
270; e-mail: [email protected]

    This invention discloses transgenic mice that have the M3 
Muscarinic Acetylcholine Receptor deleted by gene knockout technology. 
These mice were developed in order to better understand the 
physiological relevance of the M3 receptor. Unexpectedly, these 
knockout mice have a phenotype that includes significant reduction in 
food intake, weight loss, peripheral fat deposits, as well as very low 
serum leptin and insulin levels. It was also found that the M3 receptor 
is highly expressed in the hypothalamus, a region of the brain known to 
be critically involved in regulation of food uptake. The mice also show 
physiological changes (increased levels of hypothalmic agouti-related 
peptide mRNA and decreased expression of propiomelanocortin mRNA) 
consistent with those observed in fasted animals. However, the knockout 
mice also have changes

[[Page 17721]]

(reduced levels of melanin concentrating hypothalmic mRNA) inconsistent 
with fasted animals. These data point to the existence of a novel 
cholinergic pathway involving M3 cholinergic receptor mediated 
stimulation of food intake. This technology strongly suggests that 
agents which can specifically and selectively act as antagonists of the 
M3 subtype receptors may be useful in the treatment of obesity.

Methods for Preventing Strokes by Inducing Tolerance to E-selectin

John M. Hallenbeck, et al. (NINDS), Serial No. 60/206,693 filed 24 May 
2000, Licensing Contact: Norbert Pontzer; 301/496-7736 ext. 284; e-
mail: [email protected]

    This invention provides methods of treating or preventing brain 
damage in stroke through administration of E-selectin, an inducible 
adhesion molecule on endothelial cells. The expression of E-selectin is 
induced on human endothelium in response to activation by cytokines IL-
1 and TNF. E-selectin mediates the adhesion of various leukocytes, 
including neutrophils, monocytes, eosinophils, natural killer cells, 
and a subset of T cells to activated endothelium. Activation of 
vascular endothelial cells by proinflammatory cytokines is believed to 
be involved in conversion of the luminal surface of endothelium from 
anticoagulant and anti-inflammatory to procoagulant and pro-
inflammatory leading to thrombosis. Segmental vascular activation and 
thrombosis are involved in the development of strokes.
    Recently, a new method and pharmaceutical formulation have been 
found that induce tolerance mucosally, such as by intranasal 
administration. The potential of mucosally administered antigens to 
inhibit immune responses in an antigen specific fashion has encouraged 
attempts to apply these routes to counteract immune dysfunctions such 
as allergies and in particular, autoimmune disease. Intranasal 
administration of E-selectin induces tolerance to E-selectin and leads 
to immune-deviation of a subset of lymphocytes such that they can 
suppress activation of vessel segments that are beginning to express E-
selectin. Thus the ability of intranasal E-selectin treatment to 
decrease stroke lesions and delay the onset of stroke in stroke-prone 
spontaneously hypertensive rats suggests that the initial vessel 
activation and damage in stroke may be immunologically mediated. 
Production of immunosuppression via antigen-specific modulation of the 
immune response (mucosal tolerance) should have no systemic 
immunosuppressive effects.

    Dated: March 23, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-8086 Filed 4-2-01; 8:45 am]
BILLING CODE 4140-01-P