[Federal Register Volume 67, Number 152 (Wednesday, August 7, 2002)]
[Notices]
[Pages 51288-51289]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-19866]


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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.

An Obligate Domain-Swapped Dimer of Cyanovirin with Enhanced Anti-
Viral Activity

Carole A. Bewley and Brendans Kelly (NIDDK).
DHHS Reference No. E-096-02/0 filed 25 Feb 2002.
Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: 
[email protected].

    The present invention provides a purified or isolated obligate 
domain-swapped dimer of Cyanovirin-N (CVN hereafter), a method of 
making an obligate domain-swapped dimer of CVN and a method of 
inhibiting a viral infection of a mammal by administering domain-
swapped dimer of CVN. CVN is outstanding in that it potently blocks 
viral entry in all human and simian isolates by binding to HIV through 
highly avid and very specific carbohydrate-mediated interactions with 
the surface envelope glycoprotein gp120. CVN has also been shown to 
form a domain-swapped dimer under non-physiological conditions such as 
mM concentration and low pH. This invention provides an obligate 
domain-swapped dimeric mutant of CVN, called Q50-CVN, which 
has several significant advantages over the wild-type CVN: First, 
Q50-CVN can be purified form a crude bacterial cell

[[Page 51289]]

lysate in a single chromatographic step because it forms only one 
homogeneous species. Second, because this obligate dimer has four 
carbohydrate binding sites, it binds gp120 and other glycoproteins with 
greater affinity than wild-type CVN. Third, Q50-CVN shows an 
enhancing increase in efficacy in blocking viral entry in a 
quantitative HIV-1 envelope-mediated cell fusion assay. Thus, 
Q50-CVN displays enhanced anti-HIV activity relative to the 
wild-type CVN monomer and offers a great advantage over wild-type CVN 
because it is extremely easy to purify large quantities to greater than 
95% homogeneity. So, it may open the possibility that an effective drug 
treatment for HIV could reach underdeveloped countries.
    Finally, the background of this invention is further described in 
J. Am. Chem. Soc. (2002) 124:3210-3211, J. Magn. Reson. (2002) 154:329-
335, Structure (2001) 10:931-940, J. Am. Chem. Soc. (2001) 123:3892-
3902, J. Am. Chem. Soc. 122: 6009-6016, and J. Mol. Biol. (1999) 
288:403-412.

Methods and Compositions for Antagonizing Septic Shock

George Kunos (NIAAA).
DHHS Reference No. E-321-01/0 filed 15 Aug 2001.
Licensing Contact: Norbert Pontzer; 301/496-7736, ext. 284; e-mail: 
[email protected].

    Septic shock is an often fatal type of vasodilatory shock that may 
accompany microbial infections. Septic shock has therefore been an 
increasing problem in recent years because of the increasing number of 
individuals who are immunocompromised. Recent studies have indicated 
that the hypotension associated with hemorrhagic shock (Wagner et al., 
Nature 1997; 390:518-521) or septic shock (Varga et al., FASEB J. 1998; 
12:1035-1044) may be mediated by macrophage-derived endogenous 
cannabinoids such as anandamide, acting at vascular cannabinoid 
receptors. In an earlier study (PNAS, 1999; 96:14136) the NIH 
inventor(s) presented several lines of evidence indicating the 
vasodilator effect of anandamide is mediated by a receptor distinct 
from the two known cannabinoid receptors, CB1 and CB2. In particular, 
anandamide-induced vasodilation persists in mice deficient in both CB1 
and CB2 receptors. They postulated that a yet unidentified cannabinoid 
receptor was responsible for the observed effect. The invention 
described and claimed in the pending patent application provides 
compounds acting as agonists and antagonists at the newly described 
cannabinoid receptor and methods for reversing pathological 
vasodilation of blood vessels observed during conditions such as septic 
shock.

Methods of Diagnosing and Treating Schizophrenia

Daniel R. Weinberger et al. (NIMH).
DHHS Reference No. E-247-01/0 filed 31 Aug 2001.
Licensing Contact: Norbert Pontzer; 301/496-7736, ext. 284; e-mail: 
[email protected].

    Neurotrophins promote survival of neurons from both the central 
nervous system and peripheral nervous system in cell culture. More 
recently it has been shown that neurotrophins may serve as a new class 
of neuromodulators that mediate activity-dependent modifications of 
neuronal connectivity and synaptic efficacy. Brain derived neurotrophic 
factor (BDNF) is a neurotrophin that mediates LTP and hippocampus-
related spatial memory. Schizophrenia and other mental disorders appear 
to involve deficits in verbal memory and reduced hippocampal--acetyl 
aspartate (NAA), a measure of hippocampal neuronal integrity. BDNF may 
thus play a role in memory function and human diseases of the 
hippocampus such as schizophrenia.
    The human BDNF gene contains one known non-conservative SNP, 
producing a met66val substitution. The invention is related to the 
discovery that a met66val polymorphism in the gene for BDNF is 
correlated with verbal memory and risk for schizophrenia. The invention 
provides methods and kits for diagnosing and modulating verbal memory 
and risk for schizophrenia in an individual by determining the 
individual's BDNF genotype, and associating a met allele with impaired 
verbal memory and risk for schizophrenia and a val allele with enhanced 
verbal memory and protection from schizophrenia. The invention also 
provides methods of finding and using compounds which modulate BDNF 
function in order to treat human diseases of the hippocampus such as 
memory disorders and schizophrenia.

Retinoids Can Increase the Potency of Anti-Cancer Immunotoxins

You N. Wu and Richard J. Youle (NINDS).
U.S. Patent 5,942,230 issued August 24, 1999 and U.S. Patent 6,197,528 
issued March 6, 2001.
Licensing Contact: Richard Rodriguez; (301) 496-7056 ext 287; e-mail: 
[email protected].

    A unique method of potentiating the effect of anti-cancer 
immunotoxins has been developed, thus offering to significantly improve 
the treatment of a number of cancers as well as autoimmune diseases. 
Prolonged treatment of human cancers with classical methods such as 
radiation and chemotherapy, or a combination of both, may cause greater 
damage than the underlying disease because healthy tissue is often 
damaged along with diseased tissue. More recently, immunotherapy has 
emerged as a new and promising therapy for treating cancer because it 
employs monoclonal antibodies specific for tumor cells coupled to 
protein toxins. Thus, cancer cells are selectively targeted for 
destruction. These immunotoxins are being examined in numerous clinical 
trials for the treatment of cancer and autoimmune diseases. However, 
often the protein toxin coupled to the monoclonal antibody does not 
pass as readily into the cytosol of the target cell as does the native 
protein toxin. This invention improves the effectiveness of such 
immunotoxins by employing retinoic acid, which disrupts the Golgi 
apparatus of the target cell and increases the cytosolic routing of 
specific protein toxins. Also included in this invention is an in vitro 
method for assessing the ability of a retinoid to potentiate the 
activity of immunotoxins.

    Dated: July 29, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-19866 Filed 8-6-02; 8:45 am]
BILLING CODE 4140-01-P