[Federal Register Volume 67, Number 36 (Friday, February 22, 2002)]
[Notices]
[Pages 8275-8276]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-4296]


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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.

Reagents to Examine the Expression and Function of CYP2J Subfamily 
P450s

Darryl Zeldin and Alyce Bradbury (NIEHS)
DHHS Reference No. E-033-02/0--Research tool
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    Cytochromes P450 catalyze the NADPH-dependent oxidation of 
arachidonic acid to various eicosanoids found in several species. The 
eicosanoids are biosynthesized in numerous tissues including pancreas, 
intestine, kidney, heart, and lung where they are involved in many 
different biological activities.
    The NIH announces cloned cDNAs for several different CYP2J 
subfamily members and specific peptide-based antibodies to the P450 
proteins. The reagents available for licensing include: human CYP2J2 
cDNA, rat CYP2J3 cDNA, mouse CYP2J5 cDNA, mouse CYP2J9 cDNA, anti-
CYP2J2rec, anti-CYP2J2pep2, anti-CYP2J9pep2, anti-CYP2J5pep, anti-
CYP2J6pep, and insect cell microsomes expressing catalytically active 
CYP2J2. These reagents can be used to examine the expression of the 
CYP2J subfamily at the RNA and protein level and can be used to screen 
drugs for possible metabolism by the CYP2J2 subfamily P450s and/or to 
identify endogenous substrates for the enzyme. The recombinant protein 
may also be used to investigate cross-reactivity for other antibodies.

Polyclonal Antibody to Detect Human Membrane-Bound Protaglandin E 
Synthase

Dr. Thomas Eling et al. (NIEHS)
DHHS Reference No. E-032-02/0--Research Tool
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    Prostaglandin endoperoxide H2 (PGH2) is 
formed from arachidonic acid by the action of cyclooxygenases (cox)-1 
or -2. Human prostaglandin E synthase (PGES) is a member of a protein 
superfamily consisting of membrane-associated proteins involved in 
eicosanoid and glutathione metabolism. PGE2 a specific 
prostaglandin, is formed from PGH2 by PGES and is then 
further metabolized into various eicosanoids. It has been reported that 
the membrane-bound mPGES is linked to cox-2 protein, which may be 
induced by proinflammatory cytokines such as 
IL-1 at sites of inflammation.
    The NIH announces a polyclonal antibody capable of detecting human 
mPGES. It is anticipated that the use of this antibody in western 
analysis, immunostaining and immuno-precipitation studies will aid 
researchers in understanding prostaglandin creation and could 
eventually lead to the development of new anti-inflammatory agents.

Amyloid Beta is a Ligand for FPR Class Receptors

Dr. Ji Ming Wang et al. (NCI)
DHHS Reference No. E-336-01/0 filed 26 Oct 2001
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. Five to ten percent 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 has been 
identified as playing an important role in the neurodegeneration of 
Alzheimer's disease. However, the mechanism by which this occurred was 
unknown, but has been postulated to be either direct or indirect 
through an induction of inflammatory responses.
    The NIH announces the identification of the 7-transmembrane, G-
protein-coupled receptor, FPRL-1, in the cellular uptake and fibrillar 
aggregation of amyloid  (A) 
peptides. The A peptides use the FPRL-1 receptor to 
attract and activate human monocytes and mouse microglial cells 
(publications referenced below), and have been identified as a 
principal component of the amyloid plaques associated with Alzheimer's 
disease. In addition, the known anti-inflammatory drug, Colchicine, has 
been shown to inhibit the FPRL1 activation by amyloid and the 
internalization of FPRL1/amyloid beta complexes.
    This research has been published in Tiffany et al., ``Amyloid-beta 
induces chemotaxis and oxidant stress by acting at formylpeptide 
receptor 2 (FPR2), a G protein-coupled receptor expressed in phagocytes 
and brain'', J. Biol. Chem. 276(26):23645-52, 2001, and Cui et al., 
``Bacterial lipopolysaccharide selectively up-regulates the function of 
the chemotactic peptide receptor FPR2 in murine microglial cells'', J. 
Immunol.168: 434-442, 2002.

System for in vivo Site-Directed Mutagenesis Using Oligonucleotides

Dr. Francesca Storici et al. (NIEHS)
DHHS Reference No. E-204-01/0 filed 27 Jul 2001
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    Through the use of molecular techniques to induce mutagenesis, 
along

[[Page 8276]]

with genetic functionality data, a large body of information is now 
available to characterize eukaryotic genomes. Yet with all the 
advancements seen, the techniques used have been unable to produce 
clean sequence modifications that contain no heterologous material and 
are flexible and easy to use.
    The NIH announces a new technology wherein unpurified 
oligonucleotides can be used to create in vivo specific mutations that 
do not retain heterologous material following mutagenesis. This 
technology is versatile in that it will allow for site-specific 
mutagenesis as well as random mutagenesis within a localized area and 
is applicable to all organisms where homologous recombination is or can 
be performed. The technology allows for the generation of mutated 
products in vivo that contain only the desired mutation and can be used 
in multiple rounds of specific or random changes of up to 200 base 
pairs.

Fluorescent Magnesium Indicators

Drs. Robert E. London, Pieter Otten, and Louis A. Levy (NIEHS)
Serial No. 60/191,862 filed 24 Mar 2000 and Serial No. 09/816,638 filed 
on 23 Mar 2001
Licensing Contact: Pradeep Ghosh; 301/496-7736 ext. 211; e-mail: 
[email protected]

    Magnesium is essential to many physiochemical processes and plays a 
central role in the biochemistry of all cells. Many epidemiological 
studies have established close association between plasma magnesium 
levels and various diseases including ischaemic heart disease, 
hypertension, atherosclerosis, osteoporosis, neurological disorders and 
other chronic illnesses. However, methods and tools to measure 
selectively ionized magnesium levels in cell preparations or in the 
body with accuracy and reliability are still lacking in the market 
today. The present invention pertains to analytical elements and 
methods for the selective determination of magnesium. In particular, 
the present invention relates to carboxy-quinolizones and their use as 
magnesium indicators. Thus, the present invention provides novel 
fluorescent indicators that are selective for Mg2+. This 
invention utilizes fluorescence spectroscopy as a tool in monitoring 
intracellular or extracellular levels of magnesium. This is a non-
invasive approach in which ion levels or ion fluxes induced by extra-
cellular stimuli that can be monitored in real time. Current approaches 
used to measure devices to measure ionized intracellular magnesium in 
the body generally involve magnetic resonance spectroscopy to analyze 
intracellular ATP (adenosine triphosphate) signals. This approach is 
extremely expensive and subject to very poor accuracy. Unlike other 
methods and indicators, the composition and methods of this invention 
provide compounds with significantly increased abilities to accurately 
measure intracellular and extracellular Mg2+ levels in a 
wide variety of cells. Further, an extended application of this 
invention relates to the monitoring of the effects of drugs, medicines 
or toxins that alter the intracellular magnesium levels via changes in 
cellular ATP levels.

Novel Anti-Thrombin Peptide From the Salivary Gland of Anopheles 
albimanus

Jesus G. Valenzuela, Jose Ribeiro, Ivo Francischetti (NIAID)
Serial No. 60/141,423 filed 29 Jun 1999 and PCT/US00/18078 filed 29 Jun 
2000
Licensing Contact: Pradeep Ghosh; 301/496-7736 ext. 211; e-mail: 
[email protected]

    Currently, there exists a need for effective bio-pharmacogenic 
inhibitors that can inhibit clot formation and platelet aggregation 
without lethal side effects. Blood clot formation resulting from 
platelet aggregation and chemical release may lead to several fatal 
vascular diseases such as myocardial infarction, strokes, pulmonary 
embolism, deep vein thrombosis, peripheral arterial occlusion and other 
cardiovascular thromboses. This invention pertains to the isolation and 
sequencing of an anticoagulant inhibitor. In particular, the invention 
describes the nucleic acid and amino acid sequences of anti-thrombin 
peptide anophelin, isolated from the salivary glands of the mosquito 
Anopheles albimanus. Alpha-thrombin has been reported to play an 
important role in the platelet dependent arterial thrombus formation 
leading to several life-threatening vascular diseases including 
myocardial infarction and strokes. The mosquito salivary anophelin 
described in this invention, referenced in Valenzuela et. al. 
Biochemistry. 1999 Aug 24;38(34):11209-15, is a novel, specific, tight-
binding and effective inhibitor of alpha-thrombin. Biochemically, 
anophelin is a 6.5 kDa peptide that is easily synthesized, has no 
similarity to hirudin, and has no cysteines. The interaction of 
anophelin with anti-thrombin inhibits platelet aggregation and blood 
clotting. The current invention may be effectively administered in 
subjects, including humans, to inhibit alpha-thrombin activity by 
inhibiting platelet aggregation.

Identification of Compounds That Potentiate the Activity of 
Muscarinic Potassium Channels

David L. Armstrong and Desuo Wang (NIEHS)
DHHS Reference Nos. E-265-98/0 filed 30 Nov 2000 and E-265-98/1 filed 
29 Nov 2001
Licensing Contact: Pradeep Ghosh; 301/496-7736 ext. 211; e-mail: 
[email protected]

    Heart disease is one of the major causes of mortality in developed 
and developing countries. Potassium channel proteins regulate the 
excitability of heart muscle, and drugs that open potassium channels 
have been useful in treating human disease. The present invention 
describes a novel and G-protein independent mechanism for selectively 
stimulating muscarinic potassium channels (KIR 3.1/3.4 or KAch). KAch 
channels are a specific heteromeric class of potassium channels that 
regulate the excitability of atrial and modal monocytes in the heart in 
response to muscarinic receptor stimulation. Specifically, the present 
invention relates to compounds that potentiate the activity of 
muscarinic potassium channels in mammalian atrial monocytes and can 
treat cardiac disease. The present invention provides a novel mechanism 
for selectively stimulating KAch channels with tetraethylammonium (Wang 
& Armstrong 2000 J. Physiol. 529, 699-705. New drugs that selectively 
target the TEA site in the potassium channel without blocking other 
potassium channels may be able to relax the heart. Because TEA has been 
shown to enhance basal potassium channel activity without blocking or 
potentiating muscarinic stimulation, the danger of stopping the heart 
by targeting this site is minimized. In addition, because KACh channels 
are expressed primarily in atrial and nodal myocytes, the action 
potential duration would be shortened selectively in atrial and modal 
monocytes leading to slower pacemaker initiation and impulse condition 
without reducing ventricular force. Thus, identification of new drugs 
that target the TEA-site reported in this invention could have great 
market potential.

    Dated: February 12, 2002.
Jack Spiegel,
Director, Division of Technology, Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-4296 Filed 2-21-02; 8:45 am]
BILLING CODE 4140-01-P