[Federal Register Volume 64, Number 27 (Wednesday, February 10, 1999)]
[Notices]
[Pages 6668-6669]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-3238]


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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.

A Method Of Using A 2-Adrenergic Receptor 
Agonist That Selectively Activates Gs Proteins In The 
Treatment Of Cardiovascular Disease

Rui-Ping Xiao, Edward G Lakatta, Heping Cheng (NIA)
Serial No. 60/102,475 filed 30 Sep 98
Licensing Contact: Charles Maynard; 301/406-7735 ext. 243;
e-mail: [email protected]

    This technology relates to a method of using 2-
adrenergic receptor agonist that selectively activates Gs 
proteins in the treatment of cardiovascular disease. In particular, 
this invention relates to a method of using fenoterol to activate 
selectively Gs proteins in the treatment of acute heart 
failure, chronic heart failure and aging heart. In the heart, 
-adrenergic receptor (AR) stimulation provides the 
primary regulatory mechanism on cardiac function. There are at least 
two AR subtypes, namely 1AR and 
2AR, that exist in the myocardium, although 
1AR predominates. While 1AR 
couples to stimulatory G proteins (Gs), 
2AR elicits bifurcated signaling pathways mediated 
by Gs and Gi, resulting in functionally opposing 
effects on cardiac function. In failing and aged hearts, the overall 
response to AR stimulation is markedly diminished due to the 
down-regulation of 1AR and an up-regulation of 
Gi proteins.
    This invention is predicated on the surprising and unexpected 
discovery that a 2AR agonist can selectively 
activate Gs proteins, and is further predicated on the 
discovery that selective activation of Gs proteins by a 
2AR agonist can revive AR contractile 
support in failing hearts.
    An object of the present invention is to provide ligands (agonists 
and antagonists), and methods for the selective activation and 
inactivation of a subset of signaling pathways coupled to any given 
receptor of any cell or tissue type. It is another object of the 
present invention to provide ligands and methods for the selective 
activation and inactivation of a subset of signaling pathways involving 
G proteins. In particular, Gs and Gi proteins 
coupled to a cardiovascular receptor such as 2 AR 
for the treatment of cardiovascular disease.

Aminohydroxylated Adenine Derivatives

    KB Sharpless, DM Jerina, KR Dress, LJ Goossen, AS Pilcher, H Kroth, 
AR Ramesha (NIDDK)
Serial No. 60/091,900 filed 07 Jul 98
Licensing Contact: Charles Maynard; 301/496-7735 ext. 243; e-mail: 
[email protected]

    The invention herein describes a process for the addition of 
adenine and its derivatives to olefins to produce cis-vicinal 
aminoalcohols. The adenine moiety is contained in numerous drugs as 
well as plant growth regulators. In addition, adducts of purine bases 
in

[[Page 6669]]

DNA have been implicated in the transformation of normal cells to tumor 
cells. A key feature of the synthesis is that it provides a one-step 
high yield process for the production of adducts derived from the cis-
opening of diol epoxide metabolites from polycyclic aromatic 
hydrocarbons. Previously such cis-opened adducts have not been readily 
accessible.
    This technology provides compositions and synthetic methods for the 
preparation of important biologically active compounds. Typically, 
admixing adenine, olefin and ligand in the absence of oxygen with an 
appropriate catalyst produces the desired product for a wide range of 
substituted olefins and amino derivatives.

Mammalian Gene Insertion Libraries

X Zheng, CL Steward, SH Hughes, EV Barsov (NCI)
Serial No. 09/069,127 filed 28 Apr 98
Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail; 
[email protected]

    Sequencing of the genomes of higher organisms is progressing 
rapidly, but only a fraction of the open reading frames and cDNAs whose 
sequence are known have functions associated with them. There is 
therefore a great need to assign functions to these open reading 
frames. One method of achieving this goal is insertional mutagenesis 
using transposable elements. An insertion into a gene not only alters 
the structure of the gene but also serves as a molecular marker for 
characterizing and cloning the targeted gene. While effective, this 
approach has been problematic in mammals due to the large size and 
complexity of mammalian genomes and the lack of appropriate mammalian 
transposable elements. The current invention provides a mammalian 
insertional mutation library in which each cell has one or more copies 
of a vector inserted into its genome at essentially random locations, 
and the library as a whole includes insertions in the majority of the 
genes of the genome. The cells used to create the libraries can be of a 
variety of types, including totipotent cells, and can be used to 
generate a whole animal. The unique vectors used to make the libraries 
are retrovirus-based, replication-deficient in mammalian cells and are 
efficiently produced in avian cells at high titers. This technology 
allows for the efficient creation of transgenic mice in which a 
detailed investigation of the cellular processes that are affected by 
the expression of mutated gene sequences can be performed as well as an 
analysis of the consequences on the physiology of the whole animal.

Preparation of Chiral 5-Aminocarbonyl-5H-Dibenzo[A,D]Cyclohepten-
5,10-Imines by Optical Resolution

TH Jones, Kc Rice (NIDDK)
Serial No. 08/420,013 filed 11 Apr 95; U.S. Patent No. 5,686,414 issued 
11 Nov 97
Licensing Contact: Leopold Luberecki, Jr.; 301/496-7735 ext. 223; e-
mail: [email protected].

    This case discloses a means for chiral separation of 5-
Aminocarbonyl-5H-Dibenz0[A,D] Cyclohepten-5,10-Imines (ADCI), a 
compound under development by an exclusive licensee as a treatment for 
epilepsy and nervous system disorders. Approximately one percent of the 
American population suffers from epilepsy or related seizure disorders, 
and many of these patients do not respond to currently available 
antiseizure medications. It can be assumed that if one of the 
enantiomeric forms of ADCI is more active than the other, the U.S. Food 
and Drug Administration and its equivalent foreign counterparts will 
require use of that stereoisomeric form of the compound.

A Novel Mouse Model For Non-Insulin Dependent (TYPE II) Diabetes 
Mellitus

CR Kahn, JC Bruening, D Accili (NICHD)
DHHS Reference No. E-123-96/0 filed 07 Jun 96
Licensing Contact: Charles Maynard; 301/496-7735 ext. 243;
e-mail: [email protected].

    This technology relates to animal models of polygenic insulin-
related disorders and methods of using such animals. The invention 
features a ``genetically engineered'' non-human animal having a first 
and second mutation in genes important for insulin action. The double 
``knockout'' animal is useful as a model of polygenic insulin-related 
disorders, e.g., type II diabetes. Non-insulin dependent (TYPE II) 
diabetes mellitus (NIDDM) is among the most common of all metabolic 
disorders, affecting 6-7% of the U.S. population. Currently no good 
animal models exist for NIDDM. The most frequently used models are 
models of genetic obesity. In these obesity models, there is gradual 
development of insulin resistance as the obesity increases. The Goto-
Kitazak (GK) rat has been proposed as a non-obese model of NIDDM, 
although the diabetes in this case is quite mild and the pathogenesis 
is much less well understood. Thus, a need still exists to develop a 
novel mouse model that closely resembles human NIDDM disease.

    Dated: February 1, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 99-3238 Filed 2-9-99; 8:45 am]
BILLING CODE 4140-01-M