[Federal Register Volume 64, Number 37 (Thursday, February 25, 1999)]
[Notices]
[Pages 9339-9341]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-4660]
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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.
ADDRESS: 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.
Activity Dependent Neurotrophic Factor III (ADNP)
DE Brenneman (NICHD), Ilana Gozes (Tel Aviv University)
M Bassan
Serial No. 09/187,330 filed 06 Nov 1998 and claiming priority to PCT/
US98/02485 and 60/037,404.
Licensing Contact: Susan S. Rucker; 301/496-7056 ext. 245; e-mail:
sr156v@nih.gov
These application(s) disclose the identification, isolation,
cloning and sequencing of a newly discovered gene which encodes a
product known as ADNF III (Activity Dependent Neurotrophic Factor III)/
ADNP (Activity Dependent Neuroprotective Protein). The gene has been
localized to the long arm of chromosome 20 at 20q13.2--a region which
has previously been associated with autosomal dominant nocturnal
frontal lobe epilepsy (ADNFLE). In addition to describing ADNF III/
ADNP, the applications describe an eight (8) amino acid peptide
fragment NAP which is an active region ADNF III/ADNP.
ADNP and NAP exhibit neuroprotective activity, the ability to
protect neurons from cell death, with an EC50 in femtomolar range.
Neuronal cell death is suggested as one mechanism in operation in
Alzheimer's disease making ADNP or NAP attractive as candidates for the
development of therapeutics for prevention or treatment of Alzheimer's
disease. Early work using Apo-E deficient mice indicates that NAP can
ameliorate learning and memory deficiencies normally exhibited in these
mice. Other diseases involving neuronal cell death where ADNP or NAP
may be useful include stroke, Huntington's disease, epilepsy,
Parkinson's disease and Tourette's syndrome.
A Mutant OF TEV Protease That Is Resistant To Autoinactivation
David S. Waugh (NCI)
Serial No. 60/104,799 filed 19 Oct 98
Licensing Contact: Kai Chen; 301/496-7056 ext. 247; e-mail:
kc169a@nih.gov
This invention concerns a mutant of the tobacco etch virus (TEV)
proteinase. Due to its high degree of sequence specificity, the TEV
protease is valuable reagent for cleaving fusion proteins. However, the
wild-type TEV protease also cleaves itself to yield a truncated enzyme
with greatly reduced proteolytic activity. As a result, more protease
must be used to achieve complete digestion of a fusion protein
substrate, and the stability of the enzyme during long term storage
becomes problematic. This invention provides a means of avoiding
autoinactivation of TEV, thereby enhancing its utility as a reagent for
cleaving fusion proteins at a specific, predetermined site.
Fluorescent Pteridine Adenosine Analogs As DNA Probes Not Requiring
Separation of Products
ME Hawkins, FM Balis, W Pfledierer (NCI)
Serial No. 60/099,487 filed 08 Sep 98
Licensing Contact: Manja Blazer; 301/496-7056 ext. 224; e-mail;
mb379e@nih.gov
These are part of a series of nucleic acid analogs to be used as
fluorescent probes for DNA analysis. Their site-specific incorporation
into DNA through a deoxyribose linkage causes them to be much more
sensitive to changes in the DNA than traditional fluorophores.
[[Page 9340]]
Incorporated through automated DNA synthesizers, these probes are
effected by base stacking and therefore are excellent detectors of
binding, cleavage and configurational changes brought about by
interactions with proteins or other DNA. This property makes them
useful in the following commercial applications:
Study of DNA/DNA and DNA/protein interactions
Detection of positive PCR products without the use of
radioactive isotopes and gels
Highly Selective Butyrycholinesterase Inhibitors For The Treatment
And Diagnosis Of Alzheimer's Disease And Dementias
NH Greig, A Brossi, TT Soncrant, Q Yu, M Hausman (NIA)
DHHS Reference No. E-247-97/1 filed 09 Jul 98 (CIP of Provisional U.S.
Patent Application No. 60/052,087 filed 09 Jul 97)
Licensing Contact: Leopold J. Luberecki, Jr.; 301/496-7735 ext. 223; e-
mail: 1187a@nih.gov
Defects in the cholinergic system have been reported to primarily
underlie memory impairments associated with normal aging and with
Alzheimer's disease (AD). This invention describes compounds that are
selective, long-acting and reversible inhibitors of the enzyme
butyrylcholinesterase, BChE, that readily enter the brain to both
improve cognitive performance and reduce levels of -amyloid
precursor protein for the treatment of AD. Specific cholinergic
pathways within the brain are regulated by BChE, rather than by its
sister enzyme acetylcholinesterase, AChE, that regulates the vast
majority. Selective BChE inhibitors, described within this invention,
substantially improve cognitive performance in animals without the
classical peripheral and central side effects associated with
cholinesterase inhibition. They, additionally, reduce levels of
-amyloid precursor protein, the source of the toxic peptide,
-amyloid, which is elevated in the brain of patients with AD.
Since small populations of people entirely lack BChE activity and yet
live normal healthy lives, complete inhibition of BChE can be sustained
without harm. In addition to therapeutics, analogues of compounds
described in the invention can be used as potential early diagnostics
of AD. Unlike AChE, which is substantially reduced early in AD, levels
of BChE are increased, particularly in areas associated with deposits
of -amyloid. The high, selective binding of compounds of this
invention to BChE provides the means to image and quantitate the enzyme
as a marker of AD and disease progression. Hence, the compounds
described in this invention have both therapeutic and diagnostic
potential for AD.
Novel Nitric Oxide-Releasing Amidine- and Enamine-Derived
Diazeniumdiolates, Compositions and Uses Thereof and Method of
Making Same
JA Hrabie, LK Keefer (NCI)
DHHS Reference No. E-067-97/1 filed 01 Jul 98 (based on Provisional
U.S. Patent Application No. 60/051,690 filed 03 Jul 97)
Licensing Contact: Leopold J. Luberecki, Jr.; 301/496-7735 ext. 223; e-
mail: 1187a@nih.gov
Diazeniumdiolates are compounds that contain an
N2O2 functional group. These compounds are
potentially useful as prodrugs because they generate nitric oxide upon
degradation. Nitric oxide (NO) plays a role in regulation of blood
pressure, inflammation, neurotransmission, macrophage-induced
cytostasis, and cytotoxicity. NO is also important in the protection of
the gastric mucosa, relaxation of smooth muscle, and control of the
aggregation state of blood cells. A series of amidine- and enamine-
derived diazeniumdiolates have been produced that offer many advantages
over previously known derivatives.
For example, these derivatives are not expected to decompose into
carcinogenic nitrosamines and exhibit a full range of solubility in
water. Many of these derivatives are more heat stable than previous
analogs and release NO at a slow rate. Additionally, some of these
compounds are insoluble in water and thus coatings prepared from them
may not secrete component material after NO release. These properties
may make these derivatives suitable for coating medical devices,
stents, and implants to take advantage of the anti-coagulant properties
of NO. The newly developed synthetic scheme also allows for the
production of NO-releasing agents from known pharmaceuticals. Using
enamines, it may be possible to incorporate the actions of three
pharmaceuticals into a single agent, one as a carbonyl compound,
another as an amine, and the third as the NO-releasing
diazeniumdiolate. Overall, these compounds appear to be applicable
toward the wide variety of processes involving nitric oxide.
Therapeutic And Prophylactic Uses Of Sucrose Octasulfate
Thomas C. Quinn (NIAID), Manuel A. Navia
Serial No. 60/076,314 filed 27 Feb 98
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; e-mail:
ps193c@nih.gov
This invention claims methods for the use of sucrose octasulfate
against gonorrhea and chlamydia infections. Furthermore, the invention
claims compositions combining sources octasulfate with antibacterial or
anti-infective agents. Prior to this invention, sucrose octasulfate
(FDA apporoved) has been widely used as an anti-ulcerant. The methods
described in the application are characterized by one or more of the
following advantages: (1) sucrose octasulfate minimizes disruption of
the epithelial cell surface to which it is applied; (2) sucrose
octasulfate has little, if any, toxic or tumorigenic effects; (3)
sucrose octasulfate has little, if any, anticoagulant activities (in
contrast to larger anionic sulfated polysaccharides), contraceptive
effects, or other reproductive or teratogenic effects; (4) sucrose
octasulfate has affinity for damaged epithelium, which is known to be a
preferred site for bacterial entry; and (5) sucrose octasulfate forms
non-covalent gels, or remains in a liquid state depending upon the
particular salt used. The absence of contraceptive and/or teratogenci
activity demonstrated for sucralfate to date makes this compound ideal
for use in preventing sexually transmitted infections such as chlamydia
or gonorrhea. In vitro studies have been completed on the effects of
sucrose octasulfate against chlamydia and gonorrhea.
O-Linked GlcNAc Transferase (OGT): Cloning, Molecular Expression,
and Methods of Use
JA Hanover, W Lubas (NIDDK)
DHHS Reference No. E-128-97/0 filed 31 Mar 97
Licensing Contract: Manja Blazer; 301/496-7056 ext. 224; e-mail:
mb379@nih.gov
This technology relates to a post-translational modification of a
protein involving the addition of N-acetlyglucosamine in O-glycosidic
linkage to serine or threonine residues in cytoplasmic and nuclear
proteins. It is believed that such modification plays a significant
role in regulation the activity of proteins involved in transcriptional
and translational processes. It likely represents a novel signal
transduction pathway. In particular, this invention provides an enzyme
catalyzing the formation of these derivatives, uridine diphospho-N-
acetlyglucosamine:polypeptide B-N-acetylglucosaminyl transferase (O-
ClcNAc, OGT), and a nucleic acid encoding the system.
[[Page 9341]]
The invention also modifies many phosphoproteins that are
components of multimeric complexes. The sites modified by O-linked
GlcNAc often resemble phosphorylation sites, leading to a suggestion
that the modification may compete for substrate in these polypeptides.
Based on the above properties, this technology may be useful in the
following ways:
As a terminal component of the hexosamine biosynthetic
pathway, OGT may be a key target for systemic problems with glucose
homeostasis such as diabetes mellitus.
Model for glucose sensing by the pancreatic Beta cell.
Model for the study of OGT role in regulating oncogene
activity and function.
Screen for various tumors correlating OGT activity with
metastatic potential.
Tumor suppressor activity and the involvement of OGT in
transcriptional disregulation during transformation.
Dated: February 16, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer.
[FR Doc. 99-4660 Filed 2-24-99; 8:45 am]
BILLING CODE 4140-01-M
