[Federal Register Volume 68, Number 95 (Friday, May 16, 2003)]
[Notices]
[Pages 26629-26631]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-12277]


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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.

Method of Treating Ischemia/Reperfusion Injury with Nitroxyl Anion 
Donors

David Wink et al. (NCI).

DHHS Reference No. E-175-2002/0

Filed June 14, 2002, and DHHS Reference No. E-076-2003/0

Filed June 17, 2002.

Licensing Contact: Fatima Sayyid; 301/435-4521; [email protected].

    Ischemia/reperfusion injury refers to tissue damage caused by 
oxygen deprivation followed by reoxygenation causing oxidative stress.

[[Page 26630]]

    The present invention relates to the administration of a nitroxyl 
anion donating compound prior to ischemia to attenuate ischemia/
reperfusion injury. Accordingly, nitroxyl anion donating compounds such 
as Angeli's salt would be useful treatment agents to prevent or protect 
against such adverse conditions especially since the beneficial effect 
is a surprising result given that nitroxyl anion was previously 
reported to increase ischemia/reperfusion injury.

Preparation and Medical Uses of Novel Nitric Oxide Releasing Imidates, 
Amidines Derived Therefrom, and Enamines

Joseph Hrabie, Ernst Arnold, and Larry Keefer (NCI).

DHHS Reference Nos. E-149-2001

Filed June 13, 2001 and E-276-2002

Filed July 18, 2002.

Licensing Contact: Norbert Pontzer; 301/435-5502; [email protected].

    Nucleophile/nitric oxide adducts (N2O2-
diazeniumdiolates) spontaneously dissociate at physiological pH to 
release nitric oxide (NO) by stable first order kinetics. The bulk of 
the known and patented NIH compositions and methods using 
diazeniumdiolates are derived from amine nucleophiles. The formation of 
these amine-derived diazeniumdiolates requires exposure of the 
nucleophile to NO gas with the attendant occurrence of possible 
unwanted side reactions, or preparation of O2 alkylated 
diazeniumdiolates that may release toxic by-products. Also, amine-
derived diazeniumdiolates may dissociate into carcinogenic N-nitroso 
compounds and the primary amines may decompose into unstable 
diazotates. These inventors thus developed diazeniumdiolates in which 
the N2O2-functional groups are bonded to carbon 
atoms. This work has resulted in imidoester-, amidine- and enamine-
derived diazeniumdiolates that spontaneously release NO under 
physiological conditions.
    Previous amidine-linked NO releasing compounds were prepared using 
NO gas after acetamidation of amine groups. This invention provides a 
simple, robust method of preparing diazeniumdiolated imidates from 
cyano compounds. As with other imidoesters, these diazeniumdiolated 
imidoesters react with nucleophiles allowing formation of a wide range 
of NO releasing derivatives. For example, imidoesters are extensively 
used as protein crosslinking reagents because they react with primary 
amines to form amidine bonds. These already diazeniumdiolated and 
purified imidoesters can thus be used to directly attach amidine NO-
releasing groups onto molecules such as peptides and medicinals without 
exposing them to NO gas or its potentially toxic by-products. Some of 
these compounds may also release nitroxyl (HNO, NO) in solution under 
physiological conditions. See Arnold et al., Tetrahedron Lett., 41, 
8421-8424(2000).

Postnatal Stem Cells and Uses Thereof

Drs. Songtao Shi and Pamela Robey (NIDCR).

DHHS Reference No. E-018-2003/0-PCT-01.

Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].

    Many individuals with ongoing and severe dental problems are faced 
with the prospect of permanent tooth loss. Examples of such dental 
problems include: dentinal degradation due to chronic dental disease 
(caries or periodontal); mouth injury; or through surgical removal, 
such as with tumors associated with the jaw. For many, a technology 
that offers a possible alternative to artificial dentures by designing 
and transplanting a set of living teeth fashioned from an individual's 
own pulp cells would greatly improve their quality of life.
    The NIH announces a new technology wherein human postnatal 
deciduous dental pulp stem cells commonly known as ``baby teeth'', are 
used to create dentin and have been shown to differentiate into cells 
of specialized function such as neural cells, adipocytes, and 
odontoblasts. It is believed that these cells could be manipulated to 
repair damaged teeth, induce the regeneration of bone, and treat neural 
injury or disease.
    This research is described, in part, in Miura et al., ``SHED: Stem 
cells from human exfoliated deciduous teeth,'' Proc. Natl. Acad. Sci. 
USA, vol. 100 (no. 10; May 13, 2003) pp. 5807-5812.

Methanocarba Cycloalkyl Nucleoside Analogues

Dr. Kenneth Jacobson (NIDDK).

Serial No. 10/169,975

Filed July 12, 2002, (and related National Stage patent applications).

Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].

    Purines such as adenosine and ATP have been shown to play a wide 
array of roles in biological systems such as inter alia, modulator of 
vasodilation and hypotension, muscle relaxant, central depressant, 
inhibitor of platelet aggregation, regulator of energy supply/demand, 
responder to oxygen availability, neurotransmitter and neuromodulator. 
All P1 and P2 receptor nucleoside ligands suffer from chemical 
instability that is caused by the labile glycosidic linkage in the 
sugar moiety of the nucleoside. However, it has been found that 
relatively few ribose modifications are tolerated by the presently 
known agonists and antagonists of P1 and P2 receptors.
    The NIH announces a new technology wherein a new class of 
nucleoside and nucleotide analogs has been identified that serve as 
selective agonists or antagonists for P1 and P2 receptors. The 
technology relates to a chemical modification of purines and 
pyrimidines, which provide enhanced therapeutic profile and potentially 
greater in vivo stability, because of the absence of a glycosidic bond. 
The P2Y receptor agonists and antagonists could potentially be used in 
immune modulation, inflammation, cardiovascular diseases, 
neurodegeneration, diabetes, and cancer. In addition, the A3 receptor 
agonists and antagonists could be useful in cardioprotection, 
neuroprotection, and asthma.
    This research is described, in part, in J. Med. Chem., 2000, 
43:2196-2203 and J. Med. Chem., 2002, 45:208-218.

Orally Active Derivatives of 1,3,5(10)-estratriene

H.K. Kim, et al. (NICHD).

U.S. Patent 5,554,603
Issued Sep. 10, 1996.

Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].

    The utility of estrogenic substances in the practice of medicine is 
well documented. Estrogens may be used for the replacement of the 
natural hormone, estradiol, in hypogonadism, and following the removal 
of the ovaries or cessation of ovarian activity during menopause. They 
are also widely employed as a component of oral contraceptives. 
However, the orally active synthetic estrogens are associate with a 
number of side effects such as enhanced risk of endometrial carcinoma; 
induction of malignant carcinoma especially in the cervix, breast, 
vagina and liver; promotion of gallbladder disease, thromboembolic and 
thrombotic diseases, myocardial infarction, hepatic adenoma, elevated 
blood pressure, and hypercalcemia; and a worsening of glucose tolerance 
can occur.
    The NIH announces a new family of novel, active estrogens that are 
esters of estradiol. These esters possess enhanced estrogenic activity 
following oral administration in the absence of a 17-

[[Page 26631]]

ethynyl alcohol which has been implicated in many side effects. It is 
anticipated that these esters could be used in all instances where 
estrogen is prescribed as a treatment.
    Additional information about these esters may be found in U.S. 
Patent 5,554,603.

    Dated: May 9, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-12277 Filed 5-15-03; 8:45 am]
BILLING CODE 4140-01-P