[Federal Register: April 17, 2008 (Volume 73, Number 75)]
[Notices]
[Page 20929-20930]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17ap08-53]
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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, HHS.
ACTION: Notice.
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SUMMARY: The inventions listed below are owned by an agency 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.
Substituted 3,6-diphenyl-7H-[1,2,4] triazolo[3,4-b] [1,3,4]
Thiadiazines as Potent Inhibitors of PDE4A, PDE4B, and PDE4D
Description of Technology: Phosphodiesterase 4 (PDE4) is a major
cAMP-metabolizing enzyme found in immune and inflammatory cells, airway
smooth muscle, and pulmonary nerves. It plays a significant role within
the inflammatory responses associated with asthma and chronic
obstructive pulmonary disease (COPD) and its modulation has been linked
to memory enhancement and depression. Due to its widespread therapeutic
potential, PDE4 inhibitors are highly sought after agents for treating
numerous disease states. While several PDE4 inhibitors have already
advanced into clinical settings, unfavorable side effects including
emesis, nausea, and abdominal pain emphasize the need for novel
chemotypes with potent and selective PDE4 inhibition.
This technology describes a series of substituted 3,6-diphenyl-7H-
[1,2,4] triazolo[3,4-b] [1,3,4] thiadiazines that act as inhibitors of
PDE4. This core structure represents a novel chemotype within extensive
classes of PDE4 inhibitors and the structure activity relationships of
these PDE4 inhibitors identify key binding sites and substitutions
critical to the functionality for potent PDE4 inhibition. Selectivity
of this novel chemotype shows weak inhibitory potency against nine PDE
isoforms excluding PDE4 and strong inhibitory potency against PDE4A,
PDE4B, and PDE4D. In a selectivity comparison study, the novel
chemotype performs better than the PDE4 inhibitor in clinical
development. Subtype-selective PDE4 inhibitors are becoming
increasingly more important as new research shows that independent PDE
isoforms have differential effects on cells.
Applications: Treatment of numerous diseases associated with PDE4
including asthma, COPD, inflammatory bowel disease, and other anti-
inflammatory diseases with other possible treatments including
depression and psychosis.
Development Status: Pre-clinical.
Publication: AP Skoumbourdis et al. Identification of a potent new
chemotype for the selective inhibition of PDE4. Bioorg Med Chem Lett.
2008 Feb 15;18(4):1297-1303.
Inventors: Craig J. Thomas et al. (NHGRI).
Patent Status: U.S. Provisional Application No. 61/020,079 filed 09
Jan 2008 (HHS Reference No. E-055-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521;
Fatima.Sayyid@nih.hhs.gov.
[[Page 20930]]
Nitrite and Nitrite-Methemoglobin Therapy To Detoxify Stroma-Free
Hemoglobin Based Blood Substitutes
Description of Technology: Cell-free hemoglobin based oxygen
carriers (HBOCs) are blood substitutes and resuscitative agents that
can be used to replace whole blood donations, alleviate blood shortages
and reduce the risks of infections such as HIV and hepatitis. Stroma-
free HBOCs offer the advantages of increased stability, consistency of
supply, and reduced immunogenicity over the use of the alternative cell
based sources. However, the side effects associated with their use,
including vascular toxicity, pulmonary and systemic hypertension,
myocardial infarction, inflammation, and platelet aggregation severely
limit their scope of clinical applications. These adverse effects are
due in part to the ability of free deoxygenated hemoglobin (deoxyHb) to
scavenge for nitric oxide (NO) thus rendering it unavailable for
vasodilating blood vessels.
This technology is a method of using nitrites to reduce the
deleterious effects associated with HBOC use as blood substitutes. Free
nitrites or nitrite-methemoglobin when added to stroma-free HBOCs are
converted to NO and N2O3 which escapes the scavenging activity of
deoxyHb and thus is free to vasodilate blood vessels. This maintains
oxygen release and NO delivery enabling improved clinical outcomes.
Recent studies, using this technology as a blood substitute, have led
to a reversal of vasoconstriction, hypertension and hemorrhagic shock
in animal models. This new approach also reduces the toxicity
associated with the use of HBOCs as a blood substitute and may allow
the widespread use of HBOCs as an alternative to cell based sources. In
combination with this technology, HBOC blood substitutes may now be
used to efficiently deliver therapeutic agents and maintain organ
perfusion during trauma and surgery.
Advantages: Reduced toxicity of cell free hemoglobin blood
substitutes; Increased blood perfusion in patients; Decreased
dependence on blood donations.
Development Status: Pre-clinical.
Inventors: Mark T. Gladwin (NHLBI) et al.
Publication: S Basu, R Grubina, J Huang, J Conradie, Z Huang, A
Jeffers, A Jiang, X He, I Azarov, R Seibert, A Mehta, R Patel, SB King,
N Hogg, A Ghosh, MT Gladwin, DB Kim-Shapiro. Catalytic generation of
N2O3 by the concerted nitrite reductase and anhydrase activity of
hemoglobin. Nat Chem Biol. 2007 Dec;3(12):785-794.
Patent Status: U.S. Provisional Application No. 60/996,530 filed 31
Aug 2007 (HHS Reference No. E-259-2007/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521;
Fatima.Sayyid@nih.hhs.gov.
Dated: April 8, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-8218 Filed 4-16-08; 8:45 am]
BILLING CODE 4140-01-P