[Federal Register Volume 68, Number 165 (Tuesday, August 26, 2003)]
[Notices]
[Pages 51280-51281]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-21696]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

LMNA Gene and Its Involvement in Hutchinson-Gilford Progeria Syndrome 
(HGPS) and Arteriosclerosis

    B. Maria H. Eriksson and Francis S. Collins (NHGRI). Serial No. 60/
419,541 filed 18 Oct 2002 (DHHS Reference No. E-020-2003/0-US-01) and 
Serial No. 60/463,084 filed 14 Apr 2003 (DHHS Reference No. E-131-2003/
0-US-01).

    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare 
progressive childhood disorder characterized by premature aging 
(progeria). The most common cause of death is from arteriosclerosis and 
few children affected by HGPS live beyond their teens. The invention 
identifies point mutations in the LMNA gene, a gene which encodes a 
nuclear lamin protein, as the cause of HGPS. These mutations activate a 
cryptic splice site within the LMNA gene which leads to the excision of 
a portion of an exon and the subsequent generation of a Lamin A protein 
with an internal deletion of fifty (50) amino acids. The identification 
of mutations associated with HGPS could lead to breakthroughs in 
detection, diagnosis, and treatment of HGPS and related or similar 
conditions, including arteriosclerosis and aging. See also Eriksson, M. 
et al ``Recurrent de novo point mutations in lamin A cause Hutchinson-
Gilford progeria syndrome'' Nature 423, 293-298 (2003).

Synthesis of Proteins by Cell-Free Protein Expression

Deb K. Chatterjee (NCI). DHHS Reference No. E-328-2002/0-US-01 filed 11 
Mar 2003.
    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Cell-free protein expression is becoming a valuable tool for rapid 
and economical production of recombinant proteins. In conventional 
cell-free protein synthesis systems, the ATP (high energy) supply is 
accomplished by secondary energy regenerating sources containing high-
energy phosphate bonds. The sources include glucose (G), glucose-6-
phosphate (G-6P), phosphoenolpyruvate (PEP), acetyl phosphate (AP), 
creatine phosphate (CP) or pyruvate. However, for some of these systems 
(G, G-6P and pyruvate) require the addition of exogenous enzymatic 
cofactors such as NAD/NADH, adding considerable expense to the system. 
In addition, the conventional systems (PEP, AP or CP) are also mired by 
unproductive enzymatic degradation of energy sources and unproductive 
consumption of ATP resulting in lower yields of protein.
    The present invention offers a new ATP regeneration system for 
cell-free protein expression, using one of the early intermediates of 
the glycolytic pathway as the secondary energy source. The new energy 
source, costs only a fraction of the conventional substrates, provides 
chemical energy for protein synthesis without the addition of an 
exogenous enzymatic cofactor, thereby reducing the costs of the system. 
Moreover, the present system improves efficiency of protein synthesis 
by several folds by providing an improved energy regeneration system 
and protein-folding machinery.

Cycloxygenase Inhibition With Nitroxyl

David A. Wink et al. (NCI). Serial No. 60/470,320 filed 13 May 2003 
(DHHS Reference No. E-301-2002/0-US-01).
    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Inflammation is initiated and maintained by the overproduction of 
prostaglandins in injured cells. Cyclooxygenase (COX) regulates the 
production of prostaglandins. As the rate-limiting step for 
prostaglandin synthesis, the COX pathway is the primary target for 
anti-inflammatory drugs. Inhibition of COX accounts for the activity of 
the non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, 
acetaminophen, ibuprofen, naproxen, indomethacin. However, these drugs 
are nonselective COX inhibitors. While they inhibit the activity of 
COX-2 in inflammation, they also interfere with the activity of COX-1 
in non-inflamed cells. The inhibition of COX-1 produces undesirable 
side effects, such as gastrointestinal bleeding and renal failure. 
Therefore, agents that selectively inhibit COX-2 over COX-1 are 
desirable for the treatment of inflammation. Moreover, COX-2 inhibiting 
compounds have been reported to be useful in treating a variety of 
conditions, such as general pain, osteoarthritis, rheumatoid arthritis, 
menstrual pain associated with primary dysmenorrhea, cancers, 
Alzheimer's disease and diabetes.
    The present invention relates to methods of using nitroxyl to 
selectively inhibit COX-2 activity. Also disclosed are methods of using 
nitroxyl to treat conditions that respond favorably to COX-2 
inhibition. Nitroxyl-donating compounds include nitroxyl-donating

[[Page 51281]]

diazeniumdiolates such as IPA/NO 
(Na(CH3)2C(H)N(H)N(O)NO). Other embodiments 
include methods of screening candidate nitroxyl-donating compounds for 
COX-2 inhibition.

Nitroxyl Progenitors in the Treatment of Heart Failure

David Wink and Katrina Miranda (NCI). Serial No. 10/226,412 filed 21 
Aug 2002 (DHHS Reference No. E-273-2002/0-US-01).

    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Congestive Heart Failure affects nearly 5 million Americans and 
approximately 550,000 new cases are diagnosed each year.
    The present invention relates to the administration of nitroxyl 
donating compounds, such as Angeli's salt for increasing myocardial 
contractility while concomitantly lowering left ventricular preload in 
subjects experiencing heart failure. Moreover, administration of the 
nitroxyl donating compound, isopropylamine, surprisingly exhibits 
positive inotropic effects in subjects experiencing heart failure that 
were superior to those caused by Angeli's salt. Additionally, in 
contrast to the effects observed with nitric oxide donors, 
administration of a nitroxyl donating compound in combination with a 
positive inotropic agent does not impair the positive inotropic effect 
of the positive inotropic agent. Furthermore, nitroxyl donating 
compounds exert its positive inotropic effect independent of the 
adrenergic system, increasing contractility even in subjects receiving 
beta-antagonist therapy.

Vasopressor Peptide Derived From Adrenomedullin and Methods of Its Use

Frank Cuttitta et al. (NCI). Serial No. 60/416,291 filed 04 Oct 2002 
(DHHS Reference No. E-293-2002/0-US-01).

    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Systemic hypertension is the most prevalent cardiovascular disorder 
in the United States, affecting over 60 million Americans. In spite of 
increasing public awareness and rapidly expanding array of 
antihypertensive medications, hypertension remains one of the leading 
causes of cardiovascular morbidity and mortality. On the other end of 
the spectrum are hypovolemic shock (often from acute hemorrhage), 
cardiogenic shock (from arrhythmia or heart failure) and vasodilatory 
shock (from cerebral trauma, drug intoxication, heat exposure or septic 
shock accompanying a gram negative bacterial infection). In view of the 
above, there exists a need for agents that counteract aberrations in 
blood pressure, including hypertension and hypotension.
    This invention discloses compounds that are useful as 
vasoconstrictors or vasodilators and their methods of use. Specific 
embodiments include administration of AM (II-22) to reverse 
vasodilation and administration of an inhibitor of MMP-2 to reverse 
vasoconstriction.
    This research is described, in part, in J. Lopez & A. Martinez, 
``Cell and Molecular Biology of the Multifunctional Peptide, 
Adrenomedullin,'' Int. Rev. Cytol. 2002, 221:1-92.

Foamy Virus Mutant Reverse Transcriptase

Stephen H. Hughes et al. (NCI). Serial No. 60/292,994 filed 22 May 2001 
(DHHS Reference No. E-152-2001/0-US-01) and PCT/US02/16528 filed 22 May 
2002 (DHHS Reference No. E-152-2001/0-PCT-02).

    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    The present invention provides a recombinant reverse transcriptase 
(RT) obtained from a mutant Foamy Virus (FV), which has highly active 
and highly processive reverse transcriptase activity and substantially 
reduced protease activity. In particular, the FV protease-reverse 
transcriptase has been mutated to functionally inactivate the protease 
activity. The FV RT has better polymerase activity than other 
commercially available products (MLV, AMV, HIV).
    The invention discloses the production of the mutant FV RT, vectors 
and plasmids comprising nucleic acids that encode the FV RT and 
recombinant host cells. The invention also encompasses kits for the 
production of cDNA from RNA comprising the FV RT.
    This research is described, in part, in Rinke et al., J. Virol. 
76:7560, 2002.

    Dated: August 14, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-21696 Filed 8-25-03; 8:45 am]
BILLING CODE 4140-01-P