04-28688. 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 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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Novel Compounds and Methods for Treating Alzheimer's and Related Diseases

Nigel H. Greig et al. (NIA)

U.S. Provisional Application filed 22 Oct 2004 (DHHS Reference No. E-172-2004/0-US-01)

Licensing Contact: Norbert Pontzer; [phone]; [e-mail].

The brain cholinergic system is thought to play an important role in learning and memory. The loss of cholinergic neurons early in the course of Alzheimer's Disease may thus be an etiological factor in the cognitive decline that is the hallmark of that disease. Therefore, potentiating cholinergic transmission has been the main pharmacological approach for the treatment of AD patients. Inhibition of acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) enhances cholinergic transmission by reducing enzymatic degradation of acetylcholine.

AChE inhibitors are now used clinically to help restore cognitive function in AD patients. However the therapeutic index for inhibition of AChE is quite low. Drugs with this mechanism of action have to have the proper pharmacodynamic properties to achieve even a marginally useful clinical effect without unacceptable side effects. The presence of BChE in brain tissue makes this enzyme another possible target for increasing the activity of the cholinergic system.

The present invention provides a series of novel and potent tricyclic compounds that have a range of selectivity for inhibiting AchE, as compared to BchE, and possess neuroprotective activity in cell culture models. Also provided are methods of using these compounds to treat a number of different medical conditions such as Alzheimer's Disease, mild cognitive impairment, and other dementia-related disorders.

In addition to licensing, the technology is available for further development through collaborative research with the inventors via a Cooperative Research and Development Agreement (CRADA).

Novel Methods for Reducing Inflammation and Treating Diseases such as Parkinson's and Alzheimer's Disease

Jau-Shyong Hong et al. (NIEHS)

U.S. Provisional Application No. 60/570,566 filed 12 May 2004 (DHHS Reference No. E-130-2004/0-US-01)

Licensing Contact: Norbert Pontzer; [phone]; [e-mail].

Activated microglia mediate inflammation in the CNS by secreting various cytokines and free radicals that could damage neurons. Brains from patients with Parkinson disease show microglia reaction, and previous studies by this laboratory show microglia activation leads to inflammation mediated dopaminergic degeneration. Thus identification of drugs that reduce microglia activation could prevent or reverse neuronal degeneration in Parkinson's Disease, Alzheimer's Disease, ischemia and other degenerative CNS disorders.

Considerable research has shown the ability of various peptides to attenuate microglia activation and prevent neuronal degeneration in vitro with a bi-modal dose response curve. These peptides demonstrate maximum effects at femto-molar and micro-molar concentrations. These inventors have now discovered small-peptide and non-peptide molecules that also inhibit microglia and prevent neuronal degeneration with the same bi-modal dose response curve. The non-peptide compounds have also been shown to prevent dopamine neuronal degeneration in animal models. The present invention provides compositions and methods for inhibiting inflammatory mechanisms and treating inflammation-related condition by administering ultra-low (femto-molar) doses of at least one compound of the invention. These compounds include morphinans, opioid peptides, and the tripeptide GGF.

In addition to licensing, the technology is available for further development through collaborative research with the inventors via a Cooperative Research and Development Agreement (CRADA).

Multi-Domain Amphipathic Helical Peptides and Methods of Their Use

Alan Remaley et al. (NHLBI)

U.S. Provisional Application filed 15 Oct 2004 (DHHS Reference No. E-114-2004/0-US-01)

Licensing Contact: Fatima Sayyid; [phone]; [e-mail].

Mutations in the ABCA1 transporter lead to diseases characterized by the accumulation of excess cellular cholesterol, low levels of HDL and an increased risk for cardiovascular disease. Currently, there are a wide variety of treatments for dyslipidemia, which include, but are not limited to, pharmacologic regimens (mostly statins), partial ileal bypass surgery, portacaval shunt, liver transplantation, and removal of atherogenic lipoproteins by one of several apheresis procedures.

The present invention relates to the composition of peptides or peptide analogs with multiple amphipathic α-helical domains that promote lipid efflux from cells. It further relates to methods for identifying non-cytotoxic peptides that promote lipid efflux from cells that are useful in the treatment and prevention of dyslipidemic and vascular disorders. Dyslipidemic and vascular disorders amenable to treatment with the isolated multi-domain peptides include, but are not limited to, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, HDL deficiency, apoA-I deficiency, coronary artery disease, atherosclerosis, thrombotic stroke, peripheral vascular disease, restenosis, acute coronary syndrome, and reperfusion myocardial injury.

Dated: December 22, 2004.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.