03-18009. 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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Detection of Mutational Frequency in Human Bone Marrow

Neal S. Young et al. (NHLBI)

DHHS Reference No. E-320-2002 filed 06 Nov 2002

Licensing Contact: Fatima Sayyid; 301/435-4521; [e-mail]

To date there have been no adequate methods to determine the frequency of mutations in humans. This invention discloses a method of measuring the mutational frequency of a mitochondrial DNA sequence by sequencing mitochondrial DNA from clonally expanded single cells such as CD34+ human stem cells. Sequencing for mitochondrial DNA polymorphisms and mutations may also be useful as a general method to detect minimal residual disease in leukemia. The mitochondrial genome is particularly susceptible to mutations and these may be used to measure genomic mutagenesis by virtue of comparison. The application of this invention includes the determination of mutational frequency after chemotherapy, radiation, environmental toxic exposure and genetic disease. The invention also provides a screening for an agent that has a mutagenic effect on a cell.

Structurally Rigid Dopamine D3 Receptor Selective Ligands as Cocaine and Methamphetamine Abuse Therapeutics

Amy Newman et al. (NIDA)

DHHS Reference No. E-251-2002/0-US-01 filed 14 Sep 2002

Licensing Contact: Norbert Pontzer; 301/435-5502; [e-mail]

The dopamine D3 receptor subtype has been implicated in a number of central nervous system (CNS) disorders including but not limited to drug abuse, schizophrenia and Parkinson's disease. Since D3 receptor ligands show efficacy in animal models of cocaine self-administration and Parkinson's disease, there has been a significant effort to design and develop novel dopamine D3 ligands. However most currently known compounds are highly lipophilic, leading to poor bioavailablility and toxicity, or are not highly D3 selective.

The present invention provides a family of structurally rigid, potent and selective D3 receptor antagonists and partial agonists with lowered lipophilicity. Bioavailable compounds that bind with high affinity and selectivity to D3 receptors can not only provide important tools with which to study the structure and function of this receptor subtype, but may also have therapeutic uses in psychiatric, behavioral and neurologic disorders. More information on these potential therapeutic agents was recently published in Newman et al., Bioorganic Medicinal Chemistry Letters 13 (2003) 2179-2183.

Oral Treatment of Hemophilia

Oral Alpan et al. (NIAID)

DHHS Reference No. E-281-2001/0-PCT-02 filed 02 Aug 2002 (PCT/US02/24544)

Licensing Contact: Fatima Sayyid; 301/435-4521; [e-mail]

This invention portrays a simple method for treatment of antigen-deficiency diseases by orally administering to a subject a therapeutically effective amount of the deficient antigen, wherein the antigen is not present in a liposome. This method increases hemostasis in a subject having hemophilia A or B, by orally administering to the hemophiliac a therapeutically effective amount of the appropriate clotting factor, sufficient to induce oral tolerance and supply exogenous clotting factor to the subject.

Long-Acting Insulinotropic Peptides and Uses Thereof

Dr. Josephine Egan et al. (NIA)

Serial No. 60/309,076 filed 31 Jul 2001; PCT/US02/24141 filed 30 Jul 2002

Licensing Contact: Pradeep Ghosh; 301/435-5282; [e-mail]

Type-2 diabetes and neurodegeneration (e.g., Alzheimer's disease, Parkinson's disease, peripheral neuropathy, stroke) are leading causes of death in the United States and worldwide. The present invention pertains to the disclosure of novel peptide analogues of Glucagons-like peptide-1 (GLP-1) and Exendin-4 and their uses in the treatment of (i) diabetes and (ii) neurodegenerative disorders.

(i) Type-2 diabetes is caused by dysfunction of the pancreatic beta cells that may result in concomitant decrease in insulin production. Insulin replacement has been an effective therapy for the treatment of Type-2 diabetes. However, insulin therapy, although life saving, does not restore normal levels of glucose and postprandial levels of glucose continues to be excessively high in individuals on insulin therapy. Further, the therapy may result in adverse effects including hyperglycemia, hypoglycemia, metabolic acidosis and ketosis. Therefore, a better therapeutic formula may be needed that may increase the efficacy of the treatment and minimize the side effects. The present invention discloses a method of treating a subject with diabetes with novel GLP-1/Exendin-4 peptides. These are GLP-1 agonists and elicit insulinotropic actions.

(ii) The GLP-1 receptor is additionally found in the brain as well as associated to pancreatic islets cells. Its stimulation in brain has been found to be neurotrophic and neuroprotective in both tissue culture and in vivo against a variety of toxic insults. Peptides of the said invention possess activity in a variety of predictive models of neurodegeneration, and may have potential in a variety of diseases both associated (peripheral neuropathy) and unassociated (Alzheimer's disease, Parkinson's disease, stroke and peripheral neuropathy) with diabetes (J. Alz. Dis. 4: 487-96, 2002; J. Pharmacol. Exp. Ther. 300:958-66, 2002 & 302:881-888, 2002, TIPS in press).

In conclusion, compounds of the present patent application possess potent insulinotrophic, neuroprotective and neurotrophic effects that derive from their GLP-1 agonist action and may have a great market potential as therapeutic agents for the treatment of diabetes and/or neurodegenerative disorders.

Dated: July 10, 2003.

Steven M. Ferguson,

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