E7-13541. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

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.

Compounds Binding to the N-Terminal Domains of STAT Proteins as Therapeutic Agents

Description of Technology: Signal transducer and activator transcription (STAT) proteins, specifically STAT1, 2, 3, 4, 5a, 5b, and 6, are involved in the cellular and biological processes of cell proliferation, differentiation, apoptosis, host defense, and transformation. Constitutively active STAT proteins occur in many human tumor cells and cells transformed by oncoproteins. Inhibiting these STAT proteins has great therapeutic potential in the treatment of certain cancers.

The current invention describes a family of short peptides that bind to the N-terminus domains of STAT proteins and their use as therapeutic agents. These compounds are the first inhibitors that can directly bind to N-domains of STATs and exhibit a direct inhibitory effect. STAT1, 3, and 5 inhibitors can serve as potent therapeutic agents for the treatment of a variety of tumors and STAT 4 inhibitors can be used to control autoimmune disorders.

Applications and Modality: Other applications for this technology include using STAT1, STAT3 and STAT5 inhibitors for the treatment of various tumors; using STAT4 inhibitors to control autoimmune disorders; and using STAT inhibitors as research tools to study the function of STAT proteins.

Market: There were approximately 600,000 deaths from cancer related diseases estimated in 2006. In 2006, the cancer drug market was estimated to be $25 billion.

Development Status: The technology is currently in the pre-clinical stage of development.

Inventors: Nadya I. Tarasova et al. (NCI).

Relevant Publications: A manuscript directly related to the above technology will be available as soon as it is accepted for publication.

Patent Status: U.S. Provisional Application No. 60/940,916 filed 30 May 2007 (HHS Reference No. E-164-2007/0-US-01).

Licensing Status: Available for exclusive and non-exclusive license.

Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560; [e-mail].

Benztropinamine Analogs as Dopamine Transport Inhibitors

Description of Technology: Dopamine is a neurotransmitter that is directly involved in motor activity, motivation and reward, and cognition. The dopamine transporter is expressed on the plasma membrane of dopamine neurons and is responsible for clearing dopamine released into the extracellular space, thereby regulating neurotransmission. The dopamine transporter plays a significant role in neuropsychiatric diseases, such as Parkinson's disease, drug abuse (especially cocaine addiction), Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (ADD/ADHD), narcolepsy and a number of other CNS disorders. Therefore, the dopamine transporter is a target for research and potential therapeutics for the treatment of these indications.

Benztropine and its analogs are an important class of dopamine transport inhibitors that are indicated for the treatment of cocaine abuse and ADHD. They bind with high affinity to the dopamine transporter and block dopamine uptake, but generally do not produce behavioral effects comparable to those produced by cocaine. In animal models of drug abuse, many benztropine analogs have been shown to (1) Reduce cocaine-induced locomotor stimulation, (2) have long-lasting effects, and (3) lack a significant abuse liability. This suggests they may be useful medications for the treatment of human diseases where dopamine-related behavior is compromised, especially in situations in which an (partial) agonist treatment is indicated.

However, some of the reported analogs have limited or poor solubility in aqueous systems or poor stability characteristics. To remedy this, the 3-position benzhydrylether moiety of the benztropine analogs was replaced with the isosteric benzhydrylamine system in order to reduce hydrolysis of the less stable ether function, observed in the benztropine series, and further reduce lipophilicity to ultimately increase water solubility and bioavailability for improved therapeutic formulation and utility.

Inventors: Amy H. Newman et al. (NIDA).

Publication: P Grundt; TA Kopajtic, JL Katz, AH Newman. N-8-substituted-benztropinamine analogs as selective dopamine transporter ligands. Bioorg Med Chem Lett. 2005 Dec 15;15(24):5419-5423.

Patent Status: U.S. Provisional Application No. 60/689,746 filed 10 Jun 2005 (HHS Reference No. E-089-2005/0-US-01); International Application No. PCT/US2006/22401 filed 07 Jun 2006, which published as WO 2006/135715 on 21 Dec 2006 (HHS Reference No. E-089-2005/0-PCT-02).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Tara L. Kirby, Ph.D.; 301/435-4426; [e-mail]

Dated: July 5, 2007.

Steven M. Ferguson,

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