05-16138. 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.

Benztropinamine Analogs as Dopamine Transport Inhibitors

Amy H. Newman et al. (NIDA).

U.S. Provisional Application No. 60/689,746 filed 10 Jun 2005 (HHS Reference No. E-089-2005/0-US-01).

Licensing Contact: Marlene Shinn-Astor; 301-435-4426; [e-mail].

Dopamine is a neurotransmitter that is directly involved in locomotor 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.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Inhibition of SMAD-Signaling Leads To Enhanced Insulin Production and Better Glucose Control: A Potential Therapy for Diabetes and Associated Complications Due to Hyperglycemia

Sushil G. Rane et al. (NCI).

U.S. Provisional Application No. 60/665,204 filed 25 Mar 2005 (HHS Reference No. E-235-2004/0-US-01).

Licensing Contact: Marlene Shinn-Astor; 301-435-4426, [e-mail].

TGFβ and related proteins, activins and bone morphogenetic proteins (BMPs), are critical during pancreas development. Alterations in the TGFβ pathway are observed in diseases of the pancreas, including diabetes and cancer, although the precise ramifications of altered TGFβ functions are unclear. The DPC4 (deleted in pancreas cancer 4) locus that encodes the TGFβ-signaling intermediate, SMAD 4, is mutated in 55-70% of pancreatic cancers and alterations in expression of the TGFβ receptors I and II (TβRI and TβRII) are also observed during pancreatic cancer progression. These observations are consistent with an integral role of the TGFβ pathway components in pancreas biology and disease progression. However, the molecular details and the target cell population of TGFβ signals during pancreas development and disease are not known.

SMAD proteins are downstream mediators of signals from TGFβ 1,2,3 and activin, and SMAD proteins have been implicated as important factors in cellular proliferation, differentiation and migration. This invention identifies another important regulatory role for the TGFβ-signaling pathway in insulin production. The inventors have shown that low levels of TGFβ can suppress insulin production through the actions of the SMAD signaling proteins. Small molecule regulators of SMAD-dependent signaling may lead to better insulin production and allow better glucose regulation. Thus, controlled administration of TGFβ signaling regulators may be useful in the treatment of diabetes, hyperglycemia and related complications.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Anti-Marinobufagenin Antibodies and Methods for Their Use

Alexei Bagrov et al. (NIA).

U.S. Provisional Application No. 60/694,733 filed 27 Jun 2005 (HHS Reference No. E-092-2004/0-US-01).

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

Pre-eclampsia is associated with increased blood levels of marinobufagenin (MBG), a steroid that increases blood pressure by inhibiting a membrane enzyme, Na/K ATPase, in the vascular wall. Pre-eclampsia complicates up to 10% of pregnancies in the U.S. and is a significant factor in causing maternal and fetal mortality and morbidity worldwide.

The present invention relates to compositions and methods for detecting the presence of MBG in a biological sample. It also relates to methods for the use of monoclonal antibodies or antigen binding fragments as prophylactic, therapeutic, and diagnostic agents for the detection, inhibition and treatment of hypertension.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Dated: August 5, 2005.

Steven M. Ferguson,

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