[Federal Register Volume 70, Number 156 (Monday, August 15, 2005)]
[Notices]
[Pages 47844-47845]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-16138]


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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.

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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: 301-496-7057; fax: 301-402-0220. 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; 
[email protected].

    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, 
[email protected].

    TGF[beta] and related proteins, activins and bone morphogenetic 
proteins (BMPs), are critical during pancreas development. Alterations 
in the TGF[beta] pathway are observed in diseases of the pancreas, 
including diabetes and cancer, although the precise ramifications of 
altered TGF[beta] functions are unclear. The DPC4 (deleted in pancreas 
cancer 4) locus that encodes the TGF[beta]-signaling intermediate, SMAD 
4, is mutated in 55-70% of pancreatic cancers and

[[Page 47845]]

alterations in expression of the TGF[beta] receptors I and II 
(T[beta]RI and T[beta]RII) are also observed during pancreatic cancer 
progression. These observations are consistent with an integral role of 
the TGF[beta] pathway components in pancreas biology and disease 
progression. However, the molecular details and the target cell 
population of TGF[beta] signals during pancreas development and disease 
are not known.
    SMAD proteins are downstream mediators of signals from TGF[beta] 
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 
TGF[beta]-signaling pathway in insulin production. The inventors have 
shown that low levels of TGF[beta] 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 TGF[beta] 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; [email protected].

    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.
[FR Doc. 05-16138 Filed 8-12-05; 8:45 am]
BILLING CODE 4140-01-P