[Federal Register Volume 68, Number 129 (Monday, July 7, 2003)]
[Notices]
[Pages 40271-40273]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-17077]


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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 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: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will

[[Page 40272]]

be required to receive copies of the patent applications.

Computer Based Model for the Identification and Characterization of 
Noncompetitive Inhibitors of the Nicotinic Acetylcholine Receptors and 
Related Ligand Gated Ion Channels

I. W. Wainer (NIA), K. Jozwiak (NIA), S. Ravichandran (SAIC-Frederick), 
and J. R. Collins (SAIC-Frederick)
DHHS Reference No. E-158-2003/0 filed 11 Apr 2003
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    NIH announces a method for the rapid determination and 
characterization of noncompetitive inhibitors for nicotinic 
acetylcholine receptors (nAChR) and other ligand gated ion channels, to 
be used in drug discovery and development. Furthermore, inhibitors for 
AChRs are described, which form a large and chemically heterogeneous 
group of compounds that block the receptor. Inhibitors of AChRs affect 
a large variety of physiological processes and many are used for 
therapeutic purposes in different areas.
    Classical methods for the identification and characterization of 
noncompetitive inhibitors are time consuming and not effective in rapid 
screening of chemical libraries for potential new drug candidates, nor 
can they be routinely used in the new drug development process. This 
invention describes the first computer-based model of the inner lumen 
of a ligand gated ion channel, as well as unique, previously 
unidentified and unexpected binding pockets. This method allows for 
computer simulated structures of the members of chemical libraries to 
be interacted with the computer-based model of the ligand gated channel 
and the simulation used to predict and describe the pharmacological 
importance of the interaction, and to screen for unexpected 
interactions and toxicities of a drug candidate due to off-target 
interactions.
    Ligand gated ion channels are currently one of the largest targets 
for drug discovery in the pharmaceutical industry. The Ligand Gated Ion 
Channel superfamily is separated into the nicotinic receptor 
superfamily (muscular and neuronal nicotinic, GABA-A and C, glycine and 
5-HT3 receptors), the excitatory amino acid superfamily (glutamate, 
aspartate and kainate receptors) and the ATP purinergic ligand gated 
ion channels. These families only differ in the number of transmembrane 
domains found in each subunit.
    This work is partially described in Jozwiak et al., ``Displacement 
and non-linear chromatographic techniques in the investigation of the 
interaction of noncompetitive inhibitors with an immobilized 
[alpha]3[]4 nicotinic acetylcholine 
receptor liquid chromatographic stationary phase,'' Anal. Chem. 
74:4618-4624, 2002.

HeadWave Clinical Coil Designed for Magnetic Resonance Elastography

David Moore and Seth Goldstein (NINDS)
DHHS Reference No. E-041-2003/0 filed 27 Mar 2003
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    The invention is a novel device for measuring the elasticity of 
cranially encased tissue. The device is a vibrator coil for use in 
magnetic resonance elastography (MRE). The vibrator coil is applied to 
the skull of a human patient using a transcranial Doppler monitoring 
harness and applies mechanical and acoustic waves through the skull. 
The propagation of the acoustic wave through brain tissue, coupled to 
phase alteration of voxel isochromats in the presence of applied motion 
encoding magnetic field gradients permits the measuring of intracranial 
tissue elasticity.

HTLV-1 p30II and p12I Proteins as Therapeutic 
Targets in HTLV-1 Infected Individuals

Genoveffa Franchini and Christophe Nicot (NCI)
DHHS Reference No. E-173-2001/0 filed 19 Aug 2002
Licensing Contact: Sally Hu; 301/435-5606; e-mail: [email protected].
    The invention provides methods that use the HTLV-1 protein 
p30II for identification of new drugs able to contain 
expansion of HTLV-1 virus infected cells and methods of using the 
identified compounds for treating patients with retroviral infection. 
The present invention is based upon discovery that viral proteins 
p30II and p12I are likely essential for the 
survival of HTLV-1 infected cells. Working in concert these proteins 
allow the replication of the infected cells while avoiding immune 
recognition of the host. The data indicate that both p30II 
and p12I can be employed as therapeutic targets in 
containing replication of HTLV-1 infected cells, which in turn will 
decrease an HTLV-1 infected patient's chance of developing 
manifestations associated with HTLV-1 infection, e.g., adult T-cell 
leukemia/lymphoma and tropical spastic paraperesis/HTLV-1 associated 
myelopathy.

Methods and Compositions for Inhibiting HIV-Coreceptor Interactions

Oleg Chertov (NCI), Joost J. Oppenheim (NCI), Xin Chen (NCI), Connor
McGrath(NCI), Raymond C. Sowder II (NCI), Jacek Lubkowski (NCI), 
Michele Wetzel (EM), and Thomas J. Rogers (EM)
DHHS Reference No. E-190-2000/0 filed 15 Feb 2001; PCT/US02/05063 filed 
15 Feb 2002
Licensing Contact: Sally Hu; 301/435-5606; e-mail: [email protected].

    This invention provides peptides that might be potent inhibitors of 
HIV replication, in both macrophages and T lymphocytes. Specifically, 
the inventors have identified peptides, from the HIV-1 gp120 envelope 
protein, that share structural similarities with chemokines and are 
shown to block ``docking'' interactions between the HIV-1 envelope 
protein gp120 and chemokine receptors that function as ``coreceptors'' 
for HIV entry on the surface of target cells (macrophages and T 
lymphocytes). The inventors synthesized two peptides (designated 15K 
and 15D) based on this information and showed that both were effective 
in competing with chemokines for binding to CCR5- and CXCR4-expressing 
cells. These peptides efficiently inhibited infection of human monocyte 
derived macrophages and peripheral blood mononuclear cells by different 
strains of HIV. The synthesized peptides also inhibited monocyte 
chemotaxis stimulated by the chemokine RANTES. Thus, these peptides and 
other molecules based on their structure can be potentially used as 
inhibitors of HIV. Moreover, these peptides could also have anti-
inflammatory and anti-tumor activity. Further, it has been determined 
that these peptides are multi-tropic in their effects (blocking HIV 
interactions with multiple co-receptors) for blocking both T cell 
tropic (lymphotropic) and macrophage tropic (m-tropic) HIV strains.

3-D Video Image-Based Microscopic Precision Robotic Targeting

Jeffrey C. Smith (NINDS), James W. Nash (EM)
DHHS Reference No. E-162-2000/0 filed 22 Dec 2000
Licensing Contact: Michel Shmilovich; 301/435-5019; 
[email protected].

    The invention is a robotic software and hardware system that allows 
a microscopic object such as a living biological cell to be targeted in 
3-D

[[Page 40273]]

optical space for micromanipulation or probing (e.g., drug testing, 
transgenic manipulation, nucleation/anucleation). The software permits 
the selection of an object for targeting by a point and click operation 
with a computer mouse, and performs the transforms between video pixel 
space, optical space and micro-manipulator mechanical coordinate space 
to translate the point and click operation into the precision targeting 
movements of the micro-positioner. The object is viewed in real time 
through a microscope system via a video output camera and displayed on 
a computer terminal.
    Applications include a variety of biological laboratory precision 
tools such as positioning of microelectrodes for electrophysiological 
recording from living cells, micro-injection and micro-manipulation of 
cells and micro-delivery of pharmacological agents to cells for drug 
testing and diagnostics.
    The invention may also find application in microelectronics 
fabrication.

    Dated: June 27, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-17077 Filed 7-3-03; 8:45 am]
BILLING CODE 4140-01-P