National Institutes of Health, Public Health Service, DHHS.
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.
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 Start Printed Page 40272be 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; firstname.lastname@example.org.
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 α3β4 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@example.com.
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: firstname.lastname@example.org.
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@example.com.
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; firstname.lastname@example.org.
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 Start Printed Page 40273optical 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.Start Signature
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