Abstract: A method for identifying regulators of integrin activation by establishing a selected cell line which contains a functional integrin and a chimeric polypeptide having a cytoplasmic domain of an integrin subunit fused to a polypeptide containing extracellular and transmembrane domains that are not functional integrin domains, so that chimera can inhibit signaling activities of the functional integrin by interaction with integrin regulator molecules in the cytoplasm; transfecting the cell line with a selected cDNA expression library; expressing proteins of the cDNA expression library; and identifying proteins which when overexpressed overcome the inhibition of signaling activities by said chimeric polypeptide, said proteins being regulators of integrin. Methods of designing drugs to modify integrin function and cell lines for screening regulators of integrin activation are also provided.
Abstract: A method for the detection of a selected protein is provided wherein mRNA levels are correlated with the presence of protein using the technique referred to herein as immuno-aRNA.
Type:
Grant
Filed:
November 17, 1997
Date of Patent:
July 13, 1999
Assignee:
Trustees of the University of Pennsylvania
Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human c-raf and capable of inhibiting raf expression. The oligonucleotides contain a methoxyethoxy (2'--O--CH.sub.2 CH.sub.2 OCH.sub.3) modification at the 2' position of at least one nucleotide. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating abnormal proliferative conditions which employ oligonucleotides of the invention.
Abstract: The present invention provides an apparatus for noninvasive determination of bone mass, said apparatus having a platform for supporting a bone to be measured, a spring having a selected stiffness which connects the platform to a sensor capable of measuring vibration velocity and force, and a vibrating means connected to the sensor, wherein the vibrating means exposes the sensor, the spring and the platform to vibration so that vibration velocity and force can be measured by the sensor and the mass of the bone determined. A second apparatus for noninvasive determination of bone mass having a gripping means, a spring having a selected stiffness which connects the gripping means to a platform for positioning of a bone, a sensor capable of measuring vibration velocity and force which connects the platform to a vibrating means, and a vibrating means which vibrates the sensor, the platform, the spring, and the gripping means so the vibration velocity and force can be measured by the sensor is also provided.
Type:
Grant
Filed:
November 25, 1997
Date of Patent:
April 20, 1999
Assignee:
The Trustees of Stevens Institute of Technology
Abstract: This invention relates to a radiodiagnostic agent to image arterial and venous thrombi, pulmonary emboli and lesions of atherosclerosis. A composition for a thrombus imaging agent, a method and kit for preparing a thrombus imaging agent, and a radiolabeling reagent for preparing the thrombus imaging agent are provided. Methods of using the thrombus imaging agent to detect thrombi are also provided.
Type:
Grant
Filed:
May 20, 1997
Date of Patent:
March 23, 1999
Assignee:
Thomas Jefferson University
Inventors:
Mathew L. Thakur, Venkataramana R. Pallela
Abstract: Compositions and methods are provided for the prevention and treatment of allograft rejection. Compositions are provided which comprise an antisense oligonucleotide targeted to a nucleic acid sequence encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or endothelial leukocyte adhesion molecule-1 in combination with an immunosuppressive agent. Methods of preventing or treating allograft rejection by treating an allograft recipient with such a composition are provided. Methods for preventing allograft rejection comprising perfusion of the graft are also provided.
Type:
Grant
Filed:
November 23, 1994
Date of Patent:
March 16, 1999
Assignees:
ISIS Pharmaceuticals, Inc., Board of Regents, The University of Texas System
Inventors:
C. Frank Bennett, Stanislaw M. Stepkowski
Abstract: Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. The invention is thus directed to compositions for modulating, diagnostic methods for detecting, and therapeutic methods for inhibiting, the hyperproliferation of cells and formation, development and maintenance of tumors.
Abstract: Compositions and methods are provided for the modulation of ras expression. Oligonucleotides are provided which are targeted to nucleic acids encoding human ras. Oligonucleotides specifically hybridizable with mRNA encoding human H-ras, Ki-ras and N-ras are provided. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. Methods are also disclosed for modulating ras gene expression in cells and tissues using the oligonucleotides provided, and for specific modulation of expression of activated ras. Methods for diagnosis, detection and treatment of conditions associated with ras are also disclosed.
Type:
Grant
Filed:
July 8, 1997
Date of Patent:
February 16, 1999
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
Brett P. Monia, Lex M. Cowsert, Muthiah Manoharan
Abstract: Methods for producing matrices useful in bone graft onlay and inlay procedures are provided. Compositions prepared by these methods are also provided.
Type:
Grant
Filed:
November 20, 1996
Date of Patent:
February 2, 1999
Assignee:
Allegheny Health, Education and Research Foundation
Abstract: Methods for modulating the expression of viral genes are provided by selecting a portion of RNA coded by the gene, said RNA portion having subportions forming a secondary structure, and contacting the RNA with oligonucleotide of 6 to 50 which can bind with at least one of said subportions of the RNA. In accordance with the preferred embodiments, oligonucleotides are designed to bind to RNA secondary structures which are of significance to the expression of the gene coding for said RNA. In accordance with a preferred embodiment, methods of treatment of human immunodeficiency virus are similarly disclosed wherein the oligonucleotides are targeted at the CAR or gag-pol region of HIV RNA.
Type:
Grant
Filed:
April 13, 1994
Date of Patent:
February 2, 1999
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
David Ecker, Timothy A. Vickers, Thomas W. Bruice
Abstract: A vector capable of integrating into a selected site of a cell's genome is provided which contains a replication-deficient SV40 virus and a nucleic acid sequence flanked with integration promotion sequences.
Abstract: A novel controlled release device employing microporous membranes with or without a nonporous coating and aqueous-organic partitioning of the bioreactive substances to be delivered is provided. Devices and methods for delivering pharmaceuticals, pest-control substances, hormones, nutrients and fragrances to humans, animals or any environment are also provided.
Type:
Grant
Filed:
July 21, 1997
Date of Patent:
January 12, 1999
Assignee:
The Trustees of the Stevens Institute of Technology
Inventors:
Kamalesh K. Sirkar, Stephanie Farrell, Rahul Basu
Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of type I IL-1 receptor mRNA expression. In accordance with preferred embodiments, oligomers are provided which are specifically hybridizable with DNA or RNA encoding type I interleukin-1 receptor. Methods of modulating type I IL-1 receptor expression and of treating animals suffering from diseases amenable to therapeutic intervention by modulating the expression of type I interleukin-1 receptor with an oligomer specifically hybridizable with DNA or RNA encoding type I interleukin-1 receptor are disclosed.
Type:
Grant
Filed:
May 21, 1996
Date of Patent:
January 5, 1999
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
Loren Miraglia, C. Frank Bennett, Nicholas Dean, Thomas Geiger
Abstract: Methods of generating a rat having A.beta. deposits in the brain of the rat by injecting an amount of human A68 protein sufficient to result in formation of the deposits and subsequently examining the rat for the formation of the deposits are disclosed. Rats characterized by the presence of A.beta. deposits similar to those found in individuals with Alzheimer's disease are also disclosed. Methods of screening test compositions for prophylactic or therapeutic activity by generating a rat having A.beta. deposits in its brain, treating the animal with the test composition and examining the animal for therapeutic or prophylactic effectiveness are also disclosed.
Type:
Grant
Filed:
June 17, 1994
Date of Patent:
December 15, 1998
Assignee:
Trustees of the University of Pennsylvania
Inventors:
John Q. Trojanowski, Virginia M.-Y. Lee, Ryong-Woon Shin
Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3'-untranslated sequences, and intervening sequences.
Type:
Grant
Filed:
May 12, 1995
Date of Patent:
December 1, 1998
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
C. Frank Bennett, Christopher K. Mirabelli
Abstract: Assays for measuring fragility or breakage of chromosomes at trinucleotide repeats in Saccharomyces cerevisiae are provided. These assays can also be used to measure trinucleotide repeat expansion and to screen drugs, proteins and cellular conditions which increase or decrease this expansion.
Type:
Grant
Filed:
March 30, 1998
Date of Patent:
December 1, 1998
Assignee:
Princeton University
Inventors:
Virginia Zakian, Catherine Freudenreich
Abstract: A method of preventing photoaging and other types of sun damage by topically applying a composition containing Tempol is provided. Pharmaceutical compositions comprising Tempol for the prevention of photoaging and other types of sun damage are also provided.
Abstract: A process for crushing materials by feeding materials to be crushed between two crushing jaws which have a crushing force controlled by a resilient ties capable of providing synchronous vibration of each crushing jaw with respect to each other is provided.
Type:
Grant
Filed:
May 24, 1996
Date of Patent:
November 24, 1998
Assignee:
Rustec, Inc.
Inventors:
Leonid P. Zarogatsky, Vladimir Ya. Turkin
Abstract: Method for detecting thrombin-induced cell activation via a system of detection capable of determining the presence of the cleaved peptide fragment of the thrombin receptor are provided. These methods are used in diagnosing and treating a pre-thrombotic state or thrombotic disorder in a patient. Detection kits to be used with this method are also provided.
Type:
Grant
Filed:
June 6, 1996
Date of Patent:
November 24, 1998
Assignee:
Trustees of the University of Pennsylvania