Abstract: This invention relates to oligonucleotides complementary to the IGF-II genes which modulate tumor cell growth in mammals. This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells in mammals. This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.
Type:
Grant
Filed:
April 22, 1999
Date of Patent:
July 9, 2002
Assignee:
Genesense Technologies Inc.
Inventors:
Jim A. Wright, Aiping H. Young, Yoon S. Lee
Abstract: The mechanism of hypertension following acute NO synthase blockage is via endothelin-mediated vasoconstriction. Thus, NO appears to inhibit endothelin activity by blocking its expression and not as a chronic direct acting vasodilator. Administration of an endothelin antagonist to a patient in a ‘normal’ physiological state may result in specific regional vasodilation. This treatment finds utility in the treatment of erectile dysfunction.
Type:
Grant
Filed:
September 14, 1998
Date of Patent:
June 25, 2002
Assignee:
Queen's University at Kingston
Inventors:
James D. Banting, Jeremy P. W. Heaton, Michael A. Adams
Abstract: The isolation and characterization of cDNAs encoding poly(ADP-ribose) glycohydrolase (PARG) enzymes and the amino acid sequences of PARGs from several species are described. PARG is involved in the cellular response to DNA damage and its proper function is associated with the body's response to neoplastic disorder inducing agents and oxidative stress. Expression vectors containing the cDNAs and cells transformed with the vectors are described. Probes and primers that hybridize with the cDNAs are described. Expression of the cDNA in E. coli results in an enzymatically active protein of about 111 kDa and an active fragment of about 59 kDa. Methods for inhibiting PARG expression or overexpressing PARG in a subject for therapeutic benefit are described. Exemplary of PARG inhibitors are anti-sense oligonucleotides. The invention has implications for treatment of neoplastic disorder, heart attack, stroke, and neurodegenerative diseases. Methods for detecting a mutant PARG allele are also described.
Type:
Grant
Filed:
February 23, 2000
Date of Patent:
May 28, 2002
Assignee:
University of Kentucky Research Foundation
Inventors:
Myron K. Jacobson, Elaine L. Jacobson, Jean-Christophe Amé, Winston Lin
Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of clusterin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding clusterin. Methods of using these compounds for modulation of clusterin expression and for treatment of diseases associated with expression of clusterin are provided.
Abstract: The invention relates to the genetic manipulation of plants, particularly to the expression of hemoglobin genes in transformed plants. Nucleotide sequences for the hemoglobin genes and methods for their use are provided. The sequences find use in enhancing seed germination, seedling growth, and overall growth and metabolism of the plant.
Abstract: The present invention provides methods for isolating biological target materials, particularly nucleic acids, such as DNA or RNA or hybrid molecules of DNA and RNA, from other substances in a medium using silica magnetic particles. The methods of the present invention involve forming a complex of the silica magnetic particles and the biological target material in a mixture of the medium and particles, separating the complex from the mixture using external magnetic force, and eluting the biological target material from the complex. The preferred embodiments of magnetic silica particles used in the methods and kits of the present invention are capable of forming a complex with at least 2 &mgr;g of biological target material per milligram of particle, and of releasing at least 60% of the material from the complex in the elution step of the method.
Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Phosphorylase kinase beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Phosphorylase kinase beta. Methods of using these compounds for modulation of Phosphorylase kinase beta expression and for treatment of diseases associated with expression of Phosphorylase kinase beta are provided.
Abstract: The present invention relates in part to methods for screening for novel enzymatic pathways in environmental samples using metabolic selection strategies, and the isolation of the genes and proteins that make up these pathways.
Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Integrin beta 4 binding protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Integrin beta 4 binding protein. Methods of using these compounds for modulation of Integrin beta 4 binding protein expression and for treatment of diseases associated with expression of Integrin beta 4 binding protein are provided.
Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of HPK/GCK-like kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding HPK/GCK-like kinase. Methods of using these compounds for modulation of HPK/GCK-like kinase expression and for treatment of diseases associated with expression of HPK/GCK-like kinase are provided.
Abstract: The invention provides nucleic acid ligands to hepatocyte growth factor/scatter factor (HGF) and its receptor c-met. The nucleic acid ligands of the instant invention are isolated using the SELEX method. SELEX is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The nucleic acid ligands of the invention are useful as diagnostic and therapeutic agents for diseases in which elevated HGF and c-met activity are causative factors.
Type:
Grant
Filed:
July 29, 1999
Date of Patent:
February 5, 2002
Assignee:
Gilead Sciences, Inc.
Inventors:
Ross Rabin, Michael Lochrie, Nebojsa Janjic, Larry Gold
Abstract: The isolation and characterization of cDNAs encoding poly(ADP-ribose) glycohydrolase (PARG) enzymes and the amino acid sequences of PARGs from several species are described. PARG is involved in the cellular response to DNA damage and its proper function is associated with the body's response to neoplastic disorder inducing agents and oxidative stress. Expression vectors containing the cDNAs and cells transformed with the vectors are described. Probes and primers that hybridize with the cDNAs are described. Expression of the cDNA in E. coli results in an enzymatically active protein of about 111 kDa and an active fragment of about 59 kDa. Methods for inhibiting PARG expression or overexpressing PARG in a subject for therapeutic benefit are described. Exemplary of PARG inhibitors are anti-sense oligonucleotides. The invention has implications for treatment of neoplastic disorder, heart attack, stroke, and neurodegenerative diseases. Methods for detecting a mutant PARG allele are also described.
Type:
Grant
Filed:
February 23, 2000
Date of Patent:
January 8, 2002
Assignee:
University of Kentucky Research Foundation
Inventors:
Myron K. Jacobson, Elaine L. Jacobson, Jean-Christophe Amé, Winston Lin
Abstract: The isolation and characterization of cDNAs encoding poly(ADP-ribose) glycohydrolase (PARG) enzymes and the amino acid sequences of PARGs from several species are described. PARG is involved in the cellular response to DNA damage and its proper function is associated with the body's response to neoplastic disorder inducing agents and oxidative stress. Expression vectors containing the cDNAs and cells transformed with the vectors are described. Probes and primers that hybridize with the cDNAs are described. Expression of the cDNA in E. coli results in an enzymatically active protein of about 111 kDa and an active fragment of about 59 kDa. Methods for inhibiting PARG expression or overexpressing PARG in a subject for therapeutic benefit are described. Exemplary of PARG inhibitors are anti-sense oligonucleotides. The invention has implications for treatment of neoplastic disorder, heart attack, stroke, and neurodegenerative diseases. Methods for detecting a mutant PARG allele are also described.
Type:
Grant
Filed:
April 30, 1999
Date of Patent:
December 25, 2001
Assignee:
University of Kentucky Research
Inventors:
Myron K. Jacobson, Elaine L. Jacobson, Jean-Christophe Amé, Winston Lin
Abstract: A method of diagnosing exposure to a toxic agent comprising the steps of detecting the amount of protein/gene expression present in a sample of mammalian tissue or mammalian body fluids that has not been exposed to a toxic agent. Then the amount of protein/gene expression present in a sample of mammalian tissue or mammalian body fluids that has been exposed to the toxic agent is detected. A determination of the difference in the detected amount of protein/gene expression between the exposed and unexposed samples is made. A comparison of the difference to a library of expected protein/gene expression for predetermined toxic agents is made. Finally, an evaluation is made whether the difference indicates the exposure to a particular toxic agent. A treatment method for administering a therapeutic agent which inhibits the mechanistic pathways necessary to maintain the progression of lethal shock is also disclosed.
Type:
Grant
Filed:
February 1, 2000
Date of Patent:
November 13, 2001
Assignee:
The United States of America as represented by the Secretary
of the Army
Abstract: An antisense compound comprising nucleotides complementary to a nucleic acid sequence coding for amyloid precursor protein (APP), wherein the antisense compound inhibits the expression of an amyloid beta protein (A&bgr;P) portion of the amyloid precursor protein coding sequence while permitting the expression of at least a portion of the amyloid precursor protein polynucleotide 5′ to the A&bgr;P portion of the amyloid precursor protein coding sequence. Pharmaceutical compositions and formulations containing the compound and methods of using the compound to regulate A&bgr;P expression in cells and tissues and to treat disease are also provided.
Abstract: Compositions and methods are provided for modulating the expression of the replication protein A p70 subunit and for the treatment and diagnosis of diseases associated with replication protein A p70 subunit.
Type:
Grant
Filed:
September 10, 1999
Date of Patent:
October 30, 2001
Assignees:
ISIS Pharmaceuticals, Inc., Variagenics, Inc.
Inventors:
Brett P. Monia, James P. Basilion, Vincent P. Stanton, Jr.
Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of C/EBP alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding C/EBP alpha. Methods of using these compounds for modulation of C/EBP alpha expression and for treatment of diseases associated with expression of C/EBP alpha are provided.
Type:
Grant
Filed:
June 13, 2000
Date of Patent:
October 23, 2001
Assignee:
ISIS Pharmaceuticals, Inc.
Inventors:
Brett P. Monia, Madeline M. Butler, Jacqueline Wyatt
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:
January 20, 1998
Date of Patent:
October 9, 2001
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
C. Frank Bennett, Christopher K. Mirabelli
Abstract: The invention provides methods and compositions relating to intracellular delivering of agents to eukaryotic cells. The compositions include microbial delivery vehicles such as nonvirulent bacteria comprising a first gene encoding a nonsecreted foreign cytolysin operably linked to a heterologous promoter and a second gene encoding a different foreign agent. The foreign agent may be a nucleic acid or protein, and is frequently bioactive in and therapeutic to the target eukaryote. In addition, the invention provides eukaryotic cells comprising the subject nonvirulent bacteria and nonhuman eukaryotic host organisms comprising such cells.
Type:
Grant
Filed:
December 21, 1999
Date of Patent:
September 11, 2001
Assignee:
The Regents of the University of California