Patents Examined by Thomas G. Larson
  • Patent number: 6146829
    Abstract: Oligonucleotides and other macromolecules are provided that have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strand, and sub-sequences of 2'-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H enzyme. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to antisense therapeutics.
    Type: Grant
    Filed: August 31, 1998
    Date of Patent: November 14, 2000
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Phillip Dan Cook, Brett P. Monia
  • Patent number: 6146847
    Abstract: This invention provides methods and chemical agents for enhancing transient expression in eukaryotic cells. Also provided are a model system for achieving prolonged transient expression in solid tumors, a means for culturing hepatocytes without feeder cells or an extracellular matrix bonded to the substratum, a method for manipulating cellular metabolism to reduce the consumption of glucose and a means for inducing the secretion of an endogenous phosphatase activity.
    Type: Grant
    Filed: June 8, 1998
    Date of Patent: November 14, 2000
    Assignee: Genespan Corporation
    Inventors: Randal A. Goffe, Adeelia S. Goffe
  • Patent number: 6132999
    Abstract: The present invention provides a novel microbial strain and a method for effectively producing L-threonine. The novel strain can grow on a medium containing molasses, a much cheaper raw material than sucrose. The exemplary novel strain E. coli BKIIM B-5318 bears the plasmid pPRT614, which has threonine biosynthesis genes (thr A, B and C), the expression of which is regulated by a lambda-phage PR promoter and temperature-sensitive C1 repressor. The present microorganism is prototrophic with regard to isoleucine. The strain E. coli BKIIM B-5318 produces more than 70 g/l of L-threonine when cultured at C. for 32 hours in a medium containing molasses.
    Type: Grant
    Filed: January 21, 1998
    Date of Patent: October 17, 2000
    Assignee: Ajinomoto Co., Inc.
    Inventors: Vladimir Georgievich Debabov, Uri Ivanovich Kozlov, Evgenyi Moiseevich Khurges, Vytalyi Arkadievich Lifshits, Nelli Isaakovna Zhdanova, Michail Markovich Gusyatiner, Alexander Konstantinovich Sokolov, Tatiana Alexandrovna Bachina, Andrei Yurevich Christoserdov, Uri Dmitrievich Tsigankov, Nikolai Kazimirovich Yankovsky, Sergi Vladimirovich Mashko, Alla Lvovna Lapidus, Oksana Fedorovna Gavrilova, Oleg Alexandrovich Rodionov
  • Patent number: 6130092
    Abstract: A ribozyme library which comprises a collection of ribozyme genes encoding a hammerhead structure and flanking sequences of random nucleotides cloned at least once into an expression cassette for ribozyme expression.
    Type: Grant
    Filed: July 3, 1997
    Date of Patent: October 10, 2000
    Assignee: Max-Planck Gesellschaft zur Forderung der Wissenschaften e.V.
    Inventors: Andre Lieber, Michael Strauss, deceased
  • Patent number: 6127116
    Abstract: The present invention relates to the determination of an authentic HCV genome RNA sequences, to construction of infectious HCV DNA clones, and to use of the clones, or their derivatives, in therapeutic, vaccine, and diagnostic applications. The invention is also directed to HCV vectors, e.g., for gene therapy of gene vaccines.
    Type: Grant
    Filed: March 4, 1997
    Date of Patent: October 3, 2000
    Assignee: Washington University
    Inventors: Charles M. Rice, Alexander A. Kolykhalov
  • Patent number: 6127171
    Abstract: Provided are lacZ.alpha. gene fragments which have been modified to introduce multiple restriction enzyme sites. Vectors according to the present invention include at least one promoter operatively linked to a DNA sequence encoding lacZ.alpha. (.alpha.-peptide); multiple cloning sites cleavable by distinct restriction enzymes which have been introduced within a lacZ coding sequence from and including the codon for amino acid 8, and in the lacZ coding sequence downstream of the codon for amino acid 8, in forming the modified lacZ.alpha. coding sequence; and a replicon. The vector may further comprise one or more additional features useful for protein expression and other molecular manipulations. Also provided are methods of using the vectors wherein a DNA molecule is cloned into at least one restriction enzyme site in the modified lacZ.alpha.
    Type: Grant
    Filed: May 1, 1998
    Date of Patent: October 3, 2000
    Assignee: Genomics One Corporation
    Inventors: Steve N. Slilaty, Suzanne Lebel
  • Patent number: 6124115
    Abstract: A novel type 5 17.beta.-hydroxysteroid dehydrogenase is provided. Methods of producing the enzyme and using the enzyme to identify potential compounds which inhibit or alter the activity of the enzyme are described. In addition, methods of using the gene sequence or portions thereof for probes or to produce expression-disrupting sense or antisense DNA fragments thereof, or antisense RNA, are provided.
    Type: Grant
    Filed: September 22, 1995
    Date of Patent: September 26, 2000
    Assignee: Endorecherche Inc.
    Inventors: Fernand Labrie, Van Luu-The
  • Patent number: 6124271
    Abstract: A method and comjugate for treating H. pylori infection in a subject are disclosed. The conjugate is composed of (a) a nuclease-resistant antisense oligomer effective to inhibit H. pylori infection in the subject by base-specific Watson-Crick binding to an H. pylori mRNA transcript, and (b) a transport moiety conjugated to the oligomer. The transport moiety is effective to facilitate uptake of the conjugate from the environment of the stomach into the cytoplasm of H. pylori cells by active transport or by pH-gradient transport across of the cell membrane of H. pylori. The conjugate is administered by oral route, preferably in a swellable polymer bolus designed to release the conjugate in sustained release.
    Type: Grant
    Filed: January 23, 1998
    Date of Patent: September 26, 2000
    Assignees: AVI BioPharma, Inc., The Board of Regents of the University of Nebraska
    Inventors: Patrick L. Iversen, Randall Brand, Dwight D. Weller, James E. Summerton
  • Patent number: 6117847
    Abstract: Compositions and methods are provided for modulating the expression of protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. The oligonucleotides are from 5 to 50 nucleotides in length and in one referred embodiment are from 12 to 18 nucleotides in length. The oligonucleotides may be chimeric oligonucleotides and in a preferred embodiment comprise at least one 2'-O-methoxyethyl modification. Pharmaceutical compositions comprising the oligonucleotides of the invention are also provided. Methods of inhibiting protein kinase C expression and methods of treating conditions associated with expression of protein kinase C using oligonucleotides of the invention are disclosed.
    Type: Grant
    Filed: June 15, 1998
    Date of Patent: September 12, 2000
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: C. Frank Bennett, Nicholas M. Dean
  • Patent number: 6114141
    Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.
    Type: Grant
    Filed: February 16, 1999
    Date of Patent: September 5, 2000
    Assignee: The Johns Hopkins University School of Medicine
    Inventors: Boro Dropulic, Paula M. Pitha
  • Patent number: 6113946
    Abstract: A self-assembling polynucleotide delivery system comprises a dendrimer polycation aiding in the delivery of the polynucleotide to a desired address, and optionally other agents such as DNA masking agents, cell recognition agents, charge-neutralization agents, membrane-permeabilization agents, and subcellular-localization agents.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: September 5, 2000
    Assignee: The Regents of the University of California
    Inventors: Francis C. Szoka, Jr., Jean Haensler
  • Patent number: 6113816
    Abstract: A kit for detecting a first substance in a sample comprising a dioxetane having the formula: ##STR1## wherein T is a cycloalkyl or polycycloalkyl group bonded to the 4-membered ring portion of the dioxetane by a spiro linkage; Y is a fluorescent chromophore; X is H, alkyl, aryl, aralkyl, alkaryl, heteroalkyl, heteroaryl, cycloalkyl, cycloheteroalkyl, or an enzyme-cleavable group; and Z is H or an enzyme-cleavable group, provided that at least one of X or Z must be an enzyme-cleavable group; and an enzyme which cleaves the enzyme-cleavable group of the dioxetane creating an electron-rich moiety which destabilizes the dioxetane, causing it to decompose into two ketones, one ketone comprising the moiety T, and the other ketone comprising moieties X, Y and a portion of Z. The energy released by decomposition causes the moiety Y to luminesce.
    Type: Grant
    Filed: October 30, 1998
    Date of Patent: September 5, 2000
    Assignee: Tropix, Inc.
    Inventor: Irena Y. Bronstein
  • Patent number: 6107078
    Abstract: This invention is directed to improved catalytic compounds, hammerhead ribozymes, capable of hybridizing with a target RNA to be cleaved. These improved compounds have optimized stems (X)m*(X)m', loops (X)b and hybridizing arms. The invention is also directed to compositions for enhanced RNA cleavage which comprise a first synthetic non-naturally occurring oligonucleotide compound which comprises nucleotides whose sequence defines a conserved catalytic region and nucleotides whose sequence is capable of hybridizing with a predetermined target sequence and a second synthetic non-naturally occurring oligonucleotide which does not contain the predetermined target sequence and is complementary to at least a portion of the first oligonucleotide compound. The invention is also directed to synthetic non-naturally occurring oligonucleotide compounds embedded in a tRNA. The ribozymes and compositions of the present invention may be used in vitro or in vivo. They may be used as diagnostic or therapeutic agents.
    Type: Grant
    Filed: May 5, 1997
    Date of Patent: August 22, 2000
    Assignee: Gene Shears Pty Limited
    Inventors: Paul Keese, Marianne Stapper, Rhonda Perriman
  • Patent number: 6103893
    Abstract: Disclosed is a method of producing altered starch from transformed potato plants or their progeny, comprising extracting starch from a potato plant, at least the tubers of which comprise at least an effective portion of a starch branching enzyme (SBE) cDNA sequence operably linked in the antisense orientation to a suitable promoter, such that the level of SBE activity is limited to less than 0.8 units per gram tuber. Also disclosed are potato plants comprising altered starch in accordance with the invention.
    Type: Grant
    Filed: September 24, 1996
    Date of Patent: August 15, 2000
    Assignee: National Starch and Chemical Investment Holding Corporation
    Inventors: David Cooke, Michael John Gidley, Stephen Alan Jobling, Richard Safford, Christopher Michael Sidebottom, Roger J. Westcott
  • Patent number: 6100028
    Abstract: The present invention provides rapid accurate sensitive assays specific for the detection of at least one a single stranded oligonucleotide produced by the action of an enzyme on a substrate. The assays are useful to detect the presence in a sample of an enzyme which acts on an oligonucleotide substrate to generate a single stranded oligonucleotide product and to detect inhibitors of such an enzyme.
    Type: Grant
    Filed: July 31, 1998
    Date of Patent: August 8, 2000
    Assignee: Merck & Co., Inc.
    Inventors: James L. Cole, Lawrence C. Kuo, David B. Olsen
  • Patent number: 6096522
    Abstract: This invention provides isolated nucleic acid encoding human MAD2, isolated human MAD2 protein. This invention further provides a method of detecting the presence of MAD2 in a tissue sample, a method of determining whether a tumor is susceptible to treatment with a mitotic spindle inhibitor by detecting the presence of MAD2 in the tumor and a method of suppressing tumor formation in a subject which comprises administering the nucleic acid encoding human MAD2 to the subject in an amount effective to enhance expression of MAD2. This invention also provides a nucleic acid reagent capable of detecting the MAD2 gene or gene product and a method for in situ identification of tumors which may be susceptible to treatment with mitotic spindle inhibitors by detecting the absence of nucleic acid encoding MAD2 in the tumor.
    Type: Grant
    Filed: September 2, 1998
    Date of Patent: August 1, 2000
    Assignee: Sloan-Kettering Institute for Cancer Research
    Inventor: Robert Benezra
  • Patent number: 6093811
    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: December 16, 1997
    Date of Patent: July 25, 2000
    Assignee: Isis Pharmaceuticals Inc.
    Inventors: C. Frank Bennett, Christopher K. Mirabelli
  • Patent number: 6093555
    Abstract: Oligonucleotide comprising a nucleotide base having the formula: ##STR1## wherein B is a nucleotide base or hydrogen; R.sub.1, R.sub.2 and R.sub.3 independently is selected from the group consisting of hydrogen, an alkyl group containing between 2 and 10 carbon atoms inclusive, an amine, an amino acid, and a peptide containing between 2 and 5 amino acids inclusive; and the zigzag lines are independently hydrogen or a bond.
    Type: Grant
    Filed: February 10, 1998
    Date of Patent: July 25, 2000
    Assignee: Ribozyme Pharmaceuticals, Inc.
    Inventors: Lech Dudycz, Jasenka Matulic-Adamic, Leonid Beigelman
  • Patent number: 6090626
    Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. In preferred embodiments, the oligonucleotides are targeted to mRNA encoding human c-raf or human A-raf. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. 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.
    Type: Grant
    Filed: August 28, 1998
    Date of Patent: July 18, 2000
    Assignee: Isis Pharmaceuticals Inc.
    Inventors: Brett P. Monia, Russell T. Boggs
  • Patent number: 6087171
    Abstract: A method is provided for inducing DNA synthesis in differentiated neurons. According to certain embodiments of the invention, a method for inducing DNA synthesis in a differentiated neuron is provided that includes obtaining a vector comprising nucleic acid encoding an E2F regulator and/or an E1A regulator, wherein the vector can be used to express the nucleic acid in a differentiated neuron, and transfecting a differentiated neuron with the vector.
    Type: Grant
    Filed: November 18, 1996
    Date of Patent: July 11, 2000
    Assignee: Spinal Cord Society
    Inventors: Toomas Neuman, Kikuo Suda, Howard O. Nornes