Patents Represented by Attorney, Agent or Law Firm Timothy J. Gaul
  • Patent number: 5789197
    Abstract: Nucleic acid sequences, particularly DNA sequences, coding for all or part of the high molecular weight subunit of microsomal triglyceride transfer protein, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of the high molecular weight subunit of microsomal triglyceride transfer protein, and methods for producing these polypeptide molecules. The invention additionally concerns novel methods for preventing, stabilizing or causing regression of atherosclerosis and therapeutic agents having such activity. The invention concerns further novel methods for lowering serum liquid levels and therapeutic agents having such activity.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: August 4, 1998
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: John R. Wetterau, II, Daru Young Sharp, Richard E. Gregg
  • Patent number: 5744314
    Abstract: The present invention relates to:(1) a fusion protein having a dimerizing domain with or without a ligand-binding region and toxR DNA-binding and hydrophobic transmembrane regions;(2) host cells comprising the fusion protein and a nucleic acid molecule having a reporter gene operatively linked to the ctx operon, wherein dimerization (ligand-dependent or -independent) is signaled by expression of the reporter gene;(3) a nucleic acid molecule coding for the fusion protein;(4) an expression vector comprising a coding region for the fusion protein;(5) a process for detecting dimer formation (ligand dependent or ligand independent) of the fusion protein, which comprises treating a culture of the host cells with a ligand, ligand mimetic, or dimerization inhibitor, and screening for expression of the reporter gene.The present invention can be used to generate a signal from a variety of ligand-binding domains, allowing ligand binding to be indicated by a simple colorimeteric test or antibiotic resistance.
    Type: Grant
    Filed: May 3, 1996
    Date of Patent: April 28, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Rolf Menzel, Scott T. Taylor
  • Patent number: 5691189
    Abstract: A modified Saccharomyces cerevisiae cell, wherein the cell expresses the Influenza virus ion channel protein M.sub.2. Also disclosed is a process for detecting modulators of M.sub.2, which comprises (a) treating such modified Saccharomyces cerevisiae cells with a test substance, and (b) assessing growth in the presence of a test substance, wherein a change in growth signals that the test substance is an M.sub.2 modulator. M.sub.2 inhibitors are useful anti-viral agents.
    Type: Grant
    Filed: November 9, 1995
    Date of Patent: November 25, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Stephen E. Kurtz, Mark Krystal
  • Patent number: 5667989
    Abstract: CLY4 gene, protein, vectors, and host cells. The gene product pCly4 is involved in fungal cell wall biosynthesis, making it a useful target for anti-fungal agents.
    Type: Grant
    Filed: March 31, 1995
    Date of Patent: September 16, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: John E. McCullough, Judith Baymiller
  • Patent number: 5625121
    Abstract: The present invention provides mice and mouse cell lines having a homozygous or heterozygous deficiency in a gene encoding a neurotrophin receptor. In a preferred embodiment of this invention, mice and cell lines carry a trkB locus specifically targeted within its tyrosine protein kinase sequences. Mice homozygous for this mutation express gp95.sup.trkB receptor of unknown function but not the high affinity functional gp145.sup.trkB tyrosine protein kinase receptors. This mutation results in multiple CNS and PNS neuronal deficiencies and in a postembryonic lethal phenotype. Such genetically modified mice are useful in model systems for studying human diseases involving neuronal degeneration and neuronal cell loss, as well as in screening for genes, proteins, or other compounds that may prevent or impede neuronal cell death or stimulate neuronal regeneration.
    Type: Grant
    Filed: October 14, 1993
    Date of Patent: April 29, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Rudiger Klein, Alexandra Joyner, Mariano Barbacid
  • Patent number: 5620892
    Abstract: A modified Saccharomyces cerevisiae cell, wherein the cell expresses minK but does not express TRK1 and TRK2. Also disclosed is a process for detecting modulators of minK, which comprises (a) treating such modified Saccharomyces cerevisiae cells with a test compound, (b) assessing growth in the presence of a test compound and (c) determining an increase or decrease in potassium uptake into the Saccharomyces cerevisiae cells. MinK inhibitors are useful anti-arrhythmic or antifibrillatory agents; activators, anti-ischemic agents.
    Type: Grant
    Filed: September 7, 1993
    Date of Patent: April 15, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Stephen E. Kurtz, Aron M. Knickerbocker, John R. McCullough
  • Patent number: 5595872
    Abstract: Nucleic acid sequences, particularly DNA sequences, coding for all or part of the high molecular weight subunit of microsomal triglyceride transfer protein, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of the high molecular weight subunit of microsomal triglyceride transfer protein, and methods for producing these polypeptide molecules. The invention additionally concerns novel methods for preventing, stabilizing or causing regression of atherosclerosis and therapeutic agents having such activity. The invention concerns further novel methods for lowering serum liquid levels and therapeutic agents having such activity.
    Type: Grant
    Filed: September 3, 1993
    Date of Patent: January 21, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: John R. Wetterau, II, Daru Y. Sharp, Richard E. Gregg, Scott A. Biller, John K. Dickson, R. Michael Lawrence, John E. Lawson, Henry M. Holava, Richard A. Partyka
  • Patent number: 5589372
    Abstract: Nucleic acid sequences, particularly DNA sequences, coding for all or part of a squalene synthetase, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of a squalene synthetase, and methods for producing these polypeptide molecules.
    Type: Grant
    Filed: December 8, 1994
    Date of Patent: December 31, 1996
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Gordon W. Robinson
  • Patent number: 5571708
    Abstract: A new chimeric plasminogen activator with high fibrin affinity was designed to bind to a fibrin clot and initiate clot destruction in the presence of thrombin, but not plasmin. The chimeric molecule has an antibody variable region having a fibrin-specific antigen binding site and a single chain urokinase region having a thrombin activation site but not a plasmin activation site. The preferred embodiment, 59D8-ScuPA-T, has an N-terminal fragment of an anti-fibrin antibody (59DB) and a C-terminal thrombin-activatable low molecular weight single-chain urokinase plasminogen activator (scuPA-T). The scuPA-T portion was obtained by deletion of two amino acids (Phe157 and Lys 158) that make up the plasmin activation site from low molecular weight single chain urokinase-type plasminogen activator (scuPA).
    Type: Grant
    Filed: April 19, 1993
    Date of Patent: November 5, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: Wen-Pin Yang, Gary R. Matsueda, Shyh-Yu Shaw
  • Patent number: 5559017
    Abstract: A novel process comprises reducing a benzazepine or benzothiazepine at the 3-position in d-cis configuration by treatment with reductase-supplying microorganisms or enzymes derived therefrom. The process can be catalyzed in a single stage by growing microbial cultures or in a two-stage fermentation/transformation by resting cell-suspensions. The enzymes derived from the microorganisms can be used in free state or immobilized form. The microorganisms and enzymes catalyzes the specific reduction with 90 to 99% conversion efficiency to 99% or greater optical purity of the desired enantiomer.
    Type: Grant
    Filed: November 19, 1990
    Date of Patent: September 24, 1996
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ramesh N. Patel, Laszlo J. Szarka, Richard H. Mueller
  • Patent number: 5556747
    Abstract: A method for site-directed mutagenesis using a third mutagenic primer in a polymerase chain reaction (PCR) based methodology.
    Type: Grant
    Filed: July 9, 1990
    Date of Patent: September 17, 1996
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Ramesh Kumar
  • Patent number: 5534427
    Abstract: Nucleic acid sequences, particularly DNA sequences, coding for all or part of a lipase of Pseudomonas fluorescens, wherein said lipase has the amino acid sequence encoded by the nucleotide sequence of the BamHI/HindIII insert of the plasmid pRJ-Ltac1 from Escherichia coli BL21/pRJ-Ltac1 deposited with the American Type Culture Collection, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of a lipase of Pseudomonas fluorescens, wherein said lipase has the amino acid sequence encoded by the nucleotide sequence of the plasmid pRJ-Ltac1 from Escherichia coli BL21/pRJ-Ltac1 BamHI/HindIII insert of deposited with the American Type Culture Collection, and methods for producing these polypeptides.
    Type: Grant
    Filed: July 31, 1992
    Date of Patent: July 9, 1996
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Robert M. Johnston, Steven L. Goldberg, Paul M. Cino
  • Patent number: 5521066
    Abstract: The present invention relates to:(1) a fusion protein having a dimerizing domain with or without a ligand-binding region and toxR DNA-binding and hydrophobic transmembrane regions;(2) host cells comprising the fusion protein and a nucleic acid molecule having a reporter gene operatively linked to the ctx operon, wherein dimerization (ligand-dependent or -independent) is signaled by expression of the reporter gene;(3) a nucleic acid molecule coding for the fusion protein;(4) an expression vector comprising a coding region for the fusion protein;(5) a process for detecting dimer formation (ligand dependent or ligand independent) of the fusion protein, which comprises treating a culture of the host cells with a ligand, ligand mimetic, or dimerization inhibitor, and screening for expression of the reporter gene.The present invention can be used to generate a signal from a variety of ligand-binding domains, allowing ligand binding to be indicated by a simple colorimetric test or antibiotic resistance.
    Type: Grant
    Filed: September 13, 1993
    Date of Patent: May 28, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: Rolf Menzel, Scott T. Taylor
  • Patent number: 5516642
    Abstract: Disclosed herein are polypeptides of the formulaR.sup.1 --AA--A.sup.1 --A.sup.2 --A.sup.3 --A.sup.4 --A.sup.5 --A.sup.6 --A.sup.7 --A.sup.8 --A.sup.9 --A.sup.10 --A.sup.11 --A.sup.12 --A.sup.13 --R.sup.2 that are useful in treatment of diabetes mellitus, wherein:AA is a single bond or a polypeptide chain of 1 to 12 natural amino acid residues;A.sup.1 is seryl, A.sup.2 is phenylalanyl, A.sup.3 is arginyl, A.sup.4 is valyl, A.sup.5 is aspartyl, A.sup.6 is leucyl, A.sup.7 is arginyl, A.sup.8 is threonyl, A.sup.9 is leucyl, A.sup.10 is leucyl, A.sup.11 is arginyl, and A.sup.12 is tyrosyl, wherein one of A.sup.1 through A.sup.12 may be replaced with a natural amino acid residue, and wherein when A.sup.12 is phenylalanyl, tyrosyl or tryptophyl, its aromatic ring may be substituted with 1 or 2 iodo atoms;A.sup.13 is a natural amino acid residue other than tyrosyl, the D-form of a natural amino acid residue, --N(R.sup.4)--CH(R.sup.3)--C(O)--, or --N(R.sup.4)--CH(R.sup.3)--CH.sub.2 --;R.sup.
    Type: Grant
    Filed: November 16, 1992
    Date of Patent: May 14, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: Claudio Mapelli, Chester A. Meyers
  • Patent number: 5436245
    Abstract: Hypotensive activity is exhibited by new phosphonate substituted amino or imino acids of the formula ##STR1## isomeric mixtures thereof and pharmaceutically acceptable salts thereof, wherein:X is an imino or amino acid of the formula ##STR2##
    Type: Grant
    Filed: November 17, 1993
    Date of Patent: July 25, 1995
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Donald S. Karanewsky
  • Patent number: 5420123
    Abstract: Endothelin-inhibiting compounds of the formula ##STR1## wherein: one of R.sup.1 and R.sup.2 is Y.sup.2 -CO.sub.2 H and the other is R;R is(a) hydrogen,(b) alkyl,(c) alkenyl,(d) alkynyl,(e) cycloalkyl,(f) cycloalkenyl,(g) aryl,(h) cycloalkylalkyl,(i) cycloalkenylalkyl, or(j) aralkyl;R.sup.3 is aryl or heteroaryl;X.sup.1 and X.sup.2 are each independently(a) hydrogen,(b) halo or haloalkyl,(c) hydroxy,(d) alkoxy(e) cyano,(f) nitro, or(g) amino, alkylamino, or dialkylamino;and the remaining symbols are as defined in the specification.
    Type: Grant
    Filed: December 21, 1992
    Date of Patent: May 30, 1995
    Assignee: Bristol-Myers Squibb Company
    Inventor: Natesan Murugesan
  • Patent number: 5413935
    Abstract: An enantiomerically pure compound of the formula ##STR1## is prepared when the associated racemic mixture is reacted with an acrylating agent R.sup.3 --C(O)--O--R in the presence of a microorganism or enzyme derived therefrom capable of catalyzing transesterification of an alcohol. X.sup.1 and X.sup.2 are each independently halogen, R is alkyl, R.sup.1 and R.sup.2 are each independently alkyl, cycloalkyl, aralkyl or aryl and R.sup.3 is alkyl, cycloalkyl, aryl or aralkyl.
    Type: Grant
    Filed: March 24, 1993
    Date of Patent: May 9, 1995
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ramesh N. Patel, Clyde G. McNamee, Laszlo J. Szarka
  • Patent number: 5405745
    Abstract: Isolated nucleic acid molecules capable of hybridizing to sequences of Candida albicans along with methods utilizing such probes for the detection of Candida albicans in clinical and other biological samples.
    Type: Grant
    Filed: December 17, 1991
    Date of Patent: April 11, 1995
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Jessica A. Gorman, Catherine A. Bingham
  • Patent number: 5393663
    Abstract: A process is described for selectively preparing a compound of the formula ##STR1## wherein: R.sup.1 is halogen;R.sup.2 is halogen, alkyl, cycloalkyl, aryl or ##STR2## and R.sup.3 hydrogen, alkyl, cycloalkyl, aryl, ##STR3## wherein the process comprises treating the associated ketone with an oxido-reductase or a microorganism comprising an oxidoreductase. Compounds prepared by this process are useful antipsychotic agents or useful intermediates therefor.
    Type: Grant
    Filed: April 14, 1993
    Date of Patent: February 28, 1995
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ramesh N. Patel, Mark Liu, Amit Banerjee, Laszlo J. Szarka
  • Patent number: 5352584
    Abstract: Monoclonal antibodies which bind (E)-5-(2-bromovinyl)-arabinofuranosyluracil and/or immunologically related compounds, hybrid cell lines which produce these monoclonal antibodies, and immunoassay methods for detecting (E)-5-(2-bromovinyl)-arabinofuranosyluracil and/or immunologically related compounds using these monoclonal antibodies.
    Type: Grant
    Filed: January 22, 1990
    Date of Patent: October 4, 1994
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Edward M. Croze, Jan-I Tu, Marc D. Ogan