Patents Represented by Attorney, Agent or Law Firm Timothy J. Gaul
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Patent number: 5789197Abstract: 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: GrantFiled: June 7, 1995Date of Patent: August 4, 1998Assignee: E. R. Squibb & Sons, Inc.Inventors: John R. Wetterau, II, Daru Young Sharp, Richard E. Gregg
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Patent number: 5744314Abstract: 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: GrantFiled: May 3, 1996Date of Patent: April 28, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Rolf Menzel, Scott T. Taylor
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Patent number: 5691189Abstract: 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: GrantFiled: November 9, 1995Date of Patent: November 25, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Stephen E. Kurtz, Mark Krystal
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Patent number: 5667989Abstract: 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: GrantFiled: March 31, 1995Date of Patent: September 16, 1997Assignee: Bristol-Myers Squibb CompanyInventors: John E. McCullough, Judith Baymiller
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Patent number: 5625121Abstract: 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: GrantFiled: October 14, 1993Date of Patent: April 29, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Rudiger Klein, Alexandra Joyner, Mariano Barbacid
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Patent number: 5620892Abstract: 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: GrantFiled: September 7, 1993Date of Patent: April 15, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Stephen E. Kurtz, Aron M. Knickerbocker, John R. McCullough
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Patent number: 5595872Abstract: 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: GrantFiled: September 3, 1993Date of Patent: January 21, 1997Assignee: Bristol-Myers Squibb CompanyInventors: 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
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Patent number: 5589372Abstract: 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: GrantFiled: December 8, 1994Date of Patent: December 31, 1996Assignee: E. R. Squibb & Sons, Inc.Inventor: Gordon W. Robinson
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Patent number: 5571708Abstract: 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: GrantFiled: April 19, 1993Date of Patent: November 5, 1996Assignee: Bristol-Myers Squibb CompanyInventors: Wen-Pin Yang, Gary R. Matsueda, Shyh-Yu Shaw
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Patent number: 5559017Abstract: 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: GrantFiled: November 19, 1990Date of Patent: September 24, 1996Assignee: E. R. Squibb & Sons, Inc.Inventors: Ramesh N. Patel, Laszlo J. Szarka, Richard H. Mueller
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Patent number: 5556747Abstract: A method for site-directed mutagenesis using a third mutagenic primer in a polymerase chain reaction (PCR) based methodology.Type: GrantFiled: July 9, 1990Date of Patent: September 17, 1996Assignee: E. R. Squibb & Sons, Inc.Inventor: Ramesh Kumar
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Patent number: 5534427Abstract: 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: GrantFiled: July 31, 1992Date of Patent: July 9, 1996Assignee: E. R. Squibb & Sons, Inc.Inventors: Robert M. Johnston, Steven L. Goldberg, Paul M. Cino
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Patent number: 5521066Abstract: 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: GrantFiled: September 13, 1993Date of Patent: May 28, 1996Assignee: Bristol-Myers Squibb CompanyInventors: Rolf Menzel, Scott T. Taylor
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Patent number: 5516642Abstract: 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: GrantFiled: November 16, 1992Date of Patent: May 14, 1996Assignee: Bristol-Myers Squibb CompanyInventors: Claudio Mapelli, Chester A. Meyers
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Patent number: 5436245Abstract: 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: GrantFiled: November 17, 1993Date of Patent: July 25, 1995Assignee: E. R. Squibb & Sons, Inc.Inventor: Donald S. Karanewsky
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Patent number: 5420123Abstract: 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: GrantFiled: December 21, 1992Date of Patent: May 30, 1995Assignee: Bristol-Myers Squibb CompanyInventor: Natesan Murugesan
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Patent number: 5413935Abstract: 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: GrantFiled: March 24, 1993Date of Patent: May 9, 1995Assignee: E. R. Squibb & Sons, Inc.Inventors: Ramesh N. Patel, Clyde G. McNamee, Laszlo J. Szarka
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Patent number: 5405745Abstract: 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: GrantFiled: December 17, 1991Date of Patent: April 11, 1995Assignee: E. R. Squibb & Sons, Inc.Inventors: Jessica A. Gorman, Catherine A. Bingham
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Patent number: 5393663Abstract: 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: GrantFiled: April 14, 1993Date of Patent: February 28, 1995Assignee: E. R. Squibb & Sons, Inc.Inventors: Ramesh N. Patel, Mark Liu, Amit Banerjee, Laszlo J. Szarka
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Patent number: 5352584Abstract: 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: GrantFiled: January 22, 1990Date of Patent: October 4, 1994Assignee: E. R. Squibb & Sons, Inc.Inventors: Edward M. Croze, Jan-I Tu, Marc D. Ogan