Patents Represented by Attorney, Agent or Law Firm Audrey F. Sher
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Patent number: 7094874Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.Type: GrantFiled: May 23, 2001Date of Patent: August 22, 2006Assignee: Bristol-Myers Squibb Co.Inventors: Robert J. Peach, Joseph Roy Naemura, Peter S. Linsley, Jurgen Bajorath
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Patent number: 7087418Abstract: This invention relates to a recombinant Pichia pastoris formate dehydrogenase (FDH) enzyme that catalyzes the oxidation of formate to carbon dioxide and the simultaneous reduction of nicotinamide adenine dinucleotide (NAD+) to its reduced form (NADH). Also related are isolated nucleic acids encoding P. pastoris FDH polypeptides, and fragments and variants thereof, as well as vectors and host cells comprising these nucleic acids. Further related are isolated, recombinant P. pastoris FDH polypeptides, and fragments and variants thereof, and antibodies that specifically bind to P. pastoris FDH polypeptides, fragments, or variants. The invention also relates to methods of obtaining isolated P. pastoris FDH nucleic acids, polypeptides, and antibodies, and methods of using P. pastoris FDH in various reactions for industrial or pharmaceutical applications.Type: GrantFiled: December 16, 2002Date of Patent: August 8, 2006Assignee: Bristol-Myers Squibb CompanyInventors: Steven L. Goldberg, Paul M. Cino, Ramesh N. Patel, Venkata B. Nanduri, Robert M. Johnston
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Patent number: 7070776Abstract: The invention identifies the B7 antigen as a ligand that is reactive with the CD28 receptor on T cells. The invention further provides methods for using antibodies to B7, or fragments thereof, to regulate CD28 positive T cell response and immune responses mediated by T cells.Type: GrantFiled: June 2, 1995Date of Patent: July 4, 2006Assignee: Bristol-Myers Squibb CompanyInventors: Peter S. Linsley, Jeffrey A. Ledbetter, Nitin K. Damle, William Brady
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Patent number: 6929935Abstract: This invention relates to an novel Gluconobacter oxydans 2-ketoreductase useful for the synthesis of chiral alcohols. Also related are isolated nucleic acids encoding G. oxydans 2-ketoreductase enzymes, and enzyme fragments and variants thereof, as well as vectors and host cells comprising these nucleic acids. Further related are isolated G. oxydans 2-ketoreductase polypeptides, and fragments and variants thereof, and antibodies that specifically bind to G. oxydans 2-ketoreductase polypeptides, fragments, or variants. The invention also relates to methods of obtaining isolated G. oxydans 2-ketoreductase nucleic acids, polypeptides, and antibodies, and methods of using G. oxydans 2-ketoreductase in various reactions for industrial or pharmaceutical applications.Type: GrantFiled: December 16, 2002Date of Patent: August 16, 2005Assignee: Bristol-Myers Squibb CompanyInventors: Venkata B. Nanduri, Robert M. Johnston, Steven L. Goldberg, Paul M. Cino, Ramesh N. Patel
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Patent number: 6759509Abstract: Conjugates containing a targeting ligand, such as an antibody, a therapeutically active drug and a branched peptide linker. The branched peptide linker contains two or more amino acid moieties that provide an enzyme cleavage site. The number of drugs capable of being bonded to the branched linkers varies by a factor of two for each generation of branching.Type: GrantFiled: October 31, 1997Date of Patent: July 6, 2004Assignee: Bristol-Myers Squibb CompanyInventors: Dalton King, Raymond A. Firestone, Gene M. Dubowchik
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Patent number: 6730302Abstract: The present invention provides a carrier for the delivery of molecules with biological function into both cellular and nuclear compartments. The carrier disclosed is heat shock protein 70 (“Hsp70”), or a fragment of Hsp70 as described herein, as a vehicle for directed, noninvasive delivery of molecules, such as proteins, peptides, or DNA, that may modulate cellular activity. The present invention also encompasses the use of Hsp70, or a fragment thereof, to modulate cellular activity, preferably to modulate nuclear activity in a cell or cells.Type: GrantFiled: November 16, 1999Date of Patent: May 4, 2004Assignee: Bristol-Myers Squibb CompanyInventors: Sheri M. Fujihara, Steven G. Nadler
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Patent number: 6713515Abstract: Methods and compositions for treating various disorders by administering a therapeutically effective amount of a retinoic acid receptor antagonist alone or in combination or in conjunction with other therapeutic agents to promote angiogenesis are provided. Also provided are methods for obtaining additional retinoic acid receptor antagonists for use as therapeutic agents to promote angiogenesis.Type: GrantFiled: September 13, 2001Date of Patent: March 30, 2004Assignee: Bristol Myers Squibb CompanyInventors: Violetta Iotzova, Peter Reczek
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Patent number: 6699702Abstract: The invention relates to a prokaryotic cell system for monitoring protease activity. The invention also includes assays for identifying protease inhibitors and protease modulators, determining the amino acid sequence of a protease cleavage site for a known protease, identifying and cloning a protease whose cleavage site is known, and rapidly identifying a form of a protease exhibiting increased activity relative to a control protease.Type: GrantFiled: January 6, 2000Date of Patent: March 2, 2004Assignee: Bristol-Myers Squibb Co.Inventors: Pramathesh Patel, David Lach
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Patent number: 6692934Abstract: The current invention discloses nucleic acid and amino acid sequences for novel organic anion transfer proteins (“OATPs”). The invention encompasses the OATPs described herein, together with vectors containing the cDNA sequences, host cells containing the vectors and polypeptides having all or part of an OATP. Also encompasses are uses for OATPs for targeting drugs to specific organs and for modulating the concentration of endogenous substrates.Type: GrantFiled: May 19, 2000Date of Patent: February 17, 2004Assignee: Bristol-Myers Squibb Co.Inventors: Todd G. Kirchgessner, Bonnie Hsiang, Yingjie Zhu, Yuli Wu, Zhaoqing Wang, Jean S. Lynch, Xin Huang, Wen-Pin Yang
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Patent number: 6559287Abstract: Novel articifial proteoglycans containing a GAG assembly site and a control sequence required for assembly, method for enhancing the biological activity of a glycosaminoglycan binding protein using artificial proteoglycans, DNA constructs of artificial proteoglycans. The artificial proteoglycans of the present invention are useful for preparations of adjuvants for vaccination, for targeting of chemokines to non-immunogenic tumor cells to enhance cellular anti-tumor response, for preparations designed to help promote wound healing, and for treatment of immunological disorders,including rheumatoid arthritis, asthma, chronic obstructive pulmonary disorder, Lupus, inflammatory bowel disease, psoriasis, osteoarthritis, and HIV infection.Type: GrantFiled: January 21, 1999Date of Patent: May 6, 2003Assignee: Bristol-Myers Squibb Co.Inventors: Kelly L. Bennett, Edith A. Wolff, Alejandro A. Aruffo, Brad W. Greenfield
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Patent number: 6538103Abstract: The present invention concerns peptide fragments of angiostatin containing lysine-binding sites of angiostatin which can be used as anti-angiogenic agents for the treatment of cancer, diabetic retinopathy, rheumatoid arthritis, psoriasis, atherosclerotic plaque formation, and any disease process that involves angiogenesis. The lysine binding fragments are derived from kringles 1,2 and/or 4 of plasminogen.Type: GrantFiled: July 7, 1999Date of Patent: March 25, 2003Assignee: Bristol--Myers Squibb CompanyInventors: Richard Wei-Dong Ji, Pamela A. Trail
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Patent number: 6521419Abstract: A specific locus (hot spot) for recombinant gene expression has been identified in the genome of Chinese hamster ovary cells. A DNA vector containing the hot spot causes high levels of recombinant gene expression following transfection and stable integration. The selection and cloning of the specific locus and the expression of recombinant genes is disclosed, as are the DNA vectors and the host cells.Type: GrantFiled: August 31, 1999Date of Patent: February 18, 2003Inventors: Kanakaraju Koduri, John T. Miller, Pallaiah Thammana
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Patent number: 6518014Abstract: Provided in one embodiment is a non-infectious, recombinant hepadnavirus core particle composition comprising isolated hepadnavirus core particles, template RNA encapsidated in the same core particles and hepadnavirus polymerase encapsidated in the same core particles, wherein, upon addition of deoxynucleoside triphosphates to the composition, the hepadnavirus polymerase incorporates deoxynucleotides from the added deoxynucleosides into reverse transcripts of the template RNA beginning with the first deoxynucleotide of the reverse transcript or within about 10 deoxynucleotides of the first deoxynucleotide of the reverse transcript. Another embodiment provides hapadnaviral core particles with all three functional components: (1) P; (2) C; and (3) a nucleic acid that serves as a template.Type: GrantFiled: July 11, 1997Date of Patent: February 11, 2003Assignee: Bristol-Myers Squibb CompanyInventors: Maria Seifer, Robert Hamatake, David N. Standring
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Patent number: 6512101Abstract: Branched hydrazone linkers for linking a targeting ligand such as an antibody to a therapeutically active drug. The point of branching is at a polyvalent atom and the number of drugs increases by a factor of two for each generation of branching. A preferred drug is doxorubicin.Type: GrantFiled: August 19, 1998Date of Patent: January 28, 2003Assignee: Bristol Myers Squibb CompanyInventors: Dalton King, Raymond A. Firestone, Pamela Trail
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Patent number: 6482919Abstract: The present invention provides novel soluble CTLA4Ig molecules having modified Ig domains.Type: GrantFiled: March 21, 2001Date of Patent: November 19, 2002Assignee: Bristol-Myers Squibb CompanyInventors: Jeffrey A. Ledbetter, Martha S. Hayden, Peter S. Linsley, Jurgen Bajorath, H. Perry Fell, Lisa K. Gilliland
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Patent number: 6472151Abstract: The present invention provides a method for generating and isolating cell lines that functionally express molecular targets for drug discovery without utilizing information from the nucleic acid or amino acid sequence of the target protein. This procedure for the first time allows one to develop fast, high throughput screens for evaluation of test compounds that may modulate molecular targets whose specific nucleic acid or amino acid sequences are unavailable.Type: GrantFiled: August 10, 1999Date of Patent: October 29, 2002Assignee: Bristol-Myers Squibb CompanyInventors: C. David Weaver, Todd A. Verdoorn, Gordon W. Robinson
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Patent number: 6468781Abstract: Processes for stereoselective enzymatic conversion of certain keto carboxylic acid derivatives to form the corresponding alkylamino acid compounds are described. The invention also concerns an engineered yeast host cell containing recombinant nucleic acid capable of expressing a phenylalanine dehydrogenase, as well as an engineered host cell containing recombinant nucleic acid capable of expressing a phenylalanine dehydrogenase enzyme and nucleic acid capable of expressing a formate dehydrogenase enzyme.Type: GrantFiled: February 22, 2000Date of Patent: October 22, 2002Assignee: Bristol-Myers Squibb CompanyInventors: Ronald Hanson, Mary Jo Donovan, Steven Goldberg, Paul A. Jass, Wen-Sen Li, Ramesh Patel, Keith Ramig, Laszlo J. Szarka, John J. Venit
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Patent number: 6455683Abstract: Isolated novel cDNA sequences encoding a human C-type lectin and three homologues are provided. They are referred to herein as “CLAX” (C-type Lectin, Activation Expressed) proteins. The invention also includes methods of using the nucleic acid sequences, polypeptides encoded by the nucleic acid sequences disclosed herein, fusion proteins having all or a portion (e.g., an extracellular region) of the CLAX proteins, antibodies specific for the novel CLAXs, ligands and inhibitors for the novel CLAXs. The genes of CLAX are specifically expressed in lymphoid tissues and activated T lymphocytes but not resting T lymphocytes. The invention concerns the utility in pharmaceutical compositions for the prevention and treatment of infectious, inflammatory and allergic diseases.Type: GrantFiled: March 20, 2000Date of Patent: September 24, 2002Assignee: Bristol-Myers Squibb CompanyInventors: Guchen Yang, Xiaorong Chen, Patricia M. Davis, Peter A. Kiener
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Patent number: 6420403Abstract: The present invention discloses the identification of the novel inhibitors of IMPDH (inosine-5′-monophosphate dehydrogenase). The compounds and pharmaceutical compositions disclosed herein are useful in treating or preventing IMPDH-associated disorders, such as transplant rejection and autoimmune diseases.Type: GrantFiled: October 27, 1999Date of Patent: July 16, 2002Inventors: Edwin J. Iwanowicz, T. G. Murali Dhar, Katerina Leftheris, Chunjian Liu, Toomas Mitt, Scott H. Watterson, Joel C. Barrish
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Patent number: 6403356Abstract: New mutant penicillin G acylases preferably from E. coli are provided, exhibiting altered enzymatic activity. These penicillin G acylases are obtained by expression of a gene encoding said penicillin G acylase having an amino acid sequence which differs at least in one amino acid from the wild-type penicillin G acylase.Type: GrantFiled: October 31, 1997Date of Patent: June 11, 2002Assignee: Bristol-Myers Squibb Co.Inventors: Li You, John James Usher, Brenda Joyce White, Jiri Novotny