Patents Represented by Attorney, Agent or Law Firm Timothy J. Gaul
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Patent number: 7723490Abstract: The present invention concerns a process by which a misfold in an Fc fusion molecule can be prevented or corrected. In one embodiment, the process comprises (a) preparing a pharmacologically active compound comprising an Fc domain; (b) treating the fusion molecule with a copper (II) halide; and (c) isolating the treated fusion molecule. The pharmacologically active compound can be an antibody or a fusion molecule comprising a pharmacologically active domain and an Fc domain. The preferred copper (II) halide is CuCl2. The preferred concentration thereof is at least about 10 mM for fusion molecules prepared in E. coli; at least about 30 mM for fusion molecules prepared in CHO cells. The process can be employed with any number of pharmacologically active domains. Preferred pharmacologically active domains include OPG proteins, leptin proteins, soluble portions of TNF receptors (e.g., wherein the fusion molecule is etanercept), IL-1ra proteins, and TPO-mimetic peptides.Type: GrantFiled: August 24, 2004Date of Patent: May 25, 2010Assignee: Amgen Inc.Inventors: Michael J. Treuheit, Sheila R. O'Conner, Andrew A. Kosky
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Patent number: 7488590Abstract: Pharmacologically active compounds are prepared by (a) selecting at least one peptide that modulates the activity of AGP-3, (b) preparing a gene construct that comprises at least one said selected sequence, and (c) expressing the pharmacologically active compound in which an Fc domain is covalently linked to the selected peptide. The pharmacologic agent can be expressed in E. coli.Type: GrantFiled: August 18, 2003Date of Patent: February 10, 2009Assignee: Amgen Inc.Inventors: Ulrich Feige, Chuan-Fa Liu, Janet C. Cheetham, Thomas Charles Boone, Jean Marie Gudas
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Patent number: 7259137Abstract: The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae (SEQ. ID. NO: 100) a1a2a3CDa6La8a9a10Ca12a13a14, (SEQ. ID. NO: 104) b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ. ID. NO: 105) c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18 (SEQ. ID. NO: 106) d1d2d3Cd5d6d7WDd10Ld13d14d15Cd16d17d18 (SEQ. ID. NO: 107) e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18 (SEQ. ID NO: 109) f1f2f3Kf5Df7Lf9f10Qf12f13f14 wherein the substituents are as defined in the specification.Type: GrantFiled: May 13, 2002Date of Patent: August 21, 2007Assignee: Amgen Inc.Inventors: Hosung Min, Hailing Hsu, Fei Xiong
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Patent number: 7189827Abstract: The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.Type: GrantFiled: July 31, 2003Date of Patent: March 13, 2007Assignee: Amgen Inc.Inventor: Ulrich Feige
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Patent number: 7186810Abstract: The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.Type: GrantFiled: August 29, 2003Date of Patent: March 6, 2007Assignee: Amgen Inc.Inventor: Ulrich Feige
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Patent number: 7169905Abstract: The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.Type: GrantFiled: August 29, 2003Date of Patent: January 30, 2007Assignee: Amgen Inc.Inventor: Ulrich Feige
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Patent number: 7166707Abstract: The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.Type: GrantFiled: June 27, 2003Date of Patent: January 23, 2007Assignee: Amgen Inc.Inventor: Ulrich Feige
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Patent number: 7087224Abstract: The invention relates to methods of treating a blood disorder in a mammal with an interleukin-1 (IL-1) inhibitor. The invention also relates to methods of treating a blood disorder in a mammal with an IL-1 inhibitor, a TNF inhibitor and an erythropoietin (EPO) receptor agonist. The invention also relates to compositions of an IL-1 inhibitor and compositions of an IL-1 inhibitor, a TNF inhibitor and an EPO receptor agonist.Type: GrantFiled: October 2, 2001Date of Patent: August 8, 2006Assignee: Amgen Inc.Inventors: Jonathan Kay, Dorothy McCabe, Richard Newmark, Marco A. Coccia
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Patent number: 6677136Abstract: The present invention concerns therapeutic agents that antagonize the activity of glucagon. In accordance with the present invention, the compounds of the invention comprise: a. a glucagon antagonist domain, preferably the amino acid sequence of SEQ ID NO: 7, or sequences derived therefrom by phage display, RNA-peptide screening, or the other techniques; and b. a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the glucagon antagonist domain. The vehicle and the glucagon antagonist domain may be linked through the N- or C-terminus of the glucagon antagonist domain. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.Type: GrantFiled: May 2, 2001Date of Patent: January 13, 2004Assignee: Amgen Inc.Inventors: William S. Marshall, Kevin Lee Stark
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Patent number: 6660843Abstract: The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.Type: GrantFiled: October 22, 1999Date of Patent: December 9, 2003Assignee: Amgen Inc.Inventors: Ulrich Feige, Chuan-Fa Liu
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Patent number: 6552170Abstract: Compounds are disclosed having the general formula R1-X-R2, wherein R1 and R2 are biologically active groups, at least one of which is polypeptidic. X is a non-peptidic polymeric group. R1 and R2 may be the same or different. Preferred R1 and R2 groups are TNF inhibitors.Type: GrantFiled: June 14, 1994Date of Patent: April 22, 2003Assignee: Amgen Inc.Inventors: Robert C. Thompson, Michael T. Brewer, Tadahiko Kohno
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Patent number: 6294170Abstract: A protein which exhibits a therapeutic effect on inflammation and is useful for treating IL-1-mediated inflammatory diseases, particularly diseases of the joint.Type: GrantFiled: August 7, 1998Date of Patent: September 25, 2001Assignee: Amgen Inc.Inventors: Thomas C. Boone, Susan Hershenson, Michael P. Bevilacqua, David S. Collins
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Patent number: 6271242Abstract: A novel method for preventing, stabilizing or causing regression of cancer is disclosed. The method comprises administering to a patient in need thereof a tyrosine protein kinase inhibitor.Type: GrantFiled: February 10, 1992Date of Patent: August 7, 2001Assignee: Bristol-Myers Squibb Co.Inventor: Mariano Barbacid
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Patent number: 6210924Abstract: The invention concerns eukaryotic cells useful in protein expression comprising (a) an inserted nucleic acid encoding a cyclin D gene product and (b) an inserted nucleic acid encoding a protein of interest, wherein the cyclin D gene product and the protein of interest are expressed in the cell. The invention also concerns a process for producing a protein of interest, which comprises (a) inserting into a eukaryotic cell a nucleic acid encoding a cyclin D gene product and a nucleic acid encoding a protein of interest; (b) culturing the cell under conditions permitting the expression of the protein of interest; and (c) isolating the protein of interest. The cells are preferably mammalian, with CHO cells most preferred. The cyclin D gene product is preferably of human origin. Suitable proteins of interest include erythropoietin (EPO), osteoprotegerin (OPG), OPG-Fc, leptin, Fc-leptin, and Novel Erythropoiesis Stimulating Protein (NESP).Type: GrantFiled: August 10, 1999Date of Patent: April 3, 2001Assignee: Amgen Inc.Inventors: Shaw-Fen Sylvia Hu, Jean Marie Gudas, David William Brankow
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Patent number: 6051381Abstract: A two-hybrid system that can detect homo- and heterodimeric protein interactions in E. coli and other cells. This system is useful for the same applications as a yeast two-hybrid system; i.e. interaction cloning, mapping protein interaction domains, analyzing protein interactions, detecting protein interactions and detecting modulators thereof.Type: GrantFiled: December 10, 1997Date of Patent: April 18, 2000Inventor: Michael G. Kornacker
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Patent number: 5919650Abstract: Method for inactivating the function produced by a protein using an intracellularly expressed antibody or fragment thereof.Type: GrantFiled: April 22, 1990Date of Patent: July 6, 1999Assignee: Bristol-Myers Squibb Co.Inventors: Mariano Barbacid, Ximena Montano
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Patent number: 5898068Abstract: Monoclonal antibodies which bind mevalonate kinase, hybrid cell lines which produce these monoclonal antibodies, and immunoassay methods for detecting mevalonate kinase using these monoclonal antibodies.Type: GrantFiled: May 29, 1990Date of Patent: April 27, 1999Assignee: Bristol-Myers Squibb CompanyInventor: Kendra B. Eager
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Patent number: 5869055Abstract: The invention relates to anti-inflammatory polypeptides comprising soluble CD14 related polypeptides having amino acids at position 7-10 that are different from the native sequence or having amino acids 1-14 deleted.Type: GrantFiled: June 7, 1995Date of Patent: February 9, 1999Assignee: Amgen, Inc.Inventors: Shao-Chieh Juan, Henri S. Lichenstein, Samuel D. Wright
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Patent number: 5840673Abstract: Methods of treating p53-related tumors by administering (1) a modulator of IGF-BP3, wherein the modulator upregulates IGF-BP3 expression or activity, (2) IGF-BP3 itself, or (3) an expression vector comprising a nucleotide sequence encoding IGF-BP3. In the latter method, the IGF-BP3 nucleotide sequence may also be operatively linked to an inducible promoter or enhancer, wherein the method further comprises administering an inducer capable of initiating or upregulating expression of the protein. Furthermore, any of the foregoing methods may include as an additional step administration of a cytotoxic agent. These methods are specific examples of a broader method: treatment of p53-related tumors by inhibiting the binding of IGF to IGFR.Type: GrantFiled: September 12, 1996Date of Patent: November 24, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Leonard R. Buckbinder, Nikolai Kley, Bernd R. Seizinger
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Patent number: 5837852Abstract: Novel capped oligonucleotides useful in treatment of influenza infection. A synthetically derived 67-nucleotide RNA substrate, containing a ?.sup.32 P! labeled cap-1 structure was used to analyze parameters of influenza virus endonuclease activity. This substrate was specifically cleaved by the influenza virus polymerase to yield a single capped 11-nucleotide fragment capable of directly priming transcription. An analysis of systematic truncations of this RNA substrate in cleavage, elongation, and binding reactions demonstrated that the minimum chain length required for cleavage was one nucleotide past the cleavage site. In contrast, the minimum chain length required for priming activity was found to be 9 nucleotides, while a chain length of at least 4 nucleotides was required for efficient binding.Type: GrantFiled: October 14, 1993Date of Patent: November 17, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Thomas D. Y. Chung, Christopher W. Cianci, Moira Hagen, Mark Krystal, Richard J. Colonno