Patents Assigned to Cubist Pharmaceuticals, Inc.
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Patent number: 6696412Abstract: The invention discloses highly purified daptomycin and to pharmaceutical compositions comprising this compound. The invention discloses a method of purifying daptomycin comprising the sequential steps of anion exchange chromatography, hydrophobic interaction chromatography and anion exchange chromatography. The invention also discloses a method of purifying daptomycin by modified buffer enhanced anion exchange chromatography. The invention also discloses an improved method for producing daptomycin by fermentation of Streptomyces roseosporus. The invention also discloses high pressure liquid chromatography methods for analysis of daptomycin purity. The invention also discloses lipopeptide micelles and methods of making the micelles. The invention also discloses methods of using lipopeptide micelles for purifying lipopeptide antibiotics, such as daptomycin. The invention also discloses using lipopeptide micelles therapeutically.Type: GrantFiled: November 28, 2000Date of Patent: February 24, 2004Assignee: Cubist Pharmaceuticals, Inc.Inventors: Thomas J. Kelleher, Jan-Ji Lai, Joseph P. DeCourcey, Paul Lynch, Maurizio Zenoni, Auro Tagliani
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Publication number: 20040033481Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme, for example, methionyl-tRNA synthetase of Staphylococcus aureus. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.Type: ApplicationFiled: October 22, 2002Publication date: February 19, 2004Applicant: Cubist Pharmaceuticals, Inc.Inventors: Francis P. Tally, Jianshi Tao, Philip A. Wendler, Gene Connelly, Paul L. Gallant
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Patent number: 6579894Abstract: Transfer ribonucleic acid (tRNA) synthetase inhibitors, salts, and pharmaceutically acceptable compositions thereof of the general formula: wherein Ar is aryl and heteroaryl; L is —C(O)N(Q)CH2—, or —CR10R11OCR12R13—; Q is hydrido, —(CH2)mCO2H and —(CH2)mCO2CH3, m is 1, 2, 3, and 4; R1, R2, R9, R10, R11, R12 and R13 are hydrido or lower alkyl; wherein Het is a heterocyclic moiety, the inhibitors are suitable for use as antimicrobial agents.Type: GrantFiled: June 17, 2002Date of Patent: June 17, 2003Assignees: Merck & Co., Inc., Cubist Pharmaceuticals, Inc.Inventors: Milton L. Hammond, Aaron H. Leeman, Milana Maletic, Gina M. Santorelli, Sherman T. Waddell, John Finn, Michael Morytko, Siya Ram, Dennis Keith
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Publication number: 20030054537Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal.Type: ApplicationFiled: May 17, 2002Publication date: March 20, 2003Applicant: Cubist Pharmaceuticals, Inc.Inventors: Francis P. Tally, Jianshi Tao, Xiaoyu Shen, Jiansu Zhang
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Patent number: 6475726Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme, for example, methionyl-tRNA synthetase of Staphylococcus aureus. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.Type: GrantFiled: June 25, 1999Date of Patent: November 5, 2002Assignee: Cubist Pharmaceuticals, Inc.Inventors: Francis P. Tally, Jianshi Tao, Philip A. Wendler, Gene Connelly, Paul L. Gallant, Xiaoyu Shen, Jiansu Zhang
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Patent number: 6436694Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal.Type: GrantFiled: April 14, 1999Date of Patent: August 20, 2002Assignee: Cubist Pharmaceuticals, Inc.Inventors: Francis P. Tally, Jianshi Tao, Xiaoyu Shen, Jiansu Zhang
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Patent number: 6417217Abstract: Transfer ribonucleic acid (tRNA) synthetase inhibitors, salts, and pharmaceutically acceptable compositions thereof of the general formula: wherein Ar is aryl and heteroaryl; L is —C(O)N(Q)CH2—, or —CR10R11OCR12R13—; Q is hydrido, —(CH2)mCO2H and —(CH2)mCO2CH3, m is 1, 2, 3, and 4; R1, R2, R9, R10, R11, R12 and R13 are hydrido or lower alkyl; wherein Het is a heterocyclic moiety, the inhibitors are suitable for use as antimicrobial agents.Type: GrantFiled: August 22, 2001Date of Patent: July 9, 2002Assignees: Merck & Co., Inc., Cubist Pharmaceuticals, Inc.Inventors: Milton L. Hammond, Aaron H. Leeman, Milana Maletic, Gina M. Santorelli, Sherman T. Waddell, John Finn, Michael Morytko, Siya Ram, Dennis Keith
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Patent number: 6348482Abstract: Compounds, pharmaceutically acceptable salts, and compositions thereof of the general formula: wherein Ar is aryl and heteroaryl; R1, R2, R3, and R4 are hydrido, alkyl, cyano, heteroaryl, hydroxy, amino, acylamino, halo, alkoxy, aryloxy, carboxyamido, alkenyl, cycloalkyl, heterocyclyl, acyl, acyloxy, carboalkoxy, carboxy, thio, sulfinyl, sulfonyl and sulfoxy, R5, R6, R7, and R8 are hydrido and lower alkyl; and Het is a nitrogen-containing heterocyclic ring.Type: GrantFiled: May 5, 2000Date of Patent: February 19, 2002Assignees: Merck & Co., Inc., Cubist Pharmaceuticals, Inc.Inventors: Milton L. Hammond, Aaron H. Leeman, Milana Maletic, Gina M. Santorelli, Sherman T. Waddell, John Finn, Michael Morytko, Jason Hill, Dennis Keith
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Patent number: 6333344Abstract: Transfer ribonucleic acid (tRNA) synthetase inhibitors, salts, and pharmaceutically acceptable compositions thereof of the general formula: wherein Ar is aryl and heteroaryl; L is —C(O)N(Q)CH2—, or —CR10R11OCR12R13—; Q is hydrido, —(CH2)mCO2H and —(CH2)mCO2CH3, m is 1, 2, 3, and 4; R1, R2, R9, R10, R11, R12 and R13 are hydrido or lower alkyl; wherein Het is a heterocyclic moiety, the inhibitors are suitable for use as antimicrobial agents.Type: GrantFiled: May 5, 2000Date of Patent: December 25, 2001Assignees: Merck & Co., Cubist Pharmaceuticals, Inc.Inventors: Milton L. Hammond, Aaron H. Leeman, Milana Maletic, Gina M. Santorelli, Sherman T. Waddell, John Finn, Michael Morytko, Siya Ram, Dennis Keith
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Patent number: 6221640Abstract: Recombinant nucleic acids which encode aminoacyl-tRNA sythetases of enterococcal origin or portions of such enzymes, have been isolated. These nucleic acids can be used to make expression constructs and transformed host cells for the production of enterococcal aminoacyl-tRNA synthetases. They can also be used in the further isolation of nucleic acids related by DNA sequence similarities, which also encode enterococcal aminoacyl-tRNA synthetases, or portions thereof. A further embodiment of the invention is antisense nucleic acid which can hybridize to the nucleic acid which encodes the aminoacyl-tRNA synthetase of enterococci. The invention also relates to tRNA synthetases such as isolated and/or recombinant enterococcal aminoacyl-tRNA synthetases. Antibodies which bind to these enzymes can be made and can be used in the purification and study of the enzymes.Type: GrantFiled: May 14, 1997Date of Patent: April 24, 2001Assignee: Cubist Pharmaceuticals, Inc.Inventors: Jianshi Tao, Mandana Sassanfar, Paul L. Gallant, Xiaoyu Shen, Anthony S. Avruch, Russell V. Yu, Shamila Nair
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Candida cytoplasmic tryptophanyl-tRNA synthetase proteins, nucleic acids and strains comprising same
Patent number: 6174713Abstract: The present invention relates to isolated and/or recombinant nucleic acids which encode Candida cytoplasmic tryptophanyl-tRNA synthetases, portions thereof, or fusion proteins comprising a Candida cytoplasmic tryptophanyl-tRNA synthetase or portion thereof. Also disclosed are constructs comprising the nucleic acids of the present invention, host cells comprising a recombinant nucleic acid or construct, and methods of producing a Candida cytoplasmic tryptophanyl-tRNA synthetase, portion thereof, or fusion protein comprising the same. Also described are tester strains, which are cells engineered to rely on the function of a Candida cytoplasmic tryptophanyl-tRNA synthetase or functional fragment thereof encoded by an introduced cloned gene, and which can be used in a method of detecting an inhibitor of Candida cytoplasmic tryptophanyl-tRNA synthetase function.Type: GrantFiled: June 16, 1997Date of Patent: January 16, 2001Assignee: Cubist Pharmaceuticals, Inc.Inventors: Xiaoyu Shen, Fariba Houman -
Patent number: 6153645Abstract: Methods for treating infection and related compositions, compounds of formula I as defined in the application and methods for preparing same, are provided. In general, the compounds inhibit transfer ribonucleic acid (tRNA) synthetase and are useful as antimicrobial agents.Type: GrantFiled: September 10, 1999Date of Patent: November 28, 2000Assignee: Cubist Pharmaceuticals, Inc.Inventors: John Finn, Xiang Yang Yu, Zhongguo Wang, Jason Hill, Dennis Keith, Paul Gallant, Philip Wendler
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Patent number: 5912140Abstract: Recombinant nucleic acids which encode aminoacyl-tRNA sythetases of pneumocystis origin or portions of such enzymes, have been isolated. These nucleic acids can be used to make expression constructs and transformed host cells for the production of pneumocystis aminoacyl-tRNA synthetases. They can also be used in the further isolation of nucleic acids related by DNA sequence similarities, which also encode pneumocystis aminoacyl-tRNA synthetases, or portions thereof. A further embodiment of the invention is antisense nucleic acid which can hybridize to the nucleic acid which encodes the aminoacyl-tRNA synthetase of pneumocystis. The invention also relates to enzymes, isolated and/or recombinant pneumocystis aminoacyl-tRNA synthetases. Antibodies which bind to these enzymes can be made and can be used in the purification and study of the enzymes.Type: GrantFiled: April 3, 1995Date of Patent: June 15, 1999Assignee: Cubist Pharmaceuticals, Inc.Inventors: Susan K. Whoriskey, Cheryl L. Quinn, Niajun Tao, Karen I. Politis-Virk, Paul R. Schimmel
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Patent number: 5885815Abstract: The present invention relates to isolated and/or recombinant nucleic acids which encode Candida isoleucyl-tRNA synthetases, portions thereof, or fusion proteins comprising a Candida isoleucyl-tRNA synthetase or portion thereof. Also disclosed are constructs comprising the nucleic acids of the present invention, host cells comprising a recombinant nucleic acid or construct, and methods of producing a Candida isoleucyl-tRNA synthetase, portion thereof, or fusion protein comprising same. Also described are tester strains, which are cells engineered to rely on the function of a Candida isoleucyl-tRNA synthetase or functional fragment thereof encoded by an introduced cloned gene, and which can be used in a method of detecting an inhibitor of Candida isoleucyl-tRNA synthetase function.Type: GrantFiled: November 1, 1996Date of Patent: March 23, 1999Assignee: Cubist Pharmaceuticals, Inc.Inventors: Mandana Sassanfar, Christoph Kaufmann, Paul L. Gallant, Janice E. Kranz, Fariba Houman
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Patent number: 5871987Abstract: The present invention relates to isolated and/or recombinant nucleic acids which encode Candida tyrosyl-tRNA synthetases, portions thereof, or fusion proteins comprising a Candida tyrosyl-tRNA synthetase or portion thereof. Also disclosed are constructs comprising the nucleic acids of the present invention, host cells comprising a recombinant nucleic acid or construct, and methods of producing a Candida tyrosyl-tRNA synthetase, portion thereof, or fusion protein comprising same. Also described are tester strains, which are cells engineered to rely on the function of a Candida tyrosyl-tRNA synthetase or functional fragment thereof encoded by an introduced cloned gene, and which can be used in a method of detecting an inhibitor of Candida tyrosyl-tRNA synthetase function.Type: GrantFiled: November 1, 1996Date of Patent: February 16, 1999Assignee: Cubist Pharmaceuticals, Inc.Inventors: Mandana Sassanfar, Paul L. Gallant, Xiaoyu Shen, Nianjun Tao, Jianshi Tao, Fariba Houman
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Patent number: 5824657Abstract: Novel aminoacyl sulfamides are described. These compounds are effective in the treatment of hyperproliferative disorders, specifically psoriasis. Exemplary compounds of this invention are 5'-deoxy-adenosine 5'-N(N-L-phenylalanyl)sulfamide and 5'-deoxy-adenosine 5'-N-(N-L-tryptophanyl)sulfamide.Type: GrantFiled: March 18, 1997Date of Patent: October 20, 1998Assignee: Cubist Pharmaceuticals, Inc.Inventors: Jason M. Hill, Arthur F. Kluge
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Patent number: 5801013Abstract: Recombinant nucleic acids which encode aminoacyl-tRNA sythetases of helicobacter origin have been isolated. These nucleic acids can be used to make expression constructs and transformed host cells for the production of helicobacter aminoacyl-tRNA synthetases. They can also be used in the further isolation of nucleic acids related by DNA sequence similarities, which also encode helicobacter aminoacyl-tRNA synthetases, or portions thereof. A further embodiment of the invention is antisense nucleic acid which can hybridize to the nucleic acid which encodes the aminoacyl-tRNA synthetase of helicobacter. The invention also relates to isolated and/or recombinant helicobacter aminoacyl-tRNA synthetases. Antibodies which bind to these enzymes can be made and can be used in the purification and study of the enzymes.Type: GrantFiled: May 26, 1995Date of Patent: September 1, 1998Assignee: Cubist Pharmaceuticals, Inc.Inventors: Jianshi Tao, Yan Qiu, Fariba Houman, Xiaoyu Shen, Paul R. Schimmel
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Patent number: 5798240Abstract: Isolated and/or recombinant nucleic acids encoding mycobacterial methionyl-tRNA synthetase have been characterized. Recombinant DNA constructs and vectors having a sequence which encodes mycobacterial methionyl-tRNA synthetase have been made, and can be used for the construction of tester strains as well as for the production of isolated and/or recombinant methionyl-tRNA synthetases. These enzymes or portions thereof are useful in the biochemical separation of methionine and quantification of methionine or ATP, and for producing antibodies useful in the purification and study of the enzyme, for example. Host cells and methods useful for producing recombinant mycobacterial methionyl-tRNA synthetases are described, as are tester strains, which are cells engineered to rely on the function of the tRNA synthetase encoded by an introduced cloned gene.Type: GrantFiled: January 11, 1996Date of Patent: August 25, 1998Assignee: Cubist Pharmaceuticals, Inc.Inventors: Susan A. Martinis, Mandana Sassanfar, Sunghoon Kim, Sang Ho Lee, Paul R. Schimmel
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Patent number: 5759833Abstract: Isolated, recombinant nucleic acids which encode an isoleucyl-tRNA synthetase (IleRS) of human origin have been used to make expression constructs and transformed host cells for the production of a recombinant human IleRS. A recombinant enzyme has been purified, and is active in the specific aminoacylation of tRNA by isoleucine. Isolated, recombinant enzyme, and antibodies made specifically thereto, can be useful in assays to diagnose and monitor the autoimmune disease known as "antisynthetase syndrome." The essential isoleucyl-tRNA synthetases of microbes pathogenic in humans can be the targets of inhibitory agents having antimicrobial activity. A human isoleucyl-tRNA synthetase, isolated and purified, can be used to assess the toxic effect in humans of such an inhibitory agent in various biochemical activity assays. This human enzyme can also be expressed in "tester strains," whose cells rely upon the function of the human isoleucyl-tRNA synthetase for tRNA.sup.Ile charging.Type: GrantFiled: June 6, 1995Date of Patent: June 2, 1998Assignees: Cubist Pharmaceuticals, Inc., Cancer Institute, Japanese Foundation for Cancer ResearchInventors: Kiyotaka Shiba, Janice E. Kranz, Paul R. Schimmel
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Patent number: 5756327Abstract: Isolated and/or recombinant nucleic acids encoding mycobacterial isoleucyl-tRNA synthetase have been characterized. Recombinant DNA constructs and vectors having a sequence which encodes mycobacterial isoleucyl-tRNA synthetase have been made, and can be used for the construction of tester strains as well as for the production of isolated and/or recombinant isoleucyl-tRNA synthetases. These enzymes or portions thereof are useful in the biochemical separation of isoleucine and quantification of isoleucine or ATP, and for producing antibodies useful in the purification and study of the enzyme, for example. Host cells and methods useful for producing recombinant mycobacterial isoleucyl-tRNA synthetases are described, as are tester strains, which are cells engineered to rely on the function of the tRNA synthetase encoded by an introduced cloned gene.Type: GrantFiled: May 26, 1995Date of Patent: May 26, 1998Assignee: Cubist Pharmaceuticals, Inc.Inventors: Mandana Sassanfar, Paul R. Schimmel