Patents Assigned to Nektar Therapeutics AL, Corporation
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Publication number: 20090074704Abstract: Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.Type: ApplicationFiled: November 30, 2007Publication date: March 19, 2009Applicant: Nektar Therapeutics AL, CorporationInventors: Xuan Zhao, Michael David Bentley, Zhongxu Ren, Tacey X. Viegas
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Publication number: 20090054590Abstract: Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— wherein n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.Type: ApplicationFiled: September 20, 2008Publication date: February 26, 2009Applicant: Nektar Therapeutics AL, CorporationInventors: J. Milton Harris, Francesco Maria Veronese, Paolo Caliceti, Oddone Schiavon
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Publication number: 20090041714Abstract: Conjugates of a Factor VIII moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.Type: ApplicationFiled: June 6, 2008Publication date: February 12, 2009Applicant: Nektar Therapeutics AL, CorporationInventors: Mary J. Bossard, Michael D. Bentley, Ping Zhang
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Publication number: 20090012241Abstract: The present invention is directed to hydrolytically stabilized maleimide-functionalized water soluble polymers and to methods for making and utilizing such polymers and their precursors.Type: ApplicationFiled: August 26, 2008Publication date: January 8, 2009Applicant: Nektar Therapeutics AL, CorporationInventors: Antoni Kozlowski, Remy F. Gross III, Samuel P. McManus
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Publication number: 20080262166Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).Type: ApplicationFiled: June 25, 2008Publication date: October 23, 2008Applicant: Nektar Therapeutics AL, CorporationInventors: Michael David Bentley, Xuan Zhao, Xiaoming Shen, Lihong Guo
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Patent number: 7432330Abstract: The present invention is directed to hydrolytically stabilized maleimide-functionalized water soluble polymers and to methods for making and utilizing such polymers and their precursors.Type: GrantFiled: December 31, 2003Date of Patent: October 7, 2008Assignee: Nektar Therapeutics AL, CorporationInventors: Antoni Kozlowski, Remy F. Gross, III, Samuel P. McManus
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Patent number: 7432331Abstract: The present invention is directed to hydrolytically stabilized maleimide-functionalized water soluble polymers and to methods for making and utilizing such polymers and their precursors.Type: GrantFiled: March 25, 2005Date of Patent: October 7, 2008Assignee: Nektar Therapeutics AL, CorporationInventors: Antoni Kozlowski, Remy F. Gross, III, Samuel P. McManus
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Publication number: 20080234193Abstract: The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.Type: ApplicationFiled: December 27, 2007Publication date: September 25, 2008Applicants: Nektar Therapeutics AL, Corporation, Baxter International Inc., Baxter Healthcare SAInventors: Mary J. Bossard, Gayle Stephenson, Zhihao Fang, Harold Zappe, Stacy Mitchell, Ping Zhang, Friedrich Scheiflinger, Peter Turecek, Juergen Siekmann, Katalin Varadi, Herbert Gritsch
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Publication number: 20080227872Abstract: The invention provides a method for preparing a 1-benzotriazolylcarbonate ester of a water-soluble and non-peptidic polymer by reacting a terminal hydroxyl group of a water-soluble and non-peptidic polymer with di(1-benzotriazolyl)carbonate in the presence of an amine base and an organic solvent. The polymer backbone can be poly(ethylene glycol). The 1-benzotriazolylcarbonate ester can then be reacted directly with a biologically active agent to form a biologically active polymer conjugate or reacted with an amino acid, such as lysine, to form an amino acid derivative.Type: ApplicationFiled: April 25, 2008Publication date: September 18, 2008Applicant: Nektar Therapeutics AL, CorporationInventor: Antoni Kozlowski
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Patent number: 7419600Abstract: Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— wherein n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.Type: GrantFiled: August 5, 2003Date of Patent: September 2, 2008Assignee: Nektar Therapeutics AL, CorporationInventors: J. Milton Harris, Francesco Maria Veronese, Paola Caliceti, Oddone Schiavon
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Publication number: 20080194612Abstract: Provided herein are water-soluble prodrugs. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.Type: ApplicationFiled: February 11, 2008Publication date: August 14, 2008Applicant: Nektar Therapeutics AL, CorporationInventors: Xuan Zhao, Michael D. Bentley, Zhongxu Ren, Tacey X. Viegas
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Publication number: 20080188414Abstract: The present invention provides Factor IX moiety-polymer conjugates having a releaseable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.Type: ApplicationFiled: December 27, 2007Publication date: August 7, 2008Applicant: Nektar Therapeutics AL, CorporationInventors: Mary J. Bossard, Gayle Stephenson
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Patent number: 7405266Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).Type: GrantFiled: March 9, 2007Date of Patent: July 29, 2008Assignee: Nektar Therapeutics AL, CorporationInventors: Michael David Bentley, Xuan Zhao, Xiaoming Shen, Lihong Guo
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Patent number: 7378469Abstract: The invention provides a method for preparing a 1-benzotriazolylcarbonate ester of a water-soluble and non-peptidic polymer by reacting a terminal hydroxyl group of a water-soluble and non-peptidic polymer with di(1-benzotriazolyl)carbonate in the presence of an amine base and an organic solvent. The polymer backbone can be poly(ethylene glycol). The 1-benzotriazolylcarbonate ester can then be reacted directly with a biologically active agent to form a biologically active polymer conjugate or reacted with an amino acid, such as lysine, to form an amino acid derivative.Type: GrantFiled: July 24, 2006Date of Patent: May 27, 2008Assignee: Nektar Therapeutics AL, CorporationInventor: Antoni Kozlowski
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Publication number: 20080069902Abstract: The invention provides a multi-arm block copolymer for use in delivering a variety of bioactive agents. The copolymer of the invention contains a central core from which extend multiple (3 or more) copolymer arms. Each copolymer arm possesses an inner polypeptide segment and an outer hydrophilic polymer segment. Thus, the overall structure of the copolymer comprises an inner core region that includes the central core and the inner polypeptide segment, while the outer core region is hydrophilic in nature. The multi-arm copolymer of the invention is particularly useful for delivery of biologically active agents that can be entrapped within the inner core region.Type: ApplicationFiled: November 14, 2007Publication date: March 20, 2008Applicant: Nektar Therapeutics AL, CorporationInventors: Xuan Zhao, Zhongxu Ren, Kazunori Emoto
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Patent number: 7329721Abstract: The present invention is directed to maleamic acid derivatives of water soluble polymers, to chemically stable water-soluble polymer succinamic acid-active agent conjugates, and to methods for reproducibly preparing, characterizing and using such polymer reagents and their conjugates.Type: GrantFiled: December 31, 2003Date of Patent: February 12, 2008Assignee: Nektar Therapeutics AL, CorporationInventors: Antoni Kozlowski, Remy F. Gross, III, Samuel P. McManus
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Publication number: 20080015151Abstract: The present invention provides variants of cyanovirin-N and water-soluble polymer conjugates thereof, and methods of preparing such conjugates. The cyanovirin-N of the invention are particularly suited for site-selective covalent attachment of one or more water soluble polymers, to provide polymer conjugates of cyanovirin-N variants exhibiting antiviral activity.Type: ApplicationFiled: August 2, 2007Publication date: January 17, 2008Applicants: The Govt. of the U.S.A. as represented by The Secretary of The Dept. of, Nektar Therapeutics AL, CorporationInventors: M. Snell, Michael Roberts, Toshiyuki Mori, Barry O'Keefe, Michael Boyd
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Patent number: 7316811Abstract: The invention provides a multi-arm block copolymer for use in delivering a variety of bioactive agents. The copolymer of the invention contains a central core from which extend multiple (3 or more) copolymer arms. Each copolymer arm possesses an inner polypeptide segment and an outer hydrophilic polymer segment. Thus, the overall structure of the copolymer comprises an inner core region that includes the central core and the inner polypeptide segment, while the outer core region is hydrophilic in nature. The multi-arm copolymer of the invention is particularly useful for delivery of biologically active agents that can be entrapped within the inner core region.Type: GrantFiled: December 24, 2003Date of Patent: January 8, 2008Assignee: Nektar Therapeutics AL, CorporationInventors: Xuan Zhao, Zhongxu Ren, Kazunori Emoto
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Patent number: 7312301Abstract: The present invention provides both crosslinked polymer compositions capable of forming hydrogel upon exposure to an aqueous environment and thiosulfonate hydrogel-forming components. The thiosulfonate hydrogel-forming components of the invention are preferably multi-arm thiosulfonate polymer derivatives that form a crosslinked polymer composition when exposed to a base without requiring the presence of a second cross-linking reagent, redox catalyst, or radiation. Methods for forming hydrogel compositions, as well as methods for using the hydrogel, are also provided.Type: GrantFiled: December 31, 2003Date of Patent: December 25, 2007Assignee: Nektar Therapeutics AL, CorporationInventors: Zhihao Fang, Michael D. Bentley
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Patent number: 7265186Abstract: The invention provides methods for making copolymers and multi-arm block copolymers useful as drug delivery vehicles. The multi-arm block copolymers comprise a central core molecule, such as a residue of a polyol, and at least three copolymer arms covalently attached to the central core molecule, each copolymer arm comprising an inner hydrophobic polymer segment covalently attached to the central core molecule and an outer hydrophilic polymer segment covalently attached to the hydrophobic polymer segment, wherein the central core molecule and the hydrophobic polymer segment define a hydrophobic core region. The solubility of hydrophobic biologically active agents can be improved by entrapment within the hydrophobic core region of the block copolymer. The invention further includes pharmaceutical compositions including such block copolymers, pharmaceutical compositions, and methods of using the block copolymers as drug delivery vehicles.Type: GrantFiled: November 8, 2004Date of Patent: September 4, 2007Assignee: Nektar Therapeutics AL, CorporationInventor: Xuan Zhao