Patents Assigned to Shearwater Corporation
  • Patent number: 6495659
    Abstract: 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: Grant
    Filed: December 20, 2000
    Date of Patent: December 17, 2002
    Assignee: Shearwater Corporation
    Inventors: Michael David Bentley, Xuan Zhao, Xiaoming Shen, Lihong Guo
  • Publication number: 20020182172
    Abstract: The present invention provides water-soluble polymer conjugates of triazine derivatives using water soluble and non-peptidic polymer backbones, such as poly(ethylene glycol). The invention includes conjugates made using mPEG, bifunctional PEG, branched or multi-arm PEG, and forked PEG. The invention further includes a method of forming such conjugates and a method of treating conditions responsive to triazine derivatives using the conjugates.
    Type: Application
    Filed: November 30, 2001
    Publication date: December 5, 2002
    Applicant: Shearwater Corporation
    Inventors: Michael David Bentley, Xuan Zhao, Robert Shorr
  • Publication number: 20020156047
    Abstract: The invention provides multi-arm block copolymers useful as drug delivery vehicles comprising 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, methods of making such copolymers and pharmaceutical compositions, and methods of using the block copolymers as drug delivery vehicles.
    Type: Application
    Filed: January 22, 2002
    Publication date: October 24, 2002
    Applicant: Shearwater Corporation
    Inventor: Xuan Zhao
  • Patent number: 6461602
    Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.
    Type: Grant
    Filed: April 26, 2001
    Date of Patent: October 8, 2002
    Assignee: Shearwater Corporation
    Inventors: Michael David Bentley, Xuan Zhao
  • Patent number: 6461603
    Abstract: The present invention provides water-soluble polymer conjugates of the anti-malarial drug, artelinic acid, using water soluble and non-peptidic polymer backbones, such as poly(ethylene glycol). The invention includes conjugates made using mPEG, bifunctional PEG and multi-arm PEG. The invention further includes a method of forming such conjugates and a method of treating malaria using the conjugates.
    Type: Grant
    Filed: February 27, 2001
    Date of Patent: October 8, 2002
    Assignee: Shearwater Corporation
    Inventors: Michael David Bentley, Xuan Zhao, Jeremy Lloyd Clark
  • Patent number: 6448369
    Abstract: This invention provides a method for preparing, in high purity and high yield, heterobifunctional derivatives of poly(ethylene glycol) or related polymers. A chromatographic purification step is not necessary in the method. In accordance with the method of the invention, an intermediate polymer having a formula of W-Poly-OH is provided bearing a removable group W at one terminus. The intermediate polymer W-Poly-OH is first altered by modifying the OH group to a first functional group X, followed by the removal of W to generate a second hydroxyl group. The latter hydroxyl group may then be further converted to a second functional group Y, thus providing the desired heterobifunctional derivative.
    Type: Grant
    Filed: November 5, 1998
    Date of Patent: September 10, 2002
    Assignee: Shearwater Corporation
    Inventors: Michael David Bentley, J. Milton Harris, Antoni Kozlowski
  • Patent number: 6436386
    Abstract: Isolatable, hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are provided. The polymeric structure includes a linear or branched water-soluble and non-peptidic polymer backbone, such as a PEG backbone, having at least two termini, a first terminus being covalently bonded to a hydroxyapatite-targeting moiety, such as a bisphosphonate, and a second terminus covalently bonded to a chemically reactive group, wherein said chemically reactive group is protected or unprotected. Methods of preparing and using hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are also provided.
    Type: Grant
    Filed: November 14, 2000
    Date of Patent: August 20, 2002
    Assignee: Shearwater Corporation
    Inventors: Michael James Roberts, Antoni Kozlowski
  • Patent number: 6437025
    Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
    Type: Grant
    Filed: November 5, 2001
    Date of Patent: August 20, 2002
    Assignee: Shearwater Corporation
    Inventors: J. Milton Harris, Antoni Kozlowski
  • Publication number: 20020099133
    Abstract: 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: Application
    Filed: February 6, 2002
    Publication date: July 25, 2002
    Applicant: Shearwater Corporation
    Inventor: Antoni Kozlowski
  • Publication number: 20020086939
    Abstract: 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: Application
    Filed: February 6, 2002
    Publication date: July 4, 2002
    Applicant: Shearwater Corporation
    Inventor: Antoni Kozlowski
  • Patent number: 6413507
    Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.
    Type: Grant
    Filed: December 23, 1999
    Date of Patent: July 2, 2002
    Assignee: Shearwater Corporation
    Inventors: Michael David Bentley, Xuan Zhao
  • Publication number: 20020082345
    Abstract: High molecular weight derivatives of activated poly(ethylene glycol) and the like polymers are prepared in high purity by conjugating a large PEG molecule to a small PEG molecule. Most of the reaction steps can be accomplished on the more readily purified small molecule to avoid laborious purification of the high molecular weight derivatives.
    Type: Application
    Filed: December 18, 2001
    Publication date: June 27, 2002
    Applicant: Shearwater Corporation
    Inventors: Antoni Kozlowski, Xiaoming Shen, Michael David Bentley, Zhihao Fang
  • Publication number: 20020072573
    Abstract: This invention provides a method for preparing, in high purity and high yield, heterobifunctional derivatives of poly(ethylene glycol) or related polymers. A chromatographic purification step is not necessary in the method. In accordance with the method of the invention, an intermediate polymer having a formula of W-Poly-OH is provided bearing a removable group W at one terminus. The intermediate polymer W-Poly-OH is first altered by modifying the OH group to a first functional group X, followed by the removal of W to generate a second hydroxyl group. The latter hydroxyl group may then be further converted to a second functional group Y, thus providing the desired heterobifunctional derivative.
    Type: Application
    Filed: February 8, 2002
    Publication date: June 13, 2002
    Applicant: Shearwater Corporation
    Inventors: Michael David Bentley, J. Milton Harris, Antoni Kozlowski
  • Publication number: 20020052430
    Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
    Type: Application
    Filed: November 5, 2001
    Publication date: May 2, 2002
    Applicant: Shearwater Corporation
    Inventors: J. Milton Harris, Antoni Kozlowski
  • Patent number: 6376604
    Abstract: 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: Grant
    Filed: December 18, 2000
    Date of Patent: April 23, 2002
    Assignee: Shearwater Corporation
    Inventor: Antoni Kozlowski
  • Publication number: 20020040076
    Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
    Type: Application
    Filed: November 5, 2001
    Publication date: April 4, 2002
    Applicant: Shearwater Corporation
    Inventors: J. Milton Harris, Antoni Kozlowski
  • Publication number: 20020037949
    Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
    Type: Application
    Filed: November 5, 2001
    Publication date: March 28, 2002
    Applicant: Shearwater Corporation
    Inventors: J. Milton Harris, Antoni Kozlowski
  • Patent number: 6362254
    Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
    Type: Grant
    Filed: March 11, 1999
    Date of Patent: March 26, 2002
    Assignee: Shearwater Corporation
    Inventors: J. Milton Harris, Antoni Kozlowski
  • Patent number: 6348558
    Abstract: A water soluble polymer is provided having two or more oligomers linked to each other by hydrolytically degradable carbonate linkages. The polymer can be hydrolytically degraded into oligomers (e.g., oligomers of ethylene oxide) under physiological conditions. The polymer can be conjugated to biologically active agents such as proteins or peptides to impart improved water solubility, reduced immunogenicity, reduced rate of renal clearance, and increased stability. The polymer is useful in making hydrolytically degradable hydrogels which can be used in drug delivery and related biomedical applications. One example of the polymer is a poly(ether carbonate) of the formula X—O—[(—CH2CH2—O—)n—CO2—]n—(CH2CH2))n-y where X and Y are independently H, alkyl, alkenyl, aryl, or a reactive moiety, and at least one of X and Y is a reactive moiety.
    Type: Grant
    Filed: December 10, 1999
    Date of Patent: February 19, 2002
    Assignee: Shearwater Corporation
    Inventors: J. Milton Harris, Michael David Bentley, Xuan Zhoa, Xiaoming Shen
  • Publication number: 20020013266
    Abstract: A substantially hydrophilic conjugate is provided having a peptide that is capable of passing the blood-brain barrier covalently linked to a water-soluble nonpeptidic polymer such as polyethylene glycol. The conjugate exhibits improved solubility and in vivo stability and is capable of passing the blood-brain barrier of an animal.
    Type: Application
    Filed: September 19, 2001
    Publication date: January 31, 2002
    Applicant: Shearwater Corporation
    Inventors: Michael David Bentley, Michael James Roberts