Therapeutic methods employing sialylated glycoforms of soluble complement receptor 1 (SCR 1)
First Claim
1. A method of treating a disease or disorder associated with inflammation or inappropriate complement activation comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, in which said composition exhibits dominant isoforms of sCR1 glycoprotein molecules which have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
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Accused Products
Abstract
Provided are therapeutic methods employing preparations of recombinant soluble Complement Receptor type 1 (sCR1) defined with respect to the distribution of sCR1 glycoforms. The methods are suitable for treatment of disease involving inflammation, inappropriate complement activation, and in thrombotic or shock state conditions. Preferred methods employ sCR1 glycoforms that are sialylated, have a pI of ≦5.1, or have a sialic acid:mannose molar ratio of ≧0.25.
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Citations
16 Claims
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1. A method of treating a disease or disorder associated with inflammation or inappropriate complement activation comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, in which said composition exhibits dominant isoforms of sCR1 glycoprotein molecules which have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
- 2. A method of treating a disease or disorder associated with inflammation or inappropriate complement activation comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, wherein substantially all of the sCR1 glycoprotein molecules in said composition contain one or more complex oligosaccharide structures, wherein at least about 40% of said oligosaccharide structures are terminated with one or more sialic acid residues per oligosaccharide structure.
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4. A method of treating a disease or disorder associated with inflammation or inappropriate complement activation comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, in which 70% of all of said sCR1 glycoprotein molecules have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
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5. A method of treating a disease or disorder associated with inflammation or inappropriate complement activation comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, wherein all of the sCR1 glycoprotein molecules in said composition form a population of sCR1 glycoprotein molecules having a molar ratio of sialic acid to mannose of greater than or equal to 0.25.
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6. A method of treating a thrombotic condition in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising (a) a pharmaceutically acceptable carrier or excipient;
- (b) a therapeutically effective amount of a thrombolytic agent; and
(c) a therapeutically effective amount of sCR1 glycoprotein molecules, in which said composition exhibits dominant isoforms of sCR1 glycoprotein molecules which have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
- (b) a therapeutically effective amount of a thrombolytic agent; and
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7. A method of treating a thrombotic condition in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising (a) a pharmaceutically acceptable carrier or excipient;
- (b) a therapeutically effective amount of a thrombolytic agent; and
(c) a therapeutically effective amount of sCR1 glycoprotein molecules, wherein substantially all of the sCR1 glycoprotein molecules in said composition contain one or more complex oligosaccharide structures, wherein at least about 40% of said oligosaccharide structures are terminated with one or more sialic acid residues per oligosaccharide structure. - View Dependent Claims (8)
- (b) a therapeutically effective amount of a thrombolytic agent; and
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9. A method of treating a thrombotic condition in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising (a) a pharmaceutically acceptable carrier or excipient;
- (b) a therapeutically effective amount of a thrombolytic agent; and
(c) a therapeutically effective amount of sCR1 glycoprotein molecules, in which 70% of all of said sCR1 glycoprotein molecules have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
- (b) a therapeutically effective amount of a thrombolytic agent; and
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10. A method of treating a thrombotic condition in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising (a) a pharmaceutically acceptable carrier or excipient;
- (b) a therapeutically effective amount of a thrombolytic agent; and
(c) a therapeutically effective amount of sCR1 glycoprotein molecules, wherein all of the sCR1 glycoprotein molecules in said composition form a population of sCR1 glycoprotein molecules having a molar ratio of sialic acid to mannose of greater than or equal to 0.25. - View Dependent Claims (11)
- (b) a therapeutically effective amount of a thrombolytic agent; and
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12. A method of treating adult respiratory distress syndrome in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, in which said composition exhibits dominant isoforms of sCR1 glycoprotein molecules which have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
- 13. A method of treating adult respiratory distress syndrome in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, wherein substantially all of the sCR1 glycoprotein molecules in said composition contain one or more complex oligosaccharide structures, wherein at least about 40% of said oligosaccharide structures are terminated with one or more sialic acid residues per oligosaccharide structure.
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15. A method of treating adult respiratory distress syndrome in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, in which 70% of all of said sCR1 glycoprotein molecules have an isoelectric point, pI, less than or equal to 5.1 as determined by chromatofocusing, and wherein the pI of said dominant isoforms increases after neuraminidase treatment.
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16. A method of treating adult respiratory distress syndrome in a subject, comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of sCR1 glycoprotein molecules, wherein all of the sCR1 glycoprotein molecules in said composition form a population of sCR1 glycoprotein molecules having a molar ratio of sialic acid to mannose of greater than or equal to 0.25.
Specification