Glycoform fractions of recombinant soluble complement receptor 1 (sCR1) having extended half-lives in vivo
First Claim
1. A composition comprising 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 wherein the pI of said dominant isoforms increases after neuraminidase treatment.
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Abstract
The present invention relates to novel glycoforms and preparations of the soluble complement receptor type 1 (sCR1), and their uses in the therapy of complement mediated diseases and disorders involving inflammation and inappropriate complement activation and in thrombotic or shock state conditions. The invention provides novel glycoforms and methods for producing, detecting, enriching and purifying such glycoforms. The invention further provides methods of specifically producing a glycoform by recombinant or chemical means. Preferred embodiments of the invention include sialylated glycoforms and glycoforms with a pI≦5.1 determined by chromatofocusing or with a sialic acid to mannose molar ratio of >0.25. The glycoforms may be formulated alone in therapeutic compositions or in combination with thrombolytic agents.
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16 Claims
- 1. A composition comprising 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 wherein the pI of said dominant isoforms increases after neuraminidase treatment.
- 4. A composition comprising sCR1 molecules, wherein substantially all of the sCR1 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.
- 6. A composition comprising sCR1 molecules, wherein all of the sCR1 molecules in said composition form a population of sCR1 molecules having a molar ratio of sialic acid to mannose of greater than or equal to 0.25.
Specification