Factor VIII: remodeling and glycoconjugation of factor VIII
First Claim
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1. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
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Abstract
The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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Citations
110 Claims
- 1. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
- 19. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
- 27. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
- 35. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
- 43. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
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55. A covalent conjugate formed between a poly(ethylene glycol) and a glycosylated or non-glycosylated Factor VIII peptide, wherein said polymeric modifying group is conjugated to said Factor VIII peptide via an intact glycosyl linking group interposed between and covalently linked to both said Factor VIII peptide and said poly(ethylene glycol), wherein said covalent conjugate is prepared by a cell-free in vitro method comprising:
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(a) contacting said Factor VIII peptide with a mixture comprising a nucleotide sugar covalently linked to said poly(ethylene glycol), and a glycosyltransferase for which said nucleotide sugar is a substrate under conditions suitable for said at least one glycosyltransferase to transfer a modified sugar moiety of said nucleotide sugar to said Factor VIII peptide, wherein said modified sugar moiety comprises at least one modifying group which is a poly(ethylene glycol), thereby forming said covalent conjugate of said Factor VIII peptide. - View Dependent Claims (56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79)
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- 80. A covalent conjugate formed between a poly(ethylene glycol) and a Factor VIII peptide, said peptide having the formula:
- 88. A covalent conjugate formed between a Factor VIII peptide and a poly(ethylene glycol), wherein said poly(ethylene glycol) is covalently attached to said Factor VIII peptide through an intact glycosyl linking group, said Factor VIII peptide comprising a glycosyl residue having a formula which is a member selected from:
Specification