Modified factor VIII
AssigneeEmory University
InventorJohn S. Lollar
Life of this patent
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Abstract
Specific amino acid loci of human factor VIII interact with inhibitory antibodies of hemophilia patients after being treated with factor VIII. Modified factor VIII is disclosed in which the amino acid sequence is changed by a substitution at one or more of the specific loci. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory antibodies.
Claims43
A modified human factor VIII comprising at least one amino acid substitution in the C2 domain wherein the substitution is limited to at least one position selected from the group consisting of 2199, 2200, 2223, 2227, 2251, and 2252 corresponding to SEQ ID NO:2, wherein the modified factor VIII has reduced immunogenicity and/or antigenicity compared to the corresponding human factor VIII protein.
A method for modifying human factor VIII such that reactivity to an inhibitory antibody is reduced and procoagulant activity is retained comprising substituting an amino acid in the C2 domain wherein the substitution is limited to at least one of the amino acids selected from the group consisting of 2199, 2200, 2223, 2227, 2251, and 2252 corresponding to SEQ ID NO:2.
A method for modifying human factor VIII such that antigenicity is reduced and procoagulant activity is retained comprising substituting an amino acid in the C2 domain wherein the substitution is limited to at least one of the amino acids at selected from the group consisting of 2199, 2200, 2223, 2227, 2251, and 2252 corresponding to SEQ ID NO:2.
Dependencies are inferred from the claim text.