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 who have developed such antibodies 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 amino acids of positions 484-508 of the A2 domain. The modified factor VIII is useful as a clotting factor supplement for hemophiliacs.
Claims25
A modified human factor VIII comprising an amino acid substitution at one or more of positions 484-508 according to SEQ ID NO:2, said substitution being an insertion of an immunoreactivity-reducing amino acid for the naturally-occurring amino acid, said modified factor VIII having procoagulant activity.
DNA encoding modified human factor VIII A2 domain, said DNA having one or more nucleotide substitutions resulting in a coding change at one or more amino acid positions chosen from positions 484-508 according to SEQ ID NO:2, said change encoding an immunoreactivity-reducing amino acid at the chosen position.
Expression product of DNA encoding human or hybrid human/mammalian factor VIII, said DNA comprising DNA encoding a modified A2 domain, the DNA having one or more nucleotide substitutions resulting in a coding change at one or more of amino acid positions chosen from positions 484-508 according to SEQ ID NO:2, said change encoding an immunoreactivity-reducing amino acid at the chosen position. occurring amino acid.
The method of making a modified mammalian factor VIII A2 domain comprising the steps of mutating DNA encoding the domain at one or more codons encoding amino acids at positions corresponding to 484-508 of human factor VIII whereby one or more mutated codons encoding an amino acid is substituted for a corresponding naturally-occurring codon, and expressing in a host cell DNA comprising the mutated codons, either independently or in contiguous translatable sequence with DNA encoding another domain of factor VIII, whereby a modified factor VIII A2 domain is made.
Dependencies are inferred from the claim text.