Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: The invention relates to modified Factor IX polypeptides such as Factor IX polypeptides with one or more amino acid substitutions. The invention also relates to methods of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.