Patent ID: 8816054
Filing Date: 2014-08-26
Classification: A61K,A61P,C07K

Abstract:
1. A Factor VIII (FVIII) variant, consisting essentially of a modified PACE/furin-cleavage site and a B domain deletion (BDD) for modulating hemostasis, said PACE/furin cleavage site consisting of amino acids RHQR, said FVIII variant being a human FVIII variant selected from the group consisting essentially of: i) a FVIII variant with said BDD and wherein R is substituted with an H in the PACE/furin cleavage site; ii) a FVIII variant with said BDD and wherein S is substituted with an H in the PACE/furin cleavage site; iii) a FVIII variant with said BDD and wherein one amino acid at said PACE/furin cleavage site is deleted; iv) a FVIII variant with said BDD and wherein R at said PACE/furin cleavage site is substituted with an amino acid selected from the group consisting of a serine, lysine, methionine, cysteine, proline and tyrosine; and v) a FVIII variant wherein one or more amino acids at said PACE/furin cleavage site and a B domain are deleted, each of i), ii), iii), iv) and v) exhibiting increased specific activity and stability relative to human FVIII-BDD lacking said substitution and deletions.