Patent ID: 7544660
Filing Date: 2009-06-09
Classification: A61K,A61P,C07K

Abstract:
1. A pharmaceutical composition comprising a modified human Factor VIII polypeptide that has Factor VIII activity, wherein the modified human Factor VIII polypeptide differs from the human Factor VIII by: (a) at least one modification in at least one A3 domain portion, wherein the portion is selected from the group of portions, based upon the human sequence, consisting of amino acids (i) 1743 (Phe) to 1749 (Arg), (ii) 1784 (Ser) to 1831 (Asp), (iii) 1888 (Ser) to 1919 (His), (iv) 1942 (Trp) to 1947 (Met), and (v) 1959 (Ser) to 1974 (Ala); and (b) at least one modification in at least one C1 domain portion, wherein the portion is selected from the group of portions, based upon the human sequence, consisting of amino acids (i) 2037 (Ile) to 2062 (Trp), (ii) 2108 (Asp) to 2118 (Asn), and (iii) 2154 (Thr) to 2158 (Ile); wherein the modification is an amino acid substitution, deletion or addition, and wherein the modification reduces the binding affinity to low-density lipoprotein receptor-related protein (LRP).