Patent ID: 8546332
Filing Date: 2013-10-01
Classification: A61K,A61P,C07K

Abstract:
1. A pharmaceutical preparation comprising: (A) 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 at least one modification in at least one exosite of the A3 domain of said Factor VIII polypeptide, wherein said exosite is a hydrophilic moiety of the A3 domain of said modified human Factor VIII, and wherein the exosite is selected from the group of exosites, based upon the amino acid sequence of human Factor VIII polypeptide, consisting of the regions in said Factor VIII polypeptide: (i) 1743 (Phe) to 1749 (Arg), (ii) 1784 (Ser) to 1831 (Asp), (iii) 1886 (Ser) to 1919 (His), (iv) 1942 (Trp) to 1947 (Met), and (v) 1959 (Ser) to 1974 (Ala), wherein the modification is an amino acid substitution, deletion or insertion, and wherein the modification reduces the binding affinity to low-density lipoprotein receptor-related protein (LRP); and (B) an added lipoprotein receptor-related protein antagonist.