COAGULATION FACTOR VIII WITH REDUCED IMMUNOGENICITY VIII

摘要

The invention describes factor VIII molecules with reduced capacity to elicit activation of NKT cells, for use in the treatment of congenital and/or acquired haemophilia A and in bleeding disorders. Said factor VIII molecules having a domain structure Al-al-A2-a2-B-a3-A3-Cl-C2, in which A1, A2, B, A3, C1 and C2 represent domains and al, a2 and a3 acidic regions linking said domains, The factor VIII molecule is obtainable by:
a. identification of at least one NKT cell epitope wherein said epitope comprises hydrophobic aminoacid residues in position P1 and/or P7
b. modification of said epitope(s) by eliminating at least one hydrophobic aminoacid residue in position P1 and/or P7, substituting at least one hydrophobic aminoacid residue in position P1 and/or P7 with a non-hydrophobic residue, or adding a non-hydrophobic residue in position P1 and/or P7.