Coagulation factor VIII with reduced immunogenicity
AssigneeImnate Sarl
InventorJean-Marie Saint-Remy
Life of this patent
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Abstract
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 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.
Claims4
A method of treating septic shock, acute fibrinolysis, polytrauma, cerebral haemorrhage, or other bleeding disorder, the method comprising administering to a patient in need thereof a factor VIII molecule having a reduced capacity to activate NKT cells and obtained by:
- (a) identifying at least one NKT cell epitope comprising SEQ ID NO:
- 1, SEQ ID NO:
- 3, or SEQ ID NO:5 in a factor VIII molecule, wherein said epitope comprises a seven amino acid residue sequence (positions P1-P7) being [FWTHY]-X2X3-[ILMV]-X5X6-[FWTHY] (SEQ ID NO:
- 7);
- and wherein each of X2, X3, X5, and X6 can be any amino acid;
- and
- (b) modifying at least one identified NKT cell epitope by substituting the amino acid residue in position P1 with a residue other than F, W, T, H or Y, and by substituting the amino acid residue in position P7 with a residue other than F, W, T, H or Y.
Dependencies are inferred from the claim text.