ANTI-C5 ANTIBODIES WITH IMPROVED PHARMACOKINETICS

Claims

An isolated antibody, or antigen-binding fragment thereof, inhibiting the cleavage of C5 into C5a and C5b fragments, comprising: (i) a heavy-chain CDR1 comprising the amino acid sequence of SEQ ID No. 1, (ii) a heavy-chain CDR2 comprising the amino acid sequence of SEQ ID No. 2, (iii) a heavy-chain CDR3 comprising the amino acid sequence of SEQ ID No. 3, (iv) a light-chain CDR1 comprising the amino acid sequence of SEQ ID No. 4, (v) a light-chain CDR2 comprising the amino acid sequence of SEQ ID No. 5, (vi) a light-chain CDR3 comprising the amino acid sequence of SEQ ID No. 6, wherein at least one amino acid of (i) - (vi) is substituted with histidine, wherein the substitution is made at the selected amino acid position(s) of the group consisting of: (I) position 8 of SEQ ID NO: 4, (II) position 2 of SEQ ID NO: 1, (III) position 9 of SEQ ID NO: 1, (IV) position 3 of SEQ ID NO: 2,(V) position 8 of SEQ ID No. 2, (VI) position 8 of SEQ ID No. 2 and position 8 of SEQ ID No. 4, (VII) position 9 of SEQ ID No. 1, position 8 of SEQ ID No. 2 and position 8 of SEQ ID No. 4, (VIII) position 2 of SEQ ID No. 1 and position 3 of SEQ ID No. 2, (IX) position 9 of SEQ ID No. 1 and position 8 of SEQ ID No. 2, (X) position 2 of SEQ ID No. 1, position 8 of SEQ ID No. 2 and position 8 of SEQ ID No. 4, and (XI) position 2 of SEQ ID No. 1 and position 8 of SEQ ID No. 2; and wherein the antibody, or its antigen-binding fragment, has improved pharmacokinetic properties compared to an antibody comprising the heavy chain amino acid sequence of SEQ ID No. 7 and the light chain amino acid sequence of SEQ ID No. 8.