Adalimumab Variants with Reduced Immunogenic Potential

A variant of a therapeutic anti-TNF alpha antibody comprising variable domains VH and VL of sequences SEQ ID NO:

• 1 and SEQ ID NO:
• 2, said variant comprising at least two amino acid substitutions in at least one sequence overlapping one of the CDRH2 or CDRH3 regions determining the complementarity of said VH variable domain;
• where said at least two amino acid substitutions in the sequence overlapping the CDRH2 region are selected from the group consisting of:
• the substitution of S49 by another amino acid selected from A or G;
• the substitution of A50 by another amino acid selected from G, S, T or D;
• the substitution of T52 by another amino acid selected from A, N or S;
• the substitution S54G;
• and
• the substitution of I57 by another amino acid selected from A, H, N, Q, R, S, T or W;
• and when the variant comprises the residue A49 then it also comprises the residue N52, S52 or S52 and the residue G54;
• wherein said at least two amino acid substitutions in the sequence overlapping the CDRH3 region are selected from the group consisting of:
• the substitution of V89 by L;
• the substitution of V95 by another amino acid selected from A, S or T;
• the substitution of S96 by another amino acid selected from A, G, H, K, N, Q, R or T;
• the substitution of Y97 by H;
• the substitution of L98 by T;
• the substitution of S99 by P;
• and
• the substitution of T100 by another amino acid selected from P or S;
• with the exclusion of variants comprising the residues V89 or L89, V95, K96, Y97, L98, P99 and S100;
• V89, V95, A96, Y97, L98, P99 and S100;
• wherein the positions of said amino acid residues are indicated with reference to the Kabat numbering;
• and said variant presenting a reduced immunogenic potential and a TNF alpha binding affinity at least equal or superior, compared to the therapeutic anti-TNF alpha antibody from which it is derived.