Agents for treating disease

摘要

Disclosed is a method for screening for a molecule capable of binding to CD4 comprising: (a) providing one or more candidate molecules; (b) determining whether the one or more candidate molecules is capable of binding to one or more of the following regions of human CD4: amino acids 148 to 154, amino acids 164 to 168 and amino acids 185 to 192; and (c) selecting a molecule determined in step (b) to be capable of binding to CD4. Also disclosed is an antibody or antibody fragment capable of activating CD4+CD25+ regulatory T cells comprising a light chain variable domain comprising a CDR1, a CDR2 and a CDR3 and a heavy chain variable domain comprising a CDR1, a CDR2 and a CDR3, wherein the light chain variable domain and/or the heavy chain variable domain are variants of the variable domains of the BT061 antibody with at least one amino acid substitution in the sequences of the CDRs provided that: (i) the light chain CDR1 comprises: Ser32; Gly33; and Tyr 34; (ii) the light chain CDR2 comprises: Leu54; and Ile57; (iii) the heavy chain CDR1 comprises Asp31, Glu31, Thr31, Cys31, Pro31, Met31 or Tyr31; and (iv) the heavy chain CDR3 comprises Tyr103, Phe103 or His103; Arg104; Tyr105; Asp106; and Trp110, Phe110, His 110 or Tyr110, wherein the at least one amino acid substitution is an isosteric variation, wherein the light chain V domain has at least 80% sequence identity to the BT061 light chain, and the heavy chain variable domain has at least 80% sequence identity to the BT061 heavy chain.