Modification to the Fc amino acid sequence of the FcγR‐contact regions can also be used to reduce FcγR binding. A widely used modification of IgG1 is the substitution of leucine 234 and 235 in the lower hinge sequence (L234 L235 G236 G237) with alanine (L234A L235A). It is often referred to as the “LALA mutation” and effectively eliminates FcγR binding by more than 100 fold104, 105 and is used in teplizumab and spesolimab (Table 4).