Fc-engineered antibodies with immune effector functions completely abolished

Elimination of the binding of immunoglobulin Fc to Fc gamma receptors (Fc.R) is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many different approaches have been described in the literature but none of them completely eliminates binding to all of the Fc. receptors. Here we describe a set of novel variants having specific amino acid substitutions in the Fc region at L234 and L235 combined with the substitution G236R. They show no detectable binding to Fc. receptors or to C1q, are inactive in functional cell-based assays and do not elicit inflammatory cytokine responses. Meanwhile, binding to FcRn, manufacturability, stability and potential for immunogenicity are unaffected. These variants have the potential to improve the safety and efficacy of therapeutic antibodies and Fc fusion proteins.

Automated summary

Novel variants with specific amino acid substitutions at L234 and L235 combined with G236R substitution completely eliminate binding to Fc. receptors, avoiding inflammatory responses and improving the safety and efficacy of therapeutic antibodies and Fc fusion proteins.