Insights into the IgG heavy chain engineering patent landscape as applied to IgG4 antibody development.

Despite being the least abundant immunoglobulin G in human plasma, IgG4 are used therapeutically when weak effector functions are needed. The increase in engineered IgG4-based antibodies on the market led us to study the patent landscape of IgG4 Fc engineering, i.e., patents claiming modifications in the heavy chain. Thirty-seven relevant patent families were identified, comprising hundreds of IgG4 Fc variants focusing on removal of residual effector functions (since IgG4s bind to FcγRI and weakly to other FcγRs), half-life enhancement and IgG4 stability. Given the number of expired or soon to expire major patents in those 3 areas, companies developing blocking antibodies now have, or will in the near future, access to free tools to design silenced, half-life extended and stable IgG4 antibodies.