Keep an eye on your target - Why increasing the half-life of your antibody is not always the solution.

22 June, 2021

Lionel presented at the 9th Antibody Industrial Symposium (AIS 2021) our anaysis on engineered monoclonal antibodies that have a pH dependent FcRn binding to obtain a longer plasma half-life. Recent advancements in monoclonal antibody (mAb) engineering prolonged the plasma half-life via optimized FcRn interactions to ~100 days in human, raising the promise of convenient treatment regimens with potentially less than quarterly dosing. However, while a longer mAb half-life can result in a longer effect duration, there are other parameters that need to be considered. Here we show with mathematical PK/PD modelling that the effect duration of soluble target inhibition does not only depend on the mAb half-life. There is a limit of the duration of target inhibition that depends on the target production rate, mAb dose and affinity and that is independent of the mAb plasma half-life. To further prolong the effect duration in such cases additional technologies, like sweeping mAb, are needed.