On Thursday 22nd September, our CEO, Geoff Hale, will be presenting some of our recent work on the analysis of Fc sequences from antibodies and Fc fusion proteins and the range of variants used for Fc silencing.
Over the last 40 years, antibodies and antibody-related biologics have probably been the greatest growth area for pharmaceuticals. We have analysed the sequences of 819 which reached clinical trials and were granted an international non-proprietary name (INN). They represent about 371 different targets, 57 molecular formats and about 90 different variants of Fc regions, many designed to modulate binding to Fc receptors, either to suppress or to increase effector activity.
Hitherto, the relative merits of different variants have been almost impossible to assess, because of the diversity of assay methods and few have been compared head-to-head. At mAbsolve we are in the process of systematically cataloguing and synthesizing matched sets of antibodies which can then be tested using sensitive and precise methods to compare binding and cellular activity. The great majority of variants designed to eliminate binding to Fc-gamma receptors still have residual activity but we have discovered a new one which is completely ablated. This has potential applications whenever inflammatory responses are to be avoided and could improve the safety and therapeutic index of the next generation of antibody-related therapeutics.