Symposium Sessions (Day1, Day2, Day3)
Basic Sessions (Day1, Day2, Day3)
Young Researchers' Sessions (Day1, Day2, Day3)
Symposium Sessions
- Day 1, May 15（Mon.） 13:53-14:15 Room A (Special Conference Room)
-
1A-S-1353 PDF
Clip Formation in the Complementarity Determining Region of Pharmaceutical Antibody Affects its Properties and Higher Order Structure
The presence of monoclonal antibody (mAb) fragments in pharmaceutical mAb products is a critical quality attribute and should be controlled for safety. Several mAb fragments derived from clip formation in the complementarity determining regions (CDRs), as well as from cleavage in the hinge region, have been reported. However, the properties of CDR-clipped variants are not fully understood because of difficulties in separating them from intact mAbs under non-denaturing condition due to similarities in size. We have established a method for separating CDR-clipped variants under non-denaturing condition using an appropriate size exclusion chromatography column.1) We provide a comprehensive characterization of a CDR-clipped variant from bevacizumab.2) The variant exhibited a lower affinity for antigen, neonatal Fc receptor (FcRn), and Fcγ receptor (FcγR). The effects of clip formation in CDR H3 on the higher order structure were analyzed by hydrogen/deuterium exchange mass spectrometry, and the observed changes in the structures of the VH, CH2, and VL domains were in agreement with the lowered affinity for antigen, FcRn, and FcγR. These findings suggest that clip formation in the CDR may affect the efficacy, safety, and pharmacokinetics of pharmaceutical mAbs.