Analytical characterization of broadly neutralizing antibody CAP256LS heavy chain clipping during manufacturing development

Biotechnol Prog. 2022 Aug 13;e3296. doi: 10.1002/btpr.3296. Online ahead of print.

Abstract

Broadly neutralizing antibody (bNAb) CAP256-VRC26.25 (abbreviated CAP256LS), a human IgGI monoclonal antibody targeting the V1V2 site of the HIV-1 envelope, has demonstrated high therapeutic potential as a broadly neutralizing monoclonal antibody against HIV-1. During the process development, a heavy chain fragmentation (clipping) was observed, that led to a relative potency reduction. In this report, we highlighted a series of process and product mitigation strategies deployed to advance this product. We have detailed how analytical characterization tools, especially the microchip reduced capillary gel electrophoresis (CGE-SDS), played a pivotal role in identifying the development issues and in providing measurements to guide implementation of mitigation strategies.

Keywords: CAP256LS; capillary gel electrophoresis (CGE); heavy chain clipping; monoclonal antibody; protease.