OVERCOMING TECHNICAL CHALLENGES OF BISPECIFIC AND MULTI-SPECIFIC ANTIBODIES USING NOVEL TECHNOLOGY PLATFORMS

Abstract

Abstract Background Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) are a growing class of next generation biotherapeutics. However, multiple challenges, such as chain mispairing and developability issues are often associated with these complex modalities. Methods WuXi Biologics has established bsAb and msAb engineering and development platforms. By replacing CH1/CL domains of one antibody Fab by corresponding T cell receptor (TCR) Cβ/Cα domains, WuXiBody® bsAb technology can ensure the correct heavy-light chain pairing. WuXi Biologics has developed the SDArBody™ platform, which utilizes single domain antibodies (VHH) as building blocks to facilitate the exploration of more complex biologics, such as msAbs. Results as shown in case studies, the WuXiBody® technology is able to assemble regular mAbs in a ‘plug-and-play’ manner, and that the SDArBody® can be utilized to identify VHH leads and then assemble into msAbs. Both platforms can generate highly functional bsAb and msAb with good developability. Conclusions The establishment of WuXiBody® and SDArBody® platforms could greatly meet the needs of biologics developers in pursuit of different biology and therapeutic approaches through bsAbs and msAbs.