Bispecific antibodies are relative newcomers in targeting various cancers and immunological disorders, and they bring inherent processing, formulation and manufacturing related challenges and opportunities.<br/>The long-term physical stability of fully assembled Knob-in-hole bispecific antibodies showed an acceptable stability profile. However, when we studied the pre-assembly knob half antibodies, we observed that they favor pH-dependent homodimer formation. On the other hand, pre-assembly hole half antibodies form mixed population of monomer species that change conformation in a pH and temperature-dependent manner.<br/>In order to understand why these half antibodies change conformations, we employed various analytical and computer simulation tools such as SEC, HIC, DSC, static light scattering (SLS), analytical ultra centrifugation (AUC) and molecular dynamics (MD) simulations. Our results suggest that increased hydrophobic interaction between half antibodies and between domains due to algycosylation and pH-induced microenvironment modulation could be the cause of changes in conformation.

pH-induced microenvironment modulation results in conformational changes in Knob and hole half bispecific antibodies

254th National Meeting (2017)

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