Robust production of monovalent bispecific IgG antibodies through novel electrostatic steering mutations at the C_H1-C_λ interface.

ABSTRACT: Bispecific antibodies represent an increasingly large fraction of biologics in therapeutic development due to their expanded scope in functional capabilities. Asymmetric monovalent bispecific IgGs (bsIgGs) have the additional advantage of maintaining a native antibody-like structure, which can provide favorable pharmacology and pharmacokinetic profiles. The production of correctly assembled asymmetric monovalent bsIgGs, however, is a complex engineering endeavor due to the propensity for non-cognate heavy and light chains to mis-pair. Previously, we introduced the DuetMab platform as a general solution for the production of bsIgGs, which utilizes an engineered interchain disulfide bond in one of the C_H1-C_L domains to promote orthogonal chain pairing between heavy and

SUBMITTER: Bagert JD 

PROVIDER: S-EPMC10629431 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature