Enlarging the repertoire of therapeutic monoclonal antibodies platforms: domesticating half molecule exchange to produce stable IgG4 and IgG1 bispecific antibodies

- Fab arm exchange is the swapping of Heavy-Light chain units between two IgG4.
- Hinge and CH3 domain residues determine IgG4 ability to engage in Fab arm exchange.
- S228P mutation in the hinge region blocks Fab-arm exchange in vitro and in vivo.
- S228P confers stability properties to IgG4 equivalent to those of IgG1.
- IgG4 Fab arm exchange principles can be used to produce bispecific IgG1 in vitro.