Figure 3

Schematic representation of Ab configurations. Schematic representation of different Abs’ configurations. (A) HcAb has its llama hinge linker: bivalent; (B) Camelid VHH: monovalent; (C) VHH-(G4S)3-VHH: bivalent; (D) VHH-(G4S)3-VHH-(G4S)3-VHH: trivalent; (E) Human classic Ab with its hinge linker: bivalent; (F) Llama VHH-human IgG4 hinge linker-IgG4 Fc chimeric HcAb: bivalent; (G) Llama VHH-human CH1-IgG4 hinge linker-IgG4 Fc chimeric heavy chain: bivalent; (H) VHH-llama long linker-VHH-human IgG4 hinge linker-IgG4 Fc: tetravalent; (I) VHH-(G4S)3 linker-VHH-human CH1-IgG4 hinge linker-IgG4 Fc chimeric Ab: tetravalent; (J) VHH-human IgG4 hinge linker-IgG4 Fc-llama long linker-VHH chimeric Ab: tetravalent. Thus, “(G4S)3” is a 15-peptide linker (amino acid sequence: GGGGSGGGGSGGGGS). “IgG4-hinge linker” means the hinge region between the human Fab and human IgG4 Fc (amino acid sequence: PPCPSCPAPEFLGGPS). “Llama long linker” means the hinge region between the llama Fab and llama IgG2 Fc (amino acid sequence: EPKIPQPQPKPQPQPQPQPKPQPKPEPECTCPKCP).