21

Protein / Protein Interface DesignExample: Bispecific IgG Antibodies Orthogonal Fab Interface Design

Lewis et al., Nature Biotechnology, 2014

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Correct Assembly Incorrect Assembly Incorrect Assembly

CH11-CH12/CL1-CL2 CH11-CH12/CL1-CL1 CH11-CH12/CL2-CL2

Accuracy of IgG BsAb Assembly2 ml Culture

CH11 (Pertuzumab) CL1 (Pertuzumab)

VHVRD1CH1CRD2 VLVRD1CλCRD2

CH12 (Matuzumab) CL2 (Matuzumab)

VHVRD2CH1WT VLVRD2CκWT

CL

10 ways for 2 unique L+H chains to come together. Only one needed.

CH1