protein / protein interface design - cyrus bio21 protein / protein interface design...

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21 Protein / Protein Interface Design Example: 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 CH1 1 -CH1 2 /CL 1 -CL 2 CH1 1 -CH1 2 /CL 1 -CL 1 CH1 1 -CH1 2 /CL 2 -CL 2 Accuracy of IgG BsAb Assembly 2 ml Culture CH1 1 (Pertuzumab) CL 1 (Pertuzumab) VH VRD1 CH1 CRD2 VL VRD1 Cλ CRD2 CH1 2 (Matuzumab) CL 2 (Matuzumab) VH VRD2 CH1 WT VL VRD2 Cκ WT CL 10 ways for 2 unique L+H chains to come together. Only one needed. CH1

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Page 1: Protein / Protein Interface Design - Cyrus Bio21 Protein / Protein Interface Design Example:Bispecific IgG Antibodies Orthogonal Fab Interface Design Lewis et al., Nature Biotechnology,

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

Lewis et al., Nature Biotechnology, 2014

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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

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