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. Author manuscript; available in PMC: 2023 Mar 7.
Published in final edited form as: Mol Pharm. 2022 Feb 2;19(3):775–787. doi: 10.1021/acs.molpharmaceut.1c00373

Figure 1. Design of a panel of antibody variants based on four clinical-stage antibodies with grafted heavy chain CDR3s.

Figure 1.

Antibody variants were designed using the variable regions of four clinical-stage antibodies, namely humanized OKT3 (hOKT3), trastuzumab, siltuximab and lebrikizumab, that were grafted onto a common IgG1 scaffold. The heavy chain CDR3 (HCDR3) loops from ten clinical-stage antibodies (carlumab, muromonab, trastuzumab, bapineuzumab, farletuzumab, seribantumab, tocilizumab, girentuximab, lenzilumab and ustekinumab) were grafted onto each of the four clinical-stage antibody scaffolds. The panel of grafted antibodies was evaluated in terms of antibody self-association in a standard formulation condition (pH 6, 10 mM histidine) and physiological conditions (pH 7.4, PBS) to evaluate potential trade-offs between these two properties. The muromonab HCDR3 contains a cysteine residue that was mutated to serine in this study.