Figure 2.

Computational design methods for minimizing stability trade-offs during antibody humanization. (a) A novel computational design method (CoDAH) for humanizing antibodies was used to predict humanizing mutations (green) for a murine antibody that otherwise would not be mutated using traditional CDR grafting humanizing designs (purple), as well as additional mutations common to both methods (blue). (b) Both traditional CDR grafting and CoDAH humanization results in antibodies with improved humanness, but the CoDAH designs also maintain, and even improve, rotomeric stability. (c) CoDAH designs also generally exhibit similar or improved thermal stability. (d) Both humanization methods result in antibody variants with similar affinity as the parental antibody, although several CDR grafting designs display reduced affinity. The figure is adapted with permission from a previous publication.²⁷