CDR walking

Yang et al. [96] also increased the binding affinity of an antibody from 6.3 nM to 15 pM by a similar combination of CDR mutagenesis and shuffling, which they refer to as CDR walking . 

Fig. 5. Affinity maturation of antibodies by CDR walking. CDR walking involves the sequential or parallel optimization of CDRs by randomization of key recognition sequences and subsequent selection by phage display. Shown is a combination of sequential and parallel CDR optimization that was used in the affinity maturation of humanized LM609 (Rader et al, in preparation). CDR3 of the light chain was optimized first, followed by a parallel optimization of CDR1 and CDR3 of the heavy chain. Optimized CDR1 and CDR3 of the heavy chain were combined in the last step.

Yang WP, Green K, Pinz-Sweeney S, Briones ATB, Barbas CF, CDR walking mutagenesis for the affinity maturation of a potent human anti-HIV 1 antibody into the picomolar range, J. Mol. Biol., 254 392-403, 1995. 

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