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This review summarizes an illustrative set of data from our research on the reconstruction of structurally complex protein surfaces, i.e. those that fail to be mimicked properly by linear peptides. In the past 5 years, our newly developed CLIPS™ technology has proven an extremely valuable tool for 1) binding site mapping of therapeutically relevant mAbs, 2) generating hyperimmune sera via immunization with CLIPS peptides, and 3) the generation of monoclonal antibodies (mAbs) via the use of hybridoma technology. We currently have data available for more than 50 therapeutic targets. The examples described in this review illustrate the potential of this powerful new technology.