Figure 1.

Humanization of nonhuman monoclonal antibodies by a combination of CDR grafting and V gene shuffling. Nonhuman sequences are shown in gray, human sequences in white. In the first step, a chimeric nonhuman/human Fd fragment is used as a template for the selection of a human light chain that contains the grafted LCDR3 loop of the nonhuman light chain. In the second step, a human Fd fragment that contains the grafted HCDR3 loop of the nonhuman Fd fragment is selected. The sequential V gene shuffling procedure is based on phage display. LCDR3, complementarity-determining region 3 of light chain; HCDR3, complementarity-determining region 3 of heavy chain.