Patent ID: 7981843

Claim:
A method of making an antibody having a binding specificity of a reference antibody that binds to an antigen, the method comprising a) recombinantly joining a heavy chain CDR3D segment from the reference antibody, which CDR3D segment is linked to a FR4, to an unselected member of a diverse population of human FR1-CDR1-FR2-CDR2-FR3 V H segments from human cells, thereby creating a library of V H regions that comprises members that have the reference antibody heavy chain CDR3D segment linked to diverse unselected human FR1-CDR1-FR2-CDR2-FR3 V H segments; b) recombinantly joining a light chain CDR3BSD from the reference antibody, which reference antibody light chain CDR3BSD is linked to a Jκ germline FR4 to provide a light chain CDR3BSD-Jκ germline FR4, to an unselected member of a diverse population of human FR1-CDR1-FR2-CDR2-FR3V L segments obtained from human cells, thereby creating a library of V L regions that comprises members that have the CDR3BSD-Jκ germline FR4 linked to diverse unselected human FR1-CDR1-FR2-CDR2-FR3V L segments; c) combining the libraries of step a and step b to create an antibody library wherein the members of the antibody library comprise a diversity of V H regions and a diversity of V L regions that have the reference antibody heavy chain CDR3D segment and the light chain CDR3BSD-Jκ germline FR4; and d) screening the library of step c and isolating a member of the library that binds to the antigen.