methods of producing a mouse and an antibody and of selecting a human heavy chain variable region for the production of an antigen binding protein, use of a genetically modified mouse in the production of an antigen binding protein as well as chimeric antibody and hybridoma

摘要

methods of producing a mouse and an antibody and of selecting a human heavy chain variable region for the production of an antigen binding protein, use of a genetically modified mouse in the production of an antigen binding protein as well as chimeric antibody and hybridoma. The present invention relates to a method of producing genetically modified mouse, wherein the mouse is unable to rearrange and express an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two variable domains of the mouse. human light chain encoded by human immunoglobulin sequences operably linked to the mouse constant kappa (?) gene at the endogenous mouse locus?, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two segments light chain variable region genetics and a constant domain? of a mouse, and a human heavy chain variable domain and a mouse heavy chain constant domain of an endogenous mouse heavy chain locus. Bispecific epitope binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain comprising a variable domain derived from one of two different human light chain variable region gene segments.