Patent ID: 7501552

Claim:
A method for obtaining a somatically mutated antibody that binds to a predetermined antigen, which method comprises: (a) immunizing a transgenic mouse with a predetermined antigen, wherein the transgenic mouse has a genome comprising inactivated endogenous murine heavy chain variable gene regions, and further comprising an unrearranged human heavy chain immunoglobulin variable region operably linked to a mu constant region gene segment, wherein the unrearranged human heavy chain variable region comprises multiple human V H gene segments, multiple human D gene segments, and multiple human J H gene segments, and wherein the mu constant region is selected from the group consisting of (i) a human S-mu sequence and a human or mouse mu coding sequence and (ii) a mouse S-mu sequence and a human or mouse mu coding sequence, (b) removing B lymphocytes from the transgenic mouse, (c) identifying mouse IgG isotype immunoglobulin molecules that bind to the predetermined antigen expressed by the B lymphocytes; and (d) isolating the IgG isotype immunoglobulin molecules that bind to the predetermined antigen, whereby a somatically mutated antibody that binds to the predetermined antigen is obtained from the B lymphocytes of step (c).