Patent ID: 7754450

Claim:
A method for producing hybridoma cells producing antibodies from in vitro immunized immunoglobulin-producing cells comprising: (a) combining donor cells comprising immunoglobulin-producing cells with an immunogenic antigen in vitro; (b) fusing said immunoglobulin-producing cells with myeloma cells to form parental hybridoma cells; (c) incubating said parental hybridoma cells in the presence of at least one chemical inhibitor of mismatch repair, thereby forming hypermutated hybridoma cells; (d) removing said chemical inhibitor of mismatch repair from said hypermutated hybridoma cells, thereby stabilizing the genome of said hypermutated hybridoma cells, (e) screening antibodies produced from said hypermutated hybridoma cells for binding to antigen; and (f) selecting hypermutated hybridoma cells that produce antibodies with higher affinity for said antigen than antibodies produced by said parental hybridoma cells; thereby producing hybridoma cells producing antibodies having higher affinity for said antigen than antibodies produced by said parental hybridoma cells.