Patent ID: 8835712

Claim:
A method of improving transgene stability of a transgenic mouse hybridoma cell expressing a human antibody capable of specifically binding a predetermined antigen, the method comprising: breeding a first transgenic mouse, the first transgenic mouse comprising a first human immunoglobulin locus that is a human heavy chain locus carried by a transchromosome comprising a fragment of human chromosome 14 having a human chromosome 14 centromere, with a second transgenic mouse, the second transgenic mouse comprising a second human immunoglobulin locus that is a human light chain locus carried by a transgene inserted within an endogenous mouse chromosome; obtaining a third transgenic mouse from the breeding, the third transgenic mouse comprising both the first and second human immunoglobulin loci, wherein the human light chain locus transgene is integrated into the genome of the third transgenic mouse; immunizing the third transgenic mouse, or its progeny, with the predetermined antigen; isolating B cells from the immunized mouse; and fusing the B cells with immortalized cells to obtain hybridoma cells that express the human antibody capable of specifically binding the predetermined antigen and that exhibit improved transgene stability.