Animal Models and Therapeutic Molecules

摘要

The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

主权项

1. A transgenic mouse having a germline with a homozygous immunoglobulin heavy chain (IgH) locus, a said homozygous IgH locus comprising unrearranged human IgH variable region gene segments positioned upstream of a constant (C) region comprising an endogenous C gene segment of an IgH locus;
wherein said homozygous IgH locus comprises in 5′ to 3′ transcriptional orientation a human JH gene segment, a human/mouse chimeric DNA junction, an enhancer, and said C region, wherein said homozygous IgH locus comprises mouse 129 strain DNA positioned downstream of said human/mouse chimeric DNA junction and upstream of said enhancer; wherein a said homozygous IgH locus of said mouse is capable of undergoing V, D, J joining; wherein said transgenic mouse is capable, upon stimulation with antigen, of producing an antibody comprising a chimeric Ig heavy chain comprising a human heavy chain V region; and wherein said transgenic mouse is capable of breeding with a second transgenic mouse, said second transgenic mouse having a germline with a homozygous IgH locus comprising unrearranged human IgH variable region gene segments positioned upstream of a constant (C) region comprising an endogenous C segment of an IgH locus to provide subsequent generation mice comprising mice comprising males and females comprising in their germline an homozygous IgH locus comprising unrearranged human IgH variable region gene segments positioned upstream of a constant (C) region comprising an endogenous C segment of an IgH locus.