Patent ID: 9505827
Filing Date: 2016-11-29
CPC Classification: A01K,A61K,C07K,C12N

Claim Text:
1. A transgenic mouse having a germline with a homozygous immunoglobulin heavy chain (IgH) locus comprising unrearranged human IgH variable region gene segments comprising Vs, Ds and Js at an endogenous locus operatively linked to an IgH constant (C) region comprising an endogenous C segment at an IgH locus; wherein said homozygous IgH locus comprises in 5′ to 3′ transcriptional orientation said unrearranged human Vs, Ds and Js comprising a 3′ JH gene segment, a human/mouse chimeric DNA junction, an enhancer, and said operatively linked C region; wherein said homozygous chimeric IgH locus comprises a chimeric J/C intron comprising human DNA downstream of and naturally contiguous with said 3′ JH gene segment, said human DNA being contiguous with mouse J/C intronic DNA upstream of said enhancer, and wherein said human DNA joins said mouse J/C intronic DNA at said human/mouse chimeric junction within said J/C intron, wherein DNA between said 3′ human JH segment and said human/mouse chimeric DNA junction is less than 2 kb, said germline comprising all or part of mouse IgH variable region DNA; wherein 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 antibody comprising a chimeric Ig heavy chain comprising a human IgH variable 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 operatively linked to an IgH constant (C) region comprising an endogenous C segment of an IgH locus to provide subsequent generation mice, wherein a said subsequent generation mouse comprises: (a) in its germline an homozygous IgH locus comprising unrearranged human IgH variable region gene segments operatively linked to an IgH constant (C) region comprising an endogenous C segment of an IgH locus, and (b) in its germline all or part of mouse IgH variable region DNA; and (c) wherein said IgH locus of said subsequent generation mouse is capable of undergoing V, D, J joining; (d) wherein said subsequent generation mouse is capable, upon stimulation with antigen, of producing antibody comprising a chimeric Ig heavy chain comprising a human IgH variable region; and (e) is capable of breeding with a mouse having a germline with a homozygous IgH locus comprising unrearranged human IgH variable region gene segments operatively linked to an IgH constant (C) region comprising an endogenous C segment of an IgH locus to provide further subsequent generation mice.