Chimaeric surrogate light chains (SLC) comprising human VpreB
AssigneeKymab Limited
InventorsAllan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
Life of this patent
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Abstract
The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.
Claims38
A mouse whose genome comprises an antibody heavy chain transgene, the transgene comprising
- (a) one or more human VH gene segments, one or more human D gene segments and one or more human JH gene segments operably connected upstream of a constant region gene so that the transgene is capable of undergoing VDJ recombination in vivo to produce an antibody gene comprising a rearranged VDJC encoding an antibody heavy chain having a human variable region and a constant region;
- the genome further comprising
- (i) a human VpreB gene capable of expressing a human VpreB, and
- (ii) a mouse or rat λ5 gene;
- wherein the mouse is capable of expressing a chimaeric surrogate light chain comprising human VpreB and mouse or rat λ5 for pairing with the heavy chain.
Dependencies are inferred from the claim text.