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US 9,253,965 B2Granted
Animal models and therapeutic molecules
AssigneeKymab Limited
InventorsAllan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Dominik Spensberger, Hui Liu, Jasper Clube
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Abstract
The invention discloses methods for the generation of chimaeric human-nonhuman antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising the disclosed antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in the disclosed methods.
Claims23
A transgenic mouse having a genome comprising a homozygous recombinant immunoglobulin light chain (IgL) locus,
- said locus comprising unrearranged human V region light chain gene segments comprising the functional V and J gene segments from Vλ2-18 to Cλ7 of a human λ light chain locus, wherein said unrearranged human V region light chain gene segments are positioned
- (i) at an endogenous mouse immunoglobulin light chain locus comprising an endogenous enhancer and
- (ii) upstream of a constant region,
- said recombinant light chain locus being functional to rearrange to express an immunoglobulin light chain comprising a human V region,
- wherein said recombinant immunoglobulin light chain locus comprises human Vλ and Jλ gene segments,
- wherein said mouse comprises splenic B cells expressing immunoglobulin light chains comprising λ variable regions,
- wherein a plurality of said immunoglobulin light chains comprises a plurality of human λ variable regions,
- wherein said mouse comprises immunoglobulin gamma antibody comprising λ variable regions, and wherein the mouse expresses more immunoglobulin light chain comprising a human Vλ region than immunoglobulin light chain comprising a mouse Vλ region,
- wherein said mouse exhibits usage of human Jλ gene segments in splenic B cells that is typical of the usage of J λ segments in splenic B cells of humans, or wherein said mouse exhibits usage of human V λ gene segments in splenic B cells typical of the usage of Vλ gene segments in splenic B cells of humans or both.
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