Cells, vertebrates, populations and methods
AssigneeKymab Limited
InventorsE-Chiang Lee, Wei Wang, John Kenneth Blackwood, Roberto Magliozzi, Andrew Wood
Life of this patent
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Abstract
The invention relates to cells and non-human vertebrates for producing antibody chains (eg, truly common L or H chains), in particular for use in producing multi-specific antibodies useful for therapy or diagnosis.
Claims19
An isolated cell comprising a first antibody kappa light chain locus comprising in 5′ to 3′ direction:
- (a) a light chain Eiκ intronic enhancer;
- (b) a rearranged antibody variable region encoding a first rearranged antibody Vκ domain;
- and
- (c) an antibody light chain constant region encoding a kappa light chain C domain;
- wherein said kappa light chain locus is operable to express an antibody chain comprising in N- to C-terminal direction said rearranged antibody Vκ domain and said kappa light chain C domain, and wherein the isolated cell is not a human embryonic stem cell or a cell of a human embryo.
An isolated population of nonhuman mammalian cells comprising a plurality of spleen cells, bone marrow cells, B-cells or blood cells, wherein each cell in said population of cells comprises a first antibody kappa light chain locus, wherein the locus comprises in 5′ to 3′ direction:
- (a) a light chain Eiκ intronic enhancer;
- (b) a rearranged antibody variable region encoding a first rearranged antibody Vκ domain;
- and
- (c) an antibody light chain constant region encoding a kappa light chain C domain;
- wherein said kappa light chain locus is operable to express an antibody chain comprising in N- to C-terminal direction said rearranged antibody Vκ domain and said kappa light chain C domain.
An isolated population of hybridoma cells, CHO cells, HEK cells, MEF cells, COS cells, or HeLa cells, wherein each cell in said population of cells comprises a first antibody kappa light chain locus, wherein the locus comprises in 5′ to 3′ direction:
- (a) a light chain Eiκ intronic enhancer;
- (b) a rearranged antibody variable region encoding a first rearranged antibody Vκ domain;
- and
- (c) an antibody light chain constant region encoding a kappa light chain C domain;
- wherein said kappa light chain locus is operable to express an antibody chain comprising in N- to C-terminal direction said rearranged antibody Vκ domain and said kappa light chain C domain, wherein the population of cells expresses at least 10 different antibody species, wherein
- (i) at least 95% of the antibodies share the same kappa light chain VL domain and the population comprises at least 10 different VH domain species;
- or
- (ii) the antibodies comprise kappa light chain VL domains derived from the recombination of a first Vκ gene segment and a first Jκ gene segment, wherein at least 95% of all said kappa light chain VL domains derived from said recombination comprise the same VL amino acid sequence and the population comprises at least 10 different VH domain species.
Dependencies are inferred from the claim text.