Human lambda light chain mice
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
Life of this patent
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Abstract
Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.
Claims29
A method for making an antibody comprising a human λ variable domain, the method comprising the steps of:
- (a) exposing a genetically modified mouse to an antigen, wherein the genetically modified mouse has a genome comprises an immunoglobulin locus comprising human Vλ and Jλ gene segments operably linked to a mouse Cκ gene such that the mouse expresses an immunoglobulin light chain that comprises a human λ variable domain derived from the Vλ and Jλ gene segments fused with a mouse κ constant domain;
- (b) allowing the genetically modified mouse to develop an immune response to the antigen;
- and
- (c) isolating from the mouse of (b) an antibody specific for the antigen, wherein the antibody comprises the human λ variable domain derived from the human Vλ and Jλ gene segments.
A method for making a cell that expresses an antibody comprising a human λ variable domain, comprising the steps of:
- (a) exposing a genetically modified mouse to an antigen, wherein the genetically modified mouse has a genome comprises an immunoglobulin locus comprising human Vλ and Jλ gene segments operably linked to a mouse Cκ gene such that the mouse expresses an immunoglobulin light chain that comprises a human λ variable domain derived from the Vλ and Jλ gene segments fused with a mouse κ constant domain;
- (b) allowing the genetically modified mouse to develop an immune response to the antigen;
- and
- (c) isolating from the mouse of (b) a cell that expresses an antibody specific for the antigen, wherein the antibody comprises the human λ variable domain derived from the human Vλ and Jλ gene segments.
Dependencies are inferred from the claim text.