Identification and production of antigen-specific antibodies
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsYashu Liu, Chunguang Guo, Qian Zhang, Natasha Levenkova, Andrew J. Murphy, William Olson
Life of this patent
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Abstract
A method of obtaining a nucleotide sequence, from an immunized genetically modified non-human mammal, encoding an immunoglobulin variable domain of an antibody specific for a particular antigen is disclosed. A method for making antibodies against a particular antigen is also disclosed.
Claims31
A method of identifying a human immunoglobulin variable domain or CDR sequence of an antibody specific for an antigen, comprising:
- obtaining a plurality of peptide sequences of human immunoglobulin heavy chain and/or light chain variable domains that were obtained from a sample comprising a population of antibodies produced by a rodent immunized with the antigen, and
- interrogating a library of human immunoglobulin heavy chain and/or light chain variable domain sequences with the plurality of peptide sequences, wherein the library comprises a plurality of human immunoglobulin heavy chain and/or light chain variable domain sequences encoded by B cells of the immunized rodent, thereby obtaining a human immunoglobulin variable domain or CDR sequence of an antibody specific for the antigen, and
- wherein the immunized rodent comprises in its germline genome:
- an immunoglobulin heavy chain variable region comprising one or more human heavy chain V gene segments, one or more human D gene segments, and one or more human heavy chain J gene segments, wherein the heavy chain variable region is operably linked to a constant region, and
- an immunoglobulin light chain variable region comprising one or more human light chain V gene segments and one or more human light chain J gene segments, wherein the light chain is operably linked to a constant region.
A method of identifying a human immunoglobulin variable domain or CDR sequence of an antibody specific for an antigen, comprising:
- obtaining a library of human immunoglobulin heavy chain and/or light chain variable domain sequences comprising a plurality of human immunoglobulin heavy chain and/or light chain variable domain sequences encoded by B cells of a rodent immunized with the antigen,
- interrogating the library with a plurality of peptide sequences of human immunoglobulin heavy chain and/or light chain variable domains that were obtained from a sample comprising a population of antibodies produced by the rodent immunized with the antigen, and
- wherein the immunized rodent comprises in its germline genome:
- an immunoglobulin heavy chain variable region comprising one or more human heavy chain V gene segments, one or more human D gene segments, and one or more human heavy chain J gene segments, wherein the heavy chain variable region is operably linked to a murine constant region, and
- an immunoglobulin light chain variable region comprising one or more human light chain V gene segments and one or more human light chain J gene segments, wherein the light chain is operably linked to a murine constant region.
Dependencies are inferred from the claim text.