Transgenic transchromosomal rodents for making human antibodies
AssigneesE. R. Squibb & Sons, Inc., Kyowa Hakko Kirin Co., Ltd.
InventorsKazuma Tomizuka, Isao Ishida, Nils Lonberg, Edward L. Halk
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Abstract
The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.
Claims17
A method for generating a plurality of B cells expressing human antibody sequences, the method comprising immunizing a transgenic mouse to generate a plurality of B cells expressing human antibody sequences, wherein the transgenic mouse comprises two human immunoglobulin loci, wherein one human immunoglobulin locus is a human heavy chain locus located on an autonomous transchromosome comprising a fragment of human chromosome 14 having a human chromosome 14 centromere, and the other human immunoglobulin locus is a human light chain locus transgene integrated into the mouse genome.
A method for generating a human antibody that binds to a predetermined antigen, the method comprising:
- immunizing a transgenic mouse with the predetermined antigen;
- and
- isolating the human antibody from the immunized transgenic mouse,
- wherein the transgenic mouse comprises two human immunoglobulin loci, wherein one human immunoglobulin locus is a human heavy chain locus located on an autonomous transchromosome comprising a fragment of human chromosome 14 having a human chromosome 14 centromere, and the other human immunoglobulin locus is a human light chain locus transgene integrated into the mouse genome.
A method for generating antigen-specific hybridomas secreting a human antibody, the method comprising:
- immunizing a transgenic mouse with a predetermined antigen;
- fusing lymphocytes from the transgenic mouse with immortalized cells to form hybridoma cells;
- and
- identifying hybridomas that secrete a human antibody that specifically binds to the predetermined antigen,
- wherein the transgenic mouse comprises two human immunoglobulin loci, wherein one human immunoglobulin locus is a human heavy chain locus located on an autonomous transchromosome comprising a fragment of human chromosome 14 having a human chromosome 14 centromere, and the other human immunoglobulin locus is a human light chain locus transgene integrated into the mouse genome.
A method for generating a human antibody that binds to a predetermined antigen, the method comprising:
- immunizing a transgenic mouse with a predetermined antigen;
- fusing lymphocytes from the transgenic mouse with immortalized cells to form hybridoma cells;
- and
- screening hybridoma cells formed for the presence of antigen reactive antibodies, wherein the transgenic mouse comprises two human immunoglobulin loci, wherein one human immunoglobulin locus is a human heavy chain locus located on an autonomous transchromosome comprising a fragment of human chromosome 14 having a human chromosome 14 centromere, and the other human immunoglobulin locus is a human light chain locus transgene integrated into the mouse genome.
Dependencies are inferred from the claim text.