Genetic engineering of non-human animals for the production of chimeric antibodies

摘要

The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

主权项

1. An in vitro method of producing a mammalian cell whose genome comprises a synthetic transgene that encodes a chimeric immunoglobulin heavy chain, wherein said immunoglobulin heavy chain comprises a chimeric constant region, said method comprising the steps of:
designing one or more DNA constructs in silico, wherein said one or more constructs comprise polynucleotide sequences comprising one or more human V, D and/or J gene segments and a chimeric constant region comprising a human CH1 gene segment, a human upper hinge region gene segment, a non-human CH2 gene segment, and a non-human CH3 segment; producing said one or more DNA constructs; and introducing the one or more constructs into the genome of a mammalian cell, wherein the genome of the mammalian cell comprises the synthetic transgene that encodes the chimeric immunoglobulin heavy chain comprising the chimeric constant region comprising a human CH1, a human upper hinge region, a non-human CH2, and a non-human CH3.