Non-human mammals for the production of chimeric antibodies
First Claim
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1. A mouse whose genome comprises a transgene comprising an immunoglobulin heavy chain (IgH) locus, or a portion thereof, wherein said IgH locus comprises in operable linkage from 5′
- to 3′
an unrearranged DNA sequence of a human variable heavy (VH) gene segment, a diversity heavy (DH) gene segment, and a human joining heavy (JH) gene segment, operably linked to a constant region gene comprising a human CH1 exon, a human Cupper hinge exon, a human or mouse Cmiddle hinge exon, a mouse CH2 exon and a mouse CH3 exon, wherein the human CH1 exon is selected from the group consisting of a human mu constant region (Cμ
) CH1 exon, a human delta constant region (Cδ
) CH1 exon, a human gamma-1 constant region (Cγ
l) CH1 exon, a human gamma-2 constant region (Cγ
2) CH1 exon, a human gamma-4 constant region (Cγ
4) CH1 exon, a human alpha constant region (Cα
) CH1 exon, and a human epsilon constant region (Cε
) CH1 exon, wherein the IgH locus further comprise an IgH non-coding region and wherein during B cell development, the IgH locus undergoes gene rearrangement and expresses a chimeric immunoglobulin heavy chain comprising a human heavy chain variable domain and a chimeric IgH constant domain.
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Abstract
The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in 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.
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12 Claims
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1. A mouse whose genome comprises a transgene comprising an immunoglobulin heavy chain (IgH) locus, or a portion thereof, wherein said IgH locus comprises in operable linkage from 5′
- to 3′
an unrearranged DNA sequence of a human variable heavy (VH) gene segment, a diversity heavy (DH) gene segment, and a human joining heavy (JH) gene segment, operably linked to a constant region gene comprising a human CH1 exon, a human Cupper hinge exon, a human or mouse Cmiddle hinge exon, a mouse CH2 exon and a mouse CH3 exon, wherein the human CH1 exon is selected from the group consisting of a human mu constant region (Cμ
) CH1 exon, a human delta constant region (Cδ
) CH1 exon, a human gamma-1 constant region (Cγ
l) CH1 exon, a human gamma-2 constant region (Cγ
2) CH1 exon, a human gamma-4 constant region (Cγ
4) CH1 exon, a human alpha constant region (Cα
) CH1 exon, and a human epsilon constant region (Cε
) CH1 exon, wherein the IgH locus further comprise an IgH non-coding region and wherein during B cell development, the IgH locus undergoes gene rearrangement and expresses a chimeric immunoglobulin heavy chain comprising a human heavy chain variable domain and a chimeric IgH constant domain. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- to 3′
Specification