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Histidine engineered light chain antibodies and genetically modified non-human animals for generating the same

  • US 9,332,742 B2
  • Filed: 05/06/2015
  • Issued: 05/10/2016
  • Est. Priority Date: 03/16/2012
  • Status: Active Grant
First Claim
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1. A genetically modified non-human animal comprising in its germline an immunoglobulin light chain locus comprising two unrearranged human Vκ

  • gene segments and one or more unrearranged human Jκ

    gene segment(s) operably linked to an immunoglobulin light chain constant region sequence,wherein the two unrearranged human Vκ

    gene segments are human Vκ

    1-39 and Vκ

    3-20 gene segments each comprising one or more substitutions of a non-histidine codon with a histidine codon, andwherein the human Vκ and



    gene segments are capable of rearranging and the human Vκ and



    gene segments encode a human light chain variable domain comprising one or more histidines at a position selected from the group consisting of 105, 106, 107, 108, 109, 111 (according to IGMT numbering), and a combination thereof, wherein the one or more histidines are derived from the one or more substitutions.

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