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Mice that produce hybrid antibodies

  • US 10,584,364 B2
  • Filed: 10/04/2013
  • Issued: 03/10/2020
  • Est. Priority Date: 12/07/2000
  • Status: Expired due to Term
First Claim
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1. A transgenic mouse whose genome comprises unrearranged human immunoglobulin heavy chain V, D, and J gene segments, wherein the unrearranged human immunoglobulin heavy chain V, D, and J gene segments in situ replace endogenous mouse immunoglobulin heavy chain V, D, and J gene segments, and the unrearranged human immunoglobulin heavy chain V, D, and J gene segments are operably linked to an endogenous mouse immunoglobulin heavy chain constant region gene, wherein the mouse immunoglobulin heavy chain constant region gene is located at an endogenous mouse immunoglobulin heavy chain constant region locus, wherein the unrearranged human immunoglobulin heavy chain V, D, and J gene segments are present in the germline of the mouse, wherein rearrangement of the unrearranged human immunoglobulin heavy chain V, D, and J gene segments in the mouse results in a rearranged human immunoglobulin heavy chain variable region gene linked to the mouse immunoglobulin heavy chain constant region gene, wherein the mouse in response to an antigen produces a hybrid antibody that comprises a human immunoglobulin heavy chain variable region encoded by the rearranged human immunoglobulin heavy chain variable region gene and a mouse immunoglobulin heavy chain constant region encoded by the mouse immunoglobulin heavy chain constant region gene, wherein mouse V gene segments are present upstream of the unrearranged human immunoglobulin heavy chain variable region gene segments, and wherein the endogenous immunoglobulin enhancer Eμ

  • remains intact upstream of the mouse immunoglobulin heavy chain constant region gene.

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