Genetically modified mice that produce hybrid antibodies
First Claim
1. A transgenic mouse whose genome comprises unrearranged human immunoglobulin heavy chain V, D, and J gene segments contained on a human genomic DNA fragment that is greater than 100 kb, 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 heavy chain constant region gene, wherein the mouse 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 human immunoglobulin heavy chain V, D, and J gene segments in the mouse results in a rearranged human heavy chain variable region gene operably linked to the mouse heavy chain constant region gene, wherein the mouse in response to an antigen produces a hybrid antibody that comprises a human heavy chain variable region encoded by the rearranged human heavy chain variable region gene and a murine immunoglobulin Fc region encoded by the mouse heavy chain constant region gene, wherein mouse V gene segments are present upstream of the unrearranged human heavy chain immunoglobulin V, D, and J gene segments, and wherein the endogenous immunoglobulin enhancer Eμ
- remains intact upstream of the endogenous mouse heavy chain immunoglobulin constant region gene.
2 Assignments
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Accused Products
Abstract
A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
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Citations
2 Claims
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1. A transgenic mouse whose genome comprises unrearranged human immunoglobulin heavy chain V, D, and J gene segments contained on a human genomic DNA fragment that is greater than 100 kb, 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 heavy chain constant region gene, wherein the mouse 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 human immunoglobulin heavy chain V, D, and J gene segments in the mouse results in a rearranged human heavy chain variable region gene operably linked to the mouse heavy chain constant region gene, wherein the mouse in response to an antigen produces a hybrid antibody that comprises a human heavy chain variable region encoded by the rearranged human heavy chain variable region gene and a murine immunoglobulin Fc region encoded by the mouse heavy chain constant region gene, wherein mouse V gene segments are present upstream of the unrearranged human heavy chain immunoglobulin V, D, and J gene segments, and wherein the endogenous immunoglobulin enhancer Eμ
- remains intact upstream of the endogenous mouse heavy chain immunoglobulin constant region gene.
- View Dependent Claims (2)
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