Transgenic non-human animals for producing heterologous and chimeric antibodies
First Claim
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1. A method for preparing a human antibody, which method comprises culturing a host cell comprising:
- (i) a human immunoglobulin heavy chain recombinant construct comprising a nucleic acid molecule that encodes a human heavy chain variable region from a mouse B lymphocyte operably linked to a human heavy chain constant region, and (ii) a human immunoglobulin light chain recombinant construct comprising a nucleic acid molecule that encodes a human light chain variable region from a mouse B lymphocyte operably linked to a human light chain constant region, wherein the mouse B lymphocyte is from a transgenic mouse having an unrearranged human heavy chain immunoglobulin variable region comprising a plurality of human VH gene segments, a plurality of human D gene segments and a plurality of human JH gene segments, and having an unrearranged human light chain immunoglobulin variable region comprising a plurality of human VL gene segments and a plurality of human JL gene segments;
under conditions that permit expression of the human heavy chain and human light chain to form an antibody.
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Abstract
The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.
148 Citations
15 Claims
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1. A method for preparing a human antibody, which method comprises culturing a host cell comprising:
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(i) a human immunoglobulin heavy chain recombinant construct comprising a nucleic acid molecule that encodes a human heavy chain variable region from a mouse B lymphocyte operably linked to a human heavy chain constant region, and (ii) a human immunoglobulin light chain recombinant construct comprising a nucleic acid molecule that encodes a human light chain variable region from a mouse B lymphocyte operably linked to a human light chain constant region, wherein the mouse B lymphocyte is from a transgenic mouse having an unrearranged human heavy chain immunoglobulin variable region comprising a plurality of human VH gene segments, a plurality of human D gene segments and a plurality of human JH gene segments, and having an unrearranged human light chain immunoglobulin variable region comprising a plurality of human VL gene segments and a plurality of human JL gene segments;
under conditions that permit expression of the human heavy chain and human light chain to form an antibody. - View Dependent Claims (2, 3, 4, 5)
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- 6. A method for constructing a human heavy chain, which method comprises operably linking a nucleic acid molecule encoding a human heavy chain variable region to a nucleic acid molecule encoding a human heavy chain constant region, wherein the human heavy chain variable region is isolated from a mouse B lymphocyte, wherein the mouse B lymphocyte is from a transgenic mouse having an unrearranged human heavy chain immunoglobulin variable region comprising a plurality of human VH gene segments, a plurality of human D gene segments, and a plurality of human JH gene segments.
- 10. A method for constructing a human light chain, which method comprises operably linking a nucleic acid molecule encoding a human light chain variable region to a nucleic acid molecule encoding a human light chain constant region, wherein the human light chain variable region is isolated from a mouse B lymphocyte, wherein the mouse comprises an unrearranged human light chain immunoglobulin variable region comprising a plurality of human VL gene segments and a plurality of human JL gene segments.
Specification