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Transgenic non-human animals for producing chimeric antibodies

  • US 7,501,552 B2
  • Filed: 12/10/2004
  • Issued: 03/10/2009
  • Est. Priority Date: 08/28/1991
  • Status: Expired due to Fees
First Claim
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1. A method for obtaining a somatically mutated antibody that binds to a predetermined antigen, which method comprises:

  • (a) immunizing a transgenic mouse with a predetermined antigen, wherein the transgenic mouse has a genome comprising inactivated endogenous murine heavy chain variable gene regions, and further comprising an unrearranged human heavy chain immunoglobulin variable region operably linked to a mu constant region gene segment,wherein the unrearranged human heavy chain variable region comprises multiple human VH gene segments, multiple human D gene segments, and multiple human JH gene segments, and wherein the mu constant region is selected from the group consisting of (i) a human S-mu sequence and a human or mouse mu coding sequence and (ii) a mouse S-mu sequence and a human or mouse mu coding sequence,(b) removing B lymphocytes from the transgenic mouse,(c) identifying mouse IgG isotype immunoglobulin molecules that bind to the predetermined antigen expressed by the B lymphocytes; and

    (d) isolating the IgG isotype immunoglobulin molecules that bind to the predetermined antigen, whereby a somatically mutated antibody that binds to the predetermined antigen is obtained from the B lymphocytes of step (c).

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