Transgenic non-human animals for producing chimeric antibodies

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.

What is claimed is: 
     
         1 . A method for constructing a nucleic acid molecule encoding a human heavy chain immunoglobulin, 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 B lymphocyte from a transgenic mouse, wherein the genome of said transgenic mouse comprises inactivated murine variable regions and an unrearranged human heavy chain immunoglobulin variable region operably linked to a mu constant region gene segment, wherein the unrearranged 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:
 (a) a human S-mu sequence and a human or mouse mu coding sequence; and   (b) a mouse S-mu sequence and a human or mouse mu coding sequence.   
     
     
         2 . The method of  claim 1  wherein the nucleic acid molecule encoding a human heavy chain immunoglobulin is operably linked to an expression vector. 
     
     
         3 . The method of  claim 2  wherein the expression vector comprising the nucleic acid molecule encoding a human heavy chain immunoglobulin is introduced into a host cell. 
     
     
         4 . The method of  claim 3  wherein the host cell is a mammalian cell. 
     
     
         5 . The method of  claim 4  wherein the mammalian host cell is selected from the group consisting of a CHO cell, a SP20 cell, and a NS0 cell. 
     
     
         6 . The method of  claim 1  wherein the human heavy chain immunoglobulin is an IgG, IgA, or IgE isotype.