Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies

Abstract

The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

1 - 34 . (canceled) 
     
     
         35 . A chimeric immunoglobulin (Ig) that specifically binds an antigen, wherein the chimeric Ig is produced by a rat nullizygous for endogenous Ig heavy chain and light chain loci and comprises:
 a chimeric heavy chain encoded by an artificial heavy chain locus that comprises rat and human sequences, including a human variable (V) gene segment; and   a light chain encoded by a light chain locus comprising a human V gene segment and at least one human constant (C) region gene segment;   wherein the chimeric Ig has a human idiotype.   
     
     
         36 . The chimeric immunoglobulin of  claim 35 , wherein the chimeric heavy chain further comprises a human Ig diversity (D) region gene. 
     
     
         37 . The chimeric immunoglobulin of  claim 36  wherein the chimeric heavy chain further comprises a human Ig joining (J) region gene. 
     
     
         38 . The chimeric immunoglobulin of  claim 35  wherein the chimeric heavy chain further comprises a human C region gene segment. 
     
     
         39 . The chimeric immunoglobulin of  claim 35  wherein the light chain is a chimeric light chain comprising both rat and human sequences. 
     
     
         40 . A chimeric immunoglobulin (Ig) that specifically binds an antigen, wherein the chimeric Ig is produced by a rat nullizygous for the endogenous Ig heavy chain locus and comprises a chimeric heavy chain encoded by an artificial heavy chain locus that comprises rat and human sequences, including a human variable (V) gene segment, wherein the chimeric Ig has a human idiotype. 
     
     
         41 . The chimeric immunoglobulin of  claim 40  wherein the chimeric heavy chain further comprises a human Ig diversity (D) region gene. 
     
     
         42 . The chimeric immunoglobulin of  claim 41  wherein the chimeric heavy chain further comprises a human Ig joining (J) region gene. 
     
     
         43 . The chimeric immunoglobulin of  claim 40  wherein the chimeric heavy chain further comprises a human constant (C) region gene segment.