Compounds having reduced immunogenicity and a method of reducing the immunogenicity of compounds

Abstract

Reduced-immunogenic fusion compounds are disclosed. The fusion compounds of the invention comprise immunogenic compounds linked to auto-antigenic sequences which render the compound less immunogenic. In addition, a method of reducing the immunogenicity of an immunogenic compound is disclosed. The method comprises linking an auto-antigenic sequence to an otherwise immunogenic compound. Recombinant nucleotide sequence encoding auto-antigenic sequences are also disclosed.

1 . A fusion compound comprising an immunogenic compound linked to the amino terminal of an auto-antigenic sequence, the carboxy terminal of the auto-antigenic sequence being unlinked, with the proviso that the fusion compound is not c7E3 Fab.  
     
     
         2 . The fusion compound of  claim 1  wherein said auto-antigenic sequence is an IgG amino acid sequence.  
     
     
         3 . The fusion compound of  claim 1  wherein said auto-antigenic sequence is an IgG heavy chain amino acid sequence.  
     
     
         4 . The fusion compound of  claim 1  wherein said auto-antigenic sequence comprises amino acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO: 4 r SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10.  
     
     
         5 . The fusion compound of  claim 1  wherein said auto-antigenic sequence comprises SEQ ID NO:1.  
     
     
         6 . The fusion compound of  claim 1  wherein said immunogenic compound is a protein.  
     
     
         7 . The fusion compound of  claim 1  wherein said immunogenic compound is a non-human protein.  
     
     
         8 . The fusion compound of  claim 1  wherein said immunogenic compound is a murine monoclonal antibody.  
     
     
         9 . The fusion compound of  claim 1  wherein said immunogenic compound is a chimeric monoclonal antibody.  
     
     
         10 . The fusion compound of  claim 1  wherein said immunogenic compound is Streptokinase.  
     
     
         11 . The fusion compound of  claim 1  wherein said immunogenic compound is a monoclonal antibody and said auto-antigenic sequence is SEQ ID NO:1.  
     
     
         12 . A method of reducing the immunogenicity of an immunogenic compound comprising the step of linking said compound to the amino terminal of an auto-antigenic sequence, the carboxy terminal of the auto-antigenic sequence being unlinked, with the proviso that the fusion compound is not c7E3 Fab.  
     
     
         13 . The method of  claim 12  wherein said auto-antigenic sequence is an IgG amino acid sequence.  
     
     
         14 . The method of  claim 12  wherein said auto-antigenic sequence is an IgG heavy chain amino acid sequence.  
     
     
         15 . The method of  claim 12  wherein said auto-antigenic sequence comprises amino acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10.  
     
     
         16 . The method of  claim 12  wherein said auto-antigenic sequence comprises SEQ ID NO:1.  
     
     
         17 . The method of  claim 12  wherein said immunogenic compound is a protein.  
     
     
         18 . The method of  claim 12  wherein said immunogenic compound is a non-human protein.  
     
     
         19 . The method of  claim 12  wherein said immunogenic compound is a murine monoclonal antibody.  
     
     
         20 . The method of  claim 12  wherein said immunogenic compound is a chimeric monoclonal antibody.  
     
     
         21 . The method of  claim 12  wherein said immunogenic compound is Streptokinase.  
     
     
         22 . The method of  claim 12  wherein said immunogenic compound is a monoclonal antibody and said auto-antigenic sequence is SEQ ID NO:1.  
     
     
         23 . The method of  claim 12  wherein said auto-antigenic sequence is linked to said immunogenic compound by chemically binding a peptide comprising auto-antigenic sequence to said immunogenic compound.  
     
     
         24 . The method of  claim 12  wherein said immunogenic compound is a protein and said auto-antigenic sequence is linked to said immunogenic protein by binding a nucleotide sequence that encodes said auto-antigenic sequence to the 3′ terminal end of nucleotide sequence that encodes said immunogenic protein to form a chimeric gene, expression of said chimeric gene produces a fusion protein having said auto-antigenic sequence linked to said immunogenic protein.  
     
     
         25 . A recombinant nucleic acid molecule consisting a nucleotide sequence encoding an auto-antigenic sequence.  
     
     
         26 . The recombinant nucleotide sequence of  claim 25  wherein said auto-antigenic sequence comprises SEQ ID NO:1.  
     
     
         27 . The recombinant nucleotide sequence of  claim 25  further comprising a nucleotide sequence encoding an immunogenic protein wherein the 5′ end of said nucleotide sequence that encodes an auto-antigenic sequence is linked to the 3′ end of said nucleotide sequence that encodes said immunogenic protein, the 3′ end of said nucleotide sequence that encodes the auto-antigenic sequence being linked to a termination sequence without any intervening coding sequences, said immunogenic protein is a monoclonal antibody and said auto-antigenic sequence is SEQ ID NO:1.