Proteins modified with (amino) monosaccharide-biotin adduct

Abstract

A protein, e.g. an antibody, coated with a non-immunogenic molecule selected from an amino-monosaccharide-biotin adduct or a monosaccharide-biotin adduct is disclosed, wherein the coated protein, which has diminished immunogenicity relative to the uncoated protein and intact biological activity, enables, for example, cross-species vaccination.

1 . A method of reducing the immunogenicity of an immunogenic protein, the method comprising linking said immunogenic protein to a non-immunogenic protein selected from an amino-mannose-biotin adduct and a mannose-biotin-adduct, wherein said biotin is selected from biotin or a biotin-like molecule, thereby reducing the immunogenicity of an immunogenic protein. 
     
     
         2 . The method of  claim 1 , wherein said linking is covalent linking. 
     
     
         3 . The method of  claim 1 , wherein an amino group at position 1, 2, 3, 4 or 6 of said amino-mannose molecule of a hydroxyl group at position 1, 2, 3, 4 or 6 of said mannose molecule is linked to a carboxyl group of said biotin. 
     
     
         4 . The method of  claim 3 , wherein said linked to a carboxyl group is direct linkage. 
     
     
         5 . The method of  claim 3 , wherein said linked to a carboxyl group forms an amide bond or ester bond. 
     
     
         6 . The method of  claim 1 , wherein said biotin-like molecule is selected from desthiobiotin and lipoic acid. 
     
     
         7 . The method of  claim 1 , wherein said immunogenic protein is linked to an amino-mannose-biotin adduct. 
     
     
         8 . The method of  claim 7 , wherein said amino-mannose-biotin adduct is selected from a 2-amino-mannose-biotin adduct, a 2-amino-mannose-desthiobiotin adduct and a 2-amino-mannose-lipoic acid adduct. 
     
     
         9 . The method of  claim 1 , wherein said immunogenic protein is an immunogenic antibody. 
     
     
         10 . The method of  claim 9 , wherein said immunogenic antibody is selected from the group consisting of (i) a humanized or chimeric monoclonal IgG antibody; (ii) a mammalian monoclonal IgG antibody; (iii) a mammalian polyclonal IgG antibody; and (iv) a chicken IgY antibody. 
     
     
         11 . The method of  claim 10 , wherein said chicken IgY antibody is an anti-bacterium or anti-virus chicken IgY antibody. 
     
     
         12 . The method of  claim 9 , wherein said immunogenic antibody is an anti-tumor associated antigen antibody, an anti-snake venom antibody, an anti-virus antibody or an anti-bacterium antibody. 
     
     
         13 . The method of  claim 1 , wherein said immunogenic protein is linked to a plurality of non-immunogenic proteins. 
     
     
         14 . The method of  claim 13 , comprising linking said plurality of non-immunogenic proteins to said immunogenic protein to produce a ratio of between 4:1 and 24:1 non-immunogenic proteins: immunogenic protein. 
     
     
         15 . A method of producing a pharmaceutical composition with decreased immunogenicity, the method comprising producing a protein with reduced immunogenicity by a method of  claim 1  and placing it is a pharmaceutical composition. 
     
     
         16 . A method of treating a condition amenable to treatment by an immunogenic protein in a subject in need thereof, the method comprising reducing the immunogenicity of said immunogenic protein by a method of  claim 1  and administering said protein with reduced immunogenicity to said subject, thereby treating a condition. 
     
     
         17 . The method of  claim 16 , wherein said immunogenic protein is an immunogenic antibody. 
     
     
         18 . The method of  claim 17 , wherein said immunogenic antibody is selected from the group consisting of (i) a humanized or chimeric monoclonal IgG antibody; (ii) a mammalian monoclonal IgG antibody; (iii) a mammalian polyclonal IgG antibody; and (iv) a chicken IgY antibody. 
     
     
         19 . The method of  claim 18 , wherein said chicken IgY antibody is an anti-bacterium chicken IgY antibody. 
     
     
         20 . The method of  claim 17 , wherein said immunogenic antibody is an anti-tumor associated antigen antibody, an anti-snake venom antibody, an anti-virus antibody or an anti-bacterium antibody.