Composition used as a therapeutic agent against chronic viral hepatic diseases

Abstract

A combination, comprising at least one polypeptide sequence, mediating the antigenicity of one or more epitopes, and a carrier, capable of presenting this/these polypeptide sequence(s), which are useful for the production of a medicament for the treatment of chronic viral hepatitis, is provided.

1 . Use of a composition for the production of a medicament for the treatment of chronic viral hepatitis, said composition comprising a combination of 
 a) at least one polypeptide sequence having one or more antigenic T cell-activating epitopes and    b) a carrier capable of presenting the epitope sequence(s) a), wherein the polypeptide sequence(s) a) is bound to carrier b) by covalent or hydrophobic bonding.    
     
     
         2 . Use according to  claim 1  wherein said polypeptide sequence(s) a) is a polypeptide of hepatitis B virus.  
     
     
         3 . Use according to  claim 2  wherein said polypeptide sequence(s) a) is the amino acid sequence of one or more members selected from the group comprising the HB viral pre-S1, pre-S2 and S peptides and the HB core antigens.  
     
     
         4 . Use according to one of  claims 1  to  3  wherein said polypeptide sequence(s) a) may be a native polypeptide sequence modified: 
 i) by having arbitrary deletions, whereby an epitope comprising at least six consecutive amino acid residues is preserved,  
 ii) by having substitutions of one or several amino acids, or  
 iii) by carrying an additional amino acid sequence either at its N-terminus, at its C-terminus or as an insertion into the polypeptide sequence(s) a).  
 
     
     
         5 . Use according to one of  claims 1  to  4  wherein said polypeptide sequence(s) a) is myristylated.  
     
     
         6 . Use according to any one of  claims 1  to  5  wherein said polypeptide sequence(s) a) is produced by expression of a recombinant DNA molecule.  
     
     
         7 . Use according to one of  claims 1  to  6  wherein said carrier b) is a polysaccharide, a hydrophobic polymer or an inorganic molecule having particle form.  
     
     
         8 . Use according to one of  claims 1  to  7  wherein said carrier b) is a second polypeptide sequence.  
     
     
         9 . Use according to  claim 8  wherein said polypeptide sequence b) upon secretion forms particles having a diameter of at least 10 nm.  
     
     
         10 . Use according to  claim 8  or  9  wherein said polypeptide sequence b) is a substantial part of or the complete amino acid sequence of a polypeptide selected from a group consisting of the HBV S-peptide, the HBV core-, the HAV core- and the HIV core-antigen as well as the surface antigens of poliovirus, HAV or HIV.  
     
     
         11 . Use according to one of  claims 8  to  10  wherein said polypeptide sequence b) may be modified 
 i) by having arbitary deletions, whereby the particle forming capacity is preserved,  
 ii) by having substitutions of one or several amino acids, or  
 iii) by carrying an additional amino acid sequence either at its N-terminus, at its C-terminus or as an insertion into the polypeptide sequence b).  
 
     
     
         12 . Use according to one of  claims 8  to  11  wherein said polypeptide sequence b) is myristylated.  
     
     
         13 . Use according to any one of  claims 8  to  12  wherein said polypeptide sequence b) is produced by expression of a recombinant DNA expression.  
     
     
         14 . Use according to one of  claims 1  to  6  or  8  to  13  wherein said polypeptide sequences a) and b) are linked via disulfide bridges.  
     
     
         15 . Use according to one of  claims 1  to  6  or  8  to  14  wherein said polypeptide sequences a) and b) are linked via “hydrophobic anchoring” (mediated by myristic acid).  
     
     
         16 . Use according to one of  claims 1  to  6  or  8  to  15  wherein said polypeptide sequences a) and b) are linked by a peptide bond, wherein optionally a spacer sequence is inserted in between polypeptide sequence(s) a) and polypeptide sequence b), said spacer-sequence being linked via peptide bonds to polypeptide sequences a) and b).  
     
     
         17 . Use according to  claim 16  wherein said polypeptide sequence(s) a) and said polypeptide sequence b) are encoded in tandem on the same recombinant DNA molecule.  
     
     
         18 . Use according to  claim 17  wherein said polypeptide sequence(s) a) and said polypeptide sequence b) are expressed from a single open reading frame on said DNA molecule, and are optionally separated by a spacer polypeptide sequence also encoded in the single open reading frame.  
     
     
         19 . Use as claimed in any one of  claims 1  to  18  wherein said composition is for administration by intravenous or intramuscular injection.  
     
     
         20 . Method of treatment of viral hepatitis characterised in that a composition as defined in any one of  claims 1  to  19  is administered in a patient.  
     
     
         21 . A method as claimed in  claim 20  for the treatment of viral hepatitis B.