Antibodies Directed Against Hepatitis C Virus E1E2 Complex, Compositions of HCV Particles, and Pharmaceutical Compositions

Abstract

New conformational antibodies, and more particular conformational monoclonal antibodies and fragments thereof, are directed against HCV. Also provided are compositions of particles that are recognized by such antibodies, and pharmaceutical compositions containing these particles. Also described are HCV enveloped subviral particles and purified HCV enveloped complete viral particles, as well as processes for their preparation.

1 . An isolated antibody, or a functional fragment thereof, comprising:
 (a) at least one heavy chain, or fragment thereof, having an amino acid sequence comprising the amino acid sequence set forth in SEQ ID NO: 32, or a conservative variant thereof, or an antigen-binding portion thereof; or   (b) at least one light chain, or fragment thereof, having an amino acid sequence comprising the amino acid sequence set forth in SEQ ID NO: 36, or a conservative variant thereof, or an antigen-binding portion thereo; or   (c) at least one heavy chain, or fragment thereof, having an amino acid sequence comprising the amino acid sequence set forth in SEQ ID NO: 32, a conservative variant thereof, or an antigen-binding portion thereof, and at least one light chain, or fragment thereof, having an amino acid sequence comprising the amino acid sequence set forth in SEQ ID NO: 36, or a conservative variant thereof, or an antigen-binding portion thereof.   
     
     
         2 . The isolated antibody, or a functional fragment thereof, according to  claim 1 , wherein:
 the antigen-binding portion of the heavy chain comprises three complementary determining regions having amino acid sequences set forth in SEQ ID NO: 33, SEQ ID NO: 34 and SEQ ID NO: 35 or conservative variants thereof; and   the antigen-binding portion of the light chain comprises three complementary determining regions having amino acid sequences set forth in in SEQ ID NO: 37, SEQ ID NO: 41 and SEQ ID NO: 38 or conservative variants thereof.   
     
     
         3 . The isolated antibody, or a functional fragment thereof, according to  claim 1 , wherein the antibody is a chimeric, humanized or deimmunized monoclonal antibody. 
     
     
         4 . An antigen-binding molecule comprising:
 (a) three complementary determining regions having amino acid sequences set forth in SEQ ID NO: 33, SEQ ID NO: 34 and SEQ ID NO: 35 or conservative variants thereof; or   (b) three complementary determining regions having amino acid sequences set forth in in SEQ ID NO: 37, SEQ ID NO: 41 and SEQ ID NO: 38 or conservative variants thereof; or   (c) three complementary determining regions having amino acid sequences set forth in SEQ ID NO: 33, SEQ ID NO: 34 and SEQ ID NO: 35 or conservative variants thereof, and three complementary determining regions having amino acid sequences set forth in in SEQ ID NO: 37, SEQ ID NO: 41 and SEQ ID NO: 38 or conservative variants thereof.   
     
     
         5 . A pharmaceutical composition comprising at least one isolated antibody, or functional fragment thereof, according to  claim 1 , and a pharmaceutically acceptable carrier or excipient. 
     
     
         6 . An isolated nucleic acid molecule encoding an antibody, or functional fragment thereof, according to  claim 1 , comprising:
 (a) a polynucleotide having a sequence selected from the group consisting of the sequence set forth in SEQ ID NO: 39, homologous variants thereof, and fragments thereof that encode antigen-binding portions of the antibody heavy chain; or   (b) a polypeptide having a sequence selected from the group consisting of the sequence set forth in SEQ ID NO: 40, homologous variants thereof, and fragments thereof that encode antigen-binding portions of the antibody light chain; or   (c) a first polypeptide having a sequence selected from the group consisting of the sequence set forth in SEQ ID NO: 39, homologous variants thereof, and fragments thereof that encode antigen-binding portions of the antibody heavy chain, and a second polypeptide having a sequence selected from the group consisting of the sequence set forth in SEQ ID NO: 40, homologous variants thereof, and fragments thereof that encode antigen-binding portions of the antibody light chain.   
     
     
         7 . An isolated expression vector comprising the isolated nucleic acid molecule according to  claim 6 . 
     
     
         8 . An isolated host cell comprising the isolated expression vector according to  claim 7 . 
     
     
         9 . The isolated host cell according to  claim 8 , wherein the host cell is prokaryotic or eukaryotic. 
     
     
         10 . A pharmaceutical composition comprising at least an antigen-binding molecule according to  claim 4 , and a pharmaceutically acceptable carrier or excipient.