Anti-hepatitis c virus antibody and uses thereof

Abstract

Described are novel antibodies specifically recognizing conformation dependent epitopes of HCV glycoprotein E2 and that are capable of neutralizing the binding of E2 protein onto susceptible cells. Furthermore, antigens and epitopes recognized by the above-described antibodies as well as polynucleotides encoding said antibodies are provided. Also provided are to vectors comprising said polynucleotides as well as host cells transformed therewith and their use in the production of said antibodies. In addition, pharmaceutical and diagnostic compositions are provided comprising any of the aforedescribed antibodies, antigens, epitopes, polynucleotides, vectors or cells. Further described is the use of the aforementioned antibodies, antigens, polynucleotides and vectors in adoptive immunotherapy, preferably for the treatment or prevention of HCV infection during liver transplantation.

1 - 21 . (canceled) 
     
     
         22 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an antibody, wherein said antibody comprises at least a V H  complementarity determining region (CDR) 3 (CDR3) having amino acids 98-106 of SEQ ID NO: 4, which antibody specifically recognizes a conformation-dependent epitope of Hepatitis C Virus (HCV) glycoprotein E2 and precipitates covalently or non-covalently associated E2/E1 complexes. 
     
     
         23 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an antibody, wherein said antibody specifically recognizes the same conformation-dependent epitope of Hepatitis C Virus (HCV) E2 present on HCV genotypes 1a, 1b, 2a, 3a and 4 as that bound by an antibody comprising at least a V H  complementarity determining region (CDR) 3 (CDR3) having amino acids 98-106 of SEQ ID NO: 4, and precipitates covalently or non-covalently associated E2/E1 complexes. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The pharmaceutical composition of  claim 22 , wherein said antibody further comprises one or more of a V H  CDR1 having amino acids 31-35 of SEQ ID NO: 4, a V H  CDR2 having amino acids 50-65 of SEQ ID NO: 4, a V L  CDR1 having amino acids 23-33 of SEQ ID NO: 2, a V L  CDR2 having amino acids 49-55 of SEQ ID NO: 2 or a V L  CDR3 having amino acids 88-98 of SEQ ID NO: 2. 
     
     
         27 . The pharmaceutical composition of  claim 22  or  23 , wherein said antibody comprises the V H  amino acid sequence SEQ ID NO: 4. 
     
     
         28 - 29 . (canceled) 
     
     
         30 . The pharmaceutical composition of  claim 22  or  23 , wherein said pharmaceutical composition is for administering to liver transplantation subjects. 
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein said administering is prior, during and/or after said transplantation. 
     
     
         32 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof, wherein said pharmaceutical composition comprises a pharmaceutically acceptable carrier and an antibody, which antibody comprises at least a V H  complementarity determining region (CDR) 3 (CDR3) having amino acids 98-106 of SEQ ID NO: 4, and which antibody specifically recognizes a conformation-dependent epitope of Hepatitis C Virus (HCV) glycoprotein E2 and precipitates covalently or non-covalently associated E2/E1 complexes. 
     
     
         33 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof, said composition comprising a pharmaceutically acceptable carrier and an antibody, wherein said antibody specifically recognizes the same conformation-dependent epitope of HCV E2 present on HCV genotypes 1a, 1b, 2a, 3a and 4 as that bound by an antibody comprising at least a V H  complementarity determining region (CDR) 3 (CDR3) having amino acids 98-106 of SEQ ID NO: 4, and precipitates covalently or non-covalently associated E2/E1 complexes. 
     
     
         34 . The method of  claim 32  or  33 , wherein said antibody is a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a humanized antibody, a synthetic antibody, or an antigen-binding antibody fragment. 
     
     
         35 . The method of  claim 32 , wherein said antibody further comprises one or more of a V H  CDR1 having amino acids 31-35 of SEQ ID NO: 4, a V H  CDR2 having amino acids 50-65 of SEQ ID NO: 4, and a V L  CDR1 having amino acids 23-33 of SEQ ID NO: 2, a V L  CDR2 having amino acids 49-55 of SEQ ID NO: 2 or a V L  CDR3 having amino acids 88-98 of SEQ ID NO: 2. 
     
     
         36 . The method of  claim 34 , wherein said antibody is a monoclonal antibody. 
     
     
         37 . The method of  claim 32  or  33 , wherein said antibody comprises the V H  amino acid sequence SEQ ID NO: 4. 
     
     
         38 . The method of  claim 32  or  33 , wherein said antibody comprises the V H  amino acid sequence SEQ ID NO: 4 and the V L  amino acid sequence SEQ ID NO: 2. 
     
     
         39 . The method of  claim 36 , wherein said antibody is a human monoclonal antibody. 
     
     
         40 . The method of  claim 32  or  33 , wherein said treatment is the treating or preventing of infection of Hepatitis C Virus, treating or preventing of re-infection of Hepatitis C Virus, or alleviating chronic Hepatitis C in said subject. 
     
     
         41 . The method of  claim 40 , wherein said subject is a human or an animal. 
     
     
         42 . The method of  claim 32  or  33 , wherein said subject is having a liver transplant. 
     
     
         43 . The method of  claim 42 , wherein said composition is administered prior, during and/or after said transplantation.