Human monoclonal antibodies to the hepatitis B surface antigen

Abstract

Disclosed is a process for obtaining hybridoma cell lines which produce human antibodies capable of binding to the hepatitis B virus surface antigen (HBVsAg), as well as the hybridoma cell lines, and antibodies produced by the cell lines. Also disclosed are various uses of said antibodies in the prevention and treatment of HBV infection. Peripheral blood lymphocytes obtained from human donors having a high titer of anti HBVsAg antibodies are engrafted into normal strains of mice which were lethally irradiated and radioprotected with SCID bone marrow. After immunization of such chimeric mice with HBVsAg, human cells are obtained from the mice spleens and fused in vitro with heteromyeloma cells to generate hybridomas secreting human antibodies having a high affinity and specificity to HBVsAg.

1. A human monoclonal antibody being selected from the group consisting of:
 (a) the monoclonal antibody 18.5.103  18.5.1013 which is secreted by the hybridoma cell line deposited in the European Collection of Cell Cultures (ECACC) under Accession No. 96052170; and  
 (b) fragments of the antibody of (a) which retain the antigen binding characteristics  specificity of the whole  antibody of ( a ).  
 
     
     
       2. A pharmaceutical composition for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy and/or for treating HBV infections comprising as active ingredient an antibody in accordance with  claim 1  together with a pharmaceutically acceptable carrier. 
     
     
       3. A method for the treatment of HBV infections comprising administering to an individual in need a therapeutically effective amount of a pharmaceutical composition according to  claim 2  to treat HBV infection. 
     
     
       4. A method for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy, comprising administering to a population of individuals a pharmaceutical composition according to  claim 2 , to reduce the occurrence of HBV infections in the population. 
     
     
       5. A method for the treatment of HBV infections comprising administering to an individual in need a therapeutically effective amount of the antibody of  claim 1  to treat HBV infection. 
     
     
       6. A method for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy, comprising administering to a population of individuals an antibody of  claim 1 , to reduce the occurrence of HBV infections in the population. 
     
     
       7. A pharmaceutical composition for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy, and/or for treating HBV infections comprising as an active ingredient at least one antibody in accordance with  claim 1  in combination with at least one other active ingredient being an anti viral agent. 
     
     
       8. A pharmaceutical composition according to  claim 7  wherein the anti viral agent is selected from the group consisting of: interferons, anti HB polyclonal antibodies, nucleoside analogues and inhibitors of DNA polymerase. 
     
     
       9. A method for the diagnosis of HBV infections in a body fluid sample comprising:
 (a) contacting said sample with an antibody of  claim 1  under conditions enabling the formation of antibody-antigen complexes; and  
 (b) determining the level of antibody-antigen complexes formed, wherein a determination of the presence of a level of antibody-antigen complexes significantly higher than that formed in a control sample indicates an HBV infection in the tested body fluid sample.  
 
     
     
       10. A human monoclonal antibody being selected from the group consisting of:
 (a) the monoclonal antibody 19.79.5 which is secreted by the hybridoma cell line deposited in the European Collection of Cell Cultures (ECACC) under Accession No. 96052168; and  
 (b) fragments of the antibody of (a) which retain the antigen binding characteristics  of the whole  antibody of ( a ).  
 
     
     
       11. The hybridoma cell line deposited at the ECACC on May 22, 1996 under Accession No. 96052170. 
     
     
       12. The hybridoma cell line deposited at the ECACC on May 22, 1996 under Accession No. 96052168. 
     
     
       13. A pharmaceutical composition for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy and/or for treating HBV infections comprising as active ingredient an antibody in accordance with  claim 10  together with a pharmaceutically acceptable carrier. 
     
     
       14. A method for the treatment of HBV infections comprising administering to an individual in need a therapeutically effective amount of a pharmaceutical composition according to  claim 13  to treat HBV infection. 
     
     
       15. A method for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy, comprising administering to a population of individuals a pharmaceutical composition according to  claim 13 , to reduce the occurrence of HBV infections in the population. 
     
     
       16. A method for the treatment of HBV infections comprising administering to an individual in need a therapeutically effective amount of the antibody of  claim 10  to treat HBV infection. 
     
     
       17. A method for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy, comprising administering to a population of individuals an antibody of  claim 10 , to reduce the occurrence of HBV infections in the population. 
     
     
       18. A pharmaceutical composition for reducing the occurrence of HBV infections in a population of individuals by passive immunotherapy, and/or for treating HBV infections comprising as an active ingredient at least one antibody in accordance with  claim 10  in combination with at least one other active ingredient being an anti viral agent. 
     
     
       19. A pharmaceutical composition according to  claim 18  wherein the anti viral agent is selected from the group consisting of interferons, anti HB polyclonal antibodies, nucleoside analogues and inhibitors of DNA polymerase. 
     
     
       20. A method for the diagnosis of HBV infections in a body fluid sample comprising:
 ( a )  contacting said sample with an antibody of    claim 10    under conditions enabling the formation of antibody - antigen complexes; and      ( b )  determining the level of antibody - antigen complexes formed, wherein a determination of the presence of a level of antibody - antigen complexes significantly higher than that formed in a control sample indicates an HBV infection in the tested body fluid sample.