Human cytomegalovirus neutralizing antibodies and use thereof

Abstract

The invention relates to neutralizing antibodies, and antibody fragments thereof, having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for one, or a combination of two or more, hCMV gene UL products. The invention also relates to immortalized B cells that produce, and to epitopes that bind to, such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies, antibody fragments, and epitopes in screening methods as well as in the diagnosis, prevention, and therapy of disease.

1 - 70 . (canceled) 
     
     
         71 . An isolated antibody, or an antigen binding fragment thereof, which inhibits human cytomegalovirus (hCMV) infection, comprising (a) heavy chain CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 174, 175, and 176, respectively, and the light chain CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 177, 149, and 178, respectively, or (b) heavy and light chain variable region sequences set forth in SEQ ID NOs: 184 and 185, respectively. 
     
     
         72 . The antibody, or antigen binding fragment thereof, of  claim 71 , wherein the antibody or antigen binding fragment thereof is produced by a CHO cell. 
     
     
         73 . The antibody, or antigen binding fragment thereof, of  claim 72 , wherein the antibody or fragment is specific for a human cytomegalovirus (hCMV) proteins gH, gL, UL128, and UL130. 
     
     
         74 . antibody, or antigen binding fragment thereof, of  claim 72 , wherein the antibody or fragment inhibits infection of epithelial cells, wherein the concentration of antibody required for 50% inhibition of hCMV is 0.01 μg/ml or less. 
     
     
         75 . The antibody, or antigen binding fragment thereof, of  claim 72 , wherein the antibody or fragment is a human antibody, a monoclonal antibody, a single chain antibody, Fab, Fab′, F(ab′)2, Fv or scFv. 
     
     
         76 . A composition comprising the antibody or antigen binding fragment of  claim 72  and an adjuvant or a sufficient amount of a preservative. 
     
     
         77 . The composition of  claim 76 , further comprising a second antibody, or antigen binding fragment thereof, which inhibits hCMV infection. 
     
     
         78 . A method of inhibiting hCMV infection in a subject, comprising administering an effective amount of the antibody, or antigen binding fragment thereof, of  claim 72 , wherein hCMV infection is inhibited. 
     
     
         79 . The method of  claim 78 , further comprising administering a second antibody, or antigen binding fragment thereof, which inhibits hCMV infection. 
     
     
         80 . The method of  claim 79 , wherein the antibodies, or antigen binding fragments thereof, are administered sequentially or simultaneously. 
     
     
         81 . The antibody or antigen binding fragment thereof of  claim 72 , wherein the antibody or antigen binding fragment are glycosylated by the CHO cell. 
     
     
         82 . A kit comprising the antibody or antigen binding fragment thereof of  claim 72  and a package insert comprising instructions for administering of the composition for inhibiting hCMV infection. 
     
     
         83 . An isolated host cell comprising a vector which comprises one or more nucleic acid molecules encoding the variable regions of an antibody, or antigen binding fragment thereof, comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 184 and 185, respectively. 
     
     
         84 . The isolated host cell of  claim 83 , wherein the cell is a CHO cell. 
     
     
         85 . A composition comprising an isolated antibody, or an antigen binding fragment thereof, comprising
 (a) heavy chain variable region CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 174, 175, and 176, respectively, and light chain variable region CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 177, 149, and 178, respectively, or   (b) heavy and light chain variable region sequences set forth in SEQ ID NOs: 184 and 185, respectively,   wherein the composition is in lyophilized form.   
     
     
         86 . The composition of  claim 85 , wherein the antibody or fragment is specific for hCMV proteins gL, gH, UL128, and UL130. 
     
     
         87 . The composition of  claim 85 , further comprising an adjuvant or a sufficient amount of a preservative. 
     
     
         88 . The composition of  claim 85 , wherein the antibody or fragment inhibits infection of epithelial cells, wherein the concentration of antibody required for 50% inhibition of hCMV is 0.01 μg/ml or less. 
     
     
         89 . The composition of  claim 85 , wherein the antibody or antigen binding fragment thereof is a human antibody, a monoclonal antibody, a single chain antibody, Fab, Fab′, F(ab′)2, Fv or scFv. 
     
     
         90 . The composition of  claim 85 , further comprising at least one additional antibody, or an antigen binding fragment thereof, which inhibits hCMV infection. 
     
     
         91 . A method of inhibiting hCMV infection in a subject, comprising administering an effective amount of the composition of  claim 85 , wherein the composition is reconstituted prior to injection or infusion and wherein hCMV infection is inhibited. 
     
     
         92 . The method of  claim 91 , further comprising the step of administering a second composition comprising a second antibody, or an antigen binding fragment thereof, which inhibits hCMV infection, wherein the compositions are administered simultaneously or sequentially. 
     
     
         93 . A kit comprising the composition of  claim 85  and a package insert comprising instructions for administering of the composition for inhibiting hCMV infection.