Rsv-specific binding molecules and means for producing them

Abstract

The invention provides antibodies and functional equivalents thereof which are capable of specifically binding RSV, and means and methods for producing them.

1 . An isolated, synthetic or recombinant antibody or a functional part, derivative and/or analogue thereof which is capable of specifically binding Respiratory Syncytial Virus and which comprises:
 a heavy chain CDR1 sequence comprising a sequence which is at least 70% identical to the sequence NYIIN, and/or   a heavy chain CDR2 sequence comprising a sequence which is at least 75% identical to the sequence GIIPVLGTVHYAPKFQG, and/or   a heavy chain CDR3 sequence comprising a sequence which is at least 70% identical to the sequence ETALVVSTTYLPHYFDN, and/or   a light chain CDR1 sequence comprising a sequence which is at least 85% identical to the sequence QASQDIVNYLN, and/or   a light chain CDR2 sequence comprising a sequence which is at least 70% identical to the sequence VASNLET.   
     
     
         2 . An antibody, functional part, derivative or analogue according to  claim 1 , having a heavy chain sequence comprising a sequence which is at least 70% identical to the sequence QVQLVQSGAEVKKPGSSVMVSCQASGGPLRNYIINWLRQAPGQGPEWMGGIIPVLGTV HYAPKFQGRVTITADESTDTAYIHLISLRSEDTAMYYCATETALVVSTTYLPHYFDN WGQGTLVTVSS and/or having a light chain sequence which is at least 70% identical to the sequence DIQMTQSPSSLSAAVGDRVTITCQASQDIVNYLNWYQQKPGKAPKLLIYVASNLETGVP SRFSGSGSGTDFSLTISSLQPEDVATYYCQQYDNLPLTFGGGTKVEIKRTV. 
     
     
         3 . An antibody which has an IC50 value of less than 10 ng/ml, preferably less than 2 ng/ml, in an in vitro neutralization assay wherein HEp-2 cells are infected with RSV, or a functional part, derivative and/or analogue of said antibody. 
     
     
         4 - 10 . (canceled) 
     
     
         11 . An isolated, synthetic or recombinant nucleic acid sequence, or a functional part, derivative or analogue thereof, encoding an antibody, functional part, derivative or analogue according to  claim 1 . 
     
     
         12 - 15 . (canceled) 
     
     
         16 . An isolated antibody producing cell capable of producing an antibody, functional part, derivative or analogue according to  claim 1 . 
     
     
         17 . (canceled) 
     
     
         18 . An antibody producing cell according to  claim 16 , wherein BCL6 and Blimp-1 are co-expressed. 
     
     
         19 . An antibody producing cell according to  claim 16 , comprising:
 an exogenous nucleic acid sequence encoding BCL6 or a functional part, derivative and/or analogue thereof, and/or   an exogenous nucleic acid sequence encoding Bcl-xL or a functional part, derivative and/or analogue thereof.   
     
     
         20 . An antibody producing cell according to  claim 16 , wherein expression of a nucleic acid sequence encoding BCL6, Bcl-xL or a functional part, derivative and/or analogue of BCL6 or Bcl-xL, is regulated by an activator and/or repressor that is inducible by an exogenous compound. 
     
     
         21 . A method for producing an antibody producing cell, which is stable for at least three months and which is capable of producing RSV-specific antibodies, the method comprising:
 increasing an expression level of Blimp-1 in a B cell which is capable of producing RSV-specific antibodies; and   increasing and/or maintaining a BCL6 expression level in said B cell.   
     
     
         22 . A method according to  claim 21 , wherein the BCL6 expression level in said B cell is brought to, and/or maintained at, essentially the same level or at a higher level as compared to a plasmablast. 
     
     
         23 . A method according to  claim 21 , comprising providing said B cell with a nucleic acid sequence encoding BCL6 or a functional part, derivative and/or analogue thereof. 
     
     
         24 . A method according to  claim 21 , further comprising increasing an expression level of Bcl-xL in said cell. 
     
     
         25 . A method according to  claim 24 , comprising providing said cell with a nucleic acid encoding Bcl-xL or a functional part, derivative and/or analogue thereof. 
     
     
         26 . A method according to  claim 21 , comprising:
 providing a B cell capable of producing RSV-specific antibodies with BCL6, or a functional part, derivative and/or analogue thereof;   providing said B cell with Bcl-xL or a functional part, derivative and/or analogue thereof, and   culturing said B cell.   
     
     
         27 . A method according to  claim 21 , wherein said B cell is cultured in the presence of IL-21. 
     
     
         28 . A method according to  claim 21 , wherein said B cell has been obtained from an individual, which individual had been previously exposed to Respiratory Syncytial Virus. 
     
     
         29 . A method according to  claim 21 , further comprising expressing a gene of said B cell encoding the Ig heavy chain and/or Ig light chain in a second cell. 
     
     
         30 . A method for producing antibodies which are capable of specifically binding Respiratory Syncytial Virus, the method comprising:
 producing an antibody producing cell capable of producing RSV-specific antibodies with a method according to  claim 21 ; and   obtaining antibodies produced by said antibody producing cell.   
     
     
         31 . An isolated antibody obtainable by a method according to  claim 30 , or a functional part, derivative and/or analogue of said antibody. 
     
     
         32 - 34 . (canceled) 
     
     
         35 . A method for at least in part treating or preventing an RSV-related disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of an antibody or functional part, derivative or analogue according to  claim 1 .