Rsv-specific binding molecule

Abstract

The invention provides antibodies and functional equivalents thereof which are capable of specifically binding RSV. Nucleic acid sequences encoding said antibody, as well as antibody producing cells and methods for producing said antibody are also provided.

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 KLSIH, and/or   a heavy chain CDR2 sequence comprising a sequence which is at least 70% identical to the sequence GYEGEVDEIFYAQKFQH, and/or   a heavy chain CDR3 sequence comprising a sequence which is at least 70% identical to the sequence LGVTVTEAGLGIDDY, and/or   a light chain CDR1 sequence comprising a sequence which is at least 70% identical to the sequence RASQIVSRNHLA, and/or   a light chain CDR2 sequence comprising a sequence which is at least 70% identical to the sequence GASSRAT, and/or   a light chain CDR3 sequence comprising a sequence which is at least 70% identical to the sequence LSSDSSI.   
     
     
         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 QVQLVQSGAEVKKPGATVKVSCKISGHTLIKLSIHWVRQAPGKGLEWMGGYEGEVDEI FYAQKFQHRLTVIADTATDTVYMELGRLTSDDTAVYFCGTLGVTVTEAGLGIDDYWGQ GTLVTVSS and/or having a light chain sequence which is at least 70% identical to the sequence EIVLTQSPGTLSLSPGERATLSCRASQIVSRNHLAWYQQKPGQAPRLLIFGASSRATGIPV RFSGSGSGTDFTLTINGLAPEDFAVYYCLSSDSSIFTFGPGTKVDFK. 
     
     
         3 . An antibody, functional part, derivative or analogue according to  claim 1 , which is conjugated to PEG or Albumin, and/or which comprises:
 a salvage receptor binding epitope, and/or;   modified amino acid residues identified as involved in the interaction between an Fc and an FcRN receptor, and/or   non naturally occurring amino acid residues.   
     
     
         4 . An antibody, functional part, derivative or analogue according to  claim 1 , comprising an Fc region which comprises a modification at one or more positions selected from the group consisting of 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 251, 252, 254, 255, 256, 262, 263, 264, 265, 266, 267, 268, 269, 279, 280, 284, 292, 296, 297, 298, 299, 305, 313, 316, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 339, 341, 343, 370, 373, 378, 392, 416, 419, 421, 440 and 443 as numbered by the EU index as set forth in Kabat et al, said modification comprising an amino acid substitution, and/or an amino acid insertion, and/or an amino acid deletion. 
     
     
         5 . An isolated, synthetic or recombinant antibody or a functional part, derivative and/or analogue thereof which is capable of specifically binding an epitope that is recognized by an antibody of  claim 1 . 
     
     
         6 . An antibody, functional part, derivative or analogue according to  claim 5 , wherein said antibody, functional part, derivative or analogue has a dissociation constant (K d ) of less than 1×10 −2 M, 1×10 −3 M, 1×10 −4 M, 1×10 −5 M, 1×10 −6 M, 1×10 −7 M, 1×10 −8 M, 1×10 −9 M, 1×10 −10  M, 1×10 −11 M, 1×10 −12 M, 1×10 −13 M, 1×10 −14 M or less than 1×10 −15  M. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . An isolated, synthetic or recombinant nucleic acid sequence, or a functional equivalent thereof, comprising a sequence encoding an amino acid sequence which has at least 70% sequence identity to the sequence KLSIH, and/or at least 70% sequence identity to the sequence GYEGEVDEIFYAQKFQH, and/or at least 70% sequence identity to the sequence LGVTVTEAGLGIDDY, and/or at least 70% sequence identity to the sequence RASQIVSRNHLA, and/or at least 70% sequence identity to the sequence GASSRAT, and/or at least 70% sequence identity to the sequence LSSDSSI, and/or at least 70% sequence identity to the sequence QVQLVQSGAEVKKPGATVKVSCKISGHTLIKLSIHWVRQAPGKGLEWMGGYEGEVDEI FYAQKFQHRLTVIADTATDTVYMELGRLTSDDTAVYFCGTLGVTVTEAGLGIDDYWGQ GTLVTVSS, and/or at least 70% sequence identity to the sequence EIVLTQSPGTLSLSPGERATLSCRASQIVSRNHLAWYQQKPGQAPRLLIFGASSRATGIPV RFSGSGSGTDFTLTINGLAPEDFAVYYCLSSDSSIFTFGPGTKVDFK. 
     
     
         10 . An isolated, synthetic or recombinant nucleic acid sequence with a length of at least 15 nucleotides, or a functional equivalent thereof, encoding at least one CDR sequence of an antibody or a functional part, derivative and/or analogue thereof according to  claim 1 . 
     
     
         11 - 12 . (canceled) 
     
     
         13 . An isolated, synthetic or recombinant nucleic acid sequence, or a functional equivalent thereof, encoding at least one CDR sequence capable of specifically binding an epitope that is recognized by an antibody which comprises:
 a heavy chain CDR1 sequence comprising the sequence KLSIH, and/or   a heavy chain CDR2 sequence comprising the sequence GYEGEVDEIFYAQKFQH, and/or   a heavy chain CDR3 sequence comprising the sequence LGVTVTEAGLGIDDY, and/or   a light chain CDR1 sequence comprising the sequence RASQIVSRNHLA, and/or   a light chain CDR2 sequence comprising the sequence GASSRAT, and/or   a light chain CDR3 sequence comprising the sequence LSSDSSI.   
     
     
         14 - 15 . (canceled) 
     
     
         16 . A vector comprising a nucleic acid sequence or functional equivalent according to  claim 9 . 
     
     
         17 . An isolated or recombinant cell comprising a nucleic acid sequence or functional equivalent according to  claim 9 . 
     
     
         18 - 19 . (canceled) 
     
     
         20 . A combination comprising:
 an antibody, functional part, derivative or analogue according to  claim 1 , and   a different RSV-specific agent, preferably an antibody.   
     
     
         21 - 22 . (canceled) 
     
     
         23 . A combination according to  claim 20  wherein said different RSV-specific agent is Palivizumab, and/or AM14 and/or AM16, and/or AM23, and/or D25. 
     
     
         24 . Use of an antibody, functional part, derivative or analogue according to  claim 1  for the preparation of a medicament and/or prophylactic agent for at least in part treating and/or preventing a RSV-related disorder. 
     
     
         25 . A pharmaceutical composition comprising:
 an antibody, functional part, derivative or analogue according to  claim 1  and   a pharmaceutical acceptable carrier, diluent or excipient.   
     
     
         26 . An isolated or recombinant antibody producing cell capable of producing an antibody, functional part, derivative or analogue according to  claim 1 . 
     
     
         27 . A method for producing an antibody, functional part, derivative or analogue, comprising providing a cell with a nucleic acid sequence or functional equivalent according to  claim 9  and allowing said cell to translate said nucleic acid sequence or functional equivalent thereby producing said antibody, functional part, derivative or analogue thereof. 
     
     
         28 . A method according to  claim 27 , further comprising harvesting, purifying and/or isolating said antibody, functional part, derivative or analogue thereof. 
     
     
         29 . Use of a nucleic acid sequence or functional equivalent according to  claim 9  for the preparation of a medicament and/or prophylactic agent for at least in part treating and/or preventing a RSV-related disorder. 
     
     
         30 . Use of a combination according to  claim 20  for the preparation of a medicament and/or prophylactic agent for at least in part treating and/or preventing a RSV-related disorder.