Humanized antibodies specific to the protofibrillar form of the beta-amyloid peptide

Abstract

Humanized antibodies specific to the protofibrillar form of the beta-amyloid peptide are provided. Methods of using antibodies specific to the protofibrillar form of the beta-amyloid peptide in the field of Alzheimer's disease are also provided.

1 . A humanized antibody specific for the protofibrillar form of the peptide A-β. 
     
     
         2 . The antibody of  claim 1 , wherein:
 the antibody characterized in that it binds to aggregated A-β peptide-senile plaques and not to diffuse deposits of A-β peptides;   the antibody induces a reduction in amyloid plaques; or   affinity of the antibody for the protofibrillar form of A-β peptide is at least 100 times greater than affinity of the antibody for other forms of A-β peptide.   
     
     
         3 . The antibody of  claim 1 , comprising at least one CDR encoded by a nucleotide sequence having a sequence identical to one of the sequences SEQ ID NO: 9: 11, 13, 15, 17 and 19 or by sequences respectively differing by 1, 2, 3, 4 or 5 nucleotides of these sequences. 
     
     
         4 . The antibody of  claim 1 , comprising at least one CDR having an amino acid sequence identical to one of the sequences SEQ ID NO: 10, 12, 14, 16, 18 and 20 or by sequences respectively differing by one or two amino acids of these sequences. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The antibody of  claim 1 , comprising the CDR amino acid sequences of SEQ ID NO: 10, 12, 14, 16, 18 and 20; SEQ ID NO: 10, 12, 14, 32, 18 and 20; or SEQ ID NO: 10, 12, 30, 32, 18 and 20. 
     
     
         8 . The antibody of  claim 1 , comprising the CDRs encoded by the nucleotide sequences: SEQ ID NO 9, 11, 13, 31, 17 and 19; SEQ ID NO 9, 11, 29, 31, 17 and 19; or sequences differing respectively by 1, 2, 3, 4 or 5 nucleotides of these sequences. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . The antibody of  claim 1 , comprising a heavy chain variable region encoded by a sequence having at least 80% identity with a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, 5, 25, and 27. 
     
     
         13 . The antibody of  claim 1 , comprising a heavy chain variable region having at least 80% identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 6, 26, and 28. 
     
     
         14 . The antibody of  claim 1 , comprising a light chain variable region encoded by a sequence having at least 80% identity with a nucleic acid sequence selected from the group consisting of SEQ ID NO: 3, 7, 21, and 23. 
     
     
         15 . The antibody of  claim 1 , comprising a light chain variable region having at least 80% identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 4, 8, 22, and SEQ ID NO 24. 
     
     
         16 . The antibody of  claim 1 , comprising a heavy chain variable region encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO 5 and SEQ ID NO 27, or a heavy chain variable region amino acid sequence selected from the group consisting of SEQ ID NO 6 and SEQ ID NO 28. 
     
     
         17 . (canceled) 
     
     
         18 . The antibody of  claim 1 , comprising a light chain variable region encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO 7 and SEQ ID NO 23, or a light chain variable region amino acid sequence selected from the group consisting of SEQ ID NO 8 or SEQ ID NO 24. 
     
     
         19 . (canceled) 
     
     
         20 . The antibody of  claim 1 , comprising sequences encoded by the nucleotide sequences selected from the group consisting of SEQ ID NO: 5 and 7, or amino acid sequences selected from the group consisting of SEQ ID NO: 6 and 8. 
     
     
         21 - 25 . (canceled) 
     
     
         26 . The antibody of  claim 1 , comprising a pair of nucleotide sequences selected from the group consisting of SEQ ID NO: 1 and 3, SEQ ID NO: 5 and 23, and SEQ ID NO: 27 and 23, or a pair of amino acid sequences selected from the group consisting of SEQ ID NO: 2 and 4, SEQ ID NO: 6 and 24, and SEQ ID NO: 28 and 24. 
     
     
         27 - 33 . (canceled) 
     
     
         34 . A method of treating a disease associated with a neurodegenerative disorder comprising administering to the patient the antibody of  claim 1 , wherein the neurodegenerative disease is optionally Alzheimer's disease. 
     
     
         35 . (canceled) 
     
     
         36 . A pharmaceutical composition comprising the antibody of  claim 1  and one or more pharmaceutically acceptable excipients. 
     
     
         37 - 40 . (canceled) 
     
     
         41 . A polynucleotide encoding a polypeptide having at least 80% identity with one of SEQ ID NO:2, 4, 6, 8, 22, 24, 26 or 28, or a polynucleotide having at least 80% identity with one of SEQ ID NO: 1, 3, 5, 7, 21, 23, 25 or 27. 
     
     
         42 . (canceled) 
     
     
         43 . A recombinant vector comprising a nucleic acid according to  claim 41 . 
     
     
         44 . A host cell comprising a vector according to  claim 43 . 
     
     
         45 . A method of producing a humanized antibody specific for the protofibrillar form of the peptide A-β comprising culturing the host cell of  claim 44 .