Monoclonal Antibody

Abstract

The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD).

1 - 169 . (canceled) 
     
     
         170 . A nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain or the light chain of a monoclonal antibody that binds to at least two sites on β-amyloid proteins, amyloid β fibers, amyloid β monomers or amyloid β oligomers, wherein said at least two sites are selected from the group consisting of
 (i) one H is residue within SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:16, SEQ ID NO: 18, or SEQ ID NO: 20; 
 (ii) -Phe-Phe- within SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 or SEQ ID NO: 20, wherein said antibody or functional fragment thereof predominantly binds to said -Phe-Phe-; and 
 (iii) -Lys-Leu- within SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, or SEQ ID NO: 20, wherein said antibody or functional fragment thereof predominantly binds to said -Lys-Leu-. 
 
     
     
         171 . A nucleic acid molecule comprising a nucleotide sequence encoding the light chain of a monoclonal antibody, which specifically binds to monomeric, oligomeric or polymeric forms of amyloid-β, wherein:
 (i) the CDR1 of the light chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO:23; 
 (ii) the CDR2 of the light chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO:24; and 
 (iii) the CDR3 of the light chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO:25. 
 
     
     
         172 . A nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain of a monoclonal antibody, which specifically binds to monomeric, oligomeric or polymeric forms of amyloid-β, wherein:
 (i) the CDR1 of the heavy chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO:26; 
 (ii) the CDR2 of the heavy chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO:27; and 
 (iii) the CDR3 of the heavy chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO:28. 
 
     
     
         173 . The nucleic acid of  claim 170  encoding the monoclonal antibody produced by the hybridoma cell line FP 12H3, deposited as DSM ACC2752. 
     
     
         174 . The nucleic acid of  claim 170  encoding the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750. 
     
     
         175 . The nucleic acid of  claim 170  encoding the monoclonal antibody produced by the hybridoma cell line FP 12H3-G2, deposited as DSM ACC2751. 
     
     
         176 . The nucleic acid of  claim 170  encoding the monoclonal antibody produced by the hybridoma cell line ET 7E3, deposited as DSM ACC2755. 
     
     
         177 . The nucleic acid of  claim 170  encoding the monoclonal antibody produced by the hybridoma cell line EJ 7H3, deposited as DSM ACC2756. 
     
     
         178 . The nucleic acid molecule of  claim 171  wherein the nucleotide sequence encodes the light chain variable region of SEQ ID NO:7. 
     
     
         179 . The nucleic acid molecule of  claim 171 , wherein the nucleotide sequence is SEQ ID NO: 9 or the complementary sequence of SEQ ID NO:9. 
     
     
         180 . The nucleic acid molecule of  claim 172  wherein the nucleotide sequence encodes the heavy chain variable region of SEQ ID NO:8. 
     
     
         181 . The nucleic acid molecule of  claim 172 , wherein the nucleotide sequence is SEQ ID NO:11 or the complementary sequence of SEQ ID NO:11. 
     
     
         182 . A host cell comprising the nucleic acid molecule of any one of  claims 170  to  181 . 
     
     
         183 . The host cell of  claim 182 , wherein the host cell is a bacterial cell, insect cell or mammalian cell. 
     
     
         184 . A method for producing a monoclonal antibody, which specifically binds to monomeric, oligomeric or polymeric forms of amyloid-0, comprising culturing the host cell of  claim 182 .