Anti-Abeta Antibodies

Abstract

Antibodies that bind human beta-amyloid peptide, methods of detecting, measuring and treating amyloidogenic disorders with said antibodies, pharmaceutical compositions comprising the antibodies and methods of manufacture are provided.

1 . An antibody or fragment thereof that specifically binds to Aβ peptide, comprising a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 and a light chain variable region comprising light chain CDR1, CDR2 and CDR3, wherein:
 heavy chain CDR1 comprises amino acid sequence GFTFX 1 NX 2 GMS, wherein X 1  is S or A, and X 2  is Y or F (SEQ ID NO: 95); 
 heavy chain CDR2 comprises amino acid sequence SX 1 RSGX 2 X 3 RTYYSDNVKG, wherein is X 1  is I or V, X 2  is S or G and X 3  is S or G (SEQ ID NO: 96); 
 heavy chain CDR3 comprises amino acid sequence YDHYX 1 GX 2 SDY, wherein X 1  is S or T and X 2  is S or T (SEQ ID NO: 90); 
 light chain CDR1 comprises amino acid sequence X 1 SSQSLX 2 DX 3 DGKTYLN, wherein X 1  is K or R, X 2  is V, M or L, and X 3  is Y, T or S (SEQ ID NO: 97); 
 light chain CDR2 comprises amino acid sequence X 1 VX 2 NRX 3 X 4 , wherein X 1  is K or R, X 2  is S or T, and X 3  is E or D, and X 4  is S or T (SEQ ID NO: 98); and 
 light chain CDR3 comprises amino acid sequence WQGX 1 HFPRX 2 , wherein X 1  is S or T, and X 2  is S or T (SEQ ID NO: 99). 
 
     
     
         2 . The antibody or fragment thereof of  claim 1 , wherein light chain CDR3 comprises WQGTHFPRS (SEQ ID NO: 38). 
     
     
         3 . The antibody or fragment thereof of  claim 1 , wherein:
 heavy chain CDR1 comprises one of SEQ ID NO: 16, 19, or 20,   heavy chain CDR2 comprises one of SEQ ID NO: 20, 21, 22 or 23,   heavy chain CDR3 comprises one of SEQ ID NO: 18, 24, or 25,   light chain CDR1 comprises one of SEQ ID NO: 26, 29, 31, or 32,   light chain CDR2 comprises one of SEQ ID NO: 33, 34, 35 or 36, and   light chain CDR3 comprises one of SEQ ID NO: 28, 38 or 39.   
     
     
         4 . The antibody or fragment thereof of  claim 1 , wherein the heavy chain variable region, excluding the CDRs, is at least 95% identical an amino acid sequence selected from SEQ ID NOs: 3, 4, 5, 6, and 7, and the light chain variable region, excluding the CDRs, is at least 95% identical an amino acid sequence selected from SEQ ID NOs: 8, 9, 10, 11, 12, 13, 14, and 15. 
     
     
         5 . The antibody or fragment thereof of  claim 4 , wherein heavy chain variable region, excluding the CDRs is at least 98% identical to an amino acid sequence selected from SEQ ID NOs: 3, 4, 5, 6, and 7, and the light chain variable region, excluding the CDRs, is at least 98% identical to an amino acid sequence selected from SEQ ID NOs: 8, 9, 10, 11, 12, 13, 14 and 15. 
     
     
         6 . The antibody or fragment thereof of  claim 5 , wherein heavy chain variable region is selected from SEQ ID NOs: 3, 4, 5, 6, and 7, and the light chain variable region is selected from SEQ ID NOs: 8, 9, 10, 11, 12, 13, 14 and 15. 
     
     
         7 . The antibody or fragment thereof of  claim 1 , wherein the antibody is humanized. 
     
     
         8 . The antibody or fragment thereof of  claim 7 , wherein the antibody is a full antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody. 
     
     
         9 . The antibody or fragment thereof of  claim 1 , wherein the antibody is human IgG1. 
     
     
         10 . The antibody or fragment thereof of  claim 9 , wherein the antibody is a full antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody. 
     
     
         11 . The antibody or fragment thereof of  claim 1 , wherein the fragment is a Fab, Fab′, F(ab′)2, Fabc, or Fv. 
     
     
         12 . The antibody or fragment thereof of  claim 1 , further comprising heavy chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 40. 
     
     
         13 . The antibody or fragment thereof of  claim 1 , further comprising light chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 41. 
     
     
         14 . The antibody or fragment thereof of  claim 1 , wherein the antibody specifically binds to an epitope having an amino acid sequence including three or more amino acid positions from amino acids 1-7 of Aβ.