Anti-abeta antibodies
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 an antigen binding 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 the amino acid sequence of SEQ ID NO: 16,
heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20,
heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18,
light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 29,
light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34, and
light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 38.
2. The antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region, excluding the CDRs, is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, and wherein the light chain variable region, excluding the CDRs, is at least 95% identical to the amino acid sequence of SEQ ID NO: 9.
3. The antibody or antigen binding fragment thereof of claim 2 , wherein the heavy chain variable region, excluding the CDRs, is at least 98% identical to the amino acid sequence of SEQ ID NO: 3, and wherein the light chain variable region, excluding the CDRs, is at least 98% identical to the amino acid sequence of SEQ ID NO: 9.
4. The antibody or antigen binding fragment thereof of claim 3 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 3, and wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 9.
5. The antibody or antigen binding fragment thereof of claim 4 further comprising a heavy chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 40.
6. The antibody or antigen binding fragment thereof of claim 4 further comprising a light chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 41.
7. The antibody or antigen binding fragment thereof of claim 5 further comprising a light chain constant region comprising an amino acid sequence at least 95% identical to SEQ ID NO: 41.
8. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is a humanized IgG1.
9. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is a full antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody.
10. The antibody or antigen binding fragment thereof of claim 1 , wherein the antigen binding fragment is a Fab, Fab′, F(ab′)2, Fabc, or Fv.
11. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof specifically binds to an epitope having an amino acid sequence including three or more amino acid positions from amino acids 1-7 of Aβ (SEQ ID NO: 84).
12. A pharmaceutical composition, comprising:
a pharmaceutically effect amount of the antibody or antigen binding fragment thereof of claim 1 ; and
a pharmaceutically acceptable carrier or diluent.
13. A humanized IgG1 antibody or an antigen binding fragment thereof that specifically binds to Aβ peptide, comprising:
a) a heavy chain comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3; and
b) a light chain comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 9.
14. The humanized IgG1 antibody or antigen binding fragment thereof of claim 13 , wherein the antibody is a full antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody.
15. The humanized IgG1 antibody or antigen binding fragment thereof of claim 13 , wherein the antigen binding fragment is a Fab, Fab′, F(ab′)2, Fabc, or Fv.
16. A pharmaceutical composition, comprising:
a pharmaceutically effective amount of the humanized IgG1 antibody or antigen binding fragment thereof of claim 13 ; and
a pharmaceutically acceptable carrier or diluent.
17. A humanized IgG1 antibody that specifically binds to Aβ peptide, comprising:
a) a heavy chain comprising
a variable region comprising the amino acid sequence of SEQ ID NO: 3, and
a constant region comprising the amino acid sequence of SEQ ID NO: 40 with or without the C-terminal lysine; and
b) a light chain comprising
a variable region comprising the amino acid sequence of SEQ ID NO: 9, and
a constant region comprising the amino acid sequence of SEQ ID NO: 41.
18. The humanized IgG1 antibody of claim 17 , wherein the antibody is a full antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody.
19. A pharmaceutical composition, comprising:
a pharmaceutically effective amount of the humanized IgG1 antibody of claim 17 ; and
a pharmaceutically acceptable carrier or diluent.