Humanized antibodies against the β-amyloid peptide

1. An isolated antibody that selectively binds to the C-terminal part of beta-amyloid, the antibody comprising a variable light chain fragment (VL) sequence comprising the variable light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID Nos. 1, 2 and 3, respectively, and a variable heavy chain fragment (VH) sequence comprising the variable heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID Nos. 4, 5 and 6, respectively, wherein:

a) position 1 of the light chain is an aspartate residue;

b) position 43 of the light chain is a proline residue;

c) position 46 of the light chain is an alanine residue;

d) position 61 of the light chain is an arginine residue;

e) position 104 of the light chain is a leucine residue;

f) position 105 of the light chain is a glutamate residue; and

g) position 106 of the light chain is a valine residue, according to Kabat numbering.

2. The antibody of claim 1 , wherein:

a) position 9 of the heavy chain is a proline residue;

b) position 28 of the heavy chain is a threonine residue;

c) position 71 of the heavy chain is a valine residue;

d) position 73 of the heavy chain is an arginine residue;

e) position 75 of the heavy chain is a serine residue;

f) position 76 of the heavy chain is a serine residue; and

g) position 78 of the heavy chain is an alanine residue, according to Kabat numbering.

3. The antibody of claim 1 , comprising the variable heavy chain fragment (VH) sequence set forth in SEQ ID: No. 17.

4. The antibody of claim 1 , comprising the variable light chain fragment (VL) sequence set forth in SEQ ID NO: 7.

5. The antibody of claim 1 , further comprising the sequence set forth in SEQ ID NO: 25.

6. The antibody of claim 1 , demonstrating the characteristics of:

(i) binding to both beta-amyloid 40 and beta-amyloid 42 , with a high and substantially identical affinity;

(ii) displaying a high affinity for oligomeric and monomeric forms of beta-amyloid; and/or

(iii) having a solubility of at least 5 mg/ml.

7. The antibody of claim 6 , further demonstrating at least one of the following characteristics:

(iv) mediating the uptake of fibrillar beta-amyloid by microglia;

(v) binding beta-amyloid plaques; and/or

(vi) removing beta-amyloid fibrils in the brain and/or inhibiting the formation of amyloid fibrils in the brain.

8. The antibody of claim 1 , wherein the antibody inhibits oligomerization of beta-amyloid.

9. The antibody of claim 1 , wherein the antibody is a full-length antibody.

10. The antibody of claim 1 , being an antigen-binding fragment wherein the antigen-binding fragment is an Fv fragment, a single domain fragment, a single chain antibody (scFv), a Fab fragment or a F(ab′) 2 fragment.

11. The antibody of claim 1 , linked to a therapeutic agent.

12. The antibody of claim 1 , being chemically modified.

13. The antibody of claim 1 , linked to a label.

14. The antibody of claim 13 , wherein the label comprises 64 Cu.

15. A diagnostic or scientific tool comprising the antibody of any one of claim 1 , 12 or 13 .

16. A test kit comprising the antibody of any one of claim 1 , 12 or 13 .

17. A diagnostic or scientific tool comprising the antibody of claim 12 .

18. A diagnostic or scientific tool comprising the antibody of claim 13 .

19. A test kit comprising the antibody of claim 12 .

20. A test kit comprising the antibody of claim 13 .

21. A pharmaceutical composition for treating or delaying the progression of Alzheimer's disease comprising the antibody of claim 1 .

22. An isolated antibody that selectively binds to the C-terminal part of beta-amyloid, wherein the antibody comprises the variable light chain fragment (VL) sequence set forth in SEQ ID NO: 7 and the variable heavy chain fragment (VH) sequence set forth in SEQ ID NO: 17.

23. The antibody of claim 22 , wherein the antibody is a full-length antibody.

24. The antibody of claim 22 , being an antigen-binding fragment wherein the antigen-binding fragment is an Fv fragment, a single domain fragment, a single chain antibody (scFv), a Fab fragment or a F(ab′) 2 fragment.

25. An isolated antibody that selectively binds to the C-terminal part of beta-amyloid, wherein the antibody comprises SEQ ID NO: 24.

26. The antibody of claim 22 or 25 being chemically modified.

27. A diagnostic or scientific tool comprising the antibody of claim 26 .

28. A test kit comprising the antibody of claim 26 .

29. The antibody of claim 22 or 25 linked to a therapeutic agent.

30. The antibody of claim 22 or 25 linked to a label.

31. The antibody of claim 30 , wherein the label comprises 64 Cu.

32. A diagnostic or scientific tool comprising the antibody of claim 30 .

33. A test kit comprising the antibody of claim 30 .

34. The antibody of claim 22 or 25 demonstrating the characteristics of:

(i) binding to both beta-amyloid 40 and beta-amyloid 42 , with a high and substantially identical affinity;

(ii) displaying a high affinity for oligomeric and monomeric forms of beta-amyloid; and/or

(iii) having a solubility of at least 5 mg/ml.

35. The antibody of claim 34 , further demonstrating at least one of the following characteristics:

(iv) mediating the uptake of fibrillar beta-amyloid by microglia;

(v) binding beta-amyloid plaques; and/or

(vi) removing beta-amyloid fibrils in the brain and/or inhibiting the formation of amyloid fibrils in the brain.

36. A diagnostic or scientific tool comprising the antibody of claim 22 or 25 .

37. A test kit comprising the antibody of claim 22 or 25 .

38. A pharmaceutical composition for treating or delaying the progression of Alzheimer's Disease comprising the antibody of claim 22 or 25 .

39. The antibody of claim 22 or 25 , wherein the antibody inhibits oligomerization of beta-amyloid.