Methods of treating Alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof

• US 20040146512A1
• Filed: 10/09/2003
• Published: 07/29/2004
• Est. Priority Date: 10/09/2002
• Status: Abandoned Application

• Current Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Original Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Inventors: Levkowitz, Gil, Rosenthal, Arnon
• Application Number:
  US10/683,815
• Publication Number:
  US 20040146512A1
• Time in Patent Office: Days
• US Class Current: 424/146.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Monoclonal antibodies directed against amyloid beta peptide and methods of using same for treatment and prevention of Alzheimer'"'"'s disease and Down'"'"'s syndrome are described.

Claims

1. A method for treating Alzheimer'"'"'s disease comprising administering to a subject an effective amount of a pharmaceutical composition comprising an antibody that binds preferentially to amino acids 28-40 of Aβ

_1-40 peptide (SEQ ID NO;

1) and a pharmaceutical acceptable carrier.

2. The method of claim 1, wherein the antibody binds preferentially to an epitope that includes amino acid 39 and/or 40 of the Aβ

_1-40 peptide (SEQ ID NO;

1).

3. The method of claim 1 or 2, wherein the antibody does not show significant cross-reactivity with Aβ

_1-42 and Aβ

_1-43 peptide.

4. The method of claim 1, wherein the Fab fragment of the antibody binds to Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 200 nM or less.

5. The method of claim 1, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

6. The method of claim 2, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 200 nM or less.

7. The method of claim 2, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

8. The method of claim 1, wherein the antibody competitively inhibits binding of a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 to Aβ

_1-40 peptide (SEQ ID NO;

1).

9. The method of claim 1, wherein the antibody binds to the same epitope to which a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 binds.

10. The method of claim 1, wherein the antibody is monoclonal antibody.

11. The method of claim 1, wherein the antibody is a humanized antibody.

12. The method of claim 1, wherein the antibody is a human antibody.

13. A method of suppressing formation of amyloid plaques in a subject comprising administering to a subject an effective amount of a pharmaceutical composition comprising an antibody that binds preferentially to amino acids 28-40 of Aβ

_1-40 peptide (SEQ ID NO;

1) and a pharmaceutical acceptable carrier.

14. The method of claim 13, wherein the antibody binds preferentially to an epitope that includes amino acid 39 and/or 40 of the Aβ

_1-40 peptide (SEQ ID NO;

     1).

15. The method of claim 13, wherein the antibody does not show significant cross-reactivity with Aβ

_1-42 and Aβ

_1-43 peptide.

16. The method of claim 13, wherein the Fab fragment of the antibody binds to Aβ

_1-40 peptide (SEQ ID NO;

1) with an affinity of about 200 nM or less.

17. The method of claim 13, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

18. The method of claim 14, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 200 nM or less.

19. The method of claim 14, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

1) with an affinity of about 1 nM or less.

20. The method of claim 13, wherein the antibody competitively inhibits binding of a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 to Aβ

_1-40 peptide (SEQ ID NO;

1).

21. The method of claim 13, wherein the antibody binds to the same epitope to which a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 binds.

22. The method of claim 13, wherein the antibody is monoclonal antibody.

23. The method of claim 13, wherein the antibody is a humanized antibody.

24. The method of claim 13, wherein the antibody is a human antibody.

25. The method of claim 13, wherein the amyloid plaques are in the brain of the subject.

26. A method of reducing amyloid plaques in a subject comprising administering to a subject an effective amount of a pharmaceutical composition comprising an antibody that binds preferentially to amino acids 28-40 of Aβ

_1-40 peptide (SEQ ID NO;

     1) and a pharmaceutical acceptable carrier.

27. The method of claim 26, wherein the antibody binds preferentially to an epitope that includes amino acid 39 and/or 40 of the Aβ

_1-40 peptide (SEQ ID NO;

1).

28. The method of claim 26, wherein the antibody does not show significant cross-reactivity with Aβ

_1-42 and Aβ

_1-43 peptide.

29. The method of claim 26, wherein the Fab fragment of the antibody binds to Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 200 nM or less.

30. The method of claim 26, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

31. The method of claim 26, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 200 nM or less.

32. The method of claim 27, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

33. The method of claim 26, wherein the antibody competitively inhibits binding of a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 to Aβ

_1-40 peptide (SEQ ID NO;

1).

34. The method of claim 26, wherein the antibody binds to the same epitope to which a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 binds.

35. The method of claim 26, wherein the antibody is monoclonal antibody.

36. The method of claim 26, wherein the antibody is a humanized antibody.

37. The method of claim 26, wherein the antibody is a human antibody.

38. The method of claim 26, wherein the amyloid plaques are in the brain of the subject.

39. A method of delaying development of a symptom associated with Alzheimer'"'"'s disease in a subject comprising administering to the subject an effective amount of a pharmaceutical composition comprising an antibody that binds preferentially to amino acids 28-40 of Aβ

_1-40 peptide (SEQ ID NO;

1) and a pharmaceutical acceptable carrier.

40. The method of claim 39, wherein the antibody binds preferentially to an epitope that includes amino acid 39 and/or 40 of the Aβ

_1-40 peptide (SEQ ID NO;

1).

41. The method of claim 39, wherein the antibody does not show significant cross- reactivity with Aβ

_1-42 and Aβ

_1-43 peptide.

42. The method of claim 39, wherein the Fab fragment of the antibody binds to Aβ

_1-40 peptide (SEQ ID NO;

1) with an affinity of about 200 nM or less.

43. The method of claim 39, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

44. The method of claim 40, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

1) with an affinity of about 200 nM or less.

45. The method of claim 40, wherein the Fab fragment of the antibody binds Aβ

_1-40 peptide (SEQ ID NO;

     1) with an affinity of about 1 nM or less.

46. The method of claim 39, wherein the antibody competitively inhibits binding of a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 to Aβ

_1-40 peptide (SEQ ID NO;

1).

47. The method of claim 39, wherein the antibody binds to the same epitope to which a monoclonal antibody comprising amino acid sequence of SEQ ID NO:

4 and 6 binds.

48. The method of claim 39, wherein the antibody is monoclonal antibody.

49. The method of claim 39, wherein the antibody is a humanized antibody.

50. The method of claim 39, wherein the antibody is a human antibody.