Prevention and treatment of amyloidogenic disease

• US 6,866,849 B2
• Filed: 03/31/2004
• Issued: 03/15/2005
• Est. Priority Date: 12/02/1997
• Status: Expired due to Term

• Current Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson), Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: Neuralab Ltd. (Perrigo Company PLC)
• Inventors: Schenk, Dale B.
• Primary Examiner(s): SCHEINER, LAURIE A
• Application Number:
  US10/815,391
• Publication Number:
  US 20040175394A1
• Time in Patent Office: 349 Days
• Field of Search: 424/184.1, 424/185.1, 514/2, 514/4, 530/300, 530/403
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/55577 Saponins; Quil A; QS21; ISCOMS
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/605 MHC molecules or ligands thereof
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: Y10T 436/105831 Protein or peptide standard or control [e.g., hemoglobin, etc.]

Abstract

The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer'"'"'s disease. In such methods, a suitable agent is Aβ peptide or an antibody thereto.

Claims

1. A method of therapeutically treating a disease characterized by an amyloid deposit of Aβ

in a patient, comprising;

administering an Aβ

peptide in a regime effective to induce an immune response comprising antibodies to the Aβ

peptide and thereby therapeutically treat the disease in the patient; and

monitoring the patient for the immune response, wherein the monitoring comprises detecting antibodies having Aβ

binding specificity.

2. The method of claim 1, wherein the patient is a human.

3. The method of claim 1, wherein the disease is Alzheimer'"'"'s disease.

4. The method of any one of claims 1-3, wherein the patient is asymptomatic.

5. The method of any one of claims 1-3, wherein the patient is under 50.

6. The method of any one of claims 1-3, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

7. The method of any one of claims 1-3, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

8. The method of any one of claims 1-3, wherein the dose of the Aβ

peptide administered to the patient is greater than 10 μ

g.

9. The method of any one of claims 1-3, wherein the dose of the Aβ

peptide administered to the patient is at least 20 μ

g.

10. The method of any one of claims 1-3, wherein the dose of the Aβ

peptide administered to the patient is at least 50 μ

g.

11. The method of any one of claims 1-3, wherein the dose of the Aβ

peptide administered to the patient is at least 100 μ

g.

12. The method of any one of claims 1-3, wherein the Aβ

peptide is administered in aggregated form.

13. The method of any one of claims 1-3, wherein the Aβ

peptide is administered orally, subcutaneously, intramuscularly, topically or intravenously.

14. The method of any one of claims 1-3, wherein the Aβ

peptide is administered intramuscularly or subcutaneously.

15. The method of claim 1, wherein the Aβ

peptide is administered with GM-CSF in the regime.

16. The method of claim 1, further comprising administering an adjuvant, wherein the adjuvant enhances the immune response to the Aβ

peptide.

17. The method of claim 16, wherein the adjuvant and the Aβ

peptide are administered together as a composition.

18. The method of claim 16, wherein the adjuvant is administered before the Aβ

peptide.

19. The method of claim 16, wherein the adjuvant is administered after the Aβ

peptide.

20. The method of claim 16, wherein the adjuvant is alum.

21. The method of claim 16, wherein the adjuvant is QS21.

22. The method of claim 16, wherein the adjuvant is M-CSF.

23. The method of claim 16, wherein the dose of the Aβ

peptide is greater than 10 μ

g.

24. The method of claim 16, wherein the dose of the Aβ

peptide is at least 20 μ

g.

25. The method of claim 16, wherein the dose of the Aβ

peptide is at least 50 μ

g.

26. The method of claim 16, wherein the dose of the Aβ

peptide is at least 100 μ

g.

27. The method of claim 16, wherein the Aβ

peptide is Aβ

43.

28. The method of claim 27, wherein the Aβ

peptide is SEQ ID NO;

1.

29. The method of claim 16, wherein the Aβ

peptide is Aβ

42.

30. The method of claim 29, wherein the Aβ

consists of amino acids residues 1-42 of SEQ ID NO;

1.

31. The method of claim 16, wherein the Aβ

peptide is Aβ

41.

32. The method of claim 31, wherein the Aβ

consists of amino acids residues 1-41 of SEQ ID NO;

1.

33. The method of claim 16, wherein the Aβ

peptide is Aβ

40.

34. The method of claim 33, wherein the Aβ

consists of amino acids residues 1-40 of SEQ ID NO;

1.

35. The method of claim 16, wherein the Aβ

peptide is Aβ

39.

36. The method of claim 35, wherein the Aβ

consists of amino acids residues 1-39 of SEQ ID NO;

1.

37. A method of prophylaxis of a disease characterized by an amyloid deposit of Aβ

in a patient, comprising;

administering an Aβ

peptide in a regime effective to induce an immune response comprising antibodies to the Aβ

peptide and thereby effect prophylaxis of the disease in the patient; and

monitoring the patient for the immune response, wherein the monitoring comprises detecting antibodies having Aβ

binding specificity.

38. The method of claim 37, wherein the patient is a human.

39. The method of claim 37, wherein the disease is Alzheimer'"'"'s disease.

40. The method of any one of claims 37-39, wherein the patient is asymptomatic.

41. The method of any one of claims 37-39, wherein the patient is under 50.

42. The method of any one of claims 37-39, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

43. The method of any one of claims 37-39, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

44. The method of any one of claims 37-39, wherein the dose of the Aβ

peptide administered to the patient is greater than 10 μ

g.

45. The method of any one of claims 37-39, wherein the dose of the Aβ

peptide administered to the patient is at least 20 μ

g.

46. The method of any one of claim 37-39, wherein the dose of the Aβ

peptide administered to the patient is at least 50 μ

g.

47. The method of anyone of claims 37-39, wherein the dose of the Aβ

peptide administered to the patient is at least 100 μ

g.

48. The method of any one of claims 37-39, wherein the Aβ

peptide is administered in aggregated form.

49. The method of any one of claims 37-39, wherein the Aβ

peptide is administered orally, subcutaneously, intramuscularly, topically or intravenously.

50. The method of any one of claims 37-39, wherein the Aβ

peptide is administered intramuscularly or subcutaneously.

51. The method of claim 37, wherein the Aβ

peptide is administered with GM-CSF in the regime.

52. The method of claim 37, further comprising administering an adjuvant, wherein the adjuvant enhances the immune response to the Aβ

peptide.

53. The method of claim 52, wherein the adjuvant and the Aβ

peptide are administered together as a composition.

54. The method of claim 52, wherein the adjuvant is administered before the Aβ

peptide.

55. The method of claim 52, wherein the adjuvant is administered after the Aβ

peptide.

56. The method of claim 52, wherein the adjuvant is alum.

57. The method of claim 52, wherein the adjuvant is QS21.

58. The method of claim 52, wherein the adjuvant is M-CSF.

59. The method of claim 52, wherein the dose of the Aβ

peptide is greater than 10 μ

g.

60. The method of claim 52, wherein the dose of the Aβ

peptide is at least 20 μ

g.