Prevention and treatment of amyloidogenic disease

• US 6,818,218 B2
• Filed: 03/31/2004
• Issued: 11/16/2004
• 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:
  US10/816,529
• Publication Number:
  US 20040166119A1
• Time in Patent Office: 230 Days
• Field of Search: 424/184.1, 424/185.1, 514/2, 514/4, 530/300, 530/324
• 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 reponse 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 pharmaceutical composition comprising an Aβ

peptide and a pharmaceutically acceptable adjuvant effective to induce an immune response comprising antibodies to Aβ

in a patient, wherein the adjuvant enhances the immune response to Aβ

.

2. The pharmaceutical composition of claim 1, wherein the adjuvant comprises alum.

3. The pharmaceutical composition of claim 1, wherein the adjuvant comprises monophosphoryl lipid (MPL).

4. The pharmaceutical composition of claim 1, wherein the adjuvant comprises Quillaja Saponaria Molina (QS21).

5. The pharmaceutical composition of claim 1, wherein the adjuvant comprises GM-CSF.

6. The pharmaceutical composition of claim 1, wherein the adjuvant comprises M-CSF.

7. The pharmaceutical composition of claim 1, wherein the Aβ

peptide is encapsulated within a particle.

8. The pharmaceutical composition of claim 7, wherein the particle is a polylactide polyglycolide copolymer (PLPG) particle.

9. The pharmaceutical composition of claim 1, which comprises greater than 10 μ

g of the Aβ

peptide.

10. The pharmaceutical composition of claim 1, which comprises at least 20 μ

g of the Aβ

peptide.

11. The pharmaceutical composition of claim 1, which comprises at least 50 μ

g of the Aβ

peptide.

12. The pharmaceutical composition of claim 1, which comprises at least 100 μ

g of the Aβ

peptide.

13. The pharmaceutical composition of claim 1, wherein the Aβ

peptide is Aβ

43.

14. The pharmaceutical composition of claim 13, wherein the Aβ

peptide is SEQ ID NO;

1.

15. The pharmaceutical composition of claim 1, wherein the Aβ

peptide is Aβ

42.

16. The pharmaceutical composition of claim 15, wherein the Aβ

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

1.

17. The pharmaceutical composition of claim 1, wherein the Aβ

peptide is Aβ

41.

18. The pharmaceutical composition of claim 17, wherein the Aβ

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

1.

19. The pharmaceutical composition of claim 1, wherein the Aβ

peptide is Aβ

40.

20. The pharmaceutical composition of claim 19, wherein the Aβ

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

1.

21. The pharmaceutical composition of claim 1, wherein the Aβ

peptide is Aβ

39.

22. The pharmaceutical composition of claim 21, wherein the Aβ

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

1.

23. The pharmaceutical composition of claim 1, which is free of Complete Freund'"'"'s adjuvant.

24. The pharmaceutical composition of claim 1, wherein the adjuvant is selected from the group consisting of alum, monophosphoryl lipid (MPL), Quillaja Saponaria Molina (QS21), GM-CSF, and M-CSF.

25. The pharmaceutical composition of claim 24, which comprises greater than 10 μ

g of the Aβ

peptide.

26. The pharmaceutical composition of claim 24, which comprises at least 20 μ

g of the Aβ

peptide.

27. The pharmaceutical composition of claim 24, which comprises at least 50 μ

g of the Aβ

peptide.

28. The pharmaceutical composition of claim 24, which comprises at least 100 μ

g of the Aβ

peptide.

29. The pharmaceutical composition of claim 24, wherein the Aβ

peptide is Aβ

43.

30. The pharmaceutical composition of claim 29, wherein the Aβ

peptide is SEQ ID NO;

1.

31. The pharmaceutical composition of claim 24, wherein the Aβ

peptide is Aβ

42.

32. The pharmaceutical composition of claim 31, wherein the Aβ

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

1.

33. The pharmaceutical composition of claim 24, wherein the Aβ

peptide is Aβ

41.

34. The pharmaceutical composition of claim 33, wherein the Aβ

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

1.

35. The pharmaceutical composition of claim 24, wherein the Aβ

peptide is Aβ

40.

36. The pharmaceutical composition of claim 35, wherein the Aβ

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

1.

37. The pharmaceutical composition of claim 24, wherein the Aβ

peptide is Aβ

39.

38. The pharmaceutical composition of claim 37, wherein the Aβ

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

1.