Prevention and treatment of amyloidogenic disease

• US 6,962,707 B2
• Filed: 07/01/2004
• Issued: 11/08/2005
• 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
• Application Number:
  US10/884,892
• Publication Number:
  US 20050053614A1
• Time in Patent Office: 495 Days
• Field of Search: 424/193.1, 424/185.1, 424/1.57, 424/9.1, 424/9.2, 514/2, 514/21, 436/86, 530/300, 530/403, 530/350
• US Class Current: 424/193.1
• 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 therapeutic agent comprising a peptide analog of an immunogenic, natural Aβ

peptide or a fragment thereof, the analog comprising an epitope that induces a similar protective or therapeutic immune response on administration to a patient as the Aβ

peptide.

2. The therapeutic agent of claim 1, wherein the analog exhibits at least 90% sequence identity with the immunogenic Aβ

fragment.

3. The therapeutic agent of claim 1, which is the analog of an Aβ

fragment comprising at least 20 contiguous amino acids of the Aβ

peptide.

4. The therapeutic agent of claim 1, which is the analog of an Aβ

fragment comprising the N-terminal half of the Aβ

peptide.

5. The therapeutic agent of claim 1, which is the analog of an Aβ

fragment consisting of the first 20 N-terminal amino acids of SEQ ID NO;

1.

6. The therapeutic agent of claim 1, comprising a multimer of the analog.

7. The therapeutic agent of claim 1, wherein the analog comprises a carrier molecule linked at its amino terminus, its carboxyl terminus or internally to form a conjugate.

8. The therapeutic agent of claim 1, wherein the analog comprises a carrier molecule linked at its amino terminus or at its carboxyl terminus.

9. The therapeutic agent of claim 7, wherein the carrier molecule is a peptide.

10. The therapeutic agent of claim 9, wherein the peptide comprises polymeric amino acids.

11. The therapeutic agent of claim 10, wherein the peptide comprises polylysine or polyglutamic acid.

12. The therapeutic agent of claim 7, comprising a multimer of the analog linked to the carrier molecule.

13. The therapeutic agent of claim 12, wherein the carrier molecule is a peptide.

14. The therapeutic agent of claim 13, wherein the peptide comprises polymeric amino acids.

15. The therapeutic agent of claim 14, wherein the peptide comprises polylysine or polyglutamic acid.

16. A pharmaceutical composition comprising the therapeutic agent of any one of claims 1, 6, 7, or 12 and a pharmaceutically acceptable component.

17. The pharmaceutical composition of claim 16, wherein the pharmaceutically acceptable component is an adjuvant, a diluent, a stabilizer, a carrier, an auxiliary substance or an excipient.

18. The pharmaceutical composition of claim 17, wherein the adjuvant is alum.

19. The therapeutic agent of one of claims 1 or 6, wherein the analog is cross-linked to a carrier molecule to form a conjugate.

20. The therapeutic agent of claim 19, wherein the carrier molecule is a protein, peptide, or toxin.

21. The therapeutic agent of claim 20, wherein the peptide comprises polymeric amino acids.

22. The therapeutic agent of claim 21, wherein the peptide comprises polylysine or polyglutamic acid.

23. The therapeutic agent of claim 20, wherein the carrier molecule comprises a helper T cell epitope.

24. The therapeutic agent of claim 23, wherein the helper T cell epitope comprises a universal T-cell epitope.

25. The therapeutic agent of claim 24, wherein the carrier molecule comprising the helper T cell epitope is tetanus toxoid, diphtheria toxoid or hepatitus B virus surface antigen (HBsAg).

26. The therapeutic agent of claim 24, wherein the universal T-cell epitope comprises a universal T-cell epitope of tetanus toxoid, hepatitus B virus surface antigen, influenza hemagluttinin, or bacille Calmette-Guerin.

27. The therapeutic agent of claim 19, wherein the carrier molecule is a polyactide polyglycolide coploymer (PLPG).

28. A pharmaceutical composition comprising the therapeutic agent of claim 19 and a pharmaceutically acceptable component.

29. The pharmaceutical composition of claim 28, wherein the pharmaceutically acceptable component is an adjuvant, a diluent, a stabilizer, a carrier, an auxiliary substance or an excipient.

30. The pharmaceutical composition of claim 29, wherein the adjuvant is alum.

31. The therapeutic agent of one of claims 7 to 15, wherein the conjugate is cross-linked to a carrier molecule.

32. The therapeutic agent of claim 31, wherein the carrier molecule is a protein, peptide, or toxin.

33. The therapeutic agent of claim 31, wherein the peptide comprises polymeric amino acids.

34. The therapeutic agent of claim 33, wherein the peptide comprises polylysine or polyglutamic acid.

35. The therapeutic agent of claim 32, wherein the carrier molecule comprises a helper T cell epitope.

36. The therapeutic agent of claim 35, wherein the helper T cell epitope comprises a universal T-cell epitope.

37. The therapeutic agent of claim 35, wherein the carrier molecule comprising the helper T cell is tetanus toxoid, diphtheria toxoid or hepatitus B virus surface antigen (HBsAg).

38. The therapeutic agent of claim 36, wherein the universal T-cell epitope comprises a universal T-cell epitope of tetanus toxoid, hepatitus B virus surface antigen, influenza hemagluttinin, or bacille Calmette-Guerin.

39. The therapeutic agent of claim 31, wherein the carrier molecule is a polyactide polyglycoloide copolymer (PLPG).

40. A Pharmaceutical composition comprising the therapeutic agent of claim 31 and a pharmaceutically acceptable component.

41. The pharmaceutical composition of claim 40, wherein the pharmaceutically acceptable component is an adjuvant, a diluent, a stabilizer, a carrier, an auxiliary substance or an excipient.

42. The pharmaceutical composition of claim 41, wherein the adjuvant is alum.