Prevention and treatment of amyloidogenic disease

• US 6,787,138 B1
• Filed: 11/28/2000
• Issued: 09/07/2004
• 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
• Application Number:
  US09/723,927
• Time in Patent Office: 1,379 Days
• Field of Search: 514/2, 514/12, 514/21, 424/1.57, 424/185.1, 424/9.1, 424/9.2, 436/15, 436/86, 436/507, 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 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 composition comprising an Aβ

fragment linked to a canier molecule to form a conjugate and an adjuvant wherein the adjuvant enhances an immune response comprising antibodies to the Aβ

fragment.

2. The composition of claim 1, wherein the carrier molecule promotes the immune response against the Aβ

fragment.

3. The composition of claim 1, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

4. The composition of claim 2, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

5. The composition of claim 1, wherein the carrier molecule is a diphtheria toxoid.

6. The composition of claim 2, wherein the carrier molecule is a diphtheria toxoid.

7. The composition of claim 5, wherein the diphtheria toxoid is CRM 197.

8. The composition of claim 6, wherein the diphtheria toxoid is CRM 197.

9. The composition of claim 7, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

10. The composition of claim 8, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

11. A method of prophylactically or therapeutically treating a disease characterized by an amyloid deposit of Aβ

in a patient comprising;

administering an Aβ

fragment and an adjuvant in a regime effective to induce an immune response comprising antibodies to the Aβ

fragment and thereby prophylactically or therapeutically treat the disease in the patient, wherein the Aβ

fragment is linked to a carrier molecule to form a conjugate, and the adjuvant enhances the immune response to the Aβ

fragment.

12. The method of claim 11, wherein the carrier molecule promotes the immune response against the Aβ

fragment.

13. The method of claim 11, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

14. The method of claim 12, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

15. The method of claim 11, wherein the carrier molecule is a diphtheria toxoid.

16. The method of claim 12, wherein the carrier molecule is a diphtheria toxoid.

17. The method of claim 15, wherein the diphtheria toxoid is CRM 197.

18. The method of claim 16, wherein the diphtheria toxoid is CRM 197.

19. The method of claim 17, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

20. The method of claim 18, wherein the Aβ

fragment is from the N-terminal half of Aβ

.

21. The method of claim 11, wherein the patient is a human.

22. The method of claim 11 or 21, wherein the disease is Alzheimer'"'"'s disease.

23. The method of claim 11 or 21, wherein the patient is asymptomatic.

24. The method of claim 11 or 21, wherein the patient is under 50.

25. The method of claim 11 or 21, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

26. The method of claim 11 or 21, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

27. The method of claim 11 or 21, wherein the Aβ

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

28. The method of claim 11 or 21, wherein the Aβ

peptide is administered intramuscularly or subcutaneously.

29. The method of claim 12, wherein the patient is a human.

30. The method of claim 12 or 29, wherein the disease is Alzheimer'"'"'s disease.

31. The method of claim 12 or 29, wherein the patient is asymptomatic.

32. The method of claim 12 or 29, wherein the patient is under 50.

33. The method of claim 12 or 29, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

34. The method of claim 12 or 29, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

35. The method of claim 12 or 29, wherein the Aβ

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

36. The method of claim 12 or 29, wherein the Aβ

peptide is administered intramuscularly or subcutaneously.