Passive immunization treatment of Alzheimer's disease

• US 6,761,888 B1
• Filed: 05/26/2000
• Issued: 07/13/2004
• Est. Priority Date: 05/26/2000
• Status: Expired due to Term

• Current Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Original Assignee: Neuralab Ltd. (Perrigo Company PLC)
• Inventors: Schenk, Dale B.
• Primary Examiner(s): Kunz, Gary
• Assistant Examiner(s): NICHOLS, CHRISTOPHER J
• Application Number:
  US09/580,018
• Time in Patent Office: 1,509 Days
• Field of Search: 530/300, 530/350, 530/387.1, 424/130.1, 424/131.1, 424/141.1, 424/141.2
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer'"'"'s disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.

Claims

1. A method of prophylactically or therapeutically treating Alzheimer'"'"'s disease, comprising administering to the patient an effective dosage of a pharmaceutical composition comprising a humanized or chimeric antibody that specifically binds to an epitope within Aβ

1-7, and hereby prophylactically or therapeutically treating the patient.

2. The method of claim 1, wherein the antibody is of human isotype IgG1.

3. The method of any one of the preceding claims, wherein the patient is human.

4. The method of claim 1, wherein the antibody specifically binds to an epitope within residues 1-6 of Aβ

.

5. The method of claim 1, wherein the antibody specifically binds to an epitope within residues 1-5 of Aβ

.

6. The method of claim 1, wherein the antibody specifically binds to an epitope within residues 3-7 of Aβ

.

7. The method of claim 1, wherein the antibody specifically binds to an epitope within residues 1-3 of Aβ

.

8. The method of claim 1, wherein the antibody specifically binds to an epitope within residues 14 of Aβ

.

9. The method of claim 1, wherein the patient is asymptomatic.

10. The method of claim 1, wherein the patient is under 50.

11. The method of claim 1, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

12. The method of claim 1, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

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

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

15. The method of claim 1, wherein the antibody is a chimeric antibody.

16. The method of claim 1, wherein the antibody is a polyclonal antibody.

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

18. The method of claim 1, further comprising administering an effective dosage of at least one other antibody that binds to a different epitope of Aβ

.

19. The method of claim 1, wherein the isotype of the antibody is IgG1 or IgG4.

20. The method of claim 1, wherein the isotype of the antibody is IgG2 or IgG3.

21. The method of claim 1, wherein the antibody comprises two copies of the same pair of light and heavy chains.

22. The method of claim 1, wherein the dosage of antibody is at least 1 mg/kg body weight of the patient.

23. The method of claim 1, wherein the dosage of antibody is at least 10 mg/kg body weight of the patient.

24. The method of claim 1, wherein the antibody is administered with a carrier.

25. The method of claim 1, wherein the antibody specifically binds to Aβ

peptide without binding to full-length amyloid precursor protein (APP).

26. The method of claim 1, wherein the antibody is administered intraperitoneally, orally, subcutaneously, intranasally, intramuscularly, topically or intravenously.

27. The method of claim 1, further comprising monitoring the patient for level of administered antibody in the blood of the patient.

28. The method of claim 1, wherein after administration the antibody binds to an amyloid deposit in the patient and induces a clearing response against the amyloid deposit.

29. The method of claim 28, wherein the clearing response is an Fc receptor mediated phagocytosis response.

30. The method of claim 29, further comprising monitoring the clearing response.

31. The method of claims 1, wherein the antibody is a human antibody to Aβ

prepared from B cells from a human immunized with an Aβ

peptide.

32. The method of claim 31, wherein the human immunized with Aβ

peptide is the patient.

33. The method of claim 1, wherein a single dosage of the antibody is administered on multiple occasions.

34. The method of claim 33, wherein the single dosage is administered once every week, once per every two weeks, once a month, once every 3 to 6 months, or yearly.

35. The method of claim 33 or 34 wherein the occasions occur over a period of at least six months.

36. The method of claim 1, wherein the method further comprises monitoring a response to the administration of the antibody to the patient.