Passive immunization of Alzheimer's disease

• US 6,913,745 B1
• Filed: 06/01/2000
• Issued: 07/05/2005
• Est. Priority Date: 12/02/1997
• Status: Expired due to Term

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Original Assignee: Neuralab Ltd. (Perrigo Company PLC)
• Inventors: Schenk, Dale B.
• Primary Examiner(s): Kemmerer, Elizabeth
• Assistant Examiner(s): NICHOLS, CHRISTOPHER J
• Application Number:
  US09/979,952
• Time in Patent Office: 1,860 Days
• Field of Search: 424/130.1, 424/134.1, 424/141.1, 424/178.1, 424/142.1, 424/184.1, 530/387.1, 530/387.3, 530/388.1, 530/388.15, 530/300, 530/350, 514/2
• US Class Current: 424/130.1
• 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 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• 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 2319/00 Fusion polypeptide
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Disclosed are pharmaceutical compositions and methods for preventing or treating a number of amyloid diseases, including Alzheimer'"'"'s disease, prion diseases, familial amyloid neuropathies and the like. The pharmaceutical compositions include immunologically reactive amounts of amyloid fibril components, particularly fibril-forming peptides or proteins. Also disclosed are therapeutic compositions and methods which use immune reagents that react with such fibril components.

Claims

1. A method of prophylactically treating Alzheimer'"'"'s disease in a patient susceptible to the disease, comprising administering to the patient an effective dosage of a pharmaceutical composition comprising a chimeric or humanized antibody that specifically binds to an epitope within residues 1-5 of Aβ

, and thereby effecting prophylaxis of the disease.

2. The method of claim 1, wherein said effective dosage is characterized by a level in the patient of a serum amount of immunoreactivity against Aβ

that is at least about four times higher than a serum level of immunoreactivity against said component measured in a pre-treatment control serum sample.

3. The method of claim 1, wherein the pharmaceutical composition further comprises a carrier.

4. The method of claim 1, wherein the pharmaceutical composition is administered intraperitoneally, orally, subcutaneously, intramuscularly, intranasally, topically, or intravenously.

5. The method of claim 1, wherein the pharmaceutical composition is administered on multiple occasions.

6. The method of claim 1, wherein the pharmaceutical composition is administered as a sustained release composition.

7. The method of claim 5, wherein the effective dosage is administered once every week, once per every two weeks, once a month, once every 3 to 6 months, or yearly.

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

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

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

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

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

13. The method of claim 1, wherein the humanized antibody is a humanized version of monoclonal antibody 3D6 (ATCC accession number PTA-5130).

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

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

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

17. The method of claim 1, wherein the dosage of the antibody is 0.01 to 5 mg/kg body weight of the patient.

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

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

20. A method of therapeutically treating Alzheimer'"'"'s disease in a patient suffering from the disease, comprising administering to the patient an effective dosage of a pharmaceutical composition comprising a chimeric or humanized antibody or antibody fragment thereof that specifically binds to an epitope within residues 1-5 of Aβ

, and thereby therapeutically treat the disease.

21. The method of claim 20, wherein said effective dosage is characterized by a level in the patient of a serum amount of immunoreactivity against Aβ

that is at least about four times higher than a serum level of immunoreactivity against said component measured in a pre-treatment control serum sample.

22. The method of claim 20, wherein the pharmaceutical composition is administered with a carrier.

23. The method of claim 20, wherein the pharmaceutical composition is administered intraperitoneally, orally, subcutaneously, intramuscularly, intranasally, topically or intravenously.

24. The method of claim 20, wherein the pharmaceutical composition is administered on multiple occasions.

25. The method of claim 24, wherein the effective dosage administered once every week, once per every two weeks, once a month, once every 3 to 6 months, or yearly.

26. The method of claim 20, wherein the pharmaceutical composition is administered as a sustained release composition.

27. The method of claim 20, wherein the patient is human.

28. The method of claim 20, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

29. The method of claim 20, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

30. The method of claim 20, wherein the patient has Alzheimer'"'"'s disease.

31. The method of claim 20, wherein the antibody is a humanized antibody.

32. The method of claim 31, wherein the humanized antibody is a humanized version of monoclonal antibody 3D6 (ATCC accession number PTA-5130).

33. The method of claim 20, wherein the antibody is a chimeric antibody.

34. The method of claim 20, wherein the antibody is a polyclonal antibody.

35. The method of claim 20, wherein the antibody is a monoclonal antibody.

36. The method of claim 20, wherein the dosage of the antibody is 0.01 to 5 mg/kg body weight of the patient.

37. The method of claim 20, further comprising monitoring the patient for level of administered antibody in the blood of the patient.

38. The method of claim 30, wherein the method further comprises monitoring a response to the administration of the antibody to the patient.

46. The pharmaceutical composition of claim 35, wherein said composition is a liquid solution.

39. A pharmaceutical composition comprising a chimeric or humanized antibody or antibody fragment thereof that specifically binds to an epitope within residues 1-5 of Aβ

and a pharmaceutical carrier.

40. The pharmaceutical composition of claim 39, wherein the antibody is a humanized antibody.

41. The pharmaceutical composition of claim 40, wherein the humanized antibody is a humanized version of monoclonal antibody 3D6 (ATCC accession number PTA-5130).

42. The pharmaceutical composition of claim 39, wherein the antibody is a chimeric antibody.

43. The pharmaceutical composition of claim 39, wherein the antibody is a polyclonal antibody.

44. The pharmaceutical composition of claim 39, wherein the antibody is a monoclonal antibody.

45. The pharmaceutical composition of claim 39, wherein said composition is a sustained release composition.

47. The pharmaceutical composition of claim 39, wherein said composition is a solid form suitable for solubilization in a liquid solution.

48. The pharmaceutical composition of claim 39, wherein said composition is a suspension.

49. The pharmaceutical composition of claim 39, wherein said composition is a solid form suitable for suspension in a liquid solution.

50. The pharmaceutical composition of claim 39, further comprising a physiological acceptable diluent.

51. The pharmaceutical composition of claim 48, wherein said physiological acceptable diluent is selected from the group consisting of the distilled water, physiological phosphate-buffered saline, Ringer'"'"'s solution, dextrose solution, and Hank'"'"'s solution.

52. The pharmaceutical composition of claim 50, wherein the diluent is physiological phosphate-buffered saline.

53. The pharmaceutical composition of claim 50, wherein the diluent is dextrose solution.

54. The pharmaceutical composition of claim 39, further comprising a pH buffering substance.

55. The pharmaceutical composition of claim 39, further comprising a macromolecule.

56. The pharmaceutical composition of claim 55, wherein the macromolecule is selected from the group consisting of proteins, polysaccharides, polylactic acids, polyglucolic acids, copolymers, polymeric amino acids, amino acid copolymers, and lipid aggregates.

57. The pharmaceutical composition of claim 39, wherein the antibody is at 5 mg/mL, formulated in aqueous buffer consisting of 50 mM L-histidine, 150 mM NaC1, adjusted to pH 6.0 with HC1.

58. The pharmaceutical composition of claim 57, wherein the liquid carrier is propylene glycol.

59. The pharmaceutical composition of claim 57, wherein the liquid carrier is polyethylene glycol.

60. The pharmaceutical composition of claim 39, wherein the composition further comprises monoclonal antibody at 5 mg/mL, formulated in aqueous buffer consisting of 50 mM L-histidine, 150 mM NaCl, adjusted to pH 6.0 with HCl.