Prevention and treatment of amyloidgenic disease

• US 7,964,192 B1
• Filed: 05/28/1999
• Issued: 06/21/2011
• Est. Priority Date: 12/02/1997
• Status: Expired due to Fees

• Current Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Original Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Inventors: Schenk, Dale B.
• Primary Examiner(s): Kolker; Daniel E
• Application Number:
  US09/322,289
• Time in Patent Office: 4,407 Days
• Field of Search: 530/387.1, 5303381-38824, 5303911-3915, 424/130.1, 424/178.1, 514/2
• US Class Current: 424/133.1
• 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 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 2317/70 : characterized by effect upon binding to a cell or to an antigen
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: G01N 2800/2821 : Alzheimer
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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, active fragments thereof or an antibody thereto.

Claims

1. A method of treating a disease characterized by an amyloid deposit comprising Aβ

peptide, the method comprising administering to a patient having the disease an antibody that specifically binds to Aβ

peptide, in a regime effective to treat the disease, wherein the antibody is of isotype human IgG1 and is a chimeric or humanized antibody, or a human monoclonal antibody.

2. The method of claim 1, wherein the disease is Alzheimer'"'"'s disease.

3. The method of claim 2, wherein the antibody is a human monoclonal antibody.

4. The method of claim 2, wherein the antibody is a humanized antibody.

5. The method of claim 2, wherein the antibody is a chimeric antibody.

6. The method of claim 2, wherein a chain of the antibody is fused to a heterologous polypeptide.

7. The method of claim 2, wherein the dosage of antibody is at least 1 mg/kg body weight of the patient.

8. The method of claim 2, wherein the dosage of antibody is at least 10 mg/kg body weight of the patient.

9. The method of claim 2, wherein the antibody is administered with a carrier as a pharmaceutical composition.

10. The method of claim 2, wherein the antibody specifically binds to Aβ

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

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

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

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

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

15. The method of claim 1, further comprising administering an effective dosage of a second antibody that binds to the amyloid deposit or a component thereof.

16. The method of claim 1, wherein the antibody binds to an epitope within residues 1-28 of Aβ

.

17. The method of claim 16, wherein the antibody binds to an epitope within residues 1-10 of Aβ

.

18. The method of claim 16, wherein the antibody binds to an epitope within residues 1-5 of Aβ

.

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

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

21. The method of claim 20, further comprising administering an additional dosage of antibody if the level of antibody in the blood of the patient has decreased.

22. The method of claim 21, wherein a further dosage of antibody is administered if the level of antibody in the blood of the patient has declined to baseline levels that were present in the blood before administration of the antibody.

23. The method of claim 1, wherein the antibody is administered in multiple dosages over a period of at least six months.

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

25. The method of claim 1, wherein the antibody is administered at a site separated by the blood-brain barrier from the brain.

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

in disassociated form with a binding affinity of at least 10⁷ M<sup>−

1</sup>.

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

41.

28. The method of claim 27, wherein the antibody is administered with a carrier as a pharmaceutical composition to the patient.

29. The method of claim 1, wherein the administering of the antibody results in an amelioration of symptoms determined by a psychometric measure.

30. The method of claim 29, wherein the psychometric measure is a Mini-Mental State Examination score.

31. The method of claim 29, wherein the psychometric measure is an ADAS score.

32. The method of any one of claims 29-31, further comprising determining the psychometric measure.

33. The method of claim 1, further comprising monitoring progression of Alzheimer'"'"'s disease in the patient using MRI.

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

peptide in an amyloid deposit.

35. The method of claim 1 or 34, wherein the dosage of antibody is at least 1 mg/kg body weight of the patient.

36. The method of claim 1, wherein the antibody is administered on multiple occasions.

37. The method of claim 1, wherein the intervals between single dosages is once every week, once per every two weeks, once a month, once every 3 to 6 months, or yearly.

38. The method of claim 1, wherein the antibody binds both aggregated and dissociated forms of Aβ

peptide.

39. A method of reducing the risk or delaying the outset of a disease characterized by an amyloid deposit comprising Aβ

peptide, comprising administering to a patient an antibody that specifically binds to Aβ

peptide, in a regime effective to reduce the risk or delay the outset of the disease, wherein the antibody is of isotype human IgG1 and is a chimeric or humanized antibody, or a human monoclonal antibody.

40. The method of claim 39, wherein the disease is Alzheimer'"'"'s disease.

41. The method of claim 39, wherein the patient is a human.

42. The method of claim 39, wherein the patient is under 50.

43. The method of claim 39, wherein the patient has inherited risk factors indicating susceptibility to Alzheimer'"'"'s disease.

44. The method of claim 39, wherein the patient has no known risk factors for Alzheimer'"'"'s disease.

45. The method of claim 39, wherein the antibody is a human monoclonal antibody.

46. The method of claim 39, wherein the antibody is a humanized antibody.

47. The method of claim 39, wherein the antibody is a chimeric antibody.

48. The method of claim 39, further comprising administering an effective dosage of a second antibody that binds to the amyloid deposit or a component thereof.

49. The method of claim 39, wherein a chain of the antibody is fused to a heterologous polypeptide.

50. The method of claim 39, wherein the dosage of antibody is at least 1 mg/kg body weight of the patient.

51. The method of claim 39, wherein the dosage of antibody is at least 10 mg/kg body weight of the patient.

52. The method of claim 39, wherein the antibody is administered with a carrier as a pharmaceutical composition.

53. The method of claim 39, wherein the antibody specifically binds to Aβ

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

54. The method of claim 39, wherein the antibody is administered intraperitoneally, orally, subcutaneously, intramuscularly, topically or intravenously.

55. The method of claim 39, further comprising monitoring the patient for level of administered antibody in the blood of the patient.

56. The method of claim 39, wherein the antibody is administered in multiple dosages over a period of at least six months.

57. The method of claim 39, wherein the antibody is administered as a sustained release composition.

58. The method of claim 39, wherein the antibody binds to both aggregated and dissociated forms of Aβ

peptide.

59. The method of claim 39, wherein the antibody binds to an epitope within residues 1-28 of Aβ

.

60. The method of claim 39, wherein the antibody binds to an epitope within residues 1-10 of Aβ

.

61. The method of claim 39, wherein the antibody binds to an epitope within residues 1-5 of Aβ

.

62. The method of claim 39, wherein the antibody specifically binds to Aβ

peptide in an amyloid deposit.

63. The method of claim 39, wherein the antibody specifically binds to Aβ

in dissociated form with a binding affinity of at least 10⁷ M<sup>−

1</sup>.