Prevention and treatment of amyloidogenic disease

• US 8,034,339 B2
• Filed: 08/20/2004
• Issued: 10/11/2011
• 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:
  US10/923,469
• Publication Number:
  US 20050019330A1
• Time in Patent Office: 2,608 Days
• Field of Search: None
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/739 Lipopolysaccharides
• 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: A61K 47/646 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4866 : Organic macromolecular compounds
• CPC Class Codes: A61K 9/7023 : Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• 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: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide

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 Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that binds to soluble Aβ

and specifically binds to an epitope having an amino acid between positions 10-25, wherein the humanized antibody is administered peripherally to a human patient to exert its beneficial effects.

6. The method of any one of claims 1-5, wherein the antibody specifically binds to an epitope having an amino acid between positions 10-20 of Aβ

.

7. The method of any one of claims 1-5, wherein the antibody specifically binds to an epitope having an amino acid between positions 15-20 of Aβ

.

8. The method of any one of claims 1-5, wherein the antibody is an intact humanized antibody.

9. The method of any one of claims 1-5, wherein the antibody is a fragment.

10. The method of claim 9, wherein the antibody fragment is an Fab, Fab′

, F(ab′

)₂, Fabc, or Fv.

11. The method of claim 10, which is an Fab or F(ab′

)₂ fragment.

12. The method of claim 11, which is an F(ab′

)₂ fragment.

13. The method of claim 11, which is an Fab fragment.

14. The method of claim 9, wherein the antibody fragment is obtainable by enzymatic cleavage of the humanized antibody.

15. The method of any one of claims 1-5, wherein the antibody is a bispecific antibody.

16. The method of claim 15, wherein the bispecific antibody is an antibody fragment.

17. The method of any one of claims 1-5, wherein the antibody is a single chain antibody.

18. The method of any one of claims 1-5, wherein a chain of the antibody is fused to a heterologous polypeptide.

19. The method of any one of claims 1-5, wherein the antibody is produced in a host cell selected from the group consisting of a myeloma cell and a Chinese hamster ovary cell.

2. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that binds to soluble Aβ

and specifically binds to an epitope having an amino acid between positions 10-25, which, when administered peripherally to a human patient, binds to soluble Aβ

.

3. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that binds to soluble Aβ

and specifically binds to an epitope having an amino acid between positions 10-25, which, when administered peripherally to a human patient, does not require cellular responses in the patient'"'"'s brain to exert its beneficial effects.

4. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that binds to soluble Aβ

and specifically binds to an epitope having an amino acid between positions 10-25, which, when administered peripherally to a human patient, does not substantially bind aggregated Aβ

in the patient'"'"'s brain.

5. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that binds to soluble Aβ

and specifically binds to an epitope having an amino acid between positions 10-25, which, when administered peripherally to a human patient, exhibits beneficial effects without necessarily binding to Aβ

plaques in the brain.

20. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that specifically binds to dissociated Aβ

without binding to aggregated Aβ

, which is administered peripherally to a human patient to exert its beneficial effects.

22. The method of claim 20 or claim 21, wherein the antibody specifically binds to an epitope having an amino acid between positions 10-20, 10-25, or 15-20 of Aβ

.

23. The method of claim 22, wherein the antibody specifically binds to an epitope having an amino acid between positions 10-20 of Aβ

.

24. The method of claim 22, wherein the antibody specifically binds to an epitope having an amino acid between positions 10-25 of Aβ

.

25. The method of claim 22, wherein the antibody specifically binds to an epitope having an amino acid between positions 15-20 of Aβ

.

26. The method of claim 22, wherein the antibody specifically binds to an epitope within amino acid residues 10-20, 10-25, or 15-20 of Aβ

.

27. The method of claim 26, wherein the antibody specifically binds to an epitope within amino acid residues 10-20 of Aβ

.

28. The method of claim 26, wherein the antibody specifically binds to an epitope within amino acid residues 10-25 of Aβ

.

29. The method of claim 26, wherein the antibody specifically binds to an epitope within amino acid residues 15-20 of Aβ

.

30. The method of claim 20 or claim 21, wherein the antibody is an intact humanized antibody.

31. The method of claim 20 or claim 21, wherein the antibody is a fragment.

32. The method of claim 31, wherein the antibody fragment is an Fab, Fab′

, F(ab′

)₂, Fabc, or Fv.

33. The method of claim 32, wherein the antibody is an Fab or F(ab′

)₂ fragment.

34. The method of claim 33, wherein the antibody is an F(ab′

)₂ fragment.

35. The method of claim 33, wherein the antibody is an Fab fragment.

36. The method of claim 31, wherein the antibody fragment is obtainable by enzymatic cleavage of the humanized antibody.

37. The method of claim 20 or claim 21, wherein the antibody is a bispecific antibody.

38. The method of claim 37, wherein the bispecific antibody is an antibody fragment.

39. The method of claim 20 or claim 21, wherein the antibody is a single chain antibody.

40. The method of claim 20 or claim 21, wherein a chain of the antibody is fused to a heterologous polypeptide.

41. The method of claim 20 or claim 21, wherein the antibody is produced in a host cell selected from the group consisting of a myeloma cell and a Chinese hamster ovary cell.

21. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody that specifically binds to dissociated Aβ

without binding to aggregated Aβ

, which, when administered peripherally to a human patient, binds to soluble Aβ

.