Prevention and treatment of amyloidogenic diseases

• US 7,977,316 B2
• Filed: 08/20/2007
• Issued: 07/12/2011
• Est. Priority Date: 06/01/1999
• Status: Expired due to Fees

• Current Assignee: Onclave Therapeutics Limited (Prothena Corp. Plc)
• Original Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Inventors: Schenk, Dale B.
• Primary Examiner(s): Kolker; Daniel E
• Application Number:
  US11/842,046
• Publication Number:
  US 20080248023A1
• Time in Patent Office: 1,422 Days
• Field of Search: None
• US Class Current: 514/21.2
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: G01N 2800/2814 : Dementia; Cognitive disorders
• 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 therapeutically treating amyloid A amyloidosis in a human patient comprising administering to the patient amyloid A protein or serum amyloid A precursor protein, or a fragment thereof, which effects an immune response comprising antibodies against amyloid A protein, and an adjuvant that augments the immune response, to thereby treat amyloid A amyloidosis.

2. The method of claim 1, wherein the amyloid A amyloidosis is associated with a preexisting or coexisting inflammatory disease or condition, an infection, a neoplasm, or a lymphoproliferative disorder.

3. The method of claim 1, wherein the amyloid A amyloidosis is associated with a heredofamilial syndrome.

4. The method of claim 1, wherein the amyloid A protein or serum amyloid A precursor protein, or a fragment thereof, is linked to a carrier molecule.

5. The method of claim 1, wherein the adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, and alum.

6. The method of claim 1, wherein the immune response is characterized by a serum titer of the antibodies of at least 1:

1000 with respect to amyloid A protein.

7. The method of claim 6, wherein the immune response is characterized by a serum titer of the antibodies of at least 1:

5000 with respect to amyloid A protein.

8. The method of claim 1, wherein the immune response is characterized by a serum titer of the antibodies against amyloid A protein that is greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample.

9. The method of claim 1, whereby deposition of amyloid A protein fibril aggregates is inhibited.

10. The method of claim 1, whereby amyloid A protein fibril aggregates are cleared.

11. A method of reducing risk or delaying onset of amyloid A amyloidosis in a human patient at risk of amyloid A amyloidosis comprising administering to the patient amyloid A protein or serum amyloid A precursor protein, or a fragment thereof, which effects an immune response comprising antibodies against amyloid A protein, and an adjuvant that augments the immune response, to thereby delay onset of amyloid A amyloidosis and/or reduce amyloid plaque burden in the patient.

12. The method of claim 11, wherein the patient has or is at risk for an inflammatory disease or condition, an infection, a neoplasm, or a lymphoproliferative disorder.

13. The method of claim 11, wherein the patient has or is at risk for a heredofamilial syndrome.

14. The method of claim 11, wherein the amyloid A protein or serum amyloid A precursor protein, or a fragment thereof, is linked to a carrier molecule.

15. The method of claim 11, wherein the adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, and alum.

16. The method of claim 11, wherein the immune response is characterized by a serum titer of the antibodies of at least 1:

1000 with respect to the amyloid A protein.

17. The method of claim 16, wherein the immune response is characterized by a serum titer of the antibodies of at least 1:

5000 with respect to the amyloid A protein.

18. The method of claim 11, wherein the immune response is characterized by a serum titer of the antibodies against the amyloid A protein that is greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample.

19. The method of claim 11, whereby deposition of amyloid A protein fibril aggregates is inhibited.

20. The method of claim 11, whereby amyloid A protein fibril aggregates are cleared.