Prevention and treatment of amyloidogenic disease

• US 6,743,427 B1
• Filed: 11/28/2000
• Issued: 06/01/2004
• Est. Priority Date: 12/02/1997
• 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:
  US09/724,961
• Time in Patent Office: 1,281 Days
• Field of Search: 530/300, 530/350, 530/387.1, 724/130.1, 724/133.1, 724/139.1, 724/141, 724/142.1
• 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 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

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 an antibody that specifically binds to an epitope within residues 1-12 of Aβ

wherein the isotype of the antibody is human IgG1.

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

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

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

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

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

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

8. The method of claim 1, wherein the antibody is a polyconal antibody.

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

10. The method of claim 1, wherein the antibody comprises two pairs of light and heavy chains.

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

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

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

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

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

16. The method of claim 1, wherein the patient has Alzheimer'"'"'s disease.

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

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

19. The method of claim 18, 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.