Prevention and treatment of amyloidogenic disease

• US 8,642,044 B2
• Filed: 08/20/2007
• Issued: 02/04/2014
• Est. Priority Date: 12/02/1997
• Status: Expired due to Term

• Current Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Original Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Inventors: Schenk, Dale B., Vasquez, Nicki, Yednock, Theodore
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US11/842,116
• Publication Number:
  US 20090191231A1
• Time in Patent Office: 2,360 Days
• Field of Search: None
• US Class Current: 424/185.1
• 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 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 decreasing the severity or treating a disease associated with amyloid deposits of Aβ

in the brain of a patient, comprising administering to the patient suffering from the disease a polypeptide in a regime effective to induce an immune response comprising antibodies to the polypeptide and thereby decrease the severity of the disease or treat the disease in the patient, wherein the polypeptide consists of an N-terminal segment of Aβ

, the segment beginning at residue 1-3 of Aβ and

ending at residues 7-11 of Aβ

, wherein the Aβ

polypeptide is linked to a carrier molecule to form a conjugate.

5. The method of claim 1, wherein the Aβ

polypeptide is Aβ

1-7.

6. The method of claim 1, further comprising administering an adjuvant.

7. The method of claim 5, further comprising administering an adjuvant.

8. The method of claim 7, wherein the adjuvant is Quillaja Saponaria Molina (QS21).

9. The method of claim 5, wherein the carrier molecule is CRM 197.

10. The method of claim 7, wherein the carrier molecule is CRM 197.

2. A method of delaying the outset of a disease associated with amyloid deposits of Aβ

in the brain of a patient, comprising administering to a patient susceptible to the disease dosage of an agent effective to induce an immunogenic response against an N-terminal segment of Aβ

without inducing an immunogenic response against an epitope within residues 12-43 of Aβ

, and thereby delay the outset of the disease in the patient, the segment beginning at residue 1-3 of Aβ and

ending at residues 7-11 of Aβ

, wherein the agent comprises the Aβ

segment linked to a carrier molecule to form a conjugate.

11. The method of claim 2, wherein the Aβ

segment is Aβ

1-7.

12. The method of claim 2, further comprising administering an adjuvant.

13. The method of claim 11, further comprising administering an adjuvant.

14. The method of claim 13, wherein the adjuvant is Quillaja Saponaria Molina (QS21).

15. The method of claim 11, wherein the carrier molecule is CRM 197.

16. The method of claim 13, wherein the carrier molecule is CRM 197.

3. A method of delaying the outset of a disease associated with amyloid deposits of Aβ

in the brain of a patient, comprising administering to the patient susceptible to the disease a polypeptide in a regime effective to induce an immune response comprising antibodies to the polypeptide and thereby delay the outset of the disease in the patient, wherein the polypeptide consists of an N-terminal segment of Aβ

, the segment beginning at residue 1-3 of Aβ and

ending at residues 7-11 of Aβ

, wherein the Aβ

polypeptide is linked to a carrier molecule to form a conjugate.

17. The method of claim 3, wherein the Aβ

polypeptide is Aβ

1-7.

18. The method of claim 3, further comprising administering an adjuvant.

19. The method of claim 17, further comprising administering an adjuvant.

20. The method of claim 19, wherein the adjuvant is Quillaja Saponaria Molina (QS21).

21. The method of claim 17, wherein the carrier molecule is CRM 197.

22. The method of claim 19, wherein the carrier molecule is CRM 197.

4. A method of decreasing the severity or treating a disease associated with amyloid deposits of Aβ

in the brain of a patient, comprising administering to the patient suffering from the disease a dosage of an agent effective to induce an immunogenic response against an N-terminal segment of Aβ

without inducing an immunogenic response against an epitope within residues 12-43 of Aβ and

thereby decrease the severity of the disease or treat the disease in the patient, the segment beginning at residue 1-3 of Aβ and

ending at residues 7-11 of Aβ

, wherein the agent comprises the Aβ

segment linked to a carrier molecule to form a conjugate.

23. The method of claim 4, wherein the Aβ

segment is Aβ

1-7.

24. The method of claim 4, further comprising administering an adjuvant.

25. The method of claim 23, further comprising administering an adjuvant.

26. The method of claim 25, wherein the adjuvant is Quillaja Saponaria Molina (QS21).

27. The method of claim 23, wherein the carrier molecule is CRM 197.

28. The method of claim 25, wherein the carrier molecule is CRM 197.