Method of providing patient specific immune response in amyloidoses and protein aggregation disorders

Patent metadata

Field	Value
Publication number	US-9370531-B2
Application number	US-73343708-A
Country	US
Kind code	B2
Filing date	Sep 1, 2008
Priority date	Aug 31, 2007
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

A treatment of Alzheimer's disease and other disorders involving protein misfolding or aggregation is provided by enhancing or sustaining an antibody response against predominantly directed against pathological protein aggregates or neo-epitopes present on pathogenic forms of said protein or protein complex. Furthermore, therapeutic methods are also described, wherein ex vivo stimulated antigen-selected peripheral blood lymphocytes are regrafted into the cognate donor.

First claim

What is claimed is:

1. A method of treating Alzheimer's Disease pathology, which method comprises:
selecting a subject who has Alzheimer's Disease pathology; and
administering twice per week, to the selected subject an oligonucleotide or modified oligonucleotide containing at least one unmethylated B-class CpG dinucleotide motif at a dosage in a range of 0.2 mg to 20 mg per kilogram body weight of the selected subject, wherein said administering is effective to stimulate production of endogenously primed autoantibodies without co-administration of exogenous immunogens, said autoantibodies having binding specificity for one or more pathological neo-epitopes of amyloid beta or a beta-amyloid-associated protein, without stimulating production of autoantibodies having binding specificity for non-pathological epitopes of amyloid beta or a beta-amyloid-associated protein in the subject, thereby treating Alzheimer's Disease pathology.

2. The method of claim 1 , wherein the oligonucleotide is formulated as a pharmaceutical composition, optionally together with a pharmaceutically acceptable carrier.

3. The method of claim 2 , wherein said pharmaceutical composition does not include an antigen comprising said pathological protein aggregate or neo-epitope consisting of amyloid beta and beta-amyloid-associated proteins.

4. The method of claim 1 , wherein the oligonucleotide is designed to be administered at a subclinical stage of the disorder.

5. The method of claim 2 , wherein said pharmaceutical composition comprises at least one non-nucleic acid adjuvant capable of creating a depo effect.

6. The method of claim 5 , wherein the adjuvant is selected from the group consisting of alum, emulsion based formulations, mineral oil, non-mineral oil, water-in-oil emulsions, water-in-oil-in-water emulsions and the Seppic ISA series of Montanide adjuvants.

7. The method of claim 5 , wherein the adjuvant comprises an immune stimulating adjuvant.

8. The method of claim 5 , wherein the adjuvant comprises vitamin A.

9. The method of claim 5 , wherein the adjuvant comprises a compound selected from the group consisting of saponins, PCPP polymer, derivatives of lipopolysaccharides, Monophosphoryl A (MPL), muramyldipeptide (MDP), threonylmuramyl dipeptide (t-MDP), Leishmania elongation factor, and glatiramer acetate.

10. The method of claim 5 , wherein the adjuvant that creates a depo effect and stimulates the immune system is selected from the group consisting of Immune Stimulating Complexes (ISCOMS), Adjuvant System 2 (AS2), Adjuvant System 4 (AS4), non-ionic block copolymers and Syntex adjuvant formulation (SAF).

11. The method of claim 1 , wherein said administering is performed intravenously, intramuscularly, subcutaneously, intraperitoneally, intranasally, parenterally or as an aerosol.

Assignees

• Henco Karsten
• Nitsch Roger
• Grimm Jan
• Zeller Anja
• Maier Marcel
• Univ New York

Inventors

• Henco Karsten
• Nitsch Roger
• Grimm Jan
• Zeller Anja
• Maier Marcel

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title