# US 2016/0354451 A1 · Method of providing patient specific immune response in amyloidoses and protein aggregation disorders

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- Number: US 2016/0354451 A1
- Document ID: US20160354451A1
- Status: Published application
- Kind: A1
- Application number: 15/177,980
- Filed: 2016-06-09
- Published: 2016-12-08
- Earliest claimed: 2007-08-31
- Assignees: New York University
- Applicants: New York University
- Inventors: Karsten Henco; Roger Nitsch; Jan Grimm; Anja Zeller; Marcel Maier
- Web page: https://patentgrep.com/patent/US20160354451A1

## CPC

- A61K 39/0007: {Nervous system antigens; Prions}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/55511: {Organic adjuvants}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/575: {humoral response}
- 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
- C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
- G01N 2333/4709: Amyloid plaque core protein
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## 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 described, wherein ex vivo stimulated antigen-selected peripheral blood lymphocytes are regrafted into the cognate donor.

## Claims

### Claim at position 1

1-47. (canceled)

### Claim 48

A method of treating Alzheimer's Disease pathology, which method comprises:
selecting a subject who has Alzheimer's Disease pathology; and
administering, 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.

### Claim at position 3

49-50. (canceled)

### Claim 51 (depends on 48)

The method of claim 48, wherein the oligonucleotide is formulated as a pharmaceutical composition, optionally together with a pharmaceutically acceptable carrier.

### Claim 52 (depends on 51)

The method of claim 51, 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.

### Claim 53 (depends on 48)

The method of claim 48, wherein the oligonucleotide is designed to be administered at a subclinical stage of the disorder.

### Claim 54 (depends on 51)

The method of claim 51, wherein said pharmaceutical composition comprises at least one non-nucleic acid adjuvant capable of creating a depo effect.

### Claim 55 (depends on 54)

The method of claim 54, 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.

### Claim 56 (depends on 54)

The method of claim 54, wherein the adjuvant comprises an immune stimulating adjuvant.

### Claim 57 (depends on 54)

The method of claim 54, wherein the adjuvant comprises vitamin A.

### Claim 58 (depends on 54)

The method of claim 54, 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.

### Claim 59 (depends on 54)

The method of claim 54, 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).

### Claim 60 (depends on 48)

The method of claim 48, wherein said administering is performed intravenously, intramuscularly, subcutaneously, intraperitoneally, intranasally, parenterally or as an aerosol.

### Claim 61

An oligonucleotide or modified oligonucleotide containing at least one unmethylated B-class CpG dinucleotide motif for the treatment of a subject who has Alzheimer's Disease pathology.

### Claim 62 (depends on 61)

The oligonucleotide or modified oligonucleotide of claim 61, wherein the modified oligonucleotide is phosphorothioate-modified.

### Claim 63

A kit for characterizing plaque structures comprising:
an oligonucleotide or modified oligonucleotide containing at least one unmethylated B-class CpG dinucleotide motif;
reagents for detection of pathological protein aggregate or neo-epitope binding; and
instructions for use.

### Claim 64 (depends on 63)

The kit of claim 63, wherein the oligonucleotide or modified oligonucleotide is phosphorothioate-modified.