# US 8,491,890 B2 · Methods and compositions for inhibiting diseases of the central nervous system

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- Number: US 8,491,890 B2
- Document ID: US8491890B2
- Status: Granted
- Kind: B2
- Application number: 12/500,414
- Filed: 2009-07-09
- Published: 2010-02-04
- Granted: 2013-07-23
- Earliest claimed: 2008-07-09
- Assignees: Board of Regents of the University of Nebraska
- Applicants: Howard E. Gendelman; R. Lee Mosley; Ashley D. Reynolds
- Inventors: Howard E. Gendelman; R. Lee Mosley; Ashley D. Reynolds
- Web page: https://patentgrep.com/patent/US8491890B2

## CPC

- A61K 39/0008: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- A61K 39/0007: {Nervous system antigens; Prions}
- A61K 39/21: Retroviridae, e.g. equine infectious anemia virus
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/22: Immunosuppressive or immunotolerising
- A61K 40/414: {Nervous system antigens}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 2039/55511: {Organic adjuvants}
- A61K 2039/55516: {Proteins; Peptides}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/575: {humoral response}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C12N 2740/16334: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/16371: Demonstrated in vivo effect
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Methods and compositions for treating central nervous system diseases and disorders are disclosed.

## Claims

### Claim 1

An isolated composition comprising:
a) an immunogen, wherein said immunogen induces a humoral immune response against at least one abnormal protein of a central nervous system disease or disorder, and
b) at least one adjuvant that stimulates regulatory T cells,
wherein said immunogen consists of nitrated alpha synuclein or a fragment thereof,
wherein said nitrated alpha synuclein fragment is a carboxy terminal fragment consisting of the carboxy terminal 20 amino acids of alpha synuclein up to the carboxy terminal 70 amino acids of alpha synuclein.

### Claim 2 (depends on 1)

The composition of claim 1, further comprising at least one pharmaceutically acceptable carrier.

### Claim 3 (depends on 1)

The composition of claim 1, wherein said adjuvant is selected from the group consisting of vasoactive intestinal peptide, vitamin D, granulocyte macrophage colony stimulating factor, and transforming growth factor beta.

### Claim 4 (depends on 1)

The composition of claim 1, wherein said adjuvant is vasoactive intestinal peptide.

### Claim 5 (depends on 1)

The composition of claim 1, wherein said adjuvant is vasoactive intestinal peptide and said immunogen is nitrated alpha synuclein.

### Claim 6 (depends on 1)

The composition of claim 1, wherein said nitrated alpha synuclein is human nitrated alpha synuclein.

### Claim 7 (depends on 1)

The composition of claim 1, wherein said nitrated alpha synuclein comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 13.

### Claim 8 (depends on 1)

The composition of claim 1, wherein said nitrated alpha synuclein fragment comprises at least 90% identity with amino acids 101-140 of SEQ ID NO: 13.

### Claim 9 (depends on 1)

The composition of claim 1, wherein said nitrated alpha synuclein or fragment thereof comprises at least one nitrotyrosine.

### Claim 10 (depends on 3)

The composition of claim 3, wherein said adjuvant is vasoactive intestinal peptide.

### Claim 11 (depends on 3)

The composition of claim 3, wherein said adjuvant is granulocyte macrophage colony stimulating factor.

### Claim 12 (depends on 1)

A method for treating a central nervous system disease or disorder in a patient in need thereof, said method comprising administering an effective amount of the composition according to claim 1 to said patient, wherein said central nervous system disease or disorder is characterized by the presence of at least one abnormal protein and is selected from the group consisting of Parkinson's Disease, Alzheimer's Disease, amyotrophic lateral sclerosis, neuroAIDS, Crohn's Disease, and Huntington's Disease.

### Claim 13 (depends on 12)

The method of claim 12, wherein said adjuvant is selected from the group consisting of vasoactive intestinal peptide, vitamin D, granulocyte macrophages colony stimulating factor, and transforming growth factor beta.

### Claim 14 (depends on 13)

The method of claim 13, wherein said adjuvant is vasoactive intestinal peptide.

### Claim 15 (depends on 12)

The method of claim 12, wherein said central nervous disease or disorder is Parkinson's Disease and said immunogen is nitrated alpha synuclein.

### Claim 16 (depends on 12)

The method of claim 12, wherein said central nervous disease or disorder is Parkinson's Disease and said immunogen is a fragment of nitrated alpha synuclein.

### Claim 17 (depends on 12)

The method of claim 12, wherein said central nervous disease or disorder is Alzheimer's Disease and said immunogen is amyloid beta.

### Claim 18 (depends on 12)

The method of claim 12 wherein said central nervous system disease or disorder is amyotrophic lateral sclerosis and said immunogen is superoxide dismutase.

### Claim 19 (depends on 12)

The method of claim 12, wherein said composition further comprises at least one pharmaceutically acceptable carrier.