# US 9,724,399 B2 · Mimotopes of alpha-synuclein and vaccines thereof for the treatment of neurodegenerative disorders

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- Number: US 9,724,399 B2
- Document ID: US9724399B2
- Status: Granted
- Kind: B2
- Application number: 12/918,077
- Filed: 2009-02-23
- Published: 2011-04-21
- Granted: 2017-08-08
- Earliest claimed: 2008-02-22
- Assignees: Affiris AG
- Applicants: Markus Mandler; Harald Weninger; Radmila Santic; Edith Kopinits
- Inventors: Markus Mandler; Harald Weninger; Radmila Santic; Edith Kopinits
- Web page: https://patentgrep.com/patent/US9724399B2

## CPC

- A61K 39/0007: {Nervous system antigens; Prions}
- 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)}
- A61K 38/1709: {from mammals}
- A61K 47/02: Inorganic compounds
- A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- C07K 14/47: from mammals
- C07K 16/4241: {against anti-human or anti-animal Ig}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61K 47/6911: {the form being a liposome}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55516: {Proteins; Peptides}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/55572: {Lipopolysaccharides; Lipid A; Monophosphoryl lipid A}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/575: {humoral response}
- A61K 2039/58: {raising an immune response against a target which is not the antigen used for immunisation}
- A61K 2039/6031: {Proteins}
- A61K 2039/6081: {Albumin; Keyhole limpet haemocyanin [KLH]}
- A61K 2039/70: {Multivalent vaccine}
- 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
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 16/18: against material from animals or humans
- C07K 2317/21: from primates, e.g. man
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)

## Abstract

The present invention relates to the use of at least one compound comprising the amino acid sequence (Formula 1) (SEQ ID NO: 57) (X1)nX2X3PVX4X5X6(X7)m, wherein X1 is any amino acid residue, X2 is an amino acid residue selected from the group consisting of aspartic acid (D) and glutamic acid (E), X3 is any amino acid residue, X4 is any amino acid residue, X5 is an amino acid residue selected from the group consisting of proline (P) and alanine (A), X6 is an amino acid residue selected from the group consisting of aspartic acid (D) and glutamic acid (E), X7 is any amino acid residue, n and m, independently, are 0 or an integer of more than 0, and wherein the amino acid sequence according to Formula I is not identical with, or does not comprise the 8-mer polypeptide fragment of alpha-synuclein having the amino acid sequence DMPVDPDN (SEQ ID NO: 1), said compound having a binding capacity to an antibody which is specific for an epitope of alpha-synuclein comprising the amino acid sequence DMPVDPDN (SEQ ID NO: 1) for producing a medicament for preventing and/or treating synucleinopathies.

## Claims

### Claim 1

A method of reducing aggregates of α-synuclein in a subject having a disease selected from the group consisting of Lewy Body Disorders (LBDs), Parkinson's Disease (PD), Parkinson's Disease with Dementia (PDD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA), and Neurodegeneration with Brain Iron Accumulation type I (NBIA Type I), comprising administering, to a subject in need thereof, a compound comprising a peptide having the amino acid sequence of XDQPVLPD (SEQ ID NO: 59) wherein X is cysteine or not present,
wherein the compound induces an antibody that has specific binding capacity for an epitope of alpha-synuclein comprising the amino acid sequence DMPVDPDN (SEQ ID NO: 1), and wherein the antibody has no reactivity to beta-synuclein or lower immune reactivity to beta-synuclein compared to alpha synuclein epitope comprising DMPVDPDN (SEQ ID NO:1).

### Claim 2 (depends on 1)

The method according to claim 1, wherein the compound is coupled to a pharmaceutically acceptable carrier.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the compound is formulated for intravenous, subcutaneous, intradermal or intramuscular administration.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the compound is formulated with an adjuvant.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the compound is administered in the form of a medicament, wherein the medicament comprises the compound in an amount of from 0.1 ng to 10 mg based on the total weight of the medicament.

### Claim 6 (depends on 2)

The method according to claim 2, wherein the compound is coupled to KLH (Keyhole Limpet Hemocyanin).

### Claim 7 (depends on 4)

The method according to claim 4, wherein the compound is formulated with aluminium hydroxide.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the disease is Lewy Body Disorders (LBDs).

### Claim 9 (depends on 1)

The method according to claim 1, wherein the disease is Parkinson's Disease (PD).

### Claim 10 (depends on 1)

The method according to claim 1, wherein the disease is Parkinson's Disease with Dementia (PDD).

### Claim 11 (depends on 1)

The method according to claim 1, wherein the disease is Dementia with Lewy Bodies (DLB).

### Claim 12 (depends on 1)

The method according to claim 1, wherein the disease is Multiple System Atrophy (MSA).

### Claim 13 (depends on 1)

The method according to claim 1, wherein the disease is Neurodegeneration with Brain Iron Accumulation type I (NBIA Type I).