# US 9,518,101 B2 · Protein-based therapy and diagnosis of tau-mediated pathology in alzheimer's disease

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- Number: US 9,518,101 B2
- Document ID: US9518101B2
- Status: Granted
- Kind: B2
- Application number: 14/345,561
- Filed: 2012-09-14
- Published: 2015-02-19
- Granted: 2016-12-13
- Earliest claimed: 2011-09-19
- Assignees: Axon Neuroscience SE
- Applicants: Michal Novak; Eva Kontseková; Branislav Kovácech; Norbert Zilka
- Inventors: Michal Novak; Eva Kontseková; Branislav Kovácech; Norbert Zilka
- Web page: https://patentgrep.com/patent/US9518101B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 38/1709: {from mammals}
- A61K 39/0007: {Nervous system antigens; Prions}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/6843: {the antibody targeting a material from animals or humans}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 49/0004: {Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- 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
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/4711: {Alzheimer's disease; Amyloid plaque core protein}
- G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/6081: {Albumin; Keyhole limpet haemocyanin [KLH]}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- G01N 2800/2821: Alzheimer
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- 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)

## Abstract

The invention provides unique therapeutic and diagnostic antibodies, as well as their fragments, portions, derivatives, and variants thereof, that bind regions of the tau protein that contribute to the initiation and propagation of pathological tau-tau interactions, as well as methods of making them. The invention also relates to methods of using those antibodies for diagnostics, prevention, and treatment of Alzheimer's disease and related tauopathies. The present invention also provides a method for a prophylactic and therapeutic treatment of Alzheimer's disease and other neurodegenerative tauopathies. This method entails the injection of antibodies and/or peptide vaccines that elicits an immune response directed to pathological tau proteins and tau deposits in the brains of patients. Suitable vaccines represent a tau peptide carrying one or more of the tau therapeutic epitopes provided herein.

## Claims

### Claim 1

An immunogenic composition comprising a synthetic peptide whose amino acid sequence consists of KDNIKHVPGGGS (SEQ ID NO: 108), or a salt thereof, and an adjuvant containing aluminum.

### Claim 2

A synthetic peptide whose amino acid sequence consists of CKDNIKHVPGGGS (SEQ ID NO: 218), or a salt thereof.

### Claim 3 (depends on 2)

An immunogenic composition comprising the peptide according to claim 2 and a pharmaceutically acceptable excipient.

### Claim 4 (depends on 3)

The immunogenic composition of claim 3, further comprising aluminum hydroxide.

### Claim 5

A compound comprising a peptide whose amino acid sequence consists of SEQ ID NO: 218 (CKDNIKHVPGGGS) that is linked to keyhole limpet hemocyanin (KLH) at the N-terminal end of the peptide, or a salt thereof.

### Claim 6 (depends on 5)

An immunogenic composition comprising the compound according to claim 5 and an adjuvant containing aluminum.

### Claim 7 (depends on 5)

The compound according to claim 5, wherein the KLH is conjugated to the N-terminal cysteine via a maleimide crosslinker.

### Claim 8 (depends on 3, 5)

A pharmaceutical composition comprising the compound according to claim 5 or claim 3, and further comprising a pharmaceutically acceptable carrier, and/or a diluent, and/or an adjuvant.

### Claim 9 (depends on 8)

The pharmaceutical composition of claim 8, wherein the adjuvant is aluminum hydroxide.

### Claim 10 (depends on 5, 7)

A pharmaceutical composition comprising a compound according to claim 5 or claim 7 and pharmaceutically acceptable carrier.

### Claim 11 (depends on 5, 7)

A pharmaceutical composition comprising a compound according to claim 5 or claim 7 and a pharmaceutically acceptable diluent.

### Claim 12 (depends on 5, 7)

A pharmaceutical composition comprising compound according to claim 5 or claim 7 and pharmaceutically acceptable adjuvant.

### Claim 13 (depends on 12)

The pharmaceutical composition of claim 12, wherein the adjuvant is aluminum hydroxide.