# US 2019/0330293 A1 · Mutated tau protein fragment and use thereof

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- Number: US 2019/0330293 A1
- Document ID: US20190330293A1
- Status: Published application
- Kind: A1
- Application number: 16/472,022
- Filed: 2017-12-20
- Published: 2019-10-31
- Earliest claimed: 2016-12-21
- Assignees: Adel Inc.
- Applicants: Adel Inc.
- Inventors: Seung-Yong YOON; Na-Young KIM; Dong-Hou KIM
- Web page: https://patentgrep.com/patent/US20190330293A1

## CPC

- C07K 14/4711: {Alzheimer's disease; Amyloid plaque core protein}
- A61K 39/0007: {Nervous system antigens; Prions}
- 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 16/18: against material from animals or humans
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- 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)
- 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 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- G01N 2800/2814: Dementia; Cognitive disorders
- G01N 2800/2821: Alzheimer
- G01N 2800/2835: Movement disorders, e.g. Parkinson, Huntington, Tourette
- 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 present invention relates to a mutated tau protein fragment and a use thereof. The mutated tau protein fragment of the present invention consists of 12 amino acids and thus can easily be prepared. In addition, when the mutated tau protein fragment is injected into an individual as an antigen, a neutralizing antibody against the mutated tau protein is generated. Moreover, the mutated tau protein fragment reduces the aggregation of abnormal tau proteins. Accordingly, the mutated tau protein fragment of the present invention can be effectively used for the prevention or treatment of degenerative neurological diseases.

## Claims

### Claim 1

A modified tau protein fragment comprising the following sequence of 12 consecutive amino acid residues:
(SEQ ID NO: 1)
Val-Gln-Ile-Ile-Asn-Lys-Lys-Leu-Asp-Leu-Ser-Asn
where lysine, the 6th amino acid, is acetylated.

### Claim 2 (depends on 1)

A composition comprising the modified tau protein fragment of claim 1 as an active ingredient.

### Claim at position 3

-5. (canceled)

### Claim 6 (depends on 2)

The composition of claim 2, which is a vaccine composition further comprising one or more selected from the group consisting of pharmaceutically acceptable carriers, diluents, and adjuvants.

### Claim 7 (depends on 2)

The composition of claim 2, wherein the composition is administered via any one route of administration selected from the group consisting of transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous, and nasal routes of administration.

### Claim 8 (depends on 1)

An antibody or a fragment thereof which binds to the modified tau protein fragment of claim 1.

### Claim 9 (depends on 8)

The antibody or a fragment thereof of claim 8, wherein the antibody fragment is any one selected from the group consisting of Fab, scFv, F(ab)2, and Fv.

### Claim 10 (depends on 8)

A vector comprising a nucleotide sequence encoding the antibody or a fragment thereof of claim 8.

### Claim 11 (depends on 10)

A host cell transformed with the vector of claim 10.

### Claim 12 (depends on 11)

The host cell of claim 11, wherein the host cell is a prokaryotic or eukaryotic cell.

### Claim 13 (depends on 12)

The host cell of claim 12, wherein the prokaryotic cell is E. coli or yeast.

### Claim 14 (depends on 12)

The host cell of claim 12, wherein the eukaryotic cell is an NS/0 myeloma cell, a 293 cell, a Chinese hamster ovary cell (CHO cell), a HeLa cell, a CapT cell (human amniotic fluid-derived cell), or a COS cell.

### Claim 15 (depends on 8)

A pharmaceutical composition comprising the antibody or a fragment thereof of claim 8 as an active ingredient.

### Claim at position 14

-17. (canceled)

### Claim 18 (depends on 1)

A method for preventing or treating a degenerative neurological disease, comprising a step of administering a composition to an individual who is expected to develop the degenerative neurological disease or has developed the degenerative neurological disease, wherein the composition comprises
(a) the modified tau protein fragment of claim 1 as an active ingredient; and/or
(b) an antibody or a fragment thereof, which binds to the modified tau protein fragment (a).

### Claim at position 16

-23. (canceled)

### Claim 24 (depends on 1)

A diagnostic kit for a degenerative nerve disease, comprising an agent for detecting a modified tau protein of claim 1 or a gene encoding the modified tau protein, wherein the agent is selected from the group consisting of an antibody or a fragment thereof binding to the modified tau protein, a primer capable of complementarily binding to the gene encoding the modified tau protein, and a probe capable of complementarily binding to the gene encoding the modified tau protein.

### Claim 25

A method for providing information on a degenerative neurological disease, the method comprising:
i) a step of measuring an expression level of a modified tau protein, in which the 280th amino acid is acetylated, in a sample isolated from an individual suspected of having a degenerative neurological disease;
ii) a step of comparing the expression level of the modified tau protein with an expression level of the modified tau protein in a normal control sample; and
iii) a step of determining that in a case where the expression level of the modified tau protein is higher than that in the control, the individual has a high probability of developing the degenerative neurological disease.

### Claim at position 19

-29. (canceled)

### Claim 30 (depends on 18)

The method of claim 18, wherein the degenerative neurological disease is a tau protein-mediated neurological disease.

### Claim 31 (depends on 30)

The method of claim 30, wherein the tau protein-mediated neurological disease is primary age-related tauopathy, chronic traumatic encephalopathy, progressive supranuclear palsy, progressive supranuclear palsy, corticobasal degeneration, Lytico-Bodig disease, Parkinsonism, subacute sclerosing meningitis, lead encephalopathy, tuberous sclerosis, ganglioglioma, gangliocytoma, meningioangiomatosis, subacute sclerosing panencephalitis, Hallervorden-Spatz disease, or lipofuscinosis.

### Claim 32 (depends on 31)

The method of claim 31, wherein the tauopathy is Alzheimer's disease (AD), Pick's disease (PiD), a group of related disorders collectively referred to as frontotemporal dementia (FTDP-17) with Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis (ALS), Creutzfeld-Jakob disease (CJD), boxer dementia (DP), Gerstmann-Sträussler-Scheinker disease (GSSD), Lewy body disease, chronic traumatic encephalopathy (CTE), spinal cord injury, epilepsy, or Huntington's disease.