# US 11,307,208 B2 · Biomarkers for cognitive impairment and methods for detecting cognitive impairment using such biomarkers

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,307,208 B2
- Document ID: US11307208B2
- Status: Granted
- Kind: B2
- Application number: 16/791,984
- Filed: 2020-02-14
- Published: 2020-06-25
- Granted: 2022-04-19
- Earliest claimed: 2010-12-22
- Assignees: Mcbi Inc.
- Applicants: Mcbi Inc.
- Inventors: Kazuhiko Uchida; Kohji Meno; Hideaki Suzuki
- Web page: https://patentgrep.com/patent/US11307208B2

## CPC

- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- C07K 16/40: against enzymes
- G01N 2333/974: Thrombin
- G01N 2800/2814: Dementia; Cognitive disorders
- G01N 2800/2821: Alzheimer
- G01N 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis
- 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)
- 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)

## Abstract

The present invention aims to provide methods to detect cognitive impairment including mild cognitive impairment and Alzheimer disease by using a protein or its partial peptide that differs in presence or absence, or in quantity between non-cognitive impairment and patients with cognitive impairment and further aims to present biomarkers comprising said protein and said partial peptide to be used to detect cognitive impairment including Alzheimer disease or mild cognitive impairment. Specifically, a biomarker for diagnosis of psychiatry disease or cognitive impairment comprising protein fragment or peptide of not less than 5 amino acid residues arising from at least one protein or peptide selected from the group of proteins consisting of amino acid sequence expressed by SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, and 25 and selected from the group of partial peptide in these proteins consisting of amino acid sequence expressed by SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, and 27. And further aims to provide diagnostic method using these biomarker.

## Claims

### Claim 1

A method of diagnosing and treating Alzheimer's dementia, mild cognitive impairment, Dementia with Lewy bodies or frontotemporal dementia in a patient, said method comprising:
a) obtaining a biological material sample from a human patient;
b) detecting an amount of Prothrombin-derived peptide THRB consisting of SEQ NO: 14 in the biological material sample by mass spectrometry;
c) diagnosing the patient with said Alzheimer's dementia, mild cognitive impairment, Dementia with Lewy bodies or frontotemporal dementia when a higher amount of the Prothrombin-derived peptide THRB in the biological material sample is detected by comparing the amount of the Prothrombin-derived peptide THRB in the patient with an amount of the Prothrombin-derived peptide THRB in a biological material sample obtained from a non-psychiatry disease subject; and
d) administering an effective amount of an anti-acetylcholine esterase inhibitor to the diagnosed patient.

### Claim 2 (depends on 1)

The method of claim 1, wherein the biological material is serum, blood, plasma, cerebrospinal fluid, or urine.

### Claim 3 (depends on 1)

The method of claim 1, wherein the anti-acetylcholine esterase is Donepezil-hydrochloride.