# US 10,119,957 B2 · Multi-metabolites platform for diagnosis of acute coronary syndrome

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- Number: US 10,119,957 B2
- Document ID: US10119957B2
- Status: Granted
- Kind: B2
- Application number: 14/795,163
- Filed: 2015-07-09
- Published: 2016-10-20
- Granted: 2018-11-06
- Earliest claimed: 2015-04-17
- Assignees: Korea Institute of Science and Technology
- Applicants: Korea Institute of Science and Technology
- Inventors: Byung Hwa Jung; Jong Min Choi; Hong Seog Seo
- Web page: https://patentgrep.com/patent/US10119957B2

## CPC

- G01N 33/492: {Determining multiple analytes}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2405/02: Triacylglycerols
- G01N 2405/04: Phospholipids, i.e. phosphoglycerides
- G01N 2405/08: Sphingolipids
- G01N 2570/00: Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
- G01N 2800/324: Coronary artery diseases, e.g. angina pectoris, myocardial infarction
- 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 disclosure provides a multi-metabolite platform using one or more metabolite selected from a group consisting of tryptophan, homoserine, fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2), fatty acid (22:6), phosphatidylcholine (PC) (34:2), PC (34:3), lysophosphatidylcholine (lysoPC) (16:0), lysoPC (18:0), lysoPC (20:3), lysoPC (20:4), lysoPC (22:6), monoglyceride (18:1/0:0/0:0) and sphingomyelin (d18:2/16:0) as a biomarker, which can diagnose acute coronary syndrome as well as the symptoms occurring prior to the onset of the disease simply and accurately through in-vivo level analysis.

## Claims

### Claim 1

A kit for diagnosis of acute coronary syndrome, comprising:
a detector configured to detect in-vivo level of one or more metabolite selected from a group consisting of tryptophan, homoserine, phosphatidylcholine (PC) (34:2), PC (34:3), lysophosphatidylcholine (lysoPC) (16:0), lysoPC (20:4), lysoPC (22:6), monoglyceride (18:1/0:0/0:0) and sphingomyelin (d18:2/16:0) from a sample,
a composition comprising tryptophan, homoserine, phosphatidylcholine (PC) (34:2), PC (34:3), lysophosphatidylcholine (lysoPC) (16:0), lysoPC (20:4), lysoPC (22:6), monoglyceride (18:1/0:0/0:0) and sphingomyelin (d18:2/16:0) in a control level corresponding to normal control group of healthy people without the acute coronary syndrome;
a multivariate analysis system configured to analyze a difference in the in-vivo level of the one or more metabolite and the control level, and
an instruction for an acute coronary syndrome diagnosis method,
wherein the method comprises:
measuring, using the in-vivo level detector, the level of the one or more metabolite from a sample, wherein the sample comprises a biological fluid taken from a patient, to obtain a patient metabolite level; and
comparing the patient metabolite level to a normal control group level of the one or more metabolite.

### Claim 2 (depends on 1)

The kit for diagnosis of acute coronary syndrome according to claim 1, wherein the detector further detects in-vivo level of one or more metabolite selected from a group consisting of fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2), fatty acid (22:6), lysoPC (18:0) and lysoPC (20:3), and wherein the composition further comprises fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2), fatty acid (22:6), lysoPC (18:0) and lysoPC (20:3) in a control level corresponding to normal control group of healthy people without the acute coronary syndrome.

### Claim 3 (depends on 1)

The kit for diagnosis of acute coronary syndrome according to claim 1, wherein the acute coronary syndrome comprises one or more of acute myocardial infarction and unstable angina occurring prior to the onset of acute myocardial infarction.

### Claim 4 (depends on 2)

The kit for diagnosis of acute coronary syndrome according to claim 2, wherein the acute coronary syndrome comprises one or more of acute myocardial infarction and unstable angina occurring prior to the onset of acute myocardial infarction.

### Claim 5 (depends on 1)

The kit for diagnosis of acute coronary syndrome according to claim 1, wherein the detector comprises a multi-metabolite detector configured to measure the in-vivo level of metabolites comprising tryptophan, homoserine, fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2), fatty acid (22:6), phosphatidylcholine (PC) (34:2), PC (34:3), lysoPC (16:0), lysoPC (18:0), lysoPC (20:3), lysoPC (20:4), lysoPC (22:6), monoglyceride (18:1/0:0/0:0) and sphingomyelin (d18:2/16:0).

### Claim 6 (depends on 5)

The kit for diagnosis of acute coronary syndrome according to claim 5, wherein the acute coronary syndrome comprises one or more of acute myocardial infarction and unstable angina occurring prior to the onset of acute myocardial infarction.

### Claim 7 (depends on 1)

The kit for diagnosis of acute coronary syndrome according to claim 1, wherein the multivariate analysis system is configured to diagnose as acute coronary syndrome when the in-vivo level of one or more of tryptophan, PC (34:3), lysoPC (16:0) and lysoPC (18:0) is lower as compared to the control level or when the in-vivo level of one or more of homoserine, fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2), fatty acid (22:6), PC (34:2), lysoPC (20:3), lysoPC (20:4), lysoPC (22:6), monoglyceride (18:1/0:0/0:0) and sphingomyelin (d18:2/16:0) is higher as compared to the control level.

### Claim 8 (depends on 1)

A method for diagnosis of acute coronary syndrome, the method comprising:
obtaining a plasma sample from subjects by centrifugation of venous blood sample taken from a patient subject and a normal subject and placing said plasma sample for a period of time;
deproteinizing the plasma sample by pretreating with methanol;
measuring a level of one or more metabolite from the plasma sample, wherein the sample comprises a biological fluid taken from a patient, to obtain a patient metabolite level using the kit according to claim 1, wherein the one or more metabolite is selected from a group consisting of tryptophan, homoserine, phosphatidylcholine (PC) (34:2), PC (34:3), lysophosphatidylcholine (lysoPC) (16:0), lysoPC (20:4), lysoPC (22:6), monoglyceride (18:1/0:0/0:0) and sphingomyelin (d18:2/16:0);
wherein measuring the level of one or more metabolite from a sample comprises detecting the metabolite using multivariate analysis system;
comparing the patient metabolite level to a control level corresponding to normal control group of healthy people without the acute coronary syndrome using the composition according to claim 1; and
diagnosing the acute coronary syndrome based on the comparison.