# US 10,481,160 B2 · Combined anticancer drug sensitivity-determining marker

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- Number: US 10,481,160 B2
- Document ID: US10481160B2
- Status: Granted
- Kind: B2
- Application number: 15/635,293
- Filed: 2017-06-28
- Published: 2017-10-19
- Granted: 2019-11-19
- Earliest claimed: 2012-02-23
- Assignees: Keio University; Kabushiki Kaisha Yakult Honsha
- Applicants: Keio University; Kabushiki Kaisha Yakult Honsha
- Inventors: Yusuke Tanigawara; Akito Nishimuta; Junya Tsuzaki; Hiroyuki Takahashi
- Web page: https://patentgrep.com/patent/US10481160B2

## CPC

- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- A61K 31/282: Platinum compounds
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/575: for cancer
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- G01N 2560/00: Chemical aspects of mass spectrometric analysis of biological material
- 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 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- Y10T 436/143333: Saccharide [e.g., DNA, etc.]
- Y10T 436/147777: Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
- Y10T 436/163333: Organic [e.g., chemical warfare agents, insecticides, etc.]
- Y10T 436/173845: Amine and quaternary ammonium
- Y10T 436/201666: Carboxylic acid
- 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)
- 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
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

To provide an anti-cancer agent sensitivity determination marker, which marker can determine whether or not the patient has a therapeutic response to the anti-cancer agent, and novel cancer therapeutic means employing the marker. The anti-cancer agent sensitivity determination marker, the anti-cancer agent including oxaliplatin or a salt thereof and fluorouracil or a salt thereof, contains one or more substances selected from among an amino-acid-metabolism-related substance, a nucleic-acid-metabolism-related substance, a substance in the pentose phosphate pathway, a substance in the glycolytic pathway, a substance in the TCA cycle, a polyamine-metabolism-related substance, 7,8-dihydrobiopterin, 6-phosphogluconic acid, butyric acid, triethanolamine, 1-methylnicotinamide, NADH, NAD+, and a substance involved in the metabolism of any of these substances.

## Claims

### Claim 1

A method comprising
obtaining a first biological sample from a subject having cancer prior to administering an anti-cancer agent comprising oxaliplatin or a salt thereof and fluorouracil or a salt thereof;
administering the anti-cancer agent to the subject;
obtaining a second biological sample from the subject after the administering;
measuring a level of a substance, wherein the substance is cysteine-glutathione in the first and the second biological samples; and
continue administering the anti-cancer agent to the subject when the level of the substance is decreased in the second sample compared to the first sample or discontinuing the administration of the anti-cancer agent when the level of the substance is increased or unchanged in the second sample compared to the first sample.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has at least one type of cancer selected from the group consisting of pharyngeal cancer, esophageal cancer, gastric cancer, colorectal cancer, lung cancer, bone cancer, articular cartilage cancer, skin melanoma, squamous cell cancer, mesothelioma, breast cancer, uterine cancer, ovarian cancer, prostatic cancer, bladder cancer, brain tumor, thyroid cancer, endocrine cancer, non-Hodgkin lymphoma, lymphocytic leukemia, non-small-cell lung cancer, small-cell lung cancer, cervical cancer, malignant lymphoma and metastatic cancers from these cancers as primary lesions.

### Claim 3 (depends on 1)

The method of claim 1, where the measuring comprises measuring with mass spectrometry, high performance liquid chromatography (HPLC), immunological assay, biological assay, or gas chromatography.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer is colorectal cancer.

### Claim 5 (depends on 1)

The method of claim 1, wherein the measuring comprises measuring with mass spectrometry.