# US 2019/0170754 A1 · Method and reagent for detecting ovarian clear cell adenocarcinoma

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- Number: US 2019/0170754 A1
- Document ID: US20190170754A1
- Status: Published application
- Kind: A1
- Application number: 16/272,089
- Filed: 2019-02-11
- Published: 2019-06-06
- Earliest claimed: 2014-11-27
- Assignees: Public University Corporation Yokohama City University; Tosoh Corporation
- Applicants: Public University Corporation Yokohama City University; Tosoh Corporation
- Inventors: Noriaki Arakawa; Hisashi Hirano; Etsuko Miyagi; Norihisa Ohtake
- Web page: https://patentgrep.com/patent/US20190170754A1

## CPC

- G01N 33/57545: of the ovaries
- C07K 14/47: from mammals
- C07K 14/8114: {Kunitz type inhibitors}
- C07K 16/38: against protease inhibitors of peptide structure
- C12N 15/09: Recombinant DNA-technology
- G01N 33/575: for cancer
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- C07K 2317/30: characterized by aspects of specificity or valency
- G01N 2333/8114: Kunitz type inhibitors
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention aims to provide a method for detecting, with high sensitivity and specificity, ovarian clear cell adenocarcinoma, which is highly malignant, among benign and malignant ovarian tumors having various tissue types, and a reagent that can be used for the method. The present invention provides NT-TFPI2, which is a novel processed tissue factor pathway inhibitor 2 polypeptide, as a new detection marker for ovarian clear cell adenocarcinoma. The detection of ovarian clear cell adenocarcinoma is carried out by measuring the amount of NT-TFPI2, or the total amount of NT-TFPI2 and intact TFPI2. The reagent for detecting ovarian clear cell adenocarcinoma contains an antibody that specifically recognizes NT-TFPI2 and intact TFPI2.

## Claims

### Claim 1

A method for detecting ovarian clear cell adenocarcinoma, said method comprising measuring the amount of a processed tissue factor pathway inhibitor 2 (TFPI2) polypeptide in a sample,
wherein the processed TFPI2 polypeptide has the following properties (i) to (iii):
(i) a polypeptide having the amino acid sequence from the 23th residue aspartic acid to the 131st residue histidine or to the 130th residue cysteine in the TFPI2 amino acid sequence of SEQ ID NO:1, or a sequence having an identity of not less than 80% to this sequence;
(ii) a polypeptide that is fractionated into a molecular weight of about 16,000 by reducing SDS-PAGE; and
(iii) a polypeptide whose peptide fragment obtained after asparagine-linked sugar chain cleavage treatment is fractionated into a molecular weight of about 12,000 by reducing SDS-PAGE.

### Claim 2 (depends on 1)

The method according to claim 1, further comprising measuring the amount of intact TFPI2 in said sample.

### Claim 3 (depends on 2)

The method according to claim 2, wherein ovarian clear cell adenocarcinoma is judged to be detected in cases where the total of said amount of the processed TFPI2 polypeptide and said amount of intact TFPI2 exceeds a reference value calculated from a control.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said measurement is carried out by antigen-antibody reaction using an antibody that binds to an antigenic determinant in the region from the 23th residue aspartic acid to the 131st residue histidine or to the 130th residue cysteine in the TFPI2 amino acid sequence of SEQ ID NO:1.

### Claim 5 (depends on 4)

The method according to claim 4, wherein said antibody is an antibody that recognizes Kunitz domain 1 of TFPI2.

### Claim 6 (depends on 1)

The method according to claim 1, wherein said measurement is carried out using mass spectrometry.

### Claim 7

A reagent for detecting ovarian clear cell adenocarcinoma, comprising an antibody that binds to an antigenic determinant in the region from the 23th residue aspartic acid to the 131st residue histidine or to the 130th residue cysteine in the TFPI2 amino acid sequence of SEQ ID NO:1.