# US 2016/0237496 A1 · Methods for assessing status of post-transplant liver and determining and administering specific treatment regimens

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- Number: US 2016/0237496 A1
- Document ID: US20160237496A1
- Status: Published application
- Kind: A1
- Application number: 15/025,209
- Filed: 2014-09-30
- Published: 2016-08-18
- Earliest claimed: 2013-10-02
- Assignees: Hitachichemical Company Ltd.; Hitachi Chemical Company America, Ltd.; National University Corporation Kumamoto University
- Applicants: Hitachichemical Company Ltd.; Hitachi Chemical Co. America, Ltd.; National University Corporation Kumamoto University
- Inventors: Masato Mitsuhashi; Daiki YOSHII; Katsuhiro ASONUMA; Yukihiro INOMATA
- Web page: https://patentgrep.com/patent/US20160237496A1

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- B01L 3/50255: {Multi-well filtration}
- C12Q 2600/158: Expression markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

Methods and devices allow assessment of the status of a transplanted liver during the post-transplant period. The methods are particularly beneficial for identifying if a transplanted liver is subject to rejection, by what mechanisms, and thereby developing and implementing a specific treatment regime to reduce the rejection of the transplanted liver.

## Claims

### Claim at position 1

-25. (canceled)

### Claim 26

A method of identifying the status of a liver of a subject after a liver transplant, comprising:
(I) obtaining bile collected from-the liver of the subject after the liver transplant;
(II) isolating one or more of membrane particles, exosomes, exosome-like vesicles, and microvesicles from the bile;
(III) detecting expression of at least one marker of liver condition from each of the following groups of markers:
(a) IL1B, IL6 and IL8,
(b) TNF-alpha, FasL, IFNG, granzyme B, CD16 DEFA3, and PRG2,
(c) IL10, TGF beta, CTLA4, PD-1 and FOXP3, and
(d) IL2, IL4 and GMCSF
by a method comprising:
(i) liberating RNA from the isolated membrane particles, exosomes, exosome-like vesicles, and/or microvesicles;
(ii) contacting the liberated RNA with a reverse transcriptase to generate complementary DNA (cDNA); and
(iii) contacting the cDNA with sense and antisense primers that are specific for each of the markers of liver condition and a DNA polymerase in order to generate amplified DNA; and
(IV) identifying status of the liver of the subject as:
(a) in an early stage of acute rejection or early stage of acute infection when one or more of IL1B, IL6, and IL8 is detected,
(b) in acute rejection when one or more of TNF-alpha, FasL, IFNG, granzyme B, CD16, and DEFA3 is detected,
(c) in a recovery phase from acute rejection when one or more of IL10, TGF-beta, CTLA4, PD-1 and FOXP3 is detected, or
(d) in sustained rejection when one or more of IL2, IL4 and GMCSF is detected.

### Claim at position 3

-46. (canceled)