# US 11,028,425 B2 · Diagnosis and monitoring of liver disease

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

- Number: US 11,028,425 B2
- Document ID: US11028425B2
- Status: Granted
- Kind: B2
- Application number: 16/355,225
- Filed: 2019-03-15
- Published: 2019-12-12
- Granted: 2021-06-08
- Earliest claimed: 2018-06-08
- Assignees: Glympse Bio, Inc.
- Applicants: Glympse Bio, Inc.
- Inventors: Sangeeta Bhatia; Gabriel Kwong; Eric Huang; Sirshendu Roopom Banerjee; Andrew Warren; Sophie Cazanave
- Web page: https://patentgrep.com/patent/US11028425B2

## CPC

- C12Q 1/37: involving peptidase or proteinase
- G01N 2800/085: Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N 2800/56: Staging of a disease; Further complications associated with the disease
- 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
- 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

Methods and compositions for screening or diagnosis of liver disease are provided. The results may also indicate course and efficacy of treatment. The composition includes an activity sensor and a reporter releasably attached to the activity sensor. The method includes detecting the presence and/or amount of a reporter. The reporter is released from an activity sensor in the presence of diseased liver tissue but remains attached to the activity sensor in healthy tissue. The presence and/or amount of the reporter are used to characterize the liver disease. The liver disease may be nonalcoholic steatohepatitis (NASH) and results may further indicate staging of NASH.

## Claims

### Claim 1

A method for characterizing liver disease, the method comprising:
detecting, in a sample from a subject, a quantity of each of a plurality of distinct reporters that are released from activity sensors, wherein different members of the plurality of reporters are released by proteases that are differentially active in diseased liver tissue versus healthy liver tissue, the proteases comprising at least 4 different proteases selected from the group consisting of FAP, MMP2, ADAMTS2, FURIN, MMP14, GZMB, PRSS8, MMP8, ADAM 12, CTSS, CTSA, CTSZ, CASP1, ADAMTS12, CTSD, CTSW, MMP11, MMP12, GZMA, MMP23B, MMP7, ST14, MMP9, MMP15, ADAMDEC1, ADAMTS1, GZMK, KLK11, MMP19, PAPPA, CTSE, PCSK5, and PLAU;
determining and classifying that the subject has nonalcoholic steatohepatitis (NASH) at one of stages NASH F1, NASH F2, NASH F3, or NASH F4, based upon relative quantities of the detected reporters, thereby characterizing the disease.

### Claim 2 (depends on 1)

The method of claim 1, wherein the quantities of the detected reporters are collected from a urine sample obtained from the subject to whom the activity sensors was administered.

### Claim 3 (depends on 1)

The method of claim 1, further comprising measuring quantities of the plurality of detected reporters.

### Claim 4 (depends on 3)

The method of claim 3, further comprising correlating quantities of the plurality of detected reporters to a rate of progression or regression of the liver disease.

### Claim 5 (depends on 1)

The method of claim 1, wherein the proteases include at least one of a serine protease, a cysteine protease, a threonine protease, an aspartic protease, and a metalloprotease.

### Claim 6 (depends on 5)

The method of claim 5, wherein the reporters are released via enzymatic cleavage.

### Claim 7 (depends on 1)

The method of claim 1, wherein at least 10 different proteases are selected.

### Claim 8 (depends on 1)

The method of claim 1, wherein the activity sensor comprises a multi-arm polyethylene glycol (PEG) scaffold and the reporters comprise polypeptides linked to the PEG scaffold.

### Claim 9 (depends on 1)

The method of claim 1, wherein relative quantities of detected reporters released by the selected proteases determines the stage of NASH with a sensitivity and specificity comprising an area under the curve (AUC) value of 0.98.