# US 10,307,140 B2 · Device for detection of hepatocellar carcinoma (HCC) using an octanoate breath test

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- Number: US 10,307,140 B2
- Document ID: US10307140B2
- Status: Granted
- Kind: B2
- Application number: 15/459,081
- Filed: 2017-03-15
- Published: 2017-08-24
- Granted: 2019-06-04
- Earliest claimed: 2011-04-14
- Assignees: Exalenz Bioscience Ltd.
- Applicants: Exalenz Bioscience Ltd.
- Inventors: Gil Guggenheim; Ilan Ben-Oren; Avraham Hershkowitz; Yaron Ilan
- Web page: https://patentgrep.com/patent/US10307140B2

## CPC

- A61B 10/00: Instruments for taking body samples for diagnostic purposes (for taking samples of blood A61B5/15); Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
- A61B 5/082: {Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath (A61B5/083, A61B5/091 take precedence)}
- A61B 5/0836: {Measuring rate of CO2 production}
- A61B 5/4244: {liver}
- A61B 5/4842: {Monitoring progression or stage of a disease}
- A61B 5/7282: {Event detection, e.g. detecting unique waveforms indicative of a medical condition (cough events A61B5/0823; seizures A61B5/4094; sleep apnoea A61B5/4818)}
- G01N 33/497: of gaseous biological material, e.g. breath
- G01N 33/57525: of the liver or pancreas
- A61B 2010/0087: {Breath samples}
- G01N 33/4975: {other than oxygen, carbon dioxide or alcohol, e.g. organic vapours}
- G01N 2458/15: Non-radioactive isotope labels, e.g. for detection by mass spectrometry
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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 systems for diagnosis, prognosis and monitoring of hepatocellular carcinoma (HCC). Specifically, the present invention relates to the use of breath tests based on isotope-labeled octanoate in the detection and monitoring of HCC.

## Claims

### Claim 1

A device for hepatocellular carcinoma (HCC) detection comprising a processor configured to:
obtaining a level of an isotope-labeled octanoate metabolic product measured in a subject's exhaled breath with a sensor following administering the isotope-labeled octanoate;
comparing the measured level of the isotope-labeled octanoate metabolic product to a reference level; and
detecting HCC based on a difference between the measured level of the isotope-labeled octanoate metabolic product and the reference level; wherein a significantly decreased level of isotope-labeled octanoate metabolic product is indicative of active HCC.

### Claim 2 (depends on 1)

The device of claim 1, wherein the processor is further configured to distinguish between impaired liver function caused by fibrosis or cirrhosis and HCC, based on the comparing.

### Claim 3 (depends on 1)

The device of claim 1, wherein the reference level is a level of isotope-labeled octanoate metabolic product typically measured in breath of healthy subjects.

### Claim 4 (depends on 1)

The device of claim 1, wherein the sensor is configured to perform continuous measurements.

### Claim 5 (depends on 1)

The device of claim 1, wherein the isotope-labeled octanoate is selected from the group consisting of carbon-13, carbon-14 and oxygen-18.

### Claim 6 (depends on 1)

The device of claim 1, wherein the processor is configured to generate at least one of a delta over baseline (DOB) curve, a percentage dose recovery (PDR) curve and/or a cumulative PDR (CPDR) curve, and to compare at least one parameter of said DOB, PDR or CPDR curves to at least one parameter of reference DOB, PDR and/or CPDR curves.

### Claim 7 (depends on 6)

The device of claim 6, wherein the processor is configured to generate a PDR curve and to compare at least one parameter of said PDR curve to at least one parameter of a reference PDR curve, wherein the at least one parameter is selected from the group consisting of PDR maximum level (peak height), time of appearance of the peak (time to peak) and the slope of rate of metabolism.

### Claim 8 (depends on 7)

The device of claim 7, wherein the parameter is peak height and/or time to peak, and wherein decreased peak height is indicative of HCC and a longer time to peak is indicative of HCC.

### Claim 9 (depends on 1)

The device of claim 1, wherein the processor is configured to obtain a disease etiology of the subject and to normalize the measured level of isotope-labeled octanoate metabolic product according to the disease etiology.

### Claim 10 (depends on 9)

The device of claim 9, wherein the disease etiology is NASH or NAFLD.

### Claim 11 (depends on 1)

The device of claim 1, wherein the processor is further configured to obtain one or more blood test results and to normalize the measured level of isotope-labeled octanoate metabolic product according to the one or more blood test results.

### Claim 12 (depends on 11)

The device of claim 11, wherein the blood test results are selected from the group consisting of: fasting glucose levels, insulin levels, ALT levels, AST levels, ALP levels, GGTP levels, bilirubin levels, albumin levels and sodium levels.

### Claim 13 (depends on 1)

The device of claim 1, wherein the processor is further configured to obtain a treatment that the subject is receiving or has received and to normalize the measured level of isotope-labeled octanoate metabolic product according to the treatment.

### Claim 14 (depends on 13)

The device of claim 13, wherein the treatment is sorafenib.

### Claim 15 (depends on 1)

The device of claim 1, wherein the processor is further configured to obtain values indicative of CO2 levels in the subject breath.

### Claim 16 (depends on 1)

The device of claim 1, further comprising a CO2 sensor.