# US 12,006,553 B2 · Companion diagnostics for mitochondrial inhibitors

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- Number: US 12,006,553 B2
- Document ID: US12006553B2
- Status: Granted
- Kind: B2
- Application number: 16/614,581
- Filed: 2018-05-18
- Published: 2020-08-13
- Granted: 2024-06-11
- Earliest claimed: 2017-05-19
- Assignees: Lunella Biotech, Inc.
- Applicants: Lunella Biotech, Inc.
- Inventors: Michael P. Lisanti; Federica Sotgia
- Web page: https://patentgrep.com/patent/US12006553B2

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/57595: {involving intracellular compounds}
- A61P 35/00: Antineoplastic agents
- G01N 33/5079: {Mitochondria}
- C12Q 1/6816: characterised by the detection means (C12Q1/6804 takes precedence)
- C12Q 2565/00: Nucleic acid analysis characterised by mode or means of detection
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to methods of identifying patients that may be responsive to mitochondrial inhibitor therapies to target and eradicate cancer stem cells. Also described are diagnostic kits that may be used to identify patients responsive to mitochondrial inhibitor therapies.

## Claims

### Claim 1

A method for treating breast cancer in a breast cancer patient having mRNA levels of at least one of HSPD1, UQCRB, MRPL15, and COX17 mitochondrial markers exceeding a threshold level for the mitochondrial marker, the method comprising:
obtaining a breast tumor sample obtained from a breast cancer patient having measured mRNA levels of at least one of HSPD1, UQCRB, MRPL15, and COX17 mitochondrial markers exceeding a threshold level for the mitochondrial marker;
measuring an mRNA level of each of a plurality of mitochondrial markers in the breast tumor sample, the plurality comprising HSPD1, UQCRB, MRPL15, and COX17; and
administering to the breast cancer patient having measured mRNA levels of at least one of the HSPD1, UQCRB, MRPL15, and COX17 mitochondrial markers exceeding a threshold level for the mitochondrial marker, a pharmaceutically effective amount of a mitochondrial inhibitor, the mitochondrial inhibitor selected from the group consisting of a mitoriboscin, a mitoketoscin, an antimitoscin, metformin, a tetracycline family member, an erythromycin family member, atovaquone, bedaquiline, and vitamin c.

### Claim 2 (depends on 1)

The method of claim 1, wherein the breast tumor comprises drug-resistant stem cells, and further comprising administering to the patient at least one of an OXPHOS inhibitor, a glycolysis inhibitor, and an autophagy inhibitor.

### Claim 3 (depends on 1)

The method of claim 1, wherein the at least one mitochondrial inhibitor comprises at least one of an OXPHOS inhibitor, a glycolysis inhibitor, and an autophagy inhibitor.

### Claim 4 (depends on 1)

The method of claim 1, wherein the mitochondrial inhibitor is selected from the group of a tetracycline family member, a erythromycin family member, and bedaquiline.

### Claim 5 (depends on 1)

The method of claim 1, wherein the mitochondrial inhibitor is doxycycline.

### Claim 6 (depends on 1)

The method of claim 1, wherein the mitochondrial inhibitor is azithromycin.

### Claim 7 (depends on 4)

The method of claim 4, wherein the mitochondrial inhibitor is bedaquiline.

### Claim 8 (depends on 1)

The method of claim 1, wherein the mitochondrial inhibitor comprises a combination of a tetracycline family member and an erythromycin family member.

### Claim 9 (depends on 1)

The method of claim 1, wherein the measuring a level of a plurality of mitochondrial markers comprises at least one of a quantitative polymerase chain reaction (“PCR”) analysis, a quantitative reverse transcription (“RT”)-PCR, a quantitative microarray analysis, and a Northern blot analysis.