# US 12,716,887 B2 · Methods of reducing ciliogenesis with alternating electric fields

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- Number: US 12,716,887 B2
- Document ID: US12716887B2
- Status: Granted
- Kind: B2
- Application number: 18/070,957
- Filed: 2022-11-29
- Published: 2023-06-01
- Granted: 2026-08-25
- Earliest claimed: 2021-11-29
- Assignees: Novocure GmbH
- Applicants: Novocure GmbH
- Inventors: Matthew R. Sarkisian; Lilach Avigdor; Preshita Desai
- Web page: https://patentgrep.com/patent/US12716887B2

## CPC

- A61N 1/36002: {Cancer treatment, e.g. tumour}
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- A61N 1/32: alternating or intermittent currents {(applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02)}
- C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A method of determining susceptibility of cancer cells to treatment with alternating electric fields, or of reducing the viability of cancer cells by applying alternating electric fields, by measuring percentage of ciliated cancer cells or by measuring average length of a primary cilia of cancer cells. A method of treating Huntington's disease by applying alternating electric fields to a brain of a subject.

## Claims

### Claim 1

A method of determining susceptibility of cancer cells of a subject to treatment with alternating electric fields, the method comprising:
applying alternating electric fields to a first batch of cancer cells obtained or derived from a subject;
after applying the alternating electric fields to the first batch of cancer cells ascertaining via imaging or RT-PCR or by determining a level of ARG13B or OTD1 a first percentage of the cancer cells of the first batch that are ciliated;
ascertaining a second percentage of a second batch of cancer cells obtained or derived from the subject that are ciliated, wherein the second batch of cancer cells was not exposed to alternating electric fields prior to ascertaining the second percentage, wherein the first percentage of ciliated cancer cells is lower than the second percentage of ciliated cancer cells; and
after ascertaining the first and second percentages of cancer cells that are ciliated, treating cancer cells of in the subject with alternating electric fields.

### Claim 2 (depends on 1)

The method of claim 1, the first percentage of ciliated cancer cells is at least 20% lower than the second percentage of ciliated cancer cells.

### Claim 3 (depends on 1)

The method of claim 1, wherein a frequency of the alternating electric fields is between 50 kHz and 1 MHz.

### Claim 4 (depends on 1)

The method of claim 1, wherein a frequency of the alternating electric fields is 200 kHz.

### Claim 5 (depends on 1)

The method of claim 1, wherein the percentages of the cancer cells that are ciliated are ascertained by imaging cancer cells.

### Claim 6 (depends on 5)

The method of claim 5, wherein the imaging is performed by confocal microscopy or light microscopy.

### Claim 7 (depends on 1)

The method of claim 1, wherein the percentages of the cancer cells that are ciliated are ascertained by RT-PCR.

### Claim 8 (depends on 1)

The method of claim 1, wherein the percentages of the cancer cells that are ciliated are ascertained by determining a level of ARL13B in the first batch and the second batch.

### Claim 9 (depends on 1)

The method of claim 1, wherein the percentages of the cancer cells that are ciliated are ascertained by determining a level of OTD1 in the first batch and the second batch.

### Claim 10

A method of reducing the viability of cancer cells of a subject, comprising:
applying alternating electric fields to a first batch of cancer cells obtained or derived from a subject;
ascertaining, after applying the alternating electric fields to the first batch of cancer cells, a first percentage of the cancer cells of the first batch that are ciliated;
ascertaining a second percentage of a second batch of cancer cells obtained or derived from the subject that are ciliated, wherein the second batch of cancer cells was not exposed to alternating electric fields prior to ascertaining the second percentage, wherein the first percentage of ciliated cancer cells is lower than the second percentage of ciliated cancer cells; and
after ascertaining the first and second percentages of cancer cells that are ciliated, applying alternating electric fields to the subject.

### Claim 11 (depends on 10)

The method of claim 10, wherein the first percentage of ciliated cancer cells is at least 20% lower than the second percentage of ciliated cancer cells.

### Claim 12 (depends on 10)

The method of claim 10, wherein a frequency of the alternating electric fields is between 50 kHz and 1 MHz.

### Claim 13 (depends on 10)

The method of claim 10, wherein a frequency of the alternating electric fields is 200 kHz.

### Claim 14 (depends on 10)

The method of claim 10, wherein the alternating electric fields are applied for at least 12 hours.

### Claim 15 (depends on 10)

The method of claim 10, wherein the alternating electric fields are applied for at least 24 hours.

### Claim 16 (depends on 10)

The method of claim 10, wherein the alternating electric fields are applied for at least 72 hours.

### Claim 17 (depends on 10)

The method of claim 10, further comprising administering a chemotherapeutic agent to the cancer cells.

### Claim 18 (depends on 17)

The method of claim 17, wherein the chemotherapeutic agent is TMZ.

### Claim 19 (depends on 17)

The method of claim 17, wherein the chemotherapeutic agent is a checkpoint inhibitor.
