# US 11,298,422 B2 · Treating tumors with TTFields and an aurora kinase inhibitor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,422 B2 - Document ID: US11298422B2 - Status: Granted - Kind: B2 - Application number: 16/377,599 - Filed: 2019-04-08 - Published: 2019-10-10 - Granted: 2022-04-12 - Earliest claimed: 2018-04-09 - Assignees: Novocure GmbH - Applicants: Novocure Limited - Inventors: Dietmar Krex; Achim Temme; Rosa S. Shnaiderman; Moshe Giladi - Web page: https://patentgrep.com/patent/US11298422B2 ## CPC - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole - A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate - A61K 33/42: Phosphorus; Compounds thereof - A61N 1/32: alternating or intermittent currents {(applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02)} - A61N 1/36002: {Cancer treatment, e.g. tumour} - A61N 1/40: Applying electric fields by inductive or capacitive coupling (microwave apparatus A61N5/00); {Applying radio-frequency signals} - A61P 35/00: Antineoplastic agents - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The viability of cancer cells can be reduced by administering an Aurora kinase inhibitor (e.g., MLN8237 or another Aurora A kinase inhibitor, AZD1152 or another Aurora B kinase inhibitor) to the cancer cells, and applying an alternating electric field with a frequency between 100 and 300 kHz (e.g., 200 kHz) to the cancer cells. Furthermore, cancer (e.g., glioblastoma) in a subject may be treated by administering an Aurora kinase inhibitor to the subject, and applying an alternating electric field with frequency between 100 and 300 kHz (e.g., 200 kHz) to a target region of the subject (e.g., the brain). ## Claims ### Claim 1 A method of reducing viability of cancer cells, the method comprising: administering an Aurora kinase inhibitor to the cancer cells; and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 300 kHz. ### Claim 2 (depends on 1) The method of claim 1, wherein the Aurora kinase inhibitor comprises an Aurora A kinase inhibitor. ### Claim 3 (depends on 1) The method of claim 1, wherein the Aurora kinase inhibitor comprises an Aurora B kinase inhibitor. ### Claim 4 (depends on 1) The method of claim 1, wherein the Aurora kinase inhibitor comprises MLN8237. ### Claim 5 (depends on 1) The method of claim 1, wherein the Aurora kinase inhibitor comprises AZD1152. ### Claim 6 (depends on 1) The method of claim 1, wherein the Aurora kinase inhibitor comprises an Aurora kinase inhibitor selected from the group consisting of AZD1152, Alisertib (MLN8237), Danusertib (PHA-739358), AT9283, PF-03814735, and AMG 900. ### Claim 7 (depends on 1) The method of claim 1, wherein at least a portion of the applying step is performed simultaneously with at least a portion of the administering step. ### Claim 8 (depends on 1) The method of claim 1, wherein the applying step has a duration of at least 72 hours. ### Claim 9 (depends on 1) The method of claim 1, wherein the frequency of the alternating electric field is between 180 and 220 kHz. ### Claim 10 (depends on 1) The method of claim 1, wherein the Aurora kinase inhibitor is administered to the cancer cells at a therapeutically effective concentration, and wherein the alternating electric field has a field strength of at least 1 V/cm in at least some of the cancer cells. ### Claim 11 (depends on 10) The method of claim 10, wherein the therapeutically effective concentration of the Aurora kinase inhibitor is reduced by at least 50% with respect to a dosage of the Aurora kinase inhibitor known to be therapeutically effective in the absence of an alternating electric field. ### Claim 12 (depends on 10) The method of claim 10, wherein the therapeutically effective concentration of the Aurora kinase inhibitor is from about 12.5 nM to about 100 nM. ### Claim 13 (depends on 10) The method of claim 10, wherein the therapeutically effective concentration of the Aurora kinase inhibitor is from 25 nM to 75 nM. ### Claim 14 A method of treating cancer in a subject, the method comprising: administering a therapeutically effective dose of an Aurora kinase inhibitor to the subject; and applying an alternating electric field to a target region of the subject, the alternating electric field having a frequency between 100 and 300 kHz. ### Claim 15 (depends on 14) The method of claim 14, wherein the Aurora kinase inhibitor comprises an Aurora A kinase inhibitor. ### Claim 16 (depends on 14) The method of claim 14, wherein the Aurora kinase inhibitor comprises an Aurora B kinase inhibitor. ### Claim 17 (depends on 14) The method of claim 14, wherein the Aurora kinase inhibitor comprises AZD1152. ### Claim 18 (depends on 14) The method of claim 14, wherein the Aurora kinase inhibitor comprises MLN8237. ### Claim 19 (depends on 14) The method of claim 14, wherein the cancer comprises Glioblastoma. ### Claim 20 (depends on 14) The method of claim 14, wherein the Aurora kinase inhibitor comprises an Aurora kinase inhibitor selected from the group consisting of AZD1152, Alisertib (MLN8237), Danusertib (PHA-739358), AT9283, PF-03814735, and AMG 900. ### Claim 21 (depends on 14) The method of claim 14, wherein at least a portion of the applying step is performed after the administering step and before the Aurora kinase inhibitor is eliminated from the subject's body or exhausted. ### Claim 22 (depends on 14) The method of claim 14, wherein the applying step has a duration of at least 72 hours. ### Claim 23 (depends on 14) The method of claim 14, wherein the frequency of the alternating electric field is between 180 and 220 kHz. ### Claim 24 (depends on 14) The method of claim 14, wherein the alternating electric field has a field strength of at least 1 V/cm in at least a portion of the target region. ### Claim 25 (depends on 14) The method of claim 14, wherein the therapeutically effective dose of the Aurora kinase inhibitor is reduced by at least 50% with respect to a dosage of the Aurora kinase inhibitor known to be therapeutically effective in the absence of an alternating electric field. ### Claim 26 (depends on 14) The method of claim 14, wherein the therapeutically effective dose of the Aurora kinase inhibitor is from about 12.5 nM to about 100 nM. ### Claim 27 (depends on 14) The method of claim 14, wherein the therapeutically effective dose of the Aurora kinase inhibitor is from 25 nM to 75 nM.