# US 10,869,908 B2 · Inducing cell death by hyperactivation of motility networks

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- Number: US 10,869,908 B2
- Document ID: US10869908B2
- Status: Granted
- Kind: B2
- Application number: 16/080,975
- Filed: 2017-02-24
- Published: 2019-02-28
- Granted: 2020-12-22
- Earliest claimed: 2016-02-29
- Assignees: The Johns Hopkins University
- Applicants: The Johns Hopkins University
- Inventors: Peter Devreotes; Huaqing Cai; Marc Edwards; Jun Liu; Michele Vitolo; Thomas Lampert; Yu Long; Alexandra Debonnes
- Web page: https://patentgrep.com/patent/US10869908B2

## CPC

- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/22: of acyclic acids, e.g. pravastatin
- A61K 31/366: having six-membered rings, e.g. delta-lactones
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
- A61K 31/655: Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
- A61N 1/00: Electrotherapy; Circuits therefor (A61N2/00 takes precedence; irradiation apparatus A61N5/00)
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61F 7/00: Heating or cooling appliances for medical or therapeutic treatment of the human body (hyperthermia using electric or magnetic fields or ultrasound A61N)
- A61H 7/00: Devices for suction-kneading massage; Devices for massaging the skin by rubbing or brushing not otherwise provided for (electro-medical massage devices applying electric current by contact A61N1/18)
- A61H 23/00: Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms {(apparatus for passive exercising A61H1/00; generating or transmitting mechanical vibrations in general B06B)}
- C12N 2501/48: Regulators of apoptosis
- C12N 2501/999: Small molecules not provided for elsewhere
- C12N 2527/00: Culture process characterised by the use of mechanical forces, e.g. strain, vibration
- 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
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- A61H: PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY (electrotherapy, magnetotherapy, radiation therapy or ultrasound therapy A61N)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Methods of inducing cell death by hyperactivation of motility networks are provided.

## Claims

### Claim 1

A method of killing a cell with an activated motility network comprising:
stressing the cell or further activating or hyper-activating the cell's motility network,
wherein an agent or stressor is administered to the cell thereby selectively killing the cell, wherein the cell bears a mutated oncogene or mutated tumor suppressor gene, wherein the mutated gene comprises Ras, PI3K, PTEN, or another defined mutation that activates a cell migration pathway, and the agent or stressor comprises an environmental perturbation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the environmental perturbation comprises a mechanical force, a temperature change, an electrical stimulus, a sound wave, osmotic shock, or other environmental change.

### Claim 3 (depends on 1)

The method of claim 1, wherein the agent comprises a statin, a phenothiazine, an antibiotic, or an analgesic.

### Claim 4 (depends on 3)

The method of claim 3, wherein the statin comprises pitavastatin, fluvastatin, atorvastatin, lovastatin, pravastatin, rosuvastatin, or simvastatin.

### Claim 5 (depends on 4)

The method of claim 4, wherein the statin comprises pitavastatin.

### Claim 6 (depends on 3)

The method of claim 3, wherein the phenothiazine comprises promazine HCl.

### Claim 7 (depends on 3)

The method of claim 3, wherein the antibiotic comprises polymyxin B sulfate or chloroxine.

### Claim 8 (depends on 3)

The method of claim 3, wherein the analgesic comprises phenazopyridine HCl.

### Claim 9 (depends on 1)

The method of claim 1, wherein the agent is administered at concentration of 5 mg/kg- 25 mg/kg.

### Claim 10 (depends on 1)

The method of claim 1, wherein the agent is administered orally, topically, or intravenously.

### Claim 11 (depends on 1)

The method of claim 1, wherein the hyper-activation is sustained.

### Claim 12 (depends on 1)

The method of claim 1, wherein the cell migration pathway comprises an oncogenic pathway or a tumor suppressor pathway.

### Claim 13 (depends on 12)

The method of claim 12, wherein the tumor suppressor pathway comprises PTEN.

### Claim 14 (depends on 12)

The method of claim 12, wherein the oncogenic pathway comprises Ras/TorC2, Rap or PI3K.

### Claim 15 (depends on 12)

The method of claim 12, wherein the cell death by hyperactivation of a motility pathway is termed sparagmosis.

### Claim 16

A method of killing a cell comprising:
administering to a cell an agent or stressor that selectively kills the cell, wherein the cell bears a mutated oncogene or mutated tumor suppressor gene, wherein the mutated gene comprises Ras, PI3K, PTEN, or another defined mutation that activates a cell migration pathway, and the agent or stressor comprises an environmental perturbation.

### Claim 17 (depends on 16)

The method of claim 16, wherein the environmental perturbation comprises a mechanical force, a temperature change, an electrical stimulus, a sound wave, osmotic shock, or other environmental change.

### Claim 18 (depends on 16)

The method of claim 16, wherein the agent comprises a statin, a phenothiazine, an antibiotic, or an analgesic.

### Claim 19 (depends on 16)

The method of claim 16, wherein the agent is pitavastatin, fluvastatin, atorvastatin, lovastatin, pravastatin, rosuvastatin, or simvastatin.

### Claim 20

A method of killing a cell, comprising:
treating the cell with an environmental perturbation that selectively kills the cell, wherein the cell bears a mutated oncogene or mutated tumor suppressor gene, wherein the mutated gene comprises Ras, PI3K, PTEN, or another defined mutation that activates a cell migration pathway.

### Claim 21 (depends on 20)

The method of claim 20, wherein the environmental perturbation comprises a mechanical force, a temperature change, an electrical stimulus, a sound wave, osmotic shock, or other environmental change.