# US 12,004,868 B2 · Liposomal mitigation of drug-induced inhibition of the cardiac IKr channel

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- Number: US 12,004,868 B2
- Document ID: US12004868B2
- Status: Granted
- Kind: B2
- Application number: 16/432,498
- Filed: 2019-06-05
- Published: 2019-10-24
- Granted: 2024-06-11
- Earliest claimed: 2011-06-03
- Assignees: Signpath Pharma, Inc.
- Applicants: Signpath Pharma, Inc.
- Inventors: Lawrence Helson; George M. Shopp; Annie Bouchard
- Web page: https://patentgrep.com/patent/US12004868B2

## CPC

- A61B 5/4848: {Monitoring or testing the effects of treatment, e.g. of medication}
- A61B 5/364: Detecting abnormal ECG interval, e.g. extrasystoles, ectopic heartbeats
- 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 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 31/12: Ketones
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/683: Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61B 2503/42: for laboratory research
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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)

## Abstract

Compositions and methods are provided for preventing one or more cardiac channelopathies or conditions resulting from irregularities or alterations in cardiac patterns, or both, in a human or animal subject comprising: one or more pharmacologically active agents that causes at least one of IKr channel inhibition or QT prolongation by inhibiting the activity of an ether-a-go-go-related gene (hERG); and one or more liposomes, wherein the liposomes are empty liposomes and administered prior to, concomitantly, or after administration of the pharmacologically active agent.

## Claims

### Claim 1

A composition for treating one or more cardiac channelopathies or conditions resulting from irregularities or alterations in cardiac patterns, or both, in a human or animal subject consisting of:
one or more pharmacologically active agents that causes at least one of IKr channel inhibition or QT prolongation by inhibiting the activity of an ether-a-go-go-related gene, wherein the one or more active agents is selected from at least one of: aloxi; amiodarone; arsenic trioxide; astemizole; bepridil; chloroquine; chlorpheniramine; chlorpromazine; cisapride; celaxa; citalopram; clarithromycin; crizotinib; curcumin; disopyramide; dofetilide; domperidone; dronedarone; droperidol; erythromycin; gripafloxacin; haldol; haloperidol; halofantrine; ibutilide; levomethadyl; lidoflazine; loratidine; lovostatin; mesoridazone; methadone; methanesulphonanilide; moxifloxacin; nilotinib; palonasitron; pentamadine; pimozide; prenylamine; probucol; procainamide; propafenone; pyrilamine; quinidine; terfenidine; thorazine; sertindole; sotalol; sparfloxacin; terodiline; thioridazine; and vandetanib; and
empty liposomes of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), DMPG (1,2-dimyristoyl-sn-glycero-3-phospho-rac-[1-glycerol]), or both administered prior to, concomitantly, or after administration of the one or more pharmacologically active agent, wherein the DMPC is provided in an amount effective to reduce the cardiac channelopathies or conditions resulting from irregularities or alterations in cardiac patterns; and
one or more pharmaceutically acceptable dispersion mediums, solvents, or vehicles.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the cardiac channelopathy or the condition resulting from the irregularity or alteration in the cardiac pattern is inhibition of an ion channel responsible for the delayed-rectifier K+ current in the heart, polymorphic ventricular tachycardia, prolongation of the QTc, LQT2, LQTS, or torsades de pointes.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the composition is used for the treatment of prolongation of the IKr channel inhibition or QT prolongation induced by administration of one or more drugs used in the treatment of cardiac or non-cardiac related diseases.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the composition is adapted for enteral, parenteral, intravenous, intraperitoneal, or oral administration.

### Claim 5 (depends on 1)

The composition of claim 1, wherein a ratio of DMPC to DMPG is 9.7:1.

### Claim 6

A composition for treating one or more adverse reactions arising from administration of a therapeutically active agent or a drug in a human that causes at least one of IKr channel inhibition or QT prolongation by inhibiting the activity of an ether-a-go-go-related gene consisting essentially of:
one or more therapeutically active agents or drugs causes at least one of IKr channel inhibition or QT prolongation and empty liposomes of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), DMPG (1,2-dimyristoyl-sn-glycero-3-phospho-rac[1-glycero]), or both in an amount effective to reduce the adverse reactions arising from administration of the one or more therapeutically active agent or drug on IKr channel inhibition or QT prolongation, wherein the one or more active agents is selected from at least one of: aloxi; amiodarone; arsenic trioxide; astemizole; bepridil; chloroquine; chlorpheniramine; chlorpromazine; cisapride; celaxa; citalopram; clarithromycin; crizotinib; curcumin; disopyramide; dofetilide; domperidone; dronedarone; droperidol; erythromycin; gripafloxacin; haldol; haloperidol; halofantrine; ibutilide; levomethadyl; lidoflazine; loratidine; lovostatin; mesoridazone; methadone; methanesulphonanilide; moxifloxacin; nilotinib; palonasitron; pentamadine; pimozide; prenylamine; probucol; procainamide; propafenone; pyrilamine; quinidine; terfenidine; thorazine; sertindole; sotalol; sparfloxacin; terodiline; thioridazine; and vandetanib.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the one or more therapeutically active agent or a drug is used in a treatment of one or more cardiac or non-cardiac diseases in the human subject.

### Claim 8 (depends on 6)

The composition of claim 6, wherein the one or more adverse reactions resulting from the irregularity or alteration in the cardiac pattern is inhibition of an ion channel responsible for the delayed-rectifier K+ current in the heart, polymorphic ventricular tachycardia, prolongation of the QTc, LQT2, LQTS, or torsades de pointes.

### Claim 9 (depends on 6)

The composition of claim 6, wherein the composition is adapted for enteral, parenteral, intravenous, intraperitoneal, or oral administration.

### Claim 10 (depends on 6)

The composition of claim 6, wherein a ratio of DMPC to DMPG is 9.7:1.