# US 8,785,466 B2 · Methods of using proteinacious channels to identify pharmaceutical treatments and risks, and treatments resulting therefrom

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- Number: US 8,785,466 B2
- Document ID: US8785466B2
- Status: Granted
- Kind: B2
- Application number: 12/609,724
- Filed: 2009-10-30
- Published: 2010-05-06
- Granted: 2014-07-22
- Earliest claimed: 2008-10-31
- Assignees: Loyola University of Chicago
- Applicants: Kenneth L. Byron; Lioubov I. Brueggemann
- Inventors: Kenneth L. Byron; Lioubov I. Brueggemann
- Web page: https://patentgrep.com/patent/US8785466B2

## CPC

- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/415: 1,2-Diazoles
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- G01N 33/5038: {involving detection of metabolites per se}
- G01N 2800/32: Cardiovascular disorders
- 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)
- 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)

## Abstract

Methods and therapeutic strategies utilizing proteinacious channels in lipid membranes of mammalian cells. The methods entail administering a pharmaceutical to a lipid membrane of a mammalian cell, and then determining the effect of the pharmaceutical on the electrophysiology of at least one vascular proteinacious channel of the lipid membrane, wherein the vascular proteinacious channel is a vascular Kv7 potassium channel and/or a vascular L-type calcium channel. The method can be used to identify pharmaceuticals that may be used to treat hypertension and/or vasospastic conditions, or to perform drug screening to assess potential cardiovascular risk of pharmaceuticals.

## Claims

### Claim 1

A method utilizing proteinacious channels in a lipid membrane of a mammalian cell, the method comprising:
administering a pharmaceutical to a lipid membrane of a mammalian cell;
measuring an electrical activity across the lipid membrane to determine an effect of the pharmaceutical on the electrophysiology of arterial Kv7 potassium channels of the lipid membrane; and then
identifying pharmaceutical treatments for hypertensive, cancer, vasospastic, or cardiovascular medical conditions or risks of the pharmaceutical based on the electrical activity caused by the pharmaceutical,
wherein the medical conditions are affected by the electrophysiology of arterial Kv7 potassium channels; and
wherein pharmaceutical treatments for hypertensive, cancer, vasospastic, or cardiovascular medical conditions are identified if the effect of the pharmaceutical is to activate the arterial Kv7 potassium channels during the step of measuring the electrical activity, and risks of the pharmaceutical are identified if the effect of the pharmaceutical is to inhibit the arterial Kv7 potassium channels during the step of measuring the electrical activity.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the step of measuring the electrical activity determines the effect of the pharmaceutical on currents generated by the arterial Kv7 potassium channels.

### Claim 3 (depends on 1)

The method according to claim 1, further comprising administering the pharmaceutical to a living body if the effect of the pharmaceutical is to activate the arterial Kv7 potassium channels during the step of measuring the electrical activity.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the step of administering a pharmaceutical comprises administering the pharmaceutical to cultured cells engineered to express arterial Kv7 potassium channels.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the mammalian cell is an arterial smooth muscle cell.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the step of identifying pharmaceutical treatments for medical conditions or risks of the pharmaceutical is performed to identify pharmaceuticals for treating cardiovascular conditions if the effect of the pharmaceutical is to activate the arterial Kv7 potassium channels during the step of measuring the electrical activity.

### Claim 7 (depends on 1)

The method according to claim 1, further comprising administering the pharmaceutical to a living body to treat a hypertensive or vasospastic condition if the effect of the pharmaceutical is to activate the arterial Kv7 potassium channels.

### Claim 8 (depends on 6)

The method according to claim 6, further comprising administering the pharmaceutical to a living body that has suffered a subarachnoid hemorrhage if the effect of the pharmaceutical is to activate the arterial Kv7 potassium channels during the step of measuring the electrical activity.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the method is a drug screening procedure to assess potential cardiovascular risks of the pharmaceutical.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the step of measuring the electrical activity determines the effect of the pharmaceutical on currents generated by the arterial Kv7 potassium channels.

### Claim 11 (depends on 9)

The method according to claim 9, further comprising administering the pharmaceutical to a living body if the effect of the pharmaceutical is to activate or inhibit the arterial Kv7 potassium channels during the step of measuring the electrical activity.

### Claim 12 (depends on 9)

The method according to claim 9, further comprising administering the pharmaceutical to a living body to treat cancer if the effect of the pharmaceutical is to activate the arterial Kv7 potassium channels during the step of measuring the electrical activity.

### Claim 13

A method utilizing proteinacious channels in a lipid membrane of a mammalian cell, the method comprising:
administering a pharmaceutical to a lipid membrane of a mammalian cell; and then
determining an effect of the pharmaceutical on the electrophysiology of vascular Kv7 potassium channels of the lipid membrane;
wherein the pharmaceutical is a COX-2 inhibitor.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the pharmaceutical is not a COX-2 inhibitor.

### Claim 15 (depends on 13)

The method according to claim 13, wherein the pharmaceutical is celecoxib or 2,5-dimethyl-celecoxib.
