# US 7,612,033 B2 · Methods for delivering compounds into a cell

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,612,033 B2
- Document ID: US7612033B2
- Status: Granted
- Kind: B2
- Application number: 10/802,919
- Filed: 2004-03-18
- Published: 2004-09-09
- Granted: 2009-11-03
- Earliest claimed: 1994-11-29
- Assignees: ImaRx Pharmaceutical Corp.
- Inventors: Evan C. Unger; Thomas McCreery
- Web page: https://patentgrep.com/patent/US7612033B2

## CPC

- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- A61K 41/0028: {Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention is directed, inter alia, to a method for delivering a compound into a cell comprising administering to the cell the compound to be delivered, an organic halide, and/or a carrier. Ultrasound may also be applied, if desired.

## Claims

### Claim 1

A method for delivering a protein into a cell in vivo, comprising:
(a) forming a plurality of protein-halide vesicles comprising the protein to be delivered and an organic halide incorporated in the core of the vesicles; and
(b) administering the protein-halide vesicles to the cell,
wherein the organic halide is selected from the group consisting of 1-bromo-nonafluorobutane, perfluorooctyliodide, perfluoroocytlbromide, 1-chloro-1-fluoro-1-bromomethane, 1,1,1-trichloro-2,2,2-trifluoroethane, 1,2-dichloro-2,2-difluoroethane, 1,1-dichloro-1,2-difluoroethane, 1,2-dichloro-1,1,3-trifluoropropane, 1-bromoperfluorobutane, 2-iodo-1,1,1-trifluoroethane, 5-bromovaleryl chloride, 1,3-dichlorotetrafluoroacetone, 1-bromo-1,1,2,3,3,3-hexafluoropropane, 2-chloro-1,1,1,4,4,4-hexafluoro-2-butene, 2-chloropentafluoro-1,3-butadiene, iodotrifluoroethylene, 1,1,2-trifluoro-2-chloroethane, 1,2-difluorochloroethane, 1,1-difluoro-2-chloroethane, 1,1-dichlorofluoroethane, heptafluoro-2-iodopropane, bromotrifluoroethane, chlorotrifluoromethane, dibromofluoromethane, chloropentafluoroethane, bromochlorodifluoromethane, dichloro-1,1,2,2-tetrafluoroethane, 1,1,1,3,3-pentafluoropentane, perfluorotributylamine, perfluorotripropylamine, 2,2,2-trifluoroethylacrylate, 3-(trifluoromethoxy)-acetophenone, 1,1,2,2,3,3,4,4-octafluorobutane, 1,1,1,3,3-pentafluorobutane, 1-fluorobutane, 1,1,2,2,3,3,4,4-octafluorobutane, 1,1,1,3,3-pentafluorobutane, tetradecaperfluoroheptane, dodecaperfluorocyclohexane, perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane, perfluorononane, perfluorodecane, perfluorododecane, perfluoro-2-methyl-2-pentene, perfluorocyclohexane, perfluoropropylene, perfluorocyclobutane, perfluoro-2-butyne, perfluoro-2-butene, perfluorobuta-1,3-diene, perfluorobutylethyl ether, bis(perfluoroisopropyl) ether, bis(perfluoropropyl) ether, perfluoromethyl tetrahydrofuran, perfluoro t-butyl methyl ether, perfluoro isobutyl methyl ether; perfluoro n-butyl methyl ether, perfluoro isopropyl ethyl ether, perfluoro n-propyl ethyl ether, perfluoro cyclobutyl methyl ether, perfluoro cyclopropyl ethyl ether, perfluoro isopropyl methyl ether, perfluoro n-propyl methyl ether, perfluoro diethyl ether, perfluoro cyclopropyl methyl ether, perfluoro methyl ethyl ether, and perfluoro dimethyl ether,
wherein the path of administering of the protein-halide composition to the cell is selected from a group consisting of the administering through a cell membrane, cell wall, and nuclear membrane, or any combination thereof,
to achieve the intracellular delivery of the protein thereby.

### Claim 2 (depends on 1)

The method of claim 1, wherein the organic halide is selected from the group consisting of 1-bromo-nonafluorobutane, 1,1,1,3,3-pentafluoropentane, perfluorohexane, perfluorocyclohexane, 1-bromo-1,1,2,3,3,3-hexafluoropropane, heptafluoro-2-iodopropane, 1,1,2,2,3,3,4,4-octafluorobutane, 1-fluorobutane, tetradecaperfluoroheptane, and dodecaperfluorocyclohexane.

### Claim 3 (depends on 1)

The method of claim 1, wherein the organic halide is selected from the group consisting of perfluorohexane and perfluorocyclohexane.

### Claim 4 (depends on 1)

The method of claim 1, wherein the protein is selected from the group consisting of albumin, collagen, polyarginine, polylysine, polyhistidine, γ-globulin, and β-globulin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the protein is a cationic protein.

### Claim 6 (depends on 5)

The method of claim 5, wherein the cationic protein is selected from the group consisting of polylysine and polyethyleneimine.

### Claim 7 (depends on 1)

The method of claim 1, further comprising applying ultrasound to the cell.

### Claim 8 (depends on 7)

The method of claim 7, wherein the ultrasound is applied at a frequency between about 40 kHz and 25 MHz, and an energy level between about 500 mW/cm2 and 10 W/cm2.

### Claim 9 (depends on 7)

The method of claim 7, wherein the ultrasound is applied at a frequency between about 200 kHz and 500 kHz, and the energy level is between about 200 mW/cm2 and 500 W/cm2.

### Claim 10 (depends on 7)

The method of claim 7, wherein the ultrasound is applied at a frequency between about 1 MHz and 20 MHz, and the energy level is between about 100 W/cm2 and 200 W/cm2.

### Claim 11 (depends on 10)

The method of claim 10, wherein the ultrasound is applied at a duty cycle between about 1% and 100% of the treatment time.

### Claim 12 (depends on 7)

The method of claim 7, wherein the protein and the ultrasound are administered and applied simultaneously.