# US 2019/0167586 A1 · Liposomal apparatus and manufacturing methods

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

- Number: US 2019/0167586 A1
- Document ID: US20190167586A1
- Status: Published application
- Kind: A1
- Application number: 16/035,144
- Filed: 2018-07-13
- Published: 2019-06-06
- Earliest claimed: 2002-06-28
- Applicants: Arbutus Biopharma Corporation
- Inventors: Ian MacLachlan; Lloyd B. Jeffs; Lorne R. Palmer; Cory Giesbrecht
- Web page: https://patentgrep.com/patent/US20190167586A1

## CPC

- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/1277: Preparation processes; Proliposomes
- A61K 31/7084: Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

## Abstract

The present invention provides apparatus and processes for producing liposomes. By providing a buffer solution in a first reservoir, and a lipid solution in a second reservoir, continuously diluting the lipid solution with the buffer solution in a mixing chamber produces a liposome. The lipid solution preferably comprises an organic solvent, such as a lower alkanol.

## Claims

### Claim 1

A process for producing a lipid vesicle encapsulating one or more therapeutic agents within the lipid vesicle, said process comprising:
providing an aqueous solution in a first reservoir;
providing an organic lipid solution in a second reservoir, wherein the lipids present in said organic lipid solution are solubilized in a lower alkanol at a concentration of about 75% v/v to 100% v/v, wherein said aqueous solution and/or said organic lipid solution comprises one or more therapeutic agents, and wherein said one or more therapeutic agents is selected from the group consisting of a nucleic acid, a protein, an antigen, paclitaxel, protax III, taxol, and mixtures thereof; and
mixing said organic lipid solution with said aqueous solution by introducing said organic lipid solution and said aqueous solution into a mixing environment at about equal flow rates;
wherein said mixing instantaneously produces a lipid vesicle encapsulating said one or more therapeutic agents within the lipid vesicle by diluting said lower alkanol to a concentration of between 45% v/v to about 60% v/v;
wherein the mixing environment includes a mixing chamber, wherein said aqueous solution and said organic lipid solution are introduced into the mixing chamber at an angle of between about 27° and about 180° relative to each other and mixed within the mixing chamber; and
wherein said lipid vesicle has a diameter of about 150 nm or less.

### Claim 2 (depends on 1)

The process of claim 1, further comprising diluting said lipid vesicle with a buffer solution wherein said lipid vesicle undergoes a continuous stepwise dilution to further stabilize the lipid vesicle.

### Claim 3 (depends on 1)

The process of claim 1, wherein said nucleic acid is selected from the group consisting of a plasmid, an antisense polynucleotide, a ribozyme, mRNA, tRNA, snRNA, siRNA, pre-condensed DNA, and mixtures thereof.

### Claim 4 (depends on 1)

The process of claim 1, wherein said aqueous solution comprises said nucleic acid, protein, antigen, or mixtures thereof.

### Claim 5 (depends on 1)

The process of claim 1, wherein said organic lipid solution comprises said paclitaxel, protax III, taxol, or mixtures thereof.

### Claim 6 (depends on 1)

The process of claim 1, wherein said angle is between about 27° and about 90° or between about 90° and about 180°.

### Claim 7 (depends on 1)

The process of claim 1, wherein said lower alkanol is selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, isomers thereof, and mixtures thereof.

### Claim 8 (depends on 1)

The process of claim 1, wherein the lipids present in said organic lipid solution are solubilized in said lower alkanol at a concentration of between about 80% v/v to about 90% v/v or 100% v/v.

### Claim 9 (depends on 1)

The process of claim 1, wherein the lipids present in said organic lipid solution comprise a phospholipid, cholesterol, a PEG-lipid, and a cationic lipid.

### Claim 10 (depends on 2)

The process of claim 2, further comprising concentrating said lipid vesicle by tangential flow ultrafiltration.

### Claim 11

An apparatus for producing a lipid vesicle encapsulating one or more therapeutic agents within the lipid vesicle, said apparatus comprising:
a first reservoir for holding an aqueous solution;
a second reservoir for holding an organic lipid solution, wherein the lipids present in said organic lipid solution are solubilized in a lower alkanol at a concentration of about 75% v/v to 100% v/v, wherein said aqueous solution and/or said organic lipid solution comprises one or more therapeutic agents, and wherein said one or more therapeutic agents is selected from the group consisting of a nucleic acid, a protein, an antigen, paclitaxel, protax III, taxol, and mixtures thereof; and
a pump mechanism configured to pump said aqueous solution and said organic lipid solution into a mixing environment at about equal flow rates;
wherein said organic lipid solution mixes with said aqueous solution in the mixing environment to instantaneously produce a lipid vesicle encapsulating said one or more therapeutic agents within the lipid vesicle by diluting said lower alkanol to a concentration of between 45% v/v to about 60% v/v;
wherein the mixing environment includes a mixing chamber, wherein said aqueous solution and said organic lipid solution are introduced into the mixing chamber at an angle of between about 27° and about 180° relative to each other and mixed within the mixing chamber; and
wherein said lipid vesicle has a diameter of about 150 nm or less.

### Claim 12 (depends on 11)

The apparatus of claim 11, wherein said nucleic acid is selected from the group consisting of a plasmid, an antisense polynucleotide, a ribozyme, mRNA, tRNA, snRNA, siRNA, pre-condensed DNA, and mixtures thereof.

### Claim 13 (depends on 11)

The apparatus of claim 11, wherein said aqueous solution comprises said nucleic acid, protein, antigen, or mixtures thereof.

### Claim 14 (depends on 11)

The apparatus of claim 11, wherein said organic lipid solution comprises said paclitaxel, protax III, taxol, or mixtures thereof.

### Claim 15 (depends on 11)

The apparatus of claim 11, wherein said angle is between about 27° and about 90° or between about 90° and about 180°.

### Claim 16 (depends on 11)

The apparatus of claim 11, wherein said lower alkanol is selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, isomers thereof, and mixtures thereof.

### Claim 17 (depends on 11)

The apparatus of claim 11, wherein the lipids present in said organic lipid solution are solubilized in said lower alkanol at a concentration of between about 80% v/v to about 90% v/v or 100% v/v.

### Claim 18 (depends on 11)

The apparatus of claim 11, wherein the lipids present in said organic lipid solution comprise a phospholipid, cholesterol, a PEG-lipid, and a cationic lipid.

### Claim 19 (depends on 11)

The apparatus of claim 11, wherein the apparatus further comprises a tangential flow ultrafiltration system.

### Claim 20 (depends on 11)

The apparatus of claim 11, wherein the pump mechanism comprises a peristaltic pump.