# US 10,369,229 B2 · Methods and compositions for liposomal formulation of antigens and uses thereof

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- Number: US 10,369,229 B2
- Document ID: US10369229B2
- Status: Granted
- Kind: B2
- Application number: 15/943,382
- Filed: 2018-04-02
- Published: 2018-10-04
- Granted: 2019-08-06
- Earliest claimed: 2009-03-09
- Assignees: The Regents of the University of California; Molecular Express, Inc.
- Applicants: The Regents of the University of California; Molecular Express, Inc.
- Inventors: Gary Fujii; Francis C. Szoka; Douglas S. Watson
- Web page: https://patentgrep.com/patent/US10369229B2

## CPC

- A61K 47/6913: {the liposome being modified on its surface by an antibody}
- 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 39/07: Bacillus
- A61K 39/12: Viral antigens
- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 47/554: {the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid}
- A61K 47/6911: {the form being a liposome}
- A61P 37/04: Immunostimulants
- C07J 9/00: Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J 41/0055: {the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives}
- C07J 43/003: {not condensed}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55572: {Lipopolysaccharides; Lipid A; Monophosphoryl lipid A}
- A61K 2039/60: {characteristics by the carrier linked to the antigen}
- A61K 2039/6018: {Lipids, e.g. in lipopeptides}
- A61K 2039/627: {characterised by the linker}
- C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2770/00011: Details
- C12N 2770/00034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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
- C07J: STEROIDS (seco-steroids C07C)
- 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 relates to liposomal vaccine compositions, methods for the manufacture thereof, and methods for the use thereof to stimulate an immune response in an animal. These compositions comprise dimyristoylphosphatidylcholine (“DMPC”); either dimyristoylphosphatidylglycerol (“DMPG”) or dimyristoyltrimethylammonium propane (“DMTAP”) or both DMPC and DMTAP; and at least one sterol derivative providing a covalent anchor for one or more immunogenic polypeptide(s) or carbohydrate(s).

## Claims

### Claim 1

A composition comprising:
an aqueous vehicle; and
liposomes comprising
(i) dimyristoylphosphatidylcholine (“DMPC”),
(ii) dimyristoylphosphatidylglycerol (“DMPG”), dimyristoyltrimethylammonium propane (“DMTAP”), or both DMPG and DMTAP, and
(iii) at least one reactive sterol derivative, wherein between 1% and 100% of said at least one sterol derivatives comprise an influenza M2 antigen polypeptide sequence covalently linked thereto.

### Claim 2 (depends on 1)

A composition according to claim 1, wherein said relative percentages are 70%-85% (i): 5%-15% (ii): 10%-15% (iii).

### Claim 3 (depends on 1)

A composition according to claim 1, wherein said relative percentages are about 75% (i), about 10% (ii), and about 15% (iii).

### Claim 4 (depends on 1)

A composition according to claim 1, wherein said liposomes are substantially between 50 and 500 nm in diameter.

### Claim 5 (depends on 4)

A composition according to claim 4, wherein said liposomes are substantially between 50 and 200 nm in diameter.

### Claim 6 (depends on 4)

A composition according to claim 4, wherein said liposomes are substantially between 50 and 150 nm in diameter.

### Claim 7 (depends on 1)

A composition according to any of claim 1, wherein the lipid in (ii) is DMPG.

### Claim 8 (depends on 1)

A composition according to claim 1, wherein said sterol derivative(s) is/are derivative(s) of cholesterol, cholesteryl chloroformate, stigmasterol, sitosterol, ergosterol, lanosterol, desmosterol, or campesterol.

### Claim 9 (depends on 1)

A composition according to claim 1, wherein the functional moiety is a maleimide.

### Claim 10 (depends on 1)

A composition according to claim 1, further comprising an adjuvant.

### Claim 11 (depends on 10)

A composition according to claim 10, wherein the adjuvant is a Toll-like Receptor agonist.