# US 11,433,121 B1 · Lipid composition for the delivery of therapeutic cargos

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- Number: US 11,433,121 B1
- Document ID: US11433121B1
- Status: Granted
- Kind: B1
- Application number: 16/839,194
- Filed: 2020-04-03
- Granted: 2022-09-06
- Earliest claimed: 2020-04-03
- Assignees: National Technology & Engineering Solutions of Sandia, LLC
- Applicants: National Technology & Engineering Solutions of Sandia, LLC
- Inventors: Oscar Negrete; Annette Estelle LaBauve; Joseph S. Schoeniger; Edwin A. Saada
- Web page: https://patentgrep.com/patent/US11433121B1

## CPC

- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 9/226: {Class 2 CAS enzyme complex, e.g. single CAS protein}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- 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)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A construct includes a core comprising an external surface and a plurality of pores, a cargo disposed in a pore of the plurality of pores, the cargo comprising a CRISPR Cas9 component or a nucleic acid sequence encoding a CRISPR Cas9 component; and a coating coupled to the core, wherein the coating comprises a cationic lipid, a pegylated lipid, a zwitterionic lipid, and a sterol. The coating may comprise a molar ratio of about 1 cationic lipid to 1 zwitterionic lipid to 0.9 sterol to 0.15 PEGylated lipid, wherein each molar ratio optionally varies by about plus or minus 10%. A method of treatment is also provided.

## Claims

### Claim 1

A construct comprising:
a core comprising an external surface and a plurality of pores, wherein an average dimension of the plurality of pores is greater than about 2 nm;
a cargo disposed in a pore of the plurality of pores, the cargo comprising a CRISPR Cas9 component, or a nucleic acid sequence encoding a CRISPR Cas9 component; and
a coating coupled to the core, wherein the coating comprises a cationic lipid, a PEGylated lipid, a zwitterionic lipid, and a sterol.

### Claim 2 (depends on 1)

The construct of claim 1, wherein the core is a stellate mesoporous silica nanoparticle.

### Claim 3 (depends on 1)

The construct of claim 1, wherein the average diameter of the plurality of pores is of from about 3 nm to about 20 nm as determined by porosimetry with nitrogen adsorption-desorption analysis.

### Claim 4 (depends on 1)

The construct of claim 1, wherein the core has an average diameter of about 75 to about 400 nm.

### Claim 5 (depends on 2)

The construct of claim 2, wherein the mesoporous silica nanoparticle is monodisperse in particle diameter, wherein about 90% of the distribution lies within about 5% of the median diameter, as measured by dynamic light scattering.

### Claim 6 (depends on 1)

The construct of claim 1, wherein the coating comprises about 10 to about 50 mol % of the cationic lipid and zwitterionic lipid, about 5 to about 45 mol. % of the sterol, and about 2 to 8 mol. % of the PEGylated lipid.

### Claim 7 (depends on 1)

The construct of claim 1, wherein the coating comprises about 20 to about 40 mol % of the cationic lipid and zwitterionic lipid, about 10 to about 35 mol. % of the sterol, and about 2.5 to 6 mol. % of the PEGylated lipid.

### Claim 8 (depends on 1)

The construct of claim 1, wherein the coating comprises a molar ratio of about 1 cationic lipid to 1 zwitterionic lipid to 0.9 sterol to 0.15 PEGylated lipid, wherein each molar ratio optionally varies by about plus or minus 10%.

### Claim 9 (depends on 1)

The construct of claim 1, wherein the cationic lipid is 1,2-dioleoyl-3-trimethylammonium-propane, the zwitterionic lipid is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, the sterol is cholesterol, and the PEGylated lipid is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000].

### Claim 10 (depends on 8)

The construct of claim 8, wherein the cationic lipid is 1,2-dioleoyl-3-trimethylammonium-propane, the zwitterionic lipid is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, the sterol is cholesterol, and the PEGylated lipid is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000].

### Claim 11 (depends on 1)

The construct of claim 1, wherein the sterol is selected from the group consisting of: cholesterol, desmosterol, diplopterol, cholestanol, cholic acid, 12-deoxycholic acid, 7-deoxycholic acid, or a derivative thereof, and mixtures thereof and conjugated forms thereof.