# US 11,077,059 B2 · Electrospraying formation of particles including agents

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- Number: US 11,077,059 B2
- Document ID: US11077059B2
- Status: Granted
- Kind: B2
- Application number: 16/633,097
- Filed: 2018-07-25
- Published: 2020-08-13
- Granted: 2021-08-03
- Earliest claimed: 2017-07-25
- Assignees: Elektrofi, Inc.
- Applicants: Elektrofi, Inc.
- Inventors: Chase Spenser Coffman; Lyndon Fitzgerald Charles, Jr.; Paul Brown; Daniel Benjamin Dadon; Lisa Liu; Cory Robinson; Dale Arlington Thomas, III
- Web page: https://patentgrep.com/patent/US11077059B2

## CPC

- A61K 9/145: {with organic compounds}
- A61K 9/10: Dispersions; Emulsions
- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/5015: {Organic compounds, e.g. fats, sugars}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- B01J 2/06: in a liquid medium
- B01J 13/046: {combined with gelification or coagulation}
- B01J 13/12: removing solvent from the wall-forming material solution
- B01J 13/206: {Hardening; drying}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- 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)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

The invention provides methods for the preparation of particles including one or more agents, e.g., therapeutic or diagnostic agents. The particles can be formed by creating droplets of a first liquid, e.g., including an agent, and removing the first liquid, e.g., through its dispersal in a second liquid and/or evaporation, to solidify the droplets. Advantageously, the process of forming the particles does not significantly alter the structure or activity of the agents and may enhance the stability of the agents. For example, the particles may be stored for long periods of time without significant loss of activity, and in some embodiments, without the need for refrigeration. These particles may be used to generate stabilized pharmaceutical compositions for storage or other logistical purposes, pharmaceutical suspensions, pharmaceutical powder formulations (e.g., inhalable powders, injectable powders), creams or other topical pastes, nutraceuticals, or cosmetics.

## Claims

### Claim 1

A method of forming particles, the method comprising:
providing droplets comprising an aqueous first liquid and an antibody or fragment thereof, wherein the droplets are formed by electrospray;
contacting the droplets with an organic solvent, wherein the droplets float or do not float on the organic solvent; and
allowing the droplets to dry, thereby forming the particles.

### Claim 2 (depends on 1)

The method of claim 1, wherein the organic solvent has a density lower than or matching that of the droplets, wherein the droplets do not float on the organic solvent, and the aqueous first liquid disperses into the organic solvent to dry the droplets.

### Claim 3 (depends on 1)

The method of claim 1, wherein the concentration of the antibody or fragment thereof in the aqueous first liquid is from 200 to 600 mg/mL.

### Claim 4 (depends on 1)

The method of claim 1, wherein the particles have a mass loading of the antibody or fragment thereof from 50% to 70%.

### Claim 5 (depends on 1)

The method of claim 1, wherein the aqueous first liquid is selected from the group consisting of water, 0.9% saline, lactated Ringer's solution, dextrose 5%, and a buffer.

### Claim 6 (depends on 1)

The method of claim 1, wherein the aqueous first liquid further comprises a carbohydrate, a pH adjusting agent, a salt, a chelator, a mineral, a polymer, a surfactant, a protein stabilizer, an emulsifier, an antiseptic, an amino acid, an antioxidant, a protein, an organic solvent, a paraben, a bactericide, a fungicide, a vitamin, a preservative, or a nutrient media.

### Claim 7 (depends on 6)

The method of claim 6, wherein the carbohydrate is dextran, trehalose, sucrose, agarose, mannitol, lactose, sorbitol, or maltose.

### Claim 8 (depends on 6)

The method of claim 6, wherein the pH adjusting agent is acetate, citrate, glutamate, glycinate, histidine, lactate, maleate, phosphate, succinate, tartrate, bicarbonate, aluminum hydroxide, phosphoric acid, hydrochloric acid, DL-lactic/glycolic acids, phosphorylethanolamine, tromethamine, imidazole, glyclyglycine, or monosodium glutamate.

### Claim 9 (depends on 6)

The method of claim 6, wherein the salt is sodium chloride, calcium chloride, potassium chloride, sodium hydroxide, stannous chloride, magnesium sulfate, sodium glucoheptonate, sodium pertechnetate, or guanidine hydrochloride.

### Claim 10 (depends on 6)

The method of claim 6, wherein the surfactant is polysorbate, magnesium stearate, sodium dodecyl sulfate, glycerin, or polyoxyethylated castor oil.

### Claim 11 (depends on 6)

The method of claim 6, wherein the emulsifier is polysorbate 80, polysorbate 20, sorbitan monooleate, ethanolamine, polyoxyl 35 castor oil, poloxyl 40 hydrogenated castor oil, carbomer 1342, a corn oil-mono-di-triglyceride, a polyoxyethylated oleic glyceride, or a poloxamer.

### Claim 12 (depends on 6)

The method of claim 6, wherein the amino acid is alanine, aspartic acid, cysteine, isoleucine, glutamic acid, leucine, methionine, phenylalanine, pyrrolysine, serine, selenocysteine, threonine, tryptophan, tyrosine, valine, asparagine, L-arginine, histidine, glycine, glutamine, or a combination thereof.

### Claim 13 (depends on 6)

The method of claim 6, wherein the protein stabilizer is selected from the group consisting of trehalose, PEG 200, PEG 300, PEG 3350, PEG 8000, PEG 10000, PEG 20000, polyoxamers, polyvinylpyrrolidone, polyacrylic acids, poly(vinyl) polymers, polyesters, polyaldehydes, tert-polymers, polyamino acids, hydroxyethyl starch, N-methyl-2-pyrrolidone, sorbitol, sucrose, and mannitol.

### Claim 14 (depends on 1)

The method of claim 1, wherein the organic solvent is selected from the group consisting of benzyl benzoate, acetone, ethyl lactate, dimethyl isosorbide, dimethyl sulfoxide, glycofurol, diglyme, methyl tert-butyl ether, polyethylene glycol, 2-pyrrolidone, tetrahydrofurfuryl alcohol, trigylcerides, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, amyl acetate, chloroform, dichloromethane, ethanol, methanol, propanol, butanol, acetonitrile, diethyl ether, diglyme, 1,2-dimethoxyethane, dimethylformamide, pentane, toluene, and any combination thereof.

### Claim 15 (depends on 1)

The method of claim 1, further comprising removing the particles from the organic solvent through centrifugation, sieving, filtration, magnetic collection, solvent exchange, or decanting.

### Claim 16 (depends on 1)

The method of claim 1, wherein the antibody or fragment thereof in the particles has 0.5 to 1.0 activity per unit.

### Claim 17 (depends on 15)

The method of claim 15, wherein the particles are subjected to one or more secondary desiccation steps after separation from the organic solvent.