Methods and compositions for the preparation of aerosols

Patent metadata

Field	Value
Publication number	US-12083219-B2
Application number	US-202117233621-A
Country	US
Kind code	B2
Filing date	Apr 19, 2021
Priority date	Feb 11, 2010
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

The present invention relates to methods for the preparation of an aerosol. More specifically the present invention provides methods for the preparation of an aerosol of immunoglobulin single variable domains wherein the amount of aggregate formation is significantly reduced. The invention further provides aerosols prepared by the methods of the invention, as well as compositions for use in the methods of the invention. The invention further relates to methods for the preparations of such compositions, to containers, kits and aerosol delivery systems comprising such compositions and to uses of the same.

First claim

The invention claimed is:

1. A method of preparing an aerosol of immunoglobulin single variable domains comprising atomizing in a vibrating-mesh nebulizer a composition comprising an aqueous carrier and a plurality of polypeptides comprising one or more immunoglobulin single variable domains, wherein less than 6% of the polypeptides form aggregates upon atomization, as determined by SE-HPLC, and wherein the polypeptides comprising one or more immunoglobulin single variable domains are present in the composition at a concentration of 50 mg/mL to 200 mg/mL.

2. A method of preparing a plurality of polypeptides comprising one or more immunoglobulin single variable domains for atomized delivery comprising:
concentrating the plurality of polypeptides to a concentration of 50 mg/mL to 200 mg/mL in an aqueous carrier to generate a concentrate; and
adding the concentrate to a vibrating-mesh nebulizer;
wherein less than 6% of the polypeptides of the concentrate form aggregates, as determined by SE-HPLC, when atomized in the vibrating-mesh nebulizer.

3. The method of claim 2 , wherein the concentrate comprises a surfactant at a concentration between 0.001% and 1%, or between 0.001% to about 0.1%, or about 0.01% to about 0.1%, or about 0.001%, about 0.005%, about 0.01%, about 0.02%, about 0.05%, about 0.08% or about 0.1%.

4. The method of claim 3 , wherein the surfactant is selected from polysorbates and poloxamers, or wherein polyethylene glycol (PEG) is added as a surfactant-like compound.

5. The method of claim 2 , wherein the polypeptide is concentrated to a concentration of 50 mg/mL to 200 mg/mL and wherein the concentrate does not comprise a surfactant.

6. The method of claim 1 , wherein the composition further comprises a surfactant at a concentration between 0.001% and 1%.

7. The method of claim 6 , wherein the surfactant comprises a polysorbate.

8. The method of claim 6 , wherein the surfactant comprises a poloxamer.

9. The method of claim 1 , wherein the composition further comprises polyethylene glycol (PEG).

10. The method of claim 1 , wherein the composition comprising the aqueous carrier and the plurality of polypeptides lacks a surfactant.

Assignees

• Ablynx Nv

Inventors

• Depla Erik
• Sergi Mauro
• Casteels Peter

Classifications

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title