Methods and compositions for the preparation of aerosols

Patent metadata

Field	Value
Publication number	US-11007146-B2
Application number	US-201715495199-A
Country	US
Kind code	B2
Filing date	Apr 24, 2017
Priority date	Feb 11, 2010
Publication date	May 18, 2021
Grant date	May 18, 2021

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 for reducing the percentage of aggregate formation in atomized material of immunoglobulin single variable domains comprising atomizing in a vibrating-mesh nebulizer a first composition comprising an aqueous carrier and a polypeptide comprising one or more immunoglobulin single variable domains, wherein:
the concentration of the polypeptide comprising one or more immunoglobulin single variable domains present in the first composition is 50 mg/mL or more, wherein the aqueous carrier comprises saline (NaCl 0.9%), histidine, or phosphate buffered saline; and
the percentage of aggregate formation in the atomized material, as determined by SE-HPLC, is reduced compared to: (a) the percentage of aggregate formation in atomized material obtained from atomizing in a vibrating-mesh nebulizer a second composition comprising an aqueous carrier and the polypeptide comprising one or more immunoglobulin single variable domains at a concentration of 5 mg/mL; or (b) the percentage of aggregate formation in atomized material obtained from atomizing in a jet nebulizer a third composition comprising an aqueous carrier and the polypeptide comprising one or more immunoglobulin single variable domains.

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

3. The method of claim 2 , wherein the surfactant is selected from polysorbates and poloxamers, or wherein PEG is added as a surfactant-like compound.

4. The method of claim 1 , wherein the polypeptide comprising one or more immunoglobulin single variable domains is present in the first composition at a concentration of 50 mg/mL to 200 mg/mL and wherein the first composition does not comprise 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

• A61K9/0078 Primary

  for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions · 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

• A61P31/14

  for RNA viruses · CPC title

• A61K47/10

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