Nebultzation of immunoglobulin
Inventors
Vonarburg, Cédric Pierre • STEINFUEHRER, Karin • Baumann, Ulrich
Assignees
CSL Behring AG • Medizinische Hochschule Hannover • PARI Pharma GmbH
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Publication Number
US-11471617-B2
Publication Date
2022-10-18
Expiration Date
Abstract
The invention relates to methods for generating an aerosol by nebulization of a composition comprising polyclonal immunoglobulin (Ig). The selection of an efficient membrane nebulizer and a composition optimized for nebulization with such membrane nebulizer results in a particularly efficient method of generating an aerosol for administration of Ig to the respiratory tract.
Core Innovation
The invention relates to generating an aerosol by nebulizing a liquid aqueous composition comprising a polyclonal immunoglobulin (Ig) using a membrane nebulizer. The polyclonal Ig is a polyclonal immunoglobulin G (IgG), a polyclonal immunoglobulin A (IgA), and/or a polyclonal immunoglobulin M (IgM), and has an Ig concentration in a range of 40 to 200 mg per mL. Prior to nebulization, the liquid aqueous composition has a viscosity of from 1 to 17 mPa·s.
The invention further centers on using a membrane nebulizer having a reservoir filled with the liquid aqueous composition to obtain the aerosol by nebulizing under defined composition parameters. In described implementations, the device arrangement can include an isolated reservoir and pressure decrease prior to or during nebulization, and the membrane nebulizer can include a vibratable membrane with a plurality of holes forming aerosol upon vibrating. The aerosol generation is characterized using targets related to aerosol particle-size and dose characteristics.
Supporting content in the provided material indicates that nebulization preserves immunoglobulin structure and function, including Fc function, complement activation, and antigen binding, as assessed by analytical methods such as SDS-PAGE, SEC, DLS, and biological/assay readouts. The provided material also describes aerosol deposition and persistence after pulmonary administration in animals. The described use cases include therapeutic and preventive administration for chronic sinusitis and chronic respiratory infections associated with immunodeficiency.
Claims Coverage
Independent claim clm-00001 covers aerosol generation by nebulizing a high-concentration polyclonal immunoglobulin aqueous composition with a membrane nebulizer, constrained by pre-nebulization viscosity and Ig concentration (two primary quantitative composition features).
High-concentration aqueous polyclonal immunoglobulin composition with defined viscosity
Providing a liquid aqueous composition comprising a polyclonal immunoglobulin (Ig), wherein the Ig is a polyclonal immunoglobulin G (IgG), a polyclonal immunoglobulin A (IgA), and/or a polyclonal immunoglobulin M (IgM), wherein the Ig has a concentration in a range of 40 to 200 mg per mL, and wherein prior to nebulization the liquid aqueous composition has a viscosity of from 1 to 17 mPa·s.
Membrane nebulizer reservoir filled with the aqueous immunoglobulin composition
Providing a membrane nebulizer having a reservoir into which the liquid aqueous composition is filled.
Nebulizing to obtain aerosol of the polyclonal immunoglobulin composition
Nebulizing the liquid aqueous composition using the membrane nebulizer to obtain the aerosol.
Overall, the claim coverage is directed to generating an aerosol by nebulizing a liquid aqueous composition containing polyclonal IgG, IgA, and/or IgM at an Ig concentration of 40 to 200 mg per mL with a membrane nebulizer, where the viscosity of the composition prior to nebulization is 1 to 17 mPa·s.
Stated Advantages
Preserves immunoglobulin structure and activity after nebulization, including Fc function, complement activation, and antigen binding.
Achieves pulmonary deposition and persistence after aerosol administration in animals.
Enables high delivered/respirable dose with low residual volume (as described in the provided material).
Documented Applications
Therapeutic and preventive use for chronic sinusitis.
Therapeutic and preventive use for chronic respiratory infections in immunodeficiency (including primary immunodeficiency (PID)).
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