Method for modulating the pharmacokinetics of inhaled biopharmaceuticals
Fig.1. Content of proteins conjugated to a 40 kDa PEG chain and unconjugated proteins in the lung following delivery to the respiratory tract in mice. A, a Fab’ antibody fragment; B, dornase alfa. Mean values (± SEM) of 3 to 7 mice per time point.
Fig.2. Assessment of airway inflammation in a murine model of house dust mite-induced lung inflammation following delivery of anti-IL-17A antibody constructs to the respiratory tract. For comparison, the full-length anti-IL-17A was also delivered IV at a 10-times higher dose. Mean values (± SEM) of 8 mice..
Medical / Therapeutic proteins for respiratory diseases
Inhalation aerosols offer a targeted therapy for respiratory diseases. However, the therapeutic efficacy of inhaled biopharmaceuticals is limited by the rapid clearance of the macromolecules in the lungs. Fast elimination of biopharmaceuticals results in high unit doses and high administration frequency, which jeopardizes compliance and outcome of the therapy. Inhaled biopharmaceuticals would therefore benefit from a method that sustains protein availability within the pulmonary tissue.
The UCL invention
UCL researchers have demonstrated that the covalent coupling of a large polyethylene glycol (PEG) chain to proteins greatly increases their residence time within the lungs following delivery to the respiratory tract (Fig. 1). As a result, the therapeutic efficacy of the proteins is enhanced in respiratory diseases (Fig. 2).
This work is the subject of a patent application: WO2015107176.
Koussoroplis et al., J. Control. Rel. 187: 91-100, 2014
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