Inhaled JAK Inhibitor Formulation for T2-Low COPD Response
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Solution Overview
Problem
There is a need for stable dry powder formulations of respiratory drugs that exhibit desirable bioavailability and physical properties for effective delivery to the lung, particularly for treating asthma, COPD, and inflammatory processes associated with eosinophilic or non-eosinophilic inflammation, and existing formulation techniques are unpredictable and complex.
Innovation Solution
Administering a JAK inhibitor, specifically (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridine-3-yl)-1H-imidazo[4,5-b]pyridine-3(2H)-yl)piperidin-1-yl)-3-oxopropanenitrile (Compound I) or its pharmaceutically acceptable salts, in a pharmaceutical formulation with excipients like lactose and magnesium stearate, optimized for inhalation via dry powder inhalers to treat asthma, COPD, and related disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If dry powder formulations are formulated with inhalation excipients such as lactose, then the drug can be administered via inhalation devices, but the formulation becomes complicated and unpredictable
Solution Approach 1:
The patent extracts the problematic excipient components (lactose and other inhalation excipients) from the formulation, delivering the JAK inhibitor as a pure compound or with minimal necessary excipients. This eliminates the formulation complexity associated with traditional dry powder inhalation while maintaining the inhalation administration route.
Solution Approach 2:
The patent changes the physical parameters of the drug delivery system by transitioning from conventional dry powder formulations requiring multiple excipients to alternative delivery forms (such as soft gel capsules, oral formulations, or simplified inhalation powders) that maintain efficacy while reducing formulation complexity.
2Ease of operation
If conventional dry powder formulations are used, then inhalation delivery is achieved, but bioavailability and physical properties become unpredictable
Solution Approach 1:
By removing lactose and other excipients that cause unpredictable physical properties and bioavailability variations, the patent achieves more consistent and predictable drug delivery. The JAK inhibitor is delivered in a purified state or with minimal necessary components, eliminating the variability introduced by conventional excipient formulations.
Solution Approach 2:
The patent optimizes physical parameters such as particle size, morphology, and crystallinity of the JAK inhibitor to ensure predictable bioavailability and consistent performance across different batches, replacing the unreliable excipient-dependent formulation approach.
3Reliability
If JAK inhibitors are administered to COPD patients, then anti-inflammatory effects are achieved, but differential response is observed between T2 low and T2 high patient populations
Solution Approach 1:
The patent applies the principle of local quality by tailoring the treatment approach to specific patient subpopulations. Clinical data shows that JAK inhibitors particularly benefit T2 low COPD patients (those with blood eosinophils <300 cells/μL), while T2 high patients may require different therapies. This enables precision medicine approaches where treatment is optimized for the specific inflammatory phenotype of each patient.
Data Source
AI summary
The present disclosure relates to methods of treatment of asthma, COPD, Asthma-COPD Overlap Syndrome (ACOS), and chronic bronchitis, or a combination thereof, with formulations comprising (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridin-3-yl)-1,2-dihydro-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)-3-oxopropanenitrile.