DPP-I Inhibitor Dose Regimen for Neutrophilic Bronchiectasis

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Solution Overview

Problem

Current therapies for bronchiectasis fail to effectively ameliorate neutrophilic inflammation and tissue destruction mediated by uncontrolled neutrophil serine protease activity in the airways, leading to recurrent acute pulmonary exacerbations and irreversible airway damage, with no registered therapy addressing this issue independently of underlying aetiologies.

Innovation Solution

Administration of a dipeptidyl-peptidase I inhibitor, Compound (I), at a daily dose of 2.5 mg or 5 mg, to inhibit Cathepsin C, thereby reducing neutrophil extracellular trap formation and associated damage, and providing a therapeutic dosage regimen that prolongs the time to first pulmonary exacerbation, reduces exacerbation rates, improves lung function, and enhances quality of life.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used for bronchiectasis, then treatment is provided, but they fail to effectively ameliorate neutrophilic inflammation and tissue destruction mediated by uncontrolled neutrophil serine protease activity

Engineering Contradiction:

Improveefficacy in ameliorating neutrophilic inflammationVSAvoidtissue destruction mediated by neutrophil serine protease activity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and inhibits the specific harmful component (neutrophil serine proteases) from the inflammatory process by using DPP-I inhibitors that selectively target and block these enzymes, thereby removing the destructive element while preserving other aspects of the immune response

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the biochemical parameter of neutrophil serine protease activity by introducing DPP-I inhibitors that alter the enzymatic function, converting the harmful high protease activity state into a controlled low activity state, thereby reducing tissue destruction

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If no registered therapy addresses neutrophilic inflammation independently of underlying aetiologies, then treatment options are limited, but developing aetiologies-specific treatments would require multiple separate therapies

Engineering Contradiction:

Improveapplicability across different aetiologiesVSAvoidnumber of separate therapies required

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent creates a universal therapy by developing DPP-I inhibitors that target the common pathogenic mechanism (neutrophilic inflammation mediated by serine proteases) present across different bronchiectasis aetiologies, making the treatment applicable to all patients regardless of underlying cause

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If high doses of DPP-I inhibitors are administered, then enzyme inhibition is enhanced, but safety and tolerability may be compromised

Engineering Contradiction:

Improveefficacy in prolonging time to first pulmonary exacerbationVSAvoidsafety and tolerability profile

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies partial action by administering doses (2.5-5mg daily) that are sufficient to achieve therapeutic inhibition of neutrophil serine proteases and prolong time to first pulmonary exacerbation, without exceeding the threshold that would cause adverse safety or tolerability effects

Inventive Principle:

Principle #16Partial or excessive action

Data Source

PatentUS20260060930A1New crystalline Forms, new pharmaceutical Composition and Dose Regimen of a Dipeptidyl peptidase I inhibitor for the Treatment of Patients with Bronchiectasis or other DPP-I mediated Diseases

Publication Date: 2026.03.05 BOEHRINGER INGELHEIM INT GMBH

AI summary

The present invention relates to the dipeptidyl-peptidase I (DPPI or Cathepsin C) inhibitor of formula (I), which is useful in the prevention and/or treatment of bronchiectasis with certain underlying aetiologies, in the prevention and/or treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis or hidradenitis suppurativa using therapeutically efficacious dosages and to polymorphs of Compound (I) as well as to pharmaceutical compositions comprising Compound (I) and its polymorphs.