ISM1 Polypeptides Targeting GRP78 for Lung Inflammation Resolution

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Solution Overview

Problem

Current treatments for lung inflammation, particularly chronic obstructive pulmonary disease (COPD) and acute lung injuries like acute respiratory distress syndrome (ARDS), fail to effectively address underlying tissue damage and inflammation, leading to progressive lung function decline and high mortality rates.

Innovation Solution

Development of Isthmin 1 (ISM1)-based polypeptides and nucleic acids that inhibit and resolve lung inflammation by inducing alveolar macrophage apoptosis, formulated for administration via inhalation or nebulization, targeting GRP78 to modulate inflammation and prevent hyper-proliferation of alveolar cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional pharmacological interventions are used for lung inflammation, then symptomatic relief is provided, but underlying tissue damage and inflammation are not effectively targeted, leading to progressive lung function decline

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidlung function preservation

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent uses Isthmin 1 as an intermediary substance that specifically targets and binds to GRP78 on the surface of alveolar macrophages, triggering apoptosis of these pro-inflammatory cells. This mediator approach directly addresses the underlying inflammation rather than just providing symptomatic relief, thereby improving both treatment effectiveness and lung function preservation

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the fundamental parameter of inflammatory cell population by inducing apoptosis in alveolar macrophages through ISM1-GRP78 interaction. This parameter change (reducing pro-inflammatory cell count) directly tackles the root cause of lung inflammation and tissue damage, overcoming the limitations of traditional symptomatic treatments

Inventive Principle:

Principle #35Parameter changes

2Reliability

If acute inflammation is unrestrained in amplitude or duration, then protective immune response is amplified, but lung diseases characterized by excess or chronic inflammation occur including COPD and asthma

Engineering Contradiction:

Improveprotective immune responseVSAvoidchronic inflammation and tissue damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by selectively eliminating pro-inflammatory alveolar macrophages through apoptosis induction before they can cause chronic inflammation and tissue damage. By targeting GRP78-expressing macrophages with ISM1, the treatment prevents the transition from acute protective inflammation to chronic harmful inflammation, thereby maintaining reliable immune protection while preventing disease

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the harmful presence of pro-inflammatory alveolar macrophages into a benefit by selectively inducing their apoptosis through GRP78 targeting. The very cells that cause chronic inflammation and tissue damage are targeted and eliminated, transforming the inflammatory response from harmful to beneficial by removing the pathological component while preserving protective immunity

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The ISM1-based treatments effectively reduce lung inflammation, prevent chronic inflammation, and ameliorate conditions such as COPD, emphysema, and acute lung injuries by promoting apoptosis in pro-inflammatory cells and maintaining lung homeostasis.

Implementation Method 1

ISM1 may help to resolve inflammation by inducing alveolar macrophage apoptosis

Methodology Applied

Scientific EffectApoptosis:

Data Source

PatentUS12576132B2Isthmin 1 for treatment of lung inflammation

Publication Date: 2026.03.17 NATIONAL UNIVERSITY OF SINGAPORE

AI summary

Provided herein are polypeptides including an amino acid sequence having at least 70% sequence identity with an Isthmin 1 (ISM1) protein or a GRP78-activating fragment thereof, as well as expressible nucleic acids encoding said polypeptides. Uses of such agents, as well as methods for inducing apoptosis in alveolar macrophages and/or for treating, ameliorating, or preventing inflammation or lung disease such as chronic obstructive pulmonary disease (COPD), emphysema, asthma, acute lung injury (ALI), lung fibrosis, and/or acute respiratory distress syndrome.