GRP Inhibitors Mitigating Influenza Lung Damage

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Solution Overview

Problem

Current treatments for influenza infections are limited in effectiveness, particularly in reducing virally-induced lethality and lung inflammation, as they often require early administration and are hindered by viral mutation and resistance, necessitating alternative therapeutic strategies that modulate the host's innate immune response.

Innovation Solution

The use of GRP inhibitors and GRPR antagonists, such as monoclonal antibodies and small-molecule inhibitors, to target and reduce GRP activity in the lungs, thereby mitigating inflammatory responses and lung damage during influenza infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for influenza infections are used, then viral clearance may be achieved, but effectiveness is limited due to early administration requirement and viral mutation resistance

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidresistance to viral mutation
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent converts the harmful excessive inflammatory response caused by GRP into a beneficial target for therapy. By using GRP inhibitors and GRPR antagonists to block the harmful inflammatory cascade, the treatment transforms the pathogenic mechanism into a therapeutic target, achieving effectiveness against diverse influenza strains including mutated variants

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

2Object-affected harmful factors

If GRP inhibitors or GRPR antagonists are administered, then lung inflammation and lethality are reduced, but the mechanism involves modulating host immune response rather than direct antiviral action

Engineering Contradiction:
Improvelung inflammation and lethalityVSAvoidtherapeutic mechanism complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent uses GRP inhibitors and GRPR antagonists as intermediary agents that mediate between the host's immune response and the pathological outcome. These compounds do not directly kill the virus but intervene in the GRP-GRPR signaling pathway to prevent excessive inflammation, serving as a bridge that modulates the host response to protect against lung damage and lethality

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If conventional antiviral treatments are used, then direct viral inhibition is achieved, but treatment window is limited requiring early administration

Engineering Contradiction:
Improveviral clearance efficiencyVSAvoidtreatment administration window
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent employs GRP inhibitors and GRPR antagonists that can be administered as preliminary protective measures or early in the disease course to prevent the development of severe inflammation. By blocking the GRP-GRPR pathway before excessive inflammatory damage occurs, the treatment creates a protective effect that extends the effective treatment window beyond the narrow window required for conventional antivirals

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3849604B1Gastrin-releasing peptide (GRP) inhibitors or gastrin-releasing peptide receptor (GRPR) antagonists for use in treating an influenza virus infection
Publication Date: 2024.05.01 UNIV OF MARYLAND
  • EP3849604B1 patent drawingFigure 1a~2c
  • EP3849604B1 patent drawingFigure 3a~3e
  • EP3849604B1 patent drawingFigure 4a~4g

AI summary

Gastrin–releasing peptide (GRP) is a neuroendocrine peptide that acts as a novel contributor to the inflammatory response to influenza infection. Thus, inhibition of GRP or antagonizing the GRP receptor (GRPR) during influenza infection represents a novel therapeutic approach to mitigating lung damage. The present invention encompasses methods of treatment based on these novel findings and observations.