PDE4 Modulators for Influenza Immune Response

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Solution Overview

Problem

Current treatments for influenza infections are limited in effectiveness due to viral mutation, antigenic drift, and resistance to antiviral drugs, leading to high morbidity and mortality, especially in vulnerable populations such as the elderly and immunocompromised individuals.

Innovation Solution

Administration of PDE4 modulators or immunomodulatory compounds, either alone or in combination with anti-viral agents, to modulate immune responses and reduce inflammation associated with influenza infections, thereby ameliorating symptoms and potentially delaying disease progression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antiviral drugs are used to treat influenza infection, then viral replication is inhibited, but viral resistance and antigenic drift reduce treatment effectiveness over time

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidviral adaptability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces immunomodulatory compounds as intermediary substances that do not directly target the virus but rather modulate the host's immune response. These compounds act as mediators between the virus and the host immune system, enhancing the effectiveness of the immune response without directly interfering with viral replication mechanisms, thereby avoiding the selection pressure that leads to viral resistance.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the therapeutic parameter from direct antiviral action to immunomodulatory action. By altering the mechanism of action from viral targeting to immune system modulation, the treatment approach becomes less susceptible to viral resistance and antigenic drift, as the immune system's dynamic response adapts to viral variations.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If the immune response is strongly activated to clear the virus, then viral infection is controlled, but excessive inflammation causes severe symptoms and tissue damage

Engineering Contradiction:
Improveviral clearanceVSAvoidinflammation-related damage
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies partial action by using immunomodulatory compounds that selectively enhance specific aspects of the immune response without fully activating all immune pathways. This partial modulation allows for controlled viral clearance while preventing excessive inflammation, avoiding the harmful effects of over-aggressive immune activation.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The immunomodulatory compounds introduce a feedback mechanism that monitors and regulates the immune response. By modulating cytokine production and immune cell activity, these compounds create a self-regulating system that adapts the immune response to the viral load, ensuring adequate viral clearance while preventing excessive inflammation and tissue damage.

Inventive Principle:
Principle #23Feedback

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 use of PDE4 modulators and immunomodulatory compounds helps in reducing inflammation and modulating immune responses, providing a therapeutic benefit in treating, preventing, or delaying the onset of influenza symptoms, particularly in high-risk populations.

Implementation Method 1

PDE4 modulators potently inhibit TNF-α and IL-12 production

Methodology Applied
Scientific EffectPhosphodiesterase inhibition: Enzyme

Implementation Method 2

Inhibition of PDE4 activity results in increased cAMP levels leading to the modulation of LPS induced cytokines

Methodology Applied
Scientific EffectcAMP accumulation:

Implementation Method 3

PDE4 modulators potently inhibit TNF-α and IL-12 production

Methodology Applied
Scientific EffectCytokine inhibition: Enzyme

Implementation Method 4

administering an immunomodulatory compound, or a pharmaceutically acceptable salt, solvate, hydrate, and/or stereoisomer thereof

Methodology Applied
Scientific EffectImmune modulation:

Data Source

PatentEP2555769B1Methods for treating respiratory viral infection
Publication Date: 2022.01.12 AMGEN (EURO) GMBH
  • EP2555769B1 patent drawingFigure 1
  • EP2555769B1 patent drawingFigure 2
  • EP2555769B1 patent drawingFigure 3A~3D

AI summary

Provided herein are methods for modulating immune responses to a respiratory viral infection (e.g., influenza, rhinovirus, coronavirus, or paramyxovirus) in a subject, wherein the methods comprise administering to the subject a compound (e.g., a PDE4 modulator or an immunomodulatory compound), or a pharmaceutically acceptable salt, solvate, hydrate, or stereoisomer thereof. Also provided herein are methods for treating, preventing, ameliorating, and/or delaying the onset of one or more symptoms associated with or resulting from a respiratory viral infection (e.g., influenza, rhinovirus, coronavirus, or paramyxovirus) in a subject, wherein the methods comprise administering to the subject a compound (e.g., a PDE4 modulator or an immunomodulatory compound), or a pharmaceutically acceptable salt, solvate, hydrate, or stereoisomer thereof.