KLRG1 Binding Agents for ILC2-Mediated Type-2 Inflammation

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Solution Overview

Problem

The role of killer cell lectin-like receptor G1 (KLRG1) in modulating the behavior and function of group 2 innate lymphoid cells (ILC2s) is largely undefined, particularly in the context of type-2 inflammation and associated diseases such as allergic disorders, where current treatments are inadequate.

Innovation Solution

Administering a KLRG1 binding agent or antagonist, such as an antibody or RNAi agent, to target KLRG1 and disrupt its signaling, thereby reducing the accumulation of ILC2 cells and cytokine production in the lung, and alleviating eosinophilia and pathology associated with type-2 inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If KLRG1 is expressed on ILC2 cells, then ILC2 cell function is regulated, but the role of KLRG1 in modulating ILC2 behavior and function remains undefined

Engineering Contradiction:

ImproveILC2 cell function regulationVSAvoidundefined role of KLRG1

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent uses anti-KLRG1 antibodies as intermediary agents to block the interaction between KLRG1 and its ligands (cadherins) on ILC2 cells. This intermediary approach allows researchers to observe the specific effects of KLRG1 inhibition, thereby defining its previously unknown role in ILC2-mediated type-2 inflammation and allergic diseases

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If current treatments are used for allergic disorders, then existing therapeutic options are available, but treatments are inadequate for ILC2-mediated diseases

Engineering Contradiction:

Improveexisting therapeutic optionsVSAvoidtreatment adequacy

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent introduces a novel therapeutic parameter by targeting the KLRG1 receptor on ILC2 cells, which is distinct from conventional allergy treatments that typically target IgE, mast cells, or Th2 cells. This new parameter (KLRG1 inhibition) provides an adapted therapeutic mechanism specifically suited for ILC2-mediated type-2 inflammation, overcoming the inadequacy of existing treatments

Inventive Principle:

Principle #35Parameter changes

3Reliability

If KLRG1 binding agents are administered, then ILC2 accumulation and cytokine production are reduced, but the mechanism of action needs to be defined

Engineering Contradiction:

Improvetherapeutic effectVSAvoidundefined mechanism

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent extracts and isolates the specific mechanism by which KLRG1 binding agents exert their therapeutic effect: by blocking KLRG1-ligand interactions on ILC2 cells, the agents prevent ILC2 accumulation and cytokine production. This extraction of mechanism from the complex immune response clarifies the previously undefined action of KLRG1 in ILC2-mediated pathology

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS20230331853A1Methods and compositions for treating respiratory diseases or conditions related to innate lymphoid cells

Publication Date: 2023.10.19 NAT JEWISH HEALTH

AI summary

Disclosed herein are methods and compositions for treating Group 2 innate lymphoid cell (ILC2) mediated diseases or conditions comprising administering a killer cell lectin-like receptor G1 (KLRG1) binding agent or KLRG1 ligand binding agent or antagonist thereof.