FcRn-IgG Interaction Modulation for IL-12 Regulation

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Solution Overview

Problem

Current therapies lack effective methods to modulate IL-12 production for treating cancer, infectious diseases, and autoimmune disorders, as existing approaches do not adequately leverage the interactions between IgG and FcRn to regulate immune responses.

Innovation Solution

Compositions and methods that increase or decrease IL-12 production by altering the interactions between IgG and FcRn, using variants of IgG or fragments thereof, and agents such as antibodies, peptides, or siRNA to modulate signaling, thereby enhancing or inhibiting immune responses against specific antigens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If FcRn/IgG interactions are enhanced to increase IL-12 production, then anti-tumor and anti-infectious immunity is improved, but autoimmune disease risk increases

Engineering Contradiction:
Improveanti-tumor immunityVSAvoidautoimmune disease risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by directing IL-12 production to specific tissues and cell types (dendritic cells in lymph nodes and tissues) rather than systemic production. This is achieved through targeted FcRn/IgG interactions at specific anatomical locations, allowing enhanced anti-tumor immunity locally while limiting systemic autoimmune responses.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses FcRn as an intermediary molecule to mediate the interaction between IgG and immune cells. By targeting FcRn specifically, the therapy indirectly regulates IL-12 production through this intermediary, allowing for more controlled and selective immune modulation that can distinguish between anti-tumor and autoimmune pathways.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If FcRn/IgG interactions are inhibited to decrease IL-12 production, then autoimmune diseases are treated, but anti-tumor and anti-infectious immunity is reduced

Engineering Contradiction:
Improveautoimmune disease symptomsVSAvoidanti-infectious immunity
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies partial action by using antibodies that partially inhibit FcRn/IgG interactions rather than complete blockade. This partial inhibition is sufficient to reduce pathogenic IL-12 in autoimmune diseases while preserving enough FcRn function to maintain essential anti-infectious and anti-tumor immunity.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent employs dynamic regulation where the degree of FcRn inhibition can be modulated based on disease state. The therapeutic effect is not static but can be adjusted through antibody dosage and timing to achieve the optimal balance between treating autoimmune disease and maintaining protective immunity.

Inventive Principle:
Principle #15Dynamics

3Productivity

If IL-12 production is increased through FcRn modulation, then cancer and infectious diseases are treated, but immune system complexity and potential side effects increase

Engineering Contradiction:
ImproveIL-12 productionVSAvoidimmune response regulation
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts and targets the specific FcRn/IgG interaction pathway that regulates IL-12 production, separating this specific regulatory mechanism from the broader immune system. By focusing on this single extracted pathway, the therapy can increase IL-12 production for cancer and infectious disease treatment without proportionally increasing overall immune system complexity and side effects.

Inventive Principle:
Principle #2Taking out (Extraction)

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 approach effectively increases IL-12 production for anti-tumor and anti-infectious immunity or decreases it to treat autoimmune diseases, providing a targeted therapeutic strategy for immune regulation.

Implementation Method 1

FcRn ligation with IgG containing immune complexes (IgG IC) is directly involved in the production of IL-12

Methodology Applied
Scientific EffectFcRn-IgG binding interaction:

Data Source

PatentEP3663763B1Compositions and methods for modulating an immune response
Publication Date: 2022.02.16 THE BRIGHAM & WOMEN S HOSPITAL INC
  • EP3663763B1 patent drawingFigure 1A~1G
  • EP3663763B1 patent drawingFigure 2A~2D
  • EP3663763B1 patent drawingFigure 3A~3G

AI summary

Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.