IL-10 Variant Molecules Modulating Immune Response

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Solution Overview

Problem

Current IL-10 treatments for inflammatory diseases and cancer are limited by their inability to effectively modulate immune responses due to issues with receptor binding affinity and inter-domain angles, leading to inconsistent therapeutic outcomes and potential exacerbation of inflammation.

Innovation Solution

Development of IL-10 variant molecules with modified receptor binding regions and inter-domain angles, including fusion proteins with extended half-life, to enhance affinity and specificity for the IL-10 receptor, allowing for targeted immune modulation in inflammatory diseases and cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional IL-10 treatments are administered, then immune suppression is achieved, but therapeutic efficacy is limited due to inconsistent receptor binding affinity and potential exacerbation of inflammation

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidreceptor binding affinity consistency

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by modifying specific amino acid residues in the IL-10 molecule (positions 31, 75, and 104) to alter receptor binding affinity. These point mutations change the molecular parameters of IL-10 to achieve more consistent and potent immune suppression while reducing inflammatory exacerbation, directly resolving the reliability issue of traditional IL-10 treatments

Inventive Principle:

Principle #35Parameter changes

2Productivity

If high doses of IL-10 are administered, then immune suppression is enhanced, but IFNγ is induced which worsens inflammatory disease

Engineering Contradiction:

Improveimmune suppression potencyVSAvoidIFNγ induction

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by making targeted modifications at specific locations (amino acid positions 31, 75, and 104) within the IL-10 molecule structure. These localized changes selectively enhance immune suppression capability while avoiding the harmful side effect of IFNγ induction that occurs with high-dose traditional IL-10, thus resolving the contradiction between potency and harmful effects

Inventive Principle:

Principle #3Local quality

3Ease of operation

If IL-10 treatment is administered after LPS exposure, then pro-inflammatory cytokine secretion is enhanced, but therapeutic benefit is lost

Engineering Contradiction:

Improvetreatment flexibilityVSAvoidtherapeutic benefit consistency

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-modifying the IL-10 molecule with specific amino acid mutations before administration. This preliminary structural modification ensures that the IL-10 variant is pre-configured to suppress inflammation effectively regardless of timing relative to LPS exposure, eliminating the need for precise timing and ensuring consistent therapeutic benefit even when administered after LPS exposure

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20240294591A1Il-10 variant molecules and methods for treating inflammatory disease and oncology

Publication Date: 2024.09.05 IOVANCE BIOTHERAPEUTICS INC

AI summary

The application relates to compositions or formulations comprising variant IL-10 molecules, fusion proteins, and chimeric proteins thereof useful for the treatment of cancer. inflammatory diseases or disorders, and autoimmune diseases or disorders.