IL-2 TGF-beta Fusion Polypeptide Reduces Toxicity

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Solution Overview

Problem

Existing therapies using high doses of IL-2 for immune activation are associated with toxicity, limiting their effectiveness in treating pathogenic infections.

Innovation Solution

Development of fusion proteins comprising an interleukin polypeptide (such as IL-2 or IL-15) fused with two or more polypeptides that inhibit TGFβ activity, specifically designed to activate immune responses and inhibit immunosuppressive signaling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high doses of IL-2 are administered to activate immune response, then immune activation is improved, but toxicity increases

Engineering Contradiction:

Improveimmune activation efficacyVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines IL-2 with TGF-β receptor polypeptides to create a fusion protein that simultaneously activates immune cells and inhibits immunosuppressive TGF-β signaling. This merging of two functional components into a single therapeutic molecule allows the immune activation benefits of IL-2 to be achieved while the toxicities are mitigated by the concurrent TGF-β inhibition, directly resolving the contradiction between immune activation efficacy and toxicity

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The fusion protein serves multiple functions simultaneously: it acts as an immune activator through IL-2 binding to IL-2 receptors, and as an immunosuppressor inhibitor through TGF-β receptor binding. This multi-functionality allows a single molecule to address both the need for strong immune response and the need to reduce toxicity from excessive immune activation, transforming the therapeutic approach from single-function to multi-functional

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If high doses of IL-2 are administered to treat pathogenic infections, then infection treatment efficacy is improved, but toxicity increases

Engineering Contradiction:

Improveinfection treatment efficacyVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The fusion protein merges IL-2's infection-fighting capabilities with TGF-β receptor inhibition to create a therapeutic that treats infections more effectively while reducing the toxicities associated with high-dose IL-2 alone. The TGF-β inhibition component specifically counteracts the immunosuppressive effects that cause toxicity, allowing lower effective doses of the active immune stimulation component

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent converts the harmful immunosuppressive effects of TGF-β (which cause toxicity when IL-2 is over-administered) into a beneficial component of the therapy. By incorporating TGF-β receptor binding capability into the fusion protein, the previously harmful immunosuppressive pathway is harnessed to counteract excessive immune activation and its associated toxicities, turning a negative factor into a protective mechanism

Inventive Principle:

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

Data Source

PatentUS12329803B2Method of reducing or treating fibrosis by administering an interleukin-2/TGF-beta receptor fusion polypeptide

Publication Date: 2025.06.17 CURA THERAPEUTICS INC

AI summary

Provided are multi-functional and multi-valent fusion polypeptides comprising an interleukin polypeptide and two or more TGFβ ligand-binding polypeptides. The compositions and methods provided herein are useful in the application of treating and/or preventing pathogenic infections.