IL-21 Binding Protein Agonist Enhances Immune Response

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Solution Overview

Problem

Current monoclonal antibodies targeting IL-21 primarily inhibit its function, whereas there is a need for an antibody that enhances IL-21 activity to modulate immune responses effectively in therapies for allergies, cancers, and infectious diseases.

Innovation Solution

Development of an IL-21-binding protein with a specific antigen binding domain that binds to IL-21, enhancing its activity by increasing proliferation of B cells, cytotoxicity of CD8+ T cells, and half-life, thereby acting as an IL-21 agonist.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monoclonal antibodies targeting IL-21 are used, then IL-21 function is inhibited, but the need for enhancing IL-21 activity to modulate immune responses effectively remains unmet

Engineering Contradiction:

ImproveIL-21 activity enhancementVSAvoidtherapeutic application range

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of inhibiting IL-21 function as conventional monoclonal antibodies do, this invention uses an IL-21 binding protein that enhances and amplifies IL-21 activity. The binding protein acts as a super-agonist, inverting the conventional approach of cytokine modulation from inhibition to enhancement, thereby enabling effective immune response modulation for therapeutic applications.

Inventive Principle:

Principle #13The other way round (Inversion)

2Productivity

If IL-21 activity is enhanced through binding proteins, then B cell proliferation and CD8+ T cell cytotoxicity increase, but the complexity of developing specific agonist binding proteins increases

Engineering Contradiction:

ImproveB cell proliferation rateVSAvoidprotein structure complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The IL-21 binding protein serves as an intermediary that mediates enhanced interaction between IL-21 and its receptor. Rather than directly modifying IL-21 or the receptor, the binding protein acts as a mediator that amplifies the natural binding affinity and biological activity, achieving enhanced B cell proliferation and T cell cytotoxicity through this intermediate facilitator.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Duration of action of stationary object

If IL-21 half-life is prolonged through binding proteins, then therapeutic duration is extended, but the manufacturing precision requirements for the binding protein increase

Engineering Contradiction:

ImproveIL-21 half-lifeVSAvoidbinding protein purity

Core Design Contradiction:

Duration of action of stationary objectVSManufacturing precision

Solution Approach 1:

The IL-21 binding protein is designed as a recombinant protein that copies and mimics the natural binding interface of IL-21 with its receptor. By creating a precise copy of the binding interaction through recombinant DNA technology, the binding protein can be manufactured with controlled precision while achieving prolonged IL-21 half-life through stable complex formation.

Inventive Principle:

Principle #26Copying

Data Source

PatentEP3013858B1Il-21 binding proteins and uses thereof

Publication Date: 2021.07.28 MONASH UNIV

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AI summary

The present disclosure provides proteins comprising antigen binding sites of antibodies that bind to interleukin-21 (IL-21) and uses thereof, e.g., in therapy.