CD39/CD73 Bispecific Binding Protein for ATP-ADO Pathway Blockade

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Solution Overview

Problem

CD39 and CD73 proteins facilitate tumor immune escape by inhibiting the activation and function of tumor-specific T cells, promoting cancer cell growth, invasion, and angiogenesis, necessitating a targeted therapeutic approach to inhibit their enzymatic activity.

Innovation Solution

Development of a CD39/CD73 bispecific antigen-binding protein with high affinity and specificity, capable of binding to both CD39 and CD73, inhibiting their enzymatic activities, and inducing endocytosis of CD73, thereby blocking tumor-promoting pathways.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a bispecific antigen-binding protein is developed to bind both CD39 and CD73, then the capability to inhibit tumor immune escape is improved, but the device complexity increases

Engineering Contradiction:

Improvetumor immune escape inhibition capabilityVSAvoidprotein structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines two separate binding functions (anti-CD39 and anti-CD73) into a single bispecific antigen-binding protein molecule. This merging approach allows simultaneous inhibition of both CD39 and CD73-mediated immune escape pathways while maintaining a unified protein structure that can be produced and administered as a single therapeutic agent.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The bispecific antigen-binding protein is designed to perform multiple functions: binding to CD39, binding to CD73, and thereby inhibiting both enzymes' ability to suppress T cell function. This multi-functionality is achieved within a single protein molecule, allowing one therapeutic agent to address multiple mechanisms of tumor immune escape.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If high affinity binding to CD39 and CD73 is achieved, then the enzymatic activity inhibition is improved, but the manufacturing precision requirements increase

Engineering Contradiction:

Improveenzymatic activity inhibitionVSAvoidbinding affinity control

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent optimizes the binding affinity parameters of the bispecific protein by adjusting the variable regions and complementarity-determining regions (CDRs) of the antibody components. This allows control over the strength of interaction with CD39 and CD73, ensuring sufficient inhibition of enzymatic activity while maintaining feasibility for manufacturing and clinical use.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If the protein induces endocytosis of CD73, then the tumor-promoting pathway blocking is improved, but the stability requirements increase

Engineering Contradiction:

Improvetumor-promoting pathway blockingVSAvoidprotein thermal stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The bispecific antigen-binding protein is engineered with enhanced stability features, including optimized framework regions and appropriate disulfide bonding, to ensure the protein maintains its structural integrity and binding function under physiological conditions and during the endocytosis process. This prior stabilization ensures the protein can induce CD73 endocytosis without compromising its own compositional stability.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentUS20250361314A1CD39/CD73 bispecific antigen binding protein and use thereof

Publication Date: 2025.11.27 SHANGHAI HUAOTA BIOPHARMACEUTICAL CO LTD

AI summary

Provided is an isolated antigen-binding protein, which contains a first binding domain and a second binding domain, wherein the first binding domain is capable of binding to a CD39 protein, and the second binding domain is capable of binding to a CD73 protein. Also provided are a nucleic acid molecule encoding the isolated antigen-binding protein, a vector and a cell containing the nucleic acid molecule, a pharmaceutical composition containing the isolated antigen-binding protein, a method for preparing the isolated antigen-binding protein, and the use of the isolated antigen-binding protein.