Trispecific Fusion Protein for Multi-Pathway Angiogenesis Blocking
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Solution Overview
Problem
Current treatments for neovascularization-related diseases face challenges such as drug accessibility, efficacy, and patient compliance, necessitating the development of new molecules that can effectively target and improve abnormal angiogenesis processes.
Innovation Solution
A trispecific fusion protein designed to simultaneously bind to VEGFA, VEGFC, and Ang2, utilizing VHH domains and ligand capture domains from VEGF receptors, with optional dimerization domains for enhanced stability and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple separate drugs are used to target VEGFA, VEGFC, and Ang2, then comprehensive coverage of angiogenesis pathways is achieved, but treatment complexity and patient burden increase
Solution Approach 1:
The patent combines three separate drug targets (VEGFA, VEGFC, and Ang2) into a single trispecific fusion protein molecule that simultaneously binds to all three targets. This merging approach maintains comprehensive coverage of angiogenesis pathways while simplifying the treatment regimen from multiple separate drugs to a single administration, directly resolving the contradiction between pathway coverage and treatment complexity
Solution Approach 2:
The trispecific fusion protein is designed with multiple specific binding domains that enable it to perform multiple functions simultaneously: binding to VEGFA, VEGFC, and Ang2. This multi-functionality allows a single molecule to address multiple angiogenesis-related mechanisms, reducing the need for multiple specialized drugs and thereby reducing patient burden and treatment complexity
2Reliability
If combination therapy with multiple drugs is used, then therapeutic efficacy is improved, but patient compliance and treatment burden increase
Solution Approach 1:
The invention merges the therapeutic activities against VEGFA, VEGFC, and Ang2 into a single fusion protein molecule, eliminating the need for patients to manage multiple separate medications. This maintains the comprehensive therapeutic efficacy of combination therapy while significantly improving patient compliance through simplified single-drug administration
3Ease of manufacture
If monospecific antibodies are used, then manufacturing simplicity is maintained, but coverage of multiple angiogenesis targets is insufficient
Solution Approach 1:
The patent merges multiple antigen-binding domains (for VEGFA, VEGFC, and Ang2) into a single fusion protein molecule. This approach maintains relative manufacturing simplicity using fusion protein technology while achieving comprehensive coverage of multiple angiogenesis targets, resolving the contradiction between manufacturing simplicity and target coverage
Solution Approach 2:
The trisspecific fusion protein is constructed as a composite molecular structure integrating different binding domains specific for VEGFA, VEGFC, and Ang2. This composite design enables simultaneous recognition and binding to multiple targets while maintaining a manageable manufacturing process through standardized fusion protein production techniques
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 trispecific fusion protein exhibits strong binding and blocking effects on its targets, effectively inhibiting neovascularization in animal models, reducing treatment frequency, and improving patient compliance.
Implementation Method 1
a VHH domain that binds to VEGFC
Implementation Method 2
a ligand capture domain that binds to a VEGFA
Implementation Method 3
an Ang2-binding domain that binds to Ang2
Data Source
Figure 1A
Figure 1B
Figure 2A~2C
AI summary
The present invention relates to a multi-specific fusion protein, and more particularly, to a trispecific fusion protein specifically binding to VEGFA, VEGFC and Ang2. The present invention further relates to a polynucleotide encoding the protein, an expression vector and a host cell, a pharmaceutical composition of same, and a method and a use for treating neovascularization-related diseases.