VCAM-1 Binding Antibodies for Native State Detection
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Solution Overview
Problem
Current antibodies for targeting human VCAM-1 are not suitable for diagnosing and treating diseases associated with VCAM-1 upregulation, such as multiple sclerosis and tumour metastasis, as they fail to specifically bind to VCAM-1 in its native state on endothelial cells.
Innovation Solution
Development of monoclonal antibodies or their fragments that specifically bind to the extracellular domain of human VCAM-1 in its native state, with enhanced binding affinity and specificity, allowing for effective diagnosis and potential therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If currently available antibodies are used, then they can be obtained for VCAM-1 targeting, but they fail to specifically bind to VCAM-1 in its native state on endothelial cells
Solution Approach 1:
The patent applies parameter changes by modifying antibody structure and composition to achieve specific binding to native VCAM-1. The inventors developed antibodies with optimized variable regions and CDR sequences that recognize the native conformation of VCAM-1 on endothelial cells, changing the binding parameters from non-specific to highly specific for the native state.
Solution Approach 2:
The patent uses copying by creating antibodies that replicate the ability to bind native VCAM-1 through structural mimicry. The antibody designs include framework regions and CDRs that copy the binding characteristics needed to recognize VCAM-1 in its native endothelial state, effectively copying the desired binding behavior from ideal binding scenarios.
2Measurement precision
If antibodies are developed to bind VCAM-1 extracellular domain, then diagnostic capability is improved, but antibody complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into functional modules: variable regions for specific VCAM-1 binding, framework regions for structural stability, and constant regions for effector functions. This segmentation allows optimization of each region independently to achieve high diagnostic accuracy while managing overall complexity through modular design.
Solution Approach 2:
The patent implements universality by designing antibodies that perform multiple functions: specific binding to VCAM-1 extracellular domain, diagnostic detection capability, and potential therapeutic activity. The antibodies are engineered to universally recognize VCAM-1 across different contexts while maintaining the ability to fulfill multiple roles in disease diagnosis and treatment.
Data Source
AI summary
The invention provides an antibody or fragment thereof that specifically binds to human endothelial vascular cell adhesion molecule-1 (VCAM-1), wherein the antibody or fragment thereof binds to the extracellular domain of VCAM-1, and wherein the antibody or fragment thereof binds to VCAM-1 when expressed on endothelial cells, wherein the antibody or fragment thereof is a human or humanized antibody, or fragment thereof.