Anti-TEM1 Antibody Dimers via Hinge Disulfide Bonds
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Solution Overview
Problem
There is a need for antibodies and antigen-binding fragments with high stability in serum and high affinity for the endosialin tumor endothelial marker 1 (TEM1) to effectively target and treat cancer, as existing antibodies may not persist long enough in the serum to consistently bind to TEM1-expressing tumor vasculature.
Innovation Solution
Development of anti-TEM1 antibody dimers or antigen-binding fragment dimers linked with a hinge, which provides increased stability and affinity by forming disulfide bonds, allowing for effective targeting of TEM1-expressing cells and tumors, and can be conjugated with agents like radioisotopes for therapeutic or diagnostic purposes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If monovalent anti-TEM1 antibodies or antigen-binding fragments are used, then the antibody structure is simple and easy to produce, but the stability in serum and affinity for TEM1 are insufficient
Solution Approach 1:
The patent combines multiple monovalent anti-TEM1 antibody fragments into a dimeric structure through hinge regions, creating multivalent antibodies that simultaneously maintain production simplicity and enhance serum stability and target affinity through the synergistic effect of multiple binding sites
Solution Approach 2:
The patent creates composite antibody structures by combining antigen-binding fragments with hinge regions to form dimeric molecules, integrating the advantages of both simple fragment structures and the enhanced stability provided by the hinge region
2Ease of operation
If existing anti-TEM1 antibodies are used, then the treatment approach is straightforward, but the antibodies cannot persist long enough in the serum to consistently bind to TEM1-expressing tumor vasculature
Solution Approach 1:
The patent combines multiple antibody fragments into dimeric structures with hinge regions, creating molecules that persist longer in serum while maintaining straightforward administration protocols
3Reliability
If dimerized anti-TEM1 antibodies are developed, then stability in serum and affinity for TEM1 are improved, but the antibody structure becomes more complex
Solution Approach 1:
The patent segments the antibody structure into modular components (antigen-binding fragments and hinge regions) that can be systematically assembled into dimeric configurations, making the complexity manageable and production scalable
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 dimerized antibodies or antigen-binding fragments exhibit enhanced stability in human serum and increased avidity to TEM1, enabling effective targeting and treatment of tumors, including delayed tumor progression and imaging capabilities.
Implementation Method 1
antibody dimers or anti-TEM1 antigen-binding fragment dimers, the antibodies or antigen binding fragments comprising: a dimer of an anti-TEM1 antibody or antigen-binding fragment linked to a hinge, wherein said antibody or antigen-binding fragment is dimerized using said hinge
Data Source
AI summary
The invention relates to variants of an antibody or antigen-binding fragment that binds specifically to an endosialin tumor endothelial marker 1 (TEM1), and prophylactic, diagnostic, and therapeutic methods using the same.