Anti-OX40 Antibody CDR Engineering for Human Immune Modulation
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Solution Overview
Problem
Current anti-OX40 antibodies lack clear efficacy for treating human diseases, despite their potential in tumor immunotherapy, autoimmune diseases, and inflammation.
Innovation Solution
Development of an anti-OX40 antibody or antigen-binding fragment with specific CDR sequences, including HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, designed to target human OX40 with high affinity and specificity, which can be used as agonists or antagonists to modulate immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-OX40 antibodies are used, then T-cell activation can be modulated, but clear therapeutic efficacy for treating human diseases has not been achieved
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's binding affinity parameters through specific amino acid sequence modifications in the variable regions. The heavy chain variable region sequences (SEQ ID NOs: 1-5) and light chain variable region sequences (SEQ ID NOs: 6-10) are designed to achieve optimal binding characteristics to human OX40, thereby improving therapeutic efficacy while maintaining adaptability to different disease states.
2Power
If OX40 agonist antibodies are used to activate T cells, then tumor immunotherapy effectiveness increases, but cross-linking requirements complicate the mechanism
Solution Approach 1:
The antibody performs self-service by incorporating FcγR binding capability directly into its Fc region, enabling it to cross-link and activate OX40 molecules without requiring external assistance from Fc receptors on cell surfaces. This intrinsic cross-linking ability simplifies the activation mechanism while maintaining strong T-cell activating power.
Solution Approach 2:
The Fc region of the antibody serves as an intermediary that binds to FcγR on target cells, facilitating the transfer of activation signals. This intermediary mechanism enables efficient T-cell activation while distributing the cross-linking function across multiple binding sites, reducing mechanistic complexity.
3Object-affected harmful factors
If OX40 antagonist antibodies are used to block T-cell activation, then inflammatory responses are reduced, but specificity for different disease states must be maintained
Solution Approach 1:
The patent applies local quality by designing variable regions with specific amino acid sequences that confer different binding characteristics to different OX40 conformations or isoforms. The heavy chain variable region sequences (SEQ ID NOs: 1-5) and light chain variable region sequences (SEQ ID NOs: 6-10) are optimized to selectively bind to OX40 in specific disease contexts, enabling precise modulation of inflammatory responses while maintaining disease state specificity.
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 anti-OX40 antibody effectively enhances or inhibits immune reactions, providing therapeutic benefits in treating cancers, inflammation, and autoimmune diseases, and offers diagnostic capabilities for OX40-related conditions.
Implementation Method 1
The anti-OX40 antibody or antigen-binding fragment binds with high affinity to human OX40
Implementation Method 2
OX40L-OX40 signal can stimulate helper T cells to produce and secrete cytokines, stimulate effector T cells to release granzyme and perforin
Data Source
AI summary
Provided are an anti-OX40 antibody or antigen-binding fragment thereof, a preparation method thereof and the use for treating OX40-related diseases or conditions.