Anti-OX40 Antibody CDR Mutations for T Cell Activation
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Solution Overview
Problem
Current anti-OX40 antibodies do not effectively block the binding of OX40 to OX40L, limiting their ability to enhance anti-tumor immunity and treat cancer and immune-related diseases.
Innovation Solution
Development of an antibody or antibody fragment that binds to human OX40 with enhanced affinity while minimizing interference with the OX40-OX40L interaction, thereby activating T cells and promoting antitumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-OX40 antibodies are used to block OX40 binding, then T cell activation is attempted, but the binding of OX40 to OX40L is effectively blocked, limiting anti-tumor immunity enhancement
Solution Approach 1:
The patent changes the binding affinity parameter of the anti-OX40 antibody by introducing specific amino acid mutations in the complementarity determining regions (CDRs). The antibody achieves high affinity binding to OX40 while maintaining compatibility with OX40L binding, thereby resolving the contradiction between effective OX40 blocking and preservation of OX40-OX40L interaction for anti-tumor immunity enhancement
Solution Approach 2:
The patent applies local quality by making specific modifications only in the CDR regions of the antibody while maintaining the constant regions unchanged. This localized modification allows the antibody to achieve specific binding characteristics that enable T cell activation without completely blocking OX40-OX40L interaction, thus resolving the technical contradiction
2Measurement precision
If anti-OX40 antibody binds with high affinity to OX40, then T cell activation is enhanced, but interference with OX40-OX40L interaction increases
Solution Approach 1:
The patent precisely adjusts the binding affinity parameter through amino acid mutations in CDRs, achieving optimal binding strength to OX40 that enhances T cell activation while avoiding excessive interference with OX40-OX40L interaction. This parameter optimization resolves the contradiction between high affinity binding and minimal interference
3Productivity
If existing anti-OX40 antibodies are used, then some T cell activation occurs, but the ability to promote antitumor activity is limited
Solution Approach 1:
The patent enhances both T cell activation effectiveness and antitumor activity promotion by optimizing the antibody's binding parameters. The amino acid mutations in CDRs create an antibody that achieves the right balance of OX40 binding affinity to simultaneously activate T cells and promote antitumor responses, resolving the contradiction between productivity and reliability
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 antibody or fragment activates T cells, enhances immunostimulatory functions, and elicits antibody-dependent cell-mediated cytotoxicity, leading to improved anti-tumor activity and treatment of various cancers and immune-related diseases.
Implementation Method 1
an antibody or fragment thereof that binds human OX40 or cynomolgus monkey OX40
Implementation Method 2
elicits antibody-dependent cell-mediated cytotoxicity, leading to improved anti-tumor activity
Data Source
AI summary
The present invention relates to an antibody and antibody fragment that specifically binds to OX40 and to a composition comprising said antibody or antibody fragment thereof. In addition, the present invention relates to a nucleic acid encoding the antibody or antibody fragment thereof and a host cell comprising the same, and to a related use thereof. In addition, the present invention relates to the use of the antibody and antibody fragment for treatment and diagnosis.