OX40 Antagonist Antibodies for Non-Agonistic Immune Modulation
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Solution Overview
Problem
Current technologies lack effective antagonist antibodies that specifically target human OX40 without agonistic effects, which are crucial for treating OX40-mediated disorders such as autoimmunity and inflammation.
Innovation Solution
Development of antagonist antibodies or fragments thereof that bind to human OX40, comprising specific CDR sequences and variable framework regions, with humanized forms exhibiting enhanced affinity and reduced Fc-mediated cytotoxicity, capable of inhibiting OX40 signaling and reducing lymphocyte proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies are used to target OX40, then OX40 binding is achieved, but agonistic effects are activated which are harmful for treating autoimmune disorders
Solution Approach 1:
The patent applies local quality by engineering specific CDR sequences (HCDR1: SEQ ID NO: 1, HCDR2: SEQ ID NO: 2, HCDR3: SEQ ID NO: 3, LCDR1: SEQ ID NO: 4, LCDR2: SEQ ID NO: 5, LCDR3: SEQ ID NO: 6) that confer antagonist specificity to the antibody binding site, while the Fc region is modified to reduce cytotoxicity. This localized modification of specific regions achieves the desired therapeutic effect without harmful agonistic activation
Solution Approach 2:
The patent employs parameter changes by modifying the amino acid sequences of the CDR regions and Fc portion to transform the antibody's functional properties from agonistic to antagonist. Specific sequence variations in the variable regions alter the binding characteristics to block OX40 signaling, while Fc region modifications reduce complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity parameters
2Measurement precision
If humanized antibody forms are developed, then affinity and selectivity are improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional modules: variable regions with specific CDR sequences for high-affinity binding (SEQ ID NOs: 1-6), humanized framework regions for reduced immunogenicity, and engineered Fc regions for controlled effector functions. This modular approach enables precise control over binding affinity while facilitating standardized manufacturing processes for each module
Solution Approach 2:
The patent achieves universality by creating a platform technology where the specific CDR sequences can be combined with standardized humanized framework regions and Fc engineering approaches. This multi-functional design allows the same CDR sequences to be applied across different antibody formats (IgG1, IgG4, etc.) with predictable outcomes, reducing overall manufacturing complexity through reuse of validated components
Data Source
AI summary
The present invention relates to antagonist antibodies or fragments thereof that bind to human OX40. More specifically, the present invention relates to an antagonist antibody or fragment thereof that binds to human OX40 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6.