High-Affinity Anti-B7-H3 Antibody via CDR Optimization
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Solution Overview
Problem
Current anti-B7-H3 antibodies in clinical development lack high affinity and stability, limiting their effectiveness as therapeutic options for tumors and autoimmune diseases.
Innovation Solution
Development of a high-affinity, stable antibody or antigen-binding fragment specifically binding to B7-H3, including murine and humanized variants with optimized complementarity-determining regions and constant regions for enhanced specificity and reduced immunogenicity, produced using expression vectors in mammalian cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-B7-H3 antibodies are used in clinical development, then they can provide therapeutic options for tumors, but they lack high affinity and stability which limits their effectiveness
Solution Approach 1:
The patent applies parameter changes by systematically optimizing the complementarity-determining regions (CDRs) of the antibody to achieve high affinity binding to B7-H3. Through amino acid substitutions in the CDR sequences, the antibody's binding parameters were improved to reach sub-nanomolar affinity (KD < 1 nM), directly resolving the affinity and stability limitations of prior antibodies
Solution Approach 2:
The patent creates humanized antibody variants by copying and adapting the binding properties of murine antibodies to human sequences. This allows the therapeutic antibody to maintain high affinity for B7-H3 while reducing immunogenicity, effectively copying the successful binding mechanism while improving clinical suitability
2Manufacturing precision
If murine antibodies are used to achieve high binding affinity to B7-H3, then strong binding is achieved, but immunogenicity increases reducing therapeutic potential
Solution Approach 1:
The patent applies local quality by making targeted modifications only to specific regions of the antibody molecule. The CDR sequences were optimized for high affinity while the framework regions were humanized to reduce immunogenicity. This localized approach allows different parts of the antibody to have different properties: high affinity in the binding regions and low immunogenicity in the non-binding regions
Solution Approach 2:
The patent creates composite antibody structures by combining murine CDR sequences (for affinity) with human framework sequences (for low immunogenicity). This composite approach integrates the beneficial properties of both murine and human antibodies, achieving high binding affinity while minimizing immune response
Data Source
AI summary
Provided in the present invention are an antibody or an antigen-binding fragment thereof against human B7-H3. Further provided are a nucleic acid molecule encoding the antibody, an expression vector and a host cell for expressing the antibody, and a method for producing the antibody. In addition, further provided in the present invention are a pharmaceutical composition containing the antibody or the antigen-binding fragment thereof, and the use thereof in the preparation of a drug for preventing and/or treating various diseases (comprising tumors and autoimmune diseases).