IL-17A Antibody CDR Optimization for Rheumatoid Arthritis
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Solution Overview
Problem
Current IL-17A targeting antibodies, such as Secukinumab and Ixekizumab, do not show the expected therapeutic effect for certain chronic inflammatory diseases like rheumatoid arthritis, highlighting a need for more effective antibodies that can specifically bind to IL-17A.
Innovation Solution
Development of a parental anti-human IL-17A murine monoclonal antibody with specific CDR regions, leading to the creation of chimeric and humanized antibodies with enhanced binding specificity and affinity, utilizing eukaryotic cell expression systems and purification methods to produce functional fragments like scFv and bispecific antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing IL-17A targeting antibodies (Secukinumab, Ixekizumab) are used, then psoriasis treatment shows good therapeutic effect, but rheumatoid arthritis treatment does not show expected therapeutic effect
Solution Approach 1:
The patent applies local quality by engineering specific CDR regions (CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3) with optimized amino acid sequences to enhance binding affinity and neutralization activity for IL-17A. This localized optimization of antibody structure at the antigen-binding site enables the antibody to effectively neutralize IL-17A across multiple disease contexts including rheumatoid arthritis, where existing antibodies failed.
2Reliability
If parental anti-human IL-17A murine monoclonal antibody is developed, then specific binding capability is achieved, but immunogenicity and therapeutic efficacy are limited
Solution Approach 1:
The patent uses copying by creating chimeric and humanized antibody variants that replicate the antigen-binding capability of the parental murine monoclonal antibody while replacing murine constant regions with human sequences. This reduces immunogenicity while preserving the specific binding characteristics to IL-17A, allowing for better therapeutic application in human patients.
Solution Approach 2:
The patent applies parameter changes by systematically modifying the amino acid sequences in CDR regions and constant regions of the antibody. These parameter modifications optimize both binding affinity to IL-17A and reduction of immunogenicity, transforming the parental murine antibody into therapeutic candidates with improved safety and efficacy profiles.
3Reliability
If antibody structure is optimized for higher binding affinity, then neutralization activity improves, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by focusing optimization efforts on specific functional segments (CDR regions) rather than the entire antibody structure. By identifying and optimizing only the critical CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 regions responsible for antigen binding, the patent achieves enhanced neutralization activity while maintaining manageable structural complexity for manufacturing.
Data Source
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AI summary
An antibody specifically binding to IIL-17A or a functional fragment thereof. The antibody or functional fragment thereof includes an IL-17A chimeric antibody and a functional fragment thereof, and an IIL-17A humanized antibody and a functional fragment thereof.