Humanized Anti-CMKLR1 Antibodies for High-Yield Pro-Resolving Activity
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Solution Overview
Problem
Existing anti-CMKLR1 antibodies are difficult to produce in sufficient quantities and have low efficiency in enhancing the resolution of inflammation, and there is a need for molecules that can initiate or enhance the resolution stage of the inflammatory response like pro-resolving factors.
Innovation Solution
Development of humanized anti-CMKLR1 antibodies with specific CDR and framework region mutations that allow for high-yield production in cell lines such as CHO, COS-7, and HEK 293 cells, while maintaining binding affinity and Resolvin-like agonist capability on CMKLR1, thereby promoting apoptosis of neutrophils and reducing migration of inflammatory cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If wild type anti-CMKLR1 antibodies are used, then binding affinity and Resolvin-like agonist capability are maintained, but production yield is insufficient for therapeutic applications
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid mutations in the CDR and framework regions of the antibody sequences. These mutations alter the molecular parameters of the antibody structure while maintaining its functional properties, enabling high-yield production in CHO, COS-7, and HEK 293 cell lines without compromising binding affinity to CMKLR1
Solution Approach 2:
The patent creates humanized copies of the wild type antibody by grafting CDR regions onto human framework regions. This copying approach allows the antibody to be produced in human cell lines with high efficiency while preserving the essential binding characteristics through careful selection of framework residues that maintain structural integrity
2Productivity
If wild type anti-CMKLR1 antibodies are used, then Resolvin-like agonist capability is maintained, but efficiency in enhancing resolution of inflammation is insufficient
Solution Approach 1:
Specific amino acid substitutions in the CDR regions modify the antibody's interaction parameters with CMKLR1, enhancing its ability to trigger pro-resolving signaling pathways. These parameter changes improve the efficiency of inflammation resolution while maintaining the essential Resolvin-like agonist capability through preserved key interacting residues
3Object-affected harmful factors
If humanized antibodies with high human residue content are developed, then immunogenicity is reduced, but production efficiency may be compromised
Solution Approach 1:
The patent applies local quality by humanizing only specific regions (framework regions) of the antibody while preserving the non-human CDR regions that are critical for binding. This localized humanization reduces immunogenicity in the framework regions without affecting the functional CDR regions, and the selected human framework sequences are optimized for high expression in mammalian cell lines
Solution Approach 2:
The patent optimizes production efficiency by selecting specific human framework sequences and introducing mutations that enhance expression levels in CHO, COS-7, and HEK 293 cell lines. These parameter changes in the framework regions improve production efficiency while maintaining low immunogenicity through high human residue content
Data Source
AI summary
The present invention provides humanized anti-CMKLR1 compounds having an agonist capability on the interaction between Resolvin E1 and CMKLR1, and their uses for treating or preventing a disease, in particular wherein the resolution of inflammation is delayed or disrupted.