Anti-IL-31RA Antibody CDR Engineering for IL-31 Signaling Blockade
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Solution Overview
Problem
Current treatments for IL-31-related disorders such as atopic dermatitis, allergic asthma, and inflammatory bowel diseases are inadequate, as IL-31 signaling through IL-31RA contributes to inflammation and pruritus, and existing therapies like nemolizumab and lokivetamab have limitations.
Innovation Solution
Development of anti-IL-31RA antibodies and fragments that specifically bind to IL-31RA, inhibiting its interaction with IL-31 and reducing inflammation and pruritus by targeting IL-31 signaling pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies like nemolizumab and lokivetamab are used to treat IL-31-related disorders, then some therapeutic effect is achieved, but treatment efficacy is insufficient and limitations remain
Solution Approach 1:
The patent develops novel anti-IL-31RA antibodies with optimized amino acid sequences in complementarity determining regions (CDRs) to enhance binding affinity and therapeutic efficacy. By modifying specific residues in HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, the invention creates antibodies with improved parameters for treating IL-31-related disorders compared to existing therapies
2Measurement precision
If anti-IL-31RA antibodies are developed with high specificity, then binding precision to IL-31RA is improved, but development complexity increases
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions specifically in the complementarity determining regions (CDRs) of the antibody variable domains. Rather than redesigning the entire antibody structure, the invention modifies only the critical binding regions (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) to achieve high binding specificity while maintaining overall structural simplicity
Solution Approach 2:
The invention segments the antibody structure into distinct functional regions with specific amino acid sequences. The variable domains are divided into framework regions and complementarity determining regions, with further subdivision into heavy chain (HCDR1-3) and light chain (LCDR1-3) CDRs. This segmentation allows independent optimization of each binding region to achieve high specificity
Data Source
AI summary
The invention provides novel anti-IL-31RA proteins, antibodies and IL-31RA binding fragments thereof, which inhibit association of IL-31 with IL-31 receptor and are suitable for administration to a human or canine subject. The invention provides novel compositions and methods of treating, alleviating the symptoms of, or preventing, allergic/inflammatory diseases, lung diseases, cardiovascular diseases, cancers, metabolic diseases, neurological diseases, and infectious diseases, comprising administering an effective amount of an anti-IL-31RA protein, antibody, or fragment thereof. The methods and compositions are used to treat or prevent IL-31-related disorders.