IL-36R Monoclonal Antibody CDR Design for Stronger Neutralization
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Solution Overview
Problem
Current treatments for diseases mediated by IL-36R, such as psoriasis and inflammatory bowel disease, lack a monoclonal antibody with high affinity and superior neutralizing activity to effectively block IL-36 inflammatory pathways.
Innovation Solution
Development of a humanized monoclonal antibody, QX009N (HZD25-54), with specific CDR sequences (SEQ ID NOs: 1-6) that binds to IL-36R, blocking receptor agonists and downregulating pro-inflammatory signaling pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing monoclonal antibodies are used to treat IL-36R mediated diseases, then treatment is provided, but the affinity and neutralizing activity are insufficient to effectively block IL-36 inflammatory pathways
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's binding affinity parameters through specific CDR sequence design. The heavy chain CDRs (SEQ ID NOs: 1-3) and light chain CDRs (SEQ ID NOs: 4-6) are engineered to achieve superior binding affinity to IL-36R, thereby enhancing neutralizing activity and blocking capability against the inflammatory pathway.
2Reliability
If current treatment options are used, then disease management is achieved, but the inflammatory responses and pathogenic cytokine release are not sufficiently inhibited
Solution Approach 1:
The monoclonal antibody acts as an intermediary substance that binds to IL-36R, preventing the interaction between IL-36 ligands and their receptor. This intermediary action blocks the pro-inflammatory signaling pathway, inhibiting the release of pathogenic cytokines and reducing inflammatory responses in diseases such as psoriasis and inflammatory bowel disease.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
QX009N demonstrates superior neutralizing activity compared to Spesolimab, inhibiting inflammatory responses and reducing pathogenic cytokine release, showing potential for effective disease control.
Implementation Method 1
a monoclonal antibody against human interleukin-36 receptor (IL-36R)... binds to IL-36R, blocking receptor agonists
Implementation Method 2
downregulating pro-inflammatory signaling pathways... inhibiting inflammatory responses
Data Source
AI summary
The present invention provides an anti-human interleukin 36 receptor (IL-36R) monoclonal antibody and a use thereof. The monoclonal antibody comprises three heavy chain complementarity determining regions CDR-H1, CDR-H2 and CDR-H3 and three light chain complementarity determining regions CDR-L1, CDR-L2 and CDR-L3, and the amino acid sequences of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are as shown in SEQ ID NO: 1 to SEQ ID NO: 6, respectively. Compared with Spesolimab, the monoclonal antibody has comparable binding affinity to human IL-36R, and the neutralizing activity of the monoclonal antibody at the cellular level is superior to that of Spesolimab.