ST2L Antagonists Block IL-33 Interaction to Reduce Inflammation
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Solution Overview
Problem
There is a need for effective ST2L antagonists to treat immune-mediated diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease, and other conditions characterized by excessive type 2 cytokine responses and airway hyper-reactivity, as existing treatments are inadequate in managing these dysregulated immune responses.
Innovation Solution
Development of isolated antibodies or fragments that specifically bind to Domain I of human ST2L, comprising specific heavy and light chain variable regions, which inhibit IL-33/ST2L interaction and subsequent mast cell responses, thereby modulating immune system activity and reducing cytokine release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ST2L is activated by IL-33, then type 2 cytokine release is induced, but excessive cytokine responses and airway hyper-reactivity occur
Solution Approach 1:
The patent applies preliminary anti-action by developing ST2L antagonists that pre-block the ST2L receptor before IL-33 can bind and activate it. The antagonists are designed to occupy the binding site on ST2L, preventing the formation of the ST2L/IL-33 complex and thereby preventing downstream type 2 cytokine release and airway hyper-reactivity before they can occur.
Solution Approach 2:
The patent uses ST2L antagonists as intermediary molecules that mediate between IL-33 and the ST2L receptor. These antagonists act as blocking agents that interfere with the natural interaction between IL-33 and ST2L, thereby modulating the immune response and preventing excessive cytokine production without completely eliminating the signaling pathway.
2Object-generated harmful factors
If anti-ST2 antibody is administered to treat immune-mediated diseases, then cytokine production is inhibited, but treatment efficacy is limited
Solution Approach 1:
The patent applies parameter changes by developing new ST2L antagonists with optimized binding affinity and specificity parameters. The antagonists are engineered to have improved pharmacological properties including higher affinity for ST2L, better tissue penetration, and enhanced stability, thereby improving treatment efficacy compared to existing anti-ST2 antibodies.
Solution Approach 2:
The patent employs disposable single-use antibody formulations that are administered at optimized doses to achieve therapeutic effect. The antagonists are designed as ready-to-use therapeutic agents that can be administered in controlled doses, replacing the need for long-term continuous treatment with less effective antibodies.
3Ease of operation
If existing treatments are used for ST2L-mediated diseases, then some symptom relief is achieved, but inadequate disease management occurs
Solution Approach 1:
The patent applies universality by developing ST2L antagonists that can treat multiple ST2L-mediated diseases through a single mechanism of action. The antagonists are designed to block the ST2L/IL-33 pathway universally, making them effective for asthma, rheumatoid arthritis, inflammatory bowel disease, and other conditions mediated by this pathway, thereby providing comprehensive disease management.
Data Source
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AI summary
The present invention relates to ST2L antagonists, polynucleotides encoding the antagonists or fragments thereof, and methods of making and using the foregoing.