IL-33 Antibodies for Accurate Detection Amid sST2 Interference
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Solution Overview
Problem
Current assays face challenges in accurately measuring active human IL-33 concentrations in biological samples due to low levels, structural forms, and interference from soluble Interleukin 1 Receptor-Like 1 (sST2), particularly in lower sample volumes and matrices with elevated sST2 levels.
Innovation Solution
Development of antibodies with high sensitivity that specifically bind to all forms of IL-33, including unbound and bound forms, using specific amino acid sequences for the heavy and light chain variable domains, enabling accurate detection across various matrices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional IL-33 assays are used, then measurement capability is provided, but measurement precision deteriorates due to low IL-33 levels and interference from sST2
Solution Approach 1:
The patent changes the binding parameters of the antibody by selecting specific CDR sequences (H1: SEQ ID NO: 1, H2: SEQ ID NO: 2, H3: SEQ ID NO: 3, L1: SEQ ID NO: 4, L2: SEQ ID NO: 5, L3: SEQ ID NO: 6) that confer high affinity binding to IL-33. This parameter change in antibody affinity allows the assay to accurately detect IL-33 even in the presence of interfering sST2 proteins, resolving the measurement precision issue.
Solution Approach 2:
The patent replaces conventional detection mechanisms with a highly specific antibody-based detection system. The antibody's specific binding domain (comprising the six CDRs listed) provides selective recognition of IL-33, substituting the need for complex signal processing to distinguish IL-33 from sST2 interference with direct molecular recognition.
2Measurement precision
If antibodies with high affinity for IL-33 are used, then detection sensitivity is improved, but specificity may be compromised due to binding to all forms including oxidized and reduced
Solution Approach 1:
The patent applies universality by designing an antibody that can bind to multiple forms of IL-33 (oxidized, reduced, bound to sST2, unbound) with similar affinity. The CDR sequences are selected to recognize conserved epitopes across these different forms, allowing a single antibody to detect all IL-33 forms simultaneously, which improves detection sensitivity while maintaining reliability through consistent binding characteristics.
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
The antibodies provide precise binding to both oxidized and reduced IL-33, as well as IL-33 bound to sST2, with similar affinity, facilitating sensitive and accurate measurement of IL-33 in biological samples, even in conditions with low concentrations and high sST2 levels.
Implementation Method 1
The present disclosure provides antibodies with high sensitivity (e.g., binding affinity) to all forms of IL-33, both unbound and associated
Implementation Method 2
methods, assays, kits that comprise and use said antibodies... for use in detecting the presence or level of IL-33 in a biological sample
Data Source
AI summary
The invention provides interleukin-33 (IL-33) antibodies and methods of making and using the same, e.g., for detection of IL-33 in biological samples.