High-Sialic-Acid IgE Fc-Receptor Dimers for Extended Allergy Treatment
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Solution Overview
Problem
Current treatments for allergic diseases, such as those targeting IgE, suffer from insufficient efficacy and severe side effects, and there is a need for a safer and more effective therapeutic agent.
Innovation Solution
A polypeptide dimer comprising two monomers of the extracellular domain of the alpha subunit of the IgE Fc receptor with a high sialic acid content, which binds strongly to IgE and maintains high concentration in the body, is developed for subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If omalizumab is administered at high doses to maintain therapeutic effects, then therapeutic efficacy is improved, but cost burden and side effects increase
Solution Approach 1:
The patent modifies the molecular structure of the therapeutic agent by changing the sialic acid content parameter. The polypeptide dimer is engineered to have a specific sialic acid content (0.1-10 μmol/mg protein) to optimize binding affinity to IgE and extend half-life, thereby improving therapeutic efficacy at lower doses and reducing side effects
Solution Approach 2:
The patent creates a composite molecular structure by combining the extracellular domain of the alpha subunit of IgE Fc receptor with an Fc region, forming a chimeric polypeptide dimer. This composite structure integrates the binding capability of the FcεRIα-ECD with the extended half-life properties of the Fc region, achieving both high efficacy and safety
2Object-affected harmful factors
If conventional anti-allergic drugs are used, then allergic symptoms are suppressed, but drug efficacy is insufficient and serious side effects occur
Solution Approach 1:
The patent extracts and utilizes the extracellular domain of the alpha subunit of the IgE Fc receptor (FcεRIα-ECD), which is the specific binding region responsible for IgE interaction. By isolating this functional domain and combining it with an Fc region, the patent creates a therapeutic agent with high binding affinity to IgE, achieving superior efficacy compared to conventional drugs
Solution Approach 2:
The patent introduces a chimeric polypeptide dimer as an intermediary substance that mediates between IgE and the immune system response. This polypeptide dimer binds to IgE with high affinity and blocks the interaction between IgE and FcεRI, thereby preventing mast cell activation and allergic reactions with high reliability
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 polypeptide dimer with high sialic acid content exhibits enhanced binding affinity to IgE, reduces severe side effects, and provides prolonged therapeutic effects with minimal anaphylaxis risk, making it effective for preventing or treating allergic diseases.
Implementation Method 1
The polypeptide dimer with high sialic acid content exhibits enhanced binding affinity to IgE
Implementation Method 2
binds strongly to IgE
Implementation Method 3
the molar ratio of sialic acid/polypeptide dimer is at least 8
Data Source
AI summary
A modified IgE Fc receptor having a high content of sialic acid and a pharmaceutical composition contains the modified IgE Fc receptor are disclosed. The polypeptide dimer having a high content of sialic acid not only has excellent safety and persistence in a body as compared with conventionally used anti-IgE antibodies, but also shows strong binding to IgE. Thus, the polypeptide has the advantage of an extended administration cycle. The polypeptide dimer is also an IgE single target substance, and unlike conventional anti-IgE antibodies to which the Fc of IgG1 is applied, does not bind to an Fc gamma receptor. The polypeptide dimer can be usefully used for the prevention or treatment of allergic diseases.