Extracellular domain of alpha subunit of ige fc receptor, pharmaceutical composition comprising same and method for producing same
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Solution Overview
Problem
Current therapeutic methods for allergic diseases, such as allergic rhinitis and asthma, suffer from inefficacy, high costs, and severe side effects, particularly with anti-IgE antibodies like omalizumab.
Innovation Solution
A polypeptide dimer composed of two monomers, each containing an extracellular domain of an IgE Fc receptor alpha subunit linked via a modified Fc region through an IgD antibody hinge, which exhibits enhanced binding to IgE and lacks ADCC and CDC functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-IgE antibodies like omalizumab are used to treat allergic diseases, then therapeutic efficacy is improved, but severe side effects such as anaphylactic reactions and angioedema occur
Solution Approach 1:
The invention divides the antibody molecule into separate functional components: the Fc region is detached from the variable regions. This segmentation allows the Fc region to be modified independently to eliminate harmful binding activities while preserving the beneficial IgE binding capacity through the extracellular domain of the alpha subunit.
Solution Approach 2:
The invention extracts and removes the harmful Fc gamma receptor binding activity from the antibody molecule by using a modified Fc region that lacks this capability. The harmful function is separated from the useful function of IgE binding, allowing treatment without anaphylactic reactions.
2Reliability
If high-dose omalizumab is administered to maintain therapeutic effects, then treatment efficacy is improved, but cost burden and side effects increase
Solution Approach 1:
The invention changes the binding parameters of the antibody to IgE, achieving a 70-fold higher binding capacity than omalizumab. This parameter improvement allows for lower dosing requirements while maintaining therapeutic effects, thereby reducing both cost burden and side effect risks associated with high-dose administration.
3Reliability
If conventional anti-IgE antibodies are used, then IgE binding is achieved, but binding capacity is insufficient compared to the desired therapeutic level
Solution Approach 1:
The invention creates a composite molecular structure combining the modified Fc region with the extracellular domain of the IgE Fc receptor alpha subunit linked via an IgD antibody hinge. This composite design achieves enhanced IgE binding capacity (70-fold higher than omalizumab) while eliminating harmful Fc gamma receptor interactions.
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 provides safer and more persistent treatment with a 70-fold higher binding capacity to IgE than omalizumab, minimizing anaphylactic reactions and reducing side effects.
Implementation Method 1
The polypeptide dimeric protein according to the present invention not only has excellent safety and persistence in the body as compared with conventionally used anti-IgE antibodies, but also binds to IgE very strongly due to having a binding capacity to IgE which is 70-fold higher than the conventionally used anti-IgE antibody, omalizumab
Data Source
AI summary
Disclosed is a polypeptide dimeric protein containing two monomers, each of which contains an extracellular domain (FcεRIa-ECD) of an alpha subunit of an IgE Fc receptor. The dimeric protein has advantages that an excellent binding ability to IgE is exhibited as compared with a conventional therapeutic agent containing an anti-IgE antibody, and less other side effects are exhibited due to lack of ADCC and CDC functions. Thus, the dimeric protein can be applied to a medical product for treating or preventing an IgE-mediated allergic disease.