Soluble CD23 Polypeptides Sequester IgE to Treat Allergy
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Solution Overview
Problem
Current treatments for IgE-mediated diseases such as allergies and asthma are inadequate, with existing therapies being costly, having side effects, and failing to adequately manage chronic inflammation and immune responses.
Innovation Solution
Development of modified soluble CD23 polypeptides that bind IgE with high affinity, sequestering it to prevent its interaction with IgE receptors, thereby reducing allergic responses and inflammation, while minimizing CD21 binding to avoid adverse effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies for IgE-mediated diseases are used, then treatment is provided, but the treatments are costly and have side effects
Solution Approach 1:
The patent extracts and utilizes the natural IgE-binding capability of CD23 polypeptides, isolating this specific function from the complex immune system. By using recombinant CD23 polypeptides that specifically bind IgE, the therapy targets only the harmful IgE-mediated responses without disrupting other immune functions, thereby reducing side effects while maintaining effectiveness
Solution Approach 2:
CD23 polypeptides serve as an intermediary substance that mediates between IgE and its receptors. These polypeptides bind to IgE and prevent IgE from interacting with FcεRI receptors on mast cells and basophils, thereby blocking the allergic response pathway without directly attacking the immune system, reducing harmful side effects
2Reliability
If existing therapies are used, then immune responses are suppressed, but chronic inflammation is not adequately managed
Solution Approach 1:
The CD23 polypeptide therapy is administered continuously to maintain constant binding of IgE to the polypeptide, preventing IgE from binding to FcεRI receptors before allergic reactions can occur. This preliminary blocking action ensures continuous management of chronic inflammation and extends the duration of therapeutic effect
Solution Approach 2:
The recombinant CD23 polypeptides are designed to circulate in the blood and continuously bind IgE throughout the dosing period. This continuous action ensures sustained suppression of IgE-mediated inflammation, providing long-term management of chronic conditions without the need for intermittent treatment
3Reliability
If CD23 polypeptides bind IgE with high affinity, then IgE sequestration is enhanced, but CD21 binding may increase causing adverse effects
Solution Approach 1:
The patent employs CD23 polypeptides with specifically engineered local properties - the polypeptides are designed to have high affinity binding sites for IgE in specific regions while lacking or having reduced affinity for CD21 in other regions. This localized differentiation of binding properties allows selective IgE sequestration without the harmful CD21 binding effects
Solution Approach 2:
The invention uses recombinant CD23 polypeptides that are molecular copies of the natural protein, engineered to replicate the IgE-binding function while modifying or removing the CD21-binding capability. These synthetic copies provide the desired IgE sequestration activity without the harmful CD21 interaction, achieving functional separation of binding activities
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 modified CD23 polypeptides effectively reduce immune responses to allergens, decrease the severity of allergic reactions, and offer a safer, more cost-effective alternative to existing therapies by selectively binding and sequestering IgE, thus alleviating symptoms of IgE-mediated diseases.
Implementation Method 1
modified soluble CD23 polypeptides that bind IgE with high affinity, sequestering it to prevent its interaction with IgE receptors
Data Source
AI summary
The methods and compositions described herein are based, in part, on the discovery of a polypeptide of soluble CD23 (sCD23) that binds and sequesters IgE. Thus, the sCD23 peptides, polypeptides and derivatives described herein are useful for treating conditions or disorders involving increased IgE levels such as e.g., allergy, anaphylaxis, inflammation, lymphoma, and certain cancers.