Mutated IgE Proteases for Cleaving FcεRI-Bound IgE
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current technologies are inadequate in effectively reducing or eliminating IgE antibodies, which play a central role in allergy sensitization and atopic disorders such as allergic rhinitis, asthma, and atopic dermatitis.
Innovation Solution
Development of polypeptides with specific mutations that exhibit IgE protease activity, capable of cleaving IgE and potentially reducing its levels by targeting the high-affinity FcεRI receptor on mast cells and basophils.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to reduce IgE, then current treatment limitations are maintained, but the ability to effectively eliminate IgE antibodies is insufficient
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid mutations (e.g., at positions 68, 71, 75, 79, 84, 86, 88, 91, 93, 94, 102, 112, 115, 116, 117, 120, 122, 125, 126, 128, 139, 142, 143, 148, 149, 150, 152, 153, 160, 162, 164, 165, 166, 167, 174, 175, 177-183, 180, 182, 183, 185, 189, 196, 197, 199, 200-202, 201, 205, 206, 212, 219, 220, 221, 222, 224, 228, 229, 232, 233, 241, 242, 243, 244, 250, 251, 252, 254, 260, 262, 263, 268, 270, 271-287, 274, 275, 276, 279, 280, 281, 282, 293, 294, 295, 297, 301, 303, 303-326, 306, 307-322, 308-324, 309, 310, 310-320, 311-319, 311-321, 313, 314, 315-317, 316, 318, 319, 320, 324, 327, 329, 332, 333, 336, 343, 346, 347, 348, 351, 360, 363, 364, 366, 374, and 380) into the protease sequence to enhance its specificity and efficiency for cleaving IgE. These mutations modify the enzyme's binding pocket and catalytic residues to optimize recognition and degradation of the FcεRI receptor and IgE antibodies, thereby improving the reliability and productivity of IgE reduction.
2Reliability
If IgE antibodies are bound to FcεRI receptor, then mast cells and basophils are sensitized for allergen, but the high affinity binding prevents effective reduction of IgE
Solution Approach 1:
The patent applies local quality by making targeted mutations at specific positions within the protease sequence to enhance local binding affinity for the FcεRI receptor and IgE antibodies. Mutations such as those at positions 68, 71, 75, 79, 84, 86, 88, 91, 93, 94, 102, 112, 115, 116, 117, 120, 122, 125, 126, 128, 139, 142, 143, 148, 149, 150, 152, 153, 160, 162, 164, 165, 166, 167, 174, 175, 177-183, 180, 182, 183, 185, 189, 196, 197, 199, 200-202, 201, 205, 206, 212, 219, 220, 221, 222, 224, 228, 229, 232, 233, 241, 242, 243, 244, 250, 251, 252, 254, 260, 262, 263, 268, 270, 271-287, 274, 275, 276, 279, 280, 281, 282, 293, 294, 295, 297, 301, 303, 303-326, 306, 307-322, 308-324, 309, 310, 310-320, 311-319, 311-321, 313, 314, 315-317, 316, 318, 319, 320, 324, 327, 329, 332, 333, 336, 343, 346, 347, 348, 351, 360, 363, 364, 366, 374, and 380 are strategically positioned to enhance binding affinity at the interface between the protease and the FcεRI receptor/IgE complex, while maintaining overall structural integrity.
3Reliability
If IgE binds to FcεRI with high affinity, then long-lived complexes are formed on mast cells, but this binding prevents effective clearance of IgE
Solution Approach 1:
The patent applies the taking out principle by extracting and degrading the FcεRI receptor and bound IgE antibodies through the engineered protease. The protease specifically targets and cleaves the FcεRI receptor structure, thereby releasing and eliminating bound IgE antibodies from mast cells and basophils. This extraction mechanism directly addresses the problem of long-lived IgE-receptor complexes by actively removing the receptor component, enabling subsequent clearance of IgE through normal immunological processes.
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 mutated polypeptides demonstrate enhanced efficacy and selectivity in cleaving IgE, providing a potential therapeutic approach to manage IgE-related allergic disorders.
Implementation Method 1
polypeptides with specific mutations that exhibit IgE protease activity, capable of cleaving IgE
Data Source
AI summary
Embodiments provided herein, provide for polypeptides and molecules comprising a polypeptide having protease activity, pharmaceutical compositions comprising the same, and methods that can be used to treat disorders, such as IgE mediated disorders.