Anti-IgE Antigen Binding Protein for Sustained Receptor Blockade
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Solution Overview
Problem
Existing therapies for allergic diseases, particularly those mediated by immunoglobulin E (IgE), face challenges in effectively controlling IgE levels and managing hypersensitivity reactions due to the lack of stable and efficient antigen binding proteins that can inhibit IgE receptor binding.
Innovation Solution
Development of an antigen binding protein with specific CDR sequences (e.g., HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) that bind to IgE with high affinity (KD ≤ 2.4×10−9 M) and inhibit the interaction of IgE with its receptors FcεRIα and/or FcεRII, offering enhanced stability and druggability for prolonged dosing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional therapies are used to control IgE levels, then allergic symptoms can be managed, but the dosing period is short and requires frequent administration
Solution Approach 1:
The patent modifies the antigen binding protein structure by optimizing complementarity determining regions (CDRs) to enhance affinity for IgE (KD ≤ 2.4×10−9 M). This parameter change in binding affinity directly extends the dosing period and maintains efficacy consistency by ensuring prolonged blockade of IgE-receptor interactions
Solution Approach 2:
The invention creates a composite antigen binding protein structure combining optimized heavy chain variable region (SEQ ID NO: 73 or 74) and light chain variable region (SEQ ID NO: 75 or 76) with specific CDR sequences. This composite structure achieves both enhanced stability and prolonged dosing period by integrating multiple functional elements that work synergistically
2Stability of the object's composition
If existing antigen binding proteins are used, then IgE binding can be achieved, but stability and druggability are insufficient for industrial production
Solution Approach 1:
The patent optimizes amino acid sequences in the variable regions by modifying CDR sequences (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) to achieve optimal balance between stability and manufacturability. The specific sequence selections (SEQ ID NO: 73/74 and 75/76) represent parameter optimizations that enhance both protein stability and industrial production feasibility
Solution Approach 2:
The invention develops an antigen binding protein with simplified structure (variable regions only) that can be produced more easily and cost-effectively than full antibodies. This approach trades some structural complexity for ease of manufacture while maintaining sufficient functional stability for therapeutic use
3Manufacturing precision
If high affinity binding to IgE is achieved, then receptor binding is blocked, but the half-life is shortened
Solution Approach 1:
The patent separates the antigen binding function from the constant region, using only variable regions (Fab fragments or similar) that contain the CDR sequences. This segmentation allows optimization of binding affinity in the variable regions while the lack of Fc region reduces clearance, thereby extending half-life despite high affinity binding
Solution Approach 2:
The invention optimizes the balance between binding affinity (KD ≤ 2.4×10−9 M) and half-life by selecting specific CDR sequences and variable region structures. The parameter optimization ensures that high affinity binding does not lead to rapid clearance, achieving both precise blockade and prolonged circulation
Data Source
AI summary
The present application relates to an antigen binding protein comprising at least one CDR of a heavy chain variable region and at least one CDR of a light chain variable region, wherein said heavy chain variable region comprises an amino acid sequence as set forth in any one of SEQ ID NOs: 73 or 74, and the light chain variable region comprises an amino acid sequence as set forth in any one of SEQ ID NOs: 75 or 76.