Anti-IFNAR1 Antibodies for Selective IFNα/IFNω Signal Blocking
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Solution Overview
Problem
There is a need for novel anti-IFNAR1 antibodies that can selectively inhibit IFNα and IFNω-mediated activation without affecting IFNβ-mediated activities, which are crucial for treating type I IFN-related diseases.
Innovation Solution
Development of anti-IFNAR1 antibodies with specific heavy and light chain CDR sequences capable of selectively binding to IFNAR1, inhibiting IFNα and IFNω activation, while preserving IFNβ-mediated functions, and maintaining anti-viral activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-IFNAR1 antibodies are developed to inhibit type I IFN-related diseases, then disease treatment efficacy is improved, but antiviral and anti-tumor activities may be suppressed
Solution Approach 1:
The antibody is designed to bind specifically to IFNAR1 with differential affinity for different IFN subtypes. The CDR regions are engineered to recognize epitopes that are accessible when IFNα or IFNω bind to IFNAR1, but not when IFNβ binds, thereby achieving selective inhibition of pathological IFN signals while preserving protective IFNβ activities
Solution Approach 2:
The invention modifies the binding parameters of anti-IFNAR1 antibodies by optimizing CDR sequences to achieve differential binding affinities. The antibody exhibits high binding affinity for IFNα/IFNω-IFNAR1 complexes while showing reduced affinity for IFNβ-IFNAR1 complexes, thereby changing the selectivity parameter to resolve the contradiction between disease treatment and preservation of antiviral/anti-tumor activities
2Object-affected harmful factors
If broad-spectrum anti-IFNAR1 antibodies are used to treat autoimmune diseases, then disease symptoms are reduced, but beneficial immune responses are compromised
Solution Approach 1:
The antibody exhibits localized specificity toward pathological IFN signals by recognizing conformational epitopes on IFNAR1 that are formed or exposed during binding of IFNα or IFNω, but not during IFNβ binding. This local differentiation in binding specificity allows selective suppression of harmful immune responses while preserving beneficial ones
Solution Approach 2:
The invention changes the selectivity parameter of anti-IFNAR1 antibodies through CDR optimization, creating a differential binding profile that preferentially inhibits IFNα/IFNω-mediated autoimmune pathology while maintaining IFNβ-mediated protective immune responses
3Object-affected harmful factors
If IFNβ-mediated activities are preserved for antiviral protection, then viral replication is inhibited, but type I IFN-related disease pathogenesis is not addressed
Solution Approach 1:
The antibody is designed with CDR regions that specifically recognize epitopes on IFNAR1 accessible during IFNα/IFNω binding, creating a local binding preference that spares IFNβ-mediated antiviral protection while targeting IFNα/IFNω-mediated disease pathogenesis
Solution Approach 2:
The invention optimizes the binding affinity parameters of the antibody toward different IFN-IFNAR1 complexes, creating a selective inhibition profile where IFNα/IFNω binding is blocked (addressing disease pathogenesis) while IFNβ binding remains unaffected (preserving antiviral protection)
Data Source
AI summary
Provided are anti-IFNAR1 antibodies or antigen-binding fragments thereof, isolated poly nucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.