Anti-C2 Antibodies With pH-Dependent Binding for Complement Control
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Solution Overview
Problem
The complement system's over-activation and/or under-regulation, particularly involving complement component 2 (C2), can lead to autoimmune diseases affecting multiple organ systems, disrupting the balance between immune activation and regulation and causing neurological and skin diseases.
Innovation Solution
Development of anti-C2 antibodies and their fragments, including pH-dependent binding to C2 and C2a, which can modulate the activity of the classical and lectin pathways by targeting C2.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-C2 antibodies are designed to bind to C2 at neutral pH to inhibit complement activation, then autoimmune disease treatment is improved, but the antibodies may also bind to C2 at low pH causing unwanted effects
Solution Approach 1:
The patent applies parameter changes by designing antibodies with pH-dependent binding characteristics. The antibodies are engineered to have high affinity for C2 at neutral pH (physiological conditions) to effectively inhibit complement activation, while exhibiting low affinity at acidic pH (endosomal conditions), allowing them to be released and degraded without unwanted effects. This is achieved through specific amino acid sequence modifications in the CDR regions that confer pH-sensitive binding properties.
2Reliability
If conventional antibodies are used to target C2, then complement over-activation can be inhibited, but the complexity of developing antibodies with specific pH-dependent properties increases
Solution Approach 1:
The patent simplifies the design process by focusing parameter changes on specific CDR regions (particularly CDR1 and CDR2 of the heavy chain and CDR1 of the light chain) that are known to influence pH-dependent binding. This targeted approach reduces the overall design complexity compared to modifying the entire antibody structure, while still achieving the desired pH-selective binding characteristics.
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 anti-C2 antibodies help restore the balance of complement activation and regulation, potentially reducing the severity of autoimmune diseases by inhibiting excessive complement activity.
Implementation Method 1
anti-C2 antibodies having pH-dependent binding to C2 and C2a
Data Source
AI summary
This invention relates to inhibition of the complement signaling using an anti-C2 antibody or a fragment thereof. Specifically, the invention relates to methods of treating a complement-mediated disease or complement-mediated disorder in an individual by contacting the individual with the anti-C2 antibody or a fragment thereof.