Camelid-Derived IL-6 Binding Molecules for Reduced Immunogenicity
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Solution Overview
Problem
Current IL-6 binding molecules derived from non-human animals require extensive antibody engineering to reduce immunogenicity and often exhibit sub-optimal binding affinity, necessitating further engineering for improved performance.
Innovation Solution
Development of camelid-derived binding molecules with high human homology and canonical fold structures, specifically designed to bind IL-6 with high affinity, which are minimally engineered and exhibit improved manufacturability and thermal stability, thereby effectively inhibiting IL-6 biological activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If IL-6 binding molecules are derived from non-human animals, then binding specificity to IL-6 is achieved, but immunogenicity increases and extensive antibody engineering is required
Solution Approach 1:
The patent changes the species parameter from traditional non-human animals to camelids (llamas, alpacas, camels), which naturally produce antibodies with high human homology. This parameter change reduces immunogenicity while maintaining binding specificity, eliminating the need for extensive humanization engineering.
Solution Approach 2:
The patent uses camelid antibodies as a template or copy that naturally exhibits human-like characteristics. By leveraging the natural properties of camelid immunoglobulins, the invention creates binding molecules that replicate human antibody behavior without requiring extensive engineering modifications.
2Object-affected harmful factors
If extensive antibody engineering is performed to reduce immunogenicity, then human homology improves, but binding affinity deteriorates and further engineering is required
Solution Approach 1:
The patent performs preliminary selection of camelid antibodies that naturally exhibit high human homology and binding affinity before any engineering begins. This preliminary action identifies starting points that require minimal or no further engineering to achieve therapeutic criteria.
Solution Approach 2:
The camelid antibodies inherently possess the desired properties of high human homology and binding affinity without requiring external engineering intervention. The natural characteristics of camelid immunoglobulins serve the functional requirements themselves, eliminating the need for additional humanization steps that would compromise affinity.
3Reliability
If traditional IL-6 antibodies are used, then binding activity is achieved, but manufacturing complexity and time requirements increase
Solution Approach 1:
The patent extracts and utilizes the naturally occurring high-affinity binding capability from camelid antibodies, removing the time-consuming steps of humanization engineering. By taking out the essential binding function from the complex engineering process, the invention achieves therapeutic antibodies much faster.
4Reliability
If IL-6 binding molecules are engineered to improve binding affinity, then affinity increases, but manufacturing feasibility decreases
Solution Approach 1:
The patent changes the source organism parameter to camelids, which produce antibodies with naturally high binding affinity and favorable manufacturing characteristics. This parameter change simultaneously achieves high affinity and ease of manufacture, as camelid antibodies are known for their stability and expressibility in conventional systems.
Data Source
AI summary
The present invention provides binding molecules (e.g., antibodies or antigen binding fragments thereof) that specifically bind to and inhibit the biological activity of IL-6 (e.g., human, mouse and non-human primate IL-6). In a preferred embodiment, the antibodies or antigen binding fragments of the invention bind to IL-6 and inhibit its binding to an IL-6 receptor. Such antibodies or antigen binding fragments are particularly useful for treating IL-6-associated diseases or disorders (e.g., inflammatory disease and cancer).