IL-1 Binding Proteins DVD-Ig Multivalent Neutralization
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Solution Overview
Problem
There is a need for improved binding proteins that can effectively neutralize the activity of IL-1 in inflammatory responses and autoimmune disorders, as existing antibodies have limitations in mediating or detecting IL-1β.
Innovation Solution
Development of proteins that bind specifically to human IL-1α and IL-1β, including antibodies and multivalent binding proteins like DVD-Ig™, with defined antigen-binding domains and CDR sequences, capable of modulating IL-1 biological functions and neutralizing its activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to bind IL-1, then IL-1 binding is achieved, but the ability to effectively neutralize IL-1 activity in inflammatory responses and autoimmune disorders is insufficient
Solution Approach 1:
The patent describes binding proteins capable of binding both IL-1α and IL-1β isoforms through a single molecular structure. The binding protein comprises a heavy chain variable domain and light chain variable domain that can simultaneously recognize and bind to both IL-1 isoforms, providing universal neutralization activity against multiple IL-1 forms that would otherwise require separate antibodies
Solution Approach 2:
The patent employs affinity maturation techniques to optimize specific complementarity determining regions (CDRs) within the binding protein. By locally modifying the CDR sequences in the heavy and light chain variable domains, the binding protein achieves enhanced neutralization efficacy while maintaining its ability to bind both IL-1α and IL-1β isoforms
2Reliability
If binding proteins with high neutralization capability are developed, then therapeutic effectiveness improves, but the complexity of defining and producing specific antigen-binding domains increases
Solution Approach 1:
The binding protein is constructed from segmented modular components: a heavy chain variable domain (VH) and a light chain variable domain (VL), each containing three complementarity determining regions (CDR1, CDR2, CDR3). This segmentation allows for systematic design and production while maintaining high neutralization capability through optimized CDR sequences
Solution Approach 2:
The patent utilizes affinity maturation to systematically modify the amino acid sequences of the CDR regions, changing the binding parameters of the antigen-binding domains. By optimizing the CDR sequences through iterative mutation and selection, the binding protein achieves enhanced neutralization effectiveness while maintaining a defined and producible structure
Data Source
AI summary
The disclosure provides binding proteins that specifically bind to IL-1α and IL-1β. These binding proteins can be organized into DVD-Igs. These proteins can be used to modulate the activity of IL-1α and/or IL-1β and can be used for the treatment immunological diseases such as rheumatoid arthritis, osteoarthritis, psoriasis, multiple sclerosis, and other autoimmune diseases. In addition, their uses in the amelioration and/or treatment of pain in an individual suffering from a disease or disorder associated with IL-1 accumulation.