IL-18 Binding Proteins Neutralize Inflammatory Cytokines
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Solution Overview
Problem
Current treatments for acute and chronic inflammatory diseases do not effectively address the inflammatory responses mediated by interleukin-18 (IL-18), which plays a significant role in immune responses and inflammation.
Innovation Solution
Development of human antibodies and binding proteins that specifically bind to IL-18 with high affinity, neutralizing its activity and inhibiting its binding to its receptor, thereby regulating gene expression and reducing inflammatory responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for acute and chronic inflammatory diseases are used, then existing therapies can be maintained, but they do not effectively address the inflammatory responses mediated by IL-18
Solution Approach 1:
The patent introduces IL-18 binding proteins (including antibodies, Fab fragments, and F(ab')2 fragments) as intermediary substances that mediate the interaction between IL-18 and its receptor. These binding proteins selectively bind to IL-18, preventing it from activating its receptor and thereby blocking the pro-inflammatory signaling pathway. This intermediary approach allows targeted intervention in IL-18 mediated inflammation without affecting other cytokine pathways.
Solution Approach 2:
The patent modifies the binding characteristics and affinity parameters of the binding proteins to optimize their effectiveness. By engineering antibodies and fragments with specific affinity constants and binding kinetics, the treatment can effectively capture IL-18 at physiological concentrations. The patent also explores different isotypes and molecular weights of the binding proteins to achieve optimal pharmacokinetic parameters for therapeutic use.
2Object-affected harmful factors
If IL-18 binding proteins are developed to neutralize IL-18 activity, then inflammatory responses can be reduced, but the complexity of the therapeutic approach increases
Solution Approach 1:
The patent segments the full-length antibody into functional fragments (Fab and F(ab')2) that retain the critical IL-18 binding capability while reducing molecular size and simplifying the therapeutic molecule. This segmentation allows for easier production, better pharmacokinetics, and reduced immunogenicity while maintaining the core function of neutralizing IL-18. The patent also considers using single-chain variable fragments (scFv) and other mini-antibody formats to further simplify the therapeutic approach.
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 antibodies effectively neutralize IL-18 activity, providing a therapeutic approach to manage inflammatory diseases by modulating immune responses and reducing inflammation.
Implementation Method 1
a binding protein comprising an antigen binding domain capable of binding human IL-18
Implementation Method 2
the antibodies effectively neutralize IL-18 activity, providing a therapeutic approach to manage inflammatory diseases
Data Source
AI summary
The present invention encompasses IL-18 binding proteins, particularly antibodies that bind human interleukin-18 (hIL-18). Specifically, the invention relates to antibodies that are entirely human antibodies. Preferred antibodies have high affinity for hIL-18 and/or that neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-18 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.