IL-22 Derivatives Fatty Acid Modification Half-Life
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Solution Overview
Problem
Current methods for extending the half-life of Interleukin-22 (IL-22) for clinical use, such as Fc fusion and PEGylation, face issues with immunogenicity, decreased activity, and altered pharmacokinetic properties, and there is a need for biocompatible modifiers that maintain potency and avoid adverse reactions.
Innovation Solution
Derivatives of IL-22 with a fatty acid covalently attached to the protein, specifically at positions 95 or 106, using a linker, which maintains the native protein's properties and provides a prolonged half-life without significant immunogenicity or toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If Fc fusion is used to extend the half-life of IL-22, then the circulatory half-life is prolonged, but the protein structure is significantly altered and immunogenicity increases
Solution Approach 1:
The patent changes the molecular weight parameter of IL-22 by attaching fatty acid chains (C12-C24) to the protein, increasing it from 17 kDa to above 70 kDa. This parameter change allows the protein to evade renal clearance and achieve prolonged half-life without using Fc fusion, thereby avoiding the immunogenicity issue associated with Fc fusion technology
Solution Approach 2:
The patent creates a composite structure by covalently attaching fatty acid chains to the IL-22 protein backbone. This composite material approach combines the biological activity of IL-22 with the hydrophobic properties of fatty acids, achieving both prolonged circulation time and maintained potency without the immunogenicity problems of Fc fusion
2Duration of action of moving object
If PEGylation is used to extend the half-life of IL-22, then the circulatory half-life is prolonged, but the protein activity decreases and heterogeneity increases
Solution Approach 1:
The patent changes the hydrophobicity parameter of IL-22 by attaching fatty acid chains, which naturally occur in biological systems. Unlike PEGylation which adds foreign polymer chains, fatty acid modification maintains the protein's native-like properties and biological recognition, thereby preserving protein activity while achieving prolonged half-life
Solution Approach 2:
The patent attaches fatty acid chains at specific locations on the IL-22 protein structure rather than random modification. This localized modification approach ensures that the active sites and functional regions of the protein remain intact and accessible, maintaining protein activity while achieving the desired pharmacokinetic improvements
3Duration of action of moving object
If Fc fusion is used to extend the half-life of IL-22, then the circulatory half-life is prolonged, but the diffusion rate and receptor engagement kinetics are affected
Solution Approach 1:
The patent optimizes the molecular weight parameter by attaching fatty acid chains to increase size above the renal clearance threshold (70 kDa) while avoiding excessive enlargement. This moderate parameter change achieves prolonged half-life without significantly impacting diffusion rate and receptor engagement kinetics, unlike the substantial structural change caused by Fc fusion
4Duration of action of moving object
If Fc fusion is used to extend the half-life of IL-22, then the circulatory half-life is prolonged, but steric hindrance reduces potency
Solution Approach 1:
The patent attaches fatty acid chains at specific peripheral locations on the IL-22 protein structure, keeping the modification sites away from the active binding regions. This local quality approach ensures that the core functional domains remain accessible and unaffected, maintaining high potency while achieving prolonged circulation time
Solution Approach 2:
The fatty acid chains act as intermediaries that extend the protein's circulation time without directly interfering with the receptor binding interface. Unlike Fc fusion which creates a large physical barrier, the fatty acid modifiers provide a subtle pharmacokinetic enhancement while preserving the protein's native interaction capabilities
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 fatty acid attachment to IL-22 derivatives results in high potency and prolonged circulatory half-life, allowing for optimal therapeutic effects in treating metabolic, liver, pulmonary, gut, kidney, CNS, and skin diseases while minimizing adverse reactions.
Implementation Method 1
a fatty acid covalently attached to an IL-22 protein
Data Source
AI summary
The invention relates to novel derivatives of Interleukin-22 (IL-22), particularly those comprising a fatty acid covalently attached to an IL-22 protein, wherein the IL-22 protein comprises at least one amino acid substitution, and their use in therapy.