Humanized Anti-IL-17A Antibody Affinity and Half-Life
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Solution Overview
Problem
Current anti-IL-17A antibodies have limitations in terms of affinity and half-life, which affect their efficacy in treating inflammatory and autoimmune diseases.
Innovation Solution
Development of an anti-IL-17A antibody with higher affinity and longer half-life, comprising specific combinations of light and heavy chain variable regions and constant regions, optimized for binding to IL-17A, and expressed using vectors for secretion and use in pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-IL-17A antibodies are used, then IL-17 activity can be blocked, but the affinity and half-life are insufficient, limiting therapeutic efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through humanization - replacing murine constant regions with human constant regions (IgG1, IgG2, IgG3, or IgG4) while maintaining the variable regions that bind IL-17A. This structural parameter change optimizes the antibody's pharmacokinetic properties, extending half-life and improving therapeutic efficacy by reducing immunogenicity and enhancing Fc-mediated functions.
Solution Approach 2:
The invention creates composite antibody structures by combining humanized variable regions (from murine antibodies) with human constant regions. This composite structure integrates the high affinity binding capability of the murine-derived variable regions with the optimized pharmacokinetic and effector functions of human constant regions, achieving both high affinity and extended half-life.
2Strength
If current anti-IL-17A antibodies are used, then IL-17 activity can be blocked, but the affinity is insufficient, affecting binding strength
Solution Approach 1:
The patent extracts and preserves the critical binding-determining variable regions from the murine antibody while removing the immunogenic constant regions. By taking out only the essential antigen-binding portions (variable regions) and combining them with human constant regions, the invention maintains high affinity for IL-17A while reducing immunogenicity, thereby improving therapeutic efficacy.
Solution Approach 2:
The invention changes the structural parameters of the antibody by humanizing the constant regions while maintaining the variable regions intact. This parameter change preserves the high-affinity binding characteristics determined by the variable regions while modifying the constant regions to optimize pharmacokinetics and reduce immunogenicity, thereby maintaining both affinity and therapeutic efficacy.
3Adaptability or versatility
If murine antibodies are used, then IL-17A binding can be achieved, but immunogenicity is high, limiting clinical application
Solution Approach 1:
The patent applies parameter changes by transforming the antibody from a fully murine structure to a humanized structure with human constant regions. This parameter change in the amino acid sequence composition significantly reduces immunogenicity while maintaining the antigen-binding capability, thereby enabling clinical application in human patients.
Solution Approach 2:
The invention uses human constant regions as an intermediary between the murine variable regions and the human immune system. The human constant regions serve as a bridge that reduces immunogenicity and improves compatibility with human physiology, while the murine-derived variable regions maintain the necessary binding affinity for IL-17A.
Data Source
AI summary
Provided is an antibody capable of specially recognizing IL-17A and being combined with IL-17A. The antibody can be used for treating inflammations and autoimmune diseases caused by high expression of interleukin-17A, such as psoriasis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, inflammatory arthritis.