Fyn SH3 Domain Polypeptides for IL-17A Binding
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Solution Overview
Problem
Current anti-IL-17 antibodies have drawbacks such as complex mammalian cell production, instability, aggregation, limited solubility, and potential immune responses, necessitating the development of alternative high-affinity and specific IL-17A binding molecules for therapeutic applications.
Innovation Solution
Polypeptides with specific amino acid sequences derived from the human Fyn SH3 domain, which are stable, non-immunogenic, and can be expressed in bacteria, binding specifically to IL-17A with high affinity and inhibiting its activity, are developed for therapeutic and diagnostic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-IL-17 antibodies are used for therapeutic applications, then high affinity and specificity for IL-17A is achieved, but complex mammalian cell production and instability occur
Solution Approach 1:
The patent uses Fyn SH3 domain as a simplified copy or surrogate structure to replace the complex antibody molecule. The Fyn SH3 domain is a small, stable protein fold that can be produced in bacteria and engineered to bind IL-17A with high affinity, thus copying the binding function of antibodies without their production complexity and instability issues
Solution Approach 2:
The patent modifies the Fyn SH3 domain structure through site-directed mutagenesis to optimize binding affinity for IL-17A. Specific amino acid residues in the Fyn SH3 domain are mutated to enhance interactions with IL-17A, achieving high affinity binding while maintaining the simplicity and stability of the Fyn SH3 domain scaffold
2Reliability
If anti-IL-17 antibodies are used, then high affinity binding to IL-17A is achieved, but aggregation and limited solubility occur
Solution Approach 1:
The Fyn SH3 domain serves as a simplified structural copy that replaces the large, aggregation-prone antibody structure. The Fyn SH3 domain is inherently soluble and stable, providing a compact alternative that maintains binding function while eliminating aggregation issues associated with antibodies
Solution Approach 2:
The Fyn SH3 domain is a small, stable protein that can be produced recombinantly in bacteria at low cost. It is engineered to be highly stable and soluble, serving as a disposable binding reagent that does not aggregate or require complex stabilization measures needed for antibodies
3Reliability
If anti-IL-17 antibodies are used for therapeutic applications, then neutralization of IL-17A is achieved, but potential immune responses occur
Solution Approach 1:
The Fyn SH3 domain-based binders are non-immunogenic copies that perform the therapeutic function of IL-17A neutralization without triggering immune responses. Being derived from a human protein domain, they are tolerated by the host immune system, unlike foreign antibodies that may elicit immune reactions
Solution Approach 2:
The Fyn SH3 domain is a human protein domain that naturally occurs in the body, so using it as a therapeutic agent allows the body to recognize it as self rather than foreign. This self-service approach eliminates the risk of immune responses while maintaining therapeutic efficacy through IL-17A neutralization
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
These polypeptides demonstrate high specificity and affinity for IL-17A, inhibiting its function effectively and are stable in solution and in vivo, making them suitable for research, diagnostic, and medical treatments for IL-17A-mediated diseases.
Implementation Method 1
Polypeptides with specific amino acid sequences derived from the human Fyn SH3 domain... binding specifically to IL-17A with high affinity and inhibiting its activity
Data Source
Figure 1a~1B
Figure 2a~2g
Figure 3a~3f
AI summary
The present invention relates to new IL-17 inhibiting polypeptides, corresponding fusion proteins, compositions and medical uses thereof.