Adnectin Scaffold Proteins for IL-23 Binding
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Solution Overview
Problem
Current therapies lack effective solutions for targeting IL-23, a cytokine involved in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis, due to its role in promoting inflammatory responses through Th17 cells.
Innovation Solution
Development of Adnectins, a class of fibronectin-based scaffold proteins specifically designed to bind the p19 subunit of IL-23, utilizing randomized or mutated solvent-accessible loops in the Fn3 domain for high affinity and stability, and incorporating pharmacokinetic moieties like PEG for extended serum half-life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies are used to target IL-23, then specific binding can be achieved, but structural stability and solubility are compromised under certain conditions
Solution Approach 1:
The patent changes the fundamental parameters of the binding protein by replacing conventional antibody structures with fibronectin type III domain-based proteins. This structural parameter change maintains binding specificity through engineered loop regions while improving structural stability and solubility characteristics of the Fn3 domain scaffold under various physiological conditions
Solution Approach 2:
The invention creates a composite therapeutic approach by combining the IL-23 binding Fn3 domain protein with PEG (polyethylene glycol) pharmacokinetic moieties. This composite structure enhances both the binding function and the pharmacokinetic properties including serum half-life, creating a more effective therapeutic agent
2Duration of action of moving object
If short-acting therapeutic molecules are used, then rapid clearance occurs, but prolonged therapeutic effect is not achieved
Solution Approach 1:
The patent introduces PEG (polyethylene glycol) as a pharmacokinetic intermediary moiety attached to the IL-23 binding Fn3 domain protein. This PEG intermediary acts as a mediator that extends the serum half-life of the therapeutic molecule by reducing renal clearance and protecting from proteolytic degradation, thereby enabling prolonged therapeutic effect without compromising binding productivity
Data Source
AI summary
The present invention relates to fibronectin based scaffold domain protein that bind interleukin 23 (IL-23), specifically the p19 subunit of IL-23. The invention also relates to the use of the innovative proteins in therapeutic applications to treat autoimmune diseases. The invention further relates to cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative proteins.