Human IL-23 Binding Proteins Targeting p19 Subunit
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies lack fully human therapeutic agents that specifically inhibit native human IL-23, necessitating the development of IL-23 antagonists that can effectively target IL-23 without affecting IL-12, to address autoimmune and inflammatory diseases.
Innovation Solution
Development of human IL-23 antigen binding proteins that bind specifically to the unique p19 subunit of IL-23, reducing or inhibiting its biological responses, including the use of antibodies and antibody fragments that are fully human and highly specific for IL-23, allowing for reduced dosing and increased efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies use non-human or partially human therapeutic agents, then IL-23 inhibition can be achieved, but safety profile and efficacy are compromised compared to fully human agents
Solution Approach 1:
The patent changes the fundamental parameter of antibody humanization by developing fully human IL-23 antigen binding proteins through techniques such as phage display libraries and transgenic mouse models. This transformation from non-human to fully human antibodies improves safety profile by eliminating immunogenicity concerns while maintaining therapeutic efficacy against IL-23.
2Reliability
If dual inhibition of IL-12 and IL-23 is used, then broader anti-inflammatory effect is achieved, but safety profile deteriorates due to off-target effects
Solution Approach 1:
The patent segments the IL-12/IL-23 heterodimeric cytokine system by developing antibodies that specifically target the unique p19 subunit of IL-23 while sparing the p35 subunit of IL-12. This selective segmentation allows inhibition of IL-23-mediated inflammation without affecting IL-12 functions, improving safety while maintaining anti-inflammatory efficacy through precise molecular discrimination.
Solution Approach 2:
The antigen binding proteins exhibit local quality by demonstrating high specificity for the p19 subunit epitope of IL-23. The antibodies are engineered to recognize and bind exclusively to IL-23's unique subunit, creating a localized therapeutic effect at the molecular level that spares IL-12 and other cytokines, thereby improving the safety profile while maintaining targeted anti-inflammatory activity.
3Productivity
If high doses of IL-23 inhibitors are administered, then therapeutic efficacy is improved, but dosing frequency and treatment complexity increase
Solution Approach 1:
The patent develops antibody fragments and engineered variants that, while potentially having shorter half-lives, can be administered at lower doses due to their high specificity and affinity for IL-23. This approach trades off the longevity of full IgG molecules for the benefits of reduced dosing volume and simplified formulation, potentially improving ease of administration while maintaining therapeutic efficacy through precise target engagement.
Data Source
AI summary
Antigen binding proteins that bind to human IL-23 protein are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same as well as use of IL-23 antigen binding proteins for diagnostic and therapeutic purposes are also provided.