IL-36 Ocular Composition for Vascular Leakage Stabilization
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Solution Overview
Problem
Current anti-VEGF therapies for ocular disorders such as AMD, diabetic retinopathy, and macular oedema are less effective in stabilizing vascular leakage and proliferation, and long-term use can cause retinal degeneration, necessitating the development of alternative therapeutic approaches that target specific signal transduction cascades to reduce side effects.
Innovation Solution
The use of IL-36 and/or IL-18 compositions to treat or prophylaxis ocular disorders, optionally combined with anti-VEGF agents, to enhance endothelial cell barrier function and reduce vascular permeability, including administration routes like intraocular and intravitreal.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-VEGF agents are used to treat ocular disorders, then vascular leakage and proliferation are stabilized, but long-term use causes retinal degeneration and reduces treatment effectiveness
Solution Approach 1:
The patent segments the VEGF signaling pathway targeting by using IL-36 and IL-18 to specifically modulate VEGFR2-mediated angiogenesis and vascular permeability, while preserving VEGFR1-mediated neuronal survival functions. This selective segmentation allows treatment of vascular pathology without harming retinal neurons.
Solution Approach 2:
The patent introduces IL-36 and IL-18 as intermediary cytokines that indirectly regulate VEGF signaling through modulation of endothelial cell function and VEGF expression, rather than directly blocking VEGF or its receptors. This intermediary approach provides more nuanced control over the VEGF pathway.
2Object-generated harmful factors
If anti-VEGF therapies are used to treat ocular disorders, then neovascularization is inhibited, but vascular permeability stabilization is reduced
Solution Approach 1:
The patent applies local quality by targeting specific functional aspects of the VEGF pathway through IL-36 and IL-18, which preferentially affect VEGFR2-mediated processes (angiogenesis and vascular permeability) while sparing VEGFR1-mediated functions. This creates differential effects on various pathological processes.
Solution Approach 2:
The patent changes the therapeutic parameter from direct VEGF inhibition to cytokine-mediated modulation of VEGF signaling. IL-36 and IL-18 alter the biological parameters of endothelial cell function, VEGF expression, and receptor signaling dynamics, providing more comprehensive control over both neovascularization and vascular permeability.
3Duration of action of stationary object
If regular monthly intraocular injections of anti-VEGF agents are administered, then choroidal neovascularization is stabilized, but treatment refractoriness develops over time
Solution Approach 1:
The patent inverts the conventional approach by instead of inhibiting VEGF signaling, using IL-36 and IL-18 to modulate and regulate VEGF pathway activity. This inverse approach of activation/modulation rather than inhibition provides alternative mechanisms of action that bypass resistance to anti-VEGF therapies.
Solution Approach 2:
The patent fundamentally changes the therapeutic parameter from VEGF inhibition to cytokine-mediated VEGF pathway modulation. This parameter change introduces new biological mechanisms that are not subject to the same resistance patterns as anti-VEGF agents, potentially restoring treatment responsiveness.
Data Source
Figure 1A~1B
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Figure 2A~2C
AI summary
The present invention relates to a composition comprising IL-36 and/or IL-18 for use in treating ocular disorders such as age-related macular degeneration (AMD), macular oedema, retinopathy, diabetic retinopathy, and glaucoma. The present invention also relates to a method of identifying patients likely to respond to an anti-VEGF agent.