VEGF Mini-Trap Molecules Oxidation for Reduced Dosing
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Solution Overview
Problem
Current VEGF inhibitors for treating angiogenic eye disorders, such as age-related macular degeneration and diabetic macular edema, require frequent intravitreal injections, which are painful and inconvenient, and may have adverse effects, necessitating the development of less frequent dosing options with comparable efficacy.
Innovation Solution
Development of VEGF mini-trap molecules, like REGN7483F, with specific domain structures and post-translational modifications, which are designed to bind VEGF and have a shorter systemic half-life, potentially reducing adverse events and allowing fewer dosing events while maintaining therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If VEGF inhibitors are administered via frequent intravitreal injection, then therapeutic efficacy is maintained, but patient comfort deteriorates and adverse effects increase
Solution Approach 1:
The patent applies parameter changes by modifying the molecular structure of VEGF inhibitors through oxidation of histidine residues to 2-oxo-histidine and dioxidation of tryptophan residues. These chemical modifications alter the pharmacokinetic properties of the drug, specifically reducing systemic half-life while maintaining ocular efficacy, thereby enabling less frequent dosing and reducing injection-related adverse effects
2Ease of operation
If dosing frequency is reduced, then patient convenience is improved, but therapeutic efficacy may deteriorate
Solution Approach 1:
The patent modifies drug parameters through chemical oxidation to achieve a shorter systemic half-life that correlates with reduced dosing frequency. The oxidized form maintains sufficient ocular retention to preserve therapeutic efficacy while allowing extended dosing intervals, thus improving patient convenience without sacrificing treatment effectiveness
3Duration of action of moving object
If higher molar amounts of VEGF mini-trap are used, then dosing frequency can be reduced, but drug concentration requirements increase
Solution Approach 1:
The patent employs parameter changes by chemically modifying the VEGF trap structure through oxidation, which alters its pharmacokinetic behavior. The oxidized VEGF mini-trap achieves extended duration of action with higher molar amounts, allowing less frequent dosing while maintaining therapeutic efficacy through sustained VEGF inhibition
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
The VEGF mini-trap molecules provide effective inhibition of VEGF-mediated angiogenesis with fewer dosing events, potentially reducing pain and adverse effects associated with frequent intravitreal injections, while maintaining high therapeutic efficacy.
Implementation Method 1
one or more histidines of said VEGF mini-trap are oxidized to 2-oxo-histidine
Implementation Method 2
one or more tryptophans are dioxidated (e.g., to N-formylkynurenine) or oxidized to hydroxytryptophan or di-hydroxytrypophan or tri-hydroxyl tryptophan
Implementation Method 3
one or more asparagines thereof are glycosylated
Data Source
AI summary
The present invention provides VEGF mini-trap molecules and method of treating or preventing angiogenic disorders such as angiogenic eye disorders and cancer.