Fc-Linked VEGF Inhibitors for Longer-Acting Intravitreal Therapy

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Solution Overview

Problem

Current anti-VEGF agents for treating intraocular neovascular disorders have a short half-life, necessitating frequent injections and suboptimal clinical outcomes due to insufficient pharmacokinetics.

Innovation Solution

Development of an anti-VEGF agent comprising a VEGF binding portion operatively linked to an Fc-IgG, incorporating specific IgG-like domains of VEGFR-1 with enhanced heparin-binding characteristics to extend the therapeutic half-life and efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If current anti-VEGF agents are used for treating intraocular neovascular disorders, then the treatment can be administered, but the half-life is short requiring frequent injections

Engineering Contradiction:

Improvehalf-life of anti-VEGF agentVSAvoidfrequency of injections

Core Design Contradiction:

Duration of action of moving objectVSEase of operation

Solution Approach 1:

The patent creates a composite molecular structure by fusing VEGF binding domains (IgG-like domains 2 and 3 of VEGFR-1) with an Fc fragment of human IgG1. This composite construction combines the VEGF-inhibiting capability of the VEGFR-1 domains with the extended half-life properties of the Fc region, resulting in an agent with prolonged duration of action and reduced injection frequency

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent modifies the molecular parameters of anti-VEGF agents by incorporating specific IgG-like domains with enhanced heparin-binding characteristics. This parameter change in the molecular structure increases the half-life of the therapeutic agent in the eye, allowing for less frequent administration while maintaining efficacy

Inventive Principle:

Principle #35Parameter changes

2Reliability

If current anti-VEGF agents are used, then treatment can be provided, but clinical outcomes are suboptimal due to insufficient pharmacokinetics

Engineering Contradiction:

Improveclinical outcomesVSAvoidpharmacokinetic half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The fusion construct combines VEGF binding domains from VEGFR-1 with the Fc region of IgG1, creating a composite molecule that leverages the high-affinity VEGF binding of the receptor domains and the extended circulation half-life of the Fc region, thereby improving both pharmacokinetics and clinical outcomes

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The Fc-IgG portion acts as an intermediary that extends the half-life of the VEGF binding portion. By linking the VEGF-inhibiting domains to the Fc region, the molecule gains prolonged persistence in the eye, improving reliability of treatment outcomes

Inventive Principle:

Principle #24Intermediary (Mediator)

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 agent provides prolonged efficacy with reduced frequency of intravitreal injections, effectively inhibiting angiogenesis and treating conditions like age-related macular degeneration and diabetic retinopathy by maintaining therapeutic levels for extended periods.

Implementation Method 1

VEGF binds both VEGFR1 and VEGFR2... The agent provides prolonged efficacy with reduced frequency of intravitreal injections, effectively inhibiting angiogenesis

Methodology Applied

Scientific EffectProtein-ligand binding:

Implementation Method 2

incorporating specific IgG-like domains of VEGFR-1 with enhanced heparin-binding characteristics to extend the therapeutic half-life and efficacy

Methodology Applied

Scientific EffectHeparin-binding interaction:

Data Source

PatentUS12514904B2Long-acting VEGF inhibitors for intraocular neovascularization

Publication Date: 2026.01.06 RGT UNIV OF CALIFORNIA

AI summary

Compositions and methods for treating a VEGF-related ophthalmic disorder in a subject in need comprising, administering intravitreally to the subject a therapeutically effective amount of an anti-VEGF agent, comprising a VEGF binding portion operatively linked to a Fc-IgG, wherein the VEGF binding portion comprises at least one VEGF binding domain that is an IgG-like domain 2 of VEGFR-1.