Non-Aqueous Anti-VEGF Ophthalmic Composition for Stable Dosing

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Solution Overview

Problem

Current medical approaches for treating ocular neovascularization, particularly corneal neovascularization, face challenges such as lack of long-term efficacy, potential graft rejection in corneal transplants, and insurance coverage issues with anti-VEGF therapy, while existing anti-VEGF formulations suffer from instability and aggregation, leading to dosing inaccuracies and adverse reactions.

Innovation Solution

A non-aqueous ophthalmic composition comprising particles of anti-VEGF proteins, such as aflibercept or bevacizumab, suspended in a semifluorinated alkane liquid vehicle, which stabilizes the proteins and prevents aggregation, maintaining biological activity and enabling precise dosing for effective treatment of ocular neovascularization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-VEGF proteins are formulated in aqueous solutions for topical administration, then they show good short-term safety and efficacy in reducing corneal neovascularization, but they suffer from instability and aggregation leading to dosing inaccuracies and adverse reactions

Engineering Contradiction:

Improvestability of anti-VEGF proteinVSAvoiddosing accuracy

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the physical-chemical parameters of the formulation by transitioning from aqueous to non-aqueous medium. This parameter change fundamentally alters the stability characteristics of the anti-VEGF protein, preventing aggregation while maintaining biological activity, thereby resolving the contradiction between reliability and dosing accuracy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs an inert non-aqueous environment (such as fluorinated alcohols or other biocompatible non-aqueous solvents) to protect the anti-VEGF protein from degradation and aggregation. This inert environment prevents harmful interactions that occur in aqueous solutions, ensuring both stability and dosing accuracy

Inventive Principle:

Principle #39Inert atmosphere (Inert environment)

2Reliability

If anti-VEGF therapy is used for corneal neovascularization treatment, then efficacy in inhibiting blood vessel growth is achieved, but insurance coverage may be denied and special consents are required

Engineering Contradiction:

Improveefficacy of treatmentVSAvoidaccessibility of treatment

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent develops a topical formulation that can be administered as eye drops, which is a simpler, more accessible delivery method compared to intravitreal injections. This disposable-like topical application reduces procedural complexity and cost, potentially improving insurance coverage and accessibility while maintaining treatment efficacy

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If monoclonal anti-VEGF antibodies are administered topically or subconjunctivally, then short-term safety and efficacy are demonstrated, but long-term data are lacking

Engineering Contradiction:

Improveshort-term efficacyVSAvoidlong-term efficacy data

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent employs sustained-release mechanisms or stabilizing formulations that maintain therapeutic levels of anti-VEGF protein over extended periods. This preliminary structuring of the formulation ensures long-term stability and efficacy, providing the necessary long-term data without requiring repeated short-term administrations

Inventive Principle:

Principle #10Preliminary action

4Object-affected harmful factors

If corneal neovascularization is present in patients undergoing corneal transplants, then the risk of graft rejection is greatly elevated, but current treatments do not sufficiently prevent this outcome

Engineering Contradiction:

Improverisk of graft rejectionVSAvoidprevention of graft rejection

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies anti-VEGF therapy prior to and during the corneal transplant process to prevent neovascularization from developing. This preliminary anti-action blocks the angiogenic pathways before they can compromise the graft, significantly reducing rejection risk and improving transplant outcomes

Inventive Principle:

Principle #9Preliminary anti-action

Data Source

PatentUS12397039B2Compositions and methods for the treatment of ocular neovascularization

Publication Date: 2025.08.26 NOVALIQ GMBH

AI summary

The present invention relates to a non-aqueous ophthalmic composition comprising particles of a protein powder preparation suspended in a liquid vehicle comprising a semifluorinated alkane, wherein the particles of the protein powder preparation comprise an anti-VEGF protein selected from aflibercept or a sequence having at least 90% sequence identity to SEQ ID NO: 1. The composition is particularly suitable for the treatment of ocular neovascularization.