AAV2 Capsid Variant for Sustained Anti-VEGF Expression

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Solution Overview

Problem

Current treatments for ocular neovascular diseases such as wet age-related macular degeneration (AMD) and diabetic retinopathy require frequent intravitreal injections of anti-VEGF agents, leading to compliance issues and increased risks of adverse effects.

Innovation Solution

Administration of a single unit dose of recombinant adeno-associated virus (rAAV) particles encoding an anti-VEGF agent, such as aflibercept, to the eye, which provides prolonged release and reduces the need for repeated injections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If frequent intravitreal injections of anti-VEGF agents are administered, then therapeutic effectiveness is maintained, but patient compliance deteriorates and adverse effects increase

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidpatient compliance

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies preliminary action by delivering anti-VEGF therapeutic agents via AAV vector before the disease progresses to severe stages, establishing long-term therapeutic effect that prevents future need for frequent injections. The single intravitreal injection at initiation establishes prolonged expression of therapeutic protein, eliminating the need for repeated administrations and improving patient compliance.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements continuity of useful action through AAV-mediated long-term expression of anti-VEGF agents. The viral vector integrates into host DNA and maintains continuous production of therapeutic protein throughout the patient's life, ensuring uninterrupted therapeutic effect without requiring repeated injections, thus resolving the compliance issue while maintaining therapeutic reliability.

Inventive Principle:

Principle #20Continuity of useful action

2Reliability

If repeated intravitreal injections are administered, then disease control is maintained, but the risk of adverse effects increases

Engineering Contradiction:

Improvedisease controlVSAvoidadverse effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by establishing long-term therapeutic expression through a single initial injection of AAV-anti-VEGF, preventing the need for repeated injections that would accumulate adverse effects. The therapeutic agent is delivered once and maintains effective disease control indefinitely, eliminating the progressive risk of adverse effects associated with repeated administrations.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements continuity of useful action through AAV-mediated sustained expression of anti-VEGF agents. The viral vector integrates into host DNA and maintains continuous production of therapeutic protein throughout the patient's life, ensuring uninterrupted therapeutic effect without requiring repeated injections, thus resolving the compliance issue while maintaining therapeutic reliability.

Inventive Principle:

Principle #20Continuity of useful action

3Loss of time

If single unit dose of rAAV particles is administered, then injection frequency is reduced, but initial therapeutic level may be insufficient

Engineering Contradiction:

Improveinjection frequencyVSAvoidtherapeutic agent delivery

Core Design Contradiction:

Loss of timeVSQuantity of substance

Solution Approach 1:

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The patent applies parameter changes by optimizing the AAV vector characteristics, including capsid serotype selection, promoter strength, and transgene copy number, to maximize therapeutic protein expression from a single injection. By carefully controlling these parameters, the patent achieves sufficient initial therapeutic levels that last indefinitely, eliminating the need for repeated dosing.

Inventive Principle:

Principle #35Parameter changes

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 method effectively stabilizes the disease, reduces retinal fluid, and maintains or improves visual acuity, potentially eliminating the need for rescue anti-VEGF treatments and reducing adverse effects associated with frequent injections.

Implementation Method 1

administering a single unit dose of a recombinant adeno associated virus (rAAV) particles encoding an anti-VEGF agent

Methodology Applied

Scientific EffectGene delivery:

Implementation Method 2

an AAV2 capsid protein comprising, or consisting of, an amino acid sequence LGETTRP (SEQ ID NO: 14) inserted between positions 587 and 588 of the capsid protein

Methodology Applied

Scientific EffectCapsid protein modification:

Data Source

PatentUS20250137011A1Methods of treating ocular neovascular diseases using AAV2 variants encoding aflibercept

Publication Date: 2025.05.01 ADVERUM BIOTECHNOLOGIES INC

AI summary

Provided are methods for treating an ocular neovascular disease in an individual, comprising administering a unit dose of recombinant adeno-associated virus (rAAV) particles to an eye of the individual, wherein the rAAV particles comprise: a) a nucleic acid encoding a polypeptide comprising an amino acid sequence with at least about 95% identity to the amino acid sequence of SEQ ID NO: 35 and flanked by AAV2 inverted terminal repeats (ITRs), and b) an AAV2 capsid protein comprising an amino acid sequence LGETTRP (SEQ ID NO: 14) inserted between positions 587 and 588 of the capsid protein, wherein the amino acid residue numbering corresponds to an AAV2 VP1 capsid protein.