Activated NK Cell Production for Retinal Neovascular Regression

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Solution Overview

Problem

Current treatments for retinal neovascular diseases such as AMD and DR, particularly anti-VEGF therapy, are limited by resistance development and ineffective in promoting regression of neovascular lesions, with a significant proportion of patients being refractory to treatment, necessitating a need for new therapeutic approaches.

Innovation Solution

A method involving the production of activated innate lymphoid cells, specifically natural killer cells, by contacting them with cytokines like IL-18, IL-12, IL-15, or IL-2 to enhance their activation and therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-VEGF therapy is used to treat retinal neovascular diseases, then vascular permeability is prevented, but treatment resistance develops and neovascular lesions do not regress

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidduration of treatment response

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the therapeutic parameter from anti-VEGF biologics to activated innate lymphoid cells (specifically NK cells) that produce interferon-gamma. This parameter change addresses treatment resistance and promotes lesion regression while maintaining vascular permeability control, resolving the contradiction between initial treatment effectiveness and long-term durability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces activated innate lymphoid cells as an intermediary therapeutic agent between the disease state and the desired treatment outcome. These cells serve as mediators that not only prevent vascular permeability but also actively promote regression of neovascular lesions, overcoming the limitations of direct anti-VEGF therapy

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If anti-VEGF therapy is administered regularly, then neovascularization is inhibited, but fibrotic scarring occurs and treatment resistance increases

Engineering Contradiction:

Improveneovascularization inhibitionVSAvoidfibrotic scarring

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of chronic inflammation and vascular permeability into a beneficial response by using activated NK cells. These cells target and eliminate the harmful neovascularization while avoiding the fibrotic scarring associated with anti-VEGF therapy, turning the disease process against itself in a controlled manner

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent replaces the mechanical/biological mechanism of anti-VEGF protein inhibition with an immunological mechanism using activated NK cells. This substitution allows for direct targeting of neovascular lesions without the secondary fibrotic effects, achieving neovascularization inhibition through a different biological pathway

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If a large population of activated innate lymphoid cells is produced, then therapeutic efficacy is enhanced, but production complexity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidproduction process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-activating innate lymphoid cells with cytokines (IL-18, IL-12, IL-15, or IL-2) before therapeutic administration. This pre-activation step enhances the cells' cytotoxic activity and therapeutic efficacy, allowing for more effective treatment with potentially reduced production complexity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent changes the functional parameters of innate lymphoid cells through cytokine activation, transforming them from resting state cells to highly active NK cells with enhanced cytotoxicity. This parameter change in cell activation status improves therapeutic efficacy without requiring complex production methodologies

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 activated innate lymphoid cells, particularly natural killer cells, effectively inhibit neovascularization and promote regression of retinal lesions, offering a potential alternative to existing therapies with reduced resistance and improved treatment outcomes.

Implementation Method 1

contacting the population of innate lymphoid cells with at least one cytokine

Methodology Applied

Scientific EffectCytokine signaling:

Data Source

PatentUS20260069631A1A method of producing innate lymphoid cells for use in therapy

Publication Date: 2026.03.12 THE PROVOST FELLOWS FOUNDATION SCHOLARS AND THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

AI summary

The present invention relates to a method of producing a population of activated innate lymphoid cells, the population of activated innate lymphoid cells obtainable thereby, and use thereof in preventing or treating a disease in a subject. The present invention finds particular utility in the production of activated innate lymphoid cells useful in the treatment of ocular diseases such as neovascular diseases of the choroid and/or the retina.