Biodegradable Nanoparticles for Immune Tolerance

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current immunosuppressive therapies for autoimmune diseases and organ transplantation are inadequate, leading to chronic rejection and lifelong dependency on medication, with a critical shortage of donor organs and high rejection rates in transplantation.

Innovation Solution

Development of biodegradable nanoparticles with a targeting moiety that selectively binds to T lymphocytes and vascular endothelial cells, loaded with leukemia inhibitory factor (LIF) to promote immune tolerance by guiding T regulatory cells development and reducing immune response aggression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current immunosuppressive therapies are used, then immune response can be suppressed, but chronic rejection and lifelong dependency on medication occur

Engineering Contradiction:
Improvetransplant survivalVSAvoidchronic rejection
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses nanoparticles as intermediary carriers to deliver LIF to specific cell types (T lymphocytes and vascular endothelial cells). The nanoparticles act as a mediator that transports the therapeutic molecule precisely to where it is needed, improving efficacy while reducing systemic side effects and dependency on lifelong immunosuppressive therapy.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the delivery parameter from systemic immunosuppressive therapy to targeted nanoparticle delivery. By altering the delivery mechanism and targeting specific cell populations, the therapy achieves better control of immune response without the harmful chronic effects of conventional lifelong immunosuppression.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If donor organs are increased to meet demand, then transplantation availability improves, but donor organ shortage remains critical

Engineering Contradiction:
Improvetransplant availabilityVSAvoiddonor organ supply
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent converts the harmful immune recognition of donor organs as foreign into a beneficial response by using LIF to promote tolerance. This allows better matching between donors and recipients, effectively increasing the usable donor organ pool without requiring more physical donors.

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

Solution Approach 2:

The patent changes the parameter of tissue compatibility from strict HLA matching to immune tolerance induction. By modifying the immune system's response parameter through LIF treatment, the threshold for acceptable donor-recipient matches is raised, increasing transplant availability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If aggressive immune responses are allowed, then pathogen clearance improves, but self-tolerance is compromised

Engineering Contradiction:
Improveimmune defenseVSAvoidauto-immune attack
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by targeting different cell types with different functions: T lymphocytes for immune regulation and vascular endothelial cells for tissue protection. The nanoparticles deliver LIF specifically to these locations, allowing aggressive immune responses against pathogens while maintaining self-tolerance through localized modulation of regulatory cells.

Inventive Principle:
Principle #3Local quality

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 targeted delivery of LIF using nanoparticles effectively suppresses aggressive immune responses, reduces chronic vascular rejection, and promotes tolerance to transplanted tissues, potentially reducing the need for lifelong immunosuppression and expanding tissue type matching parameters.

Implementation Method 1

the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a T lymphocyte cell and/or of a vascular endothelial cell, wherein the targeting moiety is selected from a monoclonal antibody, a polyclonal antibody, or an antigen-binding antibody fragment

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 2

a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a biodegradable polymer layer

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP2219609B1Immuno-modulatory composition
Publication Date: 2017.05.24 METCALFE SUSAN MARIE
  • EP2219609B1 patent drawingFigure 1~2(a)
  • EP2219609B1 patent drawingFigure 2(b)
  • EP2219609B1 patent drawingFigure 3

AI summary

A composition for modulating the immune response in a mammal comprising a pharmaceutically acceptable carrier solution and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a T lymphocyte cell and/or of a vascular endothelial cell and wherein the nanoparticles further comprise leukaemia inhibitory factor (LIF). Nanoparticle-mediated targeted delivery of LIF can be used a means to guide tolerogenesis in a patient and has immediate clinical application for recipients of organ grafts and also for patients suffering from autoimmune disease.