IGF-1R Thioantisense Oligonucleotide Therapy for TAO

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Solution Overview

Problem

Current treatments for medium and severe active thyroid-associated ophthalmopathy (TAO) are inadequate, with glucocorticoid shock therapy causing hormone-related systemic side effects and other treatments having limited efficacy and significant side effects.

Innovation Solution

The use of a thioantisense oligonucleotide targeting the insulin-like growth factor 1 receptor (IGF-1R) gene to reduce IGF-1R and anti-thyroid peroxidase antibody concentrations, thereby improving thyroid-stimulating hormone levels and treating TAO.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If glucocorticoid shock therapy is used to treat medium and severe active TAO, then inflammatory response is suppressed, but hormone-related systemic side effects occur

Engineering Contradiction:

Improvetreatment efficacyVSAvoidsystemic side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by using antisense oligonucleotides that specifically target IGF-1R gene expression in orbital tissues, achieving localized suppression of inflammatory response without systemic hormone exposure. This targeted approach confines the therapeutic effect to the affected orbital region while avoiding whole-body side effects of glucocorticoids

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs antisense oligonucleotides as intermediary molecules that bind to IGF-1R mRNA to prevent protein synthesis. This intermediary mechanism blocks the pathological signaling pathway indirectly, avoiding direct hormonal exposure and its associated systemic side effects while still achieving anti-inflammatory effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If other immunomodulators or biological agents are used to treat TAO, then treatment options are expanded, but significant side effects and limited efficacy remain

Engineering Contradiction:

Improvetreatment optionsVSAvoidside effects

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies segmentation by dividing the treatment approach into two distinct components: (1) antisense oligonucleotides for IGF-1R gene targeting, and (2) conventional immunomodulators or biological agents. This segmented strategy allows the antisense component to provide targeted gene-level intervention with minimal side effects, while other agents can be used at reduced doses or selectively, thereby expanding treatment options without compounding side effects

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent inverts the conventional treatment paradigm by targeting gene expression (IGF-1R mRNA) rather than targeting the downstream inflammatory mediators or immune cells. This inverted approach addresses the root cause of orbital inflammation at the molecular level, potentially reducing or eliminating the need for high-dose immunomodulators and their associated side effects

Inventive Principle:

Principle #13The other way round (Inversion)

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 antisense oligonucleotide effectively reduces IGF-1R and anti-TPO-Ab levels, improving TSH levels and providing a potential treatment for TAO with fewer side effects compared to existing therapies.

Implementation Method 1

antisense oligonucleotide S-ASODN-1 with a particular sequence targeting an IGF-IR can effectively reduce concentrations of the IGF-IR

Methodology Applied

Scientific EffectComplementary base pairing:

Implementation Method 2

antisense oligonucleotide S-ASODN-1 with a particular sequence targeting an IGF-IR can effectively reduce concentrations of the IGF-IR and an anti-thyroid peroxidase antibody (TPO-Ab)

Methodology Applied

Scientific EffectGene suppression:

Data Source

PatentUS20250290077A1Use of antisense oligonucleotide in preparation of drug for treating disease caused by abnormal thyroid

Publication Date: 2025.09.18 HANGZHOU TIANLONG PHARM CO LTD

AI summary

The present disclosure relates to the field of gene therapies of thyroid-associated ophthalmopathy (TAO) and, in particular, to a use of an antisense oligonucleotide in preparation of a drug for treating a disease caused by an abnormal thyroid. Experimental results of the present application indicate that an antisense oligonucleotide S-ASODN-1 with a particular sequence targeting an insulin-like growth factor 1 receptor (IGF-1R) can effectively reduce concentrations of the IGF-1R and an anti-thyroid peroxidase antibody (TPO-Ab), thereby improving a level of thyroid-stimulating hormone (TSH) for treating thyroid-associated ophthalmopathy.