TL1A-Binding Antibodies for Crohn's Disease Therapy

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Solution Overview

Problem

Current treatments for Crohn's disease and other inflammatory and immune disorders lack specificity and often come with significant side effects, necessitating the development of targeted therapies that can effectively manage TL1A-mediated disorders without the adverse effects of existing anti-TNF-a monoclonal antibodies.

Innovation Solution

Development of antibodies or fragments that bind specifically to TL1A, including humanized and chimeric variants with enhanced affinity and specificity, capable of inhibiting TL1A's interaction with both DR3 and DcR3, thereby reducing inflammation and immune response in various inflammatory and autoimmune diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current anti-TNF-a monoclonal antibodies are used to treat Crohn's disease and other inflammatory disorders, then anti-inflammatory effect is achieved, but side effects increase and treatment specificity decreases

Engineering Contradiction:

Improveanti-inflammatory effectVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the broad anti-TNF-a therapy into a more specific anti-TL1A therapy. By targeting TL1A specifically rather than the broader TNF-a pathway, the invention isolates the therapeutic effect to the specific pathway involved in Crohn's disease and other inflammatory disorders, thereby maintaining anti-inflammatory efficacy while reducing off-target side effects associated with broader TNF-a inhibition.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by creating a therapy that acts specifically on TL1A-mediated inflammatory pathways in affected tissues. The anti-TL1A antibodies and antagonists provide localized therapeutic action at the molecular level, targeting only the TL1A-DR3 interaction that drives pathology in Crohn's disease, while leaving other immune pathways intact and functional.

Inventive Principle:

Principle #3Local quality

2Reliability

If current anti-TNF-a monoclonal antibodies are used to treat Crohn's disease and other inflammatory disorders, then anti-inflammatory effect is achieved, but treatment specificity decreases

Engineering Contradiction:

Improveanti-inflammatory effectVSAvoidtreatment specificity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If TL1A antibody is developed to target specific TL1A-mediated pathways, then treatment specificity is improved, but therapeutic efficacy in reducing inflammation may be insufficient

Engineering Contradiction:

Improvetreatment specificityVSAvoidtherapeutic efficacy

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs universality by developing a multi-functional approach that combines several types of TL1A-targeting molecules: neutralizing antibodies, competitive antagonists, and decoy receptors. Each mechanism contributes to blocking TL1A-DR3 interaction through different molecular strategies, collectively ensuring robust therapeutic efficacy while maintaining the specificity advantage of targeted TL1A inhibition.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention uses intermediary mechanisms by introducing soluble decoy receptors and Fc-fusion proteins that act as mediators to intercept TL1A before it can bind to DR3 on immune cells. These intermediary molecules serve as molecular sponges that specifically bind TL1A with high affinity, preventing its pathological interaction while maintaining the specificity of the therapeutic approach.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 antibodies effectively suppress TL1A-induced inflammation and immune responses, demonstrating therapeutic potential in conditions such as Crohn's disease, rheumatoid arthritis, and asthma by reducing eosinophils and alleviating symptoms in animal models, with a favorable safety profile compared to existing treatments.

Implementation Method 1

antibodies or fragments thereof that bind to TL1A

Methodology Applied

Scientific EffectAntibody-antigen binding:

Data Source

PatentEP2941302B1Antibodies that bind to TL1a and their uses

Publication Date: 2018.08.01 ICHNOS SCIENCES SA

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Figure 3A~3B

AI summary

The present invention relates to antibodies or fragments thereof that bind to TL1A. More specifically, the present invention relates to an antibody or fragment thereof that binds to TL1Acomprising a heavy chain CDR1comprising the amino acid sequence of SEQ ID NO: 1, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 52, 5 and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 53; and/or comprising a light chain CDR1comprising the amino acid sequence of SEQ ID NO: 54, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 55and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 56.