Anti-Tissue Factor Antibodies With Minimal Coagulation Interference

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Solution Overview

Problem

Existing treatments for cancer, inflammation, and vascular diseases related to tissue factor (TF) are not sufficiently effective and specific, and there is a need for improved therapeutic antibodies that can inhibit TF functions without significantly interfering with blood coagulation.

Innovation Solution

Development of novel human anti-TF antibodies with high affinity, capable of mediating antibody-dependent cellular cytotoxicity (ADCC), inhibiting FVIIa binding to TF, and reducing FVIIa-induced ERK phosphorylation and IL-8 release, while minimizing coagulation inhibition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments are used to inhibit tissue factor functions, then therapeutic effects are achieved, but significant interference with blood coagulation occurs

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidcoagulation interference

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody is designed to recognize and bind to specific epitopes on tissue factor with high local specificity, allowing selective inhibition of TF-mediated processes (angiogenesis, inflammation) while leaving other coagulation pathways unaffected. This localized recognition enables differential inhibition of harmful TF functions without broadly interfering with blood coagulation.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention utilizes antibodies with optimized binding affinity parameters (KD values) that allow selective interaction with tissue factor at pathologically relevant concentrations. By tuning the binding strength and specificity parameters of the antibody-TF interaction, the treatment achieves therapeutic efficacy against TF-driven diseases while maintaining physiological coagulation function.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If high affinity anti-TF antibodies are used to inhibit TF functions, then tumor growth and inflammation are suppressed, but blood coagulation may be significantly affected

Engineering Contradiction:

Improveinhibition of tumor growth and inflammationVSAvoidblood coagulation function

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The antibody acts as a selective intermediary that binds to tissue factor and blocks its interaction with coagulation factor VIIa and other ligands involved in pathological processes. This intermediary action specifically interrupts TF-mediated signaling pathways driving tumor growth and inflammation while preserving normal coagulation function through selective epitope recognition.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The antibody targets specific functional segments or epitopes on the tissue factor molecule that are critical for pathological interactions but distinct from regions involved in normal coagulation. By segmenting the TF molecule into functionally distinct binding sites, the antibody achieves selective inhibition of harmful functions while sparing essential coagulation activities.

Inventive Principle:

Principle #1Segmentation

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 inhibit TF-related processes, including tumor growth and inflammation, while maintaining minimal impact on blood coagulation, demonstrating significant therapeutic potential in cancer and vascular disease models.

Implementation Method 1

human antibody which binds human Tissue Factor

Methodology Applied

Scientific EffectAntibody-antigen binding: Absorption (physical)

Implementation Method 2

capable of mediating antibody-dependent cellular cytotoxicity (ADCC)

Methodology Applied

Scientific EffectAntibody-dependent cellular cytotoxicity:

Implementation Method 3

inhibiting FVIIa binding to TF

Methodology Applied

Scientific EffectCompetitive inhibition:

Implementation Method 4

reducing FVIIa-induced ERK phosphorylation and IL-8 release

Methodology Applied

Scientific EffectSignal transduction inhibition:

Data Source

PatentUS20250340669A1Human antibodies against tissue factor and methods of use thereof

Publication Date: 2025.11.06 GENMAB AS

AI summary

Isolated human monoclonal antibodies which bind to human TF and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, and therapeutic and diagnostic methods for using the antibodies.