Multi-Chain Tissue Factor Polypeptides for Targeted Immune Stimulation

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Solution Overview

Problem

The mechanism of 'decryption' of cell-surface tissue factor for coagulation is unclear, and existing technologies do not effectively utilize soluble tissue factor as a scaffold for chimeric polypeptides to stimulate immune cells or treat diseases.

Innovation Solution

Multi-chain chimeric polypeptides are developed, comprising a first chimeric polypeptide with a target-binding domain, soluble tissue factor domain, and a pair of affinity domains, and a second chimeric polypeptide with a domain of affinity domains and a target-binding domain, associating through affinity domain binding, to stimulate immune cells and treat conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If soluble tissue factor is used as a scaffold for chimeric polypeptides, then immune cell stimulation and therapeutic benefits are achieved, but the mechanism of tissue factor decryption for coagulation remains unclear and utilization efficiency is limited

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidmechanism understanding

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention divides the tissue factor molecule into separate functional domains (tissue factor domain, affinity domains, target-binding domains) that can be independently configured and combined in different chimeric polypeptide architectures, enabling systematic study of each domain's contribution to both coagulation and immune cell stimulation functions

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The chimeric polypeptides are designed to perform multiple functions simultaneously: they retain tissue factor's ability to bind FVIIa and initiate coagulation while also incorporating affinity domains and target-binding domains that enable immune cell stimulation, cytokine induction, and targeted delivery to specific cell types

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If multi-chain chimeric polypeptides are constructed with multiple domains, then functional versatility is improved, but molecular complexity and manufacturing difficulty increase

Engineering Contradiction:

Improvefunctional capabilityVSAvoidmolecular structure

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The multi-chain chimeric polypeptides are constructed by dividing functional elements into separate polypeptide chains, each containing specific domains (e.g., one chain with tissue factor domain and affinity domains, another chain with target-binding domains), which simplifies the design and manufacturing of each individual chain while achieving complex overall functionality when assembled

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The chimeric polypeptides employ nested domain structures where affinity domains are embedded within larger polypeptide chains that also contain tissue factor domains or target-binding domains, allowing compact organization of multiple functions within a manageable molecular architecture

Inventive Principle:

Principle #7Nested doll (Nesting)

3Productivity

If tissue factor is exposed on cell surface for coagulation, then coagulation activity is enhanced, but uncontrolled coagulation and thrombosis risks increase

Engineering Contradiction:

Improvecoagulation activityVSAvoidthrombosis risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The tissue factor domain is extracted from its native cell surface context and incorporated into soluble chimeric polypeptides that can be controlled in circulation, allowing coagulation activity to be activated only when and where the chimeric polypeptides encounter their target cells or conditions, thereby reducing uncontrolled coagulation and thrombosis risks

Inventive Principle:

Principle #2Taking out (Extraction)

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 multi-chain chimeric polypeptides effectively stimulate immune cell functions, including proliferation, differentiation, and killing of cancer or infected cells, providing therapeutic benefits for various diseases and conditions.

Implementation Method 1

the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains

Methodology Applied

Scientific EffectAffinity binding:

Data Source

PatentUS12509494B2Multi-chain chimeric polypeptides and uses thereof

Publication Date: 2025.12.30 IMMUNITYBIO INC

AI summary

Provided herein are multi-chain chimeric polypeptides that include:(a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.