Truncated VWF Variant for Factor VIII Stabilization

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Solution Overview

Problem

Current treatments for von Willebrand disease (VWD) and haemophilia, particularly haemophilia A, are inadequate due to the short half-life of coagulation factor VIII and complications from using full-length von Willebrand factor (VWF), necessitating a more effective and stable alternative.

Innovation Solution

Development of a truncated VWF variant lacking amino acid residues 1875-2720, specifically the D4-C6 domains, which retains functional properties such as multimer formation and collagen interaction, enabling its use as a stable carrier for factor VIII.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If full-length VWF is used to stabilize factor VIII, then factor VIII half-life is prolonged, but device complexity and manufacturing cost increase

Engineering Contradiction:

Improvefactor VIII half-lifeVSAvoidVWF molecule size

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The VWF molecule is segmented by deleting the C-terminal D4-C6 domains (amino acid residues 1875-2720), creating a truncated VWF variant that retains essential functions while reducing molecular complexity and size for easier manufacturing

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The non-essential C-terminal D4-C6 domains are extracted and removed from the VWF molecule, leaving a truncated variant that maintains core functions of platelet capture and FVIII stabilization without the bulk of the removed domains

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If full-length VWF is administered to haemophiliacs, then factor VIII stability is improved, but harmful effects increase due to excessive clotting

Engineering Contradiction:

Improvefactor VIII stabilityVSAvoidexcessive clotting

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The C-terminal domains are removed to create a truncated VWF that provides sufficient FVIII stabilization without the full complement of domains that could trigger excessive clotting responses in haemophiliacs with native VWF

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The molecular structure of VWF is modified by truncating the C-terminal end, changing the physical parameter of molecular size and domain composition while maintaining the functional parameter of FVIII binding and stabilization

Inventive Principle:

Principle #35Parameter changes

3Productivity

If treatment frequency is reduced to lower cost and inconvenience, then patient compliance improves, but factor VIII trough levels may decrease

Engineering Contradiction:

Improvetreatment efficiencyVSAvoidprotection from bleeding

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The truncated VWF is designed to maximize its FVIII stabilization capability per molecule, allowing preliminary establishment of adequate FVIII levels that persist longer, thereby extending the interval between treatments while maintaining protective trough levels

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentEP3619231B1Truncated vwf

Publication Date: 2026.01.28 IMPERIAL COLLEGE INNVOATIONS LTD

Figure 1~3A
Figure 3B~3C
Figure 4A~4B

AI summary

The present invention relates to novel truncated fragments of von Willebrand factor (VWF) and the use of such fragments and nucleic acids encoding such fragments in the treatment of von Willebrand disease (VWD) and haemophilia.