Chimeric Factor VIII Formulation for Extended Hemophilia A Activity

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Solution Overview

Problem

Existing Factor VIII treatments for hemophilia A have limited half-lives, requiring frequent intravenous administration and are not optimized for extended stability and efficacy.

Innovation Solution

A pharmaceutical composition comprising a chimeric protein with specific amino acid sequences linked by disulfide bonds, combined with sucrose, histidine, arginine, calcium chloride, and poloxamer, to enhance stability and prolong the half-life of Factor VIII.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional Factor VIII products are used, then the treatment is simple and well-established, but the half-life is limited to 8-12 hours requiring frequent administration

Engineering Contradiction:

Improvehalf-life of Factor VIIIVSAvoidcomplexity of pharmaceutical composition

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent employs a composite pharmaceutical formulation containing chimeric Factor VIII protein combined with multiple excipients including sucrose, histidine, arginine, calcium chloride, and poloxamer. This composite composition stabilizes the Factor VIII protein structure and extends its circulating half-life from 8-12 hours to potentially longer durations, reducing administration frequency while managing the complexity through optimized formulation chemistry

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent utilizes parameter changes by adjusting pH (using histidine buffer), ionic strength (calcium chloride), and adding stabilizing agents (sucrose, arginine, poloxamer) to optimize the physical and chemical properties of the Factor VIII formulation. These parameter optimizations enhance protein stability and extend half-life without requiring complex delivery systems

Inventive Principle:

Principle #35Parameter changes

2Reliability

If frequent intravenous administration is required, then adequate Factor VIII levels are maintained, but patient compliance and quality of life deteriorate

Engineering Contradiction:

Improvemaintenance of Factor VIII levelsVSAvoidfrequency of administration

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent implements preliminary action by formulating Factor VIII with stabilizing excipients (sucrose, histidine, arginine, poloxamer) that pre-protect the protein from degradation during storage and circulation. This preliminary stabilization allows the Factor VIII to maintain therapeutic levels for extended periods, reducing the frequency of administration while ensuring reliable therapeutic effect

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses poloxamer as an intermediary surfactant that prevents protein aggregation and adsorption to container surfaces. This intermediary agent protects the Factor VIII from degradation mechanisms, extending its functional half-life and reducing administration frequency while maintaining reliable therapeutic levels

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP4415693B1Formulations of factor viii chimeric proteins and uses thereof

Publication Date: 2026.02.18 BIOVERATIV THERAPEUTICS INC

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AI summary

The present disclosure provides pharmaceutical compositions of a chimeric protein comprising a factor VIII (FVIII) polypeptide and a von Willebrand factor (VWF) polypeptide. Also disclosed are pharmaceutical kits and methods of using the disclosed pharmaceutical compositions to treat hemophilia A.