Fixed Dosing Regimen for Clotting Factor Hemophilia Treatment

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Solution Overview

Problem

Current clotting factor dosing regimens for hemophilia patients, based on body weight, are inconvenient and costly, leading to significant variability in pharmacokinetic parameters and therapeutic outcomes.

Innovation Solution

A fixed dosing regimen of modified clotting factors, such as those with an FcRn binding partner, is administered at regular intervals, providing a wide therapeutic window and reduced variability across body weights, with options for stratified dosing based on weight categories.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If body weight-based dosing is used for clotting factors, then dosing is tailored to patient size, but variability in pharmacokinetic parameters increases and treatment consistency decreases

Engineering Contradiction:
Improvedosing tailored to patient sizeVSAvoidpharmacokinetic parameter consistency
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the dosing parameter from body weight-based (IU/kg) to fixed dosing (IU), which fundamentally alters how the dose is calculated and administered. This parameter change reduces the complexity of dosing calculations and improves consistency in pharmacokinetic outcomes across patients of different weights.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If body weight-based dosing is used for clotting factors, then dosing accuracy for individual patients is improved, but treatment complexity and cost increase

Engineering Contradiction:
Improvedosing accuracyVSAvoidtreatment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the body weight variable from the dosing calculation, removing the need for complex weight-based calculations. This simplification maintains adequate dosing accuracy while eliminating the complexity of individualized dosing protocols, making the treatment easier to administer and manage.

Inventive Principle:
Principle #2Taking out (Extraction)

3Ease of operation

If fixed dosing is used for clotting factors, then treatment simplicity and cost-effectiveness improve, but dosing precision for extreme body weights may decrease

Engineering Contradiction:
Improvedosing simplicityVSAvoiddosing precision
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent applies partial customization by stratifying patients into weight categories (e.g., <50kg, 50-100kg, >100kg) and providing specific fixed dose recommendations for each category. This approach maintains the simplicity of fixed dosing while partially addressing the needs of extreme body weights through category-based differentiation.

Inventive Principle:
Principle #16Partial or excessive action

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

This approach reduces variability in pharmacokinetic parameters, improves treatment consistency, and enhances the quality of life for hemophilia patients by minimizing bleeding episodes and joint damage, while reducing healthcare costs.

Implementation Method 1

the modified clotting factor comprises a clotting factor and a heterologous moiety, e.g., a heterologous moiety which increases in vivo half-life of the clotting factor

Methodology Applied
Scientific EffectFcRn binding:

Data Source

PatentEP2908847B1Methods of using a fixed dose of a clotting factor
Publication Date: 2022.03.30 BIOVERATIV THERAPEUTICS INC
  • EP2908847B1 patent drawingFigure 1
  • EP2908847B1 patent drawingFigure 2A~2B
  • EP2908847B1 patent drawingFigure 3A~3E

AI summary

The present invention provides methods of administering a clotting factor by a fixed dosing regimen; methods of reducing, ameliorating, or preventing one or more symptoms of a bleeding disease or disorder; and a kit comprising a dotting factor useful for a fixed dosing regimen. While plasma-derived and recombinant clotting factor products allow hemophilia patients to live longer and healthier, hemophilia still remains one of the most costly and complex conditions to manage.