PlGF-2 Protein for Atherosclerotic Heart Failure

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Solution Overview

Problem

Current treatments for heart failure, particularly those involving placental growth factor isoforms PlGF-1 and PlGF-2, lack clear therapeutic comparisons due to varying administration methods and models, leading to uncertain effectiveness in improving cardiac function and safety in atherosclerotic conditions.

Innovation Solution

A composition comprising recombinant placental growth factor 2 protein (PlGF-2) for systemic administration, specifically designed to treat or prevent heart failure phenotypes such as ventricular dysfunction, increased end-systolic volume, reduced ejection fraction, and ventricular remodeling in atherosclerotic mammals, using a porcine model that mimics human heart disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PlGF-1 or PlGF-2 is administered to treat heart failure, then cardiac function is improved, but the therapeutic effectiveness and safety remain uncertain due to lack of standardized comparison

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidadministration method variability
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent establishes a universal standardized protocol for administering both PlGF-1 and PlGF-2 that can be applied across different studies and models. This includes defining specific dosage ranges (PlGF-1: 1-100 µg/kg, PlGF-2: 1-50 µg/kg), administration routes (systemic, intramyocardial, or gene therapy), and evaluation timepoints, enabling direct comparison of therapeutic effectiveness between the two isoforms while maintaining reliability.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If PlGF-2 is administered systemically, then left ventricular function is improved and end-systolic volume is reduced, but potential adverse effects on cardiac damage or plaque instability may occur

Engineering Contradiction:
Improvecardiac function improvementVSAvoidcardiac damage risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent implements a feedback mechanism by establishing comprehensive safety monitoring protocols that assess cardiac damage markers and plaque stability parameters during PlGF-2 treatment. This includes evaluating troponin levels, imaging plaque morphology changes, and adjusting dosage based on observed effects, thereby improving cardiac function while mitigating potential harmful effects through continuous feedback-driven optimization.

Inventive Principle:
Principle #23Feedback

3Loss of information

If different administration methods are used for PlGF-1 and PlGF-2, then therapeutic effects can be evaluated, but direct comparison between isoforms becomes impossible

Engineering Contradiction:
Improvecomparability dataVSAvoidadministration flexibility
Core Design Contradiction:
Loss of informationVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by establishing standardized dosage parameters (PlGF-1: 1-100 µg/kg, PlGF-2: 1-50 µg/kg), time parameters (evaluation at 4, 8, 12 weeks), and method parameters (systemic, intramyocardial, or gene therapy routes) that enable direct comparison between isoforms. These standardized parameters maintain adaptability for different study designs while ensuring comparability of results across PlGF-1 and PlGF-2 treatments.

Inventive Principle:
Principle #35Parameter changes

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

PlGF-2 significantly improves left ventricular function, reduces end-systolic volume, and enhances ejection fraction without inducing cardiac damage or plaque instability, demonstrating therapeutic potential for heart failure treatment in atherosclerotic mammals.

Implementation Method 1

placental growth factor 2 protein (PlGF-2) for use in treating or preventing a heart failure phenotype in an atherosclerotic mammal

Methodology Applied
Scientific EffectProtein-receptor binding:

Data Source

PatentEP3003354B1Human PLGF-2 for the prevention or treatment of atherosclerotic heart failure
Publication Date: 2019.02.06 COBIORES NV
  • EP3003354B1 patent drawingFigure 1
  • EP3003354B1 patent drawingFigure 2
  • EP3003354B1 patent drawingFigure 3

AI summary

The present invention relates to treating and/or preventing heart failure or one or more individual heart failure phenotypes in mammals using placental growth factor 2 (PlGF-2).