GDF15 Polypeptide Combinations for EPO-Refractory Anemia

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Solution Overview

Problem

Existing treatments for anemia, such as erythropoietin (EPO), are not uniformly effective and can have adverse effects, particularly in patients with conditions like cancer, kidney disease, or myelodysplastic syndrome, and there is a need for alternative methods to increase red blood cell levels.

Innovation Solution

The use of GDF15 polypeptides, alone or in combination with EPO receptor activators, to stimulate erythropoiesis and increase red blood cell levels, potentially reducing the required dose of EPO receptor activators and minimizing adverse effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If EPO is used to treat anemia, then red blood cell levels increase, but adverse effects occur and response is not uniform

Engineering Contradiction:
Improvered blood cell levelsVSAvoidadverse effects
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent combines GDF15 polypeptide with EPO receptor activators to create a synergistic treatment approach. The GDF15 polypeptide enhances the efficacy of EPO receptor activators while allowing for reduced dosing, thereby increasing red blood cell levels more effectively and uniformly across different patient populations while minimizing adverse effects associated with high-dose EPO monotherapy

Inventive Principle:
Principle #5Merging (Combining)

2Productivity

If high dose EPO is administered, then red blood cell production increases, but risk of cardiovascular morbidity and tumor growth increases

Engineering Contradiction:
Improvered blood cell productionVSAvoidcardiovascular morbidity and tumor growth risk
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The combination of GDF15 polypeptide with EPO receptor activators produces a synergistic effect that achieves enhanced red blood cell production at lower doses of EPO receptor activator. This reduces the overall burden of high-dose EPO therapy, thereby minimizing the associated risks of cardiovascular morbidity and tumor growth while maintaining effective anemia treatment

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent introduces GDF15 polypeptide as an additional therapeutic parameter that modulates the erythropoietic response. This allows for a more nuanced control of red blood cell production, achieving the desired productivity increase through a combination mechanism rather than relying solely on high-dose EPO, thus reducing harmful side effects

Inventive Principle:
Principle #35Parameter changes

3Reliability

If EPO is used in refractory patients, then treatment response is expected, but many individuals show inadequate response

Engineering Contradiction:
Improvetreatment responseVSAvoidresponse variability across patient populations
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The synergistic combination of GDF15 polypeptide with EPO receptor activators addresses treatment refractoryness by activating multiple erythropoietic pathways simultaneously. This multi-pathway approach enhances treatment reliability across diverse patient populations, including those who are hyporesponsive to EPO alone, thereby improving adaptability and reducing response variability

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The GDF15 polypeptide component provides universal efficacy across different patient subpopulations with anemia, regardless of their specific underlying condition or prior EPO response. This multi-functional approach targets multiple mechanisms of erythropoiesis, making the treatment more versatile and reliable across cancer patients, kidney disease patients, and other anemic populations

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

Data Source

PatentEP3922259B1Methods and compositions using GDF15 polypeptides for increasing red blood cells
Publication Date: 2026.04.01 ACCELERON PHARMA INC
  • EP3922259B1 patent drawingFigure 1
  • EP3922259B1 patent drawingFigure 2A~2C
  • EP3922259B1 patent drawingFigure 3A~3B

AI summary

In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.