Modified Relaxin Polypeptides for Heart Failure

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current therapies for heart failure, including congestive heart failure, are plagued by adverse reactions and require balancing multiple drugs to achieve clinical needs, lacking agents that provide integrated physiological responses of arterial and venous vasodilation and cardiac inotropy without these disadvantages.

Innovation Solution

Modified relaxin polypeptides, such as RLX-A-AQ1-20KPEG, with amino acid substitutions and linked to polyethylene glycol (PEG), which retain wild-type properties like selective receptor activation and anti-fibrotic activity, and have an extended in vivo half-life, are developed for therapeutic use.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies for heart failure are used, then multiple drugs can be administered to achieve clinical needs, but adverse reactions increase and treatment complexity increases

Engineering Contradiction:

Improveclinical efficacyVSAvoidadverse reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines multiple therapeutic functions (arterial vasodilation, venous vasodilation, and cardiac inotropy) into a single modified relaxin polypeptide molecule. This integration eliminates the need for multiple separate drugs, thereby reducing adverse reactions and treatment complexity while maintaining clinical efficacy in heart failure treatment

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If multiple drugs are used to treat heart failure, then clinical needs can be met, but device complexity and treatment management increase

Engineering Contradiction:

Improveclinical efficacyVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The modified relaxin polypeptide is designed as a universal therapeutic agent that simultaneously performs multiple functions: arterial vasodilation, venous vasodilation, and cardiac inotropy. This multi-functionality allows a single agent to meet diverse clinical needs in heart failure treatment, significantly simplifying treatment management and reducing complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If wild-type relaxin is used, then selective receptor activation and anti-fibrotic activity are achieved, but in vivo half-life is limited

Engineering Contradiction:

Improvebiological activityVSAvoidin vivo half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent creates a composite molecule by conjugating wild-type relaxin with polyethylene glycol (PEG). This composite structure preserves the biological activity and selective receptor activation of wild-type relaxin while the PEG component extends the in vivo half-life, allowing for less frequent dosing and sustained therapeutic effect

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS11786578B2Modified relaxin polypeptides and their uses

Publication Date: 2023.10.17 AMBRX INC

AI summary

Modified relaxin polypeptides and their uses thereof are provided. Exemplary embodiments provide relaxin polypeptides which include one or more amino acid substitutions with natural or non-naturally encoded amino acids, and/or linkage to a water-soluble polymer, such as polyethylene glycol. Additionally, use of said relaxin polypeptides for treatment of disease, such as heart failure, is also provided.