Controlled-Release CNP Agonists for Sustained Exposure With Fewer Side Effects

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Solution Overview

Problem

The short half-life of CNP agonists and their extensive inactivation in subcutaneous tissue necessitate continuous infusion, leading to cardiovascular side-effects such as hypotension, making them challenging to administer effectively in pediatric populations.

Innovation Solution

A controlled-release CNP agonist formulation that maintains therapeutic levels for at least 6 hours, reducing side-effects and allowing higher doses without cardiovascular complications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If continuous infusion of CNP agonist is administered to overcome short half-life, then therapeutic efficacy is improved, but cardiovascular side-effects such as hypotension increase

Engineering Contradiction:

Improveduration of therapeutic effectVSAvoidcardiovascular side-effects

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent employs periodic action through controlled-release formulation that delivers CNP agonist in a sustained manner over at least 6 hours, replacing continuous infusion with intermittent controlled-release dosing that maintains therapeutic levels while reducing peak concentrations that cause hypotension

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent uses a controlled-release formulation as an intermediary system that mediates between the short half-life of native CNP and the need to avoid continuous high-dose administration. This intermediary delivery system controls the release rate to maintain therapeutic efficacy while minimizing cardiovascular side-effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If higher dose of CNP agonist is administered to increase drug exposure, then therapeutic efficacy is improved, but cardiovascular side-effects such as hypotension increase

Engineering Contradiction:

Improvedrug exposureVSAvoidcardiovascular side-effects

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent changes the administration parameters by using controlled-release formulation that delivers the same or higher total dose over an extended period (at least 6 hours), transforming the dosing regimen from acute high-dose to sustained lower-rate administration, thereby increasing overall drug exposure while reducing peak-related cardiovascular side-effects

Inventive Principle:

Principle #35Parameter changes

3Reliability

If continuous infusion is required to maintain therapeutic levels, then treatment efficacy is improved, but treatment convenience and patient compliance deteriorate

Engineering Contradiction:

Improvemaintenance of therapeutic levelsVSAvoidtreatment convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent achieves continuity of useful action through controlled-release formulation that maintains therapeutic levels of CNP agonist in the body for at least 6 hours after a single subcutaneous injection, eliminating the need for continuous infusion and providing sustained therapeutic effect with improved convenience

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentEP4710947A2Controlled-release CNP agonists with reduced side-effects

Publication Date: 2026.03.18 ASCENDIS PHARMA GROWTH DISORDERS AS

Figure 1

AI summary

The present invention relates a pharmaceutical composition comprising a controlled-release CNP agonist which reduces CNP agonist-associated side-effects, the use of such controlled-release CNP agonist and to methods of treatment.