Protein Stabilization Without Mammalian Excipients

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Solution Overview

Problem

Current protein formulations that are free of stabilizing proteins often lack stability, particularly when exposed to varying temperatures and humidity levels, leading to reduced efficacy and shelf life of proteins like Botulinum toxin.

Innovation Solution

A formulation comprising a hydrophilic polymer, a mixture of polyalcohol and sugar in a specific weight ratio, and a detergent, all without stabilizing proteins like human serum albumin or immunoglobulins, which provides enhanced stability to proteins by maintaining their physical and chemical integrity over extended storage periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If protein formulations are made free of stabilizing proteins (HSA, gelatine, immunoglobulins), then the formulation is simplified and potentially safer, but the stability and shelf life of the protein are reduced

Engineering Contradiction:
Improveformulation complexityVSAvoidprotein stability
Core Design Contradiction:
Device complexityVSStability of the object's composition

Solution Approach 1:

The patent removes stabilizing proteins (HSA, gelatine, immunoglobulins) from the formulation while replacing them with non-proteinaceous stabilizing agents. This extraction of problematic components simplifies the formulation and improves safety profile, while the patent compensates by introducing alternative stabilizing mechanisms that do not rely on protein-based excipients.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical composition parameters by substituting protein-based stabilizers with non-proteinaceous agents such as sugars (sucrose, maltose), polyols (mannitol, sorbitol), and polymers (PVP, PEG). This parameter change maintains stabilizing function while eliminating the need for stabilizing proteins, thus resolving the contradiction between formulation simplicity and protein stability.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If non-proteinaceous stabilizing agents are used instead of stabilizing proteins, then the formulation is free of mammalian excipients, but the stability under varying temperature and humidity conditions is insufficient

Engineering Contradiction:
Improvepresence of mammalian excipientsVSAvoidformulation reliability
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent employs composite stabilization strategies combining multiple non-proteinaceous agents (sugars, polyols, polymers, and sometimes detergents) to achieve reliable protein stability. This composite approach compensates for the lack of protein-based stabilizers by creating a synergistic protective environment that maintains protein integrity under varying storage conditions.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent introduces non-proteinaceous substances as intermediary agents that mediate between the protein and harsh environmental conditions. These intermediaries (sugars, polyols, polymers) form protective networks and interfaces that shield the protein from temperature and humidity variations, thereby maintaining formulation reliability without mammalian excipients.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If the formulation is stored at room temperature for extended periods, then accessibility and ease of use are improved, but the protein stability and biological activity are reduced

Engineering Contradiction:
Improvestorage accessibilityVSAvoidshelf life
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The patent optimizes the formulation composition parameters (concentrations of sugars, polyols, polymers, and detergents) to specifically enhance stability at room temperature. By adjusting these parameters, the formulation maintains protein stability and biological activity over extended storage periods at ambient conditions, enabling easy storage and use without requiring controlled cold chain infrastructure.

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

The formulation ensures that proteins retain up to 90% of their stability and biological activity for several months at room temperature and up to 12 months at controlled conditions, significantly improving the shelf life and effectiveness of proteins like Botulinum toxin.

Implementation Method 1

A formulation comprising a hydrophilic polymer, a mixture of polyalcohol and sugar in a specific weight ratio, and a detergent, all without stabilizing proteins like human serum albumin or immunoglobulins, which provides enhanced stability to proteins by maintaining their physical and chemical integrity

Methodology Applied
Scientific EffectMolecular stabilization:

Data Source

PatentEP2419089B1Formulation for stabilizing proteins, which is free of mammalian excipients
Publication Date: 2016.11.16 MERZ PHARMA GMBH & CO KGAA

AI summary

The present invention pertains to a formulation comprising a hydrophilic polymer, a mixture of a polyalcohol and a sugar, wherein the weight ratio of polyalcohol to sugar is between 2:1 to 5:1 (wt-%), a detergent, wherein said formulation is free of stabilising proteins.