MMP-7 Buffer Composition for Aggregate Monomerization

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Solution Overview

Problem

MMP-7 aggregates form under isotonic conditions with monovalent cation compounds, leading to adsorption to manufacturing apparatus and container walls, hindering large-scale production and medicinal use.

Innovation Solution

Treat MMP-7 aggregates with a solution containing a low concentration of monovalent cation chloride, such as sodium chloride or potassium chloride, and incorporate sugars or sugar alcohols to suppress aggregate formation and adsorption, using a Tris buffer at pH 6 to 8.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If MMP-7 is stored in a solution with monovalent cation compound at isotonic concentration (150 mM or more), then the osmotic pressure is appropriate for medicinal use, but MMP-7 forms aggregates and adsorbs to container walls

Engineering Contradiction:
Improveosmotic pressure appropriatenessVSAvoidMMP-7 aggregate formation
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the concentration parameter of monovalent cation compounds from conventional isotonic levels (150 mM or more) to low concentrations (130 mM or less), which fundamentally alters the solution chemistry to prevent MMP-7 aggregate formation while maintaining acceptable osmotic pressure for medicinal use

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces sugar alcohols or sugars as intermediary substances that mediate between the conflicting requirements of osmotic pressure and protein stability. These additives protect MMP-7 from aggregation at low monovalent cation concentrations while contributing to the overall osmotic balance

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If MMP-7 aggregates are formed under isotonic conditions, then the solution is stable for storage, but MMP-7 adsorbs to manufacturing apparatus and container walls

Engineering Contradiction:
Improvesolution stabilityVSAvoidMMP-7 adsorption loss
Core Design Contradiction:
Stability of the object's compositionVSLoss of substance

Solution Approach 1:

The patent changes the monovalent cation concentration parameter to low levels (130 mM or less), which simultaneously achieves solution stability and prevents adsorption losses by altering the electrochemical environment at protein-surface interfaces

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Sugar alcohols or sugars act as intermediary protective agents that prevent direct interaction between MMP-7 and container surfaces, reducing adsorption losses while maintaining solution stability during storage and processing

Inventive Principle:
Principle #24Intermediary (Mediator)

3Manufacturing precision

If conventional purification methods are used for MMP-7, then the purification process is established, but productivity and recovery efficiency are low

Engineering Contradiction:
Improvepurification qualityVSAvoidMMP-7 recovery efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent changes the monovalent cation concentration parameter throughout the purification process to low levels (130 mM or less), which prevents aggregate formation and maintains MMP-7 in a monomeric state, thereby improving recovery efficiency while maintaining purification quality

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies monomerization treatment using low monovalent cation solutions as a preliminary step before conventional purification procedures, ensuring that MMP-7 remains in a stable monomeric form that is more amenable to efficient purification and recovery

Inventive Principle:
Principle #10Preliminary action

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

Enhances MMP-7 productivity and maintains enzymatic activity, preventing adsorption to containers, thus providing a high-quality MMP-7 preparation for medicinal use.

Implementation Method 1

MMP-7 aggregates are dissociated to form monomers by the treatment with a solution such as a Tris buffer (pH 6 to 8) comprising a low concentration of a monovalent cation chloride (sodium chloride and potassium chloride)

Methodology Applied
Scientific EffectIon repulsion/attraction: Ion Repulsion/Attraction

Implementation Method 2

MMP-7 is adsorbed to gel in an apparatus normally used for the manufacture of proteins or their preparations or to a container such as a vial normally used for storage of preparations

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3147358B1Method for monomerizing matrix metalloproteinase-7 (MMP-7) aggregate
Publication Date: 2025.12.24 CUREDISC CORP
  • EP3147358B1 patent drawingFigure 1~2
  • EP3147358B1 patent drawingFigure 3~4
  • EP3147358B1 patent drawingFigure 5~6

AI summary

A method for monomerization of MMP-7 aggregates is provided. A method for monomerization of MMP-7 aggregates which comprises treating MMP-7 aggregates with a buffer solution comprising a monovalent cation chloride (sodium chloride, potassium chloride, etc.) at a low concentration or with a buffer solution not comprising a monovalent cation chloride, a process for preparing MMP-7 which involves said method for monomerization, and a (pharmaceutical) composition comprising MMP-7 in the aforementioned buffer solution. In case that a (pharmaceutical) composition comprising MMP-7 at a low concentration is prepared, the aforementioned buffer solution comprising sugar alcohols or sugars is used.