Amino Acid Addition Prevents Polypeptide Reduction

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for preventing polypeptide reduction during purification, such as adding thioredoxin inhibitors, are not versatile and require special equipment, making them unsuitable for industrial applications and potentially harmful to humans.

Innovation Solution

Adding amino acids like arginine, lysine, or histidine to the culture solution before or after removing recombinant host cells to prevent polypeptide reduction without using harmful compounds or specialized equipment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If thioredoxin inhibitors or hexokinase inhibitors are added to the culture solution to prevent polypeptide reduction, then the polypeptide stability is improved, but the ease of manufacture deteriorates due to the need for additional purification steps to remove harmful compounds

Engineering Contradiction:
Improvepolypeptide stabilityVSAvoidpurification process simplicity
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The invention extracts and removes the harmful compounds (thioredoxin inhibitors and hexokinase inhibitors) from the purification process, replacing them with a simple amino acid addition that does not require subsequent removal steps. This eliminates the manufacturing complexity associated with removing harmful substances while maintaining polypeptide stability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses inexpensive amino acids that can be easily added and do not require removal, replacing expensive and problematic inhibitor compounds. The amino acids serve their protective function and can be discarded without concern for residual harm, simplifying the overall process.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Stability of the object's composition

If thioredoxin inhibitors are added to prevent polypeptide reduction, then the polypeptide stability is improved, but the object-affected harmful factors worsen due to potential harm to human bodies

Engineering Contradiction:
Improvepolypeptide stabilityVSAvoidharmfulness to human bodies
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The invention converts the potentially harmful inhibitor compounds into harmless amino acids. By using amino acids that are naturally present in biological systems and metabolizable, the solution transforms a harmful approach into a benign one while maintaining the protective effect against polypeptide reduction.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The invention uses safe, biocompatible amino acids that pose no harm to human bodies, replacing toxic inhibitors. These amino acids can be safely present in the final product without requiring extensive purification to remove harmful residues.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Stability of the object's composition

If air is used to deplete glucose-6-phosphate and NADPH to prevent polypeptide reduction, then the polypeptide stability is improved, but the device complexity worsens due to the need for special equipment

Engineering Contradiction:
Improvepolypeptide stabilityVSAvoidequipment requirements
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The invention removes the need for complex aeration equipment and special devices by simply adding amino acids to the culture solution. This eliminates the device complexity associated with air sparging systems and specialized purification equipment while achieving the same protective effect.

Inventive Principle:
Principle #2Taking out (Extraction)

4Manufacturing precision

If multiple purification steps are used to remove cells and impurities from the culture solution, then the polypeptide purity is improved, but the productivity deteriorates due to reduced efficiency

Engineering Contradiction:
Improvepolypeptide purityVSAvoidpurification efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The invention performs the protective action of preventing polypeptide reduction at the beginning of the purification process by adding amino acids to the culture solution. This preliminary protection ensures that the polypeptide remains stable throughout subsequent purification steps, reducing the need for repeated handling and minimizing productivity losses.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS9976163B2Method for preventing reduction of polypeptide by adding amino acid to culture solution
Publication Date: 2018.05.22 KYOWA HAKKO KIRIN CO LTD

AI summary

The present invention provides a method for preventing the reduction of a desired polypeptide during purification in order to purify the polypeptide in high yield from a culture solution which contains recombinant host cells and the polypeptide.