Cell-Guard Agents for Molecular Stress Control in Bioprocessing

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Solution Overview

Problem

Current cell culture technologies face challenges in maintaining cell viability and efficiency during bioprocessing, particularly in large-scale applications, due to stressors like temperature, mechanical, and chemical stresses, which lead to significant cell loss and reduced productivity.

Innovation Solution

The development of cell-guard agents, which are supplements that target specific stress pathways such as AKT, UPR, and MPTP to reduce cellular stress responses, thereby enhancing cell survival and function during bioprocessing events like harvesting, sorting, and protein production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cell culture is performed in large-scale bioprocessing settings, then productivity increases, but cell viability and function deteriorate due to stressors

Engineering Contradiction:
ImproveproductivityVSAvoidcell viability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces molecular stress control agents as intermediary substances that mediate between the stressful bioprocessing environment and the cultured cells. These agents bind to stress pathways (such as heat shock protein pathways, apoptotic pathways, or oxidative stress pathways) and block their activation, thereby protecting cells from stress-induced damage while allowing continued high-density cultivation and production

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the chemical environment parameters by adding specific molecular compounds that alter the stress response profile of the culture system. By changing the presence and concentration of stress pathway modulators in the media, the system can maintain cell viability under high-productivity conditions that would otherwise be lethal

Inventive Principle:
Principle #35Parameter changes

2Reliability

If stress control measures are implemented, then cell viability improves, but process complexity increases

Engineering Contradiction:
Improvecell viabilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and targets specific molecular stress pathways individually using dedicated control agents. Rather than implementing a complex integrated control system, the approach isolates key stress pathways (heat shock, apoptosis, oxidative stress) and applies specific inhibitors or modulators to each, simplifying the overall control strategy while maintaining effectiveness

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs small-molecule chemical agents that are inexpensive, easy to add to the media, and act transiently to control stress pathways. These simple chemical additives replace complex monitoring and control equipment, providing effective stress management through low-cost, easily implemented solutions

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

Data Source

PatentUS10336984B2Method of molecular stress control
Publication Date: 2019.07.02 CPSI HLDG
  • US10336984B2 patent drawing
  • US10336984B2 patent drawing
  • US10336984B2 patent drawing

AI summary

A novel class of agents has been identified to serve as cell-guard agents and/or target-specific supplements to increase cell quality and yield, as well as select for target cell populations. Several additive agents (both natural and synthetic) have been identified, including Vitamin D3, NAC, resveratrol, salubrinal, AKT, and tunicamycin (among others) that hold promise for application in cell models. In one embodiment, hypothermic stress regimes are utilized. In another embodiment, normothermic conditions are utilized while other stressors are tested in the processing. The methods of maintaining mass cell cultures and/or selecting out particular cell populations for further research and clinical use represents an important step in therapeutic discovery.