Co2 Profile Cultivation

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This invention describes a method for improving the production of proteins, such as antibodies, by genetically engineering mammalian cells (like CHO cells) to express human carbonic anhydrase II (hCAII). By controlling and gradually increasing the carbon dioxide (CO2) levels during cell cultivation, these modified cells can more effectively regulate their internal pH and improve the yield and quality of the target proteins produced.

Use CasesContent extracted from patent full text and abstract with AI.

• Manufacturing of therapeutic antibodies and other recombinant proteins in the pharmaceutical industry
• Large-scale bioreactor protein production where CO2 accumulation is a challenge
• Biotechnology firms optimizing mammalian cell lines for higher productivity
• Academic or industrial research requiring efficient cell lines for protein expression studies

BenefitsContent extracted from patent full text and abstract with AI.

• Enhanced control of intracellular pH in production cells, which supports optimal enzyme activity and cell function
• Improved protein yield (notably antibodies), increasing process efficiency and reducing costs
• More stable and predictable glycosylation profiles in produced proteins, critical for therapeutic efficacy
• Better viability and resilience of production cell lines under stressful industrial scale CO2 conditions
• Shorter recovery times from acid loads, improving cell survival during batch processing
• Flexibility to optimize cultivation strategies, potentially further boosting productivity with inducible expression systems

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Inventors & Applicants

Patent Abstract

A dissolved CO2 change in aqueous solutions affects directly the intracellular pH (pHi) value as it does so by influencing therefore important cellular processes. The enzyme carbonic anhydrase II (CAII) catalyzes the equilibrium of CO2 in aqueous solutions and because it alters the speed at which this equilibrium is reached it was identified as a strong candidate for metabolic engineering. The cell line stably expressing hCAII presented a better initial re-alkalinization of cytoplasm after induced CO2 acid load. The most alkaline pHi value associated to the lowest pHi variations was observed for that cell line in long term increased CO2 levels. In general, the increased CO2 profile triggered the quicker progress of G0G1-cell cycle phase for both transfected and control cell lines.