Optimization of the Process of Chinese Hamster Ovary (CHO) Cell Fed-Batch Culture to Stabilize Monoclonal Antibody Production and Overall Quality: Effect of pH Control Strategies In this study, the effects of the pH control strategy on CHO cell fed-batch culture to produce an antibody (EA5) were first investigated in a 3 L bioreactor. The results indicate that controlling the culture pH at 7.2 during the fed-batch stage could produce a higher EA5 titer of 6.1 g/L with a lower Man5 ratio of 2.2% by day 14. Based on this, an optimized CHO cell fed-batch culture was conducted in a 15 L bioreactor to verify its effectiveness and stability. In this case, on day 14, an EA5 titer of 6.5 g/L was achieved with productivity of 0.46 g/L/day, which was 1.07-fold higher compared to that of the culture in the 3 L bioreactor. Furthermore, regarding the product quality, a monomer abundance of 96.0%, a main peak of 55.0%, and a Man5 proportion of 2.4% were maintained in the 15 L bioreactor. https://lnkd.in/gbjSJ3zE #aspenalert #biotech #bioprocess
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Custom Conformational Bioactive Soluble Cis-Dimer Proteins – ? Fast-track your Drug Discovery Program! ? Proteins form homo-, hetero-, or oligomerization in the cellular environment to regulate a range of cellular processes. An estimate of 30-50% of proteins is oligomeric and over 50% of those are dimeric proteins. Receptor dimerization is a common mechanism for receptor-target interaction and catalytic activity. Dimeric proteins possess a quaternary structure, the highest protein structural order. Targeting quaternary conformational epitopes of the dimeric interface is critical for therapeutic antibodies with better specificity and potency. ? The challenge is engineering conformationally stable bioactive cis-dimeric proteins. ? Conigen Experts are dedicated to engineering bioactive conformational dimer proteins to advance discovery of next generation therapeutics. #ProteinEngineering #ConformationalDimerProteins #BioactiveProteins ? Learn more: https://lnkd.in/eaW7BsHe
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This article explores the use of POROS Caprylate resin as a tool for high-aggregate selectivity, enabling fewer chromatography steps while increasing process yield. Advancements in modern engineered monoclonal antibody (mAb)–based therapeutics has led to a range of innovative and effective biomolecules and higher titers. However, the production process can result in high levels of aggregation and other product related impurities, posing downstream purification challenge. Learn about a purification solution that addresses these challenges. Read this article to explore a resin for use in flow-through mode to efficiently and effectively remove high levels of aggregates, leached protein A, and host cell proteins in modern mAb-based therapeutic production processes: https://lnkd.in/e2J5CSQy #bioprocessing #purification #chromatographyresin #lifesciences #bioproduction #mAbs
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At https://lnkd.in/gNJyKun4 request samples and learn how Nuvia wPrime 2A Resin increased bispecific antibody (bsAb) yield from 30% to 75%, and reduced monoclonal antibody (mAb) process host cell proteins (HCPs) and high molecular weight (HMW) aggregates, by Merck & Co., Inc.'s Michael Rauscher, Process R&D, in Rahway, NJ, USA, in this Ask the Expert webcast presented in partnership with BioProcess International! Nuvia wPrime 2A Media is coming soon - finally, a scalable weak anion exchange + hydrophobic interaction (AEX-HIC) mixed-more resin for small- to large-scale biomolecule purification that offers a wide design space and unique selectivity for difficult-to-remove impurities. #biopharma #pharmaceuticalmanufacturing #lifesciences
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Advancements in modern engineered monoclonal antibody (mAb)–based therapeutics has led to a range of innovative and effective biomolecules and higher titers. However, the production process can result in high levels of aggregation and other product related impurities, posing downstream purification challenge. Learn about a purification solution that addresses these challenges. Read this article to explore a resin for use in flow-through mode to efficiently and effectively remove high levels of aggregates, leached protein A, and host cell proteins in modern mAb-based therapeutic production processes: https://lnkd.in/e2J5CSQy #bioprocessing #purification #chromatographyresin #lifesciences #bioproduction #mAbs
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?? From Theory to Practice: Tools in ADC Early Discovery Antibody-Drug Conjugates (#ADC) represent an advantage in #biotechnology, allowing us to deliver potent payloads directly to targeted cells, minimizing side effects. There are plenty of options for attaching these payloads to large monoclonal antibodies, but conjugation to small antibody formats like VHHs needs very specific reactive 'handles'. Recently, we faced a unique challenge: a customer requested primary screening in a format with a pre-engineered handle. This modification could potentially affect the #VHH antibody’s functionality, and needed to work in high throughput. After some proof-of-concept studies to assess the risks of C-terminal cysteines, it worked much better than anyone expected. ? Curious about the results? Check out our latest blog: https://loom.ly/fflx7EM #Biotech #CRO #AntibodyDiscovery
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Advancements in modern engineered monoclonal antibody (mAb)–based therapeutics has led to a range of innovative and effective biomolecules and higher titers. However, the production process can result in high levels of aggregation and other product related impurities, posing downstream purification challenge. Learn about a purification solution that addresses these challenges. Read this article to explore a resin for use in flow-through mode to efficiently and effectively remove high levels of aggregates, leached protein A, and host cell proteins in modern mAb-based therapeutic production processes: https://lnkd.in/e2J5CSQy #bioprocessing #purification #chromatographyresin #lifesciences #bioproduction #mAbs
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Purification of bispecific antibodies has been a tedious task for too long. Nuvia wPrime 2A might just be an answer to low yields and impurities ??
At https://lnkd.in/gNJyKun4 request samples and learn how Nuvia wPrime 2A Resin increased bispecific antibody (bsAb) yield from 30% to 75%, and reduced monoclonal antibody (mAb) process host cell proteins (HCPs) and high molecular weight (HMW) aggregates, by Merck & Co., Inc.'s Michael Rauscher, Process R&D, in Rahway, NJ, USA, in this Ask the Expert webcast presented in partnership with BioProcess International! Nuvia wPrime 2A Media is coming soon - finally, a scalable weak anion exchange + hydrophobic interaction (AEX-HIC) mixed-more resin for small- to large-scale biomolecule purification that offers a wide design space and unique selectivity for difficult-to-remove impurities. #biopharma #pharmaceuticalmanufacturing #lifesciences
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Impact of Fed-Batch Process Intensification on the Productivity and Product Quality of Two CHO Cell Lines Expressing Unique Novel Molecular Format Proteins Novel molecular format (NMF) proteins, such as bispecific antibodies (BsAbs), are structures capable of multispecific binding, allowing for expanded therapeutic functionality. In this study, the impact of a high inoculation density (HID) fed-batch process on the productivity and product quality attributes of two CHO cell lines expressing unique NMFs, a monospecific antibody with an Fc-fusion protein and a bispecific antibody, compared to low inoculation density (LID) platform fed-batch processes was evaluated. It was observed that an intensified platform fed-batch process increased product concentrations by 33 and 109% for the two uniquely structured complex proteins in a shorter culture duration while maintaining similar product quality attributes to traditional fed-batch processes. https://lnkd.in/g6zkKNAK #aspenalert #biotech #bioprocess
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Producing engineered extracellular vesicles for therapeutics applications: in this study, Kristin Luther, Joe Nabhan at Vesigen Therapeutics, Inc. and collaborators evaluated two scalable strategies for generating GFP-loaded ARMM-engineered EVs: transient transfection and stable cell line-based production. The upstream ARMM production processes used a suspension HEK293-derived line called 5B8 from Lonza, with production assessed in both shake flasks and bioreactors. For downstream ARMM purification, they employed Tangential Flow Filtration and Anion Exchange Chromatography https://lnkd.in/eWs8TfSM In vivo, ARMMs demonstrated rapid biodistribution, primarily to the spleen and liver, with lesser distribution to the kidneys and lungs. The successful scale-up of ARMM production highlights the potential of engineered EVs. An article also authored by Ali Navaei, Leah Gens, Carson Semple, Pearl Moharil, Ilaria Passalacqua, Komal Vyas, Qiyu Wang, Shu-Lin Liu, Lucy Sun, Senthil Ramaswamy and Davide Zocco #extracellularvesicles #exosomes #bioengineering #translationalmedicine #cellculture #Vesiculab
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Small-Angle X-Ray Scattering as a Powerful Tool for Phase and Crystallinity Assessment of Monoclonal Antibody Crystallites in Support of Batch Crystallization Crystalline suspensions of monoclonal antibodies (mAbs) have great potential to improve drug substance isolation and purification on a large scale and to be used for drug delivery via high-concentration formulations. Crystalline mAb suspensions are expected to have enhanced chemical and physical properties relative to mAb solutions delivered intravenously, making them attractive candidates for subcutaneous delivery. This contribution describes a novel crystal structure of the antibody pembrolizumab and demonstrates the usefulness of small-angle X-ray scattering (SAXS) for characterizing its crystalline suspensions. https://lnkd.in/gEKUJ3qw #aspenalert #biotech #bioprocess
Small-Angle X-ray Scattering as a Powerful Tool for Phase and Crystallinity Assessment of Monoclonal Antibody Crystallites in Support of Batch Crystallization
pubs.acs.org
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Technical Sales Specialist for Applikon Bioreactors at Getinge
7 个月Good to know!