A5032096531- Viral Infectious Diseases and Gene Expression in Insects
- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Virus-based gene therapy research
- Microbial Natural Products and Biosynthesis
- Glycosylation and Glycoproteins Research
- Fluid Dynamics and Mixing
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Mineral Processing and Grinding
- Microbial Inactivation Methods
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Fungal and yeast genetics research
- Chemical Synthesis and Analysis
- Bacterial Genetics and Biotechnology
- Banking stability, regulation, efficiency
- Flexible and Reconfigurable Manufacturing Systems
- Transgenic Plants and Applications
- Cell Adhesion Molecules Research
- Microfluidic and Bio-sensing Technologies
- Economic, financial, and policy analysis
- Cyclone Separators and Fluid Dynamics
- Carbohydrate Chemistry and Synthesis
Bristol-Myers Squibb (United States)
2017-2025
Bristol-Myers Squibb (Germany)
2023
Boehringer Ingelheim (United States)
2020
Synthetic Biologics (United States)
2020
Boehringer Ingelheim (Germany)
2013
Biogen (United States)
2010
India Habitat Centre
2004
Energy and Resources Institute
2004
University of Minnesota
1994-2000
As of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development but also chemistry, manufacturing, controls (CMC) process at speed are required to address this highly unmet patient need. CMC consists early- late-stage ensure sufficient manufacturing yield...
Abstract The use of hybrid models is extensively described in the literature to predict process evolution cell cultures. These combine mechanistic and machine learning methods, allowing prediction complex behavior, presence many variables, without need collect a large amount data. Hybrid cannot be directly used final product critical quality attributes, or CQAs, because they are usually measured only at end process, more knowledge needed for classes CQAs. historical can instead CQAs better;...
Recombinant adeno-associated virus (rAAV) is a promising delivery vehicle for cell and gene therapies. Upstream development faces challenges like low productivity inconsistent performance despite advancements. This study presents scale-up design robust rAAV production at 250 L scale using transfection system. Initial process in shake flasks optimized plasmid ratio to improve production. However, genome titer decreased by up 50% stirred-tank bioreactors, likely due mechanical shear forces....
A recombinant monoclonal antibody produced by Chinese hamster ovary (CHO) cell fed-batch culture was found to have amino acid sequence misincorporation upon analysis intact mass and peptide mapping spectrometry. detailed revealed multiple sites for asparagine were being randomly substituted serine, pointing mistranslation as the likely source. Results from time-course of suggest that occurring midway through process correlated reduction below detectable levels in culture. Separate shake...
The importance of speed to clinic for medicines that may address unmet medical needs puts pressure on product development timelines. Historically, both toxicology and first-in-human clinical materials are generated using the same clonal-derived cells ensure safety minimize any risks. However, cell line with single cloning is time consuming, aggravated by needed screen a lead clone based stability manufacturability. In order achieve faster timelines, we have used pools up six clones earlier...
Fed-batch process intensification with a significantly shorter culture duration or higher titer for monoclonal antibody (mAb) production by Chinese hamster ovary (CHO) cells can be achieved implementing perfusion operation at the N-1 stage biomanufacturing. seed much final viable cell density (VCD) than conventional batch used to increase inoculation VCD subsequent fed-batch (referred as N stage), which results in growth phase, peak VCD, titer. In this report, we incorporated analytical...
Retrospective analysis of historic data for cell culture processes is a powerful tool to develop further process understanding. In particular, deploying retrospective analyses can identify important parameters controlling critical quality attributes, e.g., afucosylation, the production monoclonal antibodies (mAbs). However, challenge analyzing large high correlation between regressors (particularly media composition), which makes traditional analyses, such as variance and multivariate linear...
Abstract There are three main potential sources for cell shear damage existing in stirred tank bioreactors. One is the high energy dissipation immediate impeller zones; another from small gas bubble burst; and third entrance velocity (GEV) emitting sparger. While first two have been thoroughly addressed scale‐up of Chinese hamster ovary (CHO) culture knowing that a wide tolerable agitation range with non‐damaging exists use protectants like Pluronic F68 guard against caused by burst, GEV...
Abstract Single‐use bioreactors (SUBs, or disposable bioreactors) are extensively used for the clinical and commercial production of biologics. Despite widespread application, minimal results have been reported utilizing turndown ratio; an operation mode where working range bioreactor can be expanded to include low fluid volumes. In this work, a systematic investigation into free surface mass transfer cell growth in high single‐use is presented. This approach, which combines experimental...
The biosynthesis of secondary metabolites is closely linked to primary metabolism via the supply precursors, cofactors, and cellular energy. availability these precursors cofactors can potentially be rate-limiting for metabolism. A combined experimental kinetic modeling approach was used examine regulation flux in cephamycin biosynthetic pathway Streptomyces clavuligerus. parameters lysine 6-aminotransferase (LAT), first enzyme leading one which previously identified as being a enzyme, were...
The cellular distribution of the cephamycin biosynthetic enzyme lysine 6-aminotransferase (LAT) has been studied in Streptomyces clavuligerus hyphae by confocal microscopy using S65T mutant green fluorescent protein (GFP) as a reporter. LAT mediates first committed step biosynthesis secondary metabolite C S. clavuligerus. enzymic activity varies with time during growth liquid medium. To investigate if this temporal variation occurs uniformly amongst all hyphae, was transformed plasmid...
Improving productivity to reduce the cost of biologics manufacturing and ensure that therapeutics can reach more patients remains a major challenge faced by biopharmaceutical industry. Chinese hamster ovary (CHO) cell lines are commonly prepared for biomanufacturing single cloning post-transfection recovery, followed lead clone screening, generation research bank (RCB), culture process development, master (MCB) be used in early phase clinical manufacturing. In this study, it was found an...
Abstract BACKGROUND The stability of amino acids (AAs) in a highly concentrated cell culture medium is affected by preparation and storage conditions. Variability the concentration components (including AAs) can influence performance product quality attributes. RESULTS In this report, impact pH, temperature, temperature was evaluated on 16 AAs feed medium. Optimizing pH enabled an increase initial 30% plus 3.9 g L −1 tyrosine with no observed precipitation after 28 days. Up to 6.0 be...
Abstract Glycoproteins could be highly sialylated, and controlling the sialic acid levels for some therapeutic proteins is critical to ensure product consistency efficacy. N ‐acetylneuraminic (Neu5Ac, or NANA) ‐glycolylneuraminic (Neu5Gc, NGNA) are two most common forms of acids produced in mammalian cells. As Neu5Gc not humans can elicit immune responses, minimizing formation important this quality attribute complex glycoproteins. In study, a sialylated glycoprotein was used as model...
The biosynthesis of beta-lactams is one the most thoroughly studied antibiotic pathways. availability characteristics and time profiles activities enzymes involved in allows to critically evaluate potential rate-limiting steps its production. Our approach understanding control beta-lactam has been pursued using a two-stage strategy: (1) predict kinetic model (2) relax by engineering biosynthetic pathway or altering parameters predicted key enzyme. Kinetic analysis dynamics cephamycin C...