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Control of recombinant protein productivity and quality in mammalian cell cultureRendall, Mark Harcus January 2000 (has links)
No description available.
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Spotřeba podobných biologických léčivých přípravků (biosimilars) v České Republice / Similar biotherapeutic agents (Biosimilars) Consumption in Czech RepublicVlachová, Kristýna January 2021 (has links)
Consumption of similar biological medicinal products (biosimilars) in the Czech Republic Author: Kristýna Vlachová Supervisor: PharmDr. Pavel Horký, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction: Biological treatment is a modern alternative to chemotherapeutics especially in patients with difficult-to-treat diseases of autoimmune origin, as well as patients with other diseases. Biosimilars are biological medicinal products similar to the original biologics. They are increasingly used in a wide range of indications. A new biosimilar drug is registered every year, as soon as the patent protection of the original biologics expires. The assumption is that the consumption of biosimilars and biologists in the Czech Republic will increase. The question is to what extent it will increase and what is the market share of biosimilars. Objective: The aim of the diploma thesis was to analyze the consumption of biosimilar epoetin, adalimumab, infliximab and etanercept in the Czech Republic in 2010-2020. Methods: A retrospective analysis of the consumption of biosimilars epoetin, adalimumab, infliximab and etanercept was performed from 1. 1. 2010 to 31. 12. 2020. The selection of specific biosimilars was made on the basis of their wide...
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Engineering Cell-Free Protein Expression Systems for Biotherapeutics and BiosensingHunt, John Porter 18 March 2021 (has links)
Therapeutic proteins have become a cornerstone of modern medicine since the FDA approval of recombinant human insulin in 1982. Likewise, biosensors transform chemical detection and disease diagnostics by identifying biomarkers, chemical contaminants, and infective agents. Long-standing methods for creating therapeutics and biosensors employ whole cells such as Escherichia coli (E. coli). Alternatively, cell-free protein synthesis (CFPS) employs the enzymatic reactions necessary for protein production and biosensing within a cell, but in an engineered reactor environment facilitating unprecedented access to and control over biochemical machinery, preservation by cryodesiccation for portable deployment, and functionality in cytotoxic applications. This dissertation reports advances in an E. coli CFPS production platform toward creating therapeutic proteins by this means. First, an endotoxin-free CFPS platform is created by optimizing fermentation and cell-extract harvest of an endotoxin-free E. coli strain. Next, liquid cell growth culture media is specially formulated to change chemical composition during cell culture and provide a streamlined method for producing high-yielding, endotoxin-free E. coli CFPS. Then, novel CFPS bioreactor formats are mathematically validated and developed which employ "hydrofoam" and oxygen to increase therapeutic protein production yield. Additionally, advances are reported in CFPS biosensing technology. First, a chimeric fusion protein incorporating the ligand binding domain of the human estrogen receptor is expressed in CFPS to detect estrogenic chemicals in the presence of human blood and urine. Next, the molecular mechanism of this protein construct is elucidated and the assay readout is optimized with mathematical simulations and CFPS. Then, CFPS is metabolically engineered to create a biosensor of L-glutamine, the most abundant amino acid in the body. Finally, this dissertation reports the development of a synergistic platform for potentially treating Acute Lymphoblastic Leukemia wherein CFPS is engineered to both produce the therapeutic protein crisantaspase and assess its activity in the presence of human serum for improved, potentially even personalized treatment of the disease. It is anticipated that the advances reported herein will contribute to the utility of in vitro or cell-free protein synthesis for therapeutic and diagnostic applications.
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A Proteomics Based Approach to Characterizing Subcutaneous TissuesEden Nichole Schipper (13174443) 29 July 2022 (has links)
<p>Biotherapeutic compounds such as monoclonal antibodies help millions of people worldwide. Currently, one of the most popular ways to deliver these compounds is via subcutaneous (SC) injection. While it is understood that SC drug delivery does change with respect to injection location, it is not understood why, as how the composition of SC changes as a function of location is unknown. In this study, liquid chromatography mass spectrometry was used to understand and describe how the SC tissue space changes on a molecular level. SC tissue from three different locations, belly, breast, and behind the ear, of Yucatan minipigs was harvested and analyzed to understand if and how SC tissue changes when anatomical location changes. It was determined that there were distinct differences between the proteins identified in the three anatomical locations. These differences included differences in relative cell populations, indicating that different anatomical locations of SC tissue have different functions. Additionally, an ex vivo human SC tissue model was used to identify a core human proteome, as well as determine compositional differences between female and male SC tissues. This model was also compared to the Yucatan minipig model to determine compositional similarities between all groups. Finally, proteomics were also used to ascertain whether the mass of SC tissue used affected the proteomic results of the sample. These results indicated that human SC identifies the same number of proteins down to samples of 10mg. This information can be used to design a proteomic experiment that uses core needle biopsies to determine what gauge needle should be used in a wide scale clinical study characterizing the human SC proteome. </p>
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