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  • 1.
    Chotteau, Veronique
    et al.
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Jiang, Yun
    Biovitrum/SOBI, Sweden.
    westin, Jeanette
    Biovitrum/SOBI, Sweden.
    Dahlenborg, K
    Biovitrum/SOBI, Sweden.
    Sjöblom-Hallén, A
    Biovitrum/SOBI, Sweden.
    Svensson, Erik
    Biovitrum/SOBI, Sweden.
    Öberg, Mikael
    Biovitrum/SOBI, Sweden.
    Development of a fed-batch process for the production of a recombinant protein X in CHO-GS system: Case study from the cell to reactor process ready for pilot scale cultivation2010In: Cells and Culture: Proceedings of the 20th ESACT / [ed] Noll T, Springer Science+Business Media B.V., 2010, 723-725 p.Conference paper (Other academic)
    Abstract [en]

    A new cell line was created using CHO-GS system. The most promising clones were adapted to different base cultivation media leading to the selection of one medium. The fed-batch process development was performed in spinner, shake flask and bioreactor scale. It included the selection of a feed medium, the choice of the feed strategy and the optimisation of the glucose feeding. The process was then simplified by using a single feed including the feed medium and the glucose feed. Finally up-scaling parameters like aeration and CO2 stripping were studied in 3 L and 15 L bioreactors in preparation for pilot scale operation. This process proved to be robust, reproducible and suitable for large and commercial scale operation.

  • 2.
    Chotteau, Veronique
    et al.
    KTH, School of Biotechnology (BIO), Bioprocess Technology (closed 20130101).
    Lindqvist, Anna
    KTH, School of Biotechnology (BIO), Bioprocess Technology (closed 20130101).
    Study of the effect of high pH and alkali addition in a cultivation of Chinese Hamster Ovary cell2012In: Proceedings of the 21st Annual Meeting of the European Society for Animal Cell Technology (ESACT) / [ed] Jenkins, Nigel; Barron, Niall; Alves, Paula, Springer Science+Business Media B.V., 2012, 323-326 p.Conference paper (Refereed)
    Abstract [en]

    This work aimed at studying the impact of alkali addition in a Chinese Hamster Ovary cell culture. Two phenomena were studied, the kinetic rate of direct cell death in presence of high pH and the effect of transitory single contact of high pH on cell viability and growth. Contact with pH 11 or 10 did not provoke immediate cell lysis. The cells survived several minutes to such conditions. Contact with pH 11 during 2 minutes, with pH 10 during 5 minutes, with pH 9 during 5 minutes or 10 minutes did not affect the viability. In these conditions, the growth was not affected except after 5 minutes contact at pH 10 or 10 minutes contact at pH 9 for which the growth was slowed down the first day only. As expected, NaOH addition affected the cells more than Na2CO3 addition. This was due to a higher pH but could be even observed at the same pH (10).

  • 3.
    Chotteau, Veronique
    et al.
    KTH, School of Biotechnology (BIO).
    Wåhlgren, Caroline
    Biovitrum/SOBI, Sweden.
    Jiang, Yun
    Biovitrum/SOBI, Sweden.
    Svensson, Erik
    Biovitrum/SOBI, Sweden.
    Process for cultivating animal cells comprising the feeding of plant-derived peptones2005Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    A process for cultivating animal cells producing complex proteins, wherein one plant-derived peptone or a combination of plant-derived peptones is fed to the cell culture, as well as a method for reducing the toxic effect of over-feeding amino acids during a fed-batch process for cultivating animal cells producing complex proteins.

  • 4.
    Chotteau, Veronique
    et al.
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Wåhlgren, Caroline
    Biovitrum/SOBI, Sweden.
    Pettersson, Helena
    Biovitrum/SOBI, Sweden.
    Effect of Peptones and Study of Feeding Strategies in a CHO Based Fed-batch Process for the Production of a Human Monoclonal Antibody2007In: Cell Technology for Cell Products: Proceedings of the 19th ESACT Meeting, Harrogate, UK, June 5-8, 2005 / [ed] Smith R, Dordrecht, The Netherlands: Springer Netherlands, 2007, 371-374 p.Conference paper (Other academic)
    Abstract [en]

    Eight commercial peptones, derived from plants, were studied for their ability of improving the cell growth and the productivity of a CHO cell line producing a human monoclonal antibody. They were also compared to yeast, lactalbumin and meat derived peptones. Seven plant peptones were selected and further studied in combination by Design of Experiment. The best three peptones were then tested in combinations in fed-batch cultivation. The fed-batch process was based on low concentrations of glucose and glutamine with feeding of amino acids, peptones and feed medium including vitamins, metal traces and biosynthesis precursors. This process was based on Biovitrum protein-free proprietary medium for the base medium and the feeding medium. Different feeding strategies, different peptone combinations and phosphate feeding were studied for their ability to improve the cell density, the cell specific productivity and the cultivation longevity

  • 5.
    Clincke, Marie-Francoise
    et al.
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Mölleryd, Carin
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Zhang, Ye
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Lindskog, Eva
    GE Healthcare, Uppsala, Sweden.
    Walsh, Kieron
    GE Healthcare, Westborough, MA, USA.
    Chotteau, Veronique
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Study of a recombinant CHO cell line producing a monoclonal antibody by ATF or TFF external filter perfusion in a WAVE Bioreactor™2011In: BMC Proceedings, 2011, Volume 5, Supplement 8, P105, BioMed Central, 2011, 105- p.Conference paper (Refereed)
    Abstract [en]

    Major advantages of perfusion are high cell numbers and high total production in a relatively small size bioreactor. Moreover, perfusion is optimal when the product of interest is unstable or if the product yield is low. On the other hand, disadvantages are for example technical challenges originating from non-robust cell separation devices as well as sterility concerns from the more complex set-up needed.

    In the present work, the use of a WAVE Bioreactor™ system 20/50 in perfusion mode with10 L disposable Cellbag™ bioreactors customized with two dip tubes in combination with disposable hollow fiber filters as external cell separating devices were investigated. A comparison between Alternating Tangential Flow (ATF) and Tangential Flow Filtration (TFF) was performed using a recombinant CHO cell line producing a monoclonal antibody (mAb) as a model system. 

  • 6.
    Dolfe, Lisa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Process development for the control of solubility of Affibody® molecules2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this study the aim was to optimize the production of the Affibody fusion-protein Z03358-

    ABD094-(S4G)3-IL2 with regard to the amount of soluble protein produced. However,

    problems with reproducibility with this protein and the chosen expression system were

    encountered. Therefore, expression of the His-tagged Affibody His6-(Z05477)2 was

    evaluated using the same expression system as well as expression in another well

    characterized expression system.

    Both target proteins are of therapeutic interest. One of the proteins is an IL2 fusion

    protein (Z03358-ABD094-(S4G)3-IL2) that bind the platelet-derived growth factor receptor β

    (PDGFR-β). PDGF signaling is of interest in cancer treatment where, among other things, the

    effects of PDGF on tumor angiogenesis is researched. The His6-(Z05477)2 protein has a

    classified target but is developed as a therapeutic in the area of inflammation and autoimmune

    disease. Both model proteins are known to be difficult to purify due to low solubility.

    The two E. coli expression systems investigated and compared were BL21(DE3) and

    Lemo21(DE3). The fusion protein Z03358-ABD094-(S4G)3-IL2 was produced in

    BL21(DE3) in inclusion bodies with a yield of 4.95 g/l. An optimized process for the

    expression of His6-(Z05477)2 using BL21(DE3) was developed with a yield of 6.6 g/l soluble

    protein after expression at 30°C for 6 h.

  • 7.
    Eriksson, Sara
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Quality by Design (QbD) in Biochemical Applications: Possibilities and Limitations2013Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 8.
    Jiang, Yun
    et al.
    Biovitrum/SOBI, Sweden.
    Svensson, Erik
    Biovitrum/SOBI, Sweden.
    Chotteau, Veronique
    Improvement of a CHO Fed-Batch Process by Fortifying with Plant Peptones2010In: Cells and Culture: ESACT Proceedings, 2010, Volume 4, Part 3 / [ed] Noll T, Springer, 2010, 281-284 p.Conference paper (Other academic)
    Abstract [en]

    A serum-free fed-batch process was developed for production of a human monoclonal antibody in Chinese hamster ovary (CHO) cells based on Biovitrum’s proprietary low protein serum-free medium without animal derived components (BVT4). The cells were fed with glucose, glutamine and Biovitrum’s proprietary low protein serum-free feed medium without animal derived components enriched with amino acids, vitamins, metal traces, peptones, and biosynthesis precursors. To improve the performance of the fed-batch process, we developed the use of plant peptones by studying the dose and timing of the peptone feeding. Different doses of peptone cocktail and amino acid cocktail, as well as different combinations of pep- tone and amino acid cocktails were first screened in 50 ml filter tubes on an AgCell shaker table. The best combinations were then assessed in spinner and 3 L bioreactor cultures. To reinforce our findings, the antibody-producing CHO cells were adapted to a disclosed serum-free medium DMEM/F12 and the beneficial effects of pep- tones were confirmed in a fed-batch process based on the DMEM/F12 serum-free medium.

  • 9.
    Kronander, Björn
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Quantification of alpha-synuclein in cerebrospinal fluid2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analyses of blood or cerebrospinal uid. Currently, diagnosis, measurement of disease progression and response to therapeutic intervention are based on clinical observation, but the rst neuronal dysfunction precede the earliest recognition of symptom by at least 5 - 10 years. A potential diagnostic biomarker is oligomeric alpha-synuclein which in recent papers have reported a signicant quantitative dierence between PD and controls. In this master thesis, a method for measuring oligomeric levels of alpha-synuclein is presented together with a monomeric measuring commercial kit used to measure alpha-synuclein in a preclinical model of PD. A signicant dierence of monomeric levels could be detected between two weeks and four weeks post injection of a vector containing the gene for human alpha-synuclein, no signicant dierence between four and eight weeks was found.

  • 10.
    Källgren, Joanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Strukturella och funktionella studier av fyra enzymer involverade i cellväggsbiosyntes hos Mycobacterium tuberculosis2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The pathogenic bacterium Mycobacterium tuberculosis (Mt) is the causative agent of tuberculosis, a widespread and fatal infectious disease. Today, treatment against tuberculosis involves a combination of drugs, which need to be taken for at least six months and which often causes severe side effects. Therefore, new drugs that are more effective and that give fewer side effects are needed. A characteristic feature of the Mt bacterium is its very complex and thick cell wall, which prevents many potential drug molecules from penetrating it. Inhibiting any one of the enzymes that are involved in its biosynthesis would therefore seem to be a good strategy for eliminating the Mt bacteria. The aim of this study was to characterize four enzymes involved in Mt cell wall biosynthesis. In order to do that, they were produced recombinantly in E. coli and purified. Crystallization experiments were set up in order to produce diffracting crystals, with the aim of structure determination and drug design.

  • 11.
    Matheis, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Preparation of a Class A certification in the field of pharmaceutical packaging through mapping and optimization of business processes and implementation of the Oliver Wight Class A Behaviors for Business Excellence.2014Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    On the road to success, companies need to fulfil their stakeholders’ expectations. On the road to business excellence, companies need to exceed these expectations. Oliver Wight Inc. has established a certification called Class A Business, which shows that a company is exceeding stakeholders’ expectations and that it performs in the upper quartile in its respective industry. The Class A Business certification is awarded, once a company fulfils a certification checklist with Class A Business criteria. To get to this point, a company can design their road to business excellence by following a specific set of nine Class A Behaviors.

    This study focuses on four of these behaviors, divided in three parts, and how they are implemented at a pharmaceutical packaging department at Roche in Kaiseraugst, Switzerland. In addition, through employee feedback potential areas of improvement are identified.

    For a company to understand how it is running, it has to understand its underlying processes. Once the processes are in place, a process-oriented way of thinking can change a company to make decisions based on process’ needs rather than on individual preferences. Business processes and their potential for continuous improvement were the first part of the study. The second part of the study investigated the communication of different functions in the packaging process and how the flow of information could be improved. In the third part, the usage of operational metrics in the packaging department is researched by a user feedback survey.

    An innovative way to visualize meeting conversations was developed in this study to make meetings more tangible for the reader. This is a newly developed and never before described method for business research colorfully showing interactions in meetings.

    The results are very intriguing. Simple thought business elements seem to pose larger hurdles than would be expected sometimes.

  • 12.
    Strömme, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Niklasson, Gunnar A.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Ek, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Densification-induced conductivity percolation in high-porosity pharmaceutical microcrystalline cellulose compacts2003In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 82, no 4, 648-650 p.Article in journal (Refereed)
    Abstract [en]

    The percolation theory is established as a useful tool in the field of pharmaceutical materials science.It is shown that percolation theory, developed for analyzing insulator–conductor transitions, can beapplied to describe imperfect dc conduction in pharmaceutical microcrystalline cellulose duringdensification. The system, in fact, exactly reproduces the values of the percolation threshold andexponent estimated for a three-dimensional random continuum. Our data clearly show a crossoverfrom a power-law percolation theory region to a linear effective medium theory region at a celluloseporosity of ;0.7.

  • 13.
    Xia, Xin
    et al.
    Nanologica AB, Stockholm, och Dept of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University.
    Zhou, Chunfang
    Nanologica AB, Stockholm.
    Ballell, Luís
    Diseases of the Developing World, GlaxoSmithKline, Madrid, Spanien.
    Garcia-Bennett, Alfonso E
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    In vivo Enhancement in Bioavailability of Atazanavir in the Presence of Proton-Pump Inhibitors using Mesoporous Materials2012In: ChemMedChem, ISSN 1860-7179, Vol. 7, no 1, 43-8 p.Article in journal (Refereed)
    Abstract [en]

    Matters of the HAART! The current treatment for human immunodeficiency virus (HIV), HAART, makes use of a combination of antiretroviral drugs, which are poorly soluble in aqueous media. Enhancing the solubility of such drugs through the use of mesoporous materials could lead to improved treatment efficiency and might provide a solution to the drug-drug interaction problems associated with these types of therapeutic regimes.

1 - 13 of 13
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