| Contributors |
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ix | |
| Abbreviations |
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xi | |
| Preface |
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xiii | |
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Overview on mammalian cell culture |
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Cell line development and culture strategies: future prospects to improve yields |
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3 | (16) |
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3 | (2) |
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Cell line transfection and selection |
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5 | (1) |
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Increase in efficiency in selecting a producer cell line |
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6 | (2) |
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Stability of gene expression |
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8 | (1) |
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Optimization of the fermentation process |
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9 | (2) |
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11 | (1) |
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11 | (1) |
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12 | (7) |
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13 | (1) |
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13 | (6) |
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Use of DNA insulator elements and scaffold/matrix-attached regions for enhanced recombinant protein expression |
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19 | (18) |
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19 | (1) |
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20 | (1) |
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Use of insulators and S/MARs can reduce the effects of heterochromatin on transgene expression |
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20 | (2) |
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22 | (1) |
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The scaffold/matrix-attachment regions |
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23 | (2) |
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Binding proteins for DNA insulators and S/MARs |
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25 | (1) |
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DNA insulators or S/MARs can be incorporated into expression vectors |
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26 | (4) |
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DNA insulators and S/MARs act in a context-dependent manner |
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30 | (1) |
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31 | (6) |
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32 | (1) |
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32 | (5) |
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Targeted gene insertion to enhance protein production from cell lines |
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37 | (20) |
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37 | (2) |
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Identification of genomic `hot spot' loci |
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39 | (1) |
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Recombinase-mediated site-specific gene insertion |
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39 | (5) |
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Cre, Flp, and φC31 recombinase systems |
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40 | (1) |
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Recombinase-mediated cassette exchange |
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40 | (3) |
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Gene insertion at native `pseudo' recombinase sites |
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43 | (1) |
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Modification of recombinases and their target sites |
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43 | (1) |
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Emerging technologies for targeted gene insertion |
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44 | (6) |
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Homing endonucleases in HDR-mediated targeted gene insertion |
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46 | (1) |
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Targeted gene insertion into native loci by zinc finger, nucleasemediated, high-frequency, homologous recombination |
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47 | (3) |
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50 | (7) |
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52 | (5) |
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Recombinant human IgG production from myeloma and Chinese hamster ovary cells |
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57 | (24) |
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57 | (1) |
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The need for recombinant human antibodies |
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57 | (1) |
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58 | (1) |
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Decoupling antibody isolation and production |
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58 | (1) |
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59 | (1) |
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Chinese hamster ovary cells |
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60 | (1) |
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60 | (1) |
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The glutamine synthetase system |
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60 | (1) |
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61 | (1) |
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Bioreactor process strategies |
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62 | (1) |
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IgG supply during antibody development |
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62 | (1) |
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Strategies for cell line engineering during clinical development |
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63 | (1) |
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Cost of goods and intellectual property |
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64 | (1) |
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Recombinant human IgG production from myeloma and CHO cells |
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64 | (10) |
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Creation of CHO and NSO cell lines expressing IgG |
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64 | (1) |
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Cell expansion, subculture and production reactor experiments |
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65 | (1) |
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Northern and western blotting |
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65 | (1) |
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Comparison of results of transfections from GS-NSO and GS-CHO |
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65 | (1) |
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Dilution cloning and analysis of clonal heterogeneity |
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66 | (1) |
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Analysis of instability of a GS-NSO cell line |
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67 | (1) |
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Output of transfections of GS-NSO and GS-CHO |
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68 | (1) |
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IgG production stability of candidate GS-NSO clones |
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69 | (1) |
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IgG production stability of GS-CHO transfectants |
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70 | (1) |
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Fed-batch bioreactor process for GS-NSO and GS-CHO |
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71 | (1) |
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Analysis of IgG quality produced from GS-CHO and GS-NSO bioreactor processes |
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71 | (3) |
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Comparative yield of different human IgGs produced from CHO or NSO cells |
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74 | (1) |
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74 | (7) |
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76 | (1) |
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76 | (5) |
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Cell culture media development: customization of animal origin-free components and supplements |
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81 | (22) |
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81 | (1) |
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Types of cell culture media |
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82 | (1) |
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Components of animal origin |
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83 | (12) |
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85 | (2) |
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87 | (1) |
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88 | (7) |
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Summary and considerations for the future |
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95 | (8) |
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98 | (1) |
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98 | (5) |
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Post-translational modification of recombinant antibody proteins |
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103 | (28) |
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103 | (1) |
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Common post-translational modifications |
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104 | (1) |
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Recombinant antibody therapeutics |
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105 | (1) |
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Structural and functional characteristics of human antibodies |
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106 | (1) |
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The human IgG subclasses: Options for antibody therapeutics |
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106 | (2) |
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The structure of human IgG antibodies |
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108 | (2) |
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110 | (2) |
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112 | (3) |
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Cell engineering to influence glycoform profiles |
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115 | (1) |
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IgG glycoforms and Fc effector functions |
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116 | (2) |
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Glycosylation engineering |
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118 | (1) |
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Pharmacokinetics and placental transport |
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118 | (1) |
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Antibody therapeutics of the IgA class |
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119 | (1) |
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Non-antibody recombinant (glyco)protein therapeutics, `biosimilar' and `follow-on' biologics |
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120 | (3) |
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121 | (1) |
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Tissue-type plasminogen activator |
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122 | (1) |
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Granulocyte-macrophage colony stimulating factor (GM-CSF) |
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122 | (1) |
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Granulocyte-colony stimulating factor |
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122 | (1) |
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122 | (1) |
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123 | (8) |
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123 | (8) |
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Metabolic engineering to control glycosylation |
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131 | (18) |
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131 | (1) |
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Manipulation of fucose content using RNAi technology in CHO cells |
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132 | (11) |
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Metabolic engineering of fucose content with an existing antibody production line |
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132 | (4) |
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Metabolic engineering of fucose content with simultaneous new stable cell line generation |
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136 | (4) |
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Effect of fucosylation levels on FcyR binding |
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140 | (3) |
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Effects of fucose content on antibody-dependent cellular cytotoxicity |
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143 | (1) |
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143 | (6) |
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146 | (1) |
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146 | (3) |
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An alternative approach: Humanization of N-glycosylation pathways in yeast |
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149 | (24) |
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149 | (3) |
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Yeast as host for recombinant protein expression |
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152 | (1) |
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N-linked glycosylation overview: Fungal versus mammalian |
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152 | (2) |
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A brief history of efforts to humanize N-linked glycosylation in fungal systems |
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154 | (1) |
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Sequential targeting of glycosylation enzymes is a key factor |
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155 | (2) |
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Replication of human-like glycosylation in the methylotrophic yeast Pichia pastoris |
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157 | (1) |
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A library of α-1, 2 mannosidases |
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157 | (1) |
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Transfer of N-acetylglucosamine |
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158 | (1) |
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Two independent approaches towards complex N-glycans: How to eliminate more mannoses |
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159 | (2) |
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Some metabolic engineering: Transfer of galactose |
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161 | (1) |
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More metabolic engineering: Sialic acid transfer. The final step |
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162 | (1) |
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Glyco-engineered yeast as a host for production of therapeutic glycoproteins |
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162 | (2) |
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N-linked glycans and pharmacokinetics of therapeutic glycoproteins |
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164 | (1) |
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N-glycans and their role in tissue targeting of glycoproteins |
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164 | (1) |
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N-glycans can modulate the biological activity of therapeutic glycoproteins |
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165 | (1) |
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Control of N-glycosylation offers advantages |
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165 | (1) |
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166 | (7) |
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166 | (7) |
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Perfusion or fed-batch? A matter of perspective |
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173 | (10) |
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173 | (2) |
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Factors affecting the decision on choosing the manufacturing technology |
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175 | (5) |
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175 | (4) |
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Facility design and scope (product dedicated versus multi-product) |
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179 | (1) |
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Impact of switching from perfusion to fed-batch |
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180 | (1) |
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180 | (1) |
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181 | (1) |
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182 | (1) |
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182 | (1) |
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182 | (7) |
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Direct costs of manufacturing |
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182 | (7) |
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183 | (1) |
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183 | (4) |
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184 | (1) |
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184 | |
Lisainfo e-raamatute kohta