Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns

Biotechnology Progress

Volumn 26, Issue 6, 2010, Pages 1505-1527

  Del Val, Ioscani Jimenez ^a   Kontoravdi, Cleo ^a   Nagy, Judit M ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Glycosylation; Monoclonal antibodies; Quality by design

Indexed keywords

ASSESSMENT OF PROCESS; BIOLOGICAL PRODUCTS; BIOPHARMACEUTICAL INDUSTRY; CLINICAL EFFECTS; CLINICAL EFFICACY; CRITICAL PARAMETER; CRITICAL QUALITY; IN-VIVO; MANUFACTURING PROCESS; MONOCLONAL ANTIBODIES (MABS); PHARMACEUTICAL PRODUCTS; PRODUCT QUALITY; QUALITY BY DESIGN; QUALITY BY DESIGNS; REGULATORY BODIES; THERAPEUTIC MONOCLONAL ANTIBODIES;

ALLERGIES; DESIGN; ESTERIFICATION; GLYCOSYLATION; INDUSTRIAL ENGINEERING; MANUFACTURE; MERGERS AND ACQUISITIONS; MONOCLONAL ANTIBODIES; PRODUCTION ENGINEERING; SURFACE PLASMON RESONANCE;

DRUG PRODUCTS;

MONOCLONAL ANTIBODY;

ARTICLE; BIOSYNTHESIS; CHEMISTRY; DRUG DESIGN; GLYCOSYLATION; PHARMACEUTICS; QUALITY CONTROL;

ANTIBODIES, MONOCLONAL; DRUG DESIGN; GLYCOSYLATION; QUALITY CONTROL; TECHNOLOGY, PHARMACEUTICAL;

EID: 78650201043     PISSN: 87567938     EISSN: 15206033     Source Type: Journal    
DOI: 10.1002/btpr.470     Document Type: Article

References (171)

1. Reichert JM. Therapeutic monoclonal antibodies: trends in development and approval in the US. Curr Opin Mol Ther. 2002; 4: 110-118.
2. Pavlou AK, Reichert JM. Recombinant protein therapeutics: success rates, market trends and values to 2010. Nat Biotechnol. 2004; 22: 1513-1519.
3. Aggarwal S. What's fueling the biotech engine-2007. Nat Biotechnol. 2008; 26: 1227-1233.
4. Reichert JM. Monoclonal antibodies as innovative therapeutics. Curr Pharm Biotechnol. 2008; 9: 423-430.
5. Reichert JM, Wenger JB. Development trends for new cancer therapeutics and vaccines. Drug Discov Today. 2008; 13: 30-37.
6. Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004; 3: 711-715.
7. Kenett RS, Kenett DA. Quality by design applications in biosimilar pharmaceutical products. Accredit Qual Assur. 2008; 13: 681-690.
8. Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharmaceut Res. 2008; 25: 781-791.
9. Rathore AS, Winkle H. Quality by design for biopharmaceuticals. Nat Biotechnol. 2009; 27: 26-34.
10. Rathore AS, Saleki-Gerhardt A, Montgomery SH, Tyler SM. Quality by design: industrial case studies on defining and implementing design space for pharmaceutical processes part 2. BioPharm Int. 2009; 22: 36.
11. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Tripartite Guideline on Pharmaceutical Development Q8(R2). Geneva, Switzerland: ICH; 2009.
12. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Tripartite Guideline on Pharmaceutical Quality System Q10. Geneva, Switzerland: ICH; 2008.
13. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Tripartite Guideline on Quality Risk Management Q9. Geneva, Switzerland: ICH; 2005.
14. United States Food and Drug Administration. Guidance for industry: PAT-A framework for innovative pharmaceutical development, manufacturing, and quality assurance. Rockville, MD: US Food and Drug Administration; 2004.
15. Kozlowski S, Swann P. Current and future issues in the manufacturing and development of monoclonal antibodies. Adv Drug Deliv Rev. 2006; 58: 707-722.
16. Wright A, Morrison SL. Effect of glycosylation on antibody function: implications for genetic engineering. Trends Biotechnol. 1997; 15: 26-32.
17. Carter P. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer. 2001; 1: 118-129.
18. Cartron G, Watier H, Golay J, Solal-Celigny P. From the bench to the bedside: ways to improve rituximab efficacy. Blood. 2004; 104: 2635-2642.
19. Robinson M, Weiner L, Adams G. Improving monoclonal antibodies for cancer therapy. Drug Dev Res. 2004; 61: 172-187.
20. Scallon BJ, Snyder LA, Anderson GM, Chen Q, Yan L, Weiner LM, Nakada MT. A review of antibody therapeutics and antibody-related technologies for oncology. J Immunother. 2006; 29: 351-364.
21. Yamashita M, Katakura Y, Shirahata S. Recent advances in the generation of human monoclonal antibody. Cytotechnology. 2007; 55: 55-60.
22. Zhang Q, Chen G, Liu X, Qian Q. Monoclonal antibodies as therapeutic agents in oncology and antibody gene therapy. Cell Res. 2007; 17: 89-99.
23. Jefferis R. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov. 2009; 8: 226-234.
24. Jefferis R. Glycosylation of recombinant antibody therapeutics. Biotechnol Prog. 2005; 21: 11-16.
25. Liu H, Gaza-Bulseco G, Faldu D, Chumsae C, Sun J. Heterogeneity of monoclonal antibodies. J Pharm Sci. 2008; 97: 2426-2447.
26. Stern M, Herrmann R. Overview of monoclonal antibodies in cancer therapy: present and promise. Crit Rev Oncol Hematol. 2005; 54: 11-29.
27. Gaetano ND, Cittera E, Nota R, Vecchi A, Grieco V, Scanziani E, Botto M, Introna M, Golay J. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol. 2003; 171: 1581-1587.
28. Gelderman KA, Tomlinson S, Ross GD, Gorter A. Complement function in mAbmediated cancer immunotherapy. Trends Immunol. 2004; 25: 158-164.
29. Janeway CA, Travers P, Walport M. Immunobiology: The Immune System in Health and Disease, 6th ed. New York: Garland Science; 2005. 823.
30. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science. 2008; 320: 373-376.
31. Nimmerjahn F, Ravetch JV. Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol. 2008; 26: 513-533.
32. Hirayama K, Yuji R, Yamada N, Kato K, Arata Y, Shimada I. Complete and rapid peptide and glycopeptide mapping of mouse monoclonal antibody by LC/MS/MS using ion trap mass spectrometry. Anal Chem. 1998; 70: 2718-2725.
33. Leibiger H, Wüstner D, Stigler RD, Marx U. Variable domain-linked oligosaccharides of a human monoclonal IgG: structure and influence on antigen binding. Biochem J. 1999; 338 (Part 2): 529-538.
34. Kornfeld R, Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985; 54: 631-664.
35. Cumming DA. Glycosylation of recombinant protein therapeutics: control and functional implications. Glycobiology. 1991; 1: 115-130.
36. Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol. 2003; 325: 979-989.
37. Hodoniczky J, Zheng YZ, James DC. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol Prog. 2005; 21: 1644-1652.
38. Raju TS. Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol. 2008; 20: 471-478.
39. Wallick SC, Kabat EA, Morrison SL. Glycosylation of a VH residue of a monoclonal antibody against alpha (1→6) dextran increases its affinity for antigen. J Exp Med. 1988; 168: 1099-1109.
40. Tandai M, Endo T, Sasaki S, Masuho Y, Kochibe N, Kobata A. Structural study of the sugar moieties of monoclonal antibodies secreted by human-mouse hybridoma. Arch Biochem Biophys. 1991; 291: 339-348.
41. Wright A, Tao MH, Kabat EA, Morrison SL. Antibody variable region glycosylation: position effects on antigen binding and carbohydrate structure. EMBO J. 1991; 10: 2717-2723.
42. Co MS, Scheinberg DA, Avdalovic NM, McGraw K, Vasquez M, Caron PC, Queen C. Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody. Mol Immunol. 1993; 30: 1361-1367.
43. Wright A, Morrison SL. Antibody variable region glycosylation: biochemical and clinical effects. Springer Semin Immunopathol. 1993; 15: 259-273.
44. Endo T, Wright A, Morrison SL, Kobata A. Glycosylation of the variable region of immunoglobulin G-site specific maturation of the sugar chains. Mol Immunol. 1995; 32: 931-940.
45. Holland M, Yagi H, Takahashi N, Kato K, Savage COS, Goodall DM, Jefferis R. Differential glycosylation of polyclonal IgG, IgG-Fc and IgG-Fab isolated from the sera of patients with ANCA-associated systemic vasculitis. Biochim Biophys Acta. 2006; 1760: 669-677.
46. Wormald MR, Rudd PM, Harvey DJ, Chang SC, Scragg IG, Dwek RA. Variations in oligosaccharide-protein interactions in immunoglobulin G determine the site-specific glycosylation profiles and modulate the dynamic motion of the Fc oligosaccharides. Biochemistry. 1997; 36: 1370-1380.
47. Hills AE, Patel A, Boyd P, James DC. Metabolic control of recombinant monoclonal antibody N-glycosylation in GS-NS0 cells. Biotechnol Bioeng. 2001; 75: 239-251.
48. Jefferis R, Lund J, Mizutani H, Nakagawa H, Kawazoe Y, Arata Y, Takahashi N. A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. Biochem J. 1990; 268: 529-537.
49. Mimura Y, Ashton PR, Takahashi N, Harvey DJ, Jefferis R. Contrasting glycosylation profiles between Fab and Fc of a human IgG protein studied by electrospray ionization mass spectrometry. J Immunol Methods. 2007; 326: 116-126.
50. Kobata A. The N-linked sugar chains of human immunoglobulin G: their unique pattern, and their functional roles. Biochim Biophys Acta. 2008; 1780: 472-478.
51. van Berkel PHC, Gerritsen J, Perdok G, Valbjørn J, Vink T, van deWinkel JGJ, Parren PWHI. N-linked glycosylation is an important parameter for optimal selection of cell lines producing biopharmaceutical human IgG. Biotechnol Prog. 2009; 25: 244-251.
52. Lifely MR, Hale C, Boyce S, Keen MJ, Phillips J. Glycosylation and biological activity of CAMPATH-1H expressed in different cell lines and grown under different culture conditions. Glycobiology. 1995; 5: 813-822.
53. Shields RL, Lai J, Keck R, O'Connell LY, Hong K, Meng YG, Weikert SHA, Presta LG. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fc gamma RIII and antibody-dependent cellular toxicity. J Biol Chem. 2002; 277: 26733-26740.
54. Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem. 2003; 278: 3466-3473.
55. Matsumiya S, Yamaguchi Y, Saito Ji, Nagano M, Sasakawa H, Otaki S, Satoh M, Shitara K, Kato K. Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol. 2007; 368: 767-779.
56. Umaña P, Jean-Mairet J, Moudry R, Amstutz H, Bailey JE. Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat Biotechnol. 1999; 17: 176-180.
57. Ferrara C, Brünker P, Suter T, Moser S, Püntener U, Umaña P. Modulation of therapeutic antibody effector functions by glycosylation engineering: influence of Golgi enzyme localization domain and co-expression of heterologous beta1, 4-Nacetylglucosaminyltransferase III and Golgi alpha-mannosidase II. Biotechnol Bioeng. 2006; 93: 851-861.
58. Mori K, Kuni-Kamochi R, Yamane-Ohnuki N, Wakitani M, Yamano K, Imai H, Kanda Y, Niwa R, Iida S, Uchida K, Shitara K, Satoh M. Engineering Chinese hamster ovary cells to maximize effector function of produced antibodies using FUT8 siRNA. Biotechnol Bioeng. 2004; 88: 901-908.
59. Imai-Nishiya H, Mori K, Inoue M, Wakitani M, Iida S, Shitara K, Satoh M. Double knockdown of alpha1, 6-fucosyltransferase (FUT8) and GDP-mannose 4, 6-dehydratase (GMD) in antibody-producing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC. BMC Biotechnol. 2007; 7: 84.
60. Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M, Kusunoki M, Iida S, Nakano R, Wakitani M, Niwa R, Sakurada M, Uchida K, Shitara K, Satoh M. Establishment of FUT8 knockout Chinese hamster ovary cells: an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity. Biotechnol Bioeng. 2004; 87: 614-622.
61. Kanda Y, Yamane-Ohnuki N, Sakai N, Yamano K, Nakano R, Inoue M, Misaka H, Iida S, Wakitani M, Konno Y, Yano K, Shitara K, Hosoi S, Satoh M. Comparison of cell lines for stable production of fucose-negative antibodies with enhanced ADCC. Biotechnol Bioeng. 2006; 94: 680-688.
62. Alley SC, Sussman DR, Jeffrey SC, Torrey L, Burke PJ, Setter J, Gfeller B, Klussman K, Okeley NM, Senter PD, Benjamin DR. SEA technology: a novel strategy for enhancing antibody effector function. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research 2010 Apr 17-21; Washington, DC. Philadelphia, PA: AACR; 2010. Abstract number 4395.
63. Siadak T, Espling E, McGourty J, Lowe R, Baum P, Wahl A, Thompson P, Yaban-navar V. Enhancing biological activity of immunoglycoproteins by a convenient method of generating preferred glycovariants. Cell Culture Eng. 2008; XI.
64. Wright A, Morrison SL. Effect of altered CH2-associated carbohydrate structure on the functional properties and in vivo fate of chimeric mouse-human immunoglobulin G1. J Exp Med. 1994; 180: 1087-1096.
65. Dwek RA, Lellouch AC, Wormald MR. Glycobiology: the function of sugar in the IgG molecule. J Anat. 1995; 187 (Part 2): 279-292.
66. Mimura Y, Church S, Ghirlando R, Ashton PR, Dong S, Goodall M, Lund J, Jefferis R. The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: properties of a series of truncated glycoforms. Mol Immunol. 2000; 37: 697-706.
67. Wright A, Morrison SL. Effect of C2-associated carbohydrate structure on Ig effector function: studies with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese hamster ovary cells. J Immunol. 1998; 160: 3393-3402.
68. Kaneko Y, Nimmerjahn F, Ravetch JV. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science. 2006; 313: 670-673.
69. Weikert S. Engineering Chinese hamster ovary cells to maximize sialic acid content of recombinant glycoproteins. Nat Biotechnol. 1999; 17: 1116-1121.
70. Bragonzi A, Distefano G, Buckberry LD, Acerbis G, Foglieni C, Lamotte D, Campi G, Marc A, Soria MR, Jenkins N, Monaco L. A new Chinese hamster ovary cell line expressing alpha2, 6-sialyltransferase used as universal host for the production of human-like sialylated recombinant glycoproteins. Biochim Biophys Acta. 2000; 1474: 273-282.
71. Hamilton SR. Humanization of yeast to produce complex terminally sialylated glycoproteins. Science. 2006; 313: 1441-1443.
72. Butler M. Optimization of the cellular metabolism of glycosylation for recombinant proteins produced by mammalian cell systems. Cytotechnology. 2006; 50: 57-76.
73. Hossler P, Khattak SF, Li ZJ. Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology. 2009; 19: 936-949.
74. Goochee CF, Monica T. Environmental effects on protein glycosylation. Bio/Technology. 1990; 8: 421-427.
75. Moellering BJ, Tedesco JL, Townsend RR, Hardy MR, Scott RW, Prior CP. Electrophoretic differences in a mAb expressed in three media. BioPharm Int. 1989; 3: 30-38.
76. Tachibana H, Taniguchi K, Ushio Y, Teruya K, Osada K, Murakami H. Changes of monosaccharide availability of human hybridoma lead to alteration of biological properties of human monoclonal antibody. Cytotechnology. 1994; 16: 151-157.
77. Hayter PM, Curling EM, Baines AJ, Jenkins N, Salmon I, Strange PG, Tong JM, Bull AT. Glucose-limited chemostat culture of chinese hamster ovary cells producing recombinant human interferon-gamma. Biotechnol Bioeng. 1992; 39: 327-335.
78. Nyberg GB, Balcarcel RR, Follstad BD, Stephanopoulos G, Wang DIC. Metabolic effects on recombinant interferon-gamma glycosylation in continuous culture of Chinese hamster ovary cells. Biotechnol Bioeng. 1999; 62: 336-347.
79. Wong DCF, Wong KTK, Goh LT, Heng CK, Yap MGS. Impact of dynamic online fed-batch strategies on metabolism, productivity and N-glycosylation quality in CHO cell cultures. Biotechnol Bioeng. 2005; 89: 164-177.
80. Zhou Q, Shankara S, Roy A, Qiu H, Estes S, McVie-Wylie A, Culm-Merdek K, Park A, Pan C, Edmunds T. Development of a simple and rapid method for producing non-fucosylated oligomannose containing antibodies with increased effector function. Biotechnol Bioeng. 2008; 99: 652-665.
81. Wright A, Sato Y, Okada T, Chang K, Endo T, Morrison S. In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure. Glycobiology. 2000; 10: 1347-1355.
82. Chen X, Flynn GC. Analysis of N-glycans from recombinant immunoglobulin G by on-line reversed-phase high-performance liquid chromatography/mass spectrometry. Anal Biochem. 2007; 370: 147-161.
83. Rijcken WRP, Overdijk B, den Eijnden DHV, Ferwerda W. The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes. Biochem J. 1995; 305 (Part 3): 865-870.
84. Trummer E, Fauland K, Seidinger S, Schriebl K, Lattenmayer C, Kunert R, Vorauer-Uhl K, Weik R, Borth N, Katinger H, Müller D. Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors. Biotechnol Bioeng. 2006; 94: 1033-1044.
85. Chotigeat W, Watanapokasin Y, Mahler S, Gray PP. Role of environmental conditions on the expression levels, glycoform pattern and levels of sialyltransferase for hFSH produced by recombinant CHO cells. Cytotechnology. 1994; 15: 217-221.
86. Gawlitzek M, Conradt HS, Wagner R. Effect of different cell culture conditions on the polypeptide integrity and N-glycosylation of a recombinant model glycoprotein. Biotechnol Bioeng. 1995; 46: 536-544.
87. Regoeczi E, Kay JM, Chindemi PA, Zaimi O, Suyama KL. Transferrin glycosylation in hypoxia. Biochem Cell Biol. 1991; 69: 239-244.
88. Kunkel JP, Jan DCH, Jamieson JC, Butler M. Dissolved oxygen concentration in serum-free continuous culture affects N-linked glycosylation of a monoclonal antibody. J Biotechnol. 1998; 62: 55-71.
89. Kumpel BM, Rademacher TW, Rook GA, Williams PJ, Wilson IB. Galactosylation of human IgG monoclonal anti-D produced by EBV-transformed B-lymphoblastoid cell lines is dependent on culture method and affects Fc receptor-mediated functional activity. Hum Antibodies Hybridomas. 1994; 5: 143-151.
90. Borys MC, Linzer DI, Papoutsakis ET. Culture pH affects expression rates and glycosylation of recombinant mouse placental lactogen proteins by Chinese hamster ovary (CHO) cells. Bio/Technology. 1993; 11: 720-724.
91. Gawlitzek M, Ryll T, Lofgren J, Sliwkowski MB. Ammonium alters N-glycan structures of recombinant TNFR-IgG: degradative versus biosynthetic mechanisms. Biotechnol Bioeng. 2000; 68: 637-646.
92. Axelsson MA, Karlsson NG, Steel DM, Ouwendijk J, Nilsson T, Hansson GC. Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. Glycobiology. 2001; 11: 633-644.
93. Rivinoja A, Hassinen A, Kokkonen N, Kauppila A, Kellokumpu S. Elevated Golgi pH impairs terminal N-glycosylation by inducing mislocalization of Golgi glycosyltransferases. J Cell Physiol. 2009; 220: 144-154.
94. Gawlitzek M, Valley U, Wagner R. Ammonium ion and glucosamine dependent increases of oligosaccharide complexity in recombinant glycoproteins secreted from cultivated BHK-21 cells. Biotechnol Bioeng. 1998; 57: 518-528.
95. Yang M, Butler M. Effects of ammonia on CHO cell growth, erythropoietin production, and glycosylation. Biotechnol Bioeng. 2000; 68: 370-380.
96. Yoon SK, Choi SL, Song JY, Lee GM. Effect of culture pH on erythropoietin production by Chinese hamster ovary cells grown in suspension at 32.5 and 37.0 degrees C. Biotechnol Bioeng. 2005; 89: 345-356.
97. Müthing J, Kemminer SE, Conradt HS, Sagi D, Nimtz M, Kärst U, Peter-Katalinic J. Effects of buffering conditions and culture pH on production rates and glycosylation of clinical phase I anti-melanoma mouse IgG3 monoclonal antibody R24. Biotechnol Bioeng. 2003; 83: 321-334.
98. Andersen DC, Bridges T, Gawlitzek M, Hoy C. Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO-produced tissue-type plasminogen activator. Biotechnol Bioeng. 2000; 70: 25-31.
99. Yoon SK, Kim SH, Lee GM. Effect of low culture temperature on specific productivity and transcription level of anti-4-1BB antibody in recombinant Chinese hamster ovary cells. Biotechnol Prog. 2003; 19: 1383-1386.
100. Ahn WS, Jeon JJ, Jeong YR, Lee SJ, Yoon SK. Effect of culture temperature on erythropoietin production and glycosylation in a perfusion culture of recombinant CHO cells. Biotechnol Bioeng. 2008; 101: 1234-1244.
101. Kukuruzinska MA, Lennon K. Growth-related coordinate regulation of the early Nglycosylation genes in yeast. Glycobiology. 1994; 4: 437-443.
102. Barnabé N, Butler M. Effect of temperature on nucleotide pools and monoclonal antibody production in a mouse hybridoma. Biotechnol Bioeng. 1994; 44: 1235-1245.
103. Jenkins N, Castro P, Menon S, Ison A, Bull A. Effect of lipid supplements on the production and glycosylation of recombinant interferon-gamma expressed in CHO cells. Cytotechnology. 1994; 15: 209-215.
104. Serrato JA, Hernández V, Estrada-Mondaca S, Palomares LA, Ramírez OT. Differences in the glycosylation profile of a monoclonal antibody produced by hybridomas cultured in serum-supplemented, serum-free or chemically defined media. Biotechnol Appl Biochem. 2007; 47: 113-124.
105. Schmelzer AE, Miller WM. Hyperosmotic stress and elevated pCO2 alter monoclonal antibody charge distribution and monosaccharide content. Biotechnol Prog. 2002; 18: 346-353.
106. Senger RS, Karim MN. Effect of shear stress on intrinsic CHO culture state and glycosylation of recombinant tissue-type plasminogen activator protein. Biotechnol Prog. 2003; 19: 1199-1209.
107. Gu X, Wang DI. Improvement of interferon-gamma sialylation in Chinese hamster ovary cell culture by feeding of N-acetylmannosamine. Biotechnol Bioeng. 1998; 58: 642-648.
108. Lund J, Takahashi N, Nakagawa H, Goodall M, Bentley T, Hindley SA, Tyler R, Jefferis R. Control of IgG/Fc glycosylation: a comparison of oligosaccharides from chimeric human/mouse and mouse subclass immunoglobulin Gs. Mol Immunol. 1993; 30: 741-748.
109. Goldman MH, James DC, Rendall M, Ison AP, Hoare M, Bulll AT. Monitoring recombinant human interferon-gamma n-glycosylation during perfused fluidized-bed and stirred-tank batch culture of CHO cells. Biotechnol Bioeng. 1998; 60: 596-607.
110. Majid FAA, Butler M, Al-Rubeai M. Glycosylation of an immunoglobulin produced from a murine hybridoma cell line: the effect of culture mode and the anti-apoptotic gene, bcl-2. Biotechnol Bioeng. 2007; 97: 156-169.
111. Kunkel JP, Jan DC, Butler M, Jamieson JC. Comparisons of the glycosylation of a monoclonal antibody produced under nominally identical cell culture conditions in two different bioreactors. Biotechnol Prog. 2000; 16: 462-470.
112. Yoon SK, Ahn YH, Jeong MH. Effect of culture temperature on follicle-stimulating hormone production by Chinese hamster ovary cells in a perfusion bioreactor. Appl Microbiol Biotechnol. 2007; 76: 83-89.
113. Robinson DK, Chan CP, Lp CY, Tsai PK, Tung J, Seamans TC, Lenny AB, Lee DK, Irwin J, Silberklang M. Characterization of a recombinant antibody produced in the course of a high yield fed-batch process. Biotechnol Bioeng. 1994; 44: 727-735.
114. Trummer E, Fauland K, Seidinger S, Schriebl K, Lattenmayer C, Kunert R, Vorauer-Uhl K, Weik R, Borth N, Katinger H, Müller D. Process parameter shifting: Part II. Biphasic cultivation-A tool for enhancing the volumetric productivity of batch processes using Epo-Fc expressing CHO cells. Biotechnol Bioeng. 2006; 94: 1045-1052.
115. Shuler ML, Kargi F. Bioprocess Engineering: Basic Concepts, 2nd ed. Upper Saddle River, NJ: Prentice Hall PTR; 2002. 553.
116. Raju T, Briggs J, Borge S, Jones A. Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology. 2000; 10: 477-486.
117. Sheeley DM, Merrill BM, Taylor LC. Characterization of monoclonal antibody glycosylation: comparison of expression systems and identification of terminal alpha-linked galactose. Anal Biochem. 1997; 247: 102-110.
118. Beck A, Bussat MC, Zorn N, Robillard V, Klinguer-Hamour C, Chenu S, Goetsch L, Corvaïa N, Dorsselaer AV, Haeuw JF. Characterization by liquid chromatography combined with mass spectrometry of monoclonal anti-IGF-1 receptor antibodies produced in CHO and NS0 cells. J Chromatogr B Anal Technol Biomed Life Sci. 2005; 819: 203-218.
119. Stadlmann J, Pabst M, Kolarich D, Kunert R, Altmann F. Analysis of immunoglobulin glycosylation by LC-ESI-MS of glycopeptides and oligosaccharides. Proteomics. 2008; 8: 2858-2871.
120. Wagner-Rousset E, Bednarczyk A, Bussat MC, Colas O, Corvaïa N, Schaeffer C, Dorsselaer AV, Beck A. The way forward, enhanced characterization of therapeutic antibody glycosylation: comparison of three level mass spectrometry-based strategies. J Chromatogr B Anal Technol Biomed Life Sci. 2008; 872: 23-37.
121. Chung CH. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1, 3-galactose. N Engl J Med. 2008; 358: 1109-1117.
122. de Romeuf C. Chronic lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16. Br J Haematol. 2008; 140: 635-643.
123. Kowarik M, Young NM, Numao S, Schulz BL, Hug I, Callewaert N, Mills DC, Watson DC, Hernandez M, Kelly JF, Wacker M, Aebi M. Definition of the bacterial N-glycosylation site consensus sequence. EMBO J. 2006; 25: 1957-1966.
124. Kowarik M, Numao S, Feldman MF, Schulz BL, Callewaert N, Kiermaier E, Catrein I, Aebi M. N-linked glycosylation of folded proteins by the bacterial oligosaccharyltransferase. Science. 2006; 314: 1148-1150.
125. Wacker M, Linton D, Hitchen PG, Nita-Lazar M, Haslam SM, North SJ, Panico M, Morris HR, Dell A, Wren BW, Aebi M. N-linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli. Science. 2002; 298: 1790-1793.
126. Rabouille C, Hui N, Hunte F, Kieckbusch R, Berger EG, Warren G, Nilsson T. Mapping the distribution of Golgi enzymes involved in the construction of complex oligosaccharides. J Cell Sci. 1995; 108 (Part 4): 1617-1627.
127. de Graffenried CL, Bertozzi CR. The roles of enzyme localization and complex formation in glycan assembly within the Golgi apparatus. Curr Opin Cell Biol. 2004; 16: 356-363.
128. Gerngross TU. Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nat Biotechnol. 2004; 22: 1409-1414.
129. Bobrowicz P, Davidson RC, Li H, Potgieter TI, Nett JH, Hamilton SR, Stadheim TA, Miele RG, Bobrowicz B, Mitchell T, Rausch S, Renfer E, Wildt S. Engineering of an artificial glycosylation pathway blocked in core oligosaccharide assembly in the yeast Pichia pastoris: production of complex humanized glycoproteins with terminal galactose. Glycobiology. 2004; 14: 757-766.
130. Li H. Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol. 2006; 24: 210-215.
131. Tekoah Y, Ko K, Koprowski H, Harvey DJ, Wormald MR, Dwek RA, Rudd PM. Controlled glycosylation of therapeutic antibodies in plants. Arch Biochem Biophys. 2004; 426: 266-278.
132. Hooker AD, Green NH, Baines AJ, Bull AT, Jenkins N, Strange PG, James DC. Constraints on the transport and glycosylation of recombinant IFN-gamma in Chinese hamster ovary and insect cells. Biotechnol Bioeng. 1999; 63: 559-572.
133. Betenbaugh MJ, Tomiya N, Narang S, Hsu JT, Lee YC. Biosynthesis of humantype N-glycans in heterologous systems. Curr Opin Struct Biol. 2004; 14: 601-606.
134. Tomiya N. Humanization of recombinant glycoproteins expressed in insect cells. Trends Glycosci Glyc. 2009; 21: 71-86.
135. Segawa H, Kawakita M, Ishida N. Human and Drosophila UDP-galactose transporters transport UDP-N-acetylgalactosamine in addition to UDP-galactose. Eur J Biochem. 2002; 269: 128-138.
136. Altmann F, Kornfeld G, Dalik T, Staudacher E, Glössl J. Processing of asparaginelinked oligosaccharides in insect cells. N-acetylglucosaminyltransferase I and II activities in cultured lepidopteran cells. Glycobiology. 1993; 3: 619-625.
137. Léonard R, Rendic D, Rabouille C, Wilson IBH, Préat T, Altmann F. The Drosophila fused lobes gene encodes an N-acetylglucosaminidase involved in N-glycan processing. J Biol Chem. 2006; 281: 4867-4875.
138. Jarvis DL, Finn EE. Modifying the insect cell N-glycosylation pathway with immediate early baculovirus expression vectors. Nat Biotechnol. 1996; 14: 1288-1292.
139. Bakker H, Bardor M, Molthoff JW, Gomord V, Elbers I, Stevens LH, Jordi W, Lommen A, Faye L, Lerouge P, Bosch D. Galactose-extended glycans of antibodies produced by transgenic plants. Proc Natl Acad Sci USA. 2001; 98: 2899-2904.
140. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG, Black A, Passmore D, Moldovan-Loomis C, Srinivasan M, Cuison S, Cardarelli PM, Dickey LF. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol. 2006; 24: 1591-1597.
141. Umaña P, Bailey JE. A mathematical model of N-linked glycoform biosynthesis. Biotechnol Bioeng. 1997; 55: 890-908.
142. Krambeck FJ, Betenbaugh MJ. A mathematical model of N-linked glycosylation. Biotechnol Bioeng. 2005; 92: 711-728.
143. Hossler P, Mulukutla BC, Hu WS. Systems analysis of N-glycan processing in mammalian cells. PLoS ONE. 2007; 2: e713.
144. Huhn C, Selman MHJ, Ruhaak LR, Deelder AM, Wuhrer M. IgG glycosylation analysis. Proteomics. 2009; 9: 882-913.
145. Olivova P, Chen W, Chakraborty AB, Gebler JC. Determination of N-glycosylation sites and site heterogeneity in a monoclonal antibody by electrospray quadrupole ionmobility time-of-flight mass spectrometry. Rapid Commun Mass Spectrom. 2008; 22: 29-40.
146. Lim A, Reed-Bogan A, Harmon BJ. Glycosylation profiling of a therapeutic recombinant monoclonal antibody with two N-linked glycosylation sites using liquid chromatography coupled to a hybrid quadrupole time-of-flight mass spectrometer. Anal Biochem. 2008; 375: 163-172.
147. Adamo M, Qiu D, Dick LW, Zeng M, Lee AH, Cheng KC. Evaluation of oligosaccharide methods for carbohydrate analysis in a fully human monoclonal antibody and comparison of the results to the monosaccharide composition determination by a novel calculation. J Pharm Biomed Anal. 2009; 49: 181-192.
148. Serrato JA, Palomares LA, Meneses-Acosta A, Ramírez OT. Heterogeneous conditions in dissolved oxygen affect N-glycosylation but not productivity of a monoclonal antibody in hybridoma cultures. Biotechnol Bioeng. 2004; 88: 176-188.
149. Matamoros Fernandez LE, Kalume DE, Calvo L, Fernandez Mallo M, Vallin A, Roepstorff P. Characterization of a recombinant monoclonal antibody by mass spectrometry combined with liquid chromatography. J Chromatogr B Biomed Sci Appl. 2001; 752: 247-261.
150. Saba JA, Kunkel JP, Jan DCH, Ens WE, Standing KG, Butler M, Jamieson JC, Perreault H. A study of immunoglobulin G glycosylation in monoclonal and polyclonal species by electrospray and matrix-assisted laser desorption/ionization mass spectrometry. Anal Biochem. 2002; 305: 16-31.
151. Kamoda S, Ishikawa R, Kakehi K. Capillary electrophoresis with laser-induced fluorescence detection for detailed studies on N-linked oligosaccharide profile of therapeutic recombinant monoclonal antibodies. J Chromatogr A. 2006; 1133: 332-339.
152. Morelle W, Michalski JC. Analysis of protein glycosylation by mass spectrometry. Nat Protoc. 2007; 2: 1585-1602.
153. Mechref Y, Muzikar J, Novotny MV. Comprehensive assessment of N-glycans derived from a murine monoclonal antibody: a case for multimethodological approach. Electrophoresis. 2005; 26: 2034-2046.
154. Qian J, Liu T, Yang L, Daus A, Crowley R, Zhou Q. Structural characterization of N-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption/ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzymatic digestion. Anal Biochem. 2007; 364: 8-18.
155. Siemiatkoski J, Lyubarskaya Y, Houde D, Tep S, Mhatre R. A comparison of three techniques for quantitative carbohydrate analysis used in characterization of therapeutic antibodies. Carbohydr Res. 2006; 341: 410-419.
156. O'shea T, Lunte S, LaCourse W. Detection of carbohydrates by capillary electrophoresis with pulsed amperometric detection. Anal Chem. 1993; 65: 948-951.
157. Lee Y. Carbohydrate analyses with high-performance anion-exchange chromatography. J Chromatogr A. 1996; 720: 137-149.
158. Clarke A, Harmon B, DeFelippis MR. Analysis of 3-(acetylamino)-6-aminoacridinederivatized oligosaccharides from recombinant monoclonal antibodies by liquid chromatography-mass spectrometry. Anal Biochem. 2009; 390: 209-211.
159. Prater BD, Connelly HM, Qin Q, Cockrill SL. High-throughput immunoglobulin G N-glycan characterization using rapid resolution reverse-phase chromatography tandem mass spectrometry. Anal Biochem. 2009; 385: 69-79.
160. Lamari FN, Kuhn R, Karamanos NK. Derivatization of carbohydrates for chromatographic, electrophoretic and mass spectrometric structure analysis. J Chromatogr B Anal Technol Biomed Life Sci. 2003; 793: 15-36.
161. Pabst M, Kolarich D, Pöltl G, Dalik T, Lubec G, Hofinger A, Altmann F. Comparison of fluorescent labels for oligosaccharides and introduction of a new postlabeling purification method. Anal Biochem. 2009; 384: 263-273.
162. Kinoshita A, Sugahara K. Microanalysis of glycosaminoglycan-derived oligosaccharides labeled with a fluorophore 2-aminobenzamide by high-performance liquid chromatography: application to disaccharide composition analysis and exosequencing of oligosaccharides. Anal Biochem. 1999; 269: 367-378.
163. Domann PJ, Pardos-Pardos AC, Fernandes DL, Spencer DIR, Radcliffe CM, Royle L, Dwek RA, Rudd PM. Separation-based glycoprofiling approaches using fluorescent labels. Proteomics. 2007; 7 (Suppl 1): 70-76.
164. Gennaro LA, Salas-Solano O. On-line CE-LIF-MS technology for the direct characterization of N-linked glycans from therapeutic antibodies. Anal Chem. 2008; 80: 3838-3845.
165. O'shea M, Samuel M, Konik C, Morell M. Fluorophore-assisted carbohydrate electrophoresis (FACE) of oligosaccharides: efficiency of labelling and high-resolution separation. Carbohyd Res. 1998; 307: 1-12.
166. Nakano M, Higo D, Arai E, Nakagawa T, Kakehi K, Taniguchi N, Kondo A. Capillary electrophoresis-electrospray ionization mass spectrometry for rapid and sensitive N-glycan analysis of glycoproteins as 9-fluorenylmethyl derivatives. Glycobiology. 2009; 19: 135-143.
167. Wada Y. Comparison of the methods for profiling glycoprotein glycans - HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. Glycobiology. 2007; 17: 411-422.
168. Mechref Y, Novotny MV. Structural investigations of glycoconjugates at high sensitivity. Chem Rev. 2002; 102: 321-369.
169. Ma S, Nashabeh W. Carbohydrate analysis of a chimeric recombinant monoclonal antibody by capillary electrophoresis with laser-induced fluorescence detection. Anal Chem. 1999; 71: 5185-5192.
170. Elbers IJW, Stoopen GM, Bakker H, Stevens LH, Bardor M, Molthoff JW, Jordi W, Bosch D, Lommen A. Influence of growth conditions and developmental stage on N-glycan heterogeneity of transgenic immunoglobulin G and endogenous proteins in tobacco leaves. Plant Physiology. 2001; 126: 1314-1322.
171. CMC Biotech Working Group. A-Mab: a Case Study in Bioprocess Development. Emeryville, CA: CASSS; 2009.