Probing of C-terminal lysine variation in a recombinant monoclonal antibody production using Chinese hamster ovary cells with chemically defined media

Biotechnology and Bioengineering

Volumn 109, Issue 9, 2012, Pages 2306-2315

  Luo, Jun ^a   Zhang, Jian ^a   Ren, Diya ^a   Tsai, Wen Lin ^a   Li, Feng ^a   Amanullah, Ashraf ^a   Hudson, Terry ^a  

^a GENENTECH INC   (United States)

Author keywords

C terminal lysine; Carboxypeptidase; CHO cell culture; Copper; Fed batch; Monoclonal antibody; Trace elements; Zinc

Indexed keywords

C-TERMINAL LYSINE; CARBOXYPEPTIDASE; CELL CULTURE PROCESS; CELL LINES; CHINESE HAMSTER OVARY CELLS; CHO CELL; COPPER AND ZINC; COPPER CONCENTRATION; DEVELOPMENT CRITERIA; EXTRACELLULAR; FED BATCHES; IN-PROCESS; OPERATING CONDITION; OPERATIONAL PARAMETERS; PROCESS CONDITION; PRODUCT QUALITY; RECOMBINANT ANTIBODY; RECOMBINANT MONOCLONAL ANTIBODY; REPRODUCIBILITIES; THERAPEUTIC MONOCLONAL ANTIBODIES; TRACE ELEMENTS CONCENTRATION; WEAK CATION EXCHANGE CHROMATOGRAPHY; WESTERN BLOTS; ZINC CONCENTRATION;

AMINO ACIDS; COPPER; ENZYME ACTIVITY; MONOCLONAL ANTIBODIES; RECOMBINANT PROTEINS; TRACE ELEMENTS; ZINC;

BATCH CELL CULTURE;

CARBOXYPEPTIDASE B; COPPER; COPPER ZINC SUPEROXIDE DISMUTASE; MONOCLONAL ANTIBODY; ZINC;

ANIMAL CELL; ARTICLE; C TERMINAL LYSINE VARIANT; CARBOXY TERMINAL SEQUENCE; CELL CULTURE; CHO CELL; FED BATCH CULTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ION EXCHANGE CHROMATOGRAPHY; LIMIT OF DETECTION; MOLECULAR WEIGHT; NONHUMAN; OXIDATIVE STRESS; PROTEIN DEGRADATION; WESTERN BLOTTING;

ANIMALS; ANTIBODIES, MONOCLONAL; BATCH CELL CULTURE TECHNIQUES; BIOREACTORS; BLOTTING, WESTERN; CARBOXYPEPTIDASE B; CHO CELLS; COPPER; CRICETINAE; CRICETULUS; CULTURE MEDIA; LYSINE; RECOMBINANT PROTEINS; ZINC;

CRICETULUS GRISEUS;

EID: 84864306052     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.24510     Document Type: Article

References (35)

1. Antes B, Amon S, Rizzi A, Wiederkum S, Kainer M, Szolar O, Fido M, Kircheis R, Nechansky A. 2007. Analysis of lysine clipping of a humanized lewis-y specific igg antibody and its relation to fc-mediated effector function. J Chromatogr B Analyt Technol Biomed Life Sci 852(1-2): 250-256.
2. Berger J, Schneeman BO. 1986. Stimulation of bile-pancreatic zinc, protein and carboxypeptidase secretion in response to various proteins in the rat. J Nutr 116(2): 265-272.
3. Boswell CA, Tesar DB, Mukhyala K, Theil F-P, Fielder PJ, Khawli LA. 2010. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjugate Chem 21(12): 2153-2163.
4. Cai B, Pan H, Flynn GC. 2011. C-terminal lysine processing of human immunoglobulin G2 heavy chain in vivo. Biotechnol Bioeng 108(2): 404-412.
5. Davidson H, Hutton J. 1987. The insulin-secretory-granule carboxypeptidase h. Biochem J 245: 575-582.
6. Dick LW, Jr., Qiu D, Mahon D, Adamo M, Cheng KC. 2008. C-terminal lysine variants in fully human monoclonal antibodies: Investigation of test methods and possible causes. Biotechnol Bioeng 100(6): 1132-1143.
7. Fridovich I. 2004. Superoxide dismutase. In: Lennarz W, Lane M, editors. Encyclopedia of biological chemistry. Burlington, MA: Elsevier, Inc. p 135-138.
8. Gainer H, Russell JT, Loh YP. 1985. The enzymology and intracellular organization of peptide precursor processing: The secretory vesicle hypothesis. Neuroendocrinology 40(2): 171-184.
9. Harris R. 1995. Processing of c-terminal lysine and arginine residues of proteins isolated from mammalian cell culture. J Chromatogr A 705: 129-134.
10. Harris RJ, Wangner KL, Spellman MW. 1990. Structural characterization of a recombinant CD4-IgG hybrid molecule. Eur J Biochem 194: 611-620.
11. Harris RJ, Shire SJ, Winter C. 2004. Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodies. Drug Dev. Res 61: 137-154.
12. Herd SM, Camakaris J, Christofferson R, Wookey P, Danks DM. 1987. Uptake and efflux of copper-64 in menkes'-disease and normal continuous lymphoid cell lines. Biochem J 247(2): 341-347.
13. Hooper N. 1994. Families of zinc metalloproteases. FEBS Lett 354(1): 1-6.
14. Hopp J, Pritchett R, Darlucio M, Ma J, Chou JH. 2009. Development of a high throughput Protein A well-plate purification method for monoclonal antibodies. Biotechnol Prog 25(5): 1427-1432.
15. Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, Yao Z, Sreedhara A, Cano T, Tesar D, Nijem I, Allison DE, Wong PY, Kao Y-H, Quan C, Joshi A, Harris RJ, Motchnik P. 2010. Charge variants in IgG1 isolation, characterization, in vitro binding properties and pharmacokinetics in rats. mAbs 2(6): 613-624.
16. Kim MJ, Kim SH, Lee JH, Seo JH, Lee JH, Kim JH, Kim YH, Nam SW. 2008. High-level secretory expression of human procarboxypeptidase b by fed-batch cultivation of pichia pastoris and its partial characterization. J Microbiol Biotechnol 18(12): 1938-1944.
17. Liu H, Gaza-Bulseco G, Faldu D, Chumsae C, Sun J. 2008. Heterogeneity of monoclonal antibodies. J Pharm Sci 97(7): 2426-2447.
18. Luo J, Vijayasankaran N, Autsen J, Santuray R, Hudson T, Amanullah A, Li F. 2012. Comparative metabolite analysis to understand lactate metabolism shift in chinese hamster ovary cell culture process. Biotechnol Bioeng 109(1): 146-156.
19. Matsumoto A, Itoh K, Seki T, Motozaki K, Matsuyama S. 2001. Human brain carboxypeptidase b, which cleaves β-amyloid peptides in vitro, is expressed in the endoplasmic reticulum of neurons. Eur J Neurosci 13(9): 1653-1657.
20. McDonough JP, Furman TC, Bartholomew RM, Jue RA. 1992. Method for the reduction of heterogeneity of monoclonal antibodies. EP0361902A2.
21. Mezzetti A, Pierdomenico S, Costantini F, Romano F, De Cesare D, Cuccurullo F, Imbastaro T, Riario-Sforza G, Di Giacomo F, Zuliani G, Fellin R. 1998. Copper/zinc ratio and systemic oxidant load: Effect of aging and aging-related degenerative diseases. Free Radic Biol Med 25(6): 676-681.
22. Prasad AS. 1979. Clinical, biochemical, and pharmacological role of zinc. Ann Rev Pharmacol Taxicol 20: 393-426.
23. Rao P, Williams A, Baldwin-Ferro A. 1991. C-terminal modification occurs in tissue culture produced okt3. BioPharm 4: 38-43.
24. Remelli M, Conato C, Agarossi A, Pulidori F, Mlynarz P, Kozlowski H. 2000. Copper complexes of dipeptides with l-lys as c-terminal residue: A thermodynamic and spectroscopic study. Polyhedron 19: 2409-2419.
25. Satani M, Takahashi K, Sakamoto H, Harada S, Kaida Y, Noguchi M. 2003. Expression and characterization of human bifunctional peptidylglycine alpha-amidating monooxygenase. Protein Expr Purif 28(2): 293-302.
26. Skidgel RA. 1988. Basic carboxypeptidases: Regulators of peptide hormone activity. Trends Pharmacol Sci 9(8): 299-304.
27. Skidgel RA, David RM, Tan F. 1989. Human carboxypeptidase m. Purification and characterization of a membrane-bound carboxypeptidase that cleaves peptide hormones. J Biol Chem 264(4): 2236-2241.
28. Suzuki K, Shimoi H, Iwasaki Y, Kawahara T, Matsuura Y, Nishikawa Y. 1990. Elucidation of amidating reaction mechanism by frog amidating enzyme, peptidylglycine alpha-hydroxylating monooxygenase, expressed in insect cell culture. EMBO J 9: 4259-4265.
29. Urlaub G, Chasin LA. 1980. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci 77(7): 4216-4220.
30. Vallee BL, Auld DS. 1990. Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry 29(24): 5647-5659.
31. Vallee BL, Rupley JA, Coombs TL, Neurath H. 1960. The role of zinc in carboxypeptidase. J Biol Chem 235(1): 64-69.
32. Vijayasankaran N, Shawley R, Yang Y, Shiratori M, Jamison K, Varma S, Caffaleatte C, Brooks D, Meier S, Zhang B, Gawlitzek M, Kiss R. Effect of copper on metabolism and productivity of industrial Chinese hamster ovary cell cultures. Biotechnol Prog Submitted.
33. Villegas V, Vendrell J, Aviles FX. 1995. The activation pathway of procarboxypeptidase B from porcine pancreas: Participation of the active enzyme in the proteolytic processing. Prot Sci 4: 1780-1792.
34. Williams RJP. 1960. Binding of zinc in carboxypeptidase. Nature 188: 322.
35. Yang L, McRae R, Henary MM, Patel R, Lai B, Vogt S, Fahrni CJ. 2005. Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron X-ray fluorescence microscopy. PNAS 102(32): 11179-11184.