Elucidation of degradants in acidic peak of cation exchange chromatography in an IgG1 monoclonal antibody formed on long-term storage in a liquid formulation

Pharmaceutical Research

Volumn 29, Issue 1, 2012, Pages 209-224

  Gandhi, Sejal ^a   Ren, Da ^a   Xiao, Gang ^a   Bondarenko, Pavel ^a   Sloey, Christopher ^a   Ricci, Margaret Speed ^a   Krishnan, Sampathkumar ^a  

^a AMGEN INC   (United States)

Author keywords

Acidic peak; Cation exchange chromatography; Deamidation; IgGImonoclonal antibody; Protein formulation

Indexed keywords

FC RECEPTOR; GLUTAMINE; IMMUNOGLOBULIN G1 ANTIBODY; MONOCLONAL ANTIBODY; SIALIC ACID; TRYPSIN; ASPARAGINE; ASPARTIC ACID; FC RECEPTOR, NEONATAL; HLA ANTIGEN CLASS 1; IMMUNOGLOBULIN G;

ALKYLATION; ANTIGEN BINDING; ARTICLE; BIOASSAY; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DEAMINATION; DEGRADATION KINETICS; DRUG DETERMINATION; GLYCATION; INCUBATION TEMPERATURE; ION EXCHANGE CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULAR SIZE; OXIDATION KINETICS; PARTICLE SIZE; PEPTIDE MAPPING; PRIORITY JOURNAL; RECEPTOR BINDING; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SURFACE PLASMON RESONANCE; ANIMAL; CHEMISTRY; CHO CELL; COMPLEMENTARITY DETERMINING REGION; DRUG STABILITY; DRUG STORAGE; GEL CHROMATOGRAPHY; GLYCOSYLATION; HAMSTER; HUMAN; ISOELECTRIC FOCUSING; LIQUID CHROMATOGRAPHY; METHODOLOGY; REVERSED PHASE LIQUID CHROMATOGRAPHY; TEMPERATURE;

ANIMALS; ANTIBODIES, MONOCLONAL; ASPARAGINE; ASPARTIC ACID; CHEMISTRY, PHARMACEUTICAL; CHO CELLS; CHROMATOGRAPHY, GEL; CHROMATOGRAPHY, ION EXCHANGE; CHROMATOGRAPHY, LIQUID; CHROMATOGRAPHY, REVERSE-PHASE; COMPLEMENTARITY DETERMINING REGIONS; CRICETINAE; DRUG STABILITY; DRUG STORAGE; GLUTAMINE; GLYCOSYLATION; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IMMUNOGLOBULIN G; ISOELECTRIC FOCUSING; MASS SPECTROMETRY; PEPTIDE MAPPING; RECEPTORS, FC; TEMPERATURE; TRYPSIN;

EID: 84860557842     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-011-0536-0     Document Type: Article

References (50)

1. Liu H, Gaza-Bulseco G, Faldu D, Chumsae C, Sun J. Heterogeneity of monoclonal antibodies. J Pharm Sci. 2007;97:2426-47.
2. Wang W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm. 1999;185:129-88. (Pubitemid 29392904)
3. Manning MC, Patel K, Borchardt R. Stability of protein pharmaceuticals. Pharm Res. 1989;6:903-18.
4. Liu D. Deamidation: a source of microheterogeneity in pharmaceutical proteins. Trends Biotechnol. 1992;10:364-9.
5. Aswad D, Paranandi M, Schuter B. Isoaspartate in peptides and proteins: formation, significance, and analysis. J Pharm Biomed Anal. 2000;21:1129-36. (Pubitemid 30001541)
6. Johnson K, Paisley-Flango K, Tangarone B, Porter T, Rouse J. Cation exchange-HPLC and mass spectrometry reveal C-terminal amidation of an IgG1 heavy chain. Anal Biochem. 2006;360:75-83. (Pubitemid 44894347)
7. Perkins M, Theiler R, Lunte S, Jeschke M. Determination of the origin of charge heterogeneity in a murine monoclonal antibody. Pharm Res. 2000;17:1110-7.
8. Weitzhandler M, Farnan D, Rohrer J, Avdalovic N. Protein variant separations using cation exchange chromatography on grafted, polymeric stationary phases. Proteomics. 2001;1:179-85. (Pubitemid 33586713)
9. Weitzhandler M, Farnan D, Horwath J, Rohrer J, Slingsby R, Avdalovic N, et al. Protein variant separations by cation-exchange chromatography on tentacle-type polymeric stationary phases. J Chromatogr A. 1998;828:365-72. (Pubitemid 29046436)
10. Harris RJ, Kabakoff B, Macchi FD, Shen FJ, Kwong M, Andya JD, et al. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chromatogr B. 2001;752:233-45. (Pubitemid 32168159)
11. Vlasak J, Ionescu R. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods. Curr Pharm Biotechnol. 2008;9:468-81.
12. Wakankar A, Borchardt R. Formulation considerations for proteins susceptible to asparagine deamidation and aspartate isomerization. J Pharm Sci. 2006;95:2321-36. (Pubitemid 44732136)
13. Capasso S, Mazzarella L, Sica F, Zagari A, Salvadori S. Kinetics and mechanism of succinimide ring formation in the deamidation process of asparagine residues. J Chem Soc, Perkin Trans. 1993;2:679-82.
14. Patel K, Borchardt R. Chemical pathways of peptide degradation. III. Effect of primary sequence on the pathways of deamidation of asparaginyl residues in hexapeptides. Pharm Res. 1990;7:787-93. (Pubitemid 20332529)
15. Oliyai C, Borchardt R. Chemical pathways of peptide degradation. IV. Pathways, kinetics, and mechanism of degradation of an aspartyl residue in a model hexapeptide. Pharm Res. 1993;10:95-102. (Pubitemid 23020844)
16. Song Y, Schowen R, Borchardt R, Topp E. Effect of 'pH' on the rate of asparagine deamidation in polymeric formulations: 'pH'-rate profile. J Pharm Sci. 2001;90:141-56. (Pubitemid 32158042)
17. Geiger T, Clarke S. Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimidelinked reactions that contribute to protein degradation. J Biol Chem. 1987;262:785-94. (Pubitemid 17005254)
18. Patel K, Borchardt RT. Chemical pathways of peptide degradation: II. Kinetics of deamidation of an asparaginyl residue in a model hexapeptide. Pharm Res. 1990;7:703-11. (Pubitemid 20278366)
19. Kosky AA, Razzaq UO, Treuheit MJ, Brems DN. The effects of α-helix on the stability of Asn residues: deamidation rates in peptides of varying helicity. Protein Sci. 1999;8:2519-23. (Pubitemid 29536421)
20. Robinson NE, Robinson AB. Prediction of protein deamidation rates from primary and three-dimensional structure. Proc Natl Acad Sci USA. 2001;98:4367-72. (Pubitemid 32294983)
21. Capasso S. Estimation of the deamidation rate of asparagine side chains. J Pept Res. 2000;55:224-9. (Pubitemid 30126656)
22. Oliyai C, Borchardt R. Chemical pathways of peptide degradation. VI. Effect of the primary sequence on the pathways of degradation of aspartyl residues in model hexapeptides. PharmRes. 1994;11:751-8. (Pubitemid 24171774)
23. Li B, Gorman E, Moore K, Williams T, Schowen R, Topp E, et al. Effects of acidic N+1 residues on asparagine deamidation rates in solution and in the solid state. J Pharm Sci. 2005;94:666-75. (Pubitemid 40476530)
24. Yan B, Steen S, Hambly D, Valliere-Douglass J, Bos T, Smallwood S, et al. Succinimide formation at Asn 55 in the complementarity determining region of a recombinant monoclonal antibody IgG1 heavy chain. J Pharm Sci. 2009;98:3509-21.
25. Zhang Y, Martinez T, Woodruff B, Goetze A, Bailey R, Pettit D, et al. Hydrophobic interaction chromatography of soluble interleukin I receptor type II to reveal chemical degradations resulting in loss of potency. Anal Chem. 2008;80:7022-8.
26. Paranandi M, Guzzetta A, Hancock W, Aswad D. Deamidation and isoaspartate formations during in vitro aging of recombinant tissue plasminogen activator. J Biol Chem. 1994;269:243-53. (Pubitemid 24026651)
27. Stevenson C, Anderegg R, Borchardt R. Comparison of separation and detection techniques for human growth hormone releasing factor (hGRF) and the products from deamidation. J Pharm Biomed Anal. 1993;11:367-73. (Pubitemid 23201948)
28. Bongers J, Cummings J, Ebert M, Federici M, Gledhill L, Gulati D, et al. Validation of a peptide mapping method for a therapeutic monoclonal antibody: what could we possibly learn about a method we have run 100 times? J Pharm Biomed Anal. 2000;21:1099-128. (Pubitemid 30001540)
29. Chelius D, Rehder D, Bondarenko P. Identification and characterization of deamidation sites in the conserved regions of human immunoglobulin gamma antibodies. Anal Chem. 2005;77:6004-11. (Pubitemid 41324303)
30. Terashima I, Koga A, Nagai H. Identification of deamidation and isomerization sites on pharmaceutical recombinant antibody using H218O. Anal Biochem. 2007;368:49-60. (Pubitemid 47058431)
31. Ren D, Pipes GD, Liu D, Shih L, Nichols AC, Treuheit MJ, et al. An improved trypsin digestion method minimizes digestioninduced modifications on proteins. Anal Biochem. 2009;393:12-21.
32. Dong A, Caughey WS. Infrared methods for study of hemoglobin reactions and structures. Meth Enzymol. 1994;232:139-75.
33. Kendrick BS, Dong A, Allison SD, Manning MC, Carpenter JF. Quantitation of the area of overlap between second-derivative amide I infrared spectra to determine the structural similarity of a protein in different states. J Pharm Sci. 1996;85:155-8. (Pubitemid 26055795)
34. Zhang Z. Prediction of low-energy collision-induced dissociation spectra of peptides. Anal Chem. 2004;76:3908-22. (Pubitemid 38943659)
35. Zhang Z. De novo peptide sequencing based on a divide-andconquer algorithm and peptide tandem spectrum simulation. Anal Chem. 2004;76:6374-83. (Pubitemid 39458471)
36. Zhang Z. Large-scale identification and modification of covalent modifications on therapeutic proteins. Anal Chem. 2009;81:8354-64.
37. Mario N, Baudin B, Aussel C, Giboudeau J. Capillary isoelectric focusing and high-performance cation-exchange chromatography compared for qualitative and quantitative analysis of hemoglobin variants. Clin Chem. 1997;43:2137-42. (Pubitemid 27497813)
38. Rehder DS, Chelius D, McAuley A, Dillon TM, Xiao G, Crousse-Zeineddini J, et al. Isomerization of a single aspartyl residue of anti-epidermal growth factor receptor immunoglobulin gamma 2 antibody highlights the role avidity plays in antibody activity. Biochemistry. 2008;47:2518-30. (Pubitemid 351304557)
39. Martin W, Bjorkman P. Characterization of the 2:1 complex between the class I MHC-related Fc receptor and its Fc ligand in solution. Biochemistry. 1999;38:12639-47.
40. Hambly DM, Banks DD, Scavezze JL, Siska CC, Gadgil HS. Detection and quantitation of IgG 1 hinge aspartate isomerization: the fastest degradation in stressed stability studies. Anal Chem. 2009;81:7454-9.
41. Dick Jr LW, Qiu D, Cheng K. Identification and measurement of isoaspartic acid formation in the complementarity determiningregion of a fully human monoclonal antibody. J Chromatogr B. 2009;877:3841-9.
42. Lau H, Pace D, Yan B, McGrath T, Smallwood S, Patel K, et al. Investigation of degradation processes in IgG1 monoclonal antibodies by limited proteolysis coupled with weak cation exchange HPLC. J Chromatogr B. 2010;878:868-76.
43. Quan C, Alcala E, Petkovska I, Matthews D, Canova-Davis E, Taticek R, et al. A study in glycation of a therapeutic recombinant humanized monoclonal antibody: where it is, how it got there, and how it affects charge-based behavior. Anal Biochem. 2008;373:179-91.
44. Robinson NE, Robinson AB. Molecular clocks. Proc Natl Acad Sci USA. 2001;98:944-9. (Pubitemid 32121167)
45. Reissner KJ, Aswad DW. Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals? Cell Mol Life Sci. 2003;60:1281-95. (Pubitemid 36900513)
46. Weintraub SJ, Manson SR. Asparagine deamidation: a regulatory hourglass. Mech Ageing Dev. 2004;125:255-7. (Pubitemid 38438503)
47. Vlasak J, Bussat M, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, et al. Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Anal Biochem. 2009;392:145-54.
48. Yeung YA, Leabman MK, Marvin JS, Qiu J, Adams CW, Lien S, et al. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol. 2009;182:7663-71.
49. 2-microglobulin: possible protective role of FcRn. Immunology. 1996;89:573-8.
50. Capasso S, Di Cerbo P. Kinetic and thermodynamic control of the relative yield of the deamidation of asparagine and isomerization of aspartic acid residues. J Pept Res. 2000;56:382-7.