Therapeutic monoclonal antibodies and consistent ends: Terminal heterogeneity, detection, and impact on quality

Current Opinion in Biotechnology

Volumn 30, Issue , 2014, Pages 140-146

  Brorson, Kurt ^a   Jia, Audrey Y ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SURFACE PLASMON RESONANCE;

ANALYTICAL METHOD; BIOLOGICAL MACROMOLECULE; MONOCLONAL ANTIBODIES (MABS); POST-TRANSLATIONAL MODIFICATIONS; POTENTIAL IMPACTS; PRODUCT VARIANTS; REGULATORY CONSIDERATIONS; THERAPEUTIC MONOCLONAL ANTIBODIES;

MONOCLONAL ANTIBODIES;

CETUXIMAB; MONOCLONAL ANTIBODY; GLUTAMIC ACID; ISOPROTEIN; PYROGLUTAMIC ACID; GLUTAMINE;

DRUG EFFICACY; DRUG PURIFICATION; DRUG QUALITY; DRUG SAFETY; DRUG STORAGE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOGENICITY; ION EXCHANGE CHROMATOGRAPHY; ISOELECTRIC FOCUSING; MASS SPECTROMETRY; METASTASIS; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; ANIMAL; BIOTECHNOLOGY; CHEMISTRY; ISOLATION AND PURIFICATION; METABOLISM; PROTEIN PROCESSING; AMINO TERMINAL SEQUENCE; ANALYTIC METHOD; ANTIBODY DETECTION; ANTIBODY PRODUCTION; CAPILLARY ELECTROPHORESIS; CARBOXY TERMINAL SEQUENCE; CHEMICAL PARAMETERS; COMPLEMENTARITY DETERMINING REGION; CRITICAL QUALITY ATTRIBUTE; DEUTERIUM HYDROGEN EXCHANGE; ELECTROSPRAY; HEAVY CHAIN; HUMAN; LIGHT CHAIN; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN LOCALIZATION; PROTEIN POLYMORPHISM; PROTEIN QUALITY; PROTEIN STABILITY; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY;

ANIMALS; ANTIBODIES, MONOCLONAL; BIOTECHNOLOGY; DRUG STORAGE; GLUTAMIC ACID; PROTEIN ISOFORMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PYRROLIDONECARBOXYLIC ACID;

EID: 84904252193     PISSN: 09581669     EISSN: 18790429     Source Type: Journal    
DOI: 10.1016/j.copbio.2014.06.012     Document Type: Review

References (50)

1. Jenkins N., Murphy L., Tyther R. Post-translational modifications of recombinant proteins: significance for biopharmaceuticals. Mol Biotechnol 2008, 39:113-118.
2. Luo J., Vijayasankaran N., Autsen J., Santuray R., Hudson T., Amanullah A., Li F. Comparative metabolite analysis to understand lactate metabolism shift in Chinese hamster ovary cell culture process. Biotechnol Bioeng 2012, 109:146-156.
3. Jensen O.N. Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry 2004.
4. Tang L., Sundaram S., Zhang J., Carlson P., Matathia A., Parekh B., Zhou Q., Hsieh M.C. Conformational characterization of the charge variants of a human IgG1 monoclonal antibody using H/D exchange mass spectrometry. MAbs 2013, 5:114-125.
5. Yu L., Vizel A., Huff M.B., Young M., Remmele R.L., He B. Investigation of N-terminal glutamate cyclization of recombinant monoclonal antibody in formulation development. J Pharm Biomed Anal 2006, 42:455-463.
6. Chelius D., Jing K., Lueras A., Rehder D.S., Dillon T.M., Vizel A., Rajan R.S., Li T., Treuheit M.J., Bondarenko P.V. Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies. Anal Chem 2006, 78:2370-2376.
7. Liu H., Gaza-Bulseco G., Faldu D., Chumsae C., Sun J. Heterogeneity of monoclonal antibodies. J Pharm Sci 2008, 97:2426-2447.
8. Xu W., Peng Y., Wang F., Paporello B., Richardson D., Liu H. Method to convert N-terminal glutamine to pyroglutamate for characterization of recombinant monoclonal antibodies. Anal Biochem 2013, 436:10-12.
9. Dick L.W., Kim C., Qiu D., Cheng K.C. Determination of the origin of the N-terminal pyro-glutamate variation in monoclonal antibodies using model peptides. Biotechnol Bioeng 2007, 97:544-553.
10. Du Y., Walsh A., Ehrick R., Xu W., May K., Liu H. Chromatographic analysis of the acidic and basic species of recombinant monoclonal antibodies. MAbs 2012, 4:578-585.
11. Manning M.C., Chou D.K., Murphy B.M., Payne R.W., Katayama D.S. Stability of protein pharmaceuticals: an update. Pharm Res 2010, 27:544-575.
12. Liu Y.D., Goetze A.M., Bass R.B., Flynn G.C. N-terminal glutamate to pyroglutamate conversion in vivo for human IgG2 antibodies. J Biol Chem 2011, 286:11211-11217.
13. Huang K.F., Liu Y.L., Cheng W.J., Ko T.P., Wang A.H. Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation. Proc Natl Acad Sci USA 2005, 102:13117-13122.
14. Schilling S., Hoffmann T., Manhart S., Hoffmann M., Demuth H.U. Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions. FEBS Lett 2004, 563:191-196.
15. Antes B., Amon S., Rizzi A., Wiederkum S., Kainer M., Szolar O., Fido M., Kircheis R., Nechansky A. 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 2007, 852:250-256.
16. Santora L.C., Stanley K., Krull I.S., Grant K. Characterization of maleuric acid derivatives on transgenic human monoclonal antibody due to post-secretional modifications in goat milk. Biomed Chromatogr 2006, 20:843-856.
17. Kotia R.B., Raghani A.R. Analysis of monoclonal antibody product heterogeneity resulting from alternate cleavage sites of signal peptide. Anal Biochem 2010, 399:190-195.
18. Khawli L.A., Goswami S., Hutchinson R., Kwong Z.W., Yang J., Wang X., Yao Z., Sreedhara A., Cano T., Tesar D., Nijem I., Allison D.E., Wong P.Y., Kao Y.H., Quan C., Joshi A., Harris R.J., Motchnik P. Charge variants in IgG1: isolation, characterization, in vitro binding properties and pharmacokinetics in rats. MAbs 2010, 2:613-624.
19. Lin J., Tan Q., Wang S. A high-resolution capillary isoelectric focusing method for the determination of therapeutic recombinant monoclonal antibody. J Sep Sci 2011, 34:1696-1702.
20. Ahrer K., Jungbauer A. Chromatographic and electrophoretic characterization of protein variants. J Chromatogr B Analyt Technol Biomed Life Sci 2006, 841:110-122.
21. Vlasak J., Ionescu R. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods. Curr Pharm Biotechnol 2008, 9:468-481.
22. El R.Z. Electrophoretic and electrochromatographic separation of proteins in capillaries: an update covering 2007-2009. Electrophoresis 2010, 31:174-191.
23. He X.Z., Que A.H., Mo J.J. Analysis of charge heterogeneities in mAbs using imaged CE. Electrophoresis 2009, 30:714-722.
24. Meert C.D., Brady L.J., Guo A., Balland A. Characterization of antibody charge heterogeneity resolved by preparative immobilized pH gradients. Anal Chem 2010, 82:3510-3518.
25. Gerster A. High-throughput chromatography screenings for modulating charge-related isoform patterns. Edited by Rudolph f, Dieterle m. BioProcess Int 2013, 11:46-53.
26. Moorhouse K.G., Nashabeh W., Deveney J., Bjork N.S., Mulkerrin M.G., Ryskamp T. Validation of an HPLC method for the analysis of the charge heterogeneity of the recombinant monoclonal antibody IDEC-C2B8 after papain digestion. J Pharm Biomed Anal 1997, 16:593-603.
27. Thompson N.J., Rosati S., Heck A.J. Performing native mass spectrometry analysis on therapeutic antibodies. Methods 2014, 65:11-17.
28. Kaltashov I.A., Bobst C.E., Abzalimov R.R., Wang G., Baykal B., Wang S. Advances and challenges in analytical characterization of biotechnology products: mass spectrometry-based approaches to study properties and behavior of protein therapeutics. Biotechnol Adv 2012, 30:210-222.
29. Ramos J.D., Cheong N., Lee B.W., Chua K.Y. Peptide mapping of immunoglobulin E and immunoglobulin G immunodominant epitopes of an allergenic Blomia tropicalis paramyosin, Blo t 11. Clin Exp Allergy 2003, 33:511-517.
30. Ren D., Pipes G.D., Hambly D., Bondarenko P.V., Treuheit M.J., Gadgil H.S. Top-down N-terminal sequencing of Immunoglobulin subunits with electrospray ionization time of flight mass spectrometry. Anal Biochem 2009, 384:42-48.
31. Hsu J.L., Huang S.Y., Shiea J.T., Huang W.Y., Chen S.H. Beyond quantitative proteomics: signal enhancement of the a1 ion as a mass tag for peptide sequencing using dimethyl labeling. J Proteome Res 2005, 4:101-108.
32. Huang S.Y., Hsieh Y.T., Chen C.H., Chen C.C., Sung W.C., Chou M.Y., Chen S.F. Automatic disulfide bond assignment using a1 ion screening by mass spectrometry for structural characterization of protein pharmaceuticals. Anal Chem 2012, 84:4900-4906.
33. Kleifeld O., Doucet A., Prudova A., auf dem K.U., Gioia M., Kizhakkedathu J.N., Overall C.M. Identifying and quantifying proteolytic events and the natural N terminome by terminal amine isotopic labeling of substrates. Nat Protoc 2011, 6:1578-1611.
34. Nakajima C., Kuyama H., Nakazawa T., Nishimura O., Tsunasawa S. A method for N-terminal de novo sequencing of Nalpha-blocked proteins by mass spectrometry. Analyst 2011, 136:113-119.
35. Rehder D.S., Dillon T.M., Pipes G.D., Bondarenko P.V. Reversed-phase liquid chromatography/mass spectrometry analysis of reduced monoclonal antibodies in pharmaceutics. J Chromatogr A 2006, 1102:164-175.
36. Yan B., Valliere-Douglass J., Brady L., Steen S., Han M., Pace D., Elliott S., Yates Z., Han Y., Balland A., Wang W., Pettit D. Analysis of post-translational modifications in recombinant monoclonal antibody IgG1 by reversed-phase liquid chromatography/mass spectrometry. J Chromatogr A 2007, 1164:153-161.
37. Lyubarskaya Y., Houde D., Woodard J., Murphy D., Mhatre R. Analysis of recombinant monoclonal antibody isoforms by electrospray ionization mass spectrometry as a strategy for streamlining characterization of recombinant monoclonal antibody charge heterogeneity. Anal Biochem 2006, 348:24-39.
38. Dick L.W., Qiu D., Mahon D., Adamo M., Cheng K.C. C-terminal lysine variants in fully human monoclonal antibodies: investigation of test methods and possible causes. Biotechnol Bioeng 2008, 100:1132-1143.
39. Luo J., Zhang J., Ren D., Tsai W.L., Li F., Amanullah A., Hudson T. Probing of C-terminal lysine variation in a recombinant monoclonal antibody production using Chinese hamster ovary cells with chemically defined media. Biotechnol Bioeng 2012, 109:2306-2315.
40. Johnson K.A., Paisley-Flango K., Tangarone B.S., Porter T.J., Rouse J.C. Cation exchange-HPLC and mass spectrometry reveal C-terminal amidation of an IgG1 heavy chain. Anal Biochem 2007, 360:75-83.
41. Zhang Z., Pan H., Chen X. Mass spectrometry for structural characterization of therapeutic antibodies. Mass Spectrom Rev 2009, 28:147-176.
42. Beck A., Bussat M.C., Zorn N., Robillard V., Klinguer-Hamour C., Chenu S., Goetsch L., Corvaia N., Van D.A., Haeuw J.F. Characterization by liquid chromatography combined with mass spectrometry of monoclonal anti-IGF-1 receptor antibodies produced in CHO and NS0 cells. J Chromatogr B Analyt Technol Biomed Life Sci 2005, 819:203-218.
43. Melter L., Strohlein G., Butte A., Morbidelli M. Adsorption of monoclonal antibody variants on analytical cation-exchange resin. J Chromatogr A 2007, 1154:121-131.
44. Lazar A.C., Kloczewiak M.A., Mazsaroff I. Matrix-assisted laser desorption/ionization mass spectrometry for the evaluation of the C-terminal lysine distribution of a recombinant monoclonal antibody. Rapid Commun Mass Spectrom 2004, 18:239-244.
45. Dillon T.M., Bondarenko P.V., Speed R.M. Development of an analytical reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry method for characterization of recombinant antibodies. J Chromatogr A 2004, 1053:299-305.
46. Cai B., Pan H., Flynn G.C. C-terminal lysine processing of human immunoglobulin G2 heavy chain in vivo. Biotechnol Bioeng 2011, 108:404-412.
47. Harris R.J. Processing of C-terminal lysine and arginine residues of proteins isolated from mammalian cell culture. J Chromatogr A 1995, 705:129-134.
48. Kinoshita M., Nakatsuji Y., Suzuki S., Hayakawa T., Kakehi K. Quality assurance of monoclonal antibody pharmaceuticals based on their charge variants using microchip isoelectric focusing method. J Chromatogr A 2013, 1309:76-83.
49. Sundaram S., Matathia A., Qian J., Zhang J., Hsieh M.C., Liu T., Crowley R., Parekh B., Zhou Q. An innovative approach for the characterization of the isoforms of a monoclonal antibody product. MAbs 2011, 3:505-512.
50. Valliere-Douglass J., Wallace A., Balland A. Separation of populations of antibody variants by fine tuning of hydrophobic-interaction chromatography operating conditions. J Chromatogr A 2008, 1214:81-89.