Characterization of highly concentrated antibody solution - A toolbox for the description of protein long-term solution stability

mAbs

Volumn 9, Issue 7, 2017, Pages 1169-1185

  Schermeyer, Marie Therese ^a   Wöll, Anna K ^a   Kokke, Bas ^b   Eppink, Michel ^b   Hubbuch, Jürgen ^a  

^a KARLSRUHE INSTITUTE OF TECHNOLOGY   (Germany)

^b SYNTHON BV   (Netherlands)

Author keywords

Conformational and colloidal stability; monoclonal antibodies; phase diagram; thermal stability; viscoelasticity; viscosity; zeta potential

Indexed keywords

MONOCLONAL ANTIBODY;

CHEMISTRY; DRUG STABILITY; PROTEIN STABILITY;

ANTIBODIES, MONOCLONAL; DRUG STABILITY; PROTEIN STABILITY;

EID: 85025140437     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2017.1338222     Document Type: Article

References (84)

1. Rosman Z, Shoenfeld Y, Zandmann-Goddard G. Biologic therapy for autoimmune diseases: An update. BMC Med 2013; 11:88; PMID:23557513; https://doi.org/10.1186/1741-7015-11-88
2. Scott A, Wolchok J, Old L. Antibody therapy of cancer. Nat Rev Cancer 2012; 12:14; PMID:22437872; https://doi.org/10.1038/nrc3236
3. Shire SJ, Shahrokh Z, Liu JUN. Challenges in the development of high protein concentration formulations. J Pharm Sci 2004; 93:1390-402; PMID:15124199; https://doi.org/10.1002/jps.20079
4. Pindrus M, Shire S, Kelley R, Demeule B, Wong R. Solubility challenges in high concentration monoclonal antibody formulations: Relationship with amino acid sequence and intermolecular interactions. Mol Pharm 2015; 12:3896-907; PMID:26407030; https://doi.org/10.1021/acs.molpharmaceut.5b00336
5. Leckband D, Sivasankar S. Forces controlling protein interactions: Theory and experiment. Cool Surfaces B Biointerfaces 1999; 14:83-97; https://doi.org/10.1016/S0927-7765(99)00027-2
6. Chari R, Jerath K, Badkar A V, Kalonia DS. Long- and short-range electrostatic interactions affect the rheology of highly concentrated antibody solutions. Pharm Res 2009; 26:2607-18; PMID:19795191; https://doi.org/10.1007/s11095-009-9975-2
7. Dill KA. Dominant forces in protein folding. Biochemistry 1990; 29:7133-55; PMID:2207096; https://doi.org/10.1021/bi00483a001
8. Haezebrouck P, Joniau M, Van Dael H, Hooke SD, Woodruff ND, Dobson CM. An equilibrium partially folded state of human lysozyme at low pH. J Mol Biol 1995; 246:382-7; PMID:7877162; https://doi.org/10.1006/jmbi.1994.0093
9. Monahan FJ, German JB, Kinsella JE. Effect of pH and temperature on protein unfolding and thiol/disulfide interchange reactions during heat-induced gelation of whey proteins. J Agric Food Chem 1995; 43:46-52; https://doi.org/10.1021/jf00049a010
10. Kramer RM, Shende VR, Motl N, Pace CN, Scholtz JM. Toward a molecular understanding of protein solubility: Increased negative surface charge correlates with increased solubility. Biophys J 2012; 102:1907-15; PMID:22768947; https://doi.org/10.1016/j.bpj.2012.01.060
11. Kumar V, Dixit N, Zhou LL, Fraunhofer W. Impact of short range hydrophobic interactions and long range electrostatic forces on the aggregation kinetics of a monoclonal antibody and a dual-variable domain immunoglobulin at low and high concentrations. Int J Pharm 2011; 421:82-93; PMID:21959107; https://doi.org/10.1016/j.ijpharm.2011.09.017
12. Lehermayr C, Mahler HC, Mäder K, Fischer S. Assessment of net charge and protein-protein interactions of different monoclonal antibodies. J Pharm Sci 2011; 100:2551-62; PMID:21294130; https://doi.org/10.1002/jps.22506
13. Parsegian AV. Van der Waals forces: A handbook for biologists, chemists, engineers, and physicists. Cambridge: Cambridge University Press; 2006
14. Muramatsu N, Minton AP. Tracer diffusion of globular proteins in concentrated protein solutions. Proc Natl Acad Sci U S A 1988; 85:2984-8; PMID:3129721; https://doi.org/10.1073/pnas.85.9.2984
15. Baumann P, Schermeyer M-T, Burghardt H, Dürr C, Hubbuch J. Prediction and characterization of the stability enhancing effect of the Cherry-Tag in highly concentrated protein solutions by complex rheological measurements and MD simulations. Int J Pharm 2017; SUBMITTED
16. Weiss WF, Young TM, Roberts CJ. Principles, approaches, and challenges for predicting protein aggregation rates and shelf life. J Pharm Sci 2009; 98:1246-77; PMID:18683878; https://doi.org/10.1002/jps.21521
17. He F, Woods CE, Trilisky E, Bower KM, Litowski JR, Kerwin BA, Becker GW, Narhi LO, Razinkov VI. Screening of monoclonal antibody formulations based on high-throughput thermostability and viscosity measurements: Design of experiment and statistical analysis. J Pharm Sci 2011; 100:1330-40; PMID:24081468; https://doi.org/10.1002/jps.22384
18. Thiagarajan G, Semple A, James JK, Cheung JK, Shameem M. A comparison of biophysical characterization techniques in predicting monoclonal antibody stability. MAbs 2016; 8:1088-97; PMID:27210456; https://doi.org/10.1080/19420862.2016.1189048
19. Thakkar S V, Allegre KM, Joshi SB, Volkin DB, Middaugh CR. An application of ultraviolet spectroscopy to study interactions in proteins solutions at high concentrations. J Pharm Sci 2012; 101:3051-61; PMID:22581726; https://doi.org/10.1002/jps.23188
20. Scherer TM, Liu J, Shire SJ, Minton AP. Intermolecular interactions of IgG1 monoclonal antibodies at high concentrations characterized by light scattering. J Phys Chem B 2010; 114:12948-57; PMID:20849134; https://doi.org/10.1021/jp1028646
21. George A, Wilson WW. Predicting protein crystallization from a dilute solution property. Acta Crystallogr D Biol Crystallogr 1994; 50:361-5; PMID:15299385; https://doi.org/10.1107/S0907444994001216
22. Rosenbaum DF, Zukoski CF. Protein interactions and crystallization. J Cryst Growth 1996; 169:752-8; https://doi.org/10.1016/S0022-0248(96)00455-1
23. Wilson WW. Light scattering as a diagnostic for protein crystal growth: A practical approach. J Struct Biol 2003; 142:56-65; PMID:12718919; https://doi.org/10.1016/S1047-8477(03)00038-8
24. Ahamed T, Esteban B, Ottens M, van Dedem G, van der Wielen L, Bisschops M, Lee A, Pham C, Thömmes J. Phase behavior of an intact monoclonal antibody. Biophys J 2007; 93:610-9; PMID:17449660; https://doi.org/10.1529/biophysj.106.098293
25. Saluja A, Badkar A V, Zeng DL, Nema S, Kalonia DS. Application of high-frequency rheology measurements for analyzing protein-protein interactions in high protein concentration solutions using a model monoclonal antibody (IgG2). J Pharm Sci 2006; 95:1967-83; PMID:16847932; https://doi.org/10.1002/jps.20663
26. Rakel N, Baum M, Hubbuch J. Moving through three-dimensional phase diagrams of monoclonal antibodies. Biotechnol Prog 2014; 30:1103-13; PMID:25044865; https://doi.org/10.1002/btpr.1947
27. Bauer KC, Göbel M, Schwab M-L, Schermeyer M-T, Hubbuch J. Concentration-dependent changes in apparent diffusion coefficients as indicator for colloidal stability of protein solutions. Int J Pharm 2016; 511:276-87; PMID:27421911; https://doi.org/10.1016/j.ijpharm.2016.07.007
28. Liu J, Nguyen MDH, Andya JD, Shire SJ. Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution. J Pharm Sci 2005; 94:1928-40; PMID:16052543; https://doi.org/10.1002/jps.20347
29. Macosko CW. Rheology: Principles, measurements, and applications. VCH; 1994; ISBN:978-0-471-18575-8
30. Schermeyer M-T, Sigloch H, Bauer KC, Hubbuch J. Squeeze flow rheometry as a novel tool for the characterization of highly concentrated protein solutions. J Biotechnol Bioeng 2015; 113:576-587; PMID:26375304; https://doi.org/10.1002/bit.25834
31. Metzger T. The rheology handbook: For users of rotational and oscillatory rheometers. 2nd ed. Vincentz Network GmbH & Co KG; 2006
32. Webster S. Predicting long-term storage stability of therapeutic proteins. Pharm Tech 2013; 30(11).
33. Vermeer AW, Norde W. The thermal stability of immunoglobulin: Unfolding and aggregation of a multi-domain protein. Biophys J 2000; 78:394-404; PMID:10620303; https://doi.org/10.1016/S0006-3495(00)76602-1
34. Nicoud L, Sozo M, Arosio P, Yates A, Norrant E, Morbidelli M. Role of cosolutes in the aggregation kinetics of monoclonal antibodies. J Phys Chem B 2014; 118:11921-30; PMID:25243487; https://doi.org/10.1021/jp508000w
35. Ladbrooke BD, Chapman D. Thermal analysis of lipids, proteins and biological membranes - A review and summary of some recent studies. Chem Phys Lipids 1969; 3:304-56; PMID:4905514; https://doi.org/10.1016/0009-3084(69)90040-1
36. Yadav S, Shire SJ, Kalonia DS. Viscosity analysis of high concentration bovine serum albumin aqueous solutions. Pharm Res 2011; 28:1973-83; PMID:21491149; https://doi.org/10.1007/s11095-011-0424-7
37. Baumgartner K, Galm L, Nötzold J, Sigloch H, Morgenstern J, Schleining K, Suhm S, Oelmeier S a., Hubbuch J. Determination of protein phase diagrams by microbatch experiments: Exploring the influence of precipitants and pH. Int J Pharm 2015; 479:28-40; PMID:25541147; https://doi.org/10.1016/j.ijpharm.2014.12.027
38. Wang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. J Pharm Sci 2007; 96:1-26; PMID:16998873; https://doi.org/10.1002/jps.20727
39. Hussack G, Hirama T, Ding W, MacKenzie R, Tanha J. Engineered single-domain antibodies with high protease resistance and thermal stability. PLoS One 2011; 6:e28218; PMID:22140551; https://doi.org/10.1371/journal.pone.0028218
40. Youssef AMK, Winter G. A critical evaluation of microcalorimetry as a predictive tool for long term stability of liquid protein formulations: Granulocyte Colony Stimulating Factor (GCSF). Eur J Pharm Biopharm 2013; 84:145-55; PMID:23333898; https://doi.org/10.1016/j.ejpb.2012.12.017
41. Arakawa T, Tsumoto K. The effects of arginine on refolding of aggregated proteins: Not facilitate refolding, but suppress aggregation. Biochem Biophys Res Commun 2003; 304:148-52; PMID:12705899; https://doi.org/10.1016/S0006-291X(03)00578-3
42. Menzen TA. Temperature-induced unfolding, aggregation, and interaction of therapeutic monoclonal antibodies. 2014
43. Arakawa T, Timasheff SN. Theory of protein solubility. Methods Enzymol 1985; 114:49-77. PMID:4079776; https://doi.org/10.1016/0076-6879(85)14005-x
44. Mason B, Zhang-van Enk J, Zhang L, Remmele R, Zhang J. Liquid-liquid phase separation of a monoclonal antibody and nonmonotonic influence of Hofmeister anions. Biophys J 2010; 99:3792-800; PMID:21112304; https://doi.org/10.1016/j.bpj.2010.10.040
45. Wu SL, Karger BL. Hydrophobic interaction chromatography of proteins. Methods Enzymol 1996; 270:27-47. PMID:8803963; https://doi.org/10.1016/S0076-6879(96)70004-6
46. Melander W, Horváth C. Salt effect on hydrophobic interactions in precipitation and chromatography of proteins: An interpretation of the lyotropic series. Arch Biochem Biophys 1977; 183:200-15; PMID:907351; https://doi.org/10.1016/0003-9861(77)90434-9
47. Arakawa T, Bhat R, Timasheff SN. Preferential interactions determine protein solubility in three-component solutions: The MgCl2 system. Biochemistry 1990; 29:1914-23; PMID:2331471; https://doi.org/10.1021/bi00459a036
48. Curtis RA, Lue L. A molecular approach to bioseparations: Protein-protein and protein-salt interactions. Chem Eng Sci 2006; 61:907-23; https://doi.org/10.1016/j.ces.2005.04.007
49. Pusey PN, Poon WCK, Ilett SM, Bartlett P. Phase behaviour and structure of colloidal suspensions. J Phys Condens Matter 1994; 6:A29-A36; https://doi.org/10.1088/0953-8984/6/23A/004
50. Tardieu A, Bonneté F, Finet S, Vivarès D. Understanding salt or PEG induced attractive interactions to crystallize biological macromolecules. Acta Crystallogr Sect D Biol Crystallogr 2002; 58:1549-53; PMID:12351859; https://doi.org/10.1107/S0907444902014439
51. Hill TL. An introduction to statistical thermodynamics. Dover Publications; Mineola (New York); 1986
52. Luangtana-Anan M, Limmatvapirat S, Nunthanid J, Chalongsuk R, Yamamoto K. Polyethylene glycol on stability of chitosan microparticulate carrier for protein. AAPS PharmSciTech 2010; 11:1376-82; PMID:20821174; https://doi.org/10.1208/s12249-010-9512-y
53. Arakawa T, Timasheff SN. Mechanism of protein salting in and salting out by divalent cation salts: Balance between hydration and salt binding. Biochemistry 1984; 23:5912-23. PMID:6525340; https://doi.org/10.1021/bi00320a004
54. Bruździak P, Panuszko A, Stangret J. Influence of osmolytes on protein and water structure: A step to understanding the mechanism of protein stabilization. J Phys Chem B 2013; 117:11502-8; PMID:23992436; https://doi.org/10.1021/jp404780c
55. Arakawa T, Timasheff SN. Abnormal solubility behavior of beta-lactoglobulin: Salting-in by glycine and sodium chloride. Biochemistry 1987; 26:5147-53; PMID:3663650; https://doi.org/10.1021/bi00390a038
56. Arakawa T, Tsumoto K, Kita Y, Chang B, Ejima D. Biotechnology applications of amino acids in protein purification and formulations. Amino Acids 2007; 33:587-605; PMID:17357829; https://doi.org/10.1007/s00726-007-0506-3
57. Chen B-L, Arakawa T. Stabilization of recombinant human keratinocyte growth factor by osmolytes and salts. J Pharm Sci 1996; 85:419-22; PMID:8901081; https://doi.org/10.1021/js9504393
58. Zhang MZ, Wen J, Arakawa T, Prestrelski SJ. A new strategy for enhancing the stability of lyophilized protein: The effect of the reconstitution medium on keratinocyte growth factor. Pharm Res 1995; 12:1447-52; PMID:8584478; https://doi.org/10.1023/A:1016219000963
59. Jiskoot W, Crommelin D. Methods for structural analysis of protein pharmaceuticals. Springer Science & Business Media; Arlington (Virginia); 2005
60. Laurance JS, Middaugh CR. Aggregation of therapeutic proteins. Wiley; Hoboken (New Jersey); 2010
61. Piazza R. Protein interactions and association: An open challenge for colloid science. Curr Opin Colloid Interface Sci 2004; 8:515-22; https://doi.org/10.1016/j.cocis.2004.01.008
62. Halle B. Protein hydration dynamics in solution: A critical survey. Philos Trans R Soc Lond B Biol Sci 2004; 359:1207-23; PMID:15306377; https://doi.org/10.1098/rstb.2004.1499
63. Booth F. The electroviscous effect for suspensions of solid spherical particles. Proc R Soc London A Math Phys Eng Sci 1950; 203:533-551; https://doi.org/10.1098/rspa.1950.0155
64. Harding S. Dilute solution viscometry of food biopolymers. In: Hill S, Ledward D, Mitchel J, editors. Functional properties of food macromolecules. Aspen: Springer; 1998. page 10-5
65. Tanford C, Buzzell JG. The viscosity of aqueous solutions of bovine serum albumin between pH 4.3 and 10.5. J Phys Chem 1956; 60:225-31; https://doi.org/10.1021/j150536a020
66. Buzzell JG, Tanford C. The Effect of charge and ionic strength on the viscosity of ribonuclease. J Phys Chem 1956; 60:1204-7; https://doi.org/10.1021/j150543a014
67. Salinas BA, Sathish HA, Bishop SM, Harn N, Carpenter JF, Randolph TW. Understanding and modulating opalescence and viscosity in a monoclonal antibody formulation. J Pharm Sci 2010; 99:82-93; PMID:19475558; https://doi.org/10.1002/jps.21797
68. Connolly BD, Petry C, Yadav S, Demeule B, Ciaccio N, Moore JMR, Shire SJ, Gokarn YR. Weak interactions govern the viscosity of concentrated antibody solutions: high-throughput analysis using the diffusion interaction parameter. Biophys J 2012; 103:69-78; PMID:22828333; https://doi.org/10.1016/j.bpj.2012.04.047
69. Wang S, Zhang N, Hu T, Dai W, Feng X, Zhang X, Qian F. Viscosity-lowering effect of amino acids and salts on highly concentrated solutions of two IgG1 monoclonal antibodies. Mol Pharm 2015; 12:4478-87; PMID:26528726; https://doi.org/10.1021/acs.molpharmaceut.5b00643
70. Wen J, Jiang Y, Nahri L. Effect of carbohydrate on thermal stability of antibodies. Am Pharm Rev 2008; 11:1-6
71. Razvi A, Scholtz JM. Lessons in stability from thermophilic proteins. Protein Sci 2006; 15:1569-78; PMID:16815912; https://doi.org/10.1110/ps.062130306
72. Bye JW, Falconer RJ. Three stages of lysozyme thermal stabilization by high and medium charge density anions. J Phys Chem B 2014; 118:4282-6; PMID:24684707; https://doi.org/10.1021/jp412140v
73. Liu Y, Bolen DW. The peptide backbone plays a dominant role in protein stabilization by naturally occurring osmolytes. Biochemistry 1995; 34:12884-91; PMID:7548045; https://doi.org/10.1021/bi00039a051
74. Platts L, Falconer RJ. Controlling protein stability: Mechanisms revealed using formulations of arginine, glycine and guanidinium HCl with three globular proteins. Int J Pharm 2015; 486:131-5; PMID:25818064; https://doi.org/10.1016/j.ijpharm.2015.03.051
75. Street TO, Bolen DW, Rose GD. A molecular mechanism for osmolyte-induced protein stability. Proc Natl Acad Sci U S A 2006; 103:13997-4002; PMID:16968772; https://doi.org/10.1073/pnas.0606236103
76. Arakawa T, Timasheff SN. Mechanism of polyethylene glycol interaction with proteins. Biochemistry 1985; 24:6756-62; PMID:4074726; https://doi.org/10.1021/bi00345a005
77. Kirschenmann L. Aufbau zweier piezoelektrischer Sonden (PRV / PAV) zur Messung der viskoelastischen Eigenschaften weicher Substanzen im Frequenzbereich 0.5 Hz-2 kHz bzw. 0.5 Hz– 7 kHz. 2003
78. Ingham KC. Polyethylene glycol in aqueous solution: Solvent perturbation and gel filtration studies. Arch Biochem Biophys 1977; 184:59-68; PMID:921299; https://doi.org/10.1016/0003-9861(77)90326-5
79. Du W, Klibanov AM. Hydrophobic salts markedly diminish viscosity of concentrated protein solutions. Biotechnol Bioeng 2011; 108:632-6; PMID:21246510; https://doi.org/10.1002/bit.22983
80. Charlton LM, Barnes CO, Li C, Orans J, Young GB, Pielak GJ. Residue-level interrogation of macromolecular crowding effects on protein stability. J Am Chem Soc 2008; 130:6826-30; PMID:18459780; https://doi.org/10.1021/ja8005995
81. Minton AP. Influence of macromolecular crowding upon the stability and state of association of proteins: Predictions and observations. J Pharm Sci 2005; 94:1668-75; PMID:15986476; https://doi.org/10.1002/jps.20417
82. Kröner F, Hubbuch J. Systematic generation of buffer systems for pH gradient ion exchange chromatography and their application. J Chromatogr A 2013; 1285:78-87; PMID:23489486; https://doi.org/10.1016/j.chroma.2013.02.017
83. Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol 2011; 697:63-70; PMID:21116954; 10.1007/978-1-60327-198-1_6
84. Crassous JJ, Régisser R, Ballauff M, Willenbacher N. Characterization of the viscoelastic behavior of complex fluids using the piezoelastic axial vibrator. J Rheol (N Y N Y) 2005; 49:851; https://doi.org/10.1122/1.1917843