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Crystallization approach for purification of intact monoclonal antibodies: A review

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Author Affiliations

  • 1Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India
  • 2Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India
  • 3Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India
  • 4Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India

Res.J.chem.sci., Volume 13, Issue (1), Pages 65-78, February,18 (2023)

Abstract

Over the 20th century, protein crystallization had been accepted and developed as a powerful purification tool before chromatography. It has also been applied for various biologically important macromolecules for efficacious durability and contracted dosage in the field of drug formulation. Right from the evolution, intact monoclonal antibodies (mAbs) have gained prime importance in the field of therapeutic drug applications, especially in immunotherapies. The fragments of mAbs have also been used for different applications. The purification strategies researched and established for these molecules during the last 20 years are predominantly chromatographies. But considering the process cost limitations, crystallization was found to be effective to purify the intact monoclonal antibodies from a massive number of proteins in culture broth and feasible to use as an alternative platform. This review presents the success rate of crystallization in intact monoclonal antibody purification. Further, the importance of phase behavior studies, the effects of additives on monoclonal antibody crystallization is discussed with the help of case studies. Also, the comparison of different batch versus continuous crystallization methods applied is discussed. In the end, the requirement and prospects of large-scale crystallization studies of intact monoclonal antibodies invoking the accomplishment of high throughput demand are discussed.

References

  1. Abdalla, M., Dai, Y. N., Chi, C. B., Cheng, W., Cao, D. D., Zhou, K., Ali, W., Chen, Y., & Zhou, C. Z. (2016)., Crystal structure of yeast monothiol glutaredoxin Grx6 in complex with a glutathione-coordinated [2Fe-2S] cluster., Acta Crystallographica Section: F Structural Biology Communications, 72(10), 732–737.
  2. Adachi, H., Takano, K. Morikawa, M., Kanaya, S., Yoshimura, M., Mori, Y. & Sasaki, T. (2003)., Application of a two-liquid system to sitting-drop vapour-diffusion protein crystallization., Acta Crystallographica Section D: Biological Crystallography, 59(1), 194-196.
  3. Ahamed, T., Esteban, B. N., Ottens, M., Van Dedem, G. W., Van der Wielen, L. A., Bisschops, M. A., ... & Thömmes, J. (2007)., Phase behavior of an intact monoclonal antibody., Biophysical journal, 93(2), 610-619.
  4. Alvarado, U. R., DeWitt, C. R., Shultz, B. B., Ramsland, P. A. & Edmundson, A. B. (2001)., Crystallization of a human Bence–Jones protein in microgravity using vapor diffusion in capillaries., Journal of Crystal Growth, 223(3), 407-414.
  5. D, Microseed matrix screening for optimization in protein crystallization: what have we learned?., Acta Crystallographica Section F: Structural Biology Communications, 70(9), 1117-1126.
  6. D, The advantages of using a modified microbatch method for rapid screening of protein crystallization conditions., Acta Crystallographica Section D: Biological Crystallography, 59(2), 396-399.
  7. Asherie, N. (2004)., Protein crystallization and phase diagrams., Methods, 34(3), 266-272.
  8. Bolanos-Garcia, V. M. & Chayen, N. E. (2009)., New directions in conventional methods of protein crystallization., Progress in biophysics and molecular biology, 101(1-3), 3-12.
  9. Bunick, C., North, A. C. T. & Stubbs, G. (2000)., Evaporative microdialysis: an effective improvement in an established method of protein crystallization., Acta Crystallographica Section D: Biological Crystallography, 56(11), 1430-1431.
  10. Chayen, B. N. E. (2009)., High-Throughput Protein Crystallization Structural genomics projects have led to great progress in the field of structural biology. Considerable advances have been made in the automation of all stages of the pipeline from clone to structure. This chapte., Advances in Protein Chemistry and Structural Biology, 77(09). Elsevier. https://doi.org/10.1016/S1876-1623(09)77001-4
  11. Chayen, N. E., & Saridakis, E. (2008)., Protein crystallization: from purified protein to diffraction-quality crystal., Nature methods, 5(2), 147-153.
  12. Chusainow, J., Yang, Y. S., Yeo, J. H., Toh, P. C., Asvadi, P., Wong, N. S., & Yap, M. G. (2009)., A study of monoclonal antibody‐producing CHO cell lines: What makes a stable high producer?., Biotechnology and Bioengineering, 102(4), 1182-1196.
  13. Collins, K. D. (2004)., Ions from the Hofmeister series and osmolytes: effects on proteins in solution and in the crystallization process., Methods, 34(3), 300-311.
  14. Collins, K. D. (2006)., Ion hydration: Implications for cellular function, polyelectrolytes and protein crystallization., 119, 271–281. https://doi.org/10.1016/j. bpc.2005.08.010
  15. Data, R. U. S. A., Helk, B., Smejkal, B., Schulz, K. & Smejkal, B. (2015)., (12) Patent Application Publication (10) Pub., No .: US 2015 / 0133642 A1. 1(19).
  16. Yang, H., Belviso, B. D., Li, X., Chen, W., Mastropietro, T. F., Di Profio, G., ... & Heng, J. Y. (2019)., Optimization of vapor diffusion conditions for anti-CD20 crystallization and scale-up to meso batch., Crystals, 9(5), 230.
  17. Dumetz, A. C., Snellinger‐O, Patterns of protein–protein interactions in salt solutions and implications for protein crystallization., Protein Science, 16(9), 1867-1877.
  18. Fraunhofer, W. (2006)., United States Patent., 2(12).
  19. Fraunhofer, W., Krause, H., De, G., Koenigsdorfer, A., De, I., Winter, G., De, P. & Gottschalk, S. (2012)., (12) United States Patent (10) Patent No., : 2(12).
  20. Gielen, B., Jordens, J., Thomassen, L. C., Braeken, L., & Van Gerven, T. (2017)., Agglomeration control during ultrasonic crystallization of an active pharmaceutical ingredient., Crystals, 7(2), 40.
  21. Govardhan, C. P., Us, M. A., Yang, M. X., & Margolin, A. L. (2016)., (12) United States Patent (10) Patent No., no 2(12).
  22. Hebel, D., Huber, S., Stanislawski, B., & Hekmat, D. (2013)., Stirred batch crystallization of a therapeutic antibody fragment., Journal of biotechnology, 166(4), 206-211.
  23. Hebel, D., Ürdingen, M., Hekmat, D., & Weuster-Botz, D. (2013)., Development and scale up of high-yield crystallization processes of lysozyme and lipase using additives., Crystal growth & design, 13(6), 2499-2506.
  24. Hekmat, D., Hebel, D. & Weuster‐Botz, D. (2008)., Crystalline proteins as an alternative to standard formulations., Chemical Engineering & Technology: Industrial Chemistry‐Plant Equipment‐Process Engineering ‐Biotechnology, 31(6), 911-916.
  25. Hekmat, D. (2015)., Large-scale crystallization of proteins for purification and formulation., Bioprocess and biosystems engineering, 38, 1209-1231.
  26. Hekmat, D., Huber, M., Lohse, C., Von Den Eichen, N., & Weuster-Botz, D. (2017)., Continuous crystallization of proteins in a stirred classified product removal tank with a tubular reactor in bypass., Crystal Growth & Design, 17(8), 4162-4169.
  27. Henricks, L. M., Schellens, J. H., Huitema, A. D., & Beijnen, J. H. (2015)., The use of combinations of monoclonal antibodies in clinical oncology., Cancer treatment reviews, 41(10), 859-867.
  28. Hildebrandt, C., Joos, L., Saedler, R., & Winter, G. (2015)., The new polyethylene glycol dilemma: polyethylene glycol impurities and their paradox role in mAb crystallization., Journal of Pharmaceutical Sciences, 104(6), 1938-1945.
  29. Hildebrandt, C., Mathaes, R., Saedler, R., & Winter, G. (2016)., Origin of aggregate formation in antibody crystal suspensions containing PEG., Journal of Pharmaceutical Sciences, 105(3), 1059-1065.
  30. Jion, A. I., Goh, L. T., & Oh, S. K. (2006)., Crystallization of IgG1 by mapping its liquid–liquid phase separation curves., Biotechnology and bioengineering, 95(5), 911-918.
  31. Kirley, T. L., & Norman, A. B. (2015)., Characterization of a recombinant humanized anti-cocaine monoclonal antibody and its Fab fragment., Human vaccines & immunotherapeutics, 11(2), 458-467.
  32. Krauss, I. R., Merlino, A., Vergara, A., & Sica, F. (2013)., An overview of biological macromolecule crystallization., International journal of molecular sciences, 14(6), 11643-11691.
  33. Kumar, V., Dixit, N., Singh, S. N., & Kalonia, D. S. (2011). SOLUBILITY/EXCIPIENTS-Phase Separation of Proteins by Poly-ethylene Glycols: Implications in Preformulation and Early Stage Formulation Development. American Pharmaceutical Review, 14(7), 26., undefined, undefined
  34. Kuznetsov, Y. G., Malkin, A. J., & McPherson, A. (2001). The liquid protein phase in crystallization: a case study—intact immunoglobulins. Journal of crystal growth, 232(1-4), 30-39. https://doi.org/10.1016/S0022-0248(01)01058-2, undefined, undefined
  35. Larson, S. B., Kuznetsov, Y. G., Day, J., Zhou, J., Glaser, S., Braslawsky, G., & McPherson, A. (2005). Combined use of AFM and X-ray diffraction to analyze crystals of an engineered, domain-deleted antibody. Acta Crystallographica Section D: Biological Crystallography, 61(4), 416-422., undefined, undefined
  36. Vivarès, D., Kaler, E. W., & Lenhoff, A. M. (2005). Quantitative imaging by confocal scanning fluorescence microscopy of protein crystallization via liquid–liquid phase separation. Acta Crystallographica Section D: Biological Crystallography, 61(6), 819-825., undefined, undefined
  37. Lewus, R. A., Darcy, P. A., Lenhoff, A. M., & Sandler, S. I. (2011). Interactions and phase behavior of a monoclonal antibody. Biotechnology progress, 27(1), 280-289., undefined, undefined
  38. Liu, J., Yin, D. C., Guo, Y. Z., Wang, X. K., Xie, S. X., Lu, Q. Q., & Liu, Y. M. (2011). Selecting temperature for protein crystallization screens using the temperature dependence of the second virial coefficient. PloS one, 6(3), e17950., undefined, undefined
  39. Luft, J. R., Wolfley, J. R., Said, M. I., Nagel, R. M., Lauricella, A. M., Smith, J. L., ... & DeTitta, G. T. (2007). Efficient optimization of crystallization conditions by manipulation of drop volume ratio and temperature. Protein science, 16(4), 715-722., undefined, undefined
  40. Luft, J. R., Newman, J., & Snell, E. H. (2014). Crystallization screening: the influence of history on current practice. Acta Crystallographica Section F, 70(7), 835-853., undefined, undefined
  41. McPherson, A., & Gavira, J. A. (2014). Introduction to protein crystallization. Acta Crystallographica Section F: Structural Biology Communications, 70(1), 2-20., undefined, undefined
  42. Moreno, A. (2017)., Advanced methods of protein crystallization., In Methods in Molecular Biology. https://doi.org/10.1007/978-1-4939-7000-1_3
  43. Neugebauer, P., & Khinast, J. G. (2015)., Continuous crystallization of proteins in a tubular plug-flow crystallizer., Crystal growth & design, 15(3), 1089-1095.
  44. Niegowski, D., Hedrén, M., Nordlund, P., & Eshaghi, S. (2006)., A simple strategy towards membrane protein purification and crystallization., International journal of biological macromolecules, 39(1-3), 83-87.
  45. Oliva, J. A., Wu, W. L., Greene, M. R., Pal, K., & Nagy, Z. K. (2020)., Continuous spherical crystallization of lysozyme in an oscillatory baffled crystallizer using emulsion solvent diffusion in droplets., Crystal Growth & Design, 20(2), 934-947.
  46. Pandit, A., Katkar, V., Ranade, V., & Bhambure, R. (2018)., Real-time monitoring of biopharmaceutical crystallization: chord length distribution to crystal size distribution for lysozyme, rhu insulin, and vitamin B12., Industrial & Engineering Chemistry Research, 58(18), 7607-7619.
  47. Penkova, A., Chayen, N. E., Saridakis, E., & Nanev, C. (2002)., Nucleation of protein crystals in a wide continuous supersaturation gradient., Acta Crystallographica Section D: Biological Crystallography, 58(10), 1606-1610.
  48. Przybycien, T. M., Pujar, N. S., & Steele, L. M. (2004)., Alternative bioseparation operations: life beyond packed-bed chromatography., Current Opinion in Biotechnology, 15(5), 469-478.
  49. Pu, S., & Hadinoto, K. (2020)., Continuous crystallization as a downstream processing step of pharmaceutical proteins: A review., Chemical Engineering Research and Design, 160, 89-104.
  50. Reichert, P., Prosise, W., Fischmann, T. O., Scapin, G., Narasimhan, C., Spinale, A., ... & Strickland, C. (2019)., Pembrolizumab microgravity crystallization experimentation., NPJ Microgravity, 5(1), 28.
  51. Saridakis, E., & Chayen, N. E. (2000)., Improving protein crystal quality by decoupling nucleation and growth in vapor diffusion., Protein Science, 9(4), 755-757.
  52. Schmidt, S., Havekost, D., Kaiser, K., Kauling, J., & Henzler, H. J. (2005)., Crystallization for the downstream processing of proteins., Engineering in life sciences, 5(3), 273-276.
  53. Shimizu, S., McLaren, W. M., & Matubayasi, N. (2006)., The Hofmeister series and protein-salt interactions., The Journal of chemical physics, 124(23), 234905.
  54. Shire, S. J., Shahrokh, Z., & Liu, J. U. N. (2004)., Challenges in the development of high protein concentration formulations., Journal of pharmaceutical sciences, 93(6), 1390-1402.
  55. Sjuts, H., Schreuder, H., Engel, C. K., Bussemer, T., & Gokarn, Y. (2020)., Matching pH values for antibody stabilization and crystallization suggest rationale for accelerated development of biotherapeutic drugs., Drug Development Research, 81(3), 329-337. Smatanová, I. K. (2002). Crystallization of biological macromolecules. 9(1), 1–2.
  56. Smejkal, B., Agrawal, N. J., Helk, B., Schulz, H., Giffard, M., Mechelke, M., ... & Hekmat, D. (2013). Fast and scalable purification of a therapeutic full‐length antibody based on process crystallization. Biotechnology and Bioengineering, 110(9), 2452-2461., undefined, undefined
  57. Snyder, D. A., Chen, Y., Denissova, N. G., Acton, T., Aramini, J. M., Ciano, M., ... & Montelione, G. T. (2005). Comparisons of NMR spectral quality and success in crystallization demonstrate that NMR and X-ray crystallography are complementary methods for small protein structure determination. Journal of the American Chemical Society, 127(47), 16505-16511., undefined, undefined
  58. Sommerfeld, S., & Strube, J. (2005). Challenges in biotechnology production—generic processes and process optimization for monoclonal antibodies. Chemical Engineering and Processing: Process Intensification, 44(10), 1123-1137., undefined, undefined
  59. Sun, M., Tang, W., Du, S., Zhang, Y., Fu, X., & Gong, J. (2018). Understanding the roles of oiling-out on crystallization of β-alanine: unusual behavior in metastable zone width and surface nucleation during growth stage. Crystal Growth & Design, 18(11), 6885-6890., undefined, undefined
  60. Fang, L., Liu, J., Ju, S., Zheng, F., Dong, W., & Shen, M. (2010). Experimental and theoretical evidence of enhanced ferromagnetism in sonochemical synthesized BiFeO 3 nanoparticles. Applied Physics Letters, 97(24), 242501., undefined, undefined
  61. Tanaka, S., Ataka, M., Onuma, K., & Kubota, T. (2003). Rationalization of membrane protein crystallization with polyethylene glycol using a simple depletion model. Biophysical journal, 84(5), 3299-3306., undefined, undefined
  62. Trilisky, E., Gillespie, R., Osslund, T. D., & Vunnum, S. (2011). Crystallization and liquid‐liquid phase separation of monoclonal antibodies and fc‐fusion proteins: Screening results. Biotechnology progress, 27(4), 1054-1067., undefined, undefined
  63. Wang, X. K., Yin, D. C., Zhang, C. Y., Lu, Q. Q., Guo, Y. Z., & Guo, W. H. (2010). Effect of temperature programmes on protein crystallisation. Crystal Research and Technology, 45(5), 479-489., undefined, undefined
  64. Wilkins, J. A., Francisco, S., Lobo, B., & Data, R. U. S. A. (2011). (12) Patent Application Publication (10) Pub. No.: US 2011/0020322 A1. 1(19)., undefined, undefined
  65. Yamada, T., Yamamoto, K., Ishihara, T., & Ohta, S. (2017). Purification of monoclonal antibodies entirely in flow-through mode. Journal of Chromatography B, 1061, 110-116., undefined, undefined
  66. Zang, Y. (2013). Development of a crystallization step for monoclonal antibody purification: screening, optimization and aggregation control (Doctoral dissertation, Karlsruhe, Karlsruher Institut für Technologie (KIT), Diss., 2013)., undefined, undefined
  67. Zang, Y., Kammerer, B., Eisenkolb, M., Lohr, K., & Kiefer, H. (2011). Towards protein crystallization as a process step in downstream processing of therapeutic antibodies: screening and optimization at microbatch scale. PLoS One, 6(9), e25282., undefined, undefined
  68. Zang, Y., Kammerer, B., Eisenkolb, M., Lohr, K., & Kiefer, H. (2011b). Towards Protein Crystallization as a Process Step in Downstream Processing of Therapeutic Antibodies : Screening and Optimization at Microbatch Scale Towards Protein Crystallization as a Process Step in Downstream Processing of Therapeutic Antibodies : Sc. April 2016. https://doi.org/10.1371/journal.pone.0025282, undefined, undefined