Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 256135, 16 pages
http://dx.doi.org/10.1155/2014/256135
Research Article

Manufacturing Economics of Plant-Made Biologics: Case Studies in Therapeutic and Industrial Enzymes

1Intrucept Biomedicine LLC, 2695 13th Street, Sacramento, CA 95818, USA
2Department of Chemical Engineering and Materials Science, University of California, 1 Shields Avenue, Davis, CA 95616, USA

Received 7 December 2013; Accepted 28 February 2014; Published 29 May 2014

Academic Editor: Qiang “Shawn” Chen

Copyright © 2014 Daniel Tusé et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. R. Thomas, C. A. Penney, A. Majumder, and A. M. Walmsley, “Evolution of plant-made pharmaceuticals,” International Journal of Molecular Sciences, vol. 12, no. 5, pp. 3220–3236, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. G. P. Pogue, F. Vojdani, K. E. Palmer et al., “Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems,” Plant Biotechnology Journal, vol. 8, no. 5, pp. 638–654, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. T. V. Komarova, S. Baschieri, M. Donini, C. Marusic, E. Benvenuto, and Y. L. Dorokhov, “Transient expression systems for plant-derived biopharmaceuticals,” Expert Review of Vaccines, vol. 9, no. 8, pp. 859–876, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. V. Klimyuk, S. Herz, J. Butler, and H. Haydon, “Production of recombinant antigens and antibodies in Nicotiana benthamiana Using “Magnifection” technology: GMP-compliant facilities for small- and large-scale manufacturing,” Current Topics in Microbiology and Immunology, vol. 375, pp. 127–154, 2014. View at Google Scholar
  5. Y. Y. Gleba, D. Tusé, and A. Giritch, “Plant viral vectors for delivery by agrobacterium,” Current Topics in Microbiology and Immunology, vol. 375, pp. 155–192, 2014. View at Google Scholar
  6. A. Giritch, S. Marillonnet, C. Engler et al., “Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectros,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 40, pp. 14701–14706, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Werner, O. Breus, Y. Symonenko, S. Marillonnet, and Y. Gleba, “High-level recombinant protein expression in transgenic plants by using a double-inducible viral vector,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 34, pp. 14061–14066, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. H. M. Davies, “Commercialization of whole-plant systems for biomanufacturing of protein products: evolution and prospects,” Plant Biotechnology Journal, vol. 8, no. 8, pp. 845–861, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Elbehri, “Biopharming and the food system: Examining the potential benefits and risks,” AgBioForum, vol. 8, no. 1, pp. 18–25, 2005. View at Google Scholar · View at Scopus
  10. S. S. Farid, “Process economics of industrial monoclonal antibody manufacture,” Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, vol. 848, no. 1, pp. 8–18, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. E. E. Hood, S. L. Woodard, and M. E. Horn, “Monoclonal antibody manufacturing in transgenic plants: myths and realities,” Current Opinion in Biotechnology, vol. 13, no. 6, pp. 630–635, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Kaiser, “Is the drought over for pharming,” Science, vol. 320, no. 5875, pp. 473–475, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. J. K.-C. Ma, R. Chikwamba, P. Sparrow, R. Fischer, R. Mahoney, and R. M. Twyman, “Plant-derived pharmaceuticals: the road forward,” Trends in Plant Science, vol. 10, no. 12, pp. 580–585, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. R. L. Evangelista, A. R. Kusnadi, J. A. Howard, and Z. L. Nikolov, “Process and economic evaluation of the extraction and purification of recombinant β-glucuronidase from transgenic corn,” Biotechnology Progress, vol. 14, no. 4, pp. 607–614, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Nandi, D. Yalda, S. Lu et al., “Process development and economic evaluation of recombinant human lactoferrin expressed in rice grain,” Transgenic Research, vol. 14, no. 3, pp. 237–249, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. D. Klein-Marcuschamer, P. Oleskowicz-Popiel, B. A. Simmons, and H. W. Blanch, “The challenge of enzyme cost in the production of lignocellulosic biofuels,” Biotechnology and Bioengineering, vol. 109, no. 4, pp. 1083–1087, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Ernst, O. A. Garro, S. Winkler et al., “Process simulation for recombinant protein production: cost estimation and sensitivity analysis for heparinase I expressed in Escherichia coli,” Biotechnology and Bioengineering, vol. 53, no. 6, pp. 575–582, 1997. View at Google Scholar
  18. E. Zapalac, K. McDonald, E. Heinzle, A. P. Biwer, and C. L. Cooney, “Alpha-1-antitrypsin from transgenic plant cell suspension cultures,” in Development of SustaInable Bioprocesses, pp. 261–270, 2007. View at Google Scholar
  19. G. P. Pogue, J. A. Lindbo, S. J. Garger, and W. P. Fitzmaurice, “Making an ally from an enemy: plant virology and the new agriculture,” Annual Review of Phytopathology, vol. 40, pp. 45–74, 2002. View at Publisher · View at Google Scholar · View at Scopus
  20. B. De Muynck, C. Navarre, and M. Boutry, “Production of antibodies in plants: status after twenty years,” Plant Biotechnology Journal, vol. 8, no. 5, pp. 529–563, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. S. J. Streatfield and J. A. Howard, “Plant-based vaccines,” International Journal for Parasitology, vol. 33, no. 5-6, pp. 479–493, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. A. A. McCormick, S. Reddy, S. J. Reinl et al., “Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: safety and immunogenicity in a phase I clinical study,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 29, pp. 10131–10136, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Bendandi, S. Marillonnet, R. Kandzia et al., “Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma,” Annals of Oncology, vol. 21, no. 12, pp. 2420–2427, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. D. Tusé, “Safety of plant-made pharmaceuticals: product development and regulatory considerations based on case studies of two autologous human cancer vaccines,” Human Vaccines, vol. 7, no. 3, pp. 322–330, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. O. Lockridge, C. F. Bartels, and T. A. Vaughan, “Complete amino acid sequence of human serum cholinesterase,” Journal of Biological Chemistry, vol. 262, no. 2, pp. 549–557, 1987. View at Google Scholar · View at Scopus
  26. D. Ostergaard, J. Viby-Mogensen, H. K. Hanel, and L. T. Skovgaard, “Half-life of plasma cholinesterase,” Acta Anaesthesiologica Scandinavica, vol. 32, no. 3, pp. 266–269, 1988. View at Google Scholar · View at Scopus
  27. A. J. Magill, “DARPA Proposers' Day: Butyrylcholinesterase Expression in Plants,” 2012.
  28. O. Lockridge, L. M. Schopfer, G. Winger, and J. H. Woods, “Large scale purification of butyrylcholinesterase from human plasma suitable for injection into monkeys, a potential new therapeutic for protection against cocaine and nerve agent toxicity,” Journal of Medical, Chemical, Biological, and Radiological Defense, vol. 3, Article ID nihms5095, 2005. View at Google Scholar
  29. B. C. Geyer, L. Kannan, P.-E. Garnaud et al., “Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 47, pp. 20251–20256, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. P. Masson, “Expression and refolding of functional human butyrylcholinesterase from E. Coli,” in Multidisciplinary Approaches To Cholinesterase Functions, A. Shafferman and B. Velan, Eds., pp. 49–52, Plenum, New York, NY, USA, 1992. View at Google Scholar
  31. C. V. Altamirano and O. Lockridge, “Association of tetramers of human butyrylcholinesterase is mediated by conserved aromatic residues of the carboxy terminus,” Chemico-Biological Interactions, vol. 119-120, pp. 53–60, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. C. B. Millard, “Design and expression of organophosphorus acid anhydride hydrolase activity in human butyrylcholinesterase,” Biochemistry, vol. 34, no. 49, pp. 15925–15933, 1995. View at Google Scholar · View at Scopus
  33. Y.-J. Huang, Y. Huang, H. Baldassarre et al., “Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 34, pp. 13603–13608, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. R. L. Hayward, Production of Recombinant Human Butyrylcholinesterase in Nicotiana benthamiana [Master of Science], The University of Guelph, 2012.
  35. T. Mor, L. Kannan, and K. E. Larrimore, “Compositions and methods for the production and use of human cholinesterases,” Patent Application WO 2013040572 A2, 2012. View at Google Scholar
  36. J. D. Schneider, A. Castilho, L. Neumann et al., “Expression of human butyrylcholinesterase with an engineered glycosylation profile resembling the plasma-derived orthologue,” Biotechnology Journal, 2013. View at Publisher · View at Google Scholar
  37. DARPA, “DARPA Broad Agency Announcement: Butyrylcholinesterase Expression in Plants,” 2012.
  38. S. Marillonnet, C. Thoeringer, R. Kandzia, V. Klimyuk, and Y. Gleba, “Systemic Agrobacterium tumefaciens-mediated transfection of viral replicons for efficient transient expression in plants,” Nature Biotechnology, vol. 23, no. 6, pp. 718–723, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Y. Gleba and A. Giritch, “Vaccines, antibodies, and pharmaceutical proteins,” in Plant Biotechnology and Agriculture: Prospects For the 21st Century, A. Altman and P. M. Hasegawa, Eds., pp. 465–479, Elsevier, 2012. View at Google Scholar
  40. R. Burkle, C. Chew, C. Li et al., “Large-scale biomanufacturing facility for production of an antidote against sarin and other nerve agents,” in Proceedings of the AICHE Annual Meeting, 2013.
  41. M. B. Sainz and J. Dale, “Towards cellulosic ethanol from sugarcane bagasse,” Proceedings of the Australian Society of Sugar Cane Technology, vol. 31, pp. 18–23, 2009. View at Google Scholar
  42. M. B. Sainz, “Commercial cellulosic ethanol: The role of plant-expressed enzymes,” In Vitro Cellular and Developmental Biology: Plant, vol. 45, no. 3, pp. 314–329, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Hahn, A. Giritch, and Y. Gleba, “Production, storage and use of cell wall-degrading enzymes,” Patent Application EP2584042A1, 2013. View at Google Scholar
  44. R. Mundell, O. Chambers, J. P. O'Daniel, and H. M. Davies, “Evaluation of float trays with high cell numbers on stand counts and yields in a close-grown tobacco production system,” Tobacco Science, vol. 49, pp. 4–7, 2012. View at Google Scholar
  45. K. Seebold, 2013-2014 Kentucky and Tennessee Tobacco Production Guide, 2013.
  46. S. J. Sheen, “Biomass and chemical composition of tobacco plants under high density growth,” Beiträge Zur Tabakforschung International, vol. 12, no. 1, pp. 35–42, 1983. View at Google Scholar
  47. C. S. Chang, W. P. Hurng, H. Y. Hu, L. H. Chen, and D. K. Wu, “The yield of biomass and leaf protein of tobacco plants grown at high density with multiple harvest. I. Experiments on plant density,” Bulletin of Taiwan Tobacco Research Institute, Taiwan Tobacco and Wine Monopoly Bureau, no. 32, pp. 1–7, 1990. View at Google Scholar
  48. G. L. Scott and J. F. Warren, “Tobacco production system,” Patent Application WO2013028539 A2, 2013. View at Google Scholar
  49. D. Humbird, R. Davis, L. Tao et al., “Process design and economics for biochemical conversion of lignocellulosic biomass to ethanol: dilute-acid pretreatment and enzymatic hydrolysis of corn Stover,” Tech. Rep. NREL/TP-5100-47764, 2011, http://www.nrel.gov/biomass/pdfs/47764.pdf. View at Google Scholar
  50. A. Castilho, P. Gattinger, J. Grass et al., “N-Glycosylation engineering of plants for the biosynthesis of glycoproteins with bisected and branched complex N-glycans,” Glycobiology, vol. 21, no. 6, pp. 813–823, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. L. Zeitlin, J. Pettitt, C. Scully et al., “Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 51, pp. 20690–20694, 2011. View at Publisher · View at Google Scholar · View at Scopus