Journal of Flow Chemistry

, Volume 5, Issue 3, pp 151–154 | Cite as

Protein and Antibody Functionalization Using Continuous Flow Microreactor Technology

  • Meaghan M. Sebeika
  • Nicholas G. Gedeon
  • Sara Sadler
  • Nicholas L. Kern
  • Devan J. Wilkins
  • David E. Bell
  • Graham B. Jones


Interest in the field of antibody-drug conjugates (ADCs) has grown exponentially over the past decade. As the product pipeline grows, there is increasing need for robust chemistries which allow selective and efficient functionalization of the antibody cores for introduction of appropriate linkers and spacer groups. Under conventional bioconjugation conditions, product heterogeneity often results, and the drug-to-antibody ratios (DAR) are inconsistent. Based on our experience in protein derivatization, we have investigated the potential for continuous-flow microreactor technology to expedite and facilitate such processes. We demonstrate its potential using reagent proteins and the chimeric monoclonal antibody infliximab (Remicade™).


antibody antibody-drug conjugation BSA-FITC continuous flow drug-to-antibody ratio infliximab 

Supplementary material

41981_2015_5030151_MOESM1_ESM.pdf (447 kb)
Supplementary material, approximately 457 KB.


  1. 1.(a)
    Ornes, S. Proc. Natl. Acad. Sci. U. S. A 2013, 110, 13695–13695CrossRefGoogle Scholar
  2. (b).
    Li, G. N.; Wang, S. P.; Xue, X.; Qu, X. J.; Liu, H. P. Drug Discoveries Ther. 2013, 7, 178–184Google Scholar
  3. (c).
    Lambert, J. M. Br. J. Clin. Pharmacol. 2013, 76, 248–262CrossRefGoogle Scholar
  4. (d).
    Kitson, S. L.; Quinn, D. J.; Moody, T. S.; Speed, D.; Watters, W.; Rozzell, D. Chim. Oggi-Chem. Today 2013, 31, 29–35Google Scholar
  5. (e).
    Graziani, E. I.; Tumey, L. N. Recent Advances in Antibody-Drug Conjugates. In Biotherapeutics: Recent Developments Using Chemical and Molecular Biology, Jones, L. H.; McKnight, A. J., Eds.; Royal Soc Chemistry: Cambridge, 2013; pp. 145–175CrossRefGoogle Scholar
  6. (f).
    Goswami, S.; Wang, W.; Arakawa, T.; Ohtake, S. Antibodies 2013, 2, 452–500CrossRefGoogle Scholar
  7. (g).
    Chari, R. V J.; Miller, M. L.; Widdison, W. C. Angew. Chem., Int. Ed. 2014, 53, 3796–3827CrossRefGoogle Scholar
  8. (h).
    Dosio, F.; Stella, B.; Cerioni, S.; Gastaldi, D.; Arpicco, S. Recent Pat. Anti-Cancer Drug Discovery 2014, 9, 35–65.CrossRefGoogle Scholar
  9. 2.
    Vaklavas, C.; Forero-Torres, A. Ther. Adv. Hematol. 2012, 3, 209–225.CrossRefGoogle Scholar
  10. 3.
    Verma, S.; Miles, D.; Gianni, L.; Krop, I. E.; Welslau, M.; Baselga, J.; Pegram, M.; Oh, D. Y.; Dieras, V.; Guardino, E.; Fang, L.; Lu, M. W.; Olsen, S.; Blackwell, K.; Grp, E. S. N. Engl J. Med. 2012, 367, 1783–1791.CrossRefGoogle Scholar
  11. 4.(a)
    Wright, L.; Baughman, S.; Wake, A. Bioanalysis 2013, 5, 1467–1469CrossRefGoogle Scholar
  12. (b).
    Li, Y.; Medley, C. D.; Zhang, K.; Wigman, L.; Chetwyn, N. J. Pharm. Biomed. Anal. 2014, 92, 114–118.CrossRefGoogle Scholar
  13. 5.(a)
    Alley, S. C.; Anderson, K. E. Curr. Opin. Chem. Biol. 2013, 17, 406–411CrossRefGoogle Scholar
  14. (b).
    Wakankar, A.; Chen, Y.; Gokarn, Y.; Jacobson, F. S. mAbs 2011, 3, 161–172CrossRefGoogle Scholar
  15. (c).
    (c)Xiao, Y. Q.; Halford, A.; Hayes, R. N. Biopharm. Int. 2012, 25, 60–63.Google Scholar
  16. 6.(a)
    Vaddula, B. R.; Gonzalez, M. A. Chim. Oggi-Chem. Today 2013, 31, 16–21Google Scholar
  17. (b).
    Makgwane, P. R.; Ray, S. S. J. Nanosci. Nanotechnol. 2014, 14, 1338–1363CrossRefGoogle Scholar
  18. (c).
    Kulkarni, A. A. Beilstein J. Org. Chem. 2014, 10, 405–424CrossRefGoogle Scholar
  19. (d).
    Ramesh, S.; Cherkupally, P.; de la Torre, B. G.; Govender, T.; Kruger, H. G.; Albericio, F. Amino Acids 2014, 46, 2091–2104CrossRefGoogle Scholar
  20. (e).
    Pastre, J. C.; Browne, D. L.; Ley, S. V. Chem. Soc. Rev. 2013, 42, 8849–8869.CrossRefGoogle Scholar
  21. 7.
    Vaidyanathan, G.; Zalutsky, M. R. Nat. Protoc. 2006, 1, 1655–1661.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó 2015

Authors and Affiliations

  • Meaghan M. Sebeika
    • 1
  • Nicholas G. Gedeon
    • 1
  • Sara Sadler
    • 1
  • Nicholas L. Kern
    • 1
  • Devan J. Wilkins
    • 1
  • David E. Bell
    • 1
  • Graham B. Jones
    • 1
  1. 1.Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry and Chemical BiologyNortheastern UniversityBostonUSA

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