Disclosure of potential conflicts of interest
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REFERENCES
Alvarez, M., Tremintin, G., Wang, J., Eng, M., Kao, Y.-H., Jeong, J., .
. . Borisov, O. V. (2011). On-line characterization of monoclonal
antibody variants by liquid chromatography–mass spectrometry operating
in a two-dimensional format. Analytical Biochemistry, 419 (1),
17-25. doi:https://doi.org/10.1016/j.ab.2011.07.033
Amzel, L. M., & Poljak, R. J. (1979). Three-Dimensional Structure of
Immunoglobulins. Annual Review of Biochemistry, 48 (1), 961-997.
doi:10.1146/annurev.bi.48.070179.004525
Andya, J. D., Hsu, C. C., & Shire, S. J. (2015). Mechanisms of
aggregate formation and carbohydrate excipient stabilization of
lyophilized humanized monoclonal antibody formulations. AAPS
PharmSci, 5 (2), 21. doi:10.1208/ps050210
Bessa, J., Boeckle, S., Beck, H., Buckel, T., Schlicht, S., Ebeling, M.,
. . . Iglesias, A. (2015). The Immunogenicity of Antibody Aggregates in
a Novel Transgenic Mouse Model. Pharmaceutical Research, 32 (7),
2344-2359. doi:10.1007/s11095-015-1627-0
Boychyn, M., Yim, S. S. S., Bulmer, M., More, J., Bracewell, D. G., &
Hoare, M. (2004). Performance prediction of industrial centrifuges using
scale-down models. Bioprocess and Biosystems Engineering, 26 (6),
385-391. doi:10.1007/s00449-003-0328-y
Brinkmann, U., & Kontermann, R. E. (2017). The making of bispecific
antibodies. mAbs, 9 (2), 182-212.
doi:10.1080/19420862.2016.1268307
Bulleid, N. J., & Ellgaard, L. (2011). Multiple ways to make
disulfides. Trends in Biochemical Sciences, 36 (9), 485-492.
doi:https://doi.org/10.1016/j.tibs.2011.05.004
Cappel, R. E., & Gilbert, H. F. (1988). Thiol/disulfide exchange
between 3-hydroxy-3-methylglutaryl-CoA reductase and glutathione. A
thermodynamically facile dithiol oxidation. Journal of Biological
Chemistry, 263 (25), 12204-12212.
Caravella, J., & Lugovskoy, A. (2010). Design of next-generation
protein therapeutics. Current Opinion in Chemical Biology, 14 (4),
520-528. doi:https://doi.org/10.1016/j.cbpa.2010.06.175
Carter, P. (2001). Bispecific human IgG by design. Journal of
Immunological Methods, 248 (1), 7-15.
doi:https://doi.org/10.1016/S0022-1759(00)00339-2
Chakravarthi, S., & Bulleid, N. J. (2004). Glutathione Is Required to
Regulate the Formation of Native Disulfide Bonds within Proteins
Entering the Secretory Pathway. Journal of Biological Chemistry,
279 (38), 39872-39879.
Chemmalil, L., Prabhakar, T., Kuang, J., West, J., Tan, Z.,
Ehamparanathan, V., . . . Li, Z. (2020). Online/at-line measurement,
analysis and control of product titer and critical product quality
attributes (CQAs) during process development. Biotechnol Bioeng .
doi:10.1002/bit.27531
Chen, X., Nguyen, M., Jacobson, F., & Ouyang, J. (2009). Charge-based
analysis of antibodies with engineered cysteines. mAbs, 1 (6),
563-571. doi:10.4161/mabs.1.6.10058
Cheng, Y., Chen, M. T., Patterson, L. C., Yu, X. C., Zhang, Y. T.,
Burgess, B. L., & Chen, Y. (2017). Domain-specific free thiol variant
characterization of an IgG1 by reversed-phase high-performance liquid
chromatography mass spectrometry. Analytical Biochemistry, 519 ,
8-14. doi:https://doi.org/10.1016/j.ab.2016.12.003
Cherkaoui, S., Bettinger, T., Hauwel, M., Navetat, S., Allémann, E., &
Schneider, M. (2010). Tracking of antibody reduction fragments by
capillary gel electrophoresis during the coupling to microparticles
surface. Journal of Pharmaceutical and Biomedical Analysis,
53 (2), 172-178. doi:https://doi.org/10.1016/j.jpba.2010.01.039
Chung, W. K., Russell, B., Yang, Y., Handlogten, M., Hudak, S., Cao, M.,
. . . Zhu, M. (2017). Effects of antibody disulfide bond reduction on
purification process performance and final drug substance stability.Biotechnology and Bioengineering, 114 (6), 1264-1274.
doi:10.1002/bit.26265
Correia, I. (2010). Stability of IgG isotypes in serum. mAbs,
2 (3), 221-232. doi:10.4161/mabs.2.3.11788
Cromwell, M. E. M., Hilario, E., & Jacobson, F. (2006). Protein
aggregation and bioprocessing. The AAPS Journal, 8 (3), E572-E579.
doi:10.1208/aapsj080366
Cui, Y., Cui, P., Chen, B., Li, S., & Guan, H. (2017). Monoclonal
antibodies: formulations of marketed products and recent advances in
novel delivery system. Drug Development and Industrial Pharmacy,
43 (4), 519-530. doi:10.1080/03639045.2017.1278768
Dada, O. O., Rao, R., Jones, N., Jaya, N., & Salas-Solano, O. (2017).
Comparison of SEC and CE-SDS methods for monitoring hinge fragmentation
in IgG1 monoclonal antibodies. Journal of Pharmaceutical and
Biomedical Analysis, 145 , 91-97.
doi:https://doi.org/10.1016/j.jpba.2017.06.006
Davagnino, J., Wong, C., Shelton, L., & Mankarious, S. (1995). Acid
hydrolysis of monoclonal antibodies. Journal of Immunological
Methods, 185 (2), 177-180.
doi:https://doi.org/10.1016/0022-1759(95)00110-V
Delmar, J. A., Wang, J., Choi, S. W., Martins, J. A., & Mikhail, J. P.
(2019). Machine Learning Enables Accurate Prediction of Asparagine
Deamidation Probability and Rate. Molecular Therapy - Methods &
Clinical Development, 15 , 264-274.
doi:https://doi.org/10.1016/j.omtm.2019.09.008
Dowd, S. E., Halonen, M. J., & Maier, R. M. (2009). Chapter 12 -
Immunological Methods. In R. M. Maier, I. L. Pepper, & C. P. Gerba
(Eds.), Environmental Microbiology (Second Edition) (pp.
225-241). San Diego: Academic Press.
Du, C., Huang, Y., Borwankar, A., Tan, Z., Cura, A., Yee, J. C., . . .
Li, Z. J. (2018). Using hydrogen peroxide to prevent antibody disulfide
bond reduction during manufacturing process. mAbs, 10 (3),
500-510. doi:10.1080/19420862.2018.1424609
Ecker, D. M., Jones, S. D., & Levine, H. L. (2015). The therapeutic
monoclonal antibody market. mAbs, 7 (1), 9-14.
doi:10.4161/19420862.2015.989042
Edelman, G. M., & Gall, W. E. (1969). The Antibody Problem.Annual Review of Biochemistry, 38 (1), 415-466.
doi:10.1146/annurev.bi.38.070169.002215
Edelman, G. M., & Gally, J. A. (1962). The nature of Bence-Jones
proteins. Chemical similarities to polypetide chains of myeloma
globulins and normal gamma-globulins. The Journal of experimental
medicine, 116 (2), 207-227. doi:10.1084/jem.116.2.207
Elgundi, Z., Reslan, M., Cruz, E., Sifniotis, V., & Kayser, V. (2017).
The state-of-play and future of antibody therapeutics. Advanced
Drug Delivery Reviews, 122 , 2-19.
doi:https://doi.org/10.1016/j.addr.2016.11.004
Fass, D. (2012). Disulfide Bonding in Protein Biophysics. Annual
Review of Biophysics, 41 (1), 63-79.
doi:10.1146/annurev-biophys-050511-102321
García, M. C. (2005). The effect of the mobile phase additives on
sensitivity in the analysis of peptides and proteins by high-performance
liquid chromatography–electrospray mass spectrometry. Journal of
Chromatography B, 825 (2), 111-123.
doi:https://doi.org/10.1016/j.jchromb.2005.03.041
Gilbert, H. F. (1995). [2] Thiol/disulfide exchange equilibria and
disulfidebond stability. In Methods in Enzymology (Vol. 251, pp.
8-28): Academic Press.
Großhans, S., Rüdt, M., Sanden, A., Brestrich, N., Morgenstern, J.,
Heissler, S., & Hubbuch, J. (2018). In-line Fourier-transform infrared
spectroscopy as a versatile process analytical technology for
preparative protein chromatography. Journal of Chromatography A,
1547 , 37-44. doi:https://doi.org/10.1016/j.chroma.2018.03.005
Handlogten, M. W., Wang, J., & Ahuja, S. (2020). Online control of cell
culture redox potential prevents antibody interchain disulfide bond
reduction. Biotechnology and Bioengineering, 117 (5), 1329-1336.
doi:10.1002/bit.27281
Handlogten, M. W., Zhu, M., & Ahuja, S. (2017). Glutathione and
thioredoxin systems contribute to recombinant monoclonal antibody
interchain disulfide bond reduction during bioprocessing.Biotechnology and Bioengineering, 114 (7), 1469-1477.
doi:10.1002/bit.26278
Harris, R. J. (2005). Heterogeneity of recombinant antibodies: linking
structure to function. Dev Biol (Basel), 122 , 117-127. Retrieved
from https://www.ncbi.nlm.nih.gov/pubmed/16375256
Holmgren, A. (1979). Thioredoxin catalyzes the reduction of insulin
disulfides by dithiothreitol and dihydrolipoamide. Journal of
Biological Chemistry, 254 (19), 9627-9632.
Holmgren, A., & Lu, J. (2010). Thioredoxin and thioredoxin reductase:
Current research with special reference to human disease.Biochemical and Biophysical Research Communications, 396 (1),
120-124. doi:https://doi.org/10.1016/j.bbrc.2010.03.083
Hughes, B. (2010). 2009 FDA drug approvals. Nature Reviews Drug
Discovery, 9 (2), 89-92. doi:10.1038/nrd3101
Huh, J. H., White, A. J., Brych, S. R., Franey, H., & Matsumura, M.
(2013). The identification of free cysteine residues within antibodies
and a potential role for free cysteine residues in covalent aggregation
because of agitation stress. J Pharm Sci, 102 (6), 1701-1711.
doi:10.1002/jps.23505
Hutterer, K. M., Hong, R. W., Lull, J., Zhao, X., Wang, T., Pei, R., . .
. Flynn, G. C. (2013). Monoclonal antibody disulfide reduction during
manufacturing. mAbs, 5 (4), 608-613. doi:10.4161/mabs.24725
Imai, K., & Takaoka, A. (2006). Comparing antibody and small-molecule
therapies for cancer. Nature Reviews Cancer, 6 (9), 714-727.
doi:10.1038/nrc1913
Jenzsch, M., Bell, C., Buziol, S., Kepert, F., Wegele, H., & Hakemeyer,
C. (2018). Trends in Process Analytical Technology: Present State in
Bioprocessing. In B. Kiss, U. Gottschalk, & M. Pohlscheidt (Eds.),New Bioprocessing Strategies: Development and Manufacturing of
Recombinant Antibodies and Proteins (pp. 211-252). Cham: Springer
International Publishing.
Jia, L., & Sun, Y. (2017). Protein asparagine deamidation prediction
based on structures with machine learning methods. PLOS ONE,
12 (7), e0181347. doi:10.1371/journal.pone.0181347
Johnson, S., Burke, S., Huang, L., Gorlatov, S., Li, H., Wang, W., . . .
Bonvini, E. (2010). Effector Cell Recruitment with Novel Fv-based
Dual-affinity Re-targeting Protein Leads to Potent Tumor Cytolysis and
in Vivo B-cell Depletion. Journal of Molecular Biology, 399 (3),
436-449. doi:https://doi.org/10.1016/j.jmb.2010.04.001
Kao, Y.-H., Hewitt, D. P., Trexler-Schmidt, M., & Laird, M. W. (2010).
Mechanism of antibody reduction in cell culture production processes.Biotechnology and Bioengineering, 107 (4), 622-632.
doi:10.1002/bit.22848
Kelley, B., Blank, G., & Lee, A. (2009). Downstream Processing of
Monoclonal Antibodies: Current Practices and Future Opportunities. 1-23.
doi:https://doi.org/10.1002/9780470444894.ch1
Kikuchi, H., Goto, Y., & Hamaguchi, K. (1986). Reduction of the buried
intrachain disulfide bond of the constant fragment of the immunoglobulin
light chain: global unfolding under physiological conditions.Biochemistry, 25 (8), 2009-2013. doi:10.1021/bi00356a026
King, A. C., Woods, M., Liu, W., Lu, Z., Gill, D., & Krebs, M. R. H.
(2011). High-throughput measurement, correlation analysis, and
machine-learning predictions for pH and thermal stabilities of
Pfizer-generated antibodies. Protein Science, 20 (9), 1546-1557.
doi:10.1002/pro.680
Klein, C., Sustmann, C., Thomas, M., Stubenrauch, K., Croasdale, R.,
Schanzer, J., . . . Schaefer, W. (2012). Progress in overcoming the
chain association issue in bispecific heterodimeric IgG antibodies.mAbs, 4 (6), 653-663. doi:10.4161/mabs.21379
Kontermann, R. E., & Brinkmann, U. (2015). Bispecific antibodies.Drug Discovery Today, 20 (7), 838-847.
doi:https://doi.org/10.1016/j.drudis.2015.02.008
Koterba, K. L., Borgschulte, T., & Laird, M. W. (2012). Thioredoxin 1
is responsible for antibody disulfide reduction in CHO cell culture.Journal of Biotechnology, 157 (1), 261-267.
doi:https://doi.org/10.1016/j.jbiotec.2011.11.009
Krylov, S. N., & Dovichi, N. J. (2000). Capillary Electrophoresis for
the Analysis of Biopolymers. Analytical Chemistry, 72 (12),
111-128. doi:10.1021/a1000014c
Kuglstatter, A., Stihle, M., Neumann, C., Müller, C., Schaefer, W.,
Klein, C., . . . Early, D. (2017). Structural differences between
glycosylated, disulfide-linked heterodimeric Knob-into-Hole Fc fragment
and its homodimeric Knob–Knob and Hole–Hole side products.Protein Engineering, Design and Selection, 30 (9), 649-656.
doi:10.1093/protein/gzx041
Lacy, E. R., Baker, M., & Brigham-Burke, M. (2008). Free sulfhydryl
measurement as an indicator of antibody stability. Anal Biochem,
382 (1), 66-68. doi:10.1016/j.ab.2008.07.016
Lakbub, J. C., Clark, D. F., Shah, I. S., Zhu, Z., Su, X., Go, E. P., .
. . Desaire, H. (2016). Disulfide bond characterization of endogenous
IgG3 monoclonal antibodies using LC-MS: an investigation of IgG3
disulfide-mediated isoforms. Analytical Methods, 8 (31),
6046-6055. doi:10.1039/C6AY01248E
Lakbub, J. C., Shipman, J. T., & Desaire, H. (2018). Recent mass
spectrometry-based techniques and considerations for disulfide bond
characterization in proteins. Analytical and Bioanalytical
Chemistry, 410 (10), 2467-2484. doi:10.1007/s00216-017-0772-1
Li, W., Prabakaran, P., Chen, W., Zhu, Z., Feng, Y., & Dimitrov, D. S.
(2016). Antibody Aggregation: Insights from Sequence and Structure.Antibodies, 5 (3). doi:10.3390/antib5030019
Li, Y. (2019). A brief introduction of IgG-like bispecific antibody
purification: Methods for removing product-related impurities.Protein Expression and Purification, 155 , 112-119.
doi:https://doi.org/10.1016/j.pep.2018.11.011
Liu, H., Chumsae, C., Gaza-Bulseco, G., Hurkmans, K., & Radziejewski,
C. H. (2010). Ranking the Susceptibility of Disulfide Bonds in Human
IgG1 Antibodies by Reduction, Differential Alkylation, and LC−MS
Analysis. Analytical Chemistry, 82 (12), 5219-5226.
doi:10.1021/ac100575n
Liu, H., Gaza-Bulseco, G., & Chumsae, C. (2009). Analysis of reduced
monoclonal antibodies using size exclusion chromatography coupled with
mass spectrometry. Journal of the American Society for Mass
Spectrometry, 20 (12), 2258-2264. doi:10.1016/j.jasms.2009.08.015
Liu, H., Gaza-Bulseco, G., & Lundell, E. (2008). Assessment of antibody
fragmentation by reversed-phase liquid chromatography and mass
spectrometry. Journal of Chromatography B, 876 (1), 13-23.
doi:https://doi.org/10.1016/j.jchromb.2008.10.015
Liu, H., & May, K. (2012). Disulfide bond structures of IgG molecules.mAbs, 4 (1), 17-23. doi:10.4161/mabs.4.1.18347
Liu, H., Nowak, C., Shao, M., Ponniah, G., & Neill, A. (2016). Impact
of cell culture on recombinant monoclonal antibody product
heterogeneity. Biotechnology Progress, 32 (5), 1103-1112.
doi:10.1002/btpr.2327
Liu, H., Ponniah, G., Zhang, H.-M., Nowak, C., Neill, A.,
Gonzalez-Lopez, N., . . . Andrien, B. (2014). In vitro and in vivo
modifications of recombinant and human IgG antibodies. mAbs,
6 (5), 1145-1154. doi:10.4161/mabs.29883
Liu, H. F., Ma, J., Winter, C., & Bayer, R. (2010). Recovery and
purification process development for monoclonal antibody production.mAbs, 2 (5), 480-499. doi:10.4161/mabs.2.5.12645
Magnusson, C. G. M., Björnstedt, M., & Holmgren, A. (1997). Human IgG
is substrate for the thioredoxin system: Differential cleavage pattern
of interchain disulfide bridges in IgG subclasses. Molecular
Immunology, 34 (10), 709-717.
doi:https://doi.org/10.1016/S0161-5890(97)00092-8
Mamathambika, B. S., & Bardwell, J. C. (2008). Disulfide-Linked Protein
Folding Pathways. Annual Review of Cell and Developmental Biology,
24 (1), 211-235. doi:10.1146/annurev.cellbio.24.110707.175333
Manteca, A., Alonso-Caballero, Á., Fertin, M., Poly, S., De Sancho, D.,
& Perez-Jimenez, R. (2017). The influence of disulfide bonds on the
mechanical stability of proteins is context dependent. Journal of
Biological Chemistry, 292 (32), 13374-13380. Retrieved from
http://www.jbc.org/content/292/32/13374.abstractN2
Mazor, Y., Oganesyan, V., Yang, C., Hansen, A., Wang, J., Liu, H., . . .
Chowdhury, P. S. (2015). Improving target cell specificity using a novel
monovalent bispecific IgG design. mAbs, 7 (2), 377-389.
doi:10.1080/19420862.2015.1007816
Megson, S. D., Wilson, M., & MacGregor, S. A. (2002). Multiphase
Flow Investigation of a Centrifugal Filter Using Computational Fluid
Dynamics and Experiments . https://doi.org/10.1115/PVP2002-1570
Meister, A., & Anderson, M. E. (1983). GLUTATHIONE. Annual Review
of Biochemistry, 52 (1), 711-760.
doi:10.1146/annurev.bi.52.070183.003431
Molina-Miras, A., Sánchez-Mirón, A., García-Camacho, F., &
Molina-Grima, E. (2018). CFD-aided optimization of a laboratory-scale
centrifugation for a shear-sensitive insect cell line. Food and
Bioproducts Processing, 107 , 113-120.
doi:https://doi.org/10.1016/j.fbp.2017.11.005
Moussa, E. M., Panchal, J. P., Moorthy, B. S., Blum, J. S., Joubert, M.
K., Narhi, L. O., & Topp, E. M. (2016). Immunogenicity of Therapeutic
Protein Aggregates. Journal of Pharmaceutical Sciences, 105 (2),
417-430. doi:https://doi.org/10.1016/j.xphs.2015.11.002
Mullard, A. (2011). 2010 FDA drug approvals. Nature Reviews Drug
Discovery, 10 (2), 82-85. doi:10.1038/nrd3370
Mullard, A. (2012). 2011 FDA drug approvals. Nature Reviews Drug
Discovery, 11 (2), 91-94. doi:10.1038/nrd3657
Mullard, A. (2013). 2012 FDA drug approvals. Nature Reviews Drug
Discovery, 12 (2), 87-90. doi:10.1038/nrd3946
Mullard, A. (2014). 2013 FDA drug approvals. Nature Reviews Drug
Discovery, 13 (2), 85-89. doi:10.1038/nrd4239
Mullard, A. (2015). 2014 FDA drug approvals. Nature Reviews Drug
Discovery, 14 (2), 77-81. doi:10.1038/nrd4545
Mullard, A. (2016). 2015 FDA drug approvals. Nature Reviews Drug
Discovery, 15 (2), 73-76. doi:10.1038/nrd.2016.15
Mullard, A. (2017). 2016 FDA drug approvals. Nature Reviews Drug
Discovery, 16 (2), 73-76. doi:10.1038/nrd.2017.14
Mullard, A. (2018). 2017 FDA drug approvals. Nature Reviews Drug
Discovery, 17 (2), 81-85. doi:10.1038/nrd.2018.4
Mullard, A. (2019). 2018 FDA drug approvals. Nature Reviews Drug
Discovery (18), 85-89. doi:10.1038/d41573-019-00014-x
Mullard, A. (2020). 2019 FDA drug approvals. Nature Reviews Drug
Discovery 19 , 79-84. doi:10.1038/d41573-020-00001-7
Mun, M., Khoo, S., Do Minh, A., Dvornicky, J., Trexler-Schmidt, M., Kao,
Y.-H., & Laird, M. W. (2015). Air sparging for prevention of antibody
disulfide bond reduction in harvested CHO cell culture fluid.Biotechnology and Bioengineering, 112 (4), 734-742.
doi:10.1002/bit.25495
Nelson, P. N., Reynolds, G. M., Waldron, E. E., Ward, E., Giannopoulos,
K., & Murray, P. G. (2000). Demystified… Molecular Pathology,
53 (3), 111. doi:10.1136/mp.53.3.111
Nie, S., Wang, Z., Moscoso-Castro, M., D’Souza, P., Lei, C., Xu, J., &
Gu, J. (2020). Biology drives the discovery of bispecific antibodies as
innovative therapeutics. Antibody Therapeutics, 3 (1), 18-62.
doi:10.1093/abt/tbaa003
O’Mara, B., Gao, Z.-H., Kuruganti, M., Mallett, R., Nayar, G., Smith,
L., . . . Fann, J. (2019). Impact of depth filtration on disulfide bond
reduction during downstream processing of monoclonal antibodies from CHO
cell cultures. Biotechnology and Bioengineering, 116 (7),
1669-1683. doi:10.1002/bit.26964
Østergaard, H., Tachibana, C., & Winther, J. R. (2004). Monitoring
disulfide bond formation in the eukaryotic cytosol. Journal of
Cell Biology, 166 (3), 337-345. doi:10.1083/jcb.200402120
Patel, B. A., Gospodarek, A., Larkin, M., Kenrick, S. A., Haverick, M.
A., Tugcu, N., . . . Richardson, D. D. (2018). Multi-angle light
scattering as a process analytical technology measuring real-time
molecular weight for downstream process control. mAbs, 10 (7),
945-950. doi:10.1080/19420862.2018.1505178
Patel, B. A., Pinto, N. D. S., Gospodarek, A., Kilgore, B., Goswami, K.,
Napoli, W. N., . . . Richardson, D. D. (2017). On-Line Ion Exchange
Liquid Chromatography as a Process Analytical Technology for Monoclonal
Antibody Characterization in Continuous Bioprocessing. Analytical
Chemistry, 89 (21), 11357-11365. doi:10.1021/acs.analchem.7b02228
Paul, S., Connor, J., Nesspor, T., Haytko, P., Boakye, K., Chiu, M. L.,
& Jiang, H. (2016). An efficient process of generating bispecific
antibodies via controlled Fab-arm exchange using culture supernatants.Protein Expression and Purification, 121 , 133-140.
doi:https://doi.org/10.1016/j.pep.2016.01.014
Preud’homme, J.-L., Petit, I., Barra, A., Morel, J.-C. L. F., &
Lelièvre, E. (2000). Structural and functional properties of membrane
and secreted IgD. Molecular Immunology, 37 (15), 871-887.
doi:https://doi.org/10.1016/S0161-5890(01)00006-2
Pristatsky, P., Cohen, S. L., Krantz, D., Acevedo, J., Ionescu, R., &
Vlasak, J. (2009). Evidence for Trisulfide Bonds in a Recombinant
Variant of a Human IgG2 Monoclonal Antibody. Analytical Chemistry,
81 (15), 6148-6155. doi:10.1021/ac9006254
Raju, T. N. K. (1999). The Nobel Chronicles. The Lancet,
354 (9183), 1040. doi:https://doi.org/10.1016/S0140-6736(05)76658-7
Rao, P. E., & Kroon, D. J. Orthoclone OKT3. Chemical mechanisms and
functional effects of degradation of a therapeutic monoclonal antibody.
(1078-0467 (Print)).
Ratanji, K. D., Derrick, J. P., Dearman, R. J., & Kimber, I. (2014).
Immunogenicity of therapeutic proteins: Influence of aggregation.Journal of Immunotoxicology, 11 (2), 99-109.
doi:10.3109/1547691X.2013.821564
Read, E. K., Park, J. T., Shah, R. B., Riley, B. S., Brorson, K. A., &
Rathore, A. S. (2010). Process analytical technology (PAT) for
biopharmaceutical products: Part I. concepts and applications.Biotechnology and Bioengineering, 105 (2), 276-284.
doi:10.1002/bit.22528
Read, E. K., Shah, R. B., Riley, B. S., Park, J. T., Brorson, K. A., &
Rathore, A. S. (2010). Process analytical technology (PAT) for
biopharmaceutical products: Part II. Concepts and applications.Biotechnology and Bioengineering, 105 (2), 285-295.
doi:10.1002/bit.22529
Ricker, R. D., & Sandoval, L. A. (1996). Fast, reproducible
size-exclusion chromatography of biological macromolecules.Journal of Chromatography A, 743 (1), 43-50.
doi:https://doi.org/10.1016/0021-9673(96)00283-X
Rose, P. (2008). Biopharmaceutical technology: Cell harvesting —
getting cultural. Filtration & Separation, 45 (8), 29-31.
doi:https://doi.org/10.1016/S0015-1882(08)70297-0
Rosenberg, A. S. (2006). Effects of protein aggregates: An immunologic
perspective. The AAPS Journal, 8 (3), E501-E507.
doi:10.1208/aapsj080359
Rossi, E. A., Goldenberg, D. M., Cardillo, T. M., McBride, W. J.,
Sharkey, R. M., & Chang, C.-H. (2006). Stably tethered multifunctional
structures of defined composition made by the dock and lock method for
use in cancer targeting. Proceedings of the National Academy of
Sciences, 103 (18), 6841. doi:10.1073/pnas.0600982103
Runcie, K., Budman, D. R., John, V., & Seetharamu, N. (2018).
Bi-specific and tri-specific antibodies- the next big thing in solid
tumor therapeutics. Molecular Medicine, 24 (1), 50.
doi:10.1186/s10020-018-0051-4
Sankar, K., Hoi, K. H., Yin, Y., Ramachandran, P., Andersen, N.,
Hilderbrand, A., . . . Zhang, Q. (2018). Prediction of methionine
oxidation risk in monoclonal antibodies using a machine learning method.mAbs, 10 (8), 1281-1290. doi:10.1080/19420862.2018.1518887
Sedykh, S. E., Prinz, V. V., Buneva, V. N., & Nevinsky, G. A. (2018).
Bispecific antibodies: design, therapy, perspectives. Drug design,
development and therapy, 12 , 195-208. doi:10.2147/DDDT.S151282
Shukla, A. A., Hubbard, B., Tressel, T., Guhan, S., & Low, D. (2007).
Downstream processing of monoclonal antibodies—Application of platform
approaches. Journal of Chromatography B, 848 (1), 28-39.
doi:https://doi.org/10.1016/j.jchromb.2006.09.026
Simon, L. L., Pataki, H., Marosi, G., Meemken, F., Hungerbühler, K.,
Baiker, A., . . . Chiu, M.-S. (2015). Assessment of Recent Process
Analytical Technology (PAT) Trends: A Multiauthor Review. Organic
Process Research & Development, 19 (1), 3-62. doi:10.1021/op500261y
Swope, N., Chung, W. K., Cao, M., Motabar, D., Liu, D., Ahuja, S., &
Handlogten, M. (2020). Impact of enzymatic reduction on bivalent
bispecific antibody fragmentation and loss of product purity upon
reoxidation. Biotechnol Bioeng, 117 (4), 1063-1071.
doi:10.1002/bit.27264
Tan, Z., Ehamparanathan, V., Ren, T., Tang, P., Hoffman, L., Kuang, J.,
. . . Liu, S. (2020). On-column disulfide bond formation of monoclonal
antibodies during Protein A chromatography eliminates low molecular
weight species and rescues reduced antibodies. mAbs, 12 (1),
1829333. doi:10.1080/19420862.2020.1829333
Tang, P., Tan, Z., Ehamparanathan, V., Ren, T., Hoffman, L., Du, C., . .
. Liu, S. (2020). Optimization and kinetic modeling of interchain
disulfide bond reoxidation of monoclonal antibodies in bioprocesses.mAbs, 12 (1), 1829336. doi:10.1080/19420862.2020.1829336
Trexler-Schmidt, M., Sargis, S., Chiu, J., Sze-Khoo, S., Mun, M., Kao,
Y.-H., & Laird, M. W. (2010). Identification and prevention of antibody
disulfide bond reduction during cell culture manufacturing.Biotechnology and Bioengineering, 106 (3), 452-461.
doi:10.1002/bit.22699
Trivedi, M. V., Laurence, J. S., & Siahaan, T. J. (2009a). The role of
thiols and disulfides in protein chemical and physical stability.Current protein & peptide science, 10 (6), 614-625. Retrieved
from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319691/
Trivedi, M. V., Laurence, J. S., & Siahaan, T. J. (2009b). The role of
thiols and disulfides on protein stability. Current protein &
peptide science, 10 (6), 614-625. doi:10.2174/138920309789630534
Tu, B. P., Ho-Schleyer, S. C., Travers, K. J., & Weissman, J. S.
(2000). Biochemical Basis of Oxidative Protein Folding in the
Endoplasmic Reticulum. Science, 290 (5496), 1571.
doi:10.1126/science.290.5496.1571
Tustian, A. D., Endicott, C., Adams, B., Mattila, J., & Bak, H. (2016).
Development of purification processes for fully human bispecific
antibodies based upon modification of protein A binding avidity.mAbs, 8 (4), 828-838. doi:10.1080/19420862.2016.1160192
Vaks, L. L.-G., D.; Dror, S.; Shefet-Carasso, L.; Matatov, G.; Nahary,
L.; Shapira, S.; Hakim, R.; Alroy, I.; Benhar, I. (2018). Design
Principles for Bispecific IgGs, Opportunities and Pitfalls of Artificial
Disulfide Bonds. Antibodies 7 (27).
Vázquez-Rey, M., & Lang, D. A. (2011). Aggregates in monoclonal
antibody manufacturing processes. Biotechnology and
Bioengineering, 108 (7), 1494-1508. doi:10.1002/bit.23155
Wagner, E., Colas, O., Chenu, S., Goyon, A., Murisier, A., Cianferani,
S., . . . Beck, A. (2020). Determination of size variants by CE-SDS for
approved therapeutic antibodies: Key implications of subclasses and
light chain specificities. Journal of Pharmaceutical and
Biomedical Analysis, 184 , 113166.
doi:https://doi.org/10.1016/j.jpba.2020.113166
Wang, T., Liu, Y. D., Cai, B., Huang, G., & Flynn, G. C. (2015).
Investigation of antibody disulfide reduction and re-oxidation and
impact to biological activities. Journal of Pharmaceutical and
Biomedical Analysis, 102 , 519-528.
doi:https://doi.org/10.1016/j.jpba.2014.10.023
Wang, X., Kumar, S., & Singh, S. K. (2011). Disulfide Scrambling in
IgG2 Monoclonal Antibodies: Insights from Molecular Dynamics
Simulations. Pharmaceutical Research, 28 (12), 3128-3144.
doi:10.1007/s11095-011-0503-9
Wasalathanthri, D. P., Rehmann, M. S., Song, Y., Gu, Y., Mi, L., Shao,
C., . . . Li, Z. J. (2020). Technology outlook for real-time quality
attribute and process parameter monitoring in biopharmaceutical
development-A review. Biotechnol Bioeng, 117 (10), 3182-3198.
doi:10.1002/bit.27461
Wu, L., Seung, E., Xu, L., Rao, E., Lord, D. M., Wei, R. R., . . .
Nabel, G. J. (2020). Trispecific antibodies enhance the therapeutic
efficacy of tumor-directed T cells through T cell receptor
co-stimulation. Nature Cancer, 1 (1), 86-98.
doi:10.1038/s43018-019-0004-z
Xie, H., Chakraborty, A., Ahn, J., Yu, Y. Q., Dakshinamoorthy, D. P.,
Gilar, M., . . . Mazzeo, J. R. (2010). Rapid comparison of a candidate
biosimilar to an innovator monoclonal antibody with advanced liquid
chromatography and mass spectrometry technologies. mAbs, 2 (4),
379-394. doi:10.4161/mabs.11986
Xie, P., Niu, H., Chen, X., Zhang, X., Miao, S., Deng, X., . . . Fan, L.
(2016). Elucidating the effects of pH shift on IgG1 monoclonal antibody
acidic charge variant levels in Chinese hamster ovary cell cultures.Applied Microbiology and Biotechnology, 100 (24), 10343-10353.
doi:10.1007/s00253-016-7749-4
Yang, R., Tang, Y., Zhang, B., Lu, X., Liu, A., & Zhang, Y. T. (2015).
High resolution separation of recombinant monoclonal antibodies by
size-exclusion ultra-high performance liquid chromatography (SE-UHPLC).Journal of Pharmaceutical and Biomedical Analysis, 109 , 52-61.
doi:https://doi.org/10.1016/j.jpba.2015.02.032
Yang, X., Zhang, Y., Wang, F., Wang, L., Richardson, D., Shameem, M., &
Ambrogelly, A. (2015). Analysis and purification of IgG4 bispecific
antibodies by a mixed-mode chromatography. Analytical
Biochemistry, 484 , 173-179.
doi:https://doi.org/10.1016/j.ab.2015.06.014
Zhang, Q., & Flynn, G. C. (2013). Cysteine Racemization on IgG Heavy
and Light Chains. Journal of Biological Chemistry, 288 (48),
34325-34335.
Zhang, T., Zhang, J., Hewitt, D., Tran, B., Gao, X., Qiu, Z. J., . . .
Kao, Y.-H. (2012). Identification and Characterization of Buried
Unpaired Cysteines in a Recombinant Monoclonal IgG1 Antibody.Analytical Chemistry, 84 (16), 7112-7123. doi:10.1021/ac301426h
Zhang, W., & Czupryn, M. J. (2002). Free Sulfhydryl in Recombinant
Monoclonal Antibodies. Biotechnology Progress, 18 (3), 509-513.
doi:10.1021/bp025511z
Zhu, H., Dupureur, C. M., Zhang, X., & Tsai, M. D. (1995).
Phospholipase A2 engineering. The roles of disulfide bonds in structure,
conformational stability, and catalytic function. Biochemistry,
34 (46), 15307-15314. doi:10.1021/bi00046a040
Table 1: Reported approaches to prevent disulfide bond
reduction and rescue reduced mAb during manufacturing process