Structural and Functional Differences Between Glycosylated and Non-glycosylated Forms of Human Interferon-β (IFN-β)
Abstract
Purpose Two recombinant IFN-beta products have been approved for the treatment of multiple sclerosis, a glycosylated form with the predicted natural amino acid sequence (IFN-beta-1a) and a non-glycosylated form that has a Met-1 deletion and a Cys-17 to Ser mutation (IFN-beta-1b). The structural basis for activity differences between IFN-beta-1a and IFN-beta-1b, is determined. Methods In vitro antiviral, antiproliferative and immunomodulatory assays were used to directly compare the two IFN-beta products. Size exclusion chromatography (SEC), SDS-PAGE, thermal denaturation, and X-ray crystallography were used to examine structural differences. Results IFN-beta-1a was 10 times more active than IFN-beta-1b with specific activities in a standard antiviral assay of 20 x 10(7) IU/mg for IFN-beta-1a and 2 x 10(7) IU/mg for IFN-beta-1b. Of the known structural differences between IFN-beta-1a and IFN-beta-1b, only glycosylation affected in vitro activity. Deglycosylation of IFN-beta-1a produced a decrease in total activity that was primarily caused by the formation of an insoluble disulfide-linked IFN precipitate. Deglycosylation also resulted in an increased sensitivity to thermal denaturation. SEC data for IFN-beta-1b revealed large, soluble aggregates that had reduced antiviral activity (approximated at 0.7 x 10(7) IU/mg). Crystallographic data for IFN-beta-1a revealed that the glycan formed H-bonds with the peptide backbone and shielded an uncharged surface from solvent exposure. C…
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Proper glycosylation profiles can improve recombinant protein properties by increasing stability and half-life in blood circulation and decreasing immunogenicity.
“Studies have demonstrated that proper glycosylation profiles can improve recombinant protein properties such as increase their stability and half-life in blood circulation and decrease their immunogenicity (Ashwell and Harford, 1982;Runkel et al., 1998;Ghaderi et al., 2010;Ghaderi et al., 2012;Jefferis, 2016a;Jefferis, 2016b;Kuriakose et al., 2016).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Runkel et al., 1998
Cites
Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis
Jacobs, L. D., Cookfair, D. L., Rudick, R. A., Herndon, R. M., Richert, J. R., Salazar, A. Μ., Fischer, J. S., Goodkin, D. E., Granger, C. V., Simon, J. H., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410390304 · Cited by 2,446 · see citing works
Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis
The IFNB Multiple Sclerosis Study Group (1993) · Neurology · doi:10.1212/wnl.43.4.655 · Cited by 2,085 · see citing works
Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis
Paty, D. W., Li, D. K. B., the UBC MS/MRI Study Group, & the IFNB Multiple Sclerosis Study Group (1993) · Neurology · doi:10.1212/wnl.43.4.662 · Cited by 1,964 · see citing works
Girard, M., Duquette, P., & Sibley, W. A. (1993) · Cited by 1,197 · see citing works
Stewart, W. E. (1979) · Springer eBooks · doi:10.1007/978-3-7091-3432-0 · Cited by 1,165 · see citing works
Rademacher, T. W., Parekh, R. B., & Dwek, R. A. (1988) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.57.070188.004033 · Cited by 1,144 · see citing works
Lis, H., & Sharon, N. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb18347.x · Cited by 840 · see citing works
The interferon system. A bird's eye view of its biochemistry.
Sen, G. C., & Lengyel, P. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42719-6 · Cited by 633 · see citing works
Glycoproteins: what are the sugar chains for?
Paulson, J. C. (1989) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(89)90062-5 · Cited by 461 · see citing works
Influence of the Carbohydrate Moiety on the Stability of Glycoproteins
Wang, C., Eufemi, M., Turano, C., & GIARTOSIO, A. (1996) · Biochemistry · doi:10.1021/bi9517704 · Cited by 344 · see citing works
Gibson, R., Schlesinger, S., & Kornfeld, S. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50804-8 · Cited by 249 · see citing works
α and α Interferons and Their Receptor and Their Friends and Relations
Uzé, G., Lutfalla, G., & Mogensen, K. E. (1995) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.1995.15.3 · Cited by 241 · see citing works
Dubé, S., Fisher, J. W., & Powell, J. S. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77865-x · Cited by 229 · see citing works
The interferons: Biological effects, mechanisms of action, and use in multiple sclerosis
Weinstock‐Guttman, B., Ransohoff, R. M., Kinkel, R. P., & Rudick, R. A. (1995) · Annals of Neurology · doi:10.1002/ana.410370105 · Cited by 225 · see citing works
Zinc mediated dimer of human interferon-α2b revealed by X-ray crystallography
Radhakrishnan, R., Walter, L. J., Hruza, A. W., Reichert, P., Trotta, P. P., Nagabhushan, T. L., & Walter, M. R. (1996) · Structure · doi:10.1016/s0969-2126(96)00152-9 · Cited by 225 · see citing works
The crystal structure of human interferon β at 2.2-Å resolution
Karpusas, M., Nolte, M. C., Benton, C. B., Meier, W., Lipscomb, W. N., & Goelz, S. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.22.11813 · Cited by 211 · see citing works
Self-citationSite-specific mutagenesis of the human fibroblast interferon gene.
Mark, D. F., Lu, S.-D., Creasey, A. A., Yamamoto, R., & Lin, L. S. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.18.5662 · Cited by 196 · see citing works
Davis, D., Liu, X., & Segaloff, D. L. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.2.7776966 · Cited by 195 · see citing works
Expression of human fibroblast interferon gene in Escherichia coli
Derynck, R., Remaut, E., Saman, E., Stanssens, P. E., Clercq, E. D., Content, J., & Fiers, W. (1980) · Nature · doi:10.1038/287193a0 · Cited by 192 · see citing works
Modulation of protein structure and function by asparagine-linked glycosylation
O'Connor, S. E., & Imperiali, B. (1996) · Chemistry & Biology · doi:10.1016/s1074-5521(96)90064-2 · Cited by 188 · see citing works
Jost, L. M., Kirkwood, J. M., & Whiteside, T. L. (1992) · Journal of Immunological Methods · doi:10.1016/s0022-1759(12)80003-2 · Cited by 182 · see citing works
Kagawa, Y., Takasaki, S., Utsumi, J., Hosoi, K., Shimizu, H., Kochibe, N., & Kobata, A. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77864-8 · Cited by 182 · see citing works
Interferon : principles and medical applications
Baron, S. (1992) · Medical Entomology and Zoology · Cited by 158 · see citing works
Actions of cytokines on the immune response and viral interactions: An overview
Peters, M. (1996) · Hepatology · doi:10.1002/hep.510230436 · Cited by 153 · see citing works
Ng, D., Hiebert, S. W., & Lamb, R. A. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.1989 · Cited by 119 · see citing works
Conradt, H. S., Egge, H., Peter‐Katalinić, J., Reiser, W., Siklosi, T., & Schaper, K. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47838-6 · Cited by 106 · see citing works
Mitsui, Y., Senda, T., Shimazu, T., Matsuda, S., & Utsumi, J. (1993) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(93)90068-o · Cited by 71 · see citing works
Alam, J. J., Goelz, S. E., Rioux, P. P., Scaramucci, J., Jones, W. E., McAllister, A., Campion, M., & Rogge, M. C. (1997) · Pharmaceutical Research · doi:10.1023/a:1012128406432 · Cited by 57 · see citing works
Self-citationRefined Crystal Structure of Recombinant Murine Interferon-β at 2.15 Å Resolution
Senda, T., Saitoh, S., & Mitsui, Y. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0544 · Cited by 44 · see citing works
Interferons: Biochemistry and mechanisms of action
Tyring, S. K. (1995) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(95)90402-6 · Cited by 42 · see citing works
Wingfield, P. T., Graber, P., Turcatti, G., Movva, N. R., PELLETIER, M., Craig, S., Rose, K., & Miller, C. G. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb14610.x · Cited by 41 · see citing works
Folding, Unfolding, and Refolding of the Vesicular Stomatitis Virus Glycoprotein
Mathieu, M. E., Grigera, P. R., Helenius, A., & Wagner, R. R. (1996) · Biochemistry · doi:10.1021/bi952924i · Cited by 33 · see citing works
A homology model of human interferon α‐2
Murgolo, N., Windsor, W. T., Hruza, A. W., Reichert, P., Tsarbopoulos, A., Baldwin, S., Huang, E., Pramanik, B. N., Ealick, S. E., & Trotta, P. P. (1993) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340170109 · Cited by 23 · see citing works
Properties of Non-glycosylated Human Interferon-beta from MG63 Cells
Watanabe, Y., & Kawade, Y. (1983) · Journal of General Virology · doi:10.1099/0022-1317-64-6-1391 · Cited by 14 · see citing works
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Instability, stabilization, and formulation of liquid protein pharmaceuticals
Wang, W. (1999) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(99)00152-0 · Cited by 1,070 · see citing works
Post-translational modifications in the context of therapeutic proteins
Walsh, G., & Jefferis, R. (2006) · Nature Biotechnology · doi:10.1038/nbt1252 · Cited by 1,007 · see citing works
Protein aggregation and its inhibition in biopharmaceutics
Wang, W. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2004.11.014 · Cited by 990 · see citing works
Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines, Goodin, D. S., Frohman, E. M., Garmany, G. P., Halper, J., Likosky, W., LUBLIN, F. D., Silberberg, D. H., Stuart, W. H., & van den Noort, S. (2002) · Neurology · doi:10.1212/wnl.58.2.169 · Cited by 797 · see citing works
Effects of glycosylation on the stability of protein pharmaceuticals
Solá, R. J., & Griebenow, K. H. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21504 · Cited by 643 · see citing works
Glycoengineering: The effect of glycosylation on the properties of therapeutic proteins
Sinclair, A. M., & Elliott, S. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20319 · Cited by 461 · see citing works
Monk, P., Marsden, R., Tear, V. J., Brookes, J. L., Batten, T. N., Mankowski, M., Gabbay, F. J., Davies, D. E., Holgate, S. T., Ho, L., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30511-7 · Cited by 431 · see citing works
Glycosylation of Therapeutic Proteins
Solá, R. J., & Griebenow, K. H. (2010) · BioDrugs · doi:10.2165/11530550-000000000-00000 · Cited by 440 · see citing works
Impact of Product-Related Factors on Immunogenicity of Biotherapeutics
Singh, S. K. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22276 · Cited by 350 · see citing works
Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
Delivery of interferon-β to the monkey nervous system following intranasal administration
Thorne, R. G., Hanson, L. R., Ross, T. M., Tung, D., & Frey, W. H. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.013 · Cited by 256 · see citing works
Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
Kuriakose, A., Chirmule, N. B., & Nair, P. (2016) · Journal of Immunology Research · doi:10.1155/2016/1298473 · Cited by 231 · see citing works
Sørensen, P. S., Deisenhammer, F., Duda, P. W., Hohlfeld, R., Myhr, K., Palace, J. A., Polman, C. H., Pozzilli, C., Ross, C., & for the EFNS Task Force on Anti‐IFN‐β Antibodies in Multiple Sclerosis (2005) · European Journal of Neurology · doi:10.1111/j.1468-1331.2005.01386.x · Cited by 226 · see citing works
Eon‐Duval, A., Broly, H., & Gleixner, R. (2012) · Biotechnology Progress · doi:10.1002/btpr.1548 · Cited by 218 · see citing works
Oxidation of Therapeutic Proteins and Peptides: Structural and Biological Consequences
Torosantucci, R., Schöneich, C., & Jiskoot, W. (2013) · Pharmaceutical Research · doi:10.1007/s11095-013-1199-9 · Cited by 218 · see citing works
Immunological mechanism underlying the immune response to recombinant human protein therapeutics
Sauerborn, M., Brinks, V., Jiskoot, W., & Schellekens, H. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.11.001 · Cited by 207 · see citing works
Aggregation of Protein Therapeutics Enhances Their Immunogenicity: Causes and Mitigation Strategies
Lundahl, M. L. E., Fogli, S., Colavita, P. E., & Scanlan, E. M. (2021) · RSC Chemical Biology · doi:10.1039/d1cb00067e · Cited by 212 · see citing works
Hermeling, S., Schellekens, H., Maas, C., Gebbink, M. F. B. G., Crommelin, D. J. A., & Jiskoot, W. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20599 · Cited by 185 · see citing works
Goodin, D., Frohman, E. M., Hurwitz, B. J., O'Connor, P. W., Oger, J. J.-F., Reder, A. T., & Stevens, J. C. (2007) · Neurology · doi:10.1212/01.wnl.0000258545.73854.cf · Cited by 173 · see citing works
van Beers, M. M. C., & Bardor, M. (2012) · Biotechnology Journal · doi:10.1002/biot.201200065 · Cited by 172 · see citing works
Production of therapeutic antibodies with controlled fucosylation
Yamane‐Ohnuki, N., & Satoh, M. (2009) · mAbs · doi:10.4161/mabs.1.3.8328 · Cited by 170 · see citing works
Zhou, Q., & Qiu, H. (2018) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2018.11.029 · Cited by 169 · see citing works
Immunomodulatory activity of interferon‐beta
Kasper, L. H., & Reder, A. T. (2014) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.84 · Cited by 159 · see citing works
Glycosylation: impact, control and improvement during therapeutic protein production
Costa, A. R., Rodrigues, M. E., Henriques, M., Oliveira, R., & Azeredo, J. (2013) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2013.793649 · Cited by 155 · see citing works
Enhanced Production of Monomeric Interferon-β by CHO Cells through the Control of Culture Conditions
Rodriguez, J., Spearman, M., Huzel, N., & Butler, M. (2008) · Biotechnology Progress · doi:10.1021/bp049807b · Cited by 145 · see citing works
Bertolotto, A. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.2.148 · Cited by 145 · see citing works
Developments and Challenges for mAb-Based Therapeutics
Goswami, S., Wang, W., Arakawa, T., & Ohtake, S. (2013) · Antibodies · doi:10.3390/antib2030452 · Cited by 144 · see citing works
Inhaled proteins: Challenges and perspectives
Depreter, F., Pilcer, G., & Amighi, K. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.02.031 · Cited by 143 · see citing works
FTIR and nDSC as Analytical Tools for High-Concentration Protein Formulations
Matheus, S., Frieß, W., & Mahler, H. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-0142-8 · Cited by 132 · see citing works
Macrophages and cytokines in the early defence against herpes simplex virus
Ellermann‐Eriksen, S. (2005) · Virology Journal · doi:10.1186/1743-422x-2-59 · Cited by 133 · see citing works
Barnard, J. G., Babcock, K., & Carpenter, J. F. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23415 · Cited by 127 · see citing works
Pepinsky, R. B., LePage, D., Gill, A., Chakraborty, A., Vaidyanathan, S., Green, M., Baker, D. P., Whalley, E. T., Hochman, P. S., & Martin, P. L. (2001) · PubMed · Cited by 119 · see citing works
Self-citationSakamoto, I., Tezuka, K., Fukae, K., Ishii, K., Taduru, K., Maeda, M., Ouchi, M., Yoshida, K. J., Nambu, Y., Igarashi, J., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja2109079 · Cited by 116 · see citing works
van Beers, M. M. C., Sauerborn, M., Gilli, F., Brinks, V., Schellekens, H., & Jiskoot, W. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0451-4 · Cited by 115 · see citing works
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Jiskoot, W., Kijanka, G., Randolph, T. W., Carpenter, J. F., Koulov, A. V., Mahler, H., Joubert, M. K., Jawa, V., & Narhi, L. O. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.02.031 · Cited by 115 · see citing works
Nejadnik, M. R., Randolph, T. W., Volkin, D. B., Schöneich, C., Carpenter, J. F., Crommelin, D. J. A., & Jiskoot, W. (2018) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2018.04.005 · Cited by 115 · see citing works
Glycosylation of therapeutic proteins in different production systems
Werner, R. G., Kopp, K., & Schlueter, M. (2007) · Acta Paediatrica · doi:10.1111/j.1651-2227.2007.00199.x · Cited by 111 · see citing works
The structure of human interferon- ? : implications for activity
Karpusas, M., Whitty, A., Runkel, L., & Hochman, P. S. (1998) · Cellular and Molecular Life Sciences · doi:10.1007/s000180050248 · Cited by 111 · see citing works
Self-citationAggregation of therapeutic proteins
Wang, W., & Roberts, C. J. (2010) · Wiley eBooks · Cited by 104 · see citing works
Wadhwa, M., Bird, C., Dilger, P., Gaines-Das, R. E., & Thorpe, R. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(03)00206-0 · Cited by 104 · see citing works
Neutralising antibodies to interferon beta during the treatment of multiple sclerosis
Giovannoni, G. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.5.465 · Cited by 104 · see citing works
Immunogenicity of interferon beta: differences among products
Bertolotto, A., Deisenhammer, F., Gallo, P., & S�rensen, P. S. (2004) · Journal of Neurology · doi:10.1007/s00415-004-1204-7 · Cited by 103 · see citing works
Gelatinase B/matrix metalloproteinase‐9 cleaves interferon‐β and is a target for immunotherapy
Nelissen, I., Martens, E., den Steen, P. E. V., Proost, P., Ronsse, I., & Opdenakker, G. (2003) · Brain · doi:10.1093/brain/awg129 · Cited by 100 · see citing works
Diversity and Relatedness Among the Type I Interferons
Chen, J., Baig, E., & Fish, E. N. (2004) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2004.24.687 · Cited by 99 · see citing works
Muneeruddin, K., Nazzaro, M., & Kaltashov, I. A. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02982 · Cited by 98 · see citing works
Engineering Cells for Cell Culture Bioprocessing – Physiological Fundamentals
Seth, G., Hossler, P., Yee, J. C., & Hu, W. (2006) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_017 · Cited by 94 · see citing works
Bertolotto, A., Malucchi, S., Milano, E., Castello, A., Capobianco, M. A. N., & Mutani, R. (2000) · Immunopharmacology · doi:10.1016/s0162-3109(00)00182-x · Cited by 95 · see citing works
Kaltashov, I. A., Bobst, C. E., Abzalimov, R. R., Berkowitz, S. A., & Houde, D. J. (2009) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.10.013 · Cited by 92 · see citing works
van Beers, M. M. C., Sauerborn, M., Gilli, F., Brinks, V., Schellekens, H., & Jiskoot, W. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0172-0 · Cited by 90 · see citing works
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Lipiäinen, T., Peltoniemi, M., Sarkhel, S., Yrjönen, T., Vuorela, H. J., Urtti, A. O., & Juppo, A. M. (2014) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.24243 · Cited by 89 · see citing works
van Beers, M. M. C., Jiskoot, W., & Schellekens, H. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2010.0086 · Cited by 86 · see citing works
Photo-induced radical thiol–ene chemistry: a versatile toolbox for peptide-based drug design
Ahangarpour, M., Kavianinia, I., Harris, P. W. R., & Brimble, M. A. (2021) · Chemical Society Reviews · doi:10.1039/d0cs00354a · Cited by 84 · see citing works
Ealy, A. D., Larson, S. F., Liu, L., Alexenko, A. P., Winkelman, G. L., Kubisch, H. M., Bixby, J. A., & Roberts, R. M. (2001) · Endocrinology · doi:10.1210/endo.142.7.8249 · Cited by 83 · see citing works
Beta-interferon for multiple sclerosis
Rudick, R. A., & Goelz, S. E. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.03.002 · Cited by 80 · see citing works
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Weinstein, R. S. (2000) · Journal of Clinical Apheresis · doi:10.1002/(sici)1098-1101(2000)15:1/2 · Cited by 78 · see citing works
Pepinsky, R. B., LePage, D., Gill, A., Chakraborty, A., Vaidyanathan, S., Green, M., Baker, D. P., Whalley, E. T., Hochman, P. S., & Martin, P. L. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29633-6 · Cited by 77 · see citing works
Self-citationKivisäkk, P., Alm, G. V., Fredrikson, S., & Link, H. (2000) · European Journal of Neurology · doi:10.1046/j.1468-1331.2000.00002.x · Cited by 76 · see citing works
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Hermeling, S., Jiskoot, W., Crommelin, D. J. A., Bornæs, C., & Schellekens, H. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-4578-z · Cited by 72 · see citing works
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Sung, C., Nardelli, B., LaFleur, D. W., Blatter, E. E., Corcoran, M. L., Olsen, H. S., Birse, C. E., Pickeral, O. K., Zhang, J., Shah, D., et al. (2003) · Journal of Interferon & Cytokine Research · doi:10.1089/10799900360520423 · Cited by 71 · see citing works
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Interferon-β1afor the treatment of multiple sclerosis
Clerico, M., Contessa, G., & Durelli, L. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.4.535 · Cited by 64 · see citing works
Herndon, R. M., Rudick, R. A., Munschauer, F. E., Mass, M. K., Salazar, A. Μ., Coats, M. E., Labutta, R. J., Richert, J. R., COHAN, S. L., Genain, C. P., et al. (2005) · Multiple Sclerosis Journal · doi:10.1191/1352458505ms1209oa · Cited by 64 · see citing works
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Rocamora, F., Peralta, A. G., Shin, S., Sorrentino, J., Wu, M. Y. M., Toth, E. A., Fuerst, T. R., & Lewis, N. E. (2023) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108206 · Cited by 63 · see citing works
Frohman, E. M. (2003) · Medical Clinics of North America · doi:10.1016/s0025-7125(03)00008-7 · Cited by 62 · see citing works
Antonelli, G., Simeoni, E., Bagnato, F. R., Pozzilli, C., Turriziani, O., Tesoro, R., Marco, P. D., Gasperini, C., Fieschi, C., & DIANZANI, F. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00185-9 · Cited by 62 · see citing works
Bellomi, F., Scagnolari, C., Tomassini, V., Gasperini, C., Paolillo, A., Pozzilli, C., & Antonelli, G. (2003) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(03)00173-4 · Cited by 61 · see citing works
A review of disease-modifying therapies for MS: maximizing adherence and minimizing adverse events
Brandes, D. W., Callender, T., Lathi, E. S., & O’Leary, S. (2008) · Current Medical Research and Opinion · doi:10.1185/03007990802569455 · Cited by 60 · see citing works
Brickelmaier, M., Hochman, P. S., Baciu, R., Chao, B. H., Cuervo, J. H., & Whitty, A. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(99)00073-3 · Cited by 60 · see citing works
Self-citationThe implications of immunogenicity for protein-based multiple sclerosis therapies
Cohen, B. A., Oger, J., Gagnon, A. W., & Giovannoni, G. (2008) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2008.08.003 · Cited by 57 · see citing works
High productivity of human recombinant beta-interferon from a low-temperature perfusion culture
Rodriguez, J., Spearman, M. A., Tharmalingam, T., Sunley, K., Lodewyks, C. L., Huzel, N. J., & Butler, M. (2010) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2010.09.959 · Cited by 57 · see citing works
‘Biogenerics’: the off-patent biotech products
Schellekens, H., & Ryff, J. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01967-2 · Cited by 56 · see citing works
Biological responsiveness to first injections of interferon-beta in patients with multiple sclerosis
Gilli, F., Marnetto, F., Caldano, M., Sala, A., Malucchi, S., Sapio, A. D., Capobianco, M. A. N., & Bertolotto, A. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.08.006 · Cited by 54 · see citing works
Alsenaidy, M. A., Jain, N. K., Kim, J. H., Middaugh, C. R., & Volkin, D. B. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00039 · Cited by 51 · see citing works
Kosloski, M. P., Miclea, R. D., & Balu‐Iyer, S. V. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9119-y · Cited by 51 · see citing works
Scagnolari, C., Bellomi, F., Turriziani, O., Bagnato, F. R., Tomassini, V., Lavolpe, V., Ruggieri, M., Bruschi, F., Meucci, G., Dicuonzo, G., et al. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753536176 · Cited by 51 · see citing works
Spearman, M. A., Rodriguez, J., Huzel, N. J., & Butler, M. (2005) · Biotechnology Progress · doi:10.1021/bp0498084 · Cited by 50 · see citing works
Svilenov, H. L., Markoja, U., & Winter, G. (2018) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2018.01.004 · Cited by 49 · see citing works
Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge
Zettl, U. K., Hecker, M., Aktaş, O., Wagner, T. B., & Rommer, P. S. (2018) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2018.1426462 · Cited by 49 · see citing works
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
Bastard, P., Gervais, A., Taniguchi, M., Saare, L., Särekannu, K., Voyer, T. L., Philippot, Q., Rosain, J., Bizien, L., Asano, T., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20231353 · Cited by 49 · see citing works
Antonetti, F., Finocchiaro, O., Mascia, M., Terlizzese, M., & Jaber, A. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/10799900260475696 · Cited by 47 · see citing works
Courtney, A., Treadaway, K., Remington, G. M., & Frohman, E. M. (2009) · Medical Clinics of North America · doi:10.1016/j.mcna.2008.09.014 · Cited by 46 · see citing works
Hartung, H., Munschauer, F., & Schellekens, H. (2005) · European Journal of Neurology · doi:10.1111/j.1468-1331.2005.01104.x · Cited by 46 · see citing works
Arduini, R. M., Li, Z., Rapoza, A., Gronke, R. S., Hess, D. M., Wen, D., Miatkowski, K., Coots, C., Kaffashan, A., Viseux, N., et al. (2003) · Protein Expression and Purification · doi:10.1016/j.pep.2003.11.004 · Cited by 46 · see citing works
Self-citationA high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2
Yao, H., Cai, H., Li, T., Zhou, B., Qin, W., Lavillette, D., & Li, D. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009328 · Cited by 44 · see citing works
Torosantucci, R., Sharov, V. S., van Beers, M. M. C., Brinks, V., Schöneich, C., & Jiskoot, W. (2013) · Molecular Pharmaceutics · doi:10.1021/mp300665u · Cited by 44 · see citing works
The bioactivity and fractionation of peptide hydrolysates in cultures of CHO cells
Spearman, M. A., Lodewyks, C. L., Richmond, M. E. I., & Butler, M. (2014) · Biotechnology Progress · doi:10.1002/btpr.1930 · Cited by 44 · see citing works
Review: Neutralizing antibodies against interferon-beta
Sørensen, P. S. (2008) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285608095144 · Cited by 43 · see citing works
Potent Inhibitory Effects of Type I Interferons on Human Adrenocortical Carcinoma Cell Growth
van Koetsveld, P. M., Vitale, G., de Herder, W. W., Feelders, R. A., van der Wansem, K., Waaijers, M., van Eijck, C. H. J., Speel, E. M., Croze, E., van der Lely, A. J., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0620 · Cited by 41 · see citing works
Using measurements of neutralizing antibodies: the challenge of IFN‐β therapy
Hesse, D., & Sørensen, P. S. (2007) · European Journal of Neurology · doi:10.1111/j.1468-1331.2007.01769.x · Cited by 41 · see citing works
The Function of the Human Interferon-β1a Glycan Determined in Vivo
Dissing‐Olesen, L., Thaysen‐Andersen, M., Meldgaard, M., Højrup, P., & Finsen, B. R. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.138263 · Cited by 40 · see citing works
Harada, H., Tamaoka, A., Kohno, Y., Mochizuki, A., & Shoji, S. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00082-9 · Cited by 40 · see citing works
Pereiro, P., Costa, M. M., Díaz‐Rosales, P., Dios, S., Figueras, A. J., & Novoa, B. (2014) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2014.03.006 · Cited by 39 · see citing works
Baker, D. P., Pepinsky, R. B., Brickelmaier, M., Gronke, R. S., Hu, X. S., Olivier, K., Lerner, M., Miller, L., Crossman, M., Nestorov, I. A., et al. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2010.0092 · Cited by 38 · see citing works
Self-citationCurrent and Future Therapies Targeting the Immune System in Multiple Sclerosis
Loleit, V., Biberacher, V., & Hemmer, B. (2014) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201015666140617104332 · Cited by 37 · see citing works
Molecular dynamics simulation for rational protein engineering: Present and future prospectus
Rouhani, M., Khodabakhsh, F., Norouzian, D., Cohan, R. A., & Valizadeh, V. (2018) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2018.06.009 · Cited by 38 · see citing works
Interferon-β in the treatment of relapsing–remitting multiple sclerosis
Revel, M. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(03)00085-8 · Cited by 38 · see citing works
Immunogenicity of Therapeutic Proteins
Hermeling, S., Crommelin, D. J. A., Schellekens, H., & Jiskoot, W. (2010) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse315 · Cited by 38 · see citing works
- Authors
- Runkel, L., Meier, W., Pepinsky, R. B., Karpusas, M., Whitty, A., Kimball, K., Brickelmaier, M., Muldowney, C., Jones, W., & Goelz, S. E.
- Affiliations
- Biogen (United States) (US)
- Corresponding author
- Runkel, Laura
- ORCID
- Whitty, Adrian
- Venue
- Pharmaceutical Research
- Published
- 1998-04
- Volume
- 15
- Issue
- 4
- Pages
- 641-649
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W329292291
- Cited by
- 304
- References
- 34
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 10 · 2017: 8 · 2016: 16 · 2015: 10 · 2014: 16 · 2013: 16 · 2012: 13
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- interferon-beta, glycosylation, recombinant interferon, multiple sclerosis, antiviral activity, protein stability, thermal denaturation, protein aggregation, disulfide bonds, protein structure
- MeSH terms
- Interferon beta-1a, Interferon beta-1b, Adjuvants, Immunologic, Antiviral Agents, Base Sequence, Cell Division, Cell Line, Cysteine, Encephalomyocarditis virus, Glycosylation, Humans, Major Histocompatibility Complex, Molecular Sequence Data, Mutation, Recombinant Proteins, Serine, Interferon-beta, Cardiovirus Infections
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