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Review

Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies

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Pages 653-663 | Published online: 27 Aug 2012

Keep up to date with the latest research on this topic with citation updates for this article.

Read on this site (31)

Monica L. Fernández-Quintero, Katharina B. Kroell, Lukas J. Grunewald, Anna-Lena M. Fischer, Jakob R. Riccabona & Klaus R. Liedl. (2022) CDR loop interactions can determine heavy and light chain pairing preferences in bispecific antibodies. mAbs 14:1.
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Desislava Yanakieva, Lukas Pekar, Andreas Evers, Markus Fleischer, Stephan Keller, Dirk Mueller-Pompalla, Lars Toleikis, Harald Kolmar, Stefan Zielonka & Simon Krah. (2022) Beyond bispecificity: Controlled Fab arm exchange for the generation of antibodies with multiple specificities. mAbs 14:1.
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Dennis J. Underwood, Jeffrey Bettencourt & Zahra Jawad. (2022) The manufacturing considerations of bispecific antibodies. Expert Opinion on Biological Therapy 22:8, pages 1043-1065.
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Stefan Warmuth, Tea Gunde, Daniel Snell, Matthias Brock, Christopher Weinert, Alexandre Simonin, Christian Hess, Julia Tietz, Maria Johansson, Fabio Mario Spiga, Robin Heiz, Naomi Flückiger, Sandro Wagen, Julia Zeberer, Dania Diem, Dana Mahler, Belinda Wickihalder, Simone Muntwiler, Bithi Chatterjee, Benjamin Küttner, Bettina Bommer, Yasemin Yaman, Peter Lichtlen & David Urech. (2021) Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade. OncoImmunology 10:1.
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Shion A. Lim, Josef A. Gramespacher, Katarina Pance, Nicholas J. Rettko, Paige Solomon, Jing Jin, Irene Lui, Susanna K. Elledge, Jia Liu, Colton J. Bracken, Graham Simmons, Xin X. Zhou, Kevin K. Leung & James A. Wells. (2021) Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2. mAbs 13:1.
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Kathryn H. Ching, Kimberley Berg, Kevin Reynolds, Darlene Pedersen, Alba Macias, Yasmina N. Abdiche, William D. Harriman & Philip A. Leighton. (2021) Common light chain chickens produce human antibodies of high affinity and broad epitope coverage for the engineering of bispecifics. mAbs 13:1.
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Romain Ollier, Paul Wassmann, Thierry Monney, Christelle Ries Fecourt, Sunitha Gn, Vinu C A, Daniel Ayoub, Cian Stutz, Girish S Gudi & Stanislas Blein. (2019) Single-step Protein A and Protein G avidity purification methods to support bispecific antibody discovery and development. mAbs 11:8, pages 1464-1478.
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Adam R. Evans, Michael T. Capaldi, Geetha Goparaju, David Colter, Frank F. Shi, Sarah Aubert, Lian-Chao Li, Jingjie Mo, Michael J. Lewis, Ping Hu, Pedro Alfonso & Promod Mehndiratta. (2019) Using bispecific antibodies in forced degradation studies to analyze the structure–function relationships of symmetrically and asymmetrically modified antibodies. mAbs 11:6, pages 1101-1112.
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Chen Chen, Tetsuya Wakabayashi, Masaru Muraoka, Feng Shu, Chia Wei Shan, Chong Chor Kun, Ching Tim Jang, Ishin Soehano, Yuichiro Shimizu, Tomoyuki Igawa & Jun-Ichi Nezu. (2019) Controlled conductivity at low pH in Protein L chromatography enables separation of bispecific and other antibody formats by their binding valency. mAbs 11:4, pages 632-638.
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Dani Setiawan, Jeffrey Brender & Yang Zhang. (2018) Recent advances in automated protein design and its future challenges. Expert Opinion on Drug Discovery 13:7, pages 587-604.
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Marie Godar, Hans de Haard, Christophe Blanchetot & Jacobus Rasser. (2018) Therapeutic bispecific antibody formats: a patent applications review (1994-2017). Expert Opinion on Therapeutic Patents 28:3, pages 251-276.
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Nazzareno Dimasi, Ryan Fleming, Kris F. Sachsenmeier, Binyam Bezabeh, Carl Hay, Jincheng Wu, Erin Sult, Saravanan Rajan, Li Zhuang, Peter Cariuk, Andrew Buchanan, Michael A. Bowen, Herren Wu & Changshou Gao. (2017) Guiding bispecific monovalent antibody formation through proteolysis of IgG1 single-chain. mAbs 9:3, pages 438-454.
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Ulrich Brinkmann & Roland E. Kontermann. (2017) The making of bispecific antibodies. mAbs 9:2, pages 182-212.
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Yiyuan Yin, Guanghui Han, Jianhui Zhou, Michael Dillon, Luke McCarty, Lou Gavino, Diego Ellerman, Christoph Spiess, Wendy Sandoval & Paul J. Carter. (2016) Precise quantification of mixtures of bispecific IgG produced in single host cells by liquid chromatography-Orbitrap high-resolution mass spectrometry. mAbs 8:8, pages 1467-1476.
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Magdalena Malm, Fredrik Y. Frejd, Stefan Ståhl & John Löfblom. (2016) Targeting HER3 using mono- and bispecific antibodies or alternative scaffolds. mAbs 8:7, pages 1195-1209.
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Christian Klein, Wolfgang Schaefer & Jörg T. Regula. (2016) The use of CrossMAb technology for the generation of bi- and multispecific antibodies. mAbs 8:6, pages 1010-1020.
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Bram G. Sengers, Sean McGinty, Fatma Z. Nouri, Maryam Argungu, Emma Hawkins, Aymen Hadji, Andrew Weber, Adam Taylor & Armin Sepp. (2016) Modeling bispecific monoclonal antibody interaction with two cell membrane targets indicates the importance of surface diffusion. mAbs 8:5, pages 905-915.
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Markus Haberger, Michael Leiss, Anna-Katharina Heidenreich, Oxana Pester, Georg Hafenmair, Michaela Hook, Lea Bonnington, Harald Wegele, Markus Haindl, Dietmar Reusch & Patrick Bulau. (2016) Rapid characterization of biotherapeutic proteins by size-exclusion chromatography coupled to native mass spectrometry . mAbs 8:2, pages 331-339.
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Wolfgang Schaefer, Hans R Völger, Stefan Lorenz, Sabine Imhof-Jung, Jörg T Regula, Christian Klein & Michael Mølhøj. (2016) Heavy and light chain pairing of bivalent quadroma and knobs-into-holes antibodies analyzed by UHR-ESI-QTOF mass spectrometry. mAbs 8:1, pages 49-55.
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Markus Haberger, Anna-Katharina Heidenreich, Tilman Schlothauer, Michaela Hook, Jana Gassner, Katrin Bomans, Michelle Yegres, Adrian Zwick, Boris Zimmermann, Harald Wegele, Lea Bonnington, Dietmar Reusch & Patrick Bulau. (2015) Functional assessment of antibody oxidation by native mass spectrometry. mAbs 7:5, pages 891-900.
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Yariv Mazor, Vaheh Oganesyan, Chunning Yang, Anna Hansen, Jihong Wang, Hongji Liu, Kris Sachsenmeier, Marcia Carlson, Dhanesh V Gadre, Martin Jack Borrok, Xiang-Qing Yu, William Dall’Acqua, Herren Wu & Partha Sarathi Chowdhury. (2015) Improving target cell specificity using a novel monovalent bispecific IgG design. mAbs 7:2, pages 377-389.
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Yiren Xu, John Lee, Cuong Tran, Tyler H Heibeck, Willie D Wang, Junhao Yang, Ryan L Stafford, Alexander R Steiner, Aaron K Sato, Trevor J Hallam & Gang Yin. (2015) Production of bispecific antibodies in “knobs-into-holes” using a cell-free expression system . mAbs 7:1, pages 231-242.
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Janice M Reichert, Alain Beck, Alexey A Lugovskoy, Thierry Wurch, Steven Coats & Randall J Brezski. (2014) 9th Annual European Antibody Congress, November 11–13, 2013, Geneva, Switzerland. mAbs 6:2, pages 309-326.
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Markus Haberger, Katrin Bomans, Katharina Diepold, Michaela Hook, Jana Gassner, Tilman Schlothauer, Adrian Zwick, Christian Spick, Jochen Felix Kepert, Brigitte Hienz, Michael Wiedmann, Hermann Beck, Philipp Metzger, Michael Mølhøj, Constanze Knoblich, Ulla Grauschopf, Dietmar Reusch & Patrick Bulau. (2014) Assessment of chemical modifications of sites in the CDRs of recombinant antibodies. mAbs 6:2, pages 327-339.
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Ingo Schubert, Domenica Saul, Stefanie Nowecki, Andreas Mackensen, Georg H Fey & Fuat S Oduncu. (2014) A dual-targeting triplebody mediates preferential redirected lysis of antigen double-positive over single-positive leukemic cells. mAbs 6:1, pages 286-296.
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Michael J Gramer, Ewald TJ van den Bremer, Muriel D van Kampen, Amitava Kundu, Peter Kopfmann, Eric Etter, David Stinehelfer, Justin Long, Tom Lannom, Esther H Noordergraaf, Jolanda Gerritsen, Aran F Labrijn, Janine Schuurman, Patrick HC van Berkel & Paul WHI Parren. (2013) Production of stable bispecific IgG1 by controlled Fab-arm exchange. mAbs 5:6, pages 962-973.
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Thomas Spreter Von Kreudenstein, Eric Escobar-Carbrera, Paula I. Lario, Igor D’Angelo, Karine Brault, John F Kelly, Yves Durocher, Jason Baardsnes, R. Jeremy Woods, Michael Hongwei Xie, Pierre-Alain Girod, Michael D. L. Suits, Martin J. Boulanger, David K. Y. Poon, Gordon Y. Ng & Surjit B. Dixit. (2013) Improving biophysical properties of a bispecific antibody scaffold to aid developability. mAbs 5:5, pages 646-654.
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R. Jeremy Woods, Michael Hongwei Xie, Thomas Spreter Von Kreudenstein, Gordon Y. Ng & Surjit B. Dixit. (2013) LC-MS characterization and purity assessment of a prototype bispecific antibody. mAbs 5:5, pages 711-722.
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Alain Beck, Paul J. Carter, Hans-Peter Gerber, Alexey A. Lugovskoy, Thierry Wurch, Jagath R. Junutula, Roland E Kontermann & Robert Mabry. (2013) 8th Annual European Antibody Congress 2012. mAbs 5:3, pages 339-357.
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Futa Mimoto, Tomoyuki Igawa, Taichi Kuramochi, Hitoshi Katada, Shojiro Kadono, Takayuki Kamikawa, Meiri Shida-Kawazoe & Kunihiro Hattori. (2013) Novel asymmetrically engineered antibody Fc variant with superior FcγR binding affinity and specificity compared with afucosylated Fc variant. mAbs 5:2, pages 229-236.
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Lucas Gutierrez, Nina S. Cauchon, Twinkle R. Christian, Michael J. Giffin & Michael J. Abernathy. (2020) The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations. Journal of Pharmaceutical Sciences 109:12, pages 3524-3534.
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Shuyu Huang, Sander M. J. van Duijnhoven, Alice J. A. M. Sijts & Andrea van Elsas. (2020) Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy. Journal of Cancer Research and Clinical Oncology 146:12, pages 3111-3122.
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Xiujuan Chen, Ying Wang, Ying Wang & Yifeng Li. (2020) Protein L chromatography: A useful tool for monitoring/separating homodimers during the purification of IgG-like asymmetric bispecific antibodies. Protein Expression and Purification 175, pages 105711.
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Gaili Guo, Jinyu Han, Ying Wang & Yifeng Li. (2020) A potential downstream platform approach for WuXiBody-based IgG-like bispecific antibodies. Protein Expression and Purification 173, pages 105647.
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Asako Harada, Akifumi Shioda, Tatsuya Ikuno, Yoshika Iwata, Hirotake Shiraiwa, Tetsuya Wakabayashi, Yuji Sano & Masayuki Mishima. (2020) In vitro toxicological support to establish specification limit for anti-CD3 monospecific impurity in a bispecific T cell engager drug, ERY974. Toxicology in Vitro 66, pages 104841.
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Haitao Jiang, Wei Xu, Ren Liu, Balrina Gupta, Bruce Kilgore, Zhimei Du & Xiaoyu Yang. (2020) Characterization of Bispecific Antibody Production in Cell Cultures by Unique Mixed Mode Size Exclusion Chromatography. Analytical Chemistry 92:13, pages 9312-9321.
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Martina Geiger, Kay-Gunnar Stubenrauch, Johannes Sam, Wolfgang F. Richter, Gregor Jordan, Jan Eckmann, Carina Hage, Valeria Nicolini, Anne Freimoser-Grundschober, Mirko Ritter, Matthias E. Lauer, Henning Stahlberg, Philippe Ringler, Jigar Patel, Eric Sullivan, Sandra Grau-Richards, Stefan Endres, Sebastian Kobold, Pablo Umaña, Peter Brünker & Christian Klein. (2020) Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody. Nature Communications 11:1.
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Aerin Yoon, Shinai Lee, Sua Lee, Sojung Lim, Yong-Yea Park, Eunjung Song, Dong-Sik Kim, Kisu Kim & Yangmi Lim. (2020) A Novel T Cell-Engaging Bispecific Antibody for Treating Mesothelin-Positive Solid Tumors. Biomolecules 10:3, pages 399.
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Sylvia Dietrich, Alec W. Gross, Stefan Becker, Björn Hock, Gerhard Stadlmayr, Florian Rüker & Gordana Wozniak-Knopp. (2020) Constant domain-exchanged Fab enables specific light chain pairing in heterodimeric bispecific SEED-antibodies. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1868:1, pages 140250.
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Yifeng Li, Ying Wang, Peter (Keqiang) Shen & Weichang Zhou. 2020. Approaches to the Purification, Analysis and Characterization of Antibody-Based Therapeutics. Approaches to the Purification, Analysis and Characterization of Antibody-Based Therapeutics 167 179 .
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Alina Schneider, Ingo H. Gorr, Vincent Larraillet, Timo Frensing & Oliver Popp. (2019) Reduction of IL‐2 fragmentation during manufacturing of a novel immunocytokine by DoE process optimization. Biotechnology and Bioengineering 116:10, pages 2503-2513.
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Strohl & Naso. (2019) Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells. Antibodies 8:3, pages 41.
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Justin T. Huckaby, Christina L. Parker, Tim M. Jacobs, Alison Schaefer, Daniel Wadsworth, Alexander Nguyen, Anting Wang, Jay Newby & Samuel K. Lai. (2019) Engineering Polymer‐Binding Bispecific Antibodies for Enhanced Pretargeted Delivery of Nanoparticles to Mucus‐Covered Epithelium. Angewandte Chemie International Edition 58:17, pages 5604-5608.
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Justin T. Huckaby, Christina L. Parker, Tim M. Jacobs, Alison Schaefer, Daniel Wadsworth, Alexander Nguyen, Anting Wang, Jay Newby & Samuel K. Lai. (2019) Engineering Polymer‐Binding Bispecific Antibodies for Enhanced Pretargeted Delivery of Nanoparticles to Mucus‐Covered Epithelium. Angewandte Chemie 131:17, pages 5660-5664.
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Michael E. Lindquist & Mark D. Hicar. (2019) B Cells and Antibodies in Kawasaki Disease. International Journal of Molecular Sciences 20:8, pages 1834.
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Yifeng Li. (2019) A brief introduction of IgG-like bispecific antibody purification: Methods for removing product-related impurities. Protein Expression and Purification 155, pages 112-119.
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Christian Klein, Wolfgang Schaefer, Joerg T. Regula, Charles Dumontet, Ulrich Brinkmann, Marina Bacac & Pablo Umaña. (2019) Engineering therapeutic bispecific antibodies using CrossMab technology. Methods 154, pages 21-31.
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Hirotake Shiraiwa, Atsushi Narita, Mika Kamata-Sakurai, Takahiro Ishiguro, Yuji Sano, Naoka Hironiwa, Takashi Tsushima, Hiroaki Segawa, Toshiaki Tsunenari, Yosuke Ikeda, Yoko Kayukawa, Mizuho Noguchi, Tetsuya Wakabayashi, Akihisa Sakamoto, Hiroko Konishi, Taichi Kuramochi, Mika Endo, Kunihiro Hattori, Junichi Nezu & Tomoyuki Igawa. (2019) Engineering a bispecific antibody with a common light chain: Identification and optimization of an anti-CD3 epsilon and anti-GPC3 bispecific antibody, ERY974. Methods 154, pages 10-20.
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Lei Han, Huifang Zong, Yuexian Zhou, Zhidi Pan, Jie Chen, Kai Ding, Yueqing Xie, Hua Jiang, Baohong Zhang, Huili Lu, John Gilly & Jianwei Zhu. (2019) Naturally split intein Npu DnaE mediated rapid generation of bispecific IgG antibodies. Methods 154, pages 32-37.
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Xiufeng Wu & Stephen J. Demarest. (2019) Building blocks for bispecific and trispecific antibodies. Methods 154, pages 3-9.
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