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Antibody Methods and Protocols pp 247–263Cite as

Bispecific Antibody Derivatives Based on Full-Length IgG Formats

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 901))

Abstract

Monoclonal antibodies have emerged as an effective therapeutic modality, and numerous antibodies have been approved for the treatment of several severe diseases or are currently in clinical development. To improve their therapeutic potential, monoclonal antibodies are constantly evolved by protein engineering. Particularly, the generation of bispecific antibodies raised special interest because of their ability to bind two different antigens at the same time, and the efficiency of these formats has been demonstrated in several clinical and preclinical studies. Up to now, the major drawbacks in using bispecific antibodies as a therapeutic agent have been difficult design and low-yield expression of homogeneous antibody populations. However, major technological improvements were made in protein engineering during the last years. This allows the design of several new IgG-based bispecific antibody formats that can be prepared in high yields and high homogeneity using conventional expression and purification techniques. Especially, recent development of IgG-fusions with disulfide-stabilized Fv fragments and of CrossMab-technologies facilitates the generation of bispecific antibodies with IgG-like architectures. Here we describe design principles and methods to express and purify different bispecific antibody formats derived from full-length IgGs.

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Author information

Authors and Affiliations

  1. Large Molecule Research, Roche Pharma Research and Early Development, Penzberg, Germany

    Michael Grote, Alexander K. Haas, Wolfgang Schaefer & Ulrich Brinkmann

  2. Large Molecule Research, Roche Pharma Research and Early Development, Schlieren, Switzerland

    Christian Klein

Authors
  1. Michael Grote
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  2. Alexander K. Haas
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  3. Christian Klein
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  4. Wolfgang Schaefer
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  5. Ulrich Brinkmann
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Corresponding author

Correspondence to Ulrich Brinkmann .

Editor information

Editors and Affiliations

  1. The Jackson Laboratory, Main Street 600, Bar Harbor, 04609, Maine, USA

    Gabriele Proetzel

  2. Novartis Pharma AG, Postfach, Basel, 4002, Switzerland

    Hilmar Ebersbach

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Grote, M., Haas, A.K., Klein, C., Schaefer, W., Brinkmann, U. (2012). Bispecific Antibody Derivatives Based on Full-Length IgG Formats. In: Proetzel, G., Ebersbach, H. (eds) Antibody Methods and Protocols. Methods in Molecular Biology, vol 901. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-931-0_16

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  • DOI: https://doi.org/10.1007/978-1-61779-931-0_16

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-930-3

  • Online ISBN: 978-1-61779-931-0

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