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Alternative Protein Scaffolds as Novel Biotherapeutics

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Biobetters

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 19))

Abstract

Antibody technology has gone through a long evolution. This review summarizes crucial events during the development of this expanding field, with emphasis on recent advances in the design and manipulation of functional Ig fragments for therapeutic applications. Currently, the challenge is to create next generation types of antibodies that offer improvements over classical MAbs with regard to biomolecular attributes and clinical performance. Bispecifics such as BiTEs and DARTs offer high potency due to a novel mode of action but involve complicated construction. Apart from established Ig fragments such as Fabs, scFvs and domain antibodies, alternative binding proteins are increasingly exploited as therapeutics. These engineered “protein scaffolds”, which are based on non-immunoglobulin proteins furnished with novel binding sites, offer improved manufacturability, facilitate new functional combinations and, thus, likely enable unique therapeutic modes of action to yield promising biobetters. The four most advanced scaffold technologies, Adnectins, Affibodies, Anticalins and DARPins, which were developed beyond the academic research stage and have reached clinical studies, constitute another focus of this review.

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Authors and Affiliations

  1. XL-protein GmbH, 85354, Freising-Weihenstephan, Germany

    Michaela Gebauer

  2. Lehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85350, Freising-Weihenstephan, Germany

    Arne Skerra

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  1. Michaela Gebauer
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Correspondence to Arne Skerra .

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  1. Centre for Drug Evaluation and Research, Food and Drug Administration, Division of Biotechnology Review and Research III, Office of Biotechnology Products, Silver Spring, Maryland, USA

    Amy Rosenberg

  2. Genentech, Inc., South San Francisco, California, USA

    Barthélemy Demeule

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Gebauer, M., Skerra, A. (2015). Alternative Protein Scaffolds as Novel Biotherapeutics. In: Rosenberg, A., Demeule, B. (eds) Biobetters. AAPS Advances in the Pharmaceutical Sciences Series, vol 19. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2543-8_13

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