1. Academic Validation
  2. Application of platform process development approaches to the manufacturing of Mabcalin™ bispecifics

Application of platform process development approaches to the manufacturing of Mabcalin™ bispecifics

  • J Biotechnol. 2023 Nov 20:377:13-22. doi: 10.1016/j.jbiotec.2023.10.003.
Stefanie Wachter 1 Thibaut Angevin 2 Niket Bubna 3 Adelene Tan 2 Adam Cichy 2 David Brown 3 Leslie S Wolfe 3 Ryan Sappington 3 Edward Lilla 3 Luke Berry 3 Dane Grismer 3 Christian Orth 2 Milan Blanusa 2 Sigma Mostafa 3 Hitto Kaufmann 2 Karin Felderer 2
Affiliations

Affiliations

  • 1 Pieris Pharmaceuticals GmbH, Zeppelinstr. 3, Hallbergmoos 85399 Germany. Electronic address: stefaniemwachter@gmail.com.
  • 2 Pieris Pharmaceuticals GmbH, Zeppelinstr. 3, Hallbergmoos 85399 Germany.
  • 3 KBI Biopharma, 4117 Emperor Blvd, Suite 200, Durham, NC 27703, USA.
Abstract

Bispecific biotherapeutics offer potent and highly specific treatment options in oncology and immuno-oncology. However, many bispecific formats are prone to high levels of aggregation and instability, leading to prolonged development timelines, inefficient manufacturing, and high costs. The novel class of Mabcalin™ molecules consist of Anticalin® proteins fused to an IgG and are currently being evaluated in pre-clinical and clinical studies. Here, we describe a robust high-yield manufacturing platform for these therapeutic fusion proteins providing data up to commercially relevant scales. A platform upstream process was established for one of the Mabcalin bispecifics and then applied to other clinically relevant drug candidates with different IgG target specificities. Process performance was compared in 3 L bioreactors and production was scaled-up to up to 1000 L for confirmation. The Mabcalin proteins' structural and biophysical similarities enabled a downstream platform approach consisting of initial protein A capture, viral inactivation, mixed-mode anion exchange polishing, second polishing by cation exchange or hydrophobic interaction chromatography, viral filtration, buffer exchange and concentration by ultrafiltration/diafiltration. All three processes met their target specifications and achieved comparable clearance of impurities and product yields across scales. The described platform approach provides a fast and economic path to process confirmation and is well comparable to classical monoclonal antibody approaches in terms of costs and time to clinic.

Keywords

Anticalin® protein; Biologics manufacturing; Bispecifics; Fusion proteins; Mabcalin™ bispecifics; Process development.

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