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Production of monoclonal antibodies by glycoengineered Pichia pastoris

Paper ID Volume ID Publish Year Pages File Format Full-Text
24745 43534 2009 8 PDF Available
Title
Production of monoclonal antibodies by glycoengineered Pichia pastoris
Abstract

The growing antibody market and the pressure to improve productivity as well as reduce cost of production have fueled the development of alternative expression systems. The therapeutic function of many antibodies is influenced by N-linked glycosylation, which is affected by a combination of the expression host and culture conditions. This paper reports the generation of a glycoengineered Pichia pastoris strain capable of producing more than 1 g l−1 of a functional monoclonal antibody in a robust, scalable and portable cultivation process with uniform N-linked glycans of the type Man5GlcNAc2. N-linked glycan uniformity and volumetric productivity have been maintained across a range of cultivation process conditions including pH (5.5–7.5), temperature (16–24 °C), dissolved oxygen concentration (0.85–3.40 mg l−1) and specific methanol feed rate (9–19 mg g−1 h−1) as well as across different cultivation scales (0.5, 3.0, 15 and 40 l). Compared to a marketed CHO-produced therapeutic antibody, the glycoengineered yeast-produced antibody has similar motilities on SDS-PAGE, comparable size exclusion chromatograms (SEC) and antigen binding affinities. This paper provides proof of concept that glycoengineered yeast can be used to produce functional full-length monoclonal antibodies at commercially viable productivities.

Keywords
Pichia pastoris; Glycoengineering; Antibody; Fed-batch cultivation; Glycosylation
First Page Preview
Production of monoclonal antibodies by glycoengineered Pichia pastoris
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 139, Issue 4, 23 February 2009, Pages 318–325
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering