The ARC Training Centre in Biopharmaceutical Innovation aims to transform Australia’s growing biopharmaceutical industry, an advanced manufacturing capability contributing to Australia’s economic growth.

The ARC Training Centre for Biopharmaceutical Innovation is multi-million dollar Australian Government initiative under the Australian Research Council Industrial Transformation Research Programme.

The CBI combines the research and development, and manufacturing expertise and capabilities of the industry partners and The University of Queensland (UQ). Industry-driven research projects ensures industry-ready graduates drive growth in the sector.  The CBI housed within the Australian institute for Bioengineering and Nanotechnology (AIBN) at UQ and collaborates with the National Biologics Facility, also housed within the AIBN. The Centre combines the research and development, and manufacturing expertise and capabilities of the industry partners and the University of Queensland. Industry-driven research projects ensures industry-ready graduates drive growth in the sector.

The Centre will conduct research projects within three thematic areas:

  • Discovery of new biopharmaceuticals and diagnostic agents
  • Development of mammalian cells as factories for recombinant protein production
  • Manufacturing of biopharmaceuticals

 

The training and research outcomes of the CBI will lead to new biopharmaceuticals and antibody-based reagents, enhanced production methods, improved manufacturing capabilities and a cohort of specialist scientists, which will benefit the economy and positively impact health-care.

The CBI partners with leading Australian stakeholders in the biologics industry   including CSL Limited, GE Healthcare, the Australian Red Cross Blood Service and Patheon Biologics Australia Pty Ltd. The CBI aims to blend research excellence with industry partner experience and know-how.

CBI will conduct research projects within three thematic areas

Discovery of new biopharmaceuticals and diagnostic agents

The research plan for thematic research area 1 is directed towards the discovery of new biopharmaceuticals and mAbbased reagents utilising innovative methodologies in therapeutic and diagnostic mAb discovery, as well as the development of platform technologies for mAb delivery to intracellular targets. The plan incorporates five distinct projects that will run in parallel, with one student per project.

Development of mammalian cells as factories for protein manufacturing

The paradigm shift for researchers from protein expression to protein manufacturing is often an early roadblock when researchers embark on the translation of research. The objective of thematic research area 2 will be to understand cellular bottlenecks for production of therapeutic proteins and bypass those bottlenecks by identifying and modifying relevant cellular pathways, engineering the therapeutic proteins for improved expression and/or manipulating the manufacturing process.7, 8 The plan for thematic research area 2 incorporates two separate projects that will be undertaken in parallel, with one student per project.

Manufacturing of biopharmaceuticals

Large-scale cell culture and downstream processing represent the greatest driver of cost of goods (COGs) for biopharmaceuticals. Process improvements to provide gains in product quality, yield and characterisation are the objective for thematic research area 3. The plan includes seven separate projects, each to be conducted in parallel with one student per project.

Antibodies against Intracellular Targets

Antibodies against Intracellular TargetsIntracellular processes including protein transport, transcription and signalling present a range of new potential targets that could have application in the treatment of a variety of disease indications. The screening of chemical libraries for binders to intracellular targets has had limited success due to (i) the relative lack of binding clefts and hydrophobic pockets compared to those located on cell surface proteins and (ii) the small “footprint” to which a small molecule can bind on an extensive protein surface interface. As an alternative, antibody fragments are being explored as molecular entities that are capable of disrupting protein-protein interactions within the cell, traditionally thought to be undruggable.5 This project will investigate strategies for intracellular delivery of antibodies and antibody fragments, along with assessing the resulting impact on cellular processes. An antibody against the transcription factor SOX18 (created at AIBN and IMB) will be used as the initial model system for intracellular antibody delivery. A successful outcome of this project will be the establishment of platform technology for the delivery of antibody fragments to intracellular targets.

 

Project contacts

Project Leader Dr Mathias Francois
Chief Investigators Prof Stephen Mahler
Dr Martina Jones
Industry Partner CSL

Development of antibodies against human neutrophil antigens

Development of antibodies against human neutrophil antigensHuman neutrophil antigens (HNAs) are a group of 5 glycoproteins that are expressed on human neutrophils, and in some cases, also on other cells and tissues. Endogenous antibodies against HNAs have been implicated in cases of alloimmune neonatal neutropenias, autoimmune neutropenias, febrile transfusion reactions and transfusion-related acute lung injury (TRALI). The availability of mAbs to HNAs permits the use of solid phase assays to detect endogenous antibodies specific to these antigens. While mAb reagents against HNA-1, HNA-2, HNA-4 and HNA-5 antigens are available, there are not yet any mAbs available for HNA-3. This project aims to develop mAbs against the two alleles of HNA-3 that can then be used to develop cell-based assays to detect anti-HNA-3a and anti-HNA-3b antibodies in blood donors. Furthermore, this project aims to use the anti-HNA-3 mAbs in existing in vitro transfusion models to help understand the mechanisms by which TRALI develops.

Lead investigator  Prof Stephen Mahler
Research group CBI
Industry Partner ARCBS; PIs, Tung, Flower and Irving (ARCBS)

Identifying novel red blood cell targets as a basis for development of biopharmaceuticals for treatment of infectious diseases Identifying novel red blood cell targets as a basis for development of biopharmaceuticals for treatment of infectious diseases

Identifying novel red blood cell targets as a basis for development of biopharmaceuticals for treatment of infectious diseasesUsing N-ethyl-N-nitrosourea (ENU)-induced mutagenesis, ARCBS has identified a unique murine pedigree with a splice-site mutation in a functionally important domain of a gene encoding an acetyltransferase. Red Blood Cells (RBC) from homozygous mutants from this pedigree demonstrate significant modifications of carbohydrates and lack the erythroid lineage marker TER-119. We plan to investigate the extent to which these changes modify the susceptibility to infection for pathogens that target developing and mature cells of the erythroid lineage. We will compare RBC from homozygous and wild type (WT) mice to characterise the RBC surface and identify novel RBC targets to be used as a basis for the development of biopharmaceuticals for treatment of diseases where infectivity is mediated through RBC receptors (e.g. Malaria, Parvovirus (B19)).

Lead investigator Prof Kirill Alexandrov 
Research group CBI
Industry Partner ARCBS; PIs, Dean, Flower and Irving (ARCBS)

 

Isolation and characterisation of novel antibodies against cell-surface biomarkers Isolation and characterisation of novel antibodies against cell-surface biomarkers

Isolation and characterisation of novel antibodies against cell-surface biomarkersIntegral membrane proteins are attractive targets for research, diagnostic and therapeutic applications, as they act as biomarkers to define a particular cell type, developmental stage or disease type. As such, mAbs against cell-surface biomarkers are highly sought after as biological therapeutics, laboratory reagents or diagnostic reagents. Based on antibody phage display methodologies.6 AIBN has developed novel whole-cell biopanning techniques to improve the efficiency of screening antibody libraries on whole cells displaying biomarkers. The proposed collaborative project aims to pool the skills of AIBN and CSL researchers to further optimise the whole cell biopanning technique to isolate new mAbs against specific cell surface biomarkers that are of interest to CSL. The outcomes of this project would be further innovations in whole cell panning methodologies, as well as isolation of new antibodies of therapeutic significance.

Lead investigator  Prof Stephen Mahler
Research group CBI
Industry Partner CSL; PI, Panousis (CSL)

Isolation of novel typing antibodies that bind hybrid glycophorin on red blood cells

Isolation of novel typing antibodies that bind hybrid glycophorin on red blood cellsTyping reagents for hybrid glycophorin blood groups that are rare in Caucasians, but with prevalence of up to 8% in East Asian ethnic groups, are unavailable despite repeated attempts by various groups to use conventional approaches to produce useful mAbs. We will utilise naive human phage libraries to develop reagents that react with RBC with a phenotype defined by the most common hybrid glycophorin but not with pooled human RBC that do not display these antigens. The usefulness of the mAb produced as a typing reagent will be assessed by binding to the target hybrid glycophorin detected by flow cytometry. Subsequently reactivity using the standard immunohaematological agglutination based techniques will be assessed as well as characterising other features required for typing reagents, such as long term stability at room temperature.

 

Lead investigator  Prof Stephen Mahler
Research group CBI
Industry Partner ARCBS; PIs, Flower and Irving (ARCBS)

Engineering and production of recombinant proteins with appropriate glycostructures for early in vivo studies

The majority of proteins generated by the Recombinant Protein Group within CSL to date for in vivo use are mAbs that are not dependent on post-translational modifications for activity. However, CSL now has several projects that are not antibody-focussed and require the generation of complex proteins, including FVII-HSA, FVIII, AAT and C1Inhibitor. The correct glycosylation and, in particular, sialylation of these recombinant therapeutic proteins are important for in vivo animal studies, as glycostructures can influence the pharmacokinetics and immunogenicity of the protein.11 The project aims to understand the effect of host cell line, manipulation of enzymes in the protein glycosylation pathway and culture conditions on glycostructures in recombinant therapeutic proteins. The project will also compare proteins expressed in the Wave Bioreactor to those in a stirred tank bioreactor, with respect to posttranslational modifications and quality.

 

Project Leader Dr Benjamin Schulz
Chief Investigator Dr Christopher Howard
Industry Partner CSL

Investigating differential expression of antibodies and coagulation factors at the level of cellular processing

This project will investigate and compare the differential expression of different classes of proteins, namely antibodies and coagulation factors. Expression of antibodies is well characterised, with consistent yields of 3 g/L or better in optimised conditions. Commercial production of antibodies is therefore a fairly generic process. Conversely, coagulation factors are extremely difficult to express at high levels and each factor represents a unique manufacturing challenge. The project seeks to understand what cell machinery / processing mechanisms create the bottlenecks in production of recombinant coagulation factors. 9, 10 The project will involve metabolomic analysis, as well as protein and cell engineering. A successful outcome to this project will lead to yield improvements for the commercial production of recombinant coagulation factors (and potentially other therapeutic proteins), resulting in improved productivity and reduced manufacturing costs.

Project Leader Dr Benjamin Schulz
Chief investigators Dr Mark Hodson
Industry Partner CSL

Cell line development for high cell density culture Cell line development for high cell density culture

The Patheon process for high density cell culture (Patheon XD® Upstream Processing (USP) technology) can result in up to a 25 fold increase in bioreactor output (cell density). CHO cell lines can be engineered to deliver maximal performance and productivity. The proprietary Patheon XD® USP bioprocess may be improved for suitability to high density culture, by engineering CHO cell lines with acquired properties that favour high density. In this project, development of a cell line(s) optimised for high density cell culture, utilising CRISPR and other cell line engineering techniques, will be investigated.

 

Lead investigator Dr Esteban Marcellin
Research group CBI
Industry Partner Patheon; PI, Shave (Patheon)

Comparability studies of biopharmaceuticals produced by fed-batch or perfusion culture Comparability studies of biopharmaceuticals produced by fed-batch or perfusion culture

This project is focussed on upstream bioprocessing and investigates the similarity (identity) of recombinant protein biopharmaceuticals produced in batch culture compared to the same proteins produced in continuous culture. It will involve extensive physico-chemical characterisation using a variety of highly sophisticated analytical techniques. Of specific interest is the extent to which product characteristics can be manipulated using continuous process parameters (i.e. perfusion rate, bleed rate, temperature, pH, and critical media components for quality issues e.g. sugars).12, 13 The project could explore the design envelope for continuous bioprocesses and the potential for these to better meet biosimilar specifications. A successful outcome to this project will be knowledge into the effect of manufacturing process on the molecular identity of the therapeutic protein product, allowing the manufacturer to understand the potential impact of changes to the manufacturing process.

 

Lead investigator Dr Mark Hodson (AIBN)
Research group CBI
Industry Partner CSL; PIs, Glover, Sandford and Lee (CSL).

Development of continuous downstream processing strategies incorporating continuous chromatography

This project will develop and evaluate a periodic counter current (PCC) chromatography and straight-through processing (STP) continuous three-step mAb purification process. Process intensification by implementing continuous or semi-continuous downstream processes in mAb production, for example, can contribute to significant cost-savings and improved throughput. Continuous processing also offers the possibility of increased automation of the process. The project will develop these bioprocesses using model proteins, thereby developing a new, innovative bioprocess platform for the large scale production of mAbs.

 

Lead investigator  Dr Chris Howard
Research group CBI
Industry Partner Collaborative project with GE, CSL and Patheon.

Enhancing primary recovery from perfusion cultures

Primary recovery or clarification represents the first of many downstream stages for the purification of high value biopharmaceutical products such as mAbs. The clarification process for fed-batch mode may involve the use of depth or pad filtration for the removal of cells and other debris in mammalian cell cultures. However when examining perfusion cultures, there is a significant bottleneck as current technologies are unable to overcome the extreme levels of cell biomass. With new developments in continuous- and perfusion-based culturing methods, there are increasing interests in complementing these methods with innovations in downstream processing. This project will focus on developing new, efficient methods for cell separation, keeping in mind the bioengineering associated with scale-up.

 

Lead investigator  Prof Stephen Mahler
Research group CBI
Industry Partner Patheon; PI, Shave (Patheon)

Examining metabolic demands for continuous bioprocessing

The metabolic demands of a bioproduction cell line are inherited genetically, however gaining an understanding of these demands can have a significant impact on the quantity and quality of the product. As new technologies evolve around complete profiling of nutrients and metabolites in spent media analysis, the mantra is towards automation of current off-line process analytical technology (PAT) as an on-line feedback mechanism. This project will investigate real time control of critical bioprocess parameters, as a value proposition in the attempt to develop an automated bioprocess system.

Lead investigator  Prof Stephen Mahler
Research group CBI
Industry Partner

Patheon; PI, Crowley (Patheon)

Membrane-based separations for biopharmaceutical purification

Membrane-based systems have utility within a number of unit bioprocesses, and in purification offer some advantages over chromatography including overcoming solute diffusion limitations. Membrane chromatography can be used for purification of mAbs and other biomolecules. In membrane chromatography, the ligand, for example Protein A, is covalently attached to a membrane of regenerated cellulose. The pore size of the membranes is larger than those of chromatography beads enabling capture and polishing at much higher flow rates. This project will investigate integration of these technologies into biopharmaceutical manufacturing processes utilising model biopharmaceuticals.

Lead investigator  Prof Stephen Mahler
Research group CBI
Industry Partner GE and Patheon joint project; PIs, O’Meara (GE), Shave (Patheon).

Professor Stephen Mahler

Director
Centre for Biopharmaceutical innovation
Senior Group Leader
Australian Institute for Bioengineering and Nanotechnology 


Dr Martina Jones

Deputy Director
Centre for Biopharmaceutical innovation
Research Fellow
Australian Institute for Bioengineering and Nanotechnology


Nancy Eluigwe

Centre Manager
Centre for Biopharmaceutical innovation


Professor Kirill Alexandrov

Professorial Research Fellow
Institute for Molecular Bioscience 
Affiliate Professor & Group Leader
Australian Institute for Bioengineering and Nanotechnology


Professor Ross Barnard

Professor
School of Chemistry and Molecular Biosciences, Faculty of Science
Affiliated Professor
Centre for Plant Science, Queensland Alliance for Agriculture and Food Innovation


Associate Professor Mathias Francois

Principal Research Fellow
Institute for Molecular Bioscience


Professor Peter Gray

Professorial Research Fellow
Australian Institute for Bioengineering and Nanotechnology


Dr Mark Hodson

Affiliate Research Fellow
The University of Queensland Diamantina Institute, Faculty of Medicine
Affiliate Research Fellow
School of Pharmacy, Faculty of Health and Behavioural Sciences


Dr Christopher Howard

Research Fellow
Centre for Advanced Imaging 
Affiliate Research Fellow
Australian Institute for Bioengineering and Nanotechnology


Associate Professor Linda Lua

Director, PEF
Australian Institute for Bioengineering and Nanotechnology


Mr Geoffrey Osborne

Director of Flow Cytometry
Queensland Brain Institute 
Director of Flow Cytometry
Australian Institute for Bioengineering and Nanotechnology


Dr Benjamin Schulz

NHMRC Career Development Fellow
School of Chemistry and Molecular Biosciences, Faculty of Science


Professor Paul Young

Head of School
School of Chemistry and Molecular Biosciences, Faculty of Science
Affiliate Professor
Australian Institute for Bioengineering and Nanotechnology 
Affiliated Professor
Institute for Molecular Bioscience 


Professor Lars Nielsen

Senior Group Leader
Australian Institute for Bioengineering and Nanotechnology


Dr Esteban Marcellin

Associate Group Leader
Australian Institute for Bioengineering and Nanotechnology


Dr Cristiana Dal'Molin

Lecturer
School of Chemical Engineering
Research Fellow
Australian Institute for Bioengineering and Nanotechnology


 

CSL Ltd

CSL is a global specialty biotherapeutics company that aims to help people with life-threatening medical conditions live a full life by developing and delivering innovative life-saving biotherapies.

With major facilities in Australia, Germany, Switzerland, United Kingdom and the U.S., CSL employs over 17,000 employees working in more than 30 countries.


Patheon Biologics Pty Ltd

Patheon Biologics is a global company within the life and material sciences industry that delivers innovative products aimed at improving quality of life. The company's Biologics headquarters are in the Netherlands, with locations on five continents.

Patheon offers services across the value chain, combining the corporate strength of a large multi-national corporation with the focus and flexibility needed in successful partnerships with biopharmaceutical customers.


Australian Red Cross Blood Service

The Australian Red Cross Blood Service is a division of the Australian Red Cross. The organisation is funded by the federal, state and territory governments of Australia to supply the community with safe, high quality blood and blood products, as well as organ and bone marrow services for transplantation.


GE Healthcare

GE Healthcare is shaping a new age of patient care by providing transformational medical technologies and services.

GE’s broad expertise in medical imaging and information technologies, biopharmaceutical manufacturing technologies, drug discovery, patient monitoring systems, medical diagnostics, performance improvement and performance solutions services help their customers to deliver better care that is affordable to more people around the world.

Director

Professor Stephen Mahler
T: +61 7 3365 4172 
M: +61 412 012 844
E: s.mahler@eng.uq.edu.au

Centre Manager

Nancy Eluigwe 
T: +61 7 3346 4268
F: +61 7 3346 63973
E: n.eluigwe@uq.edu.au

Mailing/Delivery Address

Australian Institute for Bioengineering
and Nanotechnology (AIBN)
Corner College and Cooper Rds (Bldg 75)
The University of Queensland
Brisbane Qld 4072
Australia