Human antibody phage libraries
Challenge

Human antibody phage display libraries are a very valuable resource for isolating antibodies which have therapeutic potential.[1] Such libraries offer an alternative to using mouse immunisation and hybridoma technology which is limited in its therapeutic use due to mouse-derived sequences causing human anti mouse adverse (HAMA) reactions. However, phage display libraries are difficult for Australian researchers to access and use in their research. Such libraries are usually owned by pharmaceutical companies, unwilling to share with academia, or the few large libraries in the public domain are encumbered through licensing restrictions with international universities.

The National Biologics Facility at AIBN/UQ established the need for an Australian-owned phage display library after its experience with a library used under an international material transfer agreement. From this library, NBF isolated an antibody with therapeutic potential in treating Graft vs Host Disease.[2] This antibody is currently under clinical development, but licensing agreements were long-winded and resulted in a significant portion of milestone royalties and future returns going off-shore. NBF has experience in developing human phage display libraries, having made several research-use only libraries in recent years, however these libraries do not have any scope for products to be commercialised in the future.

How did the facility help?

NBF is currently manufacturing a human antibody phage display library which is unencumbered by commercial restrictions. Human ethics approval has been obtained to collect blood samples from healthy adult volunteers who consent for their samples to be used in the library and for future commercialisation. Blood samples are being processed to extract and amplify antibody gene sequences, which are pooled to develop a combinatorial gene library with high diversity.

Outcome

The NBF-Commercial Use human antibody phage display library will be completed early 2017. NBF has received several expressions of interest from researchers across Australia who wish to access the library for antibody discovery purposes. NBF has also had enquiries to provide antibody discovery services where the outcome will be potentially commercialised. NBF plans to distribute the library to Australian researchers under material transfer agreements, and also provide antibody discovery services which won't be restricted to research-use only or by international licensing agreements. This will enable NBF to assist with translational large molecule screening projects.

Background

NBF is a $30 million facility, composed of laboratories, clean rooms and state-of-the-art equipment housed at the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland (UQ), and at the CSIRO Manufacturing/BioMedical Manufacturing in Victoria. Together, the NBF is managed by a team of expert scientists and bioprocess engineers with world-class experience in mammalian, insect, bacterial and yeast cell line development, GLP/ISO9001/cGMP manufacturing in pharmaceutical development. Equipped with a variety of bioreactors, including traditional stirred tank and single-use disposable bioreactors, ranging from 1L to 150L capacity, a range of equipment for fed-batch and continuous perfusion cultures, automated robotic equipment for cell line development, and associated analytical capabilities, the facility is capable of processing large quantities of biologics material through its specialised upstream and downstream processing equipment.

NBF services external clients in the areas of antibody discovery and engineering, mammalian cell line generation, upstream and downstream production and bioprocess development, as well as protein analytics.

 

[1] Dantas-Barbosa C, de Macedo Brigido M, Maranhao AQ. Antibody phage display libraries: contributions to oncology. Int J Mol Sci. 2012;13(5):5420-40.

[2] Seldon TA, Pryor R, Palkova A, Jones ML, Verma ND, Findova M, et al. Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation. Leukemia. 2016 Mar;30(3):692-700.

National Biologics Facility Queensland Node

Level 14, 330 Collins St

Melbourne 3000 VIC

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