Lonza’s GS system wins Elusys anthrax Ab contract
Anthim is a high-affinity humanised antibody (AB) that targets a protein on the surface of Bacillus anthracis, the causative agent of anthrax, neutralising its lethal toxic effects.
Under the terms of its deal with Elusys, Lonza will provide manufacturing process development services and eventually produce the drug using its glutamine synthetase (GS) gene expression system.
Lonza spokesman’ Dominik Werner told Outsourcing-pharma that the collaboration will consist of several stages including the transfer of processes to the firm’s unit in Slough in the UK and the development of pilot batches of the Ab in the 130L to 400L range.
He added that: “Lonza will produce [Anthim for] all of [Elusys’] needs, including Ph III and commercialisation.”
Werner went on to say that the GS system is used by more than 85 global pharma and biotech firms and is involved in the manufacture of five licensed products, including Roche’s Zenapax and MedImmune’s Synagis.
“Lonza has itself created over 250 cell lines using the GS System, many of which have been grown at large-scale and produced product for use in clinical trials and in-market supply.”
He also revealed that: “Many investigators use the GS System, not only to develop a manufacturing process, but as a tool to create recombinant proteins for biological studies.”
In a press statement James Porter, Elusys vice president of manufacturing, said the Basel-based Lonza’s track record in Ab manufacture was the critical factor in winning the contract.
He explained: “Lonza has considerable experience in large-scale manufacturing of monoclonal antibodies and a well established reputation with regulatory agencies for the production of licensed products.”
Anthim hits 75% survival rate
In animal studies reported last year, Anthim achieved a 75 per cent survival rate in primates infected with a lethal dose of the anthracis bacterium when employed within 24 hours of the clinical onset of disease symptoms.
Elusys is developing Anthim as part of a $34m (€24m) contract with the US National Institutes of Health and Department of Defense as part of the government's bio-defense programme.
The agent has already been earmarked for fast-track approval and designated as an orphan drug (OD) by the US Food and Drug Administration (FDA).
GS system goes from strength to strength
Glutamine synthetase is the only enzyme responsible for the biosynthesis of glutamine in mammalian cells and thus, in glutamine-free growth media, is essential for cell survival..
Some biomanufacturing cell lines, such as mouse myeloma, do not express sufficient GS to survive without added glutamine, so with these cell lines a transfected GS gene can function as a selectable marker by permitting growth in a glutamine-free medium.
Others, such as Chinese Hamster Ovary (CHO) cells which are also commonly used for biomanufacture, have enough active GS to survive without exogenous glutamine.
Lonza’s approach has a solution for this as well. In CHO cells the enzyme inhibitor methionine sulphoximine (MSX), is used to inhibit endogenous GS activity such that only transfectants which have the gene can survive.
The GS expression system has proved to be a good earner in recent years, particularly through the licensing deal that Lonza signed with US biotechnology giant Genentech in 2006.
More recently, the Swiss firm agree to combine its technology with BioWa’s Potilligent platform to develop a way of making more potent antibodies with enhanced cell-killing powers.
