Catalysis
www.chemicalsknowledgehub.com Biocatalysis – How secret should it be?
Professor Tom Moody (VP Technology Development and Commercialisation), Dr Steve Taylor and Dr Stefan Mix (Head of Biocatalysis) highlight how Almac is approaching state-of-the-art technology development and how they guide their customers through the process of deciding how to best protect their commercial interests in relation to biocatalysis.
T
he pharmaceutical, health care and associated chemical industries are strategically outsourcing more and more of their activities. Recent trends indicate that this is not slowing down when it comes to procurement of advanced intermediates and building blocks for their speciality chemical products. In many cases, biocatalytic processes lie at the core of such product manufacture, bringing not just their green credentials but tangible economic benefits, too, through route shortening, reducing energy requirements and a reduction in reagent and solvent use. The service sector is changing
rapidly to meet customer demands in relation to quality, security of supply, timelines and cost, with opportunities arising for companies that can deliver on these. Quality, customer care and delivery are now baseline expectations and demonstration of additional added value with its associated intellectual property at the right price is taking centre-stage. A key question that customers are now asking is whether a process should be patented or whether it should be kept secret as industrial know-how.
The rise and rise of biocatalysis The synthetic attractiveness of enzyme technology stems from being able to use it for catalysis of many types of chemical reactions, and especially the unequalled ability of enzymes to recognize subtle differences in molecular shape. This, all under conditions that may be no more daunting than those found in a typical kitchen. Such impressive versatility is illustrated in Figure 1using a hypothetical molecule.
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Figure 1 – An illustration of enzyme versatility. Biocatalysis was once the
preserve of specialists working with limited in-house collections of enzymes and cultures. A revolution in molecular biology has enabled the rapid development of much larger and more diverse enzyme collections at Almac and other companies, and has also enabled astonishing improvements in enzyme process performance to be realized. This has elevated biocatalysis from a niche to a widely applied mainstream technology, relevant to a diverse range of chemical transformations. The reason for the surge in
the application of this green technology, in our view, is simply that success breeds success. Unlike ten years ago, we now have a suite of supporting technologies that can really make a difference in enzyme development, such as bioinformatics, enzyme evolution and high throughput screening, as well as substrate and process engineering. Figure 2 highlights the options for driving bioprocessing
from enzyme selection (enzymes are derived from metagenomics, bioinformatics, protein engineering and in silico design), process optimization (process and substrate engineering, DOE, application of process intensification tools such as ultrasound and continuous flow, and enzyme immobilization) and actual delivery of API (GMP or non-GMP), advanced intermediate or fine chemical. Inevitably, developing and exploiting cutting-edge biocatalysis technologies generates intellectual property and is accompanied by a need to protect, where possible, the processes and products surrounding it. It is useful to consider how patenting attitudes have changed as the technology has evolved and expanded in recent years.
The changing landscape of IP strategy in biocatalysis In the early days of biocatalysis it was enough to simply patent an enzyme catalyzed reaction without too much definition of the enzyme
beyond its basic classification such as dehydrogenase or nitrilase. So, a claim could be very broad as in the following example taken from EP0332379B1, granted in 1996. “A process for the production
of an L-α-amino acid which comprises causing a microorganism
having enantioselective nitrile- hydrolyzing activity to act at a pH in the range of 8-12 on one or more α-aminonitrile compounds represented by the following general formula……” Such an unspecific claim would be unacceptable today, since it quickly became common knowledge that enzymes are extremely powerful and versatile catalysts. It is no longer surprising or considered inventive that an un- specified biocatalyst might perform a certain biotransformation, even if it had never been demonstrated or published. With biocatalysis in its embryonic
years, cloning, expression and sequencing technology was driving a revolution in the health
Summer 2020
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