Overview

The legal frameworks surrounding synthetic biology are critically important because they determine what type of research can be undertaken, by selecting for research that is both legally allowable and has potential commercial implications. However, scientists often fail to most effectively lobby for frameworks that support what their research actually needs, instead acquiescing to government policy that bows to vested commercial interests.

As a result, UNSW iGEM 2018 has created a scientist’s guide to writing a policy proposal for government change and written an example submission. We have also documented our discussions with various stakeholders in the process, such as normal scientists and the government departments who receive the submissions. UNSW iGEM 2018 also collaborated with other student organisations, including the UNSW Law Society.

UNSW iGEM 2018 discovered, as part of our foray into commercialisation, that patent law for pieces of genetic information is hard to comprehend from the scientific perspective. This is particularly important for scientists, as without patents, it can make commercialisation of their discoveries hard, and thus dis-incentivise funding of their research. It is further complicated by the international nature of research meeting individual countries’ patent law regimes.

Relevance

The legal sphere may seem divorced from the practice of science in the laboratory, but in reality, they are closely intertwined, with three key points of intersection.

Analysis

The Assemblase system has posed a number of legal challenges for the team, with these challenges arising from the very beginning of the project.

Early on, the team had questions about the possibility of patenting the new, invented system. Early advice was sought from one of the team mentors (Daniel Winter), and the advice essentially stated that genetic sequences were not patentable or protectable, and therefore there was no possibility of patenting the invention. However, there was a serious lack of clarity within the advice as to the actual reasons why that was so. Further research was then done into the relevant legal decisions establishing sequence protection law, particularly the High Court of Australia decision in Myriad Genetics v D’Arcy. Such research later showed that in actuality, it was the sequences of the proteins which was not protectable – rather than the actual structure and design of the scaffold. There is an equivalent US decision as well; Association for Molecular Pathology v Myriad Genetics, although the scope of protection differs between the two decisions. Dr Alexandra George was also consulted regarding some of the particular aspects of the law in order for the team to then evaluate if our invention would fall under the protected category.

Issues about patents arose yet again when the team decided to use Spy Tag/Catcher and Snoop Tag/Catcher as part of the scaffold. Patent research revealed that Spy Tag/Catcher held a US patent, but we could not find one for Australia. There is a bilateral US – Australia agreement that governs intellectual property in addition to the worldwide TRIPPS treaty, however the agreement does not make US patents enforceable in Australia. The US-Australia agreement tends more towards ensuring that the systems have similar outcomes and protections once patents are granted, and similar terms for granting patents. As a result, we were confident that we were allowed to use the Spy Tag/Catcher system, and did end up using it in the project, as opposed to the Sdy Tag/Catcher system which wasn’t patented but was much more cross-reactive with the other Tag/Catchers. However, given the extensive research that had to be conducted to arrive at this position, the team began to think about how we might be able to push for systemic change.

As a result, consultations were sought with Lan Le (Research Ethics and Compliance Support) and Brad Walsh (CEO of Minomic International Ltd.). These consultations, in addition to speaking with Carl Stubbings (Head of Commercialisation, Minomic International Ltd.) at our team’s symposium, brought to our attention one other important impact legal protection has on science – it plays a major role in determining to which research the money flows. Lan spoke about how legal (and ethics) approval was becoming a prerequisite for any grant funding, while Brad and Carl spoke about how legal protection allows them to capitalise on their investment into research – which is essential for them to have more funds to reinvest in research. Further research into this area revealed that the link between possible legal protection and funding is quite substantial. For our iGEM team, in applying for grants we found that we our research wasn’t eligible for many opportunities, with many more opportunities for research into direct medical applications, where there is clearly a better chance for a profit to be made.

As a result, our team was convinced that the current balance between legal protection for science and not stifling innovation was not quite right. This position however is not new, being one that is constantly argued over. However, in exploring how we could contribute our voice and experience to the conversation, the team has discovered a ‘missing link’ of communication between science and the law, despite the many important effects that law has on the practice of science. One possible way to re-establish this link is through writing to government, which is why UNSW iGEM 2018 has created a policy guide and example policy submission.

The policy submission, and suggestions for improvement, were critically evaluated and analysed in light of comments from Dr Alexandra George and the Pasteur Paris iGEM team. The Pasteur team particularly gave us insight into the differences between the civil law European regime and the Australian process, and Dr Alexandra George also gave insight into how the French system’s benefits are replicated here, but in a slightly different way.

Integration

The team’s research into the legal frameworks and implications on scientific research has affected the direction of our project. Firstly, it affected the decision of whether to patent the Assemblase system, by providing the framework to discuss the likelihood of a successful protection claim. As legal information gathered suggested that a patent was an unlikely outcome, we refocused the system onto modularity, using ‘ideal’ test enzymes. It also affected the way we consulted with other academics and people in industry, as we were more open with our ideas, and they could give us better feedback (being more directed towards the project).

Figure X: The Assemblase scaffold with the Tag/Catcher systems.

Secondly, it affected the decision of which covalent protein attachment system was going to be chosen to use with the scaffold. Initial legal research had made us aware of the patent system, and further research was undertaken to establish whether an Australian patent was held for the system we wanted to use. We also researched whether that patent would stop our use of the system (educational exceptions to patents) and whether a US patent which did exist would stop our use of the system. Fortunately, using the research we came to a conclusion that the best systems to use (SpyTag/Catcher and SnoopTag/Catcher) were not protected in Australia, and that we could use them. The legal information gathered also led us to present an alternative in case of protection; the use of SnoopTag/Catcher and SdyTag/Catcher systems, being that these were not patented in both relevant countries of the United States and Australia.

There were also several indirect effects of legal systems on our project. Namely, the availability of certain methodologies in sufficient detail to allow them to be replicated within the modelling aspect of the project. It seemed that in some of the key papers, writers were trying to patent part of their research, and so did not publish very many details on their method – which proved to be challenging when our team tried to replicate part of their research using our enzymes. Additionally, it appears that the legal system fed into the lack of funding opportunities available; as outlined above, the lack of legal protection is associated with a lack of funding opportunities, particularly from independent companies, as they look for inventions which can give them a commercial edge in the market.⁵

Outcomes

• How to Write a Policy Submission (Guide for Scientists).
• Example Policy Submission.
• Public discussion on the way law affects science;
• Symposium on the Australian Synthetic Biology Landscape.
• Presentation to an Environmental Humanities university course.

References

1. Productivity Commission 2016, Intellectual Property Arrangements, Inquiry Report No. 78, Canberra. D’Arcy v Myriad Genetics (2015) 258 CLR 334 [20].
2. N V Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1995) 183 CLR 655.
3. Patents Act 1990 (Cth).
4. Andrew Stewart et al, Intellectual Property in Australia (Lexis Nexis Butterworths, 6th ed, 2018).
5. Donald W Light and Joel R Lexchin, ‘Pharmaceutical research and development: what do we get for all that money?’ (2012) 343 British Medical Journal 4348.
6. United States Congressional Budget Office, United States Congress, Research and Development in the Pharmaceutical Industry (2006), 7.
7. CCOM Pty Ltd v Jiejing Pty Ltd (1994) 28 IPR 481.
8. Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253.
9. Association for Molecular Pathology v Myriad Genetics Inc (2013) 569 US 12-389.
10. Powell, D. and Tsourkas, A. (2016). Spycatcher and spytag: universal immune receptors for t cells. WO2017112784A1.
11. US Free Trade Agreement Implementation Act 2004 (Cth) implementing the Australia-United States Free Trade Agreement.
12. Trade Related Aspects of Intellectual Property Rights (TRIPS) Agreement (1993).
13. Yajie Liu et al, ‘Tuning SpyTag–SpyCatcher mutant pairs toward orthogonal reactivity encryption’ (2017) 8 Chemical Science 6577-6582.