Innovation pursuit in synthetic biology: an analysis of the relationship between the current innovation models and the research exemption in synthetic biology
Master Law & Technology Tilburg University, Tilburg Law School by M. van der Sluis (ANR 357164) to defend on June 12, 2019 in front of the exam committee composed of Assistant Professor M. Husovec and Mr. J.P. Waterson
M van der Sluis – U1258779
Acknowledgements
This thesis: “Innovation pursuit in synthetic biology: an analysis of the relationship between the current innovation models and the research exemption in synthetic biology”, is the final element of the curriculum of the Master Law & Technology at Tilburg University. During my time as a student at Tilburg Law School, I have obtain a tremendous amount of academic knowledge and the skills necessary to start my legal career. Through my two master programs, I have come to realize how incredibly interesting intellectual property rights are and I therefore aspire to continue working in this area of law in the future.
With regard to this thesis, I would like to express my sincere gratitude towards several individuals. First, I would like to thank my supervisors M. Husovec and J.P. Waterson for their constructive comments, guidance and reassurance. Furthermore, my parents deserve full gratitude for their unconditional support, early morning wake-up calls and thorough review sessions. In addition, my brother Anton desires special credits for improving my English writing skills. Finally, I would like to thank all the friends I made during classes and consecutive days in the library as well as my partner for always being so supportive.
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TABLE OF CONTENT
1.Introduction ...... 6 1.1 Background ...... 6 1.1.2. Innovation ...... 7 1.1.3. Open source vs Closed proprietary ...... 8 1.1.4. Research exemption system ...... 8 1.2. Research purpose and research question ...... 9 1.3. Societal and scientific relevance ...... 10 1.4. Methodology and overview ...... 11 2. Synthetic biology framework ...... 13 2.1. Introduction ...... 13 2.2. Development of synthetic biology ...... 13 2.3. Research areas and applications ...... 14 2.4. Application concerns ...... 17 2.5. Regulatory framework ...... 20 2.5.1. Synthetic biology’s regulatory framework ...... 20 2.6. Conclusion ...... 22 3. Synthetic biology’s innovation models ...... 23 3.1. Introduction ...... 23 3.2. Closed proprietary model ...... 23 3.2.1. Proprietary model ...... 23 3.2.2. Closed proprietary model ...... 25 3.2.3. Requirements for patentability ...... 26 3.2.4. Synthetic biology patenting ...... 27 3.2.5. Drawbacks of closed proprietary model ...... 29 3.3. Open source model ...... 31 3.3.1. Open source software ...... 31 3.3.2. Types of openness ...... 32 3.3.3. Synthetic biology’s open source ...... 34 3.3.4. Drawbacks open source ...... 37 3.4. Conclusion ...... 40 4. Synthetic biology’s research exemption system ...... 41 4.1. Introduction ...... 41 4.2. Research exemption ...... 41 4.2.1. Background ...... 41
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4.2.2. Research exemption system ...... 43 4.2.2. Relevance for synthetic biology ...... 44 4.3. Possible flaws of the existing research exemption system ...... 45 4.3.1. Suggestions for synthetic biology ...... 50 4.4. Analysis of the (improved) innovation model ...... 54 4.4.1. Recap of the background...... 54 4.4.2. Analysis of the innovation models in synthetic biology ...... 56 4.5. Conclusion ...... 59 5. Concluding remarks ...... 61 Bibliography ...... 65
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List of abbreviations BPA BioBrick® Public Agreement DIY Do-It-Yourself E.coli Escherichia coli ed/eds editor/editors EPC European Patent Convention et al. et alia (and others) EU European Union EUSynBioS European Association of Synthetic Biology Students and Postdocs GMMs Genetically Modified Microorganism GMOs Genetically Modified Organisms gTME global transcription machinery engineering tool ibid ibidem (in the same source) iGEM International Genetically Modified Machines IGSC International Gene Synthesis Consortium MIT Massachusetts Institute of Technology n (foot)note OJ Official Journal OpenMTA Open Material Transfer Agreement OSI Open Source Initiative R&D Research and development SBOL Synthetic Biology Open Language TRIPS Trade-Related Aspects of Intellectual Property Rights UPC Unified Patent Court US United States WTO World Trade Organization
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Introduction
1.1 Background
Over the last few decades, synthetic biology emerged as a new field of technology, operating at the intersection between biotechnology, software and engineering.1 Although this new field of science has no generally accepted definition, it is characterized by the shift from creating new biological entities through the combining of naturally occurring organisms, to the manufacturing of these new biological entities from scratch.2 An increased focus on interdisciplinary research, improved technologies and the combination of several scientific research areas led to the emergence of synthetic biology.3 As this field of science has been said to: “supplant the world created by Darwinian evolution with one created by us”,4 expectations are quite high. However, scientists working in the area of synthetic biology are more modest than this and focus merely on reconstructing biological parts, genomes or cells performing new functions.5 An example of a product of synthetic biology is the previously too expensive medicine for malaria, which can now be produced on a large scale.6 Outside the medical sphere, the production of “green” synthetically created fuels in the form of cellulosic ethanol has likewise attracted attention.7 Furthermore, scientists have created a synthetic environmentally friendly version of the indigo paint used for dyeing blue denim jeans8 and scientists in the food sector are exploring the possibility of synthetic meats which could have major implications.9
1 Sapna Kumar & Arti K. Rai, ‘Synthetic Biology: The Intellectual Property Puzzle’ (2007) 85 Texas Law Review 1744, 1747. 2 Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 3-4 https://ssrn.com/abstract=2153957 accessed 1 December 2018. 3 ibid 3. 4 Michael Specter, ‘A Life of Its Own: Where Will Synthetic Biology Lead Us?’ The New Yorker (New York, 28 September 2009)
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1.1.2. Innovation
Even though these developments seem very promising, the field of synthetic biology has not yet matured and needs to grow before being industrially applicable on a large scale.10 This growth requires innovation which, in order to be responsible innovation, should not only be focused on prosperity but also on international responsibility.11 To achieve this innovation and bring synthetic biology to the next level, there is a need for incentivized scientists that create inventions while complying with relevant regulation.12 There are several views on how this innovation can be best achieved in synthetic biology.13 Some scientists working in synthetic biology, believe this innovation can be achieved through an open source system that facilitates the free exchange of ideas.14 This open source system creates a community of researchers that not only share resources and promote creativity, but most importantly, accomplish together what none can achieve individually.15 Within this community several scientists share their knowledge, in the broadest sense of the word, through the framework of institutions16 like the Registry of Standard Biological Parts (the Registry)17 and the annual International Genetically Modified Machines (iGEM) competition for example.18 These institutions, and the subsequent sharing therein, thrive on the so-called: “Get & Give principle”.19 This principle encourages synthetic biologists to use, but also reuse what colleagues have invented and is already entered in the Registry, with the intention of returning any new genetic sequences they discover to this Registry.20
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1.1.3. Open source vs Closed proprietary
In contrast, in biotechnology, the ancestor of synthetic biology, the focus has mostly been on stimulating innovation through a traditional system of ‘closed’ intellectual property rights involving patents.21 This raises questions as to why this traditional closed propriety model would not likewise be appropriate for stimulating innovation in synthetic biology. Advocates of the open source model in synthetic biology, critique this closed propriety model for hindering innovation by creating a: “tragedy of the anti-commons”22 and “patent thickets”. 23 In return, critics of the open source approach argue that this open source is lacking a platform infrastructure for the exchange of ideas and is not incorporating sufficient safety measures needed for the further development of synthetic biology.24 In addition, they argue that a closed proprietary model is necessary to incentivize investment and ensure innovation in this field.25 The reoccurring dilemma in synthetic biology seems to be how to provide intellectual property protection in a way “without stifling the openness that is so necessary to progress”.26
1.1.4. Research exemption system
Minssen et al. recognized this need to stimulate innovation and gave a few recommendations, which could be beneficial to the development of innovation in synthetic biology.27 One of the recommendations involves the ‘research exemption system’ within current intellectual property legislation, more specifically within patents.28 The research exemption system under European Member States national legislation29 provides researchers with a similar freedom to learn from each other and build on each other’s knowledge as the open source supporters desire, but does
21 Christopher M Holman, ‘Developments in Synthetic Biology Are Altering the IP Imperatives of Biotechnology’ (2014) 17 Vanderbilt Journal of Entertainment and Technology Law 385, 441. 22 Torrance (n 14) 216. 23 Minssen & Wested (n 2) 1. 24 See Grewal (n 15) and Yi-Chen Su, ‘Redefining Open Source for Synthetic Biology' (Thesis, National Chung Hsing University 2012) 5
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M van der Sluis – U1258779 so from a closed proprietary system.30 This raises questions as how this research exemption system fits into the aforementioned debate on closed proprietary model vs open source approach. As this research exemption system combines elements of both views, enquiry into the reasons why this exemption is not providing a satisfactory middle ground in this debate remains unanswered. In light of this, Minssen et al. proposed clarifying and amending this research exemption system in the European Union (EU) to improve further innovation in synthetic biology.31 Regarding the aforementioned critique on both approaches discussed in the literature, questions arise whether amendments to this research exemption system could be regarded as improving the innovation pursuit in synthetic biology. Aforementioned requires additional research to which this thesis tries to take the first steps.
1.2. Research purpose and research question
The purpose of this thesis is to research how innovation in the field of synthetic biology could best be stimulated. As mentioned, like many emerging revolutionary technologies, synthetic biology encounters regulatory challenges which can create quite a hurdle.32 Nevertheless, synthetic biology as a field of research is still maturing and has great potential for the future.33 The inventions in synthetic biology could in potential benefit society, but at the same time cause unforeseen negative consequences, effect the economy and cause danger for the environment in terms of biosafety and biosecurity.34 To guard safety and in order to attract investors, all research efforts in the field of synthetic biology have to comply with relevant legislation. Furthermore, to incentivize researchers and guide the further progress of synthetic biology in a responsible way, it is imperative to determine the best way to achieve this innovation. Important tools in stimulating this innovation, are intellectual property rights.35 To be able to determine how these intellectual property rights can be utilized to stimulate innovation within synthetic biology in a responsible way, further research is required. Within the array of intellectual property rights, synthetic biology inventions could in theory be protected under copyright36 as
30 Hans Rainer Jaenichen & Johann Pitz, ‘Research Exemption/Experimental Use in the European Union: Patents Do Not Block the Progress of Science’ (2015) 5 Cold Spring Harbor Perspectives in Medicine 1. 31 Minssen et al. (n 27). 32 Minssen & Wested (n 2) 1. 33 Minssen & Wested (n 2) 7. 34 Jennifer Kuzma & Todd Tanji, ‘Unpackaging Synthetic Biology: Identification of Oversight Policy Problems and Options’ (2010) 4 Regulation and Governance 92, 101-3. 35 Jan B Krauss & David Kuttenkeuler, ‘Intellectual Property Rights derived from academic research and their role in the modern bioeconomy – A guide for scientists’ (2018) 40 New Biotechnology 133, 133. 36 Andrew W Torrance, ‘DNA Copyright’ (2011) 46 Valparaiso University Law Review 1.
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M van der Sluis – U1258779 well as under a trademark,37 but the emphasis here will be on patents as a means of protecting inventions in synthetic biology.38 The focus of the research at hand will be on synthetic biology patents in the two aforementioned avenues of; a traditional closed proprietary model and an open source approach and the opportunities for an improved research exemption system in this regard. Abovementioned results in the following research question: ‘What benefits does an improved research exemption system in a closed proprietary model of synthetic biology patents provide in the debate between a closed propriety model and an open source approach?’ The answer to this research question will be provided along the lines of these sub-questions:
What is synthetic biology and its current framework? What are the traditional closed proprietary model (with existing research exemption system) and open source approach in synthetic biology and their drawbacks? What is currently lacking regarding the research exemption system and what benefits could several improvements to this system provide, in the aforementioned debate between the closed proprietary model and open source approach?
1.3. Societal and scientific relevance
Even though synthetic biology is not fully grown yet, there are sufficient reasons to believe that it will have a great impact in the future.39 Therefore, it is important to figure out the best way to stimulate innovation and to guide the development of synthetic biology in a responsible way.40 This is of importance not only to the qualified scientists working in the area of synthetic biology but also for the ‘synthetic hobbyist’41 and particularly for the aforementioned institutions and investors, who need to be informed regarding the regulatory specifications of synthetic biology. Lastly, given the impact synthetic biology can have on the economy at large, on particular companies and even on people’s lifestyles, the development of synthetic biology is of significance for society in general. In addition, this thesis is relevant from a scientific point
37 Andrew W Torrance, ‘Synthesizing Law for Synthetic Biology’ (2010) 11 Minnesota Journal of Law, Science & Technology 629, 649. 38 ibid 639 and Jan B Krauss & David Kuttenkeuler, ‘Intellectual Property Rights derived from academic research and their role in the modern bioeconomy – A guide for scientists’ (2018) 40 New Biotechnology 133, 133. 39Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 193-5. 40 See paragraph 1.1. 41 Jeanne Whalen, ‘In Attics and Closets, “Biohackers” Discover Their Inner Frankenstein’ (2009) Wall Street Journal 1
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M van der Sluis – U1258779 of view because of the contribution it could make. Current literature goes into depth about synthetic biology, its applications, features and characteristics, but misses a legal point of view. Some authors do discuss synthetic biology from a legal point of view by either discussing the open source approach42 or the proprietary model in synthetic biology.43 Recognizing there is interesting literature covering the open source vs proprietary approach in synthetic biology,44 the research exemption system is generally left undiscussed. Although there is literature that proposes to amend the research exemption system,45 it is not specified towards the field of synthetic biology.46 Most importantly, there are authors that propose to amend the existing research exemption system in synthetic biology, but they refrain from actually examining this further.47 Therefore there is a gap in the current literature which this thesis attempts to fill.
1.4. Methodology and overview
The answer to the central question in this research will be provided in three phases, divided in the chapters two through four. The second chapter focuses on the first sub-question which covers a brief explanation of the different strands of synthetic biology, recent developments and potential drawbacks within synthetic biology. With the focus on stimulating innovation in synthetic biology, compliance with relevant regulation is important. This chapter will therefore also map out the current legal framework aimed at regulating synthetic biology. Next, the third chapter revolves around the potential models of stimulating this innovation in synthetic biology: the traditional closed proprietary model and the open source approach. First, an in-depth analysis of the traditional closed proprietary model (focusing on patents) and its drawbacks from the view of synthetic biology will be provided. This will be contrasted to the open source approach and its possible drawbacks in relation to synthetic biology, using mostly literature. With the insights from chapter three, chapter four will focus on potentially improving the innovation pursuit in synthetic biology through examining the closed proprietary model with
42 See Yi-Chen Su, ‘Redefining Open Source for Synthetic Biology' (Thesis, National Chung Hsing University 2012)
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M van der Sluis – U1258779 the ‘research exemption system’. The chapter will start with a description and the possible flaws thereof. In addition, this chapter will examine the possibility of improving this research exemption system for providing a satisfactory solution in the current debate on open source vs closed proprietary models using mostly literature, European as well as national legislation and referral to case law. In conclusion, chapter five will provide a brief summary of the insights gained from this research and provide an answer to the research question posed above.
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2. Synthetic biology framework
2.1. Introduction
Before diving into the debate on open source vs closed proprietary, it is important to set out the context of the research, namely the field of synthetic biology. The question that will be answered in this chapter is: what is synthetic biology and its current framework? In formulating an answer to this question, attention will be paid to the different strands of synthetic biology and several developments in this field of research. Afterwards a few concerns regarding these synthetic biology applications will be discussed. With the aim of stimulating responsible innovation in mind, the relevant regulatory framework that applies to these developments will be discussed, which will serve as a stepping-stone to chapter three in which the next aspect of stimulating innovation in synthetic biology will be discussed in-depth.
2.2. Development of synthetic biology
Although lacking a generally accepted definition, most definitions of synthetic biology include two facets: redesigning natural organisms and constructing new types of living.48 Although often considered as a relatively new field of research, the emergence of synthetic biology was already envisioned by Edward L. Tatum in 1958.49 A few years later, scientists Cohen and Boyer successfully transferred DNA between one species to another, opening up the possibility of cloning genetically engineered DNA molecules in foreign cells. 50 Nonetheless, it was not until the beginning of the twenty-first century that a scientific discovery brought synthetic biology into the public’s eye.51 There was a huge break-through by a group of scientists led by Craig Venter, who announced the de novo synthesis of a functional genome composed of fully synthetic DNA.52 As revolutionary as this discovery was so high were its costs, which as a result discouraged other scientists to explore the field. This changed when due to the so-called Carlson
48 Marko Ahteensuu, ‘Synthetic Biology, Genome Editing and the Risk of Bioterrorism’ (2017) 23 Science and Engineering Ethics 1541, 1543. 49 Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 194. 50 Genome News Network, ‘Genetics and Genomics Timeline’
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Curve,53 the costs of DNA sequencing dropped considerably54 which opened up the field of research to the less wealthy.55 Since then, synthetic biology has only continued to grow.
2.3. Research areas and applications
The research in synthetic biology can be categorized into three subareas; biological parts, genomes and cells.56 The research on the first-mentioned, biological parts, mainly focuses on the building of DNA circuits.57 A DNA circuit can be described as an ‘on-off switch’ to regulate a synthetic metabolic process in a cell where material is destroyed, or constructed, in response to the cells environment.58 The second subarea of research in synthetic biology is genomes. Genome engineering is performed through the use of recombinant DNA, which is a technology where genetic tissue of multiple sources are jointly inserted into a third cell with the goal of editing a genome. As this recombinant DNA59 has existed since 1970, synthetic biologists in the twenty-first century want to step it up a notch and construct a wholly synthetic genome consisting of synthetic genes.60 The third subarea of research in synthetic biology, cells, has developed into two approaches. In the ‘top-down approach’, the content of a cell is removed to study and decipher its characteristics and functionalities that enable the cell to reproduce and evolve.61 In the ‘bottom-up approach’, synthetic biologists try to build a living cell that only contains the essentials for survival through trail-and-error. Such a cell is called: a “protocell”.62 The distinction between the research areas is not as clear-cut in practice, as these areas frequently entangle and overlap with several different disciplines in synthetic biology
53 Rob Carlson, ‘Time for New DNA Synthesis and Sequencing Cost Curves’ (SynBioBeta, 14 February 2014)
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M van der Sluis – U1258779 applications.63 An illustration of these overlapping research areas in an application is the discovery by Donnelly et al.64 Back in 2016 they started creating proteins from scratch in order to determine how entirely new genes are created.65 As proteins are chains of amino acids, the creation of these proteins could point to biological parts research, but creating new genes from scratch also indicates cell research.66 In their research they examined if these proteins would be able to catalyze a certain reaction in an E.coli bacteria.67 The E.coli bacteria was missing a gene which would normally produce this reaction essential for its survival. A few of the examined proteins did in the end produce the desired reaction that was missing but not through catalyzing - which was their intention - but through compensation.68 At the beginning of 2018, however, they stumbled upon a random string of amino acids capable of producing the desired reaction to save the E.coli bacteria, therewith replacing the activity of the essential gene missing in the E.coli bacteria.69 Their discovery does not resemble anything found in nature, yet it performs the same function as the missing gene signaling a valuable discovery for synthetic biology research.70 Synthetic biology applications can cover a wide range of industries, of which the meat industry is of particular importance. Last year, the estimated meat production was as high as 330.41 million metric tons.71 Considering that meat is an important contributor to cardiovascular diseases72 and livestock is responsible for more than 15 percent of so-called “human-induced greenhouse gas emissions”, 73 the need for change is high. Since a large group of people are opposed to switching to a completely vegetarian diet, synthetic biologists have explored the option of creating synthetic meats.74 An example of a company active in this field
63 ibid 6. 64 Ann E Donnelly et al., ‘A de Novo Enzyme Catalyzes a Life-Sustaining Reaction in Escherichia Coli’ (2018) 14(3) Nature Chemical Biology 253
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M van der Sluis – U1258779 is Impossible™ Foods.75 They wanted to create not only a substitute for traditional meats, but something even “more delicious, nutritional and affordable”.76 The result is a synthetically plant-based burger that is already being sold in several restaurants in the United States.77 The special ingredient in this burger is a heme-containing protein from the roots of soy plants. The DNA of this soy plant was inserted into a genetically engineered yeast which was subsequently fermented and supplies the burger with its special meat-like taste.78 Going one step further is a Dutch professor, Mark Post, who announced the creation of the first samples of in-vitro meats, which is essentially a completely lab-grown meat.79 After harvesting only a few muscle cells from a living cow and nurturing them in a lab, Post was able to create this in-vitro meat. Shortly after, a company called Memphis Meats created the first actual piece of synthetic meats tasting just like chicken.80 These fully lab-grown meats are generally referred to as “clean meats” and although not yet affordable at a 1000 US (United States) Dollars,81 the financial, health and environmental ramifications of these synthetic meats could be tremendous. Other applications of synthetic biology getting a lot of attention, stem from research in which synthetic biologists make humans part of their enquiry. Apart from the famous gene- editing technology CRISPR/Cas9 (used to clone gene-edited monkeys for Alzheimer disease research),82 the three-dimensional (bio) printing in the medical industry is gaining attention.83 Three-dimensional printing (3D-printing) is already being applied.84 Examples of this are customized biodegradable bronchial transplants or patient-unique titanium implants.85 Although this was already unimaginable a few decades ago, minds are blown by the latest technological advances, making the 3D bioprinting of actual human tissues and organs a
75 See
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M van der Sluis – U1258779 possibility.86 This 3D bioprinting signals the next step in the field of regenerative medicine, which combines engineering and bioscience to restore injured tissues and even entire organs.87 Compared to the traditional approaches of micro engineering in regenerative medicine - which are limited in their capability to fabricate precise biomimetic tissues constructions – 3D bioprinting, is capable to provide this required architectural accuracy of targeted tissue and organs.88 Due to the high level of difficulty and required expertise, current research is mostly restricted to the vasculature of the human body, yet attention is also being paid to the liver, kidneys and the heart. NASA is one of those that has taken an interest in this type of research and heralded the use of 3D bioprinting in space.89 There is currently a US patent pending on 3D bioprinting in a reduced gravity environment.90 Although most research is still at an in- vitro stage, when commercially applicable, this technology could be truly life changing in the sense of being able to supply synthetic organ transplants taking the pressure of donor lists and likewise provide personalized medicine saving many lives.91
2.4. Application concerns
As set out above, synthetic biology encompasses a lot of opportunities and potential advantages for the future. However, as with many cutting-edge areas of research that create great opportunities, the applications of synthetic biology are viewed with some trepidation.92 A frequently expressed concern is that genetic cell compilations not only intermingle but also adapt towards environmental changes and therefore respond differently when put in different cellular compositions. This results in unpredictable behavior and unanticipated consequences.93 As the E.coli example shows, scientists simply stumbled upon the missing essential gene function. Although this was a rather harmless accidental discovery, the uncertainty of synthetic
86 Sigaux et al. (n 83). 87 Angelo S Mao & David J Mooney, ‘Regenerative Medicine: Current Therapies and Future Directions’ (2015) 112(47) Proceedings of the National Academy of Sciences https://www.pnas.org/content/pnas/112/47/14452.full.pdf accessed 30 January 2019. 88 Yu Shrike Zhang et al., ‘3D Bioprinting for Tissue and Organ Fabrication’ (2017) 45 Annals of Biomedical Engineering 148. 89 Monsi C. Roman et al., ‘Centennial Challenges Program Update: From Humanoids to 3D-Printing Houses on Mars, How the Public Can Advance Technologies for NASA and the Nation (STUB)’ (Conference paper for the Space and Astronautics Forum of the American Institute of Aeronautics and Astronautics, Orlando, September 2018) 18 https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20180006610.pdf accessed 3 February 2019. 90 Techshot Inc., ‘Biomanufacturing System, Method, and 3D Bioprinting Hardware in a Reduced Gravity Environment’ (2018) United States Patent No. US20180163162A1 (pending) 91 Sigaux et al. (n 83) 128. 92 Raheleh Heidari Feidt et al., 'Synthetic Biology and the Translational Imperative' (2017) 25 Science and Engineering Ethics 33. 93 ibid 40.
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M van der Sluis – U1258779 biology discoveries can have severe consequences. This becomes abundantly clear in the mandatory prior testing of synthetic biology discoveries. As every new technology needs to be tested and signed off by an appropriate authority before it can be put on the market, this mandatory prior testing becomes problematic in synthetic biology experiments due to their uncertainty and unexpected effects.94 Examples where such testing went sideways are an experimental gene-editing trial back in 2001, which resulted in a participant dying95 and a receptor cell trial in 2016 where three participants died.96 Not only are there concerns about the unforeseen outcomes of experiments, there are also several ethical concerns. For instance, with regard to 3D bioprinting there are wide-spread concerns towards putting engineered DNA in human bodies.97 Ethical objections are inherent to most synthetic biology discoveries, as the moral standing of synthetic organisms and the intrinsic value of these organisms are a frequent topic of debate.98 A big part of the opposition against 3D bioprinting is formed by religious groups that accuse the scientists working in synthetic biology for ‘playing God’.99 Religious groups form quite the resistance, especially when synthetic biology is not merely used for the treatment of the ill but for the enhancement of the healthy.100 Another concern regarding this 3D bioprinting is the emergence of medical tourism. This could occur when certain cell sources are not available in one territory, leading to this form of tourism by people wanting access to these sources, much like present stem cell tourism.101 An additional disquieting issue is the ‘dual use’ of synthetic biology.102 Meaning, science can be used by the virtuous to do good but also by those who have malicious intent, compromising biosafety and potentially leading to bioterrorism. The term ‘bioterrorism’ infers an evil intent, but failing to prevent unintentional exposure to toxins or (potentially) damaging
94 ibid. 95 Julian Savulescu, ‘Harm, Ethics Committees and the Gene Therapy Death’ (2001) 27 Journal of Medical Ethics 148 96 Matthew Herper, 'Juno Therapeutics Stops Trial Of Cancer-Killing Cells After 3 Patient Deaths' (Forbes, 7 July 2016)
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M van der Sluis – U1258779 biological subject-matter or mere accidental exposure can have similar outcomes.103 This potential ‘dual use’ of synthetic biology is supported by a recent encounter between information technology specialists and synthetic biologists who discovered the possibility of storing computer data in synthetic DNA:104 one gram of DNA would be able to store around one million gigabytes for a long period of time as DNA has a life expectancy exceeding centuries.105 However, this discovery has a ‘dual use’ as shown by scientists from the University of Washington, who found a way to store malware in such synthetic DNA useable for malicious purposes.106 Contributing to this ‘dual use’ of synthetic biology are recent developments in biotechnology that have made it easier and cheaper for bioterrorists to create dangerous compounds while being harder to trace for the authorities.107 Among these developments are the better availability of technological equipment, techniques and the biological parts themselves.108 This wide circulation of the necessary know-how and new technological developments creates opportunities never thought possible and109 have led to the image of a bioterrorist as a malicious DIY – Do It Yourself – biohacker plotting from their garage.110 To support this DIY-image, reference is often made to three studies about the de novo synthesis of the poliovirus, the 20th century influenza that terrorized Spain111 and the mouzepox.112 These studies show that malicious individuals or terrorist groups can have access to the human pathogens of this mouzepox for example and use it as a biological weapon.113 All the more reason to ensure a safe and responsible use of synthetic biology.
103 Markus Schmidt et al., ‘A priority paper for the societal and ethical aspects of synthetic biology’ (2009) 3 Systems and Synthetic Biology 3, 4. 104 Abhay Saxena et al., 'New Trends in Digital Data Storage for the Internet of Things' (2018) 6(3) International Journal of Computer Sciences and Engineering 359. 105 ibid. 106 Peter Ney et al., ‘Computer Security, Privacy and DNA sequencing: Compromising Computers with Synthesized DNA, Privacy Leaks and More’ (USENIX Security Symposium, Washington, August 2017) www.usenix.org/system/files/conference/usenixsecurity17/sec17-ney.pdf accessed 28 January 2019. 107 Holm (n 102) 231. 108 Marko Ahteensuu, 'Synthetic Biology, Genome Editing and the Risk of Bioterrorism' (2017) 23 Science and Engineering Ethics 1541, 1542. 109 ibid. 110 Markus Schmidt, ‘Diffusion of Synthetic Biology: A Challenge to Biosafety’ (2008) 2 Systems and Synthetic Biology 1, 2. 111 David B Resnik, ‘H5N1 Avian Flu Research and the Ethics of Knowledge’ (2013) 43 Hastings Center Report 22
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2.5. Regulatory framework
As discussed, to ensure innovation in synthetic biology, regulatory compliance is key. When inventions are not made under regulatory compliance, the actors working in synthetic biology will probably avoid further involvement to prevent bad publicity, legal action or being responsible for a biological disaster. Such situations would stagnate the development of synthetic biology and should therefore be avoided. To avoid such situations, relevant legislation directed at counteracting these application concerns should be complied with.
2.5.1. Synthetic biology’s regulatory framework
Regulation is an important aspect, especially in the field of synthetic biology which as discussed can have catastrophic outcomes. As regulation is mostly directed towards preventing a lot of the concerns expressed in paragraph 2.4, compliance is important. The regulatory framework of the European Union however does not contain legislation specific to synthetic biology. Most branches of synthetic biology though involve genetic engineering, which is regulated for the most part in the European Union. Important European legislation covering genetic engineering are Directives 2001/18/EU and Directive 2009/41/EU. These Directives cover ‘GMOs’ and ‘GMMs’, defined as: “a genetically modified (micro-) organism (GMM or GMO) means a (micro-) organism, with the exception of human being, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination”.114 These Directives lay down: “appropriate measures to avoid adverse effects on human health and the environment caused by the deliberate release of these GMOs and GMMs”115 and as such counteract some of the unpredictability of synthetic biology experiments. With regard to the previously mentioned synthetic biology applications, some are indeed covered by these Directives, such as the E.coli missing gene function and the discoveries on synthetic meats. Whereas other innovations in synthetic biology are excluded from the scope of these Directives, such as bio-nanoscience and protocell development.116 A protocell, as discussed in paragraph 2.3, is a cell that only contains the essentials for survival.117 By not
114 Article 2 Directive 2009/41/EU and article 2 Directive 2001/18/EU. 115 Maurice Schellekens & Corien Prins, ‘Regulatory Aspects of Genomics, Genetics and Biotechnology: An Orientation on the Positions of Germany, the United Kingdom and the United States’ (2003) 7(1) Electronic Journal of Comparative Law 11 < https://www.ejcl.org//71/art71-2.html#h3 > accessed 31 May 2019. 116 Ahteensuu (n 108) 1546. 117 Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 5 https://ssrn.com/abstract=2153957 accessed 1 December 2018.
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M van der Sluis – U1258779 falling under the scope of the Directive, protocells are not subject to the mandatory safety measures set out therein.118 3D bioprinting is likewise not covered by these Directives, but there is ambiguity about where it should fall under. 3D bioprinting could be seen as a ‘medical device’ regulated under Directive 93/42, but also as a ‘medicinal product’ as regulated under Directive 2001/83 or even as ‘living cells’ regulated under Directive 2004/23. In lack of a proper definition of 3D bioprinting, it is uncertain where 3D bioprinting falls under and what safeguards will apply to counteract medical tourism for example and reassure ethical opponents. Although there is specific regulation to counteract the ‘dual use’ of synthetic biology, this is not sufficient. Council Regulation 428/2009/EU contains a Dual-Use list of certain controlled categories of items.119 The effectiveness and completeness of the regulation on these Dual-Use Goods has recently been reviewed by the European Commission.120 Together with a few Scientific Committees the European Commission published three ‘Opinions on Synthetic Biology’121 reviewing regulatory gaps. These Opinions were met with a lot of criticism, as commentators argued that the proposed minor adjustments to the current regulation in these Opinions would not be sufficient.122 Critics for example state that, there is no adequate biosafety risk assessment tool. 123 Moreover, it is difficult to properly perform any biosafety risk assessment because of the new biological systems involved.124 Additionally, the proposed process of evaluation of each biological subject-matter by the Commission is not suitable due to the increase in research and commercialization of synthetic biology.125 The current regulation therefore still leaves room for potential harmful use of synthetic biology. Evidently, even with the best possible regulation, accidents happen everywhere, even in synthetic biology labs, leading to unintentional dual uses.126
118 See for example Article 23 of Directive 2001/18/EC and Part B of Directive 2009/41/EC. 119 Hans-Jörg Buhk, ‘Synthetic Biology and Its Regulation in the European Union’ (2014) 31 New Biotechnology 528, 530. 120 Commission’s Final opinions on Synthetic Biology I-II-III at https://ec.europa.eu/health/scientific_committees/emerging/opinions_en#others accessed 10 May 2019. 121 ibid. 122 Markus Schmidt, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Alexander Kelle et al. (eds), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009). 123 Commission, 'Synthetic Biology III: Risks to the environment and biodiversity related to synthetic biology and research priorities in the field of synthetic biology’ (Final Opinion, European Commission 2015) ISBN: 978- 92-79-54973-1 and Markus Schmidt, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Alexander Kelle et al. (eds), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009) 96. 124 Commission, 'Synthetic Biology II: Risk assessment methodologies and safety aspects' (Opinion, European Commission 2015) ISBN: 978-92-79-43916-2. 125 ibid 48 and Ahteensuu (n 108) 1546. 126 See Jocelyn Kaiser, 'U.S. high-containment biosafety labs to get closer scrutiny' (Science, 29 October 2015)
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2.6. Conclusion
Although lacking a commonly accepted definition, synthetic biology is characterized by its multidisciplinary nature as it combines genetic research, chemistry, molecular biology and engineering.127 The research in synthetic biology can be categorized into three subareas; biological parts, genomes and cells.128 These research areas are frequently overlapping in practice and provide for a broad range of potential applications in many sectors. As for instance, the possibility of synthetic meats129 or the 3D bioprinting of human organs.130 However, synthetic biology could cause not only ethical but also environmental concerns and biosafety and –security risks. Therefore, regulation is key. Although not specific to synthetic biology, there is European legislation that regulates synthetic biology branches for a big part. This legislation forms a regulatory framework that needs to be improved to stimulate the development of synthetic biology in a responsible way.
accessed 1 February 2019 and Shay Weiss et al., ‘Lessons to Be Learned from Recent Biosafety Incidents in the United States’ (2015) 17(5) Israel Medical Association Journal 269. 127 Marko Ahteensuu, ‘Synthetic Biology, Genome Editing and the Risk of Bioterrorism’ (2017) 23 Science and Engineering Ethics 1541, 1543. 128 See Carolyn M.C. Lam et al., ‘An Introduction to Synthetic Biology’ in Markus Schmidt et al. (eds.), Synthetic Biology – the Technoscience and Its Societal Consequences (Springer 2009) 25. 129 Annalee Newitz, ‘One-third of Americans are willing to eat lab-grown meat regularly (Ars Technica, 7 April 2017)
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3. Synthetic biology’s innovation models
3.1. Introduction
With the regulatory framework set out in the previous chapter, this chapter will cover the next important factor in stimulating responsible innovation: intellectual property rights. In discussing the intellectual property rights framework, two innovation models will be discussed. The first part of the chapter will revolve around the traditional closed proprietary model and start with an introduction thereof, before diving into the potential drawbacks of this model. The second part of the chapter will focus on the counter-response to this former model, the open source model. In this model, there are several levels of openness, which this chapter will briefly elaborate on, before likewise pointing out the potential drawbacks of this open model. The drawbacks of both models are the driving force behind the examination of possible improvements of the current system in chapter four.
3.2. Closed proprietary model
3.2.1. Proprietary model
The first model that will be discussed is the closed proprietary model consisting of intellectual property rights. These intellectual property rights hold a special position in stimulating innovation (as confirmed by the European Union Intellectual Property Office) and are essential to the further growth of synthetic biology.131 For innovation investment in research is required and synthetic biology research is – as most types of research – costly.132 The costs of recombinant DNA research for example might have dropped but remains very high.133 Intellectual property rights are an important avenue to not only recoup these costs for researchers, but also to stimulate further research in general and unlock the full potential of
131 European Union Intellectual Property Office & European Patent Office, ‘Intellectual property rights intensive industries and economic performance in the European Union’ (Industry-Level Analysis Report 2nd edn, October 2016) 2
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M van der Sluis – U1258779 synthetic biology.134 Within the array of intellectual property rights, synthetic biology inventions could, theoretically, be protected under copyright135 as well as under a trademark,136 but the emphasis here will be on patents as they are mostly used.137 Patents provide several incentives for stimulating research and development in synthetic biology.138 First, a patent grants the inventor an exclusive right: “to make, sell, use and distribute his invention”.139 This right can be viewed as a limited monopoly over the exploitation of the patented invention.140 Second, a patent awards inventors (individuals or companies) reputational gain by improving a company’s market value and by providing scientific prestige.141 Although inventors are required to disclose their newly acquired knowledge to the public to increase general knowledge, in return they retain the exclusive rights on their invention, as a quid pro quo.142 The inventors retains these exclusive rights for a period of at least twenty years.143 Thanks to this exclusive right, the inventor is the only one who can put the invention on the market and obtain all revenue.144 This revenue is important financial gain and an opportunity for the inventor to recoup his investment costs.145 When the inventor puts his product on the market, he also gains a competitive advantage over his competitors in the relevant market, because these competitors cannot use his invention without his permission.146
134 Jan B Krauss & David Kuttenkeuler, ‘Intellectual property rights derived from academic research and their role in the modern bioeconomy – A guide for scientists’ (2018) 40 New Biotechnology 133, 133. 135 Andrew W Torrance, ‘DNA Copyright’ (2011) 46 Valparaiso University Law Review 1. 136 Andrew W Torrance, ‘Synthesizing Law for Synthetic Biology’ (2010) 11 Minnesota Journal of Law, Science & Technology 629, 649. 137 Christopher M Holman, ‘Developments in Synthetic Biology Are Altering the IP Imperatives of Biotechnology’ (2014) 17 Vanderbilt Journal of Entertainment and Technology Law 385, 442 and Jan B Krauss & David Kuttenkeuler, ‘Intellectual Property Rights derived from academic research and their role in the modern bioeconomy – A guide for scientists’ (2018) 40 New Biotechnology 133, 133. 138 Although realizing there are several, only a few will be discussed to remain within the scope of the research at hand. 139 European Union Intellectual Property Office & European Patent Office, ‘Intellectual property rights intensive industries and economic performance in the European Union’ (Industry-Level Analysis Report 2nd edn, October 2016) 31. 140 See article 64(1) Convention on the Grant of European Patents (European Patent Convention) of 5 October 1973 as revised by the Act revising Article 63 EPC of 17 December 1991 and the Act revising the EPC of 29 November 2000 (EPC), which refers to the scope of protection under Member States law. For example: article 53(1) of the Dutch Patent Act. See https://wipolex.wipo.int/en/text/228259. 141 Thomas Dreier & Annette Kur, European Intellectual Property Law: Text, Cases and Materials (Edward Elgar Publishing Inc. 2013) 9 ISBN 978 1 84844 879 7. 142 Jay Dratler Jr & Stephen M McJohn, Intellectual Property Law: Commercial, Creative and Industrial Property (Law Journal Press 2018) 2-5 ISBN 1-55852-054-4. 143 See article 63(1) EPC. This period can be extended with ‘supplementary protection certificates’. 144 Birgitte Andersen, 'The Rationales for Intellectual Property Rights: The Twenty-First Century Controversies' (DRUID Summer Conference, Copenhagen, June 2003) 7
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3.2.2. Closed proprietary model
The addition of ‘closed’ to this proprietary (patent) framework has to do with the exclusive nature of the inventions under patent protection. If third parties want to acquire a patented invention, they have to wait until the patent expires.147 As patents generally expire after a period of twenty years, the invention ‘falls back’ into the public domain: meaning it is free from individual ownership and free to use by others without a license.148 A way to acquire the invention from a patent holder during these protected twenty years is to request permission to use the invention through a license.149 The licenses in a closed proprietary model are characterized by the many specifications for the way, type, time and scope of use of the invention.150 Also, these licenses are generally granted at the discretion of the patent holder and always involve some type of royalties.151 Without such a license, the inventor can force anyone, through an injunction, to stop using this invention and to pay damages for using his invention without his permission, as this constitutes patent infringement.152 Another way in which third parties can get access to patented inventions, is through the limitations to the patent holder’s rights as these rights are not absolute.153 Because a patent holder has the exclusive right to “make, use, sell and distribute his patented invention”,154 he has the exclusive right on the so-called ‘commercialization’ of his patented invention.155 Ipso facto, any non-commercial use of his invention by others would not be covered by the rights of the patent holder.156 Other limitations to a patent holders rights can be found in the TRIPS Agreement and legislation derived therefrom.157 This Agreement not only sets out minimum requirements national patent systems have to abide by, 158 but also allows exemptions to the rights of patent holders.159 Article 30 establishes criteria under which such exemptions can be
147 See article 63(1) EPC. 148 Article 63(1) European Patent Convention. 149 See generally WIPO, ‘Guide on Licensing of Biotechnology’ 708(E) (1992) ISBN: 92-805-0410-X. 150 ibid. 151 ibid and Narendran Thiruthy, ‘Open source - Is It an Alternative to Intellectual Property?’ (2017) 20 The Journal of World Intellectual Property 68, 73. 152 Jan B Krauss & David Kuttenkeuler, ‘Intellectual property rights derived from academic research and their role in the modern bioeconomy – A guide for scientists’ (2018) 40 New Biotechnology 133, 137. 153 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 3. 154 European Union Intellectual Property Office & European Patent Office, ‘Intellectual property rights intensive industries and economic performance in the European Union’ (Industry-Level Analysis Report 2nd edn, October 2016) 31. 155 See Article 28 TRIPS Agreement as Annex IC to the Marrakesh Agreement Establishing the World Trade Organization signed on 15 April 1994(TRIPS Agreement) for example. 156 WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014) 2-3. 157 TRIPS Agreement. 158 Article 1 of the TRIPS Agreement. 159 Specified in Article 30 and ‘other uses’ in Article 31 of the TRIPS Agreement.
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M van der Sluis – U1258779 authorized. These exemptions are allowed when they: “do not unreasonably conflict with the normal exploitation of the patent”160 and “not unreasonably prejudice the legitimate interest of the patent holder and third parties”.161Although there are several limiting exemptions to a patent holder’s rights, these did not however, hamper the popularity of patenting.162
3.2.3. Requirements for patentability
To be able to recoup aforementioned investment costs and to stimulate research and innovation, synthetic biology inventions have to be eligible for a patent. To examine if a discovery qualifies for patent protection, certain criteria have to be met. These so-called ‘patentability criteria’ are embedded in the Convention on the Grant of European Patents of 5 October 1973, commonly known as the European Patent Convention (EPC).163 Patents are generally rewarded on a national basis and their legal validity is therefore territorially limited to the Member State for which the patent is granted.164 Although, this EPC needs to be implemented in European Member States national legislation to have legal effect, the EPC is widely recognized in the regulation of patents.165 The EPC demands inventions to comply with several criteria before they can be eligible for a patent. The first patentability criteria is that the discovery has to be an “invention” (a technical discovery not excluded under Article 52(2) EPC).166 Secondly, this invention must be “novel” in the sense of not belonging to the “state of the art”.167 This implies that the discovery must involve some new elements compared to what is already on the market. Thirdly, it must involve an “inventive step”.168 This third requirement raises the threshold of the ‘novelty’ requirement by requiring that the invention must “not be obvious to a person skilled in the art” (which is a co-worker of similar education and skill).169 Fourth, the invention must be capable
160 Article 30 of the TRIPS Agreement. 161 ibid. 162 See Pablo Carbonell et al., ‘Mapping the Patent Landscape of Synthetic Biology for Fine Chemical Production Pathways’ (2016) 9 Microbial Biotechnology 691
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M van der Sluis – U1258779 of industrial application.170 It suffices if an invention has the potential to be industrially applied. It does not have to be produced yet but mere speculation about potential uses is insufficient.171 Some inventions can however still be excluded from patentability as “excluded subject-matter” under Article 53 EPC. This article rules out: “any invention that is immoral or against ordre public”, specified in rule 28172 as: “cloning human beings, modifying the germ line of human beings, using human embryos for industrial/commercial purposes, processes for modifying the genetic identity of animals which causes suffering without substantial medical benefit”.173 Equally excluded in Article 53 EPC are: “plant and animal varieties or essentially biological processes for the production of plants and animals”.174 The final excluded subject matter under Article 53 EPC is: “methods for treatment of human or animal bodies including treatment by surgery, therapy, diagnostic methods”.175 The excluded subject-matter under Article 53 is of particular importance for synthetic biology, as it might exclude some areas of research from patentability.
3.2.4. Synthetic biology patenting
When reviewing the patentability of synthetic biology inventions, the following holds true.176 Microbiological processes and micro-organisms used in synthetic biology research can be patented under Article 53(b) EPC.177 An example of a synthetic biology discovery involving micro-organisms is synthetic meats.178 The company Memphis Meats has two patents pending on these synthetic meats under the titles: “Method for scalable skeletal muscle lineage
170 Article 57 European Patent Convention. 171 See Dreier & Kur (n 141) 113-4 and as confirmed in Recitals 23 and 24 and Article 5(3) of Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions (Biotech Directive). 172 Rules 26-29 form an integral part of the EPC by virtue of Art. 164(1) EPC and are linked to Directive 98/44/EC (Biotech Directive). 173 Article 53 and Rule 28 European Patent Convention. 174 Article 53(b) European Patent Convention. 175 Article 53(c) European Patent Convention. 176 Notwithstanding that every discovery will needs to be examined individually, this paragraph gives an overview of areas of research will are generally approved for patentability. 177 As Article 53(b) EPC only excludes: “essentially biological processes for the production of plants or animals” and does “not apply microbiological processes or the products thereof”. Supported by Rule 27 (c) EPC and Geertrui van Overwalle, ‘The Implementation of the Biotechnology Directive in Belgium and its After-Effects. The Introduction of a New Research Exemption and a Compulsory License for Public Health’ (2006) 37(8) International Review of Intellectual Property and Competition Law 889, 894. 178 Stitcher and Dubner Productions, 'The Future Of Meat (Ep. 367)' (Freakonomics Radio, 2019)
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M van der Sluis – U1258779 specification and cultivation”179 and “Methods for extending the replicative capacity of somatic cells during an ex vivo cultivation process”.180 In addition, synthetic biology research involving proteins or enzymes (like the E.coli discovery)181 is similarly patentable, as Rules 26 and 27 set forth.182 Equally eligible for patent protection are inventions that focus on cells,183 which encompasses a big part of synthetic biology research.184 Research regarding the 3D bioprinting of human tissue and organs for example focuses on cells, stem cells to be more precise.185 Research regarding stem cells is allowed,186 but only under certain circumstances, as patents focused on human embryonic stem cells are generally excluded.187 With regard to 3D bioprinting there are likewise patents (pending), one being: ‘Cellulose nanofibrillar bionik for 3D bioprinting for cell culturing, tissue engineering and regenerative medicine applications’188. Moreover, another important research area of synthetic biology is genes, which in accordance with Rule 27(a) of the EPC is in fact patentable. Almost famous in this regard is the gene- editing technology CRISPR/Cas9 which is involved in countless patents,189 signaling the wide- spread interest in synthetic biology (patenting).
179 Memphis Meats Inc., ‘Method for scalable skeletal muscle lineage specification and cultivation’ (2019) European Patent No. EP3071040A4 (pending) 180 Memphis Meats Inc., ‘Methods for extending the replicative capacity of somatic cells during an ex vivo cultivation process’ (2017) WIPO Patent No. WO2017124100A1 (pending) 181 Ann E Donnelly et al., ‘A de Novo Enzyme Catalyzes a Life-Sustaining Reaction in Escherichia Coli’ (2018) 14(3) Nature Chemical Biology 253
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3.2.5. Drawbacks of closed proprietary model
Despite its popularity, the traditional closed proprietary model is undergoing quite some critique. The most frequently expressed critique is that patents hinder innovation. One of the reasons why patents are conceived as hindering research, is that patents create a “tragedy of the anti-commons”.190 This concept predicts that excessive patenting will hurdle innovation. 191 Put differently, when every existing topic of research is covered by patent protection, there will be a barrier for third parties to enter into subsequent synthetic biology research.192 As the numerous licenses that will need to be purchased to enter into new research will be too high, creating a hurdle for innovation.193 Combined with this is the fear for “patent thickets”, which can be described as: “a dense web of overlapping intellectual property rights that a company must hack its way through in order to actually commercialize new technology”.194 This occurs when inventors patent every little invention, making any further research like walking through a minefield of possible patent infringements. Related to this are “foundational patents” which are characterized by their broad claims that cover important areas of research.195 Depending on the way these patents are used, they could likewise block further innovation. Also ‘normal patent’ owners could hinder innovation when they for instance, engage in “patent sharking”.196 Patent sharking is a type of business model directed at hiding your own patent protection over a biological invention, while simultaneously engaging in litigation and collecting licenses fees without actively developing the patented invention further.197 Thereby undermining the underlying idea behind patents.198 Another reason why patents are conceived as hindering research is the financial burden. Although patents are supposed to provide incentives for innovation, through among others financial gain, the process of obtaining (and keeping) a patent is very expensive199 and can take
190 See generally Michael A Heller & Rebecca S Eisenberg, ‘Can Patents Deter Innovation? The Anticommons in Biomedical Research’ (1998) 280 Science 698. 191Thomas Dreier & Annette Kur, European Intellectual Property Law: Text, Cases and Materials (Edward Elgar Publishing Inc. 2013) 7 ISBN 978 1 84844 879 7. 192 Heller & Eisenberg (n 190). 193 Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 196. 194 Carl Shapiro, ‘Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard-Setting’ in Adam B Jaffe et al. (eds), Innovation Policy and the Economy (Vol 1, National Bureau of Economic Research 2001). 195 Sapna Kumar & Arti K. Rai, ‘Synthetic Biology: The Intellectual Property Puzzle’ (2007) 85 Texas Law Review 1744, 1751. 196 Joachim Henkel & Markus Reitzig, ‘Patent sharks’ (2008) 86(6) Harvard Business Review 129. 197 Conor MW Douglas & Dirk Stemerding, ‘Governing Synthetic Biology for Global Health through Responsible Research and Innovation’ (2013) 7 Systems and Synthetic Biology 139, 145. 198 See incentives intellectual property rights in paragraph 3.2.1. 199 See Jan B Krauss & David Kuttenkeuler, ‘Intellectual property rights derived from academic research and their role in the modern bioeconomy – A guide for scientists’ (2018) 40 New Biotechnology 133, 137.
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M van der Sluis – U1258779 up to five years from the filling date.200 After a patent is applied for and costs have been made for prior searches (part of the application procedure) it is still possible for a patent application to be refused and all efforts to be in vain. Although granted patents have to be published and disclosed to the public, there is still critique that patents hinder further research.201 The critique that patents hinder innovation is also not assuaged by the limitations to the patent holder’s rights as described in the previous paragraph.202 Part of these limitations is the ‘research exemption system’. 203 The idea behind this research exemption could be seen as twofold, as it aims to exempt scientists researching a patented invention without a license from patent infringement, while simultaneously, protect the exclusive right of the patent holder to solely commercialize his invention.204 While this system is aimed at stimulating rather than hindering research, it at least in its current form, does not seem to soothe the critics of this closed proprietary system.205 Apart from the stifling effects patents themselves might have on innovation, there could be other drawbacks as well in a closed proprietary model. In a closed proprietary model synthetic biology inventions not only have to comply with the safety measures set out in synthetic biology regulation discussed in paragraph 2.5,206 but additionally to the patentability requirements of the EPC which contain additional safety checks.207 With regard to biosafety this seems reassuring, however, research indicates that it is unclear who will be held responsible if synthetic biology applications released in nature were to endanger other species.208 This has to do with the issue that the environmental and socioeconomic impact of patented inventions are often treated as an externality.209 In addition, the current regulation on biosafety has received
200 European Patent Office fees
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M van der Sluis – U1258779 critique for failing to provide among others, an adequate bio risk assessment tool.210 This critique supports the view of opponents of this closed proprietary model, who believe innovation in synthetic biology would be better stimulated by using a different approach.
3.3. Open source model
As a counter-response to the closed proprietary model, some commentators have argued for an open source approach. This approach is a form of open innovation and gives interested parties the opportunity to develop technology in a collaborative manner.211 The open source approach functions as a community of participants facilitating the free exchange of ideas and creating a peer-review system for the control of quality in this knowledge exchange.212 As opposed to a proprietary system that revolves around the ‘right to exclude’ (others from using your creation), open source is committed to a ‘right to distribute’.213
3.3.1. Open source software
The roots of this open source approach lie within the area of software development.214 In software development an open source approach arose as an alternative to traditional proprietary software development.215 This open source idea is not of recent nature, as the Free Software Foundation established in 1985 already promoted similar ‘openness’ ideas.216 Since then, the open source community in software expanded and proved to be a success, which led to other research areas following their lead.217
210 Markus Schmidt, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Alexander Kelle et al. (eds), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009). 211 Martin Husovec, ‘Standardization, Open Source, and Innovation: Sketching the Effect of IPR Policies’ (2018) in Jorge Contreras (eds.), Cambridge Handbook of Technical Standardization Law (forthcoming) 6 212 Yochai Benkler, ‘Coase’s Penguin, Or, Linux and“ The Nature of the Firm”’ (2002) 112 Yale law journal 369, 381. 213 Narendran Thiruthy, ‘Open source - Is It an Alternative to Intellectual Property?’ (2017) 20 The Journal of World Intellectual Property 68, 73. 214 Andrew W Torrance, ‘Synthesizing Law for Synthetic Biology’ (2010) 11 Minnesota Journal of Law, Science & Technology 629, 654. 215 Kumar & Rai (n 195) 1763. 216 See Table 2 for differences between FFOS and the later open source movement in Brian Fitzgerald, ‘The Transformation of Open Source Software’ (2017) 30 Management Information Systems Quarterly 587, 589-590. 217 Torrance (n 214) 655.
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Open source is nowadays being utilized in many areas, among which, nanotechnology218 and synthetic biology.219
3.3.2. Types of openness
There are several types of ‘openness’ that can be distinguished in current synthetic biology practice. The main type of ‘openness’ in synthetic biology can be characterized as the ‘commons-based peer production’.220 This type of openness creates a community of researchers that not only share resources and promote creativity, but most importantly, accomplish together what none can achieve individually.221 This approach builds upon characteristics of the proprietary model, yet it differs in the relationship it brings about between the creator and a traditional licensee, as this relationship entails less restrictions.222 Typical licenses in this commons-based production are ‘permissive licenses’.223 These licenses allow the reviewing, modifying, redistributing and selling of works, without having to pay royalties.224 In addition, these licenses offer the opportunity to use a particular work as: “part of other works distributed under other licenses, including proprietary (non-open-source) licenses”.225 Put differently, there are intellectual property rights on inventions in this approach, but the rights on these inventions are not asserted or licensed under very loose conditions.226 The focus of inventors in this approach is therefore less on collecting licensing fees, but on promoting research, as derivative works are also allowed to be patented.227 Apart from permissive licenses, there are also ‘reciprocal licenses’, which signal a second type of openness.228
218 Joshua M Pearce, ‘Open-Source Nanotechnology: Solutions to a Modern Intellectual Property Tragedy’ (2013) 8 Nano Today 339. 219 Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 1 https://ssrn.com/abstract=2153957 accessed 1 December 2018. 220 See generally Yochai Benkler, ‘Freedom in the Commons: Towards a Political Economy of Information’ (2002) 52 Duke LJ 1245, 1256 (discussing the ideal of the digital commons). 221 David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20 Stanford Technology Law Review 143, 166
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A ‘reciprocal license’ is an open source license that is based on a ‘copyleft’ idea. This essentially means that a licensee has a duty to make the work, which he or she acquired a license for and modified or improved, available under the same license terms as acquired.229 This license is also referred to as a ‘copyleft license’ or ‘commons-expanding license’.230 In contrast to the former ‘commons-based production’, these licenses are not only creating a community of open sharing but also ‘expand’ this community, in the sense of requiring so-called ‘derivative works’ to be distributed under alike licensing terms. In requiring this ‘copyleft’, these type of licenses have the effect of limiting the commercial utilization of the creation in question.231 The third type of ‘openness’ that can be pursued by inventors is to completely steer clear of any intellectual property rights. This can be done by keeping an invention in the ‘public domain’.232 Although lacking an official definition, the concept of the ‘public domain’ generally revolves around: “subject matter which is excluded from protection and thus may be accessed and used without permission”.233 The public domain is an area free from any proprietary rights and as such, does not involve any type of license and can be freely used by all.234 The public domain is therefore not about the idea of a ‘commons’ made possible by the creative utilization of intellectual property rights as the previous two types of openness.235 Although inventions necessarily fall back into the public domain when patent protection on an invention expires, an inventor could also choose not to apply for patent protection and waive ownership rights all together.236 In this way, the inventor would contribute to the public domain by creating and publishing his invention, adding to the body of knowledge of society without conferring any ownership, making it free to use by all without restrictions.237 Important to note is that when an invention is put in the public domain, the public domain functions as a blockade against intellectual property rights.238 As these inventions cannot fulfill the second patentability requirement of novelty. As public domain works are excluded from any further patentability
229 ibid 230 ibid 231 ibid. 232 See generally James Boyle, The Public Domain: Enclosing the Commons of the Mind (Yale University Press 2008) ISBN: 978-0-300-13740-8. 233 WIPO, ‘Study on patents and the public domain’ CDIP/8/INF/3 REV. (2011) 15. 234 David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20(1) Stanford Technology Law Review 143, 180
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M van der Sluis – U1258779 attempts, the open source strategy chosen can have major consequences for the development of a research area.
3.3.3. Synthetic biology’s open source
Aforementioned types of openness are visible in synthetic biology through several informal institutions. The most important informal institution is the BioBricks Foundation,239 which is the thriving force behind several initiatives asserting different types of openness in synthetic biology. First, the BioBricks Foundation adopted a standard description method of synthetic biology elements, commonly referred to as BioBricks™.240 These standard elements are often described as Lego® bricks that similarly ‘click’ together.241 Every single BioBrick™ is a unique standardized cell sequence programmed for a particular biotechnical performance.242 Through the use of these BioBricks™, qualified researchers, interested academic staff and even bio-hobbyists (DIY) can “synthesize, insert, express and modify a BioBrick with standard, relatively easy, biotechnical methods”.243 These BioBricks™ can be acquired through the Registry (which originated in MIT) or through the iGEM competition, which takes place every year.244 The Registry and the iGEM competition are two informal institutions focused on the so-called “Get & Give” principle, which mirrors the commons-expanding type of openness.245 The Registry of Standard Biological Parts (the Registry)246 was originally created to avoid spending excessive time on recreating standard parts in subsequent research.247 The Registry has played a big role in the progress in synthetic biology as it has supplied a platform where researchers can provide their discoveries on biological parts with corresponding documentation in a standardized form.248 The access to this Registry is limited to certified academic labs or participating teams of the iGEM competition.249
239 See BioBrick Foundation at
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This International Genetically Modified Machines competition (iGEM competition) is another institution which thrives on the commons-expanding type of openness.250 This competition can be seen as the ‘Olympic Games of synthetic biology’ and its prizes and reputational award the winning teams receive each year are important tools in promoting innovation in synthetic biology.251 Not all inventions submitted during the iGEM competition are of a very high quality, but even the teams that do not win anything, are obliged to comply with the ‘Get & Give principle’ and return any inventions made by use of BioBricks™ back to the Registry.252 Apart from the commons-expanding production, the BioBricks Foundation has also undertaken more ‘commons-based’ initiatives. The “free genes” project253 directed at creating DNA sequences on request is an example of this. In contrast to the Registry (which distributes only to a limited number of parties), the “free genes project” uses a more open approach in their ‘Open Material Transfer Agreement’ (OpenMTA), as it distributes to anyone (even DIY-bio hackers) and does not require inventions to be ‘given back’.254 The BioBricks Foundation also created ‘The BioBrick® Public Agreement (BPA)’,255 which entails a mixture of types of openness. The BPA is a contract between a ‘contributor’ and a ‘user’ of synthetic biological parts and functions as an intermediary tool to spread synthetic biology parts.256 Part of the BPA is a non-assertion clause which means contributors will, in the future, not assert any rights over the parts contributed towards BPA signees.257 This means that parts, unencumbered with intellectual property rights, are therewith put in the public domain. In addition, the non-assertion clause likewise covers existing intellectual property rights, signaling a commons-based approach.258 This means that applications created with BPA- contributed parts may still qualify for patent protection, provided that these applications meet the novelty requirement.259 With its BPA, the BioBricks Foundation seems to pursue some sort of ‘public domain strategy’ by keeping some BioBricks™ out of the grasp of intellectual property rights, while also pursuing a ‘commons-based approach’ regarding existing intellectual property rights.260
250 iGEM at
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The aforementioned institutions are all US-based, which comes as no surprise as the US holds a prominent position in the area of synthetic biology.261 As the US hold such a prominent place, the aforementioned institutions influence the synthetic biology research in Europe as well.262 In addition to these US institutions, there are numerous International and European organizations active in synthetic biology. The International Gene Synthesis Consortium (IGSC)263 for example. The IGSC promotes biosafety in genetic research through a biosafety Code of Conduct264 its members have to abide by.265 Among the European organizations are: the Cell-Free Technology (a start-up allowing the free use of their biotechnological tools),266 the so-called ‘Synthetic Biology Open Language’ (allowing synthetic biologists to exchange gene synthesis in an more easy standardized data format)’267 and the European Association of Synthetic Biology Students and Postdocs (sponsoring professional development events and creates internship and mentoring opportunities for its members).268 Of particular importance is also ‘ERASynBio’, a funded project by the European Commission, which started in 2012 and has about sixteen participating organizations throughout Europe.269 Although most of these institutions are simply aimed at bringing the synthetic biology community together, the Cell- Free Technology start-up seems to be pursuing a public domain approach,270 while the SBOL issued a Creative Commons License, which indicates a commons-based approach.271 Regardless of the type of openness pursued, all of the institutions mentioned above are focused at promoting synthetic biology research.
261 Helen Albert, 'Has European Synthetic Biology Come of Age?' (Labiotech, 19 November 2018)
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3.3.4. Drawbacks open source
These types of openness in synthetic biology have received quite some criticism. As discussed, the goal of these types of openness is to either steer clear from any intellectual property rights and as such, create inventions which can be freely used by all (without having to obtain a license for example) or to license patented inventions under very loose conditions to promote further research.272 A common critique is that scientists might be reluctant to contribute to a collective endeavor because of the inherent: “free rider problem”.273 This ‘free rider problem’ can be characterized as the fear that certain free riders benefit from other people’s labor without contributing in any way.274 In this regard, Grewal points out that: “the rationality of cooperation of scientists depends on thresholds effects that mark the efficaciousness of individual action in collective endeavors”.275 “These thresholds are determined by the presence or absence of a platform infrastructure”.276 With regard to synthetic biology, such a platform infrastructure that reaches a threshold for inducing social cooperation, is said to be lacking.277 Another critique is that these openness strategies lack safety measures.278 Although this critique not applies to all the types of openness to the same extent, as in the commons-based and commons-expanding approach, inventions are subject to certain safety measures in the patent application process.279 These particular safety checks are absent in the public domain strategy, opening the door for potential biohazards.280 Albeit accidental or with an evil (bioterrorist) intent, synthetic biology experiments can have horrible outcomes leading to biohazards, as set out in the previous chapter. Notwithstanding the regulation currently in place to counteract these biosafety and bioterrorism concerns, it is extremely hard for law enforcement to monitor experimenting DIY-hackers from the secrecy of their garage for example. This is aggregated by the current possibility of simply mail ordering biomaterial to your home from public domain institutions in combination with the wide-spread of know-how
272 See David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20(1) Stanford Technology Law Review 143, 180
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M van der Sluis – U1258779 through the Internet.281 These public domain institutions do monitor what is being ordered, but they fall short of communicating with other institutions what is acquired and cannot prevent dangerous home-made pathogens (like the mouzepox example).282 Apart from a lack of safety measures, funding seems to be even more problematic. Especially with regard to this system of openness, researchers pose the question: “to what extent is it possible to create a robust open access system in a field in which it will be very costly to develop marketable innovations?”283 In an open system scientists are not awarded a limited monopoly to recoup made investments costs as in the closed proprietary patent system. Within a commons-expanding strategy, the licensor might have a similar intellectual property right, but the ‘copyleft license’ limits the commercial utilization and therewith the ability to recoup investment costs and generate a profit.284 This holds even more true for the public domain strategy where no significant costs are reclaimed. As research in synthetic biology is expensive, these inventions need to get funding somehow. 285 Universities and private companies are often the driving monetary force behind these ‘open’ inventions.286 Universities however, have recently been reported exerting institutional pressures on these researchers to pursue intellectual property right protection, moving away from the open spheres.287 While private companies remain a thriving force of funding, their investment efforts have been said to be both “inadequate (as private firms are mostly focused on short planning-horizons)”288 and “inefficient (to the extent it is incentivized through the granting of monopoly rights over innovation)”.289 The state could also play a role in subsidizing synthetic biology research. In Europe there are several funding efforts.290 These efforts however
281 Gaymon Bennett et al., ‘From synthetic biology to biohacking: are we prepared?’(2009) 27(12) Nature Biotechnology 1109, 1110. 282 Thomas Douglas & Julian Savulescu, ‘Synthetic Biology and the Ethics of Knowledge’ (2010) 36(11) Journal of Medical Ethics 687, 691
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M van der Sluis – U1258779 vary significantly throughout the European Union and differ from a complete lack of funding to a lack of communities to connect to these funding efforts.291 These efforts are therefore considered flawed.292 This is particularly problematic for the public domain approach, in which some companies have to resort to some type of crowd-funding.293 Apart from the public domain approach, the commons-expanding approach of the aforementioned informal institutions seems to be equally problematic. In contrast to the idea behind the ‘commons-expanding’ approach, research shows that it is uncertain if inventors really ‘give back’ their improved biological parts to the Registry.294 Even when inventors contribute, they seem to provide inaccurate information with poor samples, undermining the principle they claim to abide by.295 Furthermore, there does not exist any enforcement capability to make sure everybody abides the ‘commons-expanding’ idea. This lack of enforcement is problematic for the iGEM competition,296 but also for the IGSC for example. The self- regulatory Code of Conduct the IGSC issued met with a lot of criticism from organizations like Greenpeace for being inadequate.297 Therefore some argue that this commons-expanding approach in synthetic biology has not (yet) flourished as well as hoped, when compared to the successful software counterpart. This is partly due to the fact that to acquire a ‘commons- expanding’ effect, intellectual property rights have to be used as leverage with regard to future derivative works.298 Unlike software development which is focused on copyright, the field of synthetic biology is mostly covered by patents.299 And applying for patents is, in contrast to copyright, costly and require lots of work, making a “patent-left” analogue to a “copyleft” approach unrealistic.300 As a result, one of the more pressing yet controversial issues seems to
291 Markus Schmidt, Lei Pei & Sibylle Gaisser, ‘Synthetic Biology in the View of European Public Funding Organisations’ (2012) 21 Public Understanding of Science 149. 292 ibid. 293 See www.kickstarter.com/projects/cellfree/bixels-dna-bio-display/updates? accessed 3 June 2019. 294 Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 200. 295 ibid. 296 ibid 201. 297 Bernadette B Vincent, ‘Ethical perspectives on synthetic biology’ (2013) 8(4) Biological Theory 368. 298 Narendran Thiruthy, ‘Open source - Is It an Alternative to Intellectual Property?’ (2017) 20 The Journal of World Intellectual Property 68, 77. 299 Christopher M Holman, ‘Developments in Synthetic Biology Are Altering the IP Imperatives of Biotechnology’ (2014) 17 Vanderbilt Journal of Entertainment and Technology Law 385, 442. 300 See David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20(1) Stanford Technology Law Review 143, 177
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M van der Sluis – U1258779 be: “how to facilitate sharing within the synthetic biology community without destroying the possibility for economic return on research effort”.301
3.4. Conclusion
Essential to the further development of synthetic biology are intellectual property rights, which hold a special position in stimulating innovation. A traditional closed proprietary system, focused on patents, provides several incentives to stimulate innovation in synthetic biology. However, this system has received critique for hindering innovation by creating among others: a “tragedy of the anti-commons”302 and “patent thickets”.303 Another approach to synthetic biology innovation is an open source approach. Within this open source model, there are several levels of openness which are currently being pursued in synthetic biology through several institutions. Supporters of a closed proprietary model, in return, critique this open source approach for lacking among others, a platform infrastructure for the exchange of ideas, inadequate funding influx and for not incorporating sufficient safety measures needed for the further development of synthetic biology.304 Having observed both innovation models, the reoccurring dilemma in synthetic biology seems to be how to provide intellectual property protection in a way “without stifling the openness that is so necessary to progress.”305
301 ERASynBio, ‘Next Steps for European Synthetic Biology: A Strategic Vision from ERASynBio’ 1, 15 https://www.erasynbio.eu/lw_resource/datapool/_items/item_59/erasynbiostrategicvision.pdf accessed 8 March 2019. 302 Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 216. 303 Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 1 https://ssrn.com/abstract=2153957 accessed 1 December 2018. 304 See Grewal (n 300) 200 and See Yi-Chen Su, ‘Redefining Open Source for Synthetic Biology' (Thesis, National Chung Hsing University 2012) 5
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4. Synthetic biology’s research exemption system
4.1. Introduction
The previous chapter described and set out the drawbacks of both the closed proprietary model and the open source approach. Against this background and with the aim of stimulating innovation in synthetic biology, Minssen et al. recommended improving the current research exemption system.306 As this research exemption system combines elements of both views, enquiry into the reasons why this exemption is not providing a satisfactory middle ground in this debate remains unanswered.307 The first part of this chapter will revolve around setting out the current research exemption system and pointing out the relevance of this system from a synthetic biology viewpoint. Next, a description of possible explanations why the current research exemption system is considered flawed is set out. Subsequently, suggestions to improve the current system will be provided. This improved research exemption system will then be viewed in relation to the previously described debate between the current closed proprietary model and an open source approach. This chapter will finish with providing the basis for chapter five, in which the research question will be answered.
4.2. Research exemption
4.2.1. Background
As set out in the previous chapter, the closed proprietary model is viewed as hindering research which implies that there is an imbalance between, on the one hand, the initial incentive to innovate and, on the other, the opportunity for subsequent innovation based on the knowledge of this initial invention.308 It is widely believed that the aim of stimulating innovation and improving public welfare is generally not met by granting exclusive patent rights without any restrictions.309 Therefore there are several exemptions and limitations to these exclusive patent
306 Timo Minssen, Berthold Rutz & Esther van Zimmeren, ‘Synthetic Biology and Intellectual Property Rights: Six Recommendations’ (2015) 10 Biotechnology Journal 236. 307 Hans Rainer Jaenichen & Johann Pitz, ‘Research Exemption/Experimental Use in the European Union: Patents Do Not Block the Progress of Science’ (2015) 5 Cold Spring Harbor Perspectives in Medicine 1. 308 Katherine J Strandburg, ‘The Research Exemption to Patent Infringement: The Delicate Balance Between Current and Future Technical Progress’ in Peter K. Yu (ed.), Intellectual Property and Information Wealth: Issues and Practices in the Digital Age (Vol 2, Praeger Publishers 2007) 110 ISBN: 0-275-98884-8. 309 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 3.
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M van der Sluis – U1258779 rights.310 Among those exemptions is the ‘research exemption system’,311 which operates within a closed proprietary system and provides researchers with the possibility to research patented inventions without a license under certain conditions.312 As mentioned, the closed proprietary model (which this research exemption system is a part of) is viewed as hindering research by causing an imbalance of interests.313 However, when realizing that the goal of this research exemption is precisely to restore the balance of these interests,314 the question arises whether the current system is functioning properly. In light of this, several authors, in addition to the World Intellectual Property Organization, argue for changing the current research exemption system.315 Realizing that there is a lack of data,316 some authors infer the malfunctioning and need for improvement of the current research exemption system from certain examples. Paradise & Janson for instance, use SmithKline Beecham Clinical Laboratories (now GlaxoSmithKline) as an illustration.317 This pharmaceutical company had demanded licensing fees for use of its patented genome to both academic and commercial institutions. As a result, one third of these institutions ceased the use of said genome in their research, which the authors believe could have been prevented.318 With this illustration they raise the issue of improving the current research exemption system to enhance innovation in synthetic biology.319 Although labelled as the ‘research exemption system’, this phrase is meant to include both the exemptions
310 The WIPO recognizes several. See WIPO, ‘Exception and limitations to patent rights: private and/or non- commercial use’ SCP/20 (2014) 1. 311 The term ‘research exemption system’ is chosen to include both the commonly used ‘private and non- commercial use’ exemption as well as the ‘experimental use’ exemption, although noticing that in literature often the latter is solely referred to as the ‘research exemption’. 312 See WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014) and WIPO, ‘Reference document on research exception’ SCP/29 (2018). 313 Strandburg (n 308). 314 WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014) 2. 315 See for example Jiyeon Kim, ‘Patent Infringement in Personalized Medicine: Limitations of the Existing Exemption Mechanisms’ (2018) 96 Washington University Law Review 623 and Jakob Wested & Timo Minssen, ‘Research and Bolar Exemptions in the U.S. and Europe: Recent Developments and Possible Scenarios’ (2018) Center for Advanced Studies in Biomedical Innovation Law 3rd webinar, 2
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4.2.2. Research exemption system
In lack of a provision in the EPC regarding this research exemption system, resource is had to national jurisdictions in the European Union. In reviewing the ‘private and non-commercial use’ exemption, it appears that some national jurisdictions do not regard this to be an actual exemption, as private non-commercial use is seen to be outside the raison d’être of the proprietary system.321 A common argument for this is that the “reward of the patent holder is an exclusive right to exploit the invention and as such does not apply to private non-commercial use”.322 However, this mere deduction appears insufficient as most countries also include a specific provision in their national legislation allowing ‘private and non-commercial use’-type activity as falling outside the scope of patent protection.323 In general, most countries agree that this private use is not prejudicial to the general exploitation of patents.324 Thereby, it promotes private creative activity and the sharing of knowledge.325 This private non-commercial use exemption is built on the assumption that a distinction can be made between the ways an invention can be used.326 Generally, there can be private and public use, commercial and non- commercial use, but also ‘experimental use’. This ‘experimental use’ exemption is the second type of exemption in the research exemption system.327 The basis for this exemption can be found in Article 30 of the TRIPS Agreement. This provision permits exemptions to a patent holder’s rights when the exemption: “does not unreasonably conflict with the ‘normal exploitation’ of the patent and not unreasonably prejudice the ‘legitimate interest’ of the patent holder and third parties”.328
320 See WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014) and WIPO, ‘Exceptions and limitations to patent rights: experimental use and/or scientific research’ SCP/20 (2014). 321 WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014) 3. 322 See (translated) Dutch Parliamentary Papers (‘Regulation of patent law for inventions’, Kamerstukken II 1904/05, 197, 3). 323 WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014). 324 ibid 2. 325 ibid 3. 326 Jakob Wested & Timo Minssen, ‘Research and Bolar Exemptions in the U.S. and Europe: Recent Developments and Possible Scenarios’ (2018) Center for Advanced Studies in Biomedical Innovation Law 3rd webinar, 2
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4.2.2. Relevance for synthetic biology
If researchers in synthetic biology could not benefit from a research exemption system, they would have to buy (expensive) licenses to be able to further develop a patented invention.329 The money for these licenses (through funding for example) is not always available which results in hindering research and slowing down further progress in synthetic biology.330 As aforementioned exemptions provide researchers with the possibility to research patented inventions without being liable for patent infringement (under certain conditions), these exemptions are of particular value to the field of synthetic biology.331 Within a research exemption system, ‘private non-commercial use’ is of particular importance to the synthetic biology ‘DIY-hobbyists’, as it allows them to research patented inventions ‘from their garage’.332 The ‘experimental use’ exemption might however be even more important in synthetic biology, as this field of research is characterized by continuous experimenting which eventually leads to scientific discoveries.333 Particularly since synthetic biology as a science is still maturing and no one can predict what the future will hold, this field of research is characterized by a “laborious process of trial-and-error”334 in which experiments happen on a day-to-day basis.335 This experimental nature of synthetic biology is also demonstrated by the discovery of the missing essential gene function of the E.coli bacteria, described in paragraph 2.3.336 In their experimenting, the scientists made their intended discovery by mere accident.337 Such experimenting is of paramount importance for the future development of synthetic biology, making research exemptions especially relevant to the field of synthetic biology. Furthermore, it is not just the experimental nature of synthetic biology which makes the research exemption system interesting. The research areas within synthetic biology also signal
329 National Research Council, Patents in the knowledge-based economy (National Academies Press 2003) 301 ISBN: 0-309-50941-6. 330 ibid. 331 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 3. 332 Markus Schmidt, ‘Diffusion of Synthetic Biology: A Challenge to Biosafety’ (2008) 2 Systems and Synthetic Biology 1, 2. 333 Roberta Kwok, ‘Five hard truths for synthetic biology’ (2010) 463 Nature 289
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M van der Sluis – U1258779 an interest in a research exemption.338 One of those research areas is genomic engineering in which, through the use of recombinant DNA, genetic tissue of multiple sources are jointly inserted into a third cell with the goal of editing a genome.339 These multiple sources from which genetic tissue is taken, might be covered by patent protection. Using these multiple sources in experiments without a license, would lead to infringement of the rights of the patent holders of these sources.340 An experimental use exemption would therefore yield benefits in this respect.
4.3. Possible flaws of the existing research exemption system
As covered in the previous chapter, the current closed proprietary model, which includes the research exemption system, is getting a lot of critique. The aim of this research exemption system is regarded to provide a (better) balance between the interests of the inventor and users of scientific knowledge to maximize societal beneficial innovation.341 As this research exemption system incorporates elements of the open source approach within the frame of a closed proprietary patent model, the questions arises why this research exemption system is not providing a better balance between these two. The biggest reason is the lack of a harmonized research exemption provision that can be applied in synthetic biology.342 Without harmonized wording but also harmonized interpretation of the research exemption system throughout the European Union,343 there exist legal uncertainty which makes scientists reluctant to experiment in fear of a lawsuit for patent infringement.344 In the past there was a research exemption in the Community Patent Convention, but this Convention was invalidated in 1989.345 Legislation currently in force that authorizes general research exemptions to a patent holder’s right is the TRIPS Agreement, as
338 See paragraph 2.3. 339 Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 5 https://ssrn.com/abstract=2153957 accessed 1 December 2018. 340 In line with Article 30 TRIPS Agreement. 341 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 4. 342 Geertrui van Overwalle et al., ‘Models for facilitating access to patents on genetic inventions’ (2006) 7 Nature 143, 144
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M van der Sluis – U1258779 described in paragraph 3.2.2. Nonetheless, there has not been a lot of guidance of the interpretation thereof, as there has only been one case elaborating on this topic, the Canada v European Communities case.346 In this case a complaint was made about Canada’s legislation which supposedly lacked protection of inventions in the area of pharmaceuticals under its Patent Act.347 In this judgement, although not the main issue, the WTO Dispute Settlement Panel provided some guidance on the interpretation of Article 30 TRIPS Agreement.348 This guidance however remained quite broad and vague, leaving considerable room for interpretation to national legislators.349 As a result of this lack of guidance, a recent study examining whether several national legislations generally complied with the TRIPS Agreement, concluded that a substantial part of national jurisdiction does not comply with the criteria under Article 30 TRIPS Agreement.350 Apart from the research exemption system under the TRIPS Agreement, there is a research exemption system in the Unitary Patent package.351 Both a ‘private non-commercial’ use and ‘experimental use’-type exemption will be embedded in Article 27 of the Agreement of a Unified Patent Court (UPC) which is a part of this Unitary Patent package.352 Yet, it is uncertain when this system will actually enter into force,353 given current developments in the European Union.354 As of now there seems to be no proper research exemption system embedded in a European-wide provision. Notwithstanding, even with a European-wide harmonized provision, there are discrepancies possible in the way this harmonized provision is
346 Canada v European Communities (Canada Patent Protection of Pharmaceutical Product case (DS114). See https://www.wipo.int/edocs/mdocs/scp/en/scp_13/scp_13_3.pdf 347 ibid. 348 Article 30 establishes three conditions, namely, (i) that the exceptions to the exclusive rights must be “limited”; (ii) that the exceptions do not unreasonably conflict with a normal exploitation of the patent; and (iii) that the exceptions do not unreasonably prejudice the legitimate interests of the patent owner, taking account of the legitimate interests of third parties. See WIPO, ‘Exclusions from patentable subject matter and exceptions and limitations to the rights’ SCP 13/3 (2009), 21-22. 349 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 7. 350 Bram de Jonge & Bernard H. Maister, ‘The Many National Formulations of the ‘Private and Non- Commercial Use’ Exception in Patent Law: Which, If Any, Satisfy Trips?’ (2016) Wageningen University Working Paper Law and Governance 2016/01 https://ssrn.com/abstract=2732502 accessed 16 May 2019. 351 Realizing that not all the Member States of the European Union will partake in the enhanced cooperation of the Unitary Patent package, all the examples mentioned in this chapter are EU Member States and signatories of the Unitary Patent package. See https://www.unified-patent-court.org/about accessed 13 May 2019. 352 Article 27 of the Agreement of a Unified Patent Court (UPC Agreement) 353 The Unitary Patent System consists of the Agreement of a Unified Patent Court and the EU regulations (No 1257/2012 and No 1260/2012), which will apply from the date of entry into force of the UPC Agreement. See
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M van der Sluis – U1258779 interpreted in national jurisdictions and subsequently applied in individual cases. Although the UCP, when in force, could provide guidance on Article 27, this supervisory check can only be performed when a case is brought before the UPC.355 As the UPC does not apply yet and there has been no further judicial evaluation of the research exemption system, numerous Member States have enacted research exemption-type acts in their national legislation that not only deviate in wording, but also in subsequent interpretation by national courts.356 The first problem regarding the current research exemption system is the wording. The regulation in the United Kingdom for example, sets out in two separate provisions that: “an act which, apart from this subsection, would constitute an infringement of a patent for an invention shall not do so if— (a) it is done privately and for purposes which are not commercial; (b) it is done for experimental purposes relating to the subject matter of the invention”.357 Subsequently, in the Monsanto case, it was set out that the United Kingdom ‘experimental use’ exemption: “covers activities that seek to generate genuinely new information but not those that seek to verify existing knowledge”, remaining quite vague.358 Austria, on the other hand, seems to be entirely lacking a provision similar to that of a research exemption, for either experimental or private non-commercial use, in their national legislation.359 In Italy, the legislators did include reference to an experimental use exemption, but bundled this with the private non-commercial use exemption into one provision and added that both exemptions applied “irrespective of the object of the invention”, contradicting other countries in wording.360 As this brief overview shows, national legislation throughout the EU differs, but there is some agreement among countries, as for instance, that the research exemption system applies regardless of the entity conducting the research or the location of the research.361 However, consensus seems to be missing regarding the relationship between the invention and subsequent research and regarding the scope and nature of the research exemption system.362
355 See the Agreement on a Unified Patent Court. 356 See for an overview of several EU national research exemptions WIPO, ‘Reference document on research exemption – Appendix’ (March 2019) at https://www.wipo.int/export/sites/www/scp/en/national_laws/exceptions.pdf. 357 §60(5)(a) + (b) U.K. Patent Act (UKPA) See https://wipolex.wipo.int/en/text/504998 358 Monsanto Co. v. Stauffer Chemical Co. (1985) RPC 515. See https://academic.oup.com/rpc/article- abstract/102/22/515/1579524. 359 § 22 of the Austrian Law on Patents 1970 (as amended up to Federal Law published in the Federal Law Gazette I No. 37/2018 (BGBI.I No. 37/2018)) https://wipolex.wipo.int/en/text/481680 and WIPO, ‘Reference document on research exception’ SCP/29 (2018) 9. 360 (translated) Article 68 of the Italian Code of Industrial Property. See https://wipolex.wipo.int/en/text/477970 361 Geertrui van Overwalle et al., ‘Models for facilitating access to patents on genetic inventions’ (2006) 7. Nature 143, 144
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This missing consensus seems to be due to the terms frequently used in national research exemption-type provisions which are ill-described and often undefined.363 Many exemptions contain the terms: “private”, “non-commercial”, “experimental purposes”,364 “scientific research or experiment”365 and “relating to the subject matter of the patented invention”.366 In examining these terms, the explanation of the term ‘private’ seems to be lacking and sometimes completely excluded from regulation.367 The emphasis seems to be on the term ‘non- commercial’, as a counter to ‘commercial use’ which is in most jurisdictions solely attributed to the patent holder.368 ‘Commercial use’ is often linked to activities for making profit.369 In some countries however, ‘commercial use’ is interpreted broadly as to include ‘all professional activities’,370 not proving much guidance on the scope of the research exemption system. Equally as problematic to define seems to be the ‘experimental purposes’ phrase. While some countries add that the research exemption system covers research that is “exclusively” experimental371 or “only” for research purposes,372 there is little guidance on the meaning of the term ‘experimental’.373 As the private use exemption is often explicitly non-commercial, the question arises whether experimental use is then inherently commercial. In contrast, in Romania for example, research is only exempted when considered experimental and non- commercial.374 While in the Netherlands, the research exemption covers experimental research in ‘professional settings’, not specifying if this entails commercial use.375 The Oxford Dictionary defines experimental as: “based on untested ideas or techniques and not yet established or finalized”.376 As this term seems to indicate research at an initial stage without formal outcomes, the question arises when research is no longer considered as experimental. Is
363 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 11. 364 See Section 3(3)(iii) of the Consolidated Patents Act of Denmark https://wipolex.wipo.int/en/text/504349 and Article L613-5 of the French Code of Intellectual Property https://wipolex.wipo.int/en/text/508699. 365Article 35 of the Patent Law of Lithuania https://wipolex.wipo.int/en/text/188692. 366 §60(5)(b) U.K. Patent Act (UKPA) https://wipolex.wipo.int/en/text/504998. 367 Section 18(d) of the Act on Inventions and Rationalization Proposals of the Czech Republic https://wipolex.wipo.int/en/text/492083 and Section 3(3)(1) of the Patent Act of Finland https://wipolex.wipo.int/en/text/468527. 368 WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014) 4. 369 WIPO, ‘Exceptions and limitations to patent rights: experimental use and/or scientific research’ SCP/20 (2014) 5. 370 ibid 6. 371 Article 102 of the Industrial Property Code of Portugal https://wipolex.wipo.int/en/text/508630. 372 Article 53(3) of the Patent Act of the Netherlands. https://wipolex.wipo.int/en/text/228259. 373 In the United Kingdom the Monsanto Co v Stauffer Chemical Co and Another (1985) RPC 515 case provided some guidance. As well as the BGH, judgment of 11 July 1995 – X ZR 99/92 – Klinische Versuche I and BGH, judgment of 17 April 1997 – X ZR 68/94 – Klinische Versuche II provided some guidance in Germany. 374 Article 34 of the Patent Law of Romania https://wipolex.wipo.int/en/text/498112. 375 (translated) Dutch Parliamentary Papers (‘Amendment to the National Patent Act’, Kamerstukken II 1984/85, 19 131 (R 1295) 3). 376 Oxford Dictionary
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M van der Sluis – U1258779 experimental research confined to a certain scale of research or meant to refrain from becoming ‘established’? These questions remain unanswered and are therefore a part of the problem. Another problematic phrase often used in the research exemption system is, that only experimental use: “relating to the subject matter of the patented invention” are included.377 Although the precise scope of this phrase is framed by national legislation, some argue that this indicates that third parties are only allowed to experiment on a patented invention.378 Examples of this are the experimenting on a patented invention for unidentified effects or the further development of the invention. In contrast, research can likewise be focused on experimenting with a patented invention.379 As with a patented research tool for example. The distinction between the research on or with a patented invention is dealt with differently throughout the European Union, as there is no harmonization and national jurisdictions take different views on the experimenting on and with a patented invention.380 For example, the Belgium legislator wanted to include both methods of experimenting, following the Italian legislator and subsequently amended their Patent Act include both in their general ‘experimental use’ research exemption system.381 The Netherlands and Germany however, limit their experimental use exemption to the research on a patented subject matter’.382 While other countries not explicitly include experimenting with in their national legislation, they interpret their research exemption system broadly so as to include research tools.383 Aforementioned lack of clarity and differences in wording and interpretation, could explain why the research exemption is presumably not properly functioning. In lack of data of instances where the research exemption system is actually utilized, it is difficult to pinpoint the instances where an improved research exemption could have benefitted.384 However, several authors in addition to the World Intellectual Property Organization do recognize this need to clarify to current research exemption system.385 This need for improvement is particularly high
377 §60(5)(b) U.K. Patent Act (UKPA)
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M van der Sluis – U1258779 for the field of synthetic biology, as due to its experimental nature it is especially hindered by the current lack of clarity.386 As a result, the innovation pursuit in synthetic biology is likewise effected.
4.3.1. Suggestions for synthetic biology
The last few years, this research exemption system has drawn more attention, due to technical and scientific advancements in the gene-editing world, but also due to recent critique on the traditional patent system in health and life sciences.387 Proposing changes to the current research exemption system appears necessary. As follows from the examination in the previous paragraph, there is a need for harmonized wording and interpretation throughout the European Union. Particularly because synthetic biologists fear that these disparities in national jurisdictions throughout the EU will result in a so-called ‘brain drain’ phenomenon of synthetic biologists relocating to other areas for their research in order to avoid any issues.388 This could lead to situation similar to the issue around stem-cell research in the United States.389 As these side-effects are impeding research, a uniform harmonized provision on a research exemption is required, which applies EU-wide.390 The provision in the (forthcoming) UPC might not be sufficient, as this UPC is limited in scope. The UPC only applies to the Contracting Parties of the UPC and391 not all EU Member States are a party to this UPC.392 Furthermore, while every EU Member State is a party to the EPC (even non-EU Member States), this EPC does not include any reference to a research exemption.393 This means first of all, that the research exemption system is lacking under the EPC and limited in territorial scope under the UPC. Especially since under the EPC, research
386 Roberta Kwok, ‘Five hard truths for synthetic biology’ (2010) 463 Nature 289
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M van der Sluis – U1258779 on patented inventions could still be conducted in territories where the invention is not patent protected or the invention in question is not eligible for patent protection (as (synthetic) pharmaceuticals used to be in Iceland).394 Under the UPC, there will be so-called ‘European patents with unitary effect’, making these ‘escapes’ towards different jurisdictions for conducting research on patented inventions without a license even more implausible. 395 A harmonized research exemption system with a broad territorial scope will ensure the continuance of research regarding these patented inventions. This could be in the shape of a harmonized research exemption for synthetic biology inventions embedded in Directive 98/44/EEG on biotechnological inventions. As Directives still need to be implemented in national jurisdictions, a regulation on synthetic biology inventions which a specific research exemption system would be even better. Most important is that there is a harmonized broad interpreted well-defined research exemption system synthetic biologists can benefit from. Apart from a harmonized provision, there is a need for harmonized interpretation of this provision. Especially from a synthetic biology viewpoint, this creates quite an issue as the meaning given to certain terms is not suitable for synthetic biology research.396 With regard to the term ‘private’ for example, research in the field of synthetic biology (specifically genetic research), is seldom performed in a completely private sphere.397 Most research is tied to academic institutes or the industrial sector, where research frequently results into the creation of new products, stepping outside the private sphere.398 The separation of private and non- private use of patented inventions is therefore viewed as impractical for synthetic biology and should be left out.399
394 Trevor M Cook, ‘A European perspective as to the extent to which experimental use, and certain other, defences to patent infringement, apply to differing types of research’ (Intellectual Property Institute Report 2006) 77
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Similar views exist regarding the term ‘(non-) commercial’.400 Historically, universities and similar public research institutions would be seen as non-commercial entities.401 Nowadays however, universities are likewise pursuing intellectual property right protection, becoming more and more like commercial entities.402 As a result, it becomes difficult to answer the question what research qualifies as ‘non-commercial’.403 As this term remains important for examining potential patent infringement cases, adopting a clear and well-balanced definition of the borders between non-commercial and commercial research would be beneficial.404 Furthermore, in the UPC the term ‘experimental’ is included.405 The earliest traces of the term ‘experimental use’ can be found in the Draft Convention relating to a European Patent Law of 1962.406 In this Convention ‘experimental’ is contrasted to ‘industrial or commercial’.407 As differentiating between these terms is not an easy task, altering these terms to better fit current views is advisable.408 Perhaps including the term ‘scientific’ rather than ‘experimental’, will put more emphasis on the research and further development of synthetic biology, while being broader than mere experimenting.409 A legal definition what is to be included in the interpretation of these ‘scientific purposes’ will need to be provided. Including an illustrative list of activities that would fall under ‘scientific purposes’, could provide additional guidance. In the draft of Article 30 of the TRIPS Agreement, there was discussion about including such an illustrative list of exemptions under this former
400 See Geertrui van Overwalle et al., ‘Models for facilitating access to patents on genetic inventions’ (2006) 7 Nature 143, 143
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‘experimental use’ exemption.410 Regrettably, this list was eventually left out of the final wording without clarification why.411 In the current research exemption system, there is no decisive tool or guidance to decide beforehand if the research regarding a certain patented invention falls within the exemption.412 If a certain research endeavor is infringing on a patent holder’s rights, will be examined when claims are brought by a patent holder and a court rules on the potentially infringing activity.413 This forced case-by-case evaluation of the current research exemption system might be impossible to fully overcome.414 Recognizing that there is always a need to take relevant circumstances into consideration, it will be impossible to provide a complete definitive list. Nevertheless, providing an indicative list will at least improve the situation somewhat by providing some guidance for synthetic biology research. Another issue that needs resolving from a synthetic biology viewpoint is the confusion regarding the experimenting on and with.415 There seems to be confusion about how a research exemption applies to inventions that are not experimented on but with (often a research tool).416 As research tools are important instruments in generating new discoveries, they hold an important position. As for instance in breast cancer research, there are certain mutations of BRCA1/2 genes that signal a higher risk of breast cancer.417 The discovery of these mutated BRCA1/2 genes and how to uncover them were patented.418 Imagine, researchers using this invention to identify other markers for breast cancer than these BRCA1/2 markers.419 In this situation, these researchers would be experimenting with the invention while using the invention to point out BRCA1/2 genetic markers.420 If this experimenting with would be prohibited for third parties, they would be refrained from detecting new breast cancer markers even though this could save many lives. Other important research tools in synthetic biology are for example the ‘global transcription machinery engineering tool (gTME)’421 which aims to develop a “mutant library of proteins responsible for transcription and subjects this library to a
410 WIPO, ‘Reference document on research exception’ SCP/29 (2018) 7. 411 See document WTO, ‘Status of work in the Negotiating Group on TRIPS’ (MTN.GNG/NG11/W/76, July 1990) 18 www.ipmall.info/sites/default/files/hosted_resources/lipa/trips/W76.pdf accessed 27 May 2019. 412 ibid. 413 ibid. 414 Paradise & Janson (n 388). 415 Katherine J Strandburg, ‘The Research Exemption to Patent Infringement: The Delicate Balance Between Current and Future Technical Progress’ in Peter K. Yu (ed.), Intellectual Property and Information Wealth: Issues and Practices in the Digital Age (Vol 2, Praeger Publishers 2007) 124 ISBN: 0-275-98884-8. 416 ibid. 417 ibid. 418 ibid. 419 ibid. 420 ibid. 421 Hongmei Liu et al., ‘gTME for improved xylose fermentation of Saccharomyces cerevisiae’ (2008) 160(2) Applied Biochemistry and Biotechnology 574.
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M van der Sluis – U1258779 chemical genetic screen”422 and the emerging and highly controversial CRISPR/Cas9 gene- editing tool.423 There are many more research tools in synthetic biology424 that can be really expensive to acquire.425 Because of the important position biomedical (including synthetic biology) research tools hold, the research exemption system should be broad enough to include experimenting with these tools.426 Synthetic biology would therefore benefit from broadening the research exemption to also include experimenting with.427 Although abovementioned suggestions are not yet definitive, they should at least improve the current research exemption on some accounts.
4.4. Analysis of the (improved) innovation model
With the clarification of the possible reasons behind the malfunctioning of the current research exemption system, possible improvements were able to be made. The remaining question seems to be how an improved research exemption system relates to the aforementioned debate between the traditional closed proprietary system and the open source approach in the innovation pursuit in synthetic biology.428
4.4.1. Recap of the background
As described, the closed proprietary model provides inventors will several benefits. It provides inventors with incentives to innovate by awarding them exclusive patent rights and reputational gain and by creating numerous opportunities for them to recoup investment costs and to make a profit.429 However, this closed proprietary model is critiqued for hindering research through expensive and lengthy procedures, the broad (limited) monopoly rights of the patent holder and expensive licenses for using patented inventions, which the current limitations to the patent
422 Eric Young & Hal Alper, ‘Synthetic biology: tools to design, build, and optimize cellular processes’ (2010) Journal of Biomedicine and Biotechnology 1, 4. 423 Richard Kelwick et al., ‘Developments in the tools and methodologies of synthetic biology’ (2014) 2(60) Frontiers in Bioengineering and Biotechnology 1, 5. 424 ibid. 425 National Research Council, Patents in the knowledge-based economy (National Academies Press 2003) 301 ISBN: 0-309-50941-6. 426 In this regard to avoid driving up transaction costs that could potentially jeopardize the development of new beneficial inventions, see Jiyeon Kim, ‘Patent Infringement in Personalized Medicine: Limitations of the Existing Exemption Mechanisms’ (2018) 96 Washington University Law Review 623, 646. 427 Timo Minssen, Berthold Rutz & Esther van Zimmeren, ‘Synthetic Biology and Intellectual Property Rights: Six Recommendations’ (2015) 10 Biotechnology Journal 236. 428 Directorate-General for Research, ‘Synthetic Biology: A NEST Pathfinder Initiative' (European Commission 2007) 15 ISBN 92-79-03832-X. 429 See page 23.
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M van der Sluis – U1258779 holder’s rights does not seem to repair.430 This is said to result in a “tragedy of the anti- commons”431, cause “patent sharking” behavior and create “patent thickets”.432 Regarding the application concerns of synthetic biology, there is no specific regulation for synthetic biology in place, but a lot of research areas in synthetic biology are covered through European regulation.433 Through this regulation and the patentability criteria under the EPC, synthetic biology inventions have to comply with ethical requirements (to be able to receive patent protection) and certain counter-bioterrorism and biosafety rules.434 However, as pointed out, the current regulation is considered flawed for unclear division of responsibilities435 and lack of proper biosafety tools, such as an adequate bio risk assessment tool.436 As a counter-response to this closed proprietary model, some commentators have argued for an open source approach.437 Although there are several different types of ‘openness’ that can be distinguished in synthetic biology research, all types pursue some form of open innovation and give interested parties the opportunity to develop technology in a collaborative manner.438 Opponents of this open source approach have criticized the types of openness in this approach for several reasons. For example, there is skepticism towards the functioning of these forms of ‘openness’ as there is no properly functioning facilitating platform and no mechanism for enforcement.439 Moreover, the open sharing is critiqued for giving rise to the so-called ‘free rider problem’.440 Furthermore, this open source approach misses certain incentives due to the lack of monetary return on investments.441 Additionally, in lack of monetary returns, funding also poses an issue. The traditional funding institutions are shifting focus (universities are acting
430 See paragraph 3.2.4. 431 See generally Michael A Heller & Rebecca S Eisenberg, ‘Can Patents Deter Innovation? The Anticommons in Biomedical Research’ (1998) 280 Science 698. 432 Joachim Henkel & Markus Reitzig, ‘Patent sharks’ (2008) 86(6) Harvard Business Review 129. 433 See paragraph 2.5.1. 434 Hans-Jörg Buhk, ‘Synthetic Biology and Its Regulation in the European Union’ (2014) 31 New Biotechnology 528, 530 and see the excluded subject-matter under Article 53 EPC. 435 Raheleh Heidari Feidt et al., 'Synthetic Biology and the Translational Imperative' (2017) 25 Science and Engineering Ethics 33, 43 and Kent H Redford et al., ‘Synthetic Biology and Conservation of Nature: Wicked Problems and Wicked Solutions’ (2013) 11(4) PLOS Biology 1. 436 Markus Schmidt, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Alexander Kelle et al. (eds), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009). 437 See paragraph 3.3.2. 438 ibid. 439 Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 200-1. 440 Explaining free rider problem is Mancur Olson, The Logic of Collective Action: Public Goods and the Theory of Groups (Harvard University Press 1965) ISBN 9780674537514. 441 See page 37.
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M van der Sluis – U1258779 increasingly like commercial entities focusing on proprietary rights) 442 and remaining funding efforts are generally flawed443 or lacking 444 and not fitting current business models which are focused on proprietary rights and returns.445
4.4.2. Analysis of the innovation models in synthetic biology
When comparing the described innovation models to the closed proprietary model, when the proposed amendments to the research exemption have been implemented (characterized as ‘the new model’), the following holds true. This ‘new model’, compared to the ‘old (closed proprietary) model’, does not hinder research, but stimulates and promotes research, as open source supporters desire. Although the sharing of knowledge is not of the same level as in the open source approach, it does alleviate some of the critique of the ‘old model’ by better promoting research during the term inventions are under patent protection. Especially in areas which can have huge societal benefits, as synthetic meats for example,446 the sharing of knowledge under a research exemption could be very beneficial. In regards to the other criticism often expressed towards the ‘old model’, the ‘new model’ will prevent the “tragedy of the anti-commons”.447 This concept predicts that excessive patenting will hurdle innovation. 448 Put differently, when every existing topic of research is covered by patent protection, there will be a barrier to for third parties to enter into subsequent synthetic biology research.449 As the numerous licenses that will need to be purchased to enter into new research will be too high, creating a hurdle for innovation.450 As the ‘new model’ is
442 David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20(1) Stanford Technology Law Review 143, 208
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M van der Sluis – U1258779 directly at enabling the use of patented inventions, it prevents this so-called tragedy. The improved research exemption system can however, not prevent “patent thickets”451 as this exemption only covers research on patented inventions and cannot as such reduce the pressure on the patent landscape.452 As this ‘new model’ combines elements and incentives of both innovation models, funding will not pose as much of a problem as in the open source approach. As discussed in regard to the open source approach, the driving monetary forces behind synthetic biology funding are either generally considered flawed (public organizations),453 inadequate for long term innovation pursuit (private companies)454 or increasingly focused on commercial exploitation (academic institutions).455 As in addition to the incentives common in the open source approach (the desire to save lives, reputational gain, innovation prizes and academic rewards), there are still opportunities to recoup investment costs and research patented inventions in a scientific way.456 This scientific research still requires funding one way or another. Although synthetic biologists will not have to acquire expensive licenses for research regarding patented inventions, funding might still pose a problem.457 Apart from monetary issues, some authors fear that when inventors are given a lot of freedom to research, they are (easily) able to design around patented invention and create rival technologies, therewith slinking the incentives for inventors to innovate.458 Yet, without this amended research exemption in the ‘new model’, inventors are less stimulated to improve on patented inventions, thus hindering the research regarding the state-of-the-art research (tools).459 Also, there are several studies proving that research exemptions not necessarily
451 Carl Shapiro, ‘Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard-Setting’ in Adam B Jaffe et al. (eds), Innovation Policy and the Economy (Vol 1, National Bureau of Economic Research 2001). 452 Perhaps patent pools of clearing houses could assist in this regard. See Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 3-4 https://ssrn.com/abstract=2153957 accessed 1 December 2018. 453 Markus Schmidt, Lei Pei & Sibylle Gaisser, ‘Synthetic Biology in the View of European Public Funding Organisations’ (2012) 21 Public Understanding of Science 149. 454 Grewal (n 442) 208 455 Douglas & Stemerding (n 443). 456 Jiyeon Kim, Patent Infringement in Personalized Medicine: Limitations of the Existing Exemption Mechanisms’ (2018) 96 Washington University Law Review 623, 644. 457 See page 37. 458 See Kevin Iles, ‘A Comparative Analysis of the Impact of Experimental Use Exemptions in Patent Law on Incentives to Innovate’ (2005) 4 Northwestern Journal of Technology and Intellectual Property 61, 64
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M van der Sluis – U1258779 negatively impact patented inventions.460 One case study showed that the enhanced genetic info improving one seed variety, might likewise improve the yield of another variety directed at a different trait.461 One company’s invention could therefore improve the quality of varieties held by other companies. This can only occur when there is access to genetic material through a research exemption-type provision.462 Another study was aimed at examining the R&D incentivizing effects of proprietary rights with a research exemption, in a sequential and cumulative innovation process.463 This study, focusing on profit and welfare implications, showed that although the selected firms might prefer full patent protection ex ante, a research exemption system was preferred on the welfare rank.464 Allowing some sort of openness in the shape of a research exemption seems beneficial. The lack of enforcement mechanisms in the open source approach, is not as problematic in the ‘new model’.465 In the ‘new model’ there are no rules for keeping research ‘open’ or in the ‘public domain’, though there are certain rules that research in the ‘new model’ has to abide by. As in this ‘new model’ research is exempted for ‘scientific purposes of non-commercial nature’, synthetic biologists will have to stay within the boundaries of these terms. When moving outside these boundaries, a patent holder claiming patent infringement will act as an enforcement agency. However, as some infringing activities might escape a patentholder’s attention, it is important that the boundaries of the research exemption system are respected to avoid having the effect of simply authorizing actual patent infringement. Although noticing that these boundaries can be quite challenging to determine in individual cases, even with an indicative list of exempted activities. Equally problematic is the regulation of synthetic biology inventions currently in place. Also in the ‘new model’, synthetic biology inventions have to comply with European regulation which is generally focused on the (unintended) ‘dual use’ of biological inventions and aims to prevent bioterrorism and to ensure biosafety.466 This regulation to counter this ‘dual use’ is
460 Jeremy Jackson & Jason Smith, ‘Innovation of Agricultural Biotechnology with Experimental Use Licensing’ (2019) 44(1) Journal of Agricultural and Resource Economics 1, 2. 461 ibid. 462 ibid. 463 GianCarlo Moschini & Oleg Yerokhin, ‘Patents, research exemption, and the incentive for sequential innovation’ (2008) 17(2) Journal of Economics & Management Strategy 379. 464 (Depending on the initial innovation and subsequent improvements made) ibid. 465 See David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20(1) Stanford Technology Law Review 143, 177
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M van der Sluis – U1258779 however considered flawed and inappropriate for providing sufficient biosafety.467 Although it is important to note that the research that is exempted under the research exemption system, is similar to the research in an open source approach in the sense that it is ‘off the radar’ (like DIY-biohackers).468 This makes it harder to monitor for illegal activity by enforcement authorities. Although this seems to imply that exempted research under the ‘new model’ poses similar risks for biosafety and bioterrorism as open source research, there is a nuance. The exempted research is research on or with a patented invention which has complied with the patentability criteria and regulatory review, so the research on the already approved invention is (slightly) less likely to cause risks than the research in an open source approach, which can be completely ‘off the radar’. This is of course notwithstanding the general unpredictability inherent to experimenting in synthetic biology, which causes unanticipated consequences.469 This can have surprisingly positive results as in the E.coli example, but it can also go sideways, as in the experimental gene-editing trials in which a participating died.470 In any case, it is important to provide for proper synthetic biology regulation. The few changes the European Commission suggested in its three Opinions on Synthetic Biology are however deemed insufficient and fails to deal with the risks and threats posed by advances in synthetic biology.471 The regulation on synthetic biology first needs to be improved and second, it also needs to catch up with technological advancements, as some research areas in synthetic biology are still unregulated, like 3D bioprinting for instance.472
4.5. Conclusion
When the closed proprietary system is viewed as hindering research, there is an imbalance between the initial incentive to innovate and the opportunity for subsequent innovation based on the knowledge of this initial invention.473 Therefore, there are some exemptions and
467 Markus Schmidt, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Alexander Kelle et al. (eds), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009). 468 Markus Schmidt, ‘Diffusion of Synthetic Biology: A Challenge to Biosafety’ (2008) 2 Systems and Synthetic Biology 1, 2. 469 Raheleh Heidari Feidt et al., 'Synthetic Biology and the Translational Imperative' (2017) 25 Science and Engineering Ethics 33, 40. 470 Julian Savulescu, ‘Harm, Ethics Committees and the Gene Therapy Death’ (2001) 27 Journal of Medical Ethics 148 471 Markus Schmidt, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Alexander Kelle et al. (eds.), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009) 472 See page 21. 473 Katherine J Strandburg, ‘The Research Exemption to Patent Infringement: The Delicate Balance Between Current and Future Technical Progress’ in Peter K. Yu (ed.), Intellectual Property and Information Wealth: Issues and Practices in the Digital Age (Vol 2, Praeger Publishers 2007) 110 ISBN: 0-275-98884-8.
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M van der Sluis – U1258779 limitations to this closed proprietary system, which are aimed at restoring the balancing of interests.474 Among those exemptions characterized as the ‘research exemption system’ are the ‘private and non-commercial use exemption’ and the ‘experimental use exemption’, which are likewise relevant for the area of synthetic biology. Due to the current debate between the closed proprietary model and open source approach in synthetic biology, attention was drawn to improving the current situation through amending the research exemption system.475 There are several possible reasons why the current system is considered flawed. Particularly from a synthetic biology perspective, there are some improvements that can be made. Among the proposed improvements are: the establishing of harmonized wording through a EU-wide provision (specific) for synthetic biology research for which the terminology is specifically revised, the scope is broadened and an indicative list is included to simultaneously ensure harmonized interpretation of said provision throughout the EU. These subsequent improvements to the current closed proprietary system are characterized as the ‘new model’. When compared to the current closed proprietary model (‘old model’) and the open source approach, the ‘new model’ provides some improvements but also poses some new challenges for innovation in synthetic biology. Having examined all innovation models, the last remaining step is to provide an answer to the research question.
474 The WIPO recognizes several. See WIPO, ‘Exception and limitations to patent rights: private and/or non- commercial use’ SCP/20 (2014) 1. 475 Timo Minssen, Berthold Rutz & Esther van Zimmeren, ‘Synthetic Biology and Intellectual Property Rights: Six Recommendations’ (2015) 10 Biotechnology Journal 236.
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5. Concluding remarks
On the basis of the sub-conclusions provided in the previous chapters, this chapter will provide an answer to the main research question: ‘What benefits does an improved research exemption in a closed proprietary model of synthetic biology patents provide in the debate between a closed propriety model and an open source approach?’ To be able to answer this research question, certain sub-questions were posed in the preceding chapters. This chapter will start with a brief overview of the answers provided to these sub-questions, before providing an answer to the research question and proposing several recommendations. In exploring the emerging field of synthetic biology, several groundbreaking discoveries such as the creation of synthetic meats476 and the 3D bioprinting of human tissue and organs, 477 showed the tremendous societal beneficial effects of synthetic biology research. However, as with many cutting-edge areas of research that create great opportunities, the applications of synthetic biology are viewed with some trepidation.478 The concerns about synthetic biology’s implications are mostly related to the inherent unpredictable nature of synthetic biology experiments, the unethical nature of some areas of research, but also to environmental and biosafety and – security risks associated with the potential ‘dual use’ of synthetic biology.479 Although the regulation currently in place to counter said risks is not specific to synthetic biology, it still plays a significant role in enabling further growth and development of synthetic biology.480 As the field of synthetic biology is not yet matured and still needs to grow before being industrially applicable on a large scale,481 chapter three focused on how this further growth could be achieved. The views on how innovation in synthetic biology can best be achieved seem
476 Kate Kelland, ‘Petri dish to dinner plate, in-vitro meat coming soon’ (Reuters, 11 November 2011)
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M van der Sluis – U1258779 to diverge.482 Some believe this innovation should be achieved through an open source system that facilitates the free exchange of ideas.483 Others believe the focus should be on stimulating innovation through a traditional system of ‘closed’ intellectual property rights involving patents.484 In analyzing the closed proprietary and open source model, both innovation models seem to provide several benefits and drawbacks. On the one hand, the closed proprietary model is critiqued for hindering innovation by expensive and lengthy procedures, broad exclusive rights of the patent holder and expensive licenses for using patented inventions, which the current limitations to the patent holder’s rights does not seem to repair.485 This is said to result in a “tragedy of the anti-commons”486 and “patent thickets”. 487 On the other hand, the open source approach is criticized for lacking an enforcement mechanism and a platform infrastructure for the exchange of ideas.488 In addition, opponents argue that the open source approach is impractical due to the “free rider problem” and the lack of sufficient safety measures needed for the further development of synthetic biology.489 In this debate the reoccurring dilemma seemed to be how to provide intellectual property protection in a way ‘without stifling the openness that is so necessary to progress’.490 Chapter four explored a possible solution in this dilemma by focusing on the so-called ‘research exemption system’. The examination of this research exemption system revealed possible reasons why the current system might be perceived as flawed, explaining why the World Intellectual Property Organization among others, believe this system should be amended.491 Based on the examination of the research exemption system, a few improvements from the view of synthetic biology were made. Among the proposed improvements are: the
482 Timo Minssen & Jakob B. Wested, ‘Standardization, IPRs and Open Innovation in Synthetic Biology’ (Bucerius IP Conference, Hamburg, October 2013) 2 https://ssrn.com/abstract=2153957 accessed 1 December 2018. 483 Andrew W Torrance, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017) 196. 484 Christopher M Holman, ‘Developments in Synthetic Biology Are Altering the IP Imperatives of Biotechnology’ (2014) 17 Vanderbilt Journal of Entertainment and Technology Law 385, 441. 485 See paragraph 3.2.4. 486 Torrance (n 466) 216. 487 Minssen & Wested (n 465) 1. 488 See David Singh Grewal, ‘Before Peer Production: Infrastructure Gaps and the Architecture of Openness in Synthetic Biology’ (2017) 20(1) Stanford Technology Law Review 143, 200
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M van der Sluis – U1258779 establishment of a harmonized EU-wide provision (specific) for synthetic biology research, which is broad enough to also include experimenting with inventions. Furthermore, a revision of the appropriate terminology to include in this provision should be conducted and combined with an indicative list of exempted activities aimed at ensuring harmonized interpretation of said provision throughout the EU. In light of the aforementioned critique expressed on both innovation models, the second part of the analysis in chapter four focused on examining whether the amendments made to this research exemption system could be regarded as improving the innovation pursuit in synthetic biology. In comparing this research exemption system (labelled as the ‘new model’), to the current closed proprietary system (labelled as the ‘old model’) and the open source approach, this ‘new model’ seems to provide several benefits among which the following are the most important. First of all, in contrast to the ‘old model’, this ‘new model’ does not hinder but rather stimulates and promotes research and development. Although the sharing of knowledge is not as open as in the open source approach, it does alleviate some of the critique by promoting research better during the term in which inventions are covered by patent protection. Moreover, it is beneficial that the ‘new model’ does not provide the same level of openness as in the open source approach, as society will be exposed to less safety risks as the research in the ‘new model’ can be monitored more effectively than in an open source approach.492 In addition, as this ‘new model’ is directly aimed at the use of patented inventions, the critique on the ‘old model’ for creating a “tragedy of the anti-commons” will be prevented.493 Second, as this ‘new model’ combines elements of both innovation models, funding will likewise pose less of a problem. In particular because the ‘new model’ not only relies on the incentives common in the open source approach (the desire to save lives, reputational gain, innovation prizes and academic rewards), but also on the opportunities to recoup investment costs and research patented inventions exempted under this ‘new model’.494 Third, the ‘new model’ does not have a lack of enforcement. As the ‘new model’ is not subject to the open source approach rules regarding keeping research ‘open’ or in the ‘public domain’ or subject to the requirement to ‘give inventions back’ as these rules do not apply in
492 See page 59. 493 See generally Michael A Heller & Rebecca S Eisenberg, ‘Can Patents Deter Innovation? The Anticommons in Biomedical Research’ (1998) 280 Science 698. 494 Jiyeon Kim, Patent Infringement in Personalized Medicine: Limitations of the Existing Exemption Mechanisms’ (2018) 96 Washington University Law Review 623, 644.
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M van der Sluis – U1258779 the ‘new model’.495 Although the research in the ‘new model’ must remain within the boundaries of the research exemption, a patent holder will act as an enforcement agency when a research endeavor steps outside the boundaries of the research exemption and becomes patent infringing. However, as some infringing activities might escape a patent holder’s attention, it is important that the boundaries of the research exemption system are respected to avoid having the effect of simply authorizing actual patent infringement. These benefits are however notwithstanding, that the ‘new model’ cannot prevent patent thickets or relieve the pressure on the patent landscape.496 The broad scope of the research exemption in the ‘new model’ also raises new challenges, as third parties could more easily design around patented inventions.497 Additionally, regulation in the ‘new model’ still needs to be improved to properly counter bioterrorism and ensure biosafety, as the existing regulation is considered flawed.498 Most importantly, an important prerequisite for the ‘new model’ is the development of a harmonized uniform research exemption system which fits the needs of synthetic biology, which will first need to be enacted. In conclusion, the ‘new model’ does seem to provide several benefits, yet achieving optimal innovation in synthetic biology will be contingent on also improving the flaws exposed. While recognizing that further research is required for an actual harmonized research exemption system that fits the needs of synthetic biology can be established, this thesis has provided a basis further research can build on. Moreover, as the analysis in this thesis exposed the flaws of the current general research exemption (which applies not just to synthetic biology, but to many areas of research), the added value of this thesis might exceed the area of synthetic biology. Although taking into account the limitations of the research at hand regarding the scope and lack of certain data, the analysis in this thesis at least provides the first steps to improving the innovation pursuit in synthetic biology. Especially since synthetic biology research is already leading to astonishing discoveries, one could only imagine what synthetic biology could be capable of when provided with the best possible tools for innovation pursuit.
495 See for an overview of the types of openness in the open source approach in synthetic biology in paragraph 3.3.2. 496 Carl Shapiro, ‘Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard-Setting’ in Adam B Jaffe et al. (eds), Innovation Policy and the Economy (Vol 1, National Bureau of Economic Research 2001). 497 See Kevin Iles, ‘A Comparative Analysis of the Impact of Experimental Use Exemptions in Patent Law on Incentives to Innovate’ (2005) 4 Northwestern Journal of Technology and Intellectual Property 61, 64
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Bibliography Primary Sources International Treaties Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement as Annex IC to the Marrakesh Agreement Establishing the World Trade Organization (1994).
European Conventions Convention for the European patent for the common market (Community Patent Convention) 76/76/EEG of 15 December 1975 OJ L17/1. Convention on the Grant of European Patents (European Patent Convention) of 13 December 2007 as amended on June 2016 (16th edition).
European Regulations Regulation (EU) No 1257/2012 of the European Parliament and of the Council of 17 December 2012 implementing enhanced cooperation in the area of the creation of unitary patent protection OJ L 361/1. Council Regulation (EU) No 1260/2012 of 17 December 2012 implementing enhanced cooperation in the area of the creation of unitary patent protection with regard to the applicable translation arrangements OJ L 361/89.
European Directives Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms (Recast) OJ L 125/75. Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC OJ L 106/1. Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions (Biotech Directive) OJ L 213/13.
European Agreements Agreement on a Unified Patent Court of 20 June 2013 (UPC Agreement) OJ C175.
WTO Report/EPO decisions WTO Panel report of 17 March 2000 on Canada-Patent Protection of Pharmaceutical Product case (DS114). EPO decision of 25 November 2008 of the Enlarged Board of Appeal T 1374/04 (Use of embryos/WARF) .
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M van der Sluis – U1258779
National case law Monsanto Co. v. Stauffer Chemical Co. (1985) RPC 515 (United Kingdom). BGH judgment of 11 July 1995 – X ZR 99/92 - Klinische Versuche I (Germany). BGH judgment of 17 April 1997 – X ZR 68/94 - Klinische Versuche II (Germany).
National legislation (translated) Act on Inventions and Rationalization Proposals of the Czech Republic https://wipolex.wipo.int/en/text/492083. (translated) Austrian Law on Patents 1970 (as amended up to Federal Law published in the Federal Law Gazette I No. 37/2018 (BGBI.I No. 37/2018)) https://wipolex.wipo.int/en/text/481680. (translated) Belgium Act of 28 April 2005 modifying the law of 28 March 1984 on patents, regarding the patentability of biotechnological inventions, MB, 13 May 2005. https://wipolex.wipo.int/en/text/490483. (translated) Consolidated Patents Act of Denmark https://wipolex.wipo.int/en/text/504349. (translated) French Code of Intellectual Property https://wipolex.wipo.int/en/text/508699. (translated) Industrial Property Code of Portugal https://wipolex.wipo.int/en/text/508630. (translated) Italian Code of Industrial Property. https://wipolex.wipo.int/en/text/477970. (translated) Patent Act of Finland https://wipolex.wipo.int/en/text/468527. (translated) Patent Act of Germany https://wipolex.wipo.int/en/text/461310. (translated) Patent Law of Lithuania https://wipolex.wipo.int/en/text/188692. (translated) Patent Act of the Netherlands https://wipolex.wipo.int/en/text/228259. (translated) Patent Law of Romania https://wipolex.wipo.int/en/text/498112. United Kingdom Patent Act (UKPA) https://wipolex.wipo.int/en/text/504998.
Secondary Sources Books Boyle J, The Public Domain: Enclosing the Commons of the Mind (Yale University Press 2008) ISBN: 978-0-300-13740-8. Dratler JJ & McJohn SM, Intellectual Property Law: Commercial, Creative and Industrial Property (Law Journal Press 2018) ISBN 1-55852-054-4. Dreier T & Kur A, European Intellectual Property Law: Text, Cases and Materials (Edward Elgar Publishing Inc. 2013) ISBN 978 1 84844 879 7. National Research Council, Patents in the knowledge-based economy (National Academies Press 2003) ISBN: 0-309-50941-6, 301. Olson M, The Logic of Collective Action: Public Goods and the Theory of Groups (Harvard University Press 1965) ISBN 9780674537514.
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Contributions to edited books Husovec M, ‘Standardization, Open Source, and Innovation: Sketching the Effect of IPR Policies’ (2018) in Jorge Contreras (eds), Cambridge Handbook of Technical Standardization Law (forthcoming). Lam CMC, Godinho M, Martins dos Santos VAP, ‘An Introduction to Synthetic Biology’ in Schmidt M, Kelle A, Ganguli-Mitra A, de Vriend H (eds), Synthetic Biology – the Technoscience and Its Societal Consequences (Springer 2009). Schmidt M, 'Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology' in Kelle A, Ganguli-Mitra A, de Vriend H (eds), Synthetic Biology. The Technoscience and its Societal Consequences (Springer 2009). Shapiro C, ‘Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard-Setting’ in Jaffe AD, Lerner J & Stern S (eds), Innovation Policy and the Economy (Vol 1, National Bureau of Economic Research 2001). Strandburg KJ, ‘The Research Exemption to Patent Infringement: The Delicate Balance Between Current and Future Technical Progress’ in Peter K. Yu (ed.), Intellectual Property and Information Wealth: Issues and Practices in the Digital Age (Vol 2, Praeger Publishers 2007) ISBN: 0-275-98884-8. Torrance AW, ‘Better to Give Than to Receive: An Uncommon Commons in Synthetic Biology’ in Katherine J Strandburg et al. (eds), Governing Medical Knowledge Commons (Cambridge University Press 2017).
(Online) Journals Ahteensuu M, ‘Synthetic Biology, Genome Editing and the Risk of Bioterrorism’ (2017) 23 Science and Engineering Ethics 1541. Arneson RJ, ‘The principle of fairness and free-rider problems’ (1984) 92(4) Ethics 616. Benkler Y, ‘Coase’s Penguin, Or, Linux and “The Nature of the Firm”’ (2002) 112 Yale law journal 369. Benkler Y, ‘Freedom in the Commons: Towards a Political Economy of Information’ (2014) 52 Duke Law Journal 1245. Bennett G, Gilman N, Stavrianakis A, Rabinow P, ‘From synthetic biology to biohacking: are we prepared?’(2009) 27(12) Nature Biotechnology 1109. Buhk HJ, ‘Synthetic Biology and Its Regulation in the European Union’ (2014) 31 New Biotechnology 528. Carbonell P, Gök A, Shapira P, Faulon JL, ‘Mapping the Patent Landscape of Synthetic Biology for Fine Chemical Production Pathways’ (2016) 9 Microbial Biotechnology
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Cyranoski D, ‘Monkeys Cloned in China’ (2018) 553 Nature 387
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Holman CM, ‘Developments in Synthetic Biology Are Altering the IP Imperatives of Biotechnology’ (2014) 17 Vanderbilt Journal of Entertainment and Technology Law 385. Hsu TM, Welner DH, Russ ZN, Cervantes B, Prathuri RL, Adams PD, Dueber JE, ‘Employing a Biochemical Protecting Group for a Sustainable Indigo Dyeing Strategy' (2018) 14 Nat Chem Biol 256
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Martin VJJ, Pitera DJ, Withers ST, Newman JD, Keasling JD, ‘Engineering a Mevalonate Pathway in Escherichia Coli for Production of Terpenoids’ (2003) 21 Nature Biotechnology 796. Merz JF, Kriss AG, Leonard DGB, Cho MK, ‘Diagnotic testing fails the test: the pitfalls of patents are illustrated by the case of haemochromatosis’ (2002) 415 Nature 577
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Schmidt M, ‘Diffusion of Synthetic Biology: A Challenge to Biosafety’ (2008) 2 Systems and Synthetic Biology 1. Schmidt M, Ganguli-Mitra A, Torgersen H, Kelle A, Deplazes A, Biller-Andorno N, ‘A priority paper for the societal and ethical aspects of synthetic biology’ (2009) 3 Systems and Synthetic Biology 4. Schmidt M, Pei L & Gaisser S, ‘Synthetic Biology in the View of European Public Funding Organisations’ (2012) 21 Public Understanding of Science 149. Schütte G, ‘What kind of innovation policy does the bioeconomy need?’ (2018) 40 New Biotechnology 82. Sigaux N, Pourchet L, Breton P, Brosset S, Louvrier A, Marquette CA, ‘3D bioprinting: principles, fantasies and prospects' (2019) 120 Journal of Stomatology, Oral and Maxillofacial Surgery
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Working/Research/Conference papers Andersen B, ‘The Rationales for Intellectual Property Rights: The Twenty-First Century Controversies’ (DRUID Summer Conference, Copenhagen, June 2003). www.scribd.com/document/327154843/Andersen-The-Rationales-for-IPRS-pdf accessed 2 April 2019. Cook TM, ‘A European perspective as to the extent to which experimental use, and certain other, defences to patent infringement, apply to differing types of research’ (Intellectual Property Institute Report 2006)
European Commission documents Commission, 'Synthetic Biology II: Risk assessment methodologies and safety aspects' (Opinion, European Commission 2015) ISBN: 978-92-79-43916-2. Commission, 'Synthetic Biology III: Risks to the environment and biodiversity related to synthetic biology and research priorities in the field of synthetic biology’ (Final Opinion, European Commission 2015) ISBN: 978-92-79-54973-1. Directorate-General for Research, ‘Synthetic Biology: A NEST Pathfinder Initiative' (European Commission 2007) ISBN 92-79-03832-X.
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European Group on Ethics in Science and New Technologies, ‘Ethical aspects of patenting inventions involving human stem cells’ (Opinion no. 16, European Commission 2002) ISBN: 92-894-3065-6. European IPR Helpdesk, 'Fact Sheet Intellectual Property in Biotechnology' (European Commission, June 2014)
WIPO documents WIPO, ‘Guide on Licensing of Biotechnology’ 708(E) (1992) ISBN: 92-805-0410-X. WIPO, ‘Exclusions from patentable subject matter and exceptions and limitations to the rights’ SCP 13/3 (2009). WIPO, ‘Study on patents and the public domain’ CDIP/8/INF/3 REV. (2011). WIPO, ‘Exception and limitations to patent rights: private and/or non-commercial use’ SCP/20 (2014). WIPO, ‘Exceptions and limitations to patent rights: experimental use and/or scientific research’ SCP/20 (2014). WIPO, ‘Reference document on research exception’ SCP/29 (2018).
WTO/EPO documents
European Union Intellectual Property Office & European Patent Office, ‘Intellectual property rights intensive industries and economic performance in the European Union’ (Industry-Level Analysis Report 2nd edn, October 2016)
National parliamentary documents (translated) Dutch Parliamentary Papers (‘Regulation of patent law for inventions’, Kamerstukken II 1904/05, 197, 3). (translated) Dutch Parliamentary Papers (‘Amendment to the National Patent Act’, Kamerstukken II 1984/85, 19 131 (R 1295) 3).
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(translated) Belgium Parliamentary Papers (‘Proposal to amend the Law of 28 March 1984 on patents to provide legal protection to biotechnological inventions’, Kamer van Volksvertegenwoordigers 2004-2005, Doc 51 1348/006) www.dekamer.be/FLWB/PDF/51/1348/51K1348006.pdf.
Theses Christiansen A, 'The Ethics of Synthetic Biology: Respecting Life and Managing Risk' (DPhil thesis, Københavns Universitet 2016). Su YC, ‘Redefining Open Source for Synthetic Biology' (Thesis, National Chung Hsing University 2012)
Websites and blogs
BioBrick Foundation at
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European Patent Office fees
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Oxford Dictionary
Newspaper articles/podcast Friedman L, Pierre-Louis K, Sengupta S, ‘The Meat question, by the Numbers’ The New Yorker (New York, 25 January 2018) www.nytimes.com/2018/01/25/climate/cows-global-warming.html accessed on 1 February 2019. Rosenwald MS, ‘J. Craig Venter's Next Little Thing: The man who mapped the human genome has a new focus: using microbes to create alternative fuels’ The Washington Post (Washington, 27 February 2006) www.washingtonpost.com/archive/business/2006/02/27/j-craig-venters-next-little- thing-span-classbankheadthe-man-who-mapped-the-human-genome-has-a-new-focus- using-microbes-to-create-alternative-fuelsspan/74635901-7e86-410e-8bf0- edae10bdd990/?noredirect=on&utm_term=.82bd9ac5644a accessed 10 January 2019. Specter M, ‘A Life of Its Own: Where Will Synthetic Biology Lead Us?’ The New Yorker (New York, 28 September 2009)
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Patent (applications) CELLINK AB, ‘Cellulose nanofibrillar bionik for 3d bioprinting for cell culturing, tissue engineering and regenerative medicine applications’ (2019) European Patent No. EP3233493A1 (pending). Memphis Meats Inc., ‘Method for scalable skeletal muscle lineage specification and cultivation’ (2019) European Patent No. EP3071040A4 (pending). Memphis Meats Inc., ‘Methods for extending the replicative capacity of somatic cells during an ex vivo cultivation process’ (2017) WIPO Patent No. WO2017124100A1 (pending). Techshot Inc., ‘Biomanufacturing System, Method, and 3D Bioprinting Hardware in a Reduced Gravity Environment’ (2018) United States Patent No. US20180163162A1 (pending).
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