Inside Green Innovation: Progress Report - Fourth Edition highlights:
- The number of patent filings related to the use of CRISPR mediated gene editing has generally seen rapid growth in the last ten years. However, although the use of CRISPR in agriculture initially followed a similarly rapid rise, since 2018 filings have fluctuated.
- Innovators of genetically modified crops face several hurdles, ranging from differing, and sometimes complex, regulatory restrictions in different countries to a complex ownership/licensing situation for the underlying CRISPR technology.
- The US has no official legislation banning genetically modified organisms (GMOs), whereas in the EU all GMOs, including plants, must undergo a strict and complex regulatory process.
- Several institutions, including universities and large biotech companies, have been locked in long-running patent disputes over ownership of the underlying technology.
- Despite difficulties, it is encouraging that patent filings are generally on an upward trend.
Feeding an ever-increasing global population in a sustainable way is an ongoing challenge. Issues such as crop failure and susceptibility to disease or pests, which are compounded by more extreme weather conditions linked to climate change, mean that global food security is a growing concern. Manipulating crops to make them more resilient to climate change has been the focus of significant research while genetically modifying crops to introduce commercially desirable traits – either by mutation breeding or introducing novel genes by genome editing techniques, is not a new idea. Indeed, the debate around the safety of genetically modified organisms (GMOs) is decades old. However, modifying crops by CRISPR mediated gene editing technology has received attention recently. CRISPR is undoubtedly one of the biggest breakthroughs in biotech in recent years. It is an efficient and highly selective technique that allows the DNA of organisms to be easily and precisely modified. Unsurprisingly, since its discovery there has been a great deal of activity in CRISPR-mediated gene editing across multiple sectors, including agriculture. Indeed, its huge potential means that the market for the technology is predicted to be billions, if not trillions, of US dollars.
Forecasts suggest that the use of CRISPR will have a significant impact on food production. “Applications of CRISPR-Cas in agriculture and plant biotechnology”, published in Nature Reviews, says this technology “allows precise genetic manipulation of crop species to develop…more sustainable agricultural systems”, and cites the most important applications of the technology as “increasing plant yield, quality, disease resistance, herbicide resistance, breeding and accelerated domestication”. Against the background of a growing global population and increasing concern for food security in a changing environment, could CRISPR-mediated gene manipulation be the key to unlocking more productive, disease-resistant, and environmentally sustainable crops?
Global patent activity
The number of patent filings for the use of CRISPR in general has seen rapid growth in the last ten years (Figure 1). While the use in agriculture initially followed a similarly rapid rise, since 2018 filings have fluctuated (Figure 2). The US remains the biggest patent filer in the area by far and the changes seen from 2018 was largely driven by fluctuations in US filings (Figure 3). Interestingly, 2021-2022 showed a sharp rise in filings coinciding with the end of the COVID-19 pandemic and the associated lockdowns. Although this could be entirely coincidental, it is possible that the diversion of resources into vaccine research during the pandemic could have played a part. It is unclear whether the current upward trend will continue.
Figure 1: Ten-year trend (2013-2022) - global priority filings - the use of CRISPR
(Priority filing = the first time a patent application for a unique invention has been filed (the first filing))
Figure 2: Ten-year trend (2013-2022) - global priority filings - CRISPR in agriculture
Figure 3: Ten-year trend (2013-2022) - global priority filings - US, Europe, Australia, China - CRISPR in agriculture
(Patent assignee = the owner of a patent/application, also known as the ‘applicant’ (for a patent application), patentee (for a granted patent), or proprietor.)
Notable companies
As discussed in the 2021 edition of our Inside Green Innovation Report, early patent applications in this area were filed by universities for underlying CRISPR research. However, industry quickly pulled ahead: out of the top 10 filers in the last 10 years, only one is an academic institution (the University of California). As shown in Figure 4, the top filers remain the same, indicating that the industry is dominated by the same key players. Recently granted patents in the name of Pioneer Hi-Bred Inc., which remains the highest filer in the area, include a transgenic soybean to express increased protein and a method to generate maize plants with enhanced resistance to northern leaf blight.
Figure 4: Ten-year overview (2013-2022) - top ten global filers - CRISPR in agriculture
Regulatory restrictions
Although the reason for the fluctuation in filings from 2018-2021 is difficult to speculate, it could be regulatory frameworks. Indeed, genetically modified plants are subject to varying regulatory restrictions in different countries. The US The US has no official legislation banning GMOs, with food produced using new breeding techniques (NBTs), including CRISPR technology, currently subject to similar standards as conventional foods. Nevertheless, all plants in the US are assessed for their “plant pest risk.” Under US Department of Agriculture (USDA) regulations, an engineered plant is considered a potential plant pest if it contains exogenous DNA from an organism on its list of plant pests, or if the method of introducing DNA into the genome involved an organism on the list (Agrobacterium is an example of an organism deemed a plant pest). The use of CRISPR may mitigate the actual risk from a new, modified crop, and so be an attractive technology to innovators. This is because, unlike traditional genetic modification methods which involve adding new genes to plants, the use of CRISPR does not necessarily involve inserting foreign DNA into the plant genome. Rather, new traits can be introduced by making small changes to existing genes. Indeed, gene editing using CRISPR could be seen as akin to crossbreeding in terms of the result, albeit with the dual advantage that it is much faster and much more precise. In 2017, the USDA withdrew an Obama-era plan to overhaul how it regulated biotechnology products such as genetically engineered (GE) crops, leaving the status of gene-edited plants uncertain. This may have led to a drop in US filings in the 2017-2018 period (as seen by the fall in publications in 2019). However, greater clarity was given in 2019 when President Trump signed an executive order to streamline the approval process for genetically engineered plants by exempting low-risk products from existing rules. In 2020, the Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient (‘SECURE’) Rule was finalised. The aim of the rule, which is now called the Revised Biotechnology Regulations, is to regulate modified organisms with greater precision, further reducing regulatory burden for developers. Importantly, it exempts plants with a single sequence edit from oversight, as well as any genetically engineered plant that has the same “plant-trait-mechanism of action” as one previously regulated by the USDA. The steep rise in patent publications since 2021 coincides with the introduction of this rule (bearing in mind the 18-month lag between filing and publication). Overall, the US is an attractive jurisdiction for innovation in the field of genetically engineered crops, particularly using CRISPR technology. This could perhaps explain why it has led the way in patent filings related to the use of CRISPR in agriculture. It will be interesting to see whether the upward trend continues, particularly with the more lenient regulatory framework introduced in the Revised Biotechnology Regulations. Europe In contrast, in the EU all GMO plants must undergo the same strict and complex regulatory process. This includes transgenic plants and those created by new genomic techniques (NGTs), i.e., those edited without introducing foreign genetic material, meaning that few GMO plants get approval in the EU. This may in part explain the lower number of European priority filings compared to the US. However, since 2019 priority filings have risen steadily and not fluctuated in the same way as in the US, suggesting that Europe may be an emerging major player (Figure 3). The EU Commission recently proposed a new regulation to relax the rules for lower risk NGT plants. The proposal was to create two categories of NGT plants:
1) NGT1 plants which comprise fewer than 20 genetic modifications and could occur naturally or by conventual breeding, and
2) NGT2 plants which have greater than 20 genetic modifications. NGT1, but not NGT2, plants would be exempt from GMO regulatory legislation under the new regulation. However, in February 2024 the EU Parliament, as part of its negotiations with the Commission, put forward an amendment to exclude from patentability “NGT plants, parts thereof, genetic information, and the process features they contain”. The aim of the proposal is “to avoid legal uncertainties, increased costs and new dependencies for farmers and breeders” and would be introduced by way of amendment to the EU Biotech Directive. The European Patent Convention (EPC) typically harmonises itself with this directive. Importantly for innovators, the proposal, if accepted, would exclude all NGT plants from patentability. In other words, it does not distinguish between NGT1 and NGT2 plants. Unsurprisingly, the proposals have been highly controversial. Innovators and intellectual property professionals have raised concerns that while the regulations may lower barriers for NGT1 plants to enter the market in the EU, the suggested ban on being able to obtain patent protection may deter investment. Alternative proposals, as a compromise, include excluding only NGT1 plants from patentability, or requiring patent holders to waive their rights in respect of NGT1 plants (in exchange for the reduced regulatory process). Whether the new regulation and the amendments to the Biotech Directive are enacted in their current form remains to be seen. In any case, it will be interesting to how the legal uncertainty affects patent filings for plants modified by NGTs, be it via CRISPR or otherwise. For example, will filings continue the upward trajectory – whereby innovators try to obtain patent protection for NGT plants while they can – or will the uncertainty make innovators and investors nervous? UK Since Brexit, the UK is no longer bound by EU laws, including the EU Biotech Directive. Therefore, if the EPC aligns itself with any future-amended EU Biotech Directive to ban patents for plants modified by NGTs, the UK may become a more attractive jurisdiction for innovators. The Genetic Technology (Precision Breeding) Act was passed by the government in 2023. It did not refer to any proposals to ban patents for NGT plants, so paving the way for producers to sell genetically modified food commercially in the UK. However, secondary legislation required to bring the act into effect was not passed before the recent general election, so the law has been paused. The new Labour government has pledged closer alignment with the European Union, particularly on regulations that might affect trade, leaving the industry and innovators in limbo. Leading scientists across the UK have urged the Department for Food and Rural Affairs (Defra) to act “quickly and decisively” to pass the secondary legislation. However, whether the law finally gets enacted and what the impact may be on innovation remains unclear.
Licensing Another factor which may impact the use of CRISPR to edit plant genomes is the availability of the technology. As already discussed, CRISPR is one of the most important new technologies of recent years and is rightly deemed to be a game changer by many. As a result, not only have many patent applications been filed for the underlying technology, they have also been the subject of a series of high-profile ownership disputes. Institutions including Vilnius University (which filed first but has an invalid priority claim), the Broad Institute/MIT/Harvard (‘Broad’), the University of California/University of Vienna/Charpentier (‘CVC’; which has the earliest priority date), Sigma and Toolgen, have been locked in long-running patent disputes. In the US, Broad has been found to own the rights to use CRISPR in eukaryotic cells. Broad licences the technology to Editas Medicine for human therapeutics. However, it also grants non-exclusive licenses to any company wishing to use CRISPR in tool development. In 2017 Pioneer Hi-Bred Inc. and the Broad Institute collaborated to license CRISPR technology, agreeing to jointly provide non-exclusive licenses for the commercial use of CRISPR in crop agriculture as well as making the intellectual property freely available to academic research institutions. The provision of licenses to underlying CRISPR technology is key to encouraging research into the genetic modification of crops. Resolving ongoing ownership disputes, giving third parties more certainty about who owns the technology and, therefore, where to obtain a licence, is likely to further promote innovation in the field. It will be interesting to see if this translates into more patent filings in the future. Conclusion Providing crops with desirable traits is likely to be critically important as uncertainty around food security increases globally. Innovators in genetically modified crops face several hurdles, ranging from differing, and sometimes complex, regulatory restrictions in different countries to a complex ownership/licensing situation for the underlying CRISPR technology. However, despite these difficulties, it is encouraging that patent filings are generally on an upward trend. Data collection This article reports patent filings where CRISPR technology has been used in the Examples section of the patent application, i.e., where experimental data using CRISPR-mediated gene editing has been provided to support the invention. This is therefore a more stringent requirement than CRISPR being mentioned anywhere in the patent application, which would also pick up patent applications where the applicant speculates that CRISPR technology could be used to alter desired plant traits (without actually having done so). Due to an 18-month lag between priority filing (first patent filing) and publication, data for 2023 and 2024 has not been reported.
Sarah Gibbs Senior Associate
Oliver Herd Trainee Patent Attorney