CRISPR Technology in the Agriculture Industry: Patent and Regulatory Updates | Jones Day
The ability to edit eukaryotic DNA implies an almost unlimited ability to alter the genetic makeup of the plants that become our food. Recently, scientific attention has focused on the application of a class of new gene editing techniques that use CRISPR to food crops for the introduction of commercially desirable traits. GM crops can have a positive impact on food productivity, quality, and environmental sustainability, and CRISPR is unique in its relative simplicity, robust flexibility, cost-effectiveness, and wide scope of use. The increased use of CRISPR in agriculture has endless applications, the consequences of which have only recently been analyzed.
CRISPR and the power of gene editing
The term CRISPR generally refers to a class of gene editing mechanisms derived from prokaryotic immune systems. These mechanisms have two main components: guiding RNA molecules that direct the second component, CRISPR-associated (“Cas”) proteins, to the target region of cellular DNA. These Cas proteins induce a double strand break in DNA and allow targeted manipulation of the desired genetic code. There is incredible diversity in the CRISPR-Cas system and a host of different Cas proteins that can be fine-tuned to induce desired changes with high specificity, including turning on or off individual genes, or inserting genes other organisms in the target genome.
The flexibility of CRISPR stands in stark contrast to the previous generation of gene-editing technologies, such as zinc finger nucleases and transcriptional activator-type effector nucleases (“TALENs”), which require massive amounts of research and development. preventive development and have a much more limited scope. useful. This simultaneous precision and flexibility therefore offers many opportunities for genetic optimization of food crops and has already been used in some cases to create, for example, browning resistant fungi. End of 2021, in Japan, the first food product edited by CRISPR was introduced to the world market: tomatoes with high levels of GABA, a natural neurotransmitter, due to a gene inactivated by CRISPR.
The power of CRISPR has incredible potential for innovation, but the rights and regulations associated with CRISPR have been elusive and, at times, controversial. CRISPR’s groundbreaking technology has been the subject of a series of disputes over patent, inventor and, therefore, ownership priority between leading research institutes, with recent results having important implications for the world. global food supply.
Like most breakthrough technologies, the invention of CRISPR was accompanied by a flurry of patent filings in the United States and elsewhere, as researchers who brought CRISPR to light sought to protect and monetize their rights as inventors. Many academic institutions, including the Broad Institute of Harvard and MIT, University of California, University of Vienna, Vilnius University, Rockefeller University, and companies such as ToolGen, Inc., Sigma-Aldrich (Millipore Sigma), Caribou Biosciences, Inc., Editas Medicine, Inc., Keygene NV, Depixus, Blueallele Corp. and CRISPR Therapeutics AG, among many other institutions and companies, have obtained US and foreign patent rights related to applications of CRISPR technology. As CRISPR continues to expand, particularly in the case of CRISPR-edited agriculture which escapes many regulations that other GMO foods cannot, the complexity of the patent landscape will almost certainly continue to grow.
EU regulatory landscape
In general, the EU subjects agricultural products modified with CRISPR technology to the full suite of genetically modified organism (“GMO”) approval, safety and labeling requirements before commercialization. The main EU regulation on the point, Directive 2001/18/EC (the “GMO Directive”), was enacted in 2001 by the European Parliament and the Council of the European Union. The GMO Directive obliges all EU Member States to create appropriate precautionary measures regarding the release of GMOs on the market. However, the definition of GMO in the GMO Directive apparently excludes CRISPR modification, stating that a GMO is like “an organism, except human beings, whose genetic material has been modified in a way that does not occur naturally by mating and/or natural recombination.”
It was only in 2018 that the EU filled this gap in the GMO Directive. In July 2018, the Court of Justice of the European Union explained in Case C-528/16 that organisms obtained by mutagenesis are GMOs within the meaning of the GMO Directive. “Only organisms obtained by means of mutagenesis techniques/methods which have been used conventionally in a number of applications and which have a long history of safety are excluded from the scope of this guideline.”
The following year, in November 2019, the Council of the EU has formally requested that the European Commission “present a study in the light of the judgment of the Court of Justice in case C-528/16 concerning the status of new genomic techniques with regard to Union law, and a proposal, the appropriate given the results of the study.” The 117 page study was published in April 2021, and finally confirms the conclusion in case C-528/16, stating that “the study clearly shows that organisms obtained by new genomic techniques [including CRISPR] are subject to GMO legislation.” Based on the results of the study, the The European Commission has requested public input on a legislative proposal for “plants obtained by targeted mutagenesis and cisgenesis and for their products intended for human and animal consumption”. The public comment period expired July 22, 2022. The European Commission expects to finalize the proposed framework in 2023.
Regulatory landscape in the United States
Unlike the EU approach, the US does not currently regulate CRISPR-modified agricultural products as GMOs. The United States regulates biotechnology and genetic modification of foods through a “Coordinated framebetween the United States Department of Agriculture (“USDA”), the Food and Drug Administration (“FDA”) and the Environmental Protection Agency (“EPA”).
At a high level, the USDA regulates the use of biotechnology in plant products by the Plant Protection Act. The The USDA explains that the Plant Protection Act gives the USDA’s Animal and Plant Health Inspection Service (“APHIS”) the authority to regulate “organisms and products that are known or suspected to be plant pests or pose a pest risk, including those that have been altered or produced by genetic engineering.” Additionally, in 2018, the USDA Agricultural Marketing Service promulgated the National Standard for Disclosure of Bioengineered Foods, 7 CFR Part 66 (the “BE Disclosure Standard”), which created a “new mandatory national code  the Food Disclosure Standard” and associated record keeping requirements, effective January 1, 2022. The BE Disclosure Standard defines foods derived from biotechnology as food products that contain “genetic material that has been modified by in vitro [DNA]” and ” for which the modification could not otherwise be obtained by conventional breeding or found in nature. Notably, the USDA has not explicitly clarified whether CRISPR-edited agricultural products are considered “foods derived from biotechnology” and subject to the BE disclosure standard. presentation from 2020the USDA said it “intends to determine on a case-by-case basis whether a specific modification would be considered ‘discovered in nature’ or obtained by ‘conventional reproduction‘. (For more information on the standard BE Disclosure, see Jones Day May 2022 publication, Are your labels up to date? Ensure compliance with the USDA National Bioengineered Food Disclosure Standard.)
Additionally, the FDA regulates the use of biotechnology in plants with an emphasis on ensuring that foods are safe for human consumption. In 1992, the FDA issued a Policy Statement Regarding Foods Derived from New Plant Varietiesin which the FDA stated that “[t]The regulatory status of a food, regardless of the method by which it is developed, depends on the objective characteristics of the food and the intended use of the food (or its components). Since then, the FDA has reviewed genetic modifications made to foods. in the context of food additives, so FDA approval is required to use food additives unless they are generally recognized as safe (“GRAS”). In the opinion of the FDA, a GMO is not GRAS if the modified substance “differs significantly in structure, function, or composition from substances currently found in food.” In contrast, a GMO is GRAS if it is “naturally present” in the food product, even if it is bio-engineered to be present at a “higher level” than that found in nature or if there are “minor variations in the molecular structure that do not affect safety.” As explained in the introduction, CRISPR technology differs from conventional gene editing because it does not introduce new substances into a product that are not naturally present t. As a result, CRISPR-edited agricultural products are generally not regulated by the FDA as food additives.
The EPA is also reviewing the use of biotechnology in plants because it regulates the distribution, sale and use of pesticides to ensure that they “will not pose unreasonable risks to human health or the environment when used according to label directions”. In addition, when the EPA evaluates Plant Incorporated Protection Agents (“PIPs”), which are genetically modified pesticides, the EPA “requires extensive studies containing many factors, such as risks to human health , non-target organisms and the environment; the potential for gene flow and the need for insect resistance management plans.” As such, CRISPR-edited pesticides may be regulated by the EPA as PIPs.
The patent and regulatory landscape for the use of CRISPR technology in food continues to unfold across the world. Therefore, agricultural businesses and the agriculture industry as a whole should pay close attention to all developments.