Biodiversity and patents: Overview of plants and fungi covered by patents

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors, Plants, People, Planet © New Phytologist Foundation 1Royal Botanic Gardens, Kew, Richmond, UK 2Department of Environmental and Geographical Science, University of Cape Town, Rondebosch, South Africa 3Vice-Presidency of Research and Biological Collections, Fundação Oswaldo Cruz – Fiocruz, Rio de Janeiro, Brazil 4The Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing, China 5Department of Plant Biology & Biodiversity Management, College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia


Social Impact Statement
Patents can be used as a measure of innovation and to illustrate the commercial potential of plant and fungal biodiversity. The proportion of plant species named in patents represents only 6.2% of plant species, whereas the proportion of fungi is likely less than 0.4%. Fungi clearly justify further research. Innovation on a species usually drives more innovation on that species. We suggest that we should ensure that commercialization frameworks encourage studies on a greater diversity of plants and fungi. This could not only increase the range of biodiversity-based products and associated income but also incentivize their conservation and encourage more fundamental research.

Summary
In this review, patents are used as a measure of innovation, and data show that a low proportion of plant and fungal biodiversity is mentioned in patents. The proportion of plant species named in patents represents only 6.2% of plant species, whereas the proportion of fungi is most likely less than 0.4%. The number of species within a plant family mentioned in patents varies greatly. The following families having the greatest numbers: Asteraceae with 1,445 species (4.5% of species), Fabaceae with 1,299 species (5.8%), Poaceae with 1,008 species (8.5%), and Rosaceae with 718 species (12.7%). Case studies from Brazil, Ethiopia, and South Africa explore some of the controversies associated with patenting, especially when patents have not taken prior art into account. In contrast, a case study on plants and fungi used in traditional Chinese medicine illustrates their economic value and their potential to support new innovations. Innovative ways to use plant and fungal biodiversity has the potential to generate wealth, reduce poverty, improve human well-being and in theory incentivize biodiversity conservation. International and national policies and laws that aim to facilitate equitable benefit-sharing associated with access to and use of genetic diversity need to be reviewed to help facilitate innovation, as well as ensure that the rights of communities to use these resources are recognized and supported.

| INTRODUC TI ON
This review provides an overview of the diversity of species of plants and fungi subject to patents and some of the challenges associated with patenting these resources. As a species, Homo sapiens has evolved using available biodiversity and domesticated those species that were found to be highly beneficial for consumption and trade (Meyer, DuVal, & Jensen, 2012). Over time, we have concentrated on commercializing a narrow range of plants and fungi to support our day-to-day activities, especially those living in urban environments. The plants and fungi we use are fundamental to the quality of our lives (Keune et al., 2013), yet it is not always easy to identify, retrospectively, the steps made to optimize the economic benefits of some species over others.
One way to monitor the diversity of plants and fungi subject to commercial use is to monitor those that are subject to different forms of Intellectual Property Rights, such as patents, and also record which species have and are being traditionally used (see reviews by Grace et al. (2020), Howes et al. (2020), Prescott et al. (2018) and Ulian et al. (2020)). In this review, we use patents as one way to illustrate innovation in the use of plant and fungal resources. The commercialization of plant and fungal genetic resources via patents has the potential to generate wealth, reduce poverty, improve human well-being and in theory incentivize biodiversity conservation. Therefore, a case could be made to increase the diversity of plants and fungi being commercialized. To help realize this potential, international policy agreements have been established that govern access to and sharing of benefits from the utilization of genetic resources and associated traditional knowledge. However, these policies and their related national laws have so far largely failed to achieve the intended outcomes (Laird et al., 2020). Laws also differ among countries in the legal frameworks for patents (Jarvie, 2016).
For example, some laws allow whole plants/fungi and the products from those materials to be subject to patent restriction, which could include restrictions for their use as food or feed (Correa, Correa, & De Jonge, 2020). Therefore, in some cases patents may not be the appropriate commercial pathway.
Value chain analysis provides a route to evaluate the role of different groups in the commercialization process and shows that usually the provider of the raw material gains less than those involved in producing the final product (Hishe, Asfaw, & Giday, 2016;FDA, 2018;Havardi-Burger, Mempel, & Bitsch, 2020). How to increase the utilization of biodiversity in ways that provide income for all involved is a huge challenge, especially for those in low-and middle-Gross Domestic Product economies (Stannard & Moeller, 2013) at a time when we are witnessing a substantial increase in the loss in biodiversity (IPBES, 2019;Nic Lughadha et al., 2020). Patents are in themselves only one step in the commercialization process and will require investment and a market, but if supported by appropriate agreements could illustrate the economic importance of plant and fungal diversity.

| P OLICIE S A SSO CIATED WITH THE US E OF B IODIVER S IT Y
The Convention on Biological Diversity (CBD) aims to provide a fairer system associated with the exploitation of genetic resources.
The CBD prescribes that agreements should be founded on mutually agreed terms, with equitable benefits to countries and local communities that provide resources and knowledge and help conserve biodiversity and support its sustainable use (https://www.cbd.int). A series of additional agreements and protocols have been developed, including the Nagoya Protocol (https://www.cbd.int/abs) and its Internationally Recognized Certificates of Compliance and the Aichi Biodiversity Targets (https://www.cbd.int/sp/targe ts/) (see review by Williams et al. (2020)).
Ethnobotanical reviews such as those undertaken by Pushpangadan, George, Ijinu, and Chithra (2018) in India can provide insight into the traditional uses of biodiversity and also enable that information to be available to others, including patents agents.  Gebru (2018) provides examples of controversies that have arisen because those filing patents did not provide full information about the background of their innovation, especially traditional knowledge about the uses of the named genetic resources, this can lead to accusations of "biopiracy." The term was coined to illustrate the practice of commercially exploiting biological resources and/or traditional knowledge, especially through the patent system, without sharing the financial and/or non-monetary benefits with the source community, country, or knowledge holder (Amusan, 2014; Dutfield, 2007;Hamilton, 2006 Oldham, Hall, and Forero (2013)   The Crops for the Future (http://www.under utili zed-speci es.org/ speci es/about_speci es.asp). However, most of these patents relate to non-food uses of these plants. Vincent et al. (2013) identified 3,546 species that are classified as relatives of crop plants and thus could contain economically important traits. There is clearly greater potential to realizing the commercialization of these underutilized plants, with some innovations justifying patents.

| E XIS TING PATENTS ON PL ANTS AND FUNG I
Jarvie (2016) found little evidence that legislative changes due to TRIPS had encouraged an increased diversity of species to be commercialized. Correa et al. (2020) in their overview of patents on food plants showed that 40% of countries in the Global South excludes the patentability of plants in their patent regimes. In contrast, most have followed the European approach that excludes plant varieties from patenting, but allows patenting of nucleic sequences that could enable the production and commercialization of by-products from the plant/fungi as sources of food. In taking these patents forward, it is important that the commercialization being studied but, in their review they highlight the need for having scientists from both low-income (often biodiversity-rich) and high-income countries (often lower biodiversity) involved in the research-supporting greater ownership and knowledge about the patent process. A critical element is that the source country should collaborate, as an equal partner, in the supply and potential production of the leads that result from their biodiversity. This is, of course, easier to achieve with leads that still require the original genetic resources; it is not so easy to achieve when a synthetic compound is involved that is derived from a natural ingredient. and a mixture of "murumuru butter, Acai berry extract and Inca Inchi oil" to increase hair shine (EP3395410A1).

| OVERVIE W OF PL ANT B I OD IVER S IT Y B EING PATENTED, AND THOS E S PECIE S ALRE ADY K NOWN TO HAVE US E S
The most complete overview of species of plants covered by patents is that reported by Oldham et al. (2013). We used this list to provide an overview of the distribution of patents among different plant families.

F I G U R E 1
Overview and phylogenetic distribution of the number of plant species per family that have been subject to patents over the period 1976 to 2010 (based on data from Oldham et al., 2013). The phylogenetic tree has been modified from the "ALLMB" tree of Smith and Brown (2018) to include only one tip for each family of angiosperms        We first compared the list of plants collated by Oldham et al. (2013) with the accepted names and synonyms within Kew's World Checklist of Vascular Plants (WCVP, 2020) and International Plant Names Index (IPNI, 2020). The number of species collated by Oldham et al. (2013) was 26,111 names and this was reduced to 21,395, since some were ambiguous and the list also included the same species several times under alternative scientific synonyms (Data S1    (Hawksworth & Lücking, 2017). Second, if countries are to increase the economic wealth derived from their biodiversity, it is important that they increase the research undertaken on these resources. This in turn will improve the opportunities for the discovery of attributes directly or indirectly associated with species that could be patented. However, it is critical to emphasize that patents are not the only route to successful commercialization; many species in trade today do not have associated patents, and factors such as value-adding, market access, and knowledge networks are often much more important attributes than patents (Wynberg, Silveston, & Lombard, 2009). It is also clear that there needs to be more support to enable current ABS policies to work. Patent agencies and those filing patents need to be more aware of the traditional uses of the genetic resource associated with the patents and the origin of these genetic resources. This also requires a legal obligation for those filing patents to disclose this information, alongside proof of appropriate benefit-sharing agreements. This disclosure requirement has been increasing adopted by countries, but agreement on an international approach remains stalled.

| CON CLUDING REMARK S
Currently, it is very difficult to map the economic benefits from the exploitation of a species of plant or fungi as a result of a patent.
Value chain analysis would suggest that those involved in the supply of the raw material gain less that those involved in the production of the final product. However, communities in biodiverse-rich source countries could clearly benefit from commercialization of their genetic resources. If public and private research bodies are to invest in biodiversity research and the commercialization of products based on genetic resources, then those investing in the commercialization of any resulting patents need confidence that risks associated with ABS issues have been minimized. Source countries, in turn, need to be assured that this knowledge will be used to benefit both people and conservation in a fair and equitable manner.
Teff is an Ethiopian ancient grain used to make injera, a spongy  (2012), "It was a pilot case of the implementation of the CBD in terms of ABS, and expectations were high. However, implementation of the agreement failed as HPFI was declared bankrupt in 2009." As part of the ABS agreement, HPFI was given access to teff varieties, with the right to use these varieties to produce a wide range of specified food and beverage products not traditional in Ethiopia. In return, the company was to share monetary and non-monetary benefits with Ethiopia.
By the time HPFI was declared bankrupt, Ethiopia had received only EUR 4,000. However, prior to the bankruptcy, the HPFI directors had transferred IP to new companies. These companies continued to produce and sell teff flour and teff products, expanding their activities to other countries. The new companies are not party to the original agreement, and thus not bound by the obligations of HPFI toward Ethiopia, although they did operate under the same directors.
The patent also covers the milling of flour from these grains to a fine powder and then mixing with water to make a dough. These activities are common in Ethiopia and therefore lack novelty. The teff patent excludes all other parties, including Ethiopia, in utilizing teff for most forms of relevant production and marketing in the countries where the patent is granted. This marginalized Ethiopia from utilizing its own teff genetic resources. The teff patent created a monopoly that made it impossible for Ethiopia to enter into ABS agreements on teff with other companies in countries where the patent is valid, even after termination of the teff agreement. After delays, the Ethiopian Attorney General's Office announced in May 2018 that it was filing a case against those involved in the teff patent at the International Court of Arbitration in Paris. However, before the case was launched, the patent owners sued another Dutch company, Bakels, that had been marketing its own teff baked goods for patent infringement. The Dutch patent office declared that HPFI's patents were invalid in the Netherlands because they "lack inventiveness." This decision was upheld by the District Court in the Hague. However, the patents are still valid in Belgium, Germany, Austria, Italy, and the UK. Thus, although the patent dispute was between two Dutch companies, the ruling gives the Attorney General's Office of Ethiopia a good opportunity to claim and register the patent right on the use patenting of teff to the concerned international body.
This example illustrates a breakdown in the spirit of the original CBD that stakeholders in a country from which a genetic resource comes should have been involved in the initial patents and it also highlights a lack of rigor by the patent agents to have spotted prior art associated with the use of teff when the patent was filed.

| C A S E S TUDY 2 . DE VELOPMENT OF A SOAP FROM MURUMUR A
Since the 1990s, the Ashaninka Indians, of the Amonia River Kampa

| C A S E S TUDY 3 . PATENTS FILED ON ANDIROBA
Patents filed on two species of plants known collectively as andiroba

| C A S E S TUDY 4. SOUTH AFRI C A E X AMPLE S OF PATENTS
South Africa is the third most biodiverse country in the world, with some 22,000 plant species (https://www.sa-venues.com/plant -life/) and 1,160 fungal species (Kinge, Goldman, Jacobs, Ndiritu, & Gryzenhout, 2020) identified. It has also been at the global forefront of regulating access and benefit sharing (Crouch, Douwes, Wolfson, Smith, & Edwards, 2008;Wynberg, 2018). Over the past 20 years a suite of benefit-sharing agreements has been negotiated, many triggered by the lodging of patents-and associated disregard of traditional knowledge.
The first, and perhaps best known, case was that of the succulent plant Hoodia gordonii (Masson) Sweet ex Decne., long used to stave off hunger and thirst by the indigenous San, the oldestand most marginalized-human inhabitants of Africa (Deacon & Deacon, 1999). The active ingredients of the plant were patented in 1998 by the South African-based Council for Scientific and Industrial Research (CSIR) for the purpose of developing anti-obesity products (Wynberg & Chennells, 2009 The number of patent publications that the species appear in from 1976 to 2010 data from Oldham et al. (2013). c C. cassia is the species used in TCM. However, sometimes publications do not differentiate between C. cassia and C. verum J.Presl. In the Oldham et al. (2013) list the only species of Cinnamomum mentioned is C. verum. It is possible that some of the 134 patent publications cited in Oldham et al. (2013) refer to C. cassis. That is why the number is in brackets.
In the case of Pelargonium sidoides DC., a plant that occurs across the eastern part of South Africa and in Lesotho, pharmaceutical company Schwabe lodged several patents related to the plant's use for treating upper respiratory infections. This led to accusations of "biopiracy" (ACB, 2008) and a patent challenge was brought by NGOs and Schwabe competitors objecting to the patent on the conventional grounds of lack of novelty, lack of inventive step, and insufficiency. Although the biopiracy arguments were rejected by the EPO, the patent was later revoked for lack of an inventive step.
Finally, the endemic rooibos plant (Aspalathus linearis (Burm.f.) R.Dahlgren) reveals how sometimes the patent and innovation landscape may be overlooked in the wider quest for justice. Since 2010, indigenous San and Khoi organizations have demanded that the 100-year-old rooibos industry recognize the role that their traditional knowledge played in its development (Wynberg, 2017).
This led to the conclusion of a benefit-sharing agreement in 2019.
However, little attention has been given by the government to the surge of interest in the plant's biochemical and health properties.
Much of this research is linked to more than 140 foreign patents. While many might be commercially dormant, they raise questions about how material was accessed and compliance with South Africa's Biodiversity Act.

| C A S E S TUDY 5. VALUE AND PATENTS ON KE Y PL ANTS AND FUNG I US ED IN TR AD ITI ONAL CHINE S E MED I CINE
Plants and fungi used in traditional Chinese medicines (TCM) are of economic importance to China. Table 1 provides a list of the top 19 species of plants and fungi used in TCM that are exported internationally, the volumes exported and the value. Added to this Table is the number of patents associated with each species as reported by Oldham et al. (2013). In contrast, to the patents discussed in Case studies 1-4, this case study is provided to illustrate that plants and fungi with a well-documented history of use can still generate a high number of patents. These patents do not restrict those using the plants and fungi traditionally. Prior art of the plants and fungi is also well documented in Chinese Pharmacopoeia and Materia Medica available to patent agencies when checking for innovation.
These patents illustrate the commercial interest in these resources. For example, patents for Panax ginseng C.A. Mey. include new methods to process the material (EP1467627B1) that can impact efficacy, whereas Rajabian, Rameshrad, and Hosseinzadeh  (2018) reviewed the data on the availability of O. sinensis and showed that supply is negatively impacted by both over harvesting but also by climate change. Patents US8008060B2 and CN102550300A cover different methods of growing the fungus in artificial conditions that result in material with a similar chemical composition to wild harvested material. Other patents relate to non-medical uses, for example, Nestlé S.A. and L'Oréal S.A. are sharing a cosmetic patent using Lycium barbarum L. fruit extract as an agent to restore skin tone and firmness (ES2523853T3). A Korean patent with Codonopsis pilosula (Oliv.) D.Y.Hong as the active ingredient claims to control insects (KR20190057010A).

ACK N OWLED G EM ENTS
The