from Nature Reviews via Checkbiotech.org
by Barbara Fleck & Claire Baldock
Barbara Fleck and Claire Baldock are at the Boult Wade Tennant, Verulam Gardens, 70 Gray's Inn Road, London WC1X 8BT, United Kingdom.

The economic and political issues that accompany the commercial growing of genetically modified crops, as well as the risk of transgene spread, are often top of the agenda for debate. But one important aspect is frequently overlooked — the intellectual property protection of plant-related inventions. What protection does European patent law afford to such inventions, how does it compare with the United States law and what are the consequences of the differences between them?

Genetic modification (GM) is one of the most controversial technologies of the twenty-first century and governments worldwide are grappling with legislation problems. In the United Kingdom, for example, the GM Science Review Panel has recently published its review of scientific knowledge on GM crops and foods in an effort to assist the government with future policy decisions. The public was also invited to take part in the debate and to submit their comments and thoughts on GM food, which will be released in a report later this year¹.

The debate has become increasingly political, with the threat of a trade war between the United States and Europe over the labelling of GM food. In Europe, food that is derived from GM crops must be labelled, but such labelling is not required in the United States². Together with Argentina, Canada, China, South Africa and Australia, the United States is one of the principal countries where GM food is grown — in 2002, it accounted for 68% of the global transgenic crop area^{3, 4}.

The public and many scientists are often unaware of a crucial aspect of the GM debate: the intellectual property protection of plant-related inventions. This is important because access to patents for plant-related inventions can influence the funding that is available for research, in particular in the private biotechnology sector. If and how patents (Box 1) can be obtained for GM plants is determined by national patent law.

The advent of molecular biotechnology and the development of new techniques, ranging from genetic sequencing to the creation of transgenic animals and plants, have set a new challenge to the patent system. National and international patent laws have been devised for technical inventions, but at the time when the rules and regulations for such laws were established, the development of inventions that involved life forms was not conceivable. For those countries that now do allow, in principle, patents that are directed to life forms, the boundaries of what can and cannot be patented in the biotechnology field are determined by the national courts.

In Europe, the European Commission introduced a directive in 1998 in an effort to clarify what should and should not be patentable in biotechnology; however, so far, the directive has been implemented in less than half of the member states^{5, 6}. The European Patent Convention (EPC), which governs European patent law, has recently been amended to include regulations on the patentability of biotechnology inventions⁷.

Here, we provide an overview of how plant-related subject matter, such as new transgenic plant varieties or gene sequences, can be protected, particularly in Europe. We review the systems that are available to obtain such protection, including plant breeder rights and the patent system, taking into account recent developments in European patent law. We also discuss the protection that is available in the United States for plant-related inventions, as well as recent decisions in this field.

Plant breeder rights

Before the advent of targeted genetic engineering, new plant varieties were generally obtained by traditional breeding methods that involved the selection and crossing of individual plants with improved traits. Today, a new variety might be produced using either conventional breeding methods or genetic engineering. The International Convention for the Protection of New Varieties of Plants (UPOV Convention) is a multilateral agreement that provides a system for the protection of new plant varieties. It was first adopted in 1961 and was revised in 1991 (Ref. 8). So far, the Union for the Protection of New Varieties of Plants (UPOV), which is the independent intergovernmental body established by the UPOV Convention, comprises 52 members, including member states of the European Union, the United States, Canada, Argentina and China.

According to the UPOV Convention, a plant variety that is developed by a breeder is defined as a plant grouping in a single botanical taxon of the lowest known rank. It is further defined by the expression of at least one characteristic that results from a given genotype and distinguishes the variety from other plant groupings. Furthermore, a variety is considered as a unit with respect to its suitability for being propagated unchanged⁹.

The UPOV Convention definition of variety has become an important factor in assessing the patentability of inventions that are developed by GM technologies in Europe, as it has been used to interpret Article 53(b) of the EPC, which excludes patents that are directed to plant varieties^{7, 10}.

Whereas patents provide protection for variants that fall within the scope of the invention, plant breeder rights refer to a single variety. Accordingly, the criteria for obtaining a right for a plant variety are different from those for obtaining a patent. There are four basic requirements that a variety must fulfil before a plant breeder right can be granted: the variety must be new, distinct, uniform and stable¹¹. Under the revised 1991 version of the UPOV Convention, a plant breeder right is granted for a minimum of 20 years¹².

The revised UPOV Convention also contains a provision that, in certain situations, entitles the farmer who grows a protected variety to save and reuse seed for the production of a subsequent crop on his or her farm¹³. This provision is of particular relevance for subsistence farmers in developing countries who use plant varieties for their own food production. Another important feature of the UPOV Convention that differs from the protection provided by the patent system is the exclusion of the rights with regard to the use of the protected variety for further breeding¹³. This exclusion ensures that important genetic resources can be freely used by the worldwide community for further breeding.

The UPOV Convention, as adopted in 1961, imposed a ban on the dual protection of the same invention by both the plant breeder rights system and the patent system, but this was removed in the revised 1991 UPOV Convention⁸. This change made it possible for the contracting states to issue patents that covered plant varieties, particularly transgenic plants, according to national patent law, provided that this law did not contain exclusions to the patentability of life forms. Dual protection is possible in the United States.

Protection in Europe

As mentioned above, many European countries are members of the UPOV. However, to make the protection of plant variety rights in the European member states easier by creating a single European procedure, the Council of the European Union established the community plant variety right (CPVR) on the basis of the provisions of the UPOV Convention¹⁴. A plant variety right can be granted by the Community Plant Variety Office for a single plant variety that has been generated by traditional breeding or through genetic engineering, provided that the variety fulfils the criteria of distinctness, uniformity, stability and novelty¹⁵.

Although a community plant variety right gives protection for a new plant variety, other plant-related inventions can be protected by a patent. In Europe, patent law is governed by the European Patent Convention (EPC), which was signed in 1973 and now comprises 27 member states. Based on the UPOV Convention, which did not allow the dual patenting of plant varieties, Article 53(b) of the EPC excludes plant varieties, animal varieties and essentially biological processes for the production of plants or animals, from patentability. However, this provision does not apply if they are the products of microbiological processes⁷.

The way in which the regulations that cover biotechnology inventions (as set out in the EPC) are applied and interpreted is best exemplified by recent decisions that have been made by the European Patent Office (EPO) on individual patent cases. With the development of genetic engineering and the possibility of creating GM plants or animals, the EPO, which operates under the EPC, found itself in untested waters with a lack of guidance from patent law. Unsurprisingly, the early case-law decisions on applications that relate to both GM animals and plants created more confusion than useful guidelines as to how GMOs might be protected by patents in Europe.

In 1993, the Technical Board of Appeal at the EPO decided that a broad claim in a patent application by Plant Genetic Systems to a transgenic plant applied to plant varieties and was therefore excluded from patentability¹⁶. In an earlier case, the Technical Board of Appeal had allowed broad claims to transgenic non-human mammals per se when characterized by their method of production. Here, the Technical Board of Appeal reasoned that a claim to a transgenic mammal does not specifically claim individual animal varieties¹⁷. On the basis of these decisions, it seemed that it would be possible to obtain patents in Europe for transgenic animals as long as the patent was not directed to a single variety, but not to obtain patents that were directed to more than one plant variety. However, when the Plant Genetic Systems case was referred to the Enlarged Board of Appeal, which is the highest authority of the EPO, the Board did not recognize the apparent conflict between the two decisions¹⁸. These decisions illustrated that there was a need for further legislation with regard to biotechnology. The rules set out in the EPC, which had seemed applicable when it was drafted, were no longer sufficient for the examination of complex biotechnology patent applications.

In an effort to clarify the law as to what is patentable in biotechnology and also to harmonize the law in the European Union member states, Directive 98/44/EC of the European Parliament and the Council on the Legal Protection of Biotechnological Inventions (European Directive) came into force in 1998 after 10 years of debate and political struggle⁵. Although this directive remains controversial among the member states, it clearly represents a much-needed landmark in patent law relating to biotechnology inventions. Again, this directive deems plant and animal varieties unpatentable¹⁹. Although the concept of a plant variety is defined as in the UPOV Convention, the directive further specifies that a plant variety is defined by its whole genome. Accordingly, a plant grouping that is defined by a particular gene only is not considered to be a plant variety²⁰.

An amended version of the EPC implementing regulations came into force on 1 September 1999, in which certain provisions of the European Union Directive were incorporated, including the definitions of a plant variety as specified in the UPOV Convention and the CPVR. Under Rule 23c(b)of the EPC, inventions that are directed to plants or animals are patentable if the technical feasibility of the invention is not confined to a particular variety. Patents can also be granted for microbiological processes or their products, unless the products are plant or animal varieties⁷.

Armed with this new piece of legislation, EPO decisions on claims relating to more than one plant variety took a decisive turn. A milestone in patent case law that relates to plant biotechnology inventions was the decision on case number G1/98 (Ref. 10). In 1991, the EPO received a patent application that contained claims that were directed to transgenic plants transformed by recombinant DNA techniques to introduce pathogen resistance, and also claims directed to methods for preparing such plants. In line with the earlier decision in the Plant Genetics Systems case¹⁸, the Technical Board of Appeal initially found that the claims embraced plant varieties and refused the application on the basis of Article 53(b)²¹. This decision was opposed by the patent holder Novartis. By the time the case was examined by the Enlarged Board of Appeal, the EPC had been amended in response to the European Union Directive.

The Enlarged Board of Appeal reversed the decision of the Technical Board of Appeal and held that the claims were allowable. The reasons for this were based on the assessment that the claims did not relate to a single plant variety, as the method of the invention can be applied to an infinite number of plant varieties. The Board argued that the transgenic plants of the invention did not form a grouping that could be characterized as a single variety, as they differ from other plants by a particular gene and not the entire genome. It also found that transgenic plants cannot be defined as the product of microbiological processes, because the generation of such plants often involves transformation of the whole multicellular organism¹⁰.

The decision in the Novartis application overturned the earlier decision and interpretation of the EPC that was based on the Plant Genetic Systems decision and exemplified the state of patent law with regard to GM plants: GM plants can be protected by a patent in Europe if the invention is not limited to a single variety. Single varieties that have been generated using GM technology can be protected under the plant breeder rights legislation.

This Novartis case received an unusual amount of public attention, which reflects the controversial way in which the public perceives GM plants. The EPO received more than 600 letters from individuals and organizations expressing concerns about the grant of patents that relate to living matter. Many expressed the view that such patents would be contrary to 'ordre public' or morality and are therefore excluded from patentability (Article 53(a) of the EPC). The Enlarged Board of Appeal argued that the contracting states of the EPC have not agreed on condemning the genetic engineering of plants per se because it is contrary to morality. The Board also referred to Directive 98/44/EC of the European Parliament, which considers the protection of biotechnology inventions to be essential to encourage investment in the field^{5, 10}.

At first glance, it now seems possible to assess the patentability of plant-related inventions in Europe on the basis of the amended EPC, the European Directive and recent European case law. However, the situation is more complicated as most states of the European Union failed to implement the European Directive in the time limit given by the European Parliament and the European Commission. So far, only seven member states have implemented the directive owing to fierce political opposition, in particular with regard to articles that relate to the patenting of human genes.

The harmonization of national patent laws for biotechnology-related inventions seems to be a long way off⁶. It is uncertain whether claims to transgenic plants or animals that embrace several varieties would be allowable in those countries that have not yet implemented the directive.

The above cases exemplify the state of European patent law with regard to GM plants and general methods for making such plants. However, it is important to bear in mind that any patent application that is directed to a plant-related invention must also fulfil other criteria that are laid out in the EPC, such as novelty, inventiveness and sufficiency of disclosure. For example, a controversial 'soya' patent owned by Monsanto was limited after it had been granted, owing to opposition from third parties. The soya patent concerned a method of genetically engineering plants, in particular soybean, by introducing a foreign gene through particle mediation. The patent also covered soybean seeds and tissue that were obtained through this method²². Under European patent law, a patent description must be sufficiently clear and complete so that it can be carried out by another party with a general knowledge of the field concerned²³. The Opposition Division found that the soya patent did not meet this requirement for sufficiency and limited the patent to soybean plants only, rather than to any kind of plant engineered using particle mediation²⁴.

Gene patents. The process of making a GM plant involves many components that might individually be subject to a patent. For example, vectors that comprise microbiological sequences and enhancer sequences, such as the 35S cauliflower mosaic virus promoter, are commonly used to transform plants and the plant gene sequence of interest might be inserted into such a vector for subsequent transformation²⁵. Patent claims could be directed to methods for transformation, to individual gene sequences or to vectors that might ultimately be involved in the process of making a transgenic plant²⁶. As well as the issue of GM animals and plants, another controversial and challenging question for the application of patent law to biotechnology inventions is whether individual genes that are isolated from nature can be patented.

Biological material that is isolated from its natural environment or produced by means of a technical process is patentable, even if this material has previously occurred in nature²⁷. In theory, this means that a plant gene sequence that has been isolated from the organism can be the subject of a patent. However, in view of the increasing amount of available sequence data, including the complete genomes of Arabidopsis thaliana and rice^28-30, inventions that cover plant gene sequences might not always fulfil the criteria of novelty and inventiveness. Also, the EPO adopts the position with regard to nucleic-acid related inventions that it is not usually sufficient to show in silico evidence of gene function merely on the basis of sequence homology with a known gene. Experimental evidence of a specific, substantial and credible use is invariably required to meet the sufficiency requirement³¹.

Protection in the United States

In the United States, there are three different ways of obtaining intellectual property protection for plant-related inventions. Plant breeder rights can be obtained through the Plant Variety Protection Act (PVPA), which is based on the UPOV Convention³². Uniquely, property rights to plants in the United States can also be obtained through plant patents under the Plant Patent Act (PPA)³³. Such patents are only available for stable and asexually produced plants, and do not extend to plants that have been found in the wild. Similar to plant variety rights, a plant patent is limited to an organism that is characterized by a specific genetic makeup. As well as these two schemes, it is also possible to obtain a patent for a plant under the Utility Patent Act (UPA)³⁴. Utility patents are available in all technical fields for novel, non-obvious and useful inventions, and grant the owner of the patent a monopoly over the invention in exchange for its disclosure. Under the UPA "whoever invents or discovers any new or useful process, machine, manufacture or composition of matter, or any new and useful improvement thereof may obtain a patent therefore" (United States Code (USC) 101)³⁵. In a landmark decision in 1980, the United States Supreme Court held that the question of whether or not an invention embraces living subject matter is irrelevant to the issue of patentability and referred to the committee reports that accompany the 1952 Act, which indicate statutory subject matter "to include anything under the sun made by man"³⁶. Following this decision, the United States Patent and Trademark Office (USPTO) held that plants are within the definition of USC 101 (Ref. 37).

In a recent decision, the United States Supreme Court confirmed that plants can be the subject matter of patents under the utility patent system, even though protection is also available through the PVPA and PPA³⁸. In this case, Pioneer Hi-bred sued J.E.M. Agricultural Supply for infringement of its patent on hybrid and inbred corn lines. The defendant argued that the protection of plants is excluded from the patent act as protection is already provided by the PPA and the PVPA. The court rejected this argument on the basis that neither the PVPA nor the PPA state that the respective systems are the exclusive means by which plants should be protected. Although this decision might leave some issues unresolved³⁹, it seems clear that there are no restrictions on the protection of a genetically engineered plant variety by a utility patent and the lack of exclusion of plant varieties from the patent system represents a fundamental difference between United States and European patent law.

With regard to the patenting of individual gene sequences in the United States, the position of the USPTO is similar to that of the EPO: as well as being novel and inventive, isolated nucleic-acid sequences are required to show credible uses⁴⁰. This means that a function of the gene or protein must be indicated in the application.

Infringements of patents

Patents give the inventor the right to exclude others from exploiting their invention for a certain period of time (Box 1). During this time, he or she might of course license the invention to third parties and thereby gain financial benefit. With regard to conventional products, it is comparatively straightforward to assess if a competitor infringes the rights of a patentee to an invention by producing and marketing a product that is covered by a patent without being authorized to do so. However, as plants are self-propagating organisms that spread through pollen, the assessment of infringement is much more difficult for transgenic plants.

This issue was illustrated by a recent case in Canada in which Monsanto sued the Canadian farmer Percy Schmeiser for infringement of its patent directed to glyphosate-resistant plant cells. During the routine spraying of canola plants around power poles and road borders with the herbicide Roundup, Schmeiser discovered that a large number of plants survived the spraying, presumably because they derived from pollen from Roundup Ready canola plants in a neighbouring field. Schmeiser then treated more of his plants with Roundup and found that 60% were resistant to the herbicide. The following year, he sowed seed from resistant and non-resistant canola plants for the planting of a new crop. Monsanto claimed that because Schmeiser had not entered into a licensing agreement about the use of Roundup Ready canola, the use of the herbicide-resistant seed amounted to an infringement of the patent. The Canadian Federal Court awarded Monsanto remedies for patent infringement and held that by using seeds that he must have known derived from Roundup Ready canola, Schmeiser infringed the patent. The court also held that Schmeiser was liable, although he did not actually use Roundup to treat the resulting crop, because of the nature of the patent claims, which were not limited to the use of Roundup but directed towards chimeric genes in the glyphosate-resistant plant cells. In response to claims by Schmeiser that Monsanto had not taken enough precautions to prevent pollen contamination and had thereby waived its patent rights, the court found that the company had taken a range of measures to control unwanted pollen spread. However, the court also indicated that a decision might be different in cases in which there was "innocent or unintentional infringement" in which farmers tolerated the presence of a plant without promoting its propagation by harvesting and planting its seeds⁴¹.

With increasing quantities of GM crops grown worldwide³, it seems that the issue of contamination through pollen drift might not only be of concern to environmentalists, but will probably also influence the number of lawsuits in connection with patent infringements³⁹. Similarly, the legal implications of gene introgression with regard to, for example, a patented construct, might also be important in the future.

Another issue relating to the infringement of patents that might lead to controversial decisions by the courts is the reuse of seeds by farmers who have paid for a license to grow a specific plant that is protected by a patent. Unlike plant variety rights, United States utility patents for plants do not provide the farmer with a right to save and reuse seed. In a recent decision, the United States Federal Court of Appeal confirmed that the "right to save seed of plants registered under the US Plant Variety Protection Act (which is based on the UPOV Convention) does not impart the right to save seed of plants patented under the Patent Act" (Monsanto versus McFarling)⁴². In Europe however, the European Biotechnology Directive restricts the rights of the holder of the patent under the limitations of the UPOV Convention, so if the patent covers propagating material that is sold to a subsistence farmer, the farmer can use the product of the harvest for further propagation on his or her own farm⁴³. However, a case similar to Monsanto versus McFarling has not yet been reported in Europe and it remains to be seen what decision would be taken, bearing in mind that the European Biotechnology Directive has not been implemented in all member states and that the right of the patentees with regard to the reuse of seed is not anchored in the articles or regulations of the EPC.

Final comments

With the introduction of some of the provisions of the European Biodirective into the EPC, the requirements for obtaining patents for plant-related inventions in Europe have been clarified and recent case law has supplied guidelines for interpreting these provisions. Although single plant varieties cannot be protected by a patent, but only through CPVR, patents can be granted for inventions that cover more than a single variety. However, the situation in Europe has not yet been harmonized as several member states, whose national courts might set different standards with regard to what can and cannot be patented in biotechnology, have failed to implement the European Directive. In the United States, three different systems are available to protect plant-related inventions and patents that concern single or multiple plant varieties.

Although one of the future challenges with regard to patents that cover plant-related inventions will be the issue of infringement through pollen drift, another challenge will be the availability of patented plants or plant technology to the developing world. One recent development in this field concerns the use of 'golden rice', which is a type of GM rice that contains increased amounts of -carotene (the precursor of vitamin A)⁴⁴. Golden rice is grown in many countries, including India, China, Bangladesh and Indonesia. In this case, patent owners who hold rights to the application of this technology have issued free licenses to subsistence farmers in developing countries under their national intellectual property rights⁴⁵.

Boxes