Genetically Modified crops
Patenting and the impact of genomics
3.40 The definitive analysis of the genetic make up of organisms through the DNA sequencing of entire genomes is already having a major impact on research in the life sciences. The best known of these is the human genome which is currently being sequenced in both the public and the private sector. The entire complement of human genes is expected to be sequenced by 2000. This structural characterisation is already revealing many genes of unknown function and the next stage of the project will be functional analysis. The genome of yeast has already been completely sequenced and a large-scale collaborative research project to determine the function of unknown genes is in progress. The fact that many genes from a wide range of organisms show homology underlines the value of this approach where the genome of a model organism is sequenced. In other words, some of the genes identified and studied in the model organism can be matched with genes having the same or very similar structure in other organisms.
3.41 A large-scale global DNA sequencing effort is now also in progress in a model plant, Arabidopsis. This species has much more DNA than yeast and will be completed by the end of 2001. Functional analysis of the results will spread over the next 10–15 years. However, these estimates may well be reduced as DNA sequencing and microarray technologies improve. As particular genes are identified in the model species, so too will homologous genes be identified in a wide range of crop species. The fact that the genomes of some related species such as the cereals show extensive homology or synteny means that there will be further economies of scale through the Japanese public rice genome sequencing project.
3.42 In the human genome, two broadly opposing information strategies have been pursued. The large public sector sequencing programmes have viewed DNA sequence information as pre-competitive and have accordingly released the data rapidly into the public domain. In contrast, the private sector, together with some public sector institutions, has instead been filing patents on partial and full length gene sequences. A similar pattern is emerging in plant genomics research programmes.
3.43 Recent private sector initiatives to apply more rapid 'shotgun' genome sequencing techniques to the human genome and the rice genome have met with a mixed reaction. The US company Celera plans to sequence the human genome by 2001, four to five years earlier than the publicly funded international collaborative project intended. It now intends to 'sequence the rice genome' in a few weeks, eight years ahead of the Japanese-led public sector US$200 million rice project. (33) What are the implications of these developments? Celera's proposed method of analysis, while much quicker, is much less thorough in that it will yield partial rather than full gene sequences. Although it is too early to assess the impact of Celera's plans, the company intends to patent some of the human and rice DNA sequences and make most of them available in due course by database subscription. The leading public sector funding agencies for the human genome project have responded by providing a substantial increase in funding to bring forward their own completion date to the year 2000. The prospect of a similar response from the plant sequencing community would appear less likely as the funding agencies involved are more fragmented. This would make it difficult for potential sponsors to react quickly enough to match Celera's plans.
3.44 The large agrochemical and seed companies are also investing heavily in genome sequencing programmes. For example, the Du Pont-Pioneer sequencing project in maize, plans to sequence 200,000 partial gene sequences or ESTs (expressed sequence tags). (34) The prospects of patents being allowed for partial gene sequences of unknown function has alarmed many researchers. Although the USPTO rejected a patent application for human ESTs with no known genetic function in 1991, a similar patent has recently been granted in the US. (35) The USPTO has indicated that EST patents are allowable in the context of inventions using partial DNA sequences as molecular markers or probes to identify specific sequences. The Working Party considers partial DNA sequences such as ESTs or SNPs (single nucleotide polymorphisms) (36) are research tools and as such should not be patented. The Working Party welcomes the recent initiative involving a consortium of ten pharmaceutical companies and the biomedical charity, the UK Wellcome Trust, to pool efforts to create a public SNP map of the human genome. The non-profit SNP Consortium will accelerate the search for disease-associated genes by making the map available to all researchers. The initiative will also avoid duplication of effort and prevent those companies developing private maps from tying up large areas of the human genome with patent claims. (37) We consider that the extension of this approach to other genome projects may be worth pursuing.
3.45 There is concern over the extent to which patents on partial gene sequences may impose dependency or 'reach through' to subsequent patent applications with full-length DNA sequences and functional genetic data. A proliferation of patents on individual ESTs held by different owners would require costly future transactions to bundle licences together before a firm could acquire the rights to develop future commercial products. (38) The 'reach-through' licence agreements essentially give the owner of a patented invention used in early (upstream) research, rights in subsequent (downstream) development. Although it has been suggested that benefits may accrue to patent holders, who gain licensees, and researchers, who gain access to the technology, there are fears that a patent 'stacking' effect may inhibit innovation downstream. Upstream owners risk stacking overlapping and inconsistent claims which may be difficult and expensive to resolve. We therefore recommend that national patent offices, the EPO and the World Intellectual Property Organisation (WIPO), limit patent claims for ESTs strictly to their specified uses to avoid dependency on subsequent patents which have overlapping DNA sequences. We further recommend that WIPO and the EC (39) closely monitor the development of EST patents worldwide.
Footnotes33 Saegusa A (1999) US firm's bid to sequence rice genome causes stir in Japan, Nature 398: 545.
34 ESTs are partial DNA sequences which represent genes that are turned on in a particular tissue type or organism.
35 The US company Incyte was granted a patent in 1999 for human kinase homologues based on 12 EST sequences for use as molecular probes (US patent US5817479).
36 SNPs are single DNA base pair mutations. In the human genome project they are being used as markers to locate disease genes. Most SNPs fall within the non-coding regions of human DNA and make no difference to the individual. A given set of SNPs is likely to be inherited with a particular gene and can be used to identify it.
37 Masood E (1999) Consortium plans free SNP map of human genome, Nature 398: 545-546.
38 Heller M and Eisenberg R (1998) Can patents deter innovation? The anticommons in biomedical research, Science 280:698-701.
39 The EC has a specific duty to report annually to the European Parliament on 'the development and implications of patent law in the field of biotechnology and genetic engineering' (Directive 98/44/EC Article 16 (c)).