Industrial Application: Human Genome v Eli Lilly
The new UK Supreme Court has made its first decision in a patent case. Human Genome Sciences (HGS) applied for patent EP0939894 (‘the patent’) in 1996. The patent in question identified a gene sequence coding for a human protein named neutrokine-α, along with the tissue distribution, expression information and antibodies to the protein. Eli Lilly challenged the validity of the patent in the UK on the basis of insufficiency and, unusually, industrial application.
The referral of this case to the UK Supreme Court came after a long history of opposition and appeal for the patent.
The European patent application was granted in August 2005, after nine years of prosecution. This was opposed centrally at the European Patent Office (EPO) by Eli Lilly, which action resulted in revocation of the patent. However, the EPO Technical Board of Appeal later reversed the decision and ordered that the patent be maintained.
The UK Patents Court revoked the patent in parallel proceedings on the basis that a person skilled in the art would have understood that the functions of neutrokine-α “were, at best, a matter of expectation and then at far too high a level of generality to constitute a sound or concrete basis for anything except a research project”. This decision was based on a lack of industrial application (Article 57 of the European Patent Convention (EPC)) and insufficient disclosure (Article 53 EPC).
The Patents Court decision was then upheld by the UK Court of Appeal after consideration of Article 57 EPC only.
It is very common for gene sequences to be identified and classified using bioinformatics techniques. Essentially this means deducing the function of the gene based on existing data, in this case similarity to previously characterised gene sequences, rather than specifically conducting experimental tests on the new sequence. Such techniques make use of widely available databases and computer programs.
At the time of filing their patent application, in this case HGS had identified, based on sequence similarity, that neutrokine-α was likely a member of a protein family known as TNF ligand superfamily. Other members of this protein superfamily were known at the time of filing to be involved in regulation of cell proliferation, activation and differentiation. Therefore it was proposed that neutrokine-α shared the properties of the other TNF ligand proteins.
In the UK Supreme Court decision, as summarised by Lord Neuberger, the patent in question:
describes the claimed invention as potentially useful for the diagnosis, prevention, or treatment of an extraordinarily large and disparate number of, sometimes widely expressed, categories of disorders of the immune system, and other conditions and actions, either through neutrokine-α itself or through its antagonists. However, nowhere in the patent is there any data or any suggestion of in vitro or in vivo studies, so there is no experimental evidence to support any of those suggestions… In very summary terms, the disclosure of the patent thus includes the following features: (i) the existence and amino acid sequence of neutrokine-α, (ii) the nucleotide sequence of the gene encoding for neutrokine-α, (iii) the tissue distribution of neutrokine-α, (iv) the expression of neutrokine-α by its mRNA (the encoding gene) in T-cell and B-cell lymphomas, and (v) the information that neutrokine-α is a member of the TNF ligand superfamily.
Eli Lilly were of the belief that the functions of neutrokine-α given in the application as filed were purely speculative and not based on experimental evidence.
Article 52(1) EPC states that, in order to obtain a European patent, an invention must be “susceptible of industrial application”. Article 57 EPC furthermore states that an invention is susceptible of industrial application if it can be made or used in any kind of industry, including agriculture. Section 4 of the UK Patent Act is derived from this.
There is relatively little UK case law on the subject of industrial application, and the Supreme Court was loath to disagree with the lower courts. However, in this particular case a notable intervention was made.
The BioIndustry Association (BIA), a UK bioscience trade association with 36,000 members, submitted that clarity and certainty was required in this area of law because it is important for bioscience companies to be able to decide at what stage to file for patent protection. Specifically the BIA submitted the following:
If the application is filed early, . [t]he company will be left with no patent protection, but would have disclosed its invention in the published patent application to competitors. If the application is filed late, there is a risk in such a competitive environment where several companies may be working on the same type of research projects, that a third party will already have filed a patent application covering the same or a similar invention, in which case the company may not be able to gain any patent protection for its work and by continuing their programme they may risk infringing that third party’s patents. In both cases, the company will have lost much of the benefit of its costly research and development.
The BIA further suggested that if the Supreme Court upheld the decision of the Court of Appeal there is at least a risk that it will
make it appreciably harder for patentees to satisfy the requirement of industrial applicability in future cases.
would cause UK bioscience companies great difficulty in attracting investment at an early stage in the research and development process.
Lord Neuberger in particular was sympathetic to the BIA’s case and did not agree that determining the precise uses of neutrokine-α would entail a substantial research project. In particular he considered,
Just as it would be undesirable to let someone have a monopoly over a particular biological molecule too early, because it risks closing down competition, so it would be wrong to set the hurdle for patentability too high, essentially for the reasons advanced by the BIA.
The result is, the earlier UK court decisions were overturned, and the patent maintained.
In the judgment, Lord Neuberger states that though this case raises an important question of principle, its resolution is fact-sensitive. Therefore, any answer may be of limited value in other cases. It remains to be seen whether this judgment will be applied to other cases, especially in the biotechnology field. However, it is clear that the Supreme Court aimed to bring the UK into line with fellow European countries with this decision, and also did not wish to negatively impact the UK biotech industry.