The recent judgment of the United Kingdom’s High Court in Eli Lilly and Company v Human Genome Sciences, Inc. provides a cautionary tale as to when to file a patent application. It provides a useful insight into the particularities of patenting in the biologics area.
It is crucial when patenting in the biologics area for an applicant to describe a specific use of their invention. This avoids invalidity for lack of sufficiency or utility. Patentees now have some guidance in assessing their portfolios in order to analyse whether their patents would withstand a concerted attack on these bases.
The discovery
Human Genome Sciences Inc (HGS) found the gene that encodes a protein which it named Neutrokine-alpha (Neutrokine-a). Neutrokine-a was discovered by means of its structural similarity to a group of proteins known as the TNF ligand superfamily by means of bioinformatics rather than via traditional sequencing methods. Members of the TNF ligand superfamily have important roles in the regulation of the cell cycle and have therefore been targets in the development of therapies for a range of diseases.
The patent
Shortly after its discovery of Neutrokine-a, HGS filed for a patent, EP (UK) 0,939,804. That patent claimed full-length nucleic acid and amino acid sequences for Neutrokine-a as well as antibodies that specifically bind to the disclosed polypeptide sequences (although no examples were provided). The specification of the patent claimed that such antibodies as well as Neutrokine-a polypeptides are useful diagnostically and therapeutically for a wide range of diseases and conditions, including:
tumour and tumour metastasis, infections by bacteria, viruses and other parasites, immunodeficiencies, inflammatory diseases, lymphadenopathy (diseases of the lymph nodes), autoimmune diseases, graft versus host disease and to stimulate peripheral tolerance, destroy some transformed cells lines, mediate cell activation and proliferation, and are functionally linked as primary mediators of immune regulation and inflammatory responses.
This range of uses was based on the activities of other members of the TNF ligand superfamily rather than analysis of the properties of Neutrokine-a itself. The patent contained very little detail as to the tissues in which Neutrokine-a had been found, the levels of expression that are normal or abnormal and whether abnormal levels of expression are associated with any particular diseases or conditions.
The mistake
The lack of practical detail in the patent was quite apparent and this was noted in the judgment of Justice Kitchin. Importantly, what were very wide claims (in terms of the therapeutic applications) were supported by very little substantiation. The lack of detail of a specific application for the ‘invention’ left the patent exposed to invalidation due to it not being capable of industrial application.
Justice Kitchin held that the patent contained nothing more than speculation as to how Neutrokine-a might be useful. The patent was found not to be capable of industrial application as it did not disclose any practical way of exploiting the ‘invention’ without conducting substantial further research. His Honour was bolstered in this view by the fact that after the patent had been filed several research groups had conducted considerable and lengthy research into how knowledge of Neutrokine-a might be used to generate a new therapeutic product.
The situation would have been different had the identification of the protein immediately suggested a practical application (as was the case with some early biological therapeutics such as HGH and EPO). However, the evidence was that TNF Ligand superfamily members have numerous and varied activities and it is impossible to accurately predict the function of any particular member.
In the course of his judgment, Justice Kitchin cited with approval the United State’s Supreme Court in Brenner v Manson, which had commented that ‘... a patent is not a hunting licence. It is not a reward for the search, but compensation for its successful conclusion.’
In Australia, for an invention to be patentable it must be ‘useful’. The Australian concept of utility is analogous to the English requirement for industrial application (and indeed shares a common derivation). An invention will have utility if it ‘does what it is intended by the patentee to do, and the end attained is itself useful’ (Fawcett v Homan). Given the considerable research beyond the teaching of the patent that was undertaken in order to try to find a therapeutically effective product it is difficult to say that the patent achieves its promised result of therapeutic or diagnostic usefulness.
The concept of usefulness is also relevant to the requirement that an invention constitutes a manner of manufacture under section 18 (1)(a) Patents Act 1990 (Cth). A patent may not satisfy this requirement where its specification does not indicate an area of usefulness and such use is not self evident. Accordingly, the ‘manner of manufacture’ would also have been relevant to the HGS patent, had it been litigated in Australia.
The lack of information as to the function of the protein, normal expression levels and the correlation of abnormal expression levels to specific diseases led Justice Kitchin to rule that the patent was insufficient because it did not describe the invention clearly and completely enough for it to be performed. It is quite possible that the Australian courts would take the same line as their English counterparts. The IP Australia guidance paper ‘Australian Patents for Biological Inventions’ states:
Patent specifications must also describe a specific use for biological material. For example, if the invention relates to a gene, the specification must disclose a specific use for the gene such as its use in the diagnosis or treatment of a specific disease or its use in a specific enzymatic reaction or industrial process.
and
… the treatment of human diseases such as cancer or multiple sclerosis, must be fully described. This means that there must be an actual use for an invention rather than speculation as to future uses.
The lesson
The patenting of biological inventions, discovery of the nucleotide and polypeptide sequences is one thing, but a useful end result is quite another. In order to obtain a valid patent it is generally necessary to describe either the function of the protein or a disease which is associated with an excess or deficiency in that protein.
While bioinformatics techniques are a powerful tool in the development of new biologic therapeutics, it must be remembered that the identification of sequences is only the first step on the road to a patentable invention. In the United Kingdom’s court’s opinion, HGS applied for its patent too early, when it had nothing firm to go on as to how its ‘invention’ might be used in practice. This was evidenced by the enormous range of potential applications that were claimed. Such practice was quite common at the time that the application was filed. However, it is now clear that such patents may be susceptible to revocation. Patentees may wish to reassess their and possibly their competitors’ patent portfolios.
There will always be pressure to file as soon as possible in ‘first to file’ jurisdictions such as Australia and the United Kingdom. Competitors’ activities and the threat of being beaten to the line loom large in the mind. However, premature applications will prove vulnerable so a balance needs to be struck in order to minimise the risk of refusal or invalidation while providing due protection for research and development activities.
This article was written by Tomos Shillingford, Senior Associate, Melbourne.
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