Whilst data mining, gene sequencing and bioinformatics have become fundamental tools in biotechnology, unless the function of a gene or a protein immediately suggests a practical application further work will be required before an enforceable patent in the UK can be obtained. Due consideration will need to be given to carrying out further investigative research before filing a gene or protein sequence patent.
Human Genome Sciences, Inc (HGS) filed a patent application disclosing the nucleic acid and amino acid sequences of a new member of the TNF superfamily, which they called Neutrokine-α. A European patent was granted but it soon became the subject of opposition proceedings at the European Patent Office (EPO). One of the opponents was Eli Lilly & Company. They had been investigating and developing a therapeutic product based upon Neutrokine-α. It has been reported that Eli Lilly have spent some £25m developing an antibody to Neutrokine-α and expect to spend another £125m taking the drug through clinical trials. The Opposition Division of the EPO has recently revoked the patent, which HGS can appeal.
The subject of the proceedings before the High Court was the corresponding UK patent. Eli Lilly could have awaited the outcome of the opposition (and probable appeal) proceedings at the EPO. Revocation of the European patent would invalidate the patent in all contracting states, including the UK. However, it seems that Eli Lilly were in no mood to await the outcome in Europe. They therefore brought revocation proceedings against the patent in the UK. The principle point of law upon which this decision was based was that the invention was not capable of industrial application. This is a point of law that has rarely come before the English courts.
One of Eli Lilly’s main attacks was that HGS failed to properly characterise Neutrokine-α, its function, or any therapeutic or diagnostic utility for it such that it could not have any application in industry. It is a requirement of patentability in Europe that an invention is susceptible of industrial application. This is derived from Articles 52(1) and 57 of the European Patent Convention. These Articles correspond to Sections 1(1)(c) and 4 of the UK Patents Act 1977. The purpose of these provisions is to ensure that an invention has a real world practical application. Whilst this is normally readily apparent (and thus, rarely contested) it is not always the case for biotechnology inventions, especially when the function of protein is not understood.
The Biotechnology Directive (98/44/EC) states that a DNA sequence without an indication of function does not contain any technical information and is therefore not a patentable invention and that the industrial application of a sequence or partial sequence of a gene must be disclosed in the patent application. The Rules of the European Patent Convention also have similar requirements.
Mr Justice Kitchin arrived at the following (abbreviated) principles on industrial applicability:
- The notion of industry must be construed broadly.
- The industrial exploitation must be derivable by the skilled person from the description read with the benefit of the common general knowledge.
- The description must disclose a practical way of exploiting the invention in at least one field of industrial activity.
- There is a need to disclose in definite technical terms the purpose of the invention and how it can be used to solve a given technical problem.
- The requirement will not be satisfied if what is described is merely an interesting research result that might yield a yet-to-be-identified industrial application.
- The purpose of granting a patent is not to reserve an unexplored field of research for the applicant nor to give the patentee unjustified control over others who are actively investigating in that area.
- If a substance is disclosed and its function is essential for human health, then the identification of the substance having that function will immediately suggest a practical application. If, on the other hand, the function of that substance is not known or is incompletely understood, no disease has been identified which is attributable to an excess or a deficiency of it, and no other practical use is suggested for it, then the requirement of industrial applicability is not satisfied.
- Using the claimed invention to find out more about its own activities is not in itself an industrial application.
- It is no bar to patentability that the invention has been found by homology studies using bioinformatics techniques although this may have a bearing on how the skilled person would understand the disclosure.
HGS argued that at the date of filing, members of the TNF ligand superfamily had proved to have industrial applicability and that any skilled person reading the patent would appreciate that both the protein sequence and antibodies raised to it would have the potential for commercial exploitation. However, the Judge was of the view that simply identifying a protein does not necessarily confer industrial utility upon it. This might be so when the identification of the protein immediately suggests a practical application (such as with insulin, human growth hormone and erythropoietin). However, if the function of the protein is not known or is incompletely understood and if no disease has been attributed to a deficiency or excess of it, then the industrial utility must be identified in some other way. Whilst the Judge accepted that Neutrokine-α might be expected to play a role in regulating the activities of B cells and T cells and play an unspecified role in regulating the immune and inflammatory response, he still concluded that this did not reveal how it could be used to solve any particular problem. Accordingly, the patent did not meet the requirement of industrial applicability.
Eli Lilly also alleged that the specification did not disclose the invention clearly enough and completely enough for it to be performed by a person skilled in the art, and that the invention was obvious to the skilled person. Whilst a detailed discussion of those points is beyond the scope of this article, the Judge held that the sequences and the antibodies were sufficiently disclosed, but that the pharmaceutical and diagnostic composition claims were insufficient. The decision on obviousness was similarly split; the Judge held that the claims were not obvious over an EST and a clone, but that the claims made no contribution to the art because the patent does not teach the person skilled how to solve any technical problem using Neutrokine-α.