The general law of patents is just as applicable to inventions relating to genes and gene therapy as any other technical field. Thus, for example, to be patentable, inventions related to a gene or a gene therapy must, like all other inventions, be new, not obvious and sufficiently disclosed in the patent specification.
Gene and gene therapy patents do, however, give rise to a number of specific issues including the following:
- the "product of nature" problem
- ethical considerations
- utility considerations
- the method of treatment problem
- the problem of broad claims
The first two issues have been dealt with in the context of the Biotechnology Directive in another article in this publication. In this article, I propose to comment further on both of them and then address each of the remaining three issues in turn.
The "Product of Nature" Problem
As stated in the Biotechnology Directive article, the "product of nature" problem is a non-issue in the sense that, all other things being equal, a previously unknown substance freely occurring in nature if discovered may be patentable per se.
One of the major problems faced by the biotechnology sector in the early days of its development was that many of the substances for which protection was sought once they had been sequenced and could be produced by means of recombinant technology were not new in the sense of having had no previously recognised existence. They were already found in nature in the human body. Patent protection to the products per se was not therefore available. Furthermore, given that, in many cases, it was clearly obvious to try to sequence and produce them using recombinant technology, given their previously known utility, and also that the techniques to obtain them were well known, patent protection for product-by-process claims were also unavailable.
Again, as stated in the Biotechnology Directive article, the narrow scope of the morality exclusion from patentability means that, in the vast majority of cases, ethical considerations will not prevent patent protection from being obtained for biotechnology inventions. Gene therapy however is one of the few areas where the morality exclusion has an impact.
Gene therapy itself can broadly be divided into somatic cell therapy where the alterations are not passed on to successive generations and germ line therapy where the alterations will be passed on to successive generations.
The Biotechnology Directive makes it clear that processes for modifying the germ line genetic identity of human beings are unpatentable. By implication, therefore, all other things being equal, the morality exclusion does not apply to inventions relating somatic cell therapy.
Like all other inventions, the patentability of a previously unknown substance freely occurring in nature depends on the discovery not merely of the substance alone but also some useful application for it. This requirement for utility has proved fatal to the well publicised applications filed by both the National Institute of Health in the US and the Medical Research Council in the UK in relation to the results of the Human Genome Project. The patent applications related to gene sequences of unknown function i.e., they did not disclose any useful application or utility for the gene sequences and were therefore destined to be rejected.
By contrast, patent applications for previously unknown genes but having a known function such as the gene sequence in the Relaxin case1 which was discovered to code for a previously unknown protein, relaxin.
The Method of Treatment Problem
The EPC excludes as a general matter from patentability inventions for gene therapy in the following way. To be patentable, an invention must be capable of industrial application and Article 52(4) of the EPC provides that:
"Methods for treatment of the human or animal body by surgery or therapy or diagnostic methods practised on the human or animal body shall not be regarded as inventions which are susceptible of industrial application in particular within the meaning of paragraph 1. This provision shall not apply to products, in particular substances or compositions, for use in any of these methods."
Thus, although patent protection can be obtained for drugs and other materials which are used in surgical or therapeutic treatments, it cannot be obtained for methods of treatment as such.
This raises the question as to what constitutes a method of "treatment by surgery or therapy."
Therapy has been held to include the relief of symptoms as much as underlying causes. Thus in Dysmenorrhoea/RORER2, a treatment for relieving discomfort associated with menstruation was held to be therapy within the meaning of Article 52(4). Furthermore, in Pigs II/DUPHAR3, both prophylactic and curative treatments have been also been held to be within the scope of the exclusion on the ground that the purpose of both is to maintain or restore health.
In practice, protection for methods of gene therapy can nearly always be obtained by presenting the invention in such a way as to avoid the scope of the exclusion. For instance, claims are frequently drafted so as to claim the vector or cells which have been so treated rather the method of treatment as such.
The Problem of Broad Claims
It is one of the central tenets of patent law that there should be a correspondence between the disclosure of the invention to the public provided by the patentee in the specification of the patent and the breadth of the protection sought by the patentee in the claims of the patent.
In practice, an isolated discovery in relation to one substance will frequently enable others to predict success in relation to other substances. The skill of the patent agent is to draft a claim the width of which represents a reasonable prediction of success based on the isolated discovery. The legal issue in relation to such claims is the extent to which the law permits such predictions in particular in circumstances where there are substances within the scope of the claim that do not work or cannot be made to work without the exercise of further invention or ingenuity.
The problem of claiming too broadly needs to be put into the context of the grounds on which the validity of patents in Europe can be challenged. These grounds can be summarised as follows:
- not new
- obvious or lacking inventive step
- inutility or not capable of industrial application
- exclusions such as discovery, plant variety, method of treatment, etc
- Granted to a person not entitled
- Insufficient disclosure
- Impermissible amendment
- added matter
- extended protection
It can be seen from the above that there is no ground of "having an overbroad claim." There is, however, the ground of "insufficient disclosure" which at least to the uninitiated could be seen as an alternative but equally promising approach to challenging a lack of correspondence between the disclosure in the specification and the claims. Up until fairly recently, such an approach had not met with much success. However, as a result of a serious of cases before the EPO and the English Courts and in particular, the House of Lords decision in the Biogen v Medeva4 case, it now seems that it is possible to challenge broad claims on the ground of insufficient disclosure.
By way of background, up until Biogen, it had generally been accepted that regardless of the width of the claim, an invention was sufficiently disclosed if the skilled man could make a single embodiment i.e., the disclosure of only one way of performing the invention was sufficient to survive a challenge based on insufficient disclosure. See for instance, Polypeptide Expression/Genentech I5, an EPO decision, and Molnlycke v Proctor & Gamble6, an English High Court decision.
The House of Lords decision in Biogen, however, marked a radical departure from this approach.
The patent in Biogen was concerned a genetically engineered hepatitis B vaccine. Biogen's objective was to produce antigens to HBV which could then be used to diagnose and immunise against HBV. At the outset, Biogen was faced with two alternative approaches to achieving this objective: the first, was certain of success but was known to take a long time, the second, was less certain of success. Biogen choose to go down the latter route and, against expectation, achieved the desired objective in a relatively short period of time. In their first UK patent application, Biogen described the results of their initial research work. In their second European patent application, Biogen claimed in effect HBV antigens howsoever they were produced. However, between filing their initial UK patent application and their subsequent European patent application, the HBV genome was sequenced thereby rendering the second route open to all.
The main attacks on the patent were (1) that the patent was not entitled to its priority date on the ground that the invention claimed in the patent was not supported by the matter disclosed in the priority document (section 5(2)(a)) and (2) that the specification of the patent did not disclose the invention in a manner which was clear and complete enough for it to be performed by a person skilled in the art (section 72(1)(c)). It was accepted by Biogen that, as at the application date as a result of the subsequent publication of the HBV genome sequence, the invention was obvious. In other words, if the patent lost its claim to priority then the patent would be rendered invalid for obviousness.
In the leading speech, Lord Hoffman emphasised that the central concept underlying the requirement for support in the context of priority, support and sufficiency was that of enablement and stated the general principles on the issue of sufficiency as follows:
"If the invention discloses a principle capable of general application, the claims may be in correspondingly general terms. The patentee need not show that he has proved its application in every individual instance. On the other hand, if the claims include a number of discrete methods or products, the patentee must enable the invention to be performed in respect of each of them.
If the patentee has hit upon a new product which has a beneficial effect but cannot demonstrate that there is a common principle by which the effect will be shared by other products of the same class, he will be entitled to a patent for that product but not for the class, even though some may subsequently turn out to have the same beneficial effect.... On the other hand, if he has disclosed a beneficial property which is common to the class, he will be entitled to a patent for all products of that class (assuming them to new) even though he has not himself made more than one of them."
And that the critical issue in the case was:
"... not whether the claimed invention could deliver the goods [across the full width of the patent or priority document], but whether the claims cover other ways in which they might be delivered: ways which owe nothing to the teaching of the patent or any principle which it disclosed ... there is more than one way in which the breadth of a claim may exceed the technical contribution to the art embodied by the invention. The patent may claim results which it does not enable, such as making a wide class of products when it enables one of those products and discloses no principle which would enable others to be made. Or it may claim every way of achieving a result when it enables only one way and it is possible to envisage other ways of achieving that result which make no use of the invention."
In the case itself, Hoffman held that Biogen's contribution was not sufficient to justify a claim to a monopoly on any recombinant method of making hepatitis B virus antigens and therefore that the claims in the European patent were not supported by the disclosure in the priority document. Since obviousness at the application date was conceded, the House of Lords did not need to give judgment on the issue of insufficiency as such although they indicated that as the principles were the same, so would the result have been on this ground.
The present position in both the UK and the EPO (as confirmed by the subsequent EPO decision in Mycogen7), is that to be sufficient a claim has to be enabled across its entire width which in certain cases may require the enablement of more than one embodiment. Furthermore, the old UK law on fair basis (namely, having claims which are broader than the invention described in the specification) appears at least in the UK to have been re-introduced by the back of door door in the guise of insufficiency. As Lord Hoffman commented in Biogen:
"But the disappearance of "lack of fair basis" as an express ground for revocation does not in my view mean that the general principle which it expressed has been abandoned. The jurisprudence of the EPO shows that it is still in full vigour and embodied in Article 83 and 84 of the EPC ..."
Whilst there are certainly specific issues raised by the patenting of genes and gene therapy, for the most part, the problems thrown up by these issues are surmountable. Like the rest of the biotechnology sector, the innovators in this particular field can be reasonably confident about the ability of properly drafted patents to protect their R & D investment.
First published in Patents World in January 2001.
1. T?/94, OJEPO 1995, 388
2. T 81/84 OJEPO 1988 207
3. T19/86 OJEPO 1988 24
4.  RPC 1
5. T292/85 - OJEPO 7/1989 p275
6.  FSR 549
7. T 694/93 OJEPO (1997) 408