Clinical trials in the UK are governed by, what can at times appear, like a complex arrangement of provisions and exemptions. In this article, we summarise these provisions and provide a guide on how to ensure that intellectual property rights are not infringed in the process of carrying out a clinical trial.
Exemptions from patent infringement for clinical trials
The Patents Act 1977 sets out several exemptions to infringement relating to experimental purposes and clinical trials.
Section 60(5)(b) of The Patents Act 1977, states that “an act which, apart from this subsection, would constitute an infringement of a patent for an invention shall not do so if… it is done for experimental purposes relating to the subject-matter of the invention”.
For this exemption to apply, it must be demonstrated that the act (relating to the subject-matter of the invention) was performed for an experimental purpose and that it would be an infringement if it wasn’t done for experimental purposes.
As to whether an act was done for “experimental purposes” or not, the Court of Appeal in Monsanto Co v Stauffer Chemical Co and another [1985] RPC 515, held that:
‘Trials carried out in order to discover something unknown or to test a hypothesis or even in order to find out whether something which is known to work in specific conditions, e.g. of soil or weather, will work in different conditions can fairly, in my judgment, be regarded as experiments. But trials carried out in order to demonstrate to a third party that a product works or, in order to amass information to satisfy a third party, whether a customer or a body such as the PSPS or ACAS, that the product works as its maker claims are not, in my judgment, to be regarded as acts done “for experimental purposes”.’
It was however also held that a mixture of commercial and non-commercial, i.e., experimental activity, may still fall within the exemption, depending upon if the primary purpose is to generate new scientific or technical information or if it is for commercial purposes.
In CoreValve v Edwards Lifesciences [2009] EWHC 6 Pat Ct, the Deputy High Court Judge looked to the Federal Supreme Court of Germany in the case of Klinische Versuche (Clinical Trials) I [1997] RPC 623, in which it was stated that:
“An act for experimental purposes which is related to the subject-matter of the invention and therefore legitimate can exist if a patented pharmaceutically active substance is used in clinical trials with the aim of finding whether and, where appropriate, in what form the active substance is suitable for curing or alleviating certain other human diseases.”
The Deputy Judge was of the opinion that there must be an “outward limit” to that principle and stated that consideration as to “whether the immediate purpose of the transaction in question is to generate revenue” should be taken into account.
With regard to determining if the experimental purposes relate to the subject-matter of the invention, it was held in the case of Smith Kline & French Laboratories Limited v Evans Medical Limited [1989] 1 FSR 513 that the experiments must have a “real and direct” connection with the claimed subject matter of the patent. This may have therefore limited usefulness in providing an exception to infringement for clinical trials because it only relates to experiments to determine something new relating to the claimed subject matter of a patent, and not for gaining regulatory approval.
The Patents Act 1977 does however have a set of provisions, often termed the “Bolar exemption”, specifically providing an exception to infringement for performing clinical trials to obtain regulatory approval. However, Bolar exemptions come with their own complications, not least because there is what can be termed the “original Bolar exemption” and the “New Experimental Use Exemption”.
The original Bolar exemption is set out in Section 60(5)(i) which came into force in October 2005. It relates to i) an act done in conducting a study, test or trial which is necessary for and is conducted with a view to the application of paragraphs 1 to 5 of article 13 of Directive 2001/82/EC or paragraphs 1 to 4 of article 10 of Directive 2001/83/EC, or ii) any other act which is required for the purpose of the application of those. The original Bolar exemption in the UK was therefore only applicable for the purposes of obtaining an abridged marketing authorisation application, i.e. for bringing a generic drug to market.
It should be noted that different countries within the EU enacted the provisions of the above-mentioned EU Directives in different ways. This has led to a difference in scope for this exemption across EU countries.
Perhaps more applicable to the governments aspirations, to turn the UK into an attractive place to conduct commercial clinical trials, is the New Experimental Use Exemption, which was brought into force in 2014 by the introduction of Section 60(6D)-(6G). Under the previous requirements, only research to obtain an abridged marketing authorisation application for generics fell into the exemption. However, under the New Experimental Use Exemption, anything done in or for the purposes of a medicinal product assessment, e.g. a new medicinal product, which would otherwise constitute an infringement of a patent for an invention is to be regarded as done for experimental purposes relating to the subject-matter of the invention.
The UKIPO Manual of Patent Practice 60.24.3 states:
“It remains to be seen how the courts will interpret the exception set out in sub-sections 6D to 6F however the following activities would appear to fall within its scope:
a) Activities carried out to provide data to regulatory authorities
b) Activities carried out to provide data to bodies carrying out health technology assessments
c) Post approval studies to comply with regulatory requirements
d) Activities carried out to amend an authorisation for a medicine
e) Activities done to obtain an authorisation for a new indication of an existing drug
f) Any tests or studies required by regulatory bodies
g) Activities carried out for the purposes of obtaining full authorisation of a generic drug or biosimilar e.g. where the abridged procedure exempted by the Bolar exception (see 60.28) is not used
h) Activities related to health technology assessment of a generic or biosimilar product
i) Activities carried out to provide data for obtaining regulatory approval for a generic or biosimilar product in another country”
The definition of “medicinal product assessment” provided in Sub-section 6E covers activities carried out to provide information required by regulatory authorities, e.g. clinical trials, or activities carried out to enable a government or public body to assess if a medicine should be used in the provision of healthcare, e.g. health technology assessments. Examples of regulatory authorities include the Medicines and Healthcare Products Regulatory Authority (MHRA) and the European Medicines Agency (EMA). An example of a body which assesses if a new drug should be used in the provision of healthcare is the National Institute for Health and Care Excellence (NICE) (UKIPO Manual of Patent Practice 60.24.2).
The territorial scope of the New Experimental Use Exemption differs from the original Bolar Exemption. The original exemption only applies to acts performed within the UK, but the New Experimental Use Exemption applies to clinical trials for innovative, generic, or biosimilar medicinal products for the purposes of obtaining regulatory approval anywhere in the world.
Much of these provisions have not been tested by the courts and one possible grey area relates to the question of if the use of a patented research tool in a medical product assessment, falls within the scope of the exemption? The UKIPO Guidance relating to the introduction of these provisions indicates that this may be the case:
“Research tools may be an integral part of a drug therapy and when they are used in, or for, the purposes of a medicinal product assessment, they are within the scope of the amendment. However, their use is only exempt for the specific activities defined in the Order, and a licence agreement would be needed to use a research tool once the product is commercialised.”
Guidance from the courts will be needed to fully understand the limitations of the exemption in relation to the use of research tools.
It should however be noted that, “only products which fall within the definition of medicinal product provided by the Directive on the Community code relating to medicinal products for human use (2001/83/EC) or the Directive on the Community code relating to veterinary medicinal products (2001/82/EC) are covered by this exception…” (UKIPO Manual for Patent Practice (60.24.1)). There are therefore limits to this exemption. For example, the “medicinal product assessment” exception does not extend to commercial activities. However, it does cover assessments of combinations where the patented drug is part of the combination (UKIPO Manual for Patent Practice (60.24.2)). Therefore, while a clinical trial for a new medicament (comprising the claimed subject matter of a patent) may be exempt, commercially selling the new medicament does not fall within the exemption.
Those engaging in commercial clinical trials should be aware of these limits to the exemption and act accordingly to seek licences before bringing a product based on patented technology to the market.
Another important area to consider in relation to clinical trials is contributory infringement. Section 60(2) of the Patents Act 1977 states:
“Subject to the following provisions of this section, a person (other than the proprietor of the patent) also infringes a patent for an invention if while the patent is in force and without the consent of the proprietor, he supplies or offers to supply in the United Kingdom a person other than a licensee or other person entitled to work the invention with any of the means, relating to an essential element of the invention, for putting the invention into effect when he knows, or it is obvious to a reasonable person in the circumstances, that those means are suitable for putting, and are intended to put, the invention into effect in the United Kingdom.”
This provision does not apply to the supply or offer of a staple commercial product, unless it is made for the purpose of inducing the person supplied to do an act which constitutes an infringement.
It should be noted however that section 60(6) provides that a person who does an act falling within the “experimental purposes” exemption is not treated as a ‘person entitled to work the invention’, for the purposes of contributory infringement.
According to the UKIPO Manual for Patent Practice (60.31):
“As a consequence of s.60(5)(b) and (6), a person doing an act for experimental purposes does not thereby become entitled to work the invention. It may therefore be an infringing act under s.60(2) to supply that person with the material for carrying out that experimental act. In Monsanto Co v Stauffer Chemical Co and another [1985] RPC 515 (see 60.24) where the material was a herbicide and the person carrying out tests would benefit by eradication of weeds on their land, it was observed that there was at least force in the argument that such supply would constitute infringement.”
Due to the lack of guidance from the courts, how the Bolar exemptions relate to contributory infringement is ambiguous. The UKIPO’s guidance suggests that commercially supplying a product as part of a clinical trial may not be exempted on the basis that it is a commercial activity:
“Does the amendment cover commercial use of a patented drug in a product? The new provisions do not extend to commercial activities, such as sale, commercial supply, or manufacture in preparation for sale or supply. A licence, or other agreement, will be required from the patent holder before a product can be sold or supplied commercially”.
In contrast, sub-section 6D of the New Experimental Use Exemption, contains broad language to “anything done in or for the purpose of a medicinal product assessment”, which may indicate a more lenient approach.
It may depend on if the patented products used in clinical trials are supplied commercially or non-commercially, but it would be beneficial for the courts to provide guidance on this matter. In particular, further clarity would be welcome relating to the question of whether supplying patented products for use in a clinical trial by a third-party supplier, and/or a clinical trial sponsor, is permissible within the exemption. Further, it is yet unclear if a Contract Research Organization (CRO) preparing medicaments for use in a clinical trial is covered by the exemption.
Summary
Those engaging in commercial clinical trials should ensure that they meet the requirements set out above for the Bolar exemption to patent infringement. We strongly recommend consulting your IP advisor prior to commencement of any commercial clinical trial to ensure that you are free to act without a potential infringement issues. This is particularly important for any third-party supplier of patented products for use in commercial clinical trials.
