UK: Methods Of Treatment: Is There Any Protection Available In Europe?

Methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body are not patentable in Europe because they are not regarded as inventions which are susceptible of industrial application. This provision, which is set out in Article 52(4) of the European Patent Convention (EPC), is also embodied in the National laws of the member states of the EPC. The exclusion is included solely on the grounds of public policy to ensure that those who carry out such methods as part of their medical or veterinary duties are not inhibited by the existence of patents.

Pharmaceutical companies, however, carry out significant research to identify new therapeutic uses for known compounds. Because these compounds are already known, patent claims directed to the compounds per se are not available. In the United States developments of this type may be protected using method of treatment claims. So how then can protection be achieved for such new therapeutic applications within the legislative framework that is in place in Europe?

Firstly, Article 52(4) EPC, being an exclusionary clause, must be interpreted narrowly. It does not, of course, apply to those treatments that do not include a therapeutic element or constitute a surgical or diagnostic method. A single step in a claim that involves a therapeutic, surgical or diagnostic procedure will be sufficient to render the claim unpatentable. A considerable body of case law has developed in Europe that provides guidance on the types of methods that are considered to fall outside the exclusion.

Generally, therapy is interpreted broadly and embraces prophylactic methods as well as curative treatments, so trying to argue that a method does not result in therapy because it is merely preventative will not work. The question of whether a medical practitioner is required to carry out the method, while providing a useful indicator, is not sufficient in its own right to decide whether a particular method will be excluded. However, if a medical practitioner must carry out the procedure, it is a likely indication that a method of treatment is being performed.

Non-therapeutic treatments are patentable if the non-therapeutic effect is distinct and separate from any therapeutic effect. Thus, for example, cosmetic methods will be patentable if it can be shown that the cosmetic effect is not inextricably linked to any therapeutic effect that may also be occurring. If the effects are not separable, merely calling the method "a cosmetic method" will be insufficient to meet the requirements of Article 52(4).

A diagnostic method must, of course, be practiced on the human or animal body for it to be excluded, in which case any diagnostic method performed on cells in culture, or a sample obtained from a patient, should fall outside the exclusion. A surgical procedure is prohibited from patentability regardless of its intended purpose, therapeutic or otherwise.

Article 52(5) EPC explicitly provides that any substance or composition for use in a method of treatment may still be patentable. Therefore, the Article 52(4) exclusion is designed to control what a doctor administers to a patient as opposed to how he administers it. This concept of novelty is not available in any other technical field. For example, in the mechanical field, a claim worded as "apparatus for use in a field Y", will not be novel if the apparatus per se is known. The prescribed use is not considered limiting to the apparatus features. In the event that a known compound does not have any previously recognised use in any medical application, the Enlarged Board of Appeal of the European Patent Office (EPO) in the landmark decision of G5/93¹ ruled that such a new use can be claimed broadly as "composition X for use as a medicament", and no specific indication of the therapeutic use is required for the claim to be considered allowable.

Whereas broad protection seemed to be available for first medical indications of a known compound, the same was not the case for discoveries of new and further therapeutic applications of compounds that had already been used in a medicinal context. This is because Article 54(5) EPC provides that a substance or composition comprised in the state of the art for use in a method of treatment is patentable "provided that its use for any method referred to in Article 52(4) is not comprised in the state of the art". This, therefore, seemed to preclude from protection known medicinal compositions that were found to have another medical application, in that the wording of Article 54(5) EPC excludes from protection compounds which were used in any medical application. So how then could protection be obtained for these potentially valuable new medical applications of such known compounds?

"Use claims are not applicable because a claim worded as "use of compound X for treating disease Y" is interpreted by the EPO as a method claim, and methods of treatment claims are not allowable. The Enlarged Board of Appeal in G5/83 also decided, however, that a claim generally worded as "use of compound X in the manufacture of a medicament for treatment of disease Y" would be acceptable to cover the new medical applications on the basis that there was no intention in the EPC to exclude second (and further) medical indications generally from patent protection and the novelty of the claim resided in the new therapeutic use and not the method of manufacture. This wording has become the generally accepted format for "second medical use" or "Swiss-type" claims and they are routinely granted by the EPO.

At a recent diplomatic conference of the member states of the EPC², it was proposed to amend Article 54(5) to dispense with the requirement for a Swiss-type claim, so that the article would read as follows: "...the provisions of this article shall not exclude the patentability of any substance or composition referred to in paragraph 4 for any specific use in any method referred to in Article 53(c), provided that such use is not comprised in the state of the art". Thus, first medical use claims may still be phrased "compound X for use in therapy", whereas second or further medical uses can be claimed as "compound X for use in treating disease Y". However, no date has yet been set for when these revisions will come into effect.

In addition to the standard Swiss-type claim where protection is afforded to the new medical use of the known pharmaceutical compound, the EPO has also gone a stage further and ruled that a new mode of administration of a compound can of itself constitute a new medical use if it is a critical factor in a medical treatment. If the mode of administration was not previously disclosed a claim of this type will be allowable. In the Board of Appeal case, T51/93 (unpublished), the mode of administration claimed was subcutaneous as opposed to the traditional intramuscular method normally used. Even though the medical use itself was not novel, administration of the compound subcutaneously was considered sufficient to confer novelty to the claim.

The EPO has also allowed claims in the Swiss-type form where the only novel feature resided, not in the new therapeutic use, but in a new dosage regime for administering a compound that was already known for treating the same disease but offered, for example, less toxic side effects. Claims of this type must, however, be of questionable validity in light of some recent decisions of the national courts of the member states of the EPC, where issues of infringement are addressed.

There have only been very few cases decided before the national courts concerning Swiss type claims, but a number of them do cast doubt on the validity of claims for which the only novel feature resides in the dosage regime or the mode of administration. The UK Court of Appeal, in the case of Bristol-Myers Squibb (BMS) v. Baker Norton Pharmaceuticals and NaPro Biotherapeutics, ruled that a claim that read: "use of taxol and sufficient medications to prevent severe anaphylactic reactions for manufacturing a medicament for simultaneous separate or sequential application for the administration of 135mg/m² up to 175mg/m² taxol over a period of about 3 hours or less as a means of treating cancer and simultaneously reducing neutropenia", was not a valid second medical use claim because the only novel feature was the dosage regime. The compound or medicament was already known for treating cancer and the dosage regime only represented further information about how to treat it. According to the Court there was, therefore, no new therapeutic use. The claim was considered to be a method of treatment and as such was declared invalid.

A similar conclusion was reached by the Dutch Court of Appeal in Bristol-Myers Squibb v Yew Tree of 25 June 1998. The courts in the Netherlands have also in the past refused to acknowledge the novelty of second medical use claims on the basis they are considered to be dressed up methods of treatment. In the latest decision from the Netherlands, General Hospital -v- Air Products,⁴ this interpretation was confirmed.

Although issues of validity have been addressed, what has been lacking to date is an indication of how the national courts will deal with the question of infringement of first and second medical use claims. In the first instance decision of BMS -v- Baker Norton and NaPro, the trial judge did not address the issue of infringement because the claims were considered invalid. The Court of Appeal did, however, consider infringement to assist in clarification of how the terms in the claims should be interpreted. They were of the view that clinical trials carried out on women with ovarian cancer in which taxol (175mg/m²) was administered intravenously every 21 days as a 3h infusion did amount to an infringement of the Swiss-type claim. However, not all cases of infringement will be as clear cut.

In the UK, a person infringes a patent for an invention if he commits any of the following acts in the UK during the term of the patent; (the relevant passages of Section 60 of the UK Patents Act only being provided):

1. where the invention is a process, he uses or offers it for use in the UK when he knows or it is obvious to a reasonable person in the circumstances that its use there without the consent of the proprietor would be an infringement of the patent; and....
2. if he supplies or offers to supply in the UK a person not entitled to work the invention, with any of the means, relating to an essential element of the invention, for putting the invention into effect....

Similar provisions apply in the other EPC countries. Where, for example, a third party sells only a composition, to prove infringement of a Swiss type claims it is necessary to establish whether the sale of the compound is for the purpose of treating the claimed illness, otherwise known as "contributory infringement". The primary infringers will be the medical practitioners who eventually administer the drug and who are exempt from infringement, unless they are using the compound in a manner which is not for private and non-commercial purposes. Thus, reference to the product literature accompanying any such composition will be required to establish contributory infringement, but this may not provide all of the answers if the drug is formulated in the same way to treat both the first and second medical conditions. Administration of the compound may have the effect of treating both the first and second medical indications. In the Air Products case in the Netherlands, the court did consider infringement. In this case, Air Products were selling a gas mixture but did not, itself carry out the steps of treating the illness covered by the patent. The court held that supplying the compound to put the invention into effect did not amount to contributory infringement because, first the gas mixture is readily available and second it was not shown that Air Products had incited its customers to carry out the method described in the patent.

One of the areas which is not at all clear is the question of Supplementary Protection Certificates (SPC) based on a Swiss-type claim in a granted European patent. EU Council Directive 1768/92⁵ allows for the provision of SPCs for medicinal products and extends the period of protection for up to five years for these products, provided they are subject to regulatory approval before they can be placed on the market. The SPC is granted only for the active ingredient of the medicinal product that is the subject of the marketing authorisation permitting sale of the product on the market in the territory concerned and which product must be protected by a patent for that territory. However, an SPC cannot be granted for a product the active ingredient for which has, or is already, the subject of such a marketing authorisation. Thus, an SPC will not be allowed based on a second medical use claim if the active ingredient has already been the subject of a marketing authorisation. If a medicinal product has been sold for the treatment of the first medical indication, it will inevitably have been the subject of such an authorisation. To sell a product for any medicinal use, irrespective of whether it is for a first or second medical use, a marketing authorisation, including details of various clinical trials, is required. Thus, a product for treating a second or further medical use will be subjected to the same regulatory procedures but will not be eligible for an SPC if there exists a previous marketing authorisation for the same active ingredient.

In summary, useful protection for methods of treatment may be obtained in Europe by way of first and second medical use (Swiss) type claims, and such claims appear to be acceptable in principle to the courts of most of the member states of the EPC. The proposed revision of the EPC to specifically allow protection for such claims should clarify the position further. However, there are some issues to be addressed, such as their enforcement, which can only be decided in the national courts and which may well result in different outcomes between the member states.

© 2001. Boult Wade Tennant

This article appeared in the May 2001 issue of Nature Biotechnology magazine.