Infringement of Swiss-type second medical use claims

Review article looking at the different approaches taken by the Courts across Europe to enforcing second medical use patents for pharmaceuticals​.

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In this review article we look at the different approaches taken by courts across Europe to enforcing second medical use patents for known pharmaceuticals using Swiss-type claims. The latest decisions show that some jurisdictions are more patentee friendly (such as the Netherlands and Germany) compared to others (such as the UK and France) giving some forum shopping opportunities when looking to enforce patent rights against generic manufacturers.

Before the EPC 2000 introduced a new article 54(5) EPC, allowing purpose limited product claims to cover a known product for a new and inventive therapeutic application, patent protection for a known drug for a new and inventive therapeutic application was only possible in the form of a purpose limited process claims in the Swiss-type form: use of a substance or composition X for the manufacture of a medicament for Y.

The question of direct and indirect infringement of Swiss-type claims has recently been the subject of decisions in most major European patent litigation jurisdictions, most recently in the UK ([2018] UKSC 56 (Warner Lambert v Mylan & Actavis)). That decision again shows that Courts across Europe are far from aligned on how to deal with the question of infringement of a Swiss-type claim.

Below is an overview of the current status of the case law in the Netherlands, France, Germany, the UK and Italy.

The Netherlands

Recent developments in Dutch case law revolved around two cases: Novartis v Sun (zoledronic acid for a new indication) and MSD v Teva (ribavirin for a specific patient population).

In MSD v Teva (ECLI:NL:GHDHA:2017:2807) the Supreme Court found that a Swiss-type claim is directly infringed by a manufacturer or distributor if he foresees or should have foreseen that the product will be used for the purpose that is the subject of the Swiss-type claim. This would be the case if the skilled person, based on the SmPC, the product information leaflet or any other circumstances, would find that the generic product is intended or suitable for the claimed indication.

The manufacturer and/or distributor can nevertheless avoid an injunction if he has taken all measures that can be reasonably required of him to prevent the product from being dispensed downstream for the claimed indication. In this regard it was confirmed in Novartis v Sun (ECLI:NLGHDHA:2015:1769) that a carve-out in the SmPC and product information leaflet would generally not be sufficient to avoid infringement.

In MSD v Teva the Supreme Court also found that Swiss-type claims can be indirectly infringed. The Court noted that if one followed the literal wording of the claim, indirect infringement (by eg a distributor) of a Swiss-type claim would not be possible as he does not offer means to put the claimed method into effect downstream. However, the Court found there were policy reasons to find infringement such as the fact that Swiss-type claims were accepted to provide reasonable protection for the patentee and the fact that indirect infringement of second medical use patents (in the form of a purpose limited product claim) was made explicitly possible with the revision of the EPC 2000.

The Supreme Court found that a manufacturer can indirectly infringe a Swiss-type patent if he supplies or offers the product and knows, or if it is obvious given the circumstances, that the drug is suitable and intended for the claimed indication. Thus, in certain cases, as recognised by the Supreme Court, a generic company can be found to infringe a Swiss-type claim both directly and indirectly.

To conclude: in the Netherlands the scope of protection of a Swiss-type claim is basically equated with that of a purpose limited product claim. Generics bear a considerable evidentiary burden to prove that they have taken all reasonable measures to prevent use of their generic product for the claimed indication. Not taking such measures may result in an injunction both for direct and indirect infringement.

France

In France, two Court decisions on the infringement of Swiss-type second medical use claims have been handed down in the context of a PI application. In both decisions, the Paris District Court dismissed the preliminary injunction sought by Warner-Lambert and its licensee, Pfizer, against several groups of generic companies.

In the first decision, dated October 26, 2015, the PI application was rejected since Sandoz carved out the pain indication covered by the second medical use patent owned by Warner-Lambert from its SmPC and its label and, in addition, informed more than 50,000 French professionals that its generic version of pregabalin should not be prescribed/dispensed for the treatment of pain.

The Paris District Court found that Sandoz could not reasonably be held liable for either direct or indirect infringement, it being irrelevant that French professionals may prescribe or dispense the generic version for the patented indication.

In the second decision, dated December 2, 2016, the Paris District Court gave several directions on how Swiss-type second medical use claims should be construed by the French courts.

First, the Court confirmed that Swiss-type claims should be considered as process claims, and not as product claims. The Court, therefore, concluded that there can be no direct infringement in cases such as the one heard by the Court where the manufacture of the generic medicine took place outside France, since there was no downstream manufacture after sale in France.

Second, the Court rejected the indirect infringement claim and pointed out that all the generic manufacturers (i) limited their marketing authorization to the two unprotected indications, clearly indicated as such on the SmPC, and most importantly, (ii) carried out an important information campaign among pharmacists and prescribing practitioners who were advised of the precautions to take when prescribing/dispensing the generic medicine.

Thus, the Court found that a generic manufacturer, that took all necessary measures when launching the generic version to avoid this version being used for the patented indication, should not be held liable for patent infringement.

The Court further held that it could not be seriously argued that the generic manufacturer had encouraged medical professionals to replace the originator product with the generic one in the case of prescriptions for the patented indication when they had, of their own accord, informed the professionals that their marketing authorization was limited to the non-patented indication and this important information campaign had resulted in significant costs for the generic manufacturer.

This case law indicates that if generic manufacturers are able to provide evidence that they have taken all reasonable measures to avoid any cross-label dispensing for the patented indication, they should not be held liable for indirect infringement.

Germany

Germany has always been known for the patentee friendliness of its patent court system (not least due to the split between infringement and invalidity litigation). The enforcement of second medical use claims (in Swiss-type format or EPC 2000 format) was, for a while, an exception to that rule and made it easy for generics to avoid infringement by carving out the infringing use from the product information. However, following the case-law of the German Federal Supreme Court (FSC) and the lower courts the situation has changed very significantly in favour of the patentee in recent years.

In Germany no distinction is made between the enforcement of second medical use claims in the Swiss-type format and those in the EPC 2000 format. They are all universally regarded as giving purpose-limited product protection (cf. FSC, GRUR 2014, 461 – Kollagenase I; GRUR 2016, 921 - Pemetrexed). Therefore, for both kinds of claims direct infringement is primarily at issue, with indirect infringement basically coming up only if components of the drug are supplied.

The crux of second medical use claims is that the suitability for the second medical use is an inherent characteristic of the drug itself but there is no protection for the drug as such, only for the specific use. Thus, a balance must be struck to ensure that the patentee gets the benefit of the use protection, but that the use protection does not serve to achieve drug protection as such.

In the past German case-law required for infringement that the substance was “sinnfällig hergerichtet” (manifestly arranged) for the claimed use, ie either (i.) prepared by formulation or other design for the claimed use or (ii.) sold with product information indicating the claimed use. Further, the category of manifest arrangement was very restrictively applied by the lower courts. For example, it was considered insufficient for such manifest arrangement that (i.) the patient group to which the second medical use related was so sizable that a patented use was basically inevitable (District Court Duesseldorf, GRUR-RR 2004, 193 - Ribavirin), (ii.) whether due to substitution the patented used could be expected (District Court Duesseldorf, decision in the case Chronische Hepatitis C-Behandlung) or (iii.) where despite the carve-out in the product information leaflet the product had otherwise been marketed for the claimed use (Duesseldorf Appeals Court, decision in the Cistus Incanus case). Thus, if there was a carve-out in the product information leaflet and the SmPC, the generic was basically safe, even if in practice there was very significant cross-label use.

Since 2015, however, a number of decisions have been handed down directed at preventing generics from profiting from cross-label use for patented indications. In 2015, the District Court Hamburg in the pregabalin case prohibited a generic from participating in tender proceedings with sickness funds which did not exclude the patented indication, on the basis that this was considered a manifest arrangement because it was instrumental for substitution (GRUR-RR 2015, 330 - Rabattvertrag). Since 2017, the Duesseldorf Courts have gone even further and declared that manifest arrangement is not required but that it is sufficient for infringement if (i.) the manufacturer/distributor knows or should have known that the product will be used for the patented use to a sufficient extent (eg known cross-label use) and (ii.) does not take the steps which could be reasonably expected from him to minimize the risk of infringing use (Appeals Court Duesseldorf, GRUR 2017, 1107 - Oestrogenblocker; PharmR 2018, 306; District Court Duesseldorf, GRUR-RS 2018, 15604; BeckRS 2018, 15431; BeckRS 2018, 15603, the District Court Duesseldorf’s decisions having just been upheld by the Appeals Court Duesseldorf in a decision announced on January 9, 2019).

The reason why injunctions were not granted in these cases (relating to fulvestrant) was (solely) that sufficient cross-label use had not been established to the courts’ satisfaction. The courts concluded that (as shown by amended guidelines for physicians) medical practice had moved away from the claimed therapy. However, it appears clear that injunctions will be granted when sufficient (patented) cross-label use can be established and the defendant cannot show that he has taken reasonable measures to prevent the patented use. The question, however, remains what measures will be expected? It is clearly not possible to participate in tenders which include the patented indication. Other measures which have been discussed are the inclusion of warnings in the databases used by doctors and pharmacists and informing the sickness funds as well as doctors’ and pharmacists’ associations. However, including such a warning in the product information leaflet, the SmPC or on the packaging, would probably require a change in pharma regulatory law.

In addition to enforcing second medical use claims through patent litigation, litigation under public procurement law is also a powerful tool in Germany to force sickness funds not only to exclude the patented indication in tenders for generics (and ensure that this is observed in practice, which the sickness fund can do because they have the information about the drug and the indication) but also to inform doctors about the existing patent protection so that they prescribe the originator product for the patented indication (cf. Appeals Court Duesseldorf (public procurement senate), BeckRS 2016, 13255). 

United Kingdom

Although the Supreme Court’s comments on infringement in the Warner Lambert case were obiter (given the claim in question was found to be invalid), they are still a useful indication of how the UK courts will approach the question of infringement of a Swiss-type claim in relation to “skinny label” products (with indications protected by the second medical use patent carved out). While the five judges were divided in their reasoning, which may suggest some flexibility in the Court’s approach in the UK in the future, they all reached a conclusion favouring the generic manufacturer in this case.

The Supreme Court noted that a skinny label stating that the generic drug is not for the patented purpose (here the prevention of pain) will not prevent it from being dispensed for that purpose as the pharmacist (and the manufacturer) does not generally know the condition for which it has been prescribed.

The Court of Appeal had already acknowledged the struggle faced by the law between giving the patentee a proper reward for its contribution to the art by elucidating a new use for a known drug, while not excluding a generic manufacturer from making and marketing the drug for its known (non-patented) use. Both Courts noted in their judgments the spectrum of approaches to the interpretation of the Swiss-type claims adopted in various EPC states (including Germany, France and the Netherlands). While accepting that there was no settled answer to the problem, the Supreme Court found that a broad foreseeability test of the kind proposed by the patentee had not found favour across Europe. The Supreme Court also rejected Warner Lambert’s secondary case, preferred by the Court of Appeal (and the Dutch courts), namely foreseeability tempered by the taking of all reasonable steps by the generic manufacturer to stop leakage in the market for the patented use.

For direct infringement, the majority of the Supreme Court favoured a compromise position - leaning towards a form of “subjective intention” test. This was said to be a departure from the original German “only packaging will do” approach by permitting any means of proof of the manufacturer’s purpose while acknowledging that in most cases the packaging, label and product information leaflet will be the best evidence of the manufacturer’s intention. Lords Sumption and Reed had proposed an (admittedly imperfect) “outward presentation” test, where the intention of the generic manufacturer as to what its product is to be used for (ie for patented or non-patented indications) is limited to the intention indicated on the product itself – ie on its packaging, label or product information leaflet. This would be an objective test and would mean that a generic manufacturer who sold its product under a skinny-label would be protected from claims of infringement (as would downstream actors such as pharmacists and doctors). However, Lords Briggs, Hodge, and to a degree Lord Mance, thought that strictly limiting evidence of the manufacturer’s intention in this way may prejudice patentees, who would be unable to succeed in a direct infringement claim if they had other evidence which showed that the generic manufacturer in fact intended its product to be sold for the patented indications, notwithstanding the skinny label.

In contrast to their decision on direct infringement (and while still obiter), the Supreme Court was unanimous on indirect infringement, agreeing that Swiss claims are purpose-limited process claims and so have a more limited degree of protection than standard product claims. In this way, the Supreme Court agreed with the first instance decision which originally struck out Warner Lambert’s claim for indirect infringement (which had been overturned by the Court of Appeal) and found that the essential ‘manufacturing’ feature would be fatal to any attempt to construe a Swiss claim as extending to any steps downstream of manufacture, for example those taken by the dispensing pharmacist.

Ultimately, it appears that, in most cases, direct infringement may be avoided in the UK if the generic manufacturer uses a skinny-label. However, if there is evidence that the manufacturer intended to sell the product for the patented purpose, the patentee may still be able to run a successful infringement claim. As for indirect infringement, this may be impossible if dependent on any steps downstream of manufacture.

So, when considering Swiss-type claims, it seems that the UK courts may adopt a middle ground, but if the circumstances of Warner Lambert are repeated (and if there is no evidence of intention for the generic product be used for the new, patented indication), then this would favour the generic manufacturer.

Italy

Upon implementing the 1973 European Patent Convention, Italy had introduced into Italian law a regulation which allowed new use patents, without any distinction being made between sectors of application or between first use and further uses in the same sector. Therefore, it has never been necessary to use the Swiss-type claim structure to obtain patent protection in Italy for inventions concerning a second medical use of an active ingredient already known for a different medical use. The only Italian decision to examine Swiss-type claims expressly, in relation to the Italian part of a European patent, was that of the Court of First Instance of Turin of 7 July 2009 which merely ruled that claims formulated as Swiss-type claims were admissible in Italy.

In Italy, second medical use claims are construed as normal purpose-limited claims. Moreover, second medical use claims may be enforced on the basis of both direct and indirect infringement, depending on the circumstances.

With regard to drugs which may have multiple uses, such as pregabalin in the Warner Lambert case, one of which is covered by a second medical use patent, what is, first and foremost, of importance in Italy are the notes and communiqués issued by the Italian Medicines Agency (AIFA). In Italy, Warner-Lambert, the patentee, decided instead of immediately bringing patent actions against generics which sold pregabalin which could also be used for the patented use, to ask AIFA to take steps to avoid pregabalin-based generics from being prescribed for the treatment of the patented indications. Following the request, AIFA issued a Note 4 in which it stated that pregabalin-based generics could only be charged to the national health service if prescribed for the treatment of indications other than neuropathic pain. In a communiqué of 16 September 2015 AIFA then stated that for the indications covered by the Warner-Lambert patent a doctor could only prescribe the patentee’s drug Lyrica® at the expense of the national health service and not generics based on the active ingredient pregabalin. In its Note 4 and the following communiqué, AIFA therefore adopted measures which were particularly favourable to patentees.

There are a number of other important decisions of the Italian courts that do not deal with infringement of Swiss-type claims per se but more generally with indirect infringement. A landmark decision in this respect was the Italian Supreme Court judgment in Leeds & Northrup Italy v. Sidermes of 1996. This decision supported the conclusion that a Judge could find indirect infringement if there was evidence that the manufacturer/distributor knew or should have known that its product would be used for the patented indication. In following these principles, the Court of First Instance of Milan, which considered the indirect infringement of a pharmaceutical patent in its Order dated 12 September 2017, gave particular weight to the indications contained in the product information leaflet of the allegedly infringing drug. It stated that, in the case at hand, there was no indirect infringement since the manufacturer in the summary of the product characteristics expressly required the user to prepare the solution of the product in a way which was completely different to that indicated in the patent. On the basis of this decision it seems that the trend in Italian case law is towards holding that infringement may be avoided if the generic manufacturer uses a skinny-label. However, there are as yet no other decisions on this matter and we cannot, therefore, speak of a clear trend. Furthermore, Note 4 and the AIFA communiqué may influence the Italian courts to decide the issues concerning skinny label products with greater attention and strictness.

Closing remarks

Some key points arising from the diverging case law across the European patent litigation jurisdictions described above are set out in the table below:

Country

Swiss claim - type?

Direct infringement

Indirect infringement

Comment

UK  Purpose-limited process claim
(distinct from EPC 2000).
Element of subjective intention required. Impossible if reliant on any steps downstream of manufacture. More patentee unfriendly.
France Purpose-limited process claim
(distinct from EPC 2000).  
Element of foreseeability. Skinny label and notification may be enough to avoid infringement (and injunction). Impossible if reliant on any steps downstream of manufacture. More patentee unfriendly.
The Netherlands Purpose-limited product claim
(indistinct from EPC 2000).
Elements of foreseeability (objectivity) and requirement to take all reasonable steps to avoid infringement. Possible in light of approach to claim. More patentee friendly and evidentiary burden higher on alleged infringer.
Germany Purpose-limited product claim
(indistinct from EPC 2000).
Similar to NL, but remains to be seen what measures will be needed in view of existing cross-label use to avoid an injunction. Possible in light of approach to claim. Trend changing to become more patentee friendly than in past, though evidentiary burden remains less clear.
Italy Purpose-limited product claim
(indistinct from EPC 2000).
No clear guidance or precedent case in this area. Possible in light of approach to claim. Use claims introduced with EPC 1973 so less need to rely on Swiss-type claims in Italy.

Such divergences provide patentees with interesting opportunities for forum shopping in Europe and of course, where multi-national litigation ensues, presents considerable complexity in coordinating and addressing the differing approaches across key jurisdictions.

No doubt we will see further developments in the assessment of infringement of second medical use patents in years to come, given the wealth of Swiss-type claims present in patents already granted and how these issues will impact on the EPC 2000 medical use claim format. Whether this will result in further alignment remains to be seen, including in particular how such matters will be dealt with by the Unified Patent Court, if or when it comes into being.

This document (and any information accessed through links in this document) is provided for information purposes only and does not constitute legal advice. Professional legal advice should be obtained before taking or refraining from any action as a result of the contents of this document.