What do recent SPC decisions mean for life sciences companies?

Obtaining and enforcing supplementary protection certificates (SPCs) is a top priority for life sciences innovators operating in the European Union. As harmonised national IP rights, SPCs are granted to owners of patent-protected medicinal products and provide five years’ additional market exclusivity after patent expiry. Introduced in 1992, the sui generis rights are intended to compensate biopharma innovators for the lengthy and expensive R&D and regulatory processes that they must undertake to bring a product to market – processes which mean that an invention is well into its patent term by the time it is launched. The initial SPC regulation was replaced by the re-codified EU SPC Regulation 469/2009.

SPCs are crucial to commercial strategies in the sector, not only because they provide a significant IP extension, but also because they do so at the end of the patent term when a product’s profitability and market share is typically at its highest, and when even a short continuation of exclusivity can be worth millions. It is often said that as much as 80% of a product’s revenue can be generated during its SPC term.

Life sciences IP professionals must also pay close attention to SPCs because of the distinctive set of legal questions that have arisen concerning the rights. While the EU Commission’s Explanatory Memorandum for the 2009 regulation states that the SPC regime is intended to be a “simple, transparent system that can easily be applied”, a slew of disputes have occurred over the past decade regarding the interpretation of several key articles in the regulation. Reflecting a lack of clarity on fundamental questions relating to when a product is eligible for an SPC, these articles have produced a steady stream of European Court of Justice (ECJ) referrals.

According to Darts IP data, national courts have sought preliminary judgments from the ECJ in 39 SPC cases, leading to 30 decisions between 2009 and July 2018. Several recent ECJ decisions have overturned established interpretations of the SPC regulation with significant legal and commercial implications for originators and generics alike. It is therefore essential for biotech and pharmaceutical IP professionals to keep a close eye on developments in this area.

The past 12 months have produced several major decisions: Gilead (C-121/17), Boston Scientific (C-527/17) and Abraxis Biosciences (C-443/17) – each of which has implications for organisations in the industry. As such, IAM reached out to a number of leading in-house and private practice pharmaceutical IP practitioners to review the recent judgments, their impact on the commercial and legal strategies of biopharma companies and the questions that they leave unanswered.

What is meant by “protected by a basic patent in force”?

Perhaps the most notable SPC-related decision handed down by the ECJ in the past year was its 25 July 2018 Gilead (or Truvada) judgment, which many hoped would clear up a number of uncertainties relating to Article 3(a) of the EU SPC Regulation 469/2009.

Article 3 sets out the conditions under which an extension right can be obtained by an applicant, with Article 3(a) requiring that “the product is protected by a basic patent in force”. While at first glance this article might seem straightforward to interpret and apply, it has in fact been at the heart of a plethora of disputes, with 10 cases being referred to the ECJ since 2009.

Gilead arose from a UK High Court of Justice (England and Wales) dispute between Teva (and other generic companies) and Gilead Sciences, over the validity of the latter’s SPC for its HIV/AIDS treatment branded Truvada. This is a product that combines two active ingredients – tenofovir disoproxil and emtricitabine. But Truvada, the generics argued, was not “protected by a basic patent in force”, because only one of its two active ingredients – tenofovir disoproxil – was identified in the patent on which the application had been based.

While the patent does not claim the use of tenofovir disoproxil in combination with any other specific active ingredient, it does include a broad claim (Number 27) for “a pharmaceutical composition comprising a compound according to any of claims 1-25 together with a pharmaceutically acceptable carrier and optionally other therapeutic ingredients”.

Both sides cited recent ECJ case law in their favour. The generics argued that under the court’s 2011 Medeva ruling, which stated that the active ingredients of a product must be “specified in the wording of the claims of the basic patent”, Truvada does not qualify for an SPC. Gilead in turn cited the ECJ’s Eli Lilly judgment of 2013, which stated that a patent need not name the product for the purposes of Article 3(a), but its claims must “relate, implicitly but necessarily and specifically” to the product. The phrase “other therapeutic ingredients” in Claim 27 of the patent, it argued, implicitly and necessarily relates to emtricitabine.

Table 1. National courts requesting an ECJ preliminary injunction on an SPC case

Source: Darts IP presentation, IAM Pharma and Biotech event 2019

Uncertainty since Medeva

The dispute occurred against a backdrop of significant uncertainty concerning the application of Article 3(a) – especially with regard to combination products. Unlike similar extension IP rights that are available for medicinal products elsewhere in the world, EU SPCs can be awarded for combinations of active ingredients as well as for individual active ingredients (according to Article 1(b)). Certificates can be acquired by innovators for new approved combinations of existing active ingredients. However, this raises challenging questions around what is required for a patent to “protect” such products for the sake of obtaining an SPC.

From the point of view of patent law, a patent that claims one active ingredient only provides protection for that substance in whatever circumstances; including in combination with other therapeutic agents. A prima facie reading of Article 3(a) would suggest that such a patent is all that is required to secure an SPC for a combination product. In fact, before 2011 a simple infringement test was applied to assess whether a patent in force protected a particular product.

Medeva made a sharp break from this approach, laying out a considerably more restrictive criteria for making that assessment. It emphasised that all of the active ingredients in a product must be “specified in the wording of claims of the basic patent”. This addressed concerns that many had about a simple infringement test, as Tomos Shillingford, associate general counsel at Insud Pharma, told IAM.

“The infringement test was dismissed by Medeva, because it was perceived to have a problem with combination products, providing for the possibility of SPC ‘evergreening’. If the test simply considers what infringes the patent claims, you could have multiple further SPCs for numerous uninventive combinations”, Shillingford comments.

But the approach spelled out in Medeva created new problems and has been heavily criticised by observers. “The disclosure test also has problems though”, Shillingford confirms. “The court said that the active ingredients needed to be specified in the claims, which means that they have to be expressly identified. That is potentially harsh, especially on biologic inventors. Early-stage biological innovation often revolves around target identification – so a lot of the related patent claims are to an antibody that binds to targets, without specifying a particular antibody.”

Oswin Ridderbusch of Vossius & Partner echoes this argument: “The requirement set out in Medeva was wholly inconsistent with the function of the claims in patent law. The claims provide the boundaries of what is protected by a patent; set the outer limits. They do not specifically identify what is protected in the sense that it is required by Medeva.”

“This creates difficulties”, Ridderbusch adds. “Identifying the exact active ingredient is possible in the small molecule drugs, but if you look at biologics, this does not reflect the actual contribution of the fundamental invention that makes available certain antibodies. The specific antibody that will eventually receive market authorisation is very often not disclosed in detail with the full sequence in the corresponding basic patent.”

The decision also created confusion regarding when and whether products consisting of a single active ingredient satisfy Article 3(a) if they are identified by a Markush formula. Markush formulae represent chemical structures and indicate (potentially large numbers of) potential chemical compounds rather than listing each compound individually. How Article 3(a) applies to drugs protected by functional claims was also not made clear in the aftermath of Medeva.

Perhaps recognising these difficulties, the ECJ seemed to soften its stance slightly in subsequent decisions (notably Eli Lilly), which reaffirmed the disclosure test while moderating it. However, in moving away from the strict standard expressed in Medeva, the court created confusion about the type of disclosure required in the patent. For example, most parties have found that what is meant by claims to “relate, implicitly but necessarily and specifically” to a product is unclear.

Others reacted more favourably to the ruling. For example, Ulrich Doerries of German law firm DFMP told IAM last year that “my personal sense is that we have slightly more clarity now, but not as much as we would have hoped for; perhaps that is to be expected given the complexity of the topic.” The initial part of the test, he says, provided clarification and was seemingly influenced by Judge Arnold’s proposed inventive advance test. Similarly, Ridderbusch comments: “Personally, I think that the ECJ has done quite well with recent Article 3(a) judgments. In terms of consistency, it is difficult to criticise these decisions.”

Nevertheless, all the lawyers that IAM spoke to believed that further clarification is needed on Article 3(a) – and not just as it relates to combination products. While Judge Arnold framed his question as broadly as possible, the Truvada decision did not address important Article 3(a) issues, such as when a product is protected by a Markush formula – which is the question at the heart of a pending ECJ referral, Sandoz v Searle (C-114/18) – or when functionally worded claims protect a product, which is at issue in Royalty Pharma/Sitagliptin (C-650/17).

The ECJ is said to have reached out to the national courts involved in these two cases following Truvada and asked whether a ruling in those referrals was still needed. “Both courts said ‘of course they are!’, because there is still so much uncertainty”, explains Bristows’ Laura Reynolds. “It is slightly frustrating that when the court knows what other questions are in the pipeline, and refers to them often in the footnotes of the judgment, it remains reluctant to giving a judgment that answers all of them in one go.”

This continues a pattern in recent ECJ judgments, as Shillingford comments: “I think the law on Article 3(a) has been developing incrementally according to the particular cases before the court, and the judgments have lacked a holistic view.” Europe’s highest court, it has also been pointed out, is hampered to some extent by the fact that it is not a specialist IP court. So, although the ECJ is set to hand down judgments on two pending Article 3(a) referrals in the coming years, the issue is likely to be shrouded in considerable uncertainty for the foreseeable future.

However, “further judgments are likely to be in line with Truvada”, predicts Ridderbusch, whose colleague Von Uexküll anticipates that “the ECJ will now consolidate its case law. Medeva is likely to be more closely defined in keeping with Truvada.”

While innovators face a lack of clarity, there are rules of thumb that they can follow to put themselves in a good position to acquire strong SPC protections. “Identifying possible combinations as early as possible and getting patents for them is a good idea, so that they are the subject of the invention and the patent per se,” Cordery adds, “be mindful of the opportunity to amend your claims.”

New formulations excluded from SPCs

The ECJ handed down another major SPC-related ruling in March 2019, this time addressing the proper interpretation of Article 3(d) of the regulation, which states that the marketing authorisation (MA) needed for a product to qualify for a certificate must be the “first authorisation to place the product on the market as a medicinal product”.

The question of what constitutes a ‘product’ has been contested in recent years and was at the centre of the court’s decision in Abraxis Biosciences. This arose from a dispute over whether Abraxis’ cancer treatment Abraxane qualifies for an SPC. The main constituent of Abraxane is nab-paclitaxel, a patented new formulation of a previously approved active ingredient, paclitaxel. By coating nanoparticles of paclitaxel with albumin, it improves the drug’s efficacy in treating cancer.

In 2016 the UK Comptroller General of Patents refused to grant an SPC for Abraxane, because in its view new formulations of existing active ingredients do not qualify as new products for the purpose of the SPC regulation and therefore its MA was not the first to put the product on the market under Article 3(d).

Until 2012 it was widely understood that only new active ingredients and combinations of active ingredients are entitled to SPC protection. But the situation was changed radically by the ECJ’s ground-breaking Neurim decision. This held that a medical product for human use was not prevented from being granted an SPC by the fact that the same drug had previously been approved for use on animals, “provided that the application is within the limits of the protection conferred by the basic patent”.

Seeming to break the old mould, Neurim prompted large numbers of SPC applications for new therapeutic uses, as well as new formulations, of existing drugs. Indeed, Abraxis argued in an appeal before an English court that the more permissive interpretation laid out in Neurim should extend to new formulations. Considering the law to be unclear, the national court referred the case to the ECJ, asking it to give guidance on the correct interpretation of Article 3(d).

Restrictive Article 3(d) interpretation could exclude important innovations

The ECJ rejected Abraxis’ argument, holding that Article 3(d) is informed by Article 1(b), which states that a “product” is an active ingredient or combination of active ingredients. This interpretation of Article 3(d), it reasoned, is also supported by the 11 April 1990 Explanatory Memorandum – which proposed the creation of the SPC – which notes that the term ‘product’ means an active substance in the narrow sense of the term (eg, excluding new formulations).

Though crystal clear on the question of new formulations, Abraxis is a blow for innovators, clarifying that a major category of medical inventions is ineligible for SPC rights. Cordery comments: “Abraxis seems to have sounded a death knell for SPCs based on patents for new formulations. Neurim was a great decision for patentees and originators, who then tried to push Neurim to see what its logical conclusion was. The ECJ has now said that you definitely cannot have SPCs for formulations.”

Von Uexküll told IAM that this will be especially disappointing given the high expectations that were produced by Neurim. “You can have significant inventions that do not depend on new chemical entities. Going through the approval process for a new formulation requires going through a costly and risky development process similar to developing a new compound. The prospect of five years’ SPC protection was an important incentive for this.”

Echoing this point, Cordery cites the example of Neoral, a then-new formulation of cyclosporine developed at great cost by Novartis, which radically improved the success rate of organ transplants. “Novartis had a patent, but it was a new formulation of an old drug, so under the current law, it would not be entitled to an SPC”, he explains.

Neurim to be chipped away?

A small relief for innovators is that Abraxis, while seeming to depart from Neurim, did not overturn the previous decision. At least some new therapeutic uses, therefore, are still likely to be eligible for SPCs. But a lack of clarity in both Neurim and Abraxis means that originators are none the wiser on whether extension rights are to be:

• available for all new therapeutic uses;
• restricted to products where the previous MA was for a veterinary use; or
• restricted only to new therapeutic uses of drugs whose previous MA was for a veterinary use.

As Damerell explains: “The Abraxis judgment is relatively brief. It does not engage with Abraxis’ analogy relying on the earlier Neurim case, namely that for policy reasons new and inventive formulations should be treated in the same way as new and inventive therapeutic uses – instead the ECJ simply stated that Neurim was not relevant as it concerned therapeutic uses and not formulations. As a result it is unclear how broadly the previous ECJ judgment in Neurim will be applied.”

“This is disappointing”, he continues, “because the Advocate General’s opinion in the case discussed these issues at length and analysed various possibilities. It seems likely that Neurim will be treated as a very narrow judgment based on its facts, although there is likely to be further litigation to determine how narrowly it will be applied.”

Such guidance will hopefully be forthcoming in the ECJ’s pending Santen (C-673/18) referral, which is set to address the question of Article 3(d)’s interpretation in the light of Neurim head on. However, this referral was only made in late 2018, so we may have to wait another two years for a decision to be handed down in that case.

A narrow reading will not be unpopular across the board. “Neurim was another misstep by the court, unfortunately”, Shillingford comments. “I can understand the rationale of wanting to provide some reward for a first MA in human therapeutics. But the way the decision was framed was not restricted to that. It was potentially much broader. The memorandum is really very clear in itself though. SPCs were intended to be granted in respect of active substances in the strict sense. I think in the Abraxis decision, the court has taken a step in the right direction; and it might well be that Neurim is chipped away down to the adaptation of veterinary products for human use. Personally, I hope that the court carries on restricting the scope of Neurim.”

Bad news for medical device innovators

The ECJ was entirely clear in its October 2018 decision pertaining to the SPC eligibility of Boston Scientific’s restenosis reduction product Taxus – a device-drug combination product that was approved under the EU Medical Devices Directive, 93/42/EEC.

Article 2 of the EU SPC Regulation 469/2009 specifies that products must be authorised under the procedures set out in EU Directive 2001/83/EC, relating to medicinal products in human use, in order to qualify for an SPC. After its application for an SPC turned down on Article 2 grounds by the German Patent Office, Boston Scientific appealed to the German Federal Patents Court, where it argued that the approval process undergone by Taxus should be regarded as equivalent to that in the Medicinal Products Directive for the purposes of SPC eligibility. Although approved as a medical device, Taxus incorporates a medicinal substance, paclitaxel, and therefore underwent extensive safety, quality and utility tests, similar to those required by the Medicinal Products Directive.

The German Federal Patents Court expressed agreement with Boston Scientific’s interpretation of Article 2, but referred the case to the ECJ because of the inconsistent way that the article has been interpreted by national courts across the European Union. While German courts have been liberal in their approach, granting an SPC for TheraSphere to BTG Interventional Medicine, the UK Intellectual Property Office has taken a strict line, rejecting SPC applications for combination products such as Cerus’ Intercept and the Leibniz Institute for New Materials’ NanoTherm.

The ECJ ruled against Boston Scientific, finding that in accordance with the wording of the article only products approved by procedures laid down in the Medicinal Product Directive qualify for SPCs. The terms ‘medicinal product’ and ‘medical device’, it stated, “are mutually exclusive in such a way that a product that falls within the definition of ‘medicinal product’ within the meaning of Directive 2001/83 may not be classified as a medical device within the meaning of Directive 93/42”. The court elaborated that the Medical Devices Directive states that competent authorities should decide whether a product’s “principal mode of action” is that of a device or of a medicinal product.

Unfairness towards medical device innovators?

The Boston Scientific decision leaves little room for confusion about the law, unlike some of the ECJ’s other recent rulings. However, despite being clear, the decision is a blow for medical device innovators, many of which have sought SPCs in recent years for expensively developed drug-device combination products – and which face a harsher regulatory burden as the result of the new EU Medical Devices Directive (2017/745).

The strict interpretation of Article 2 also seems to go somewhat against the purpose of the SPC regulation: to compensate healthcare innovators for time-consuming regulatory approval processes that eat into a patent’s term – something that applies to combination drug-device product invention. The United States, in contrast, provides patent extensions for medical devices. As such, Boston Scientific may well fuel legislative debate about potential reforms to the SPC regulation or the introduction of a new medical device IP extension right.

In the meantime, it has significant strategic implications for drug-device combination innovators. The distinction between products whose “principal mode of action” is that of a device, and those whose is that of a drug is often far from clear. The ECJ’s judgment in Laboratoires Lyocentre, C-109/12, even allows the same product to be categorised as a medical device in one member state and as a medicinal product in another. As such, inventors of combination devices should factor in the implications of Boston Scientific when considering which regulatory pathway to go down or even how to proceed with the development of their product.

Where do we stand now?

Compared to 12 months ago, life sciences companies have more clarity on specific SPC questions: the ECJ has ruled in no uncertain terms that drug-device combination products approved under the EU Medical Devices Directive and new formulations of existing drugs, are not SPC-eligible. But the nature of the patent protection required for a product to qualify for an SPC remains unclear; and recent decisions have also created new uncertainties (eg, around the eligibility of new therapeutic uses).

Other questions that confront innovators, such as whether an SPC can be acquired on the basis of a third-party’s marketing authorisation – a practice permitted by national offices across Europe – remain unaddressed by the ECJ. (However, the first ever referral on this question was recently made by Judge Arnold in Eli Lilly v Genentech).

“Insofar as it is possible to identify a particular direction of travel expressed in these judgments, it is generally to interpret the SPC regulation narrowly and thereby restrict the situations in which SPCs are available”, Damerell states.

Another common thread in the court’s recent decision-making seems to be “to answer the questions narrowly rather than to provide explanations that would provide greater clarity on how the SPC regulation should be interpreted more broadly”, he adds. So, while there are several pending referrals before the ECJ, it seems likely that clarity on certain questions – such as the interpretation of Article 3(a) – will at best be provided incrementally by the court.

Recent decisions remind industry innovators – if it were needed – of the crucial importance of factoring in SPC considerations at the earliest stages of patent strategy – and even regulatory strategy. As Reynolds and Cordery point out, in circumstances of uncertainty surrounding Article 3(a), it is important to acquire separate patents for a range of potential combination products early on, even if most will never come to market. Given the sharp distinction made between regulatory pathways in Boston Scientific, inventors of drug-device combination products need to consider from early in the R&D process whether their products could be approved under the Medicinal Products Directive in order to qualify for a highly valuable SPC.