Tempus fugit. It’s hard to believe that the UPC opened for business over two years ago and, after a relatively slow start, is now flourishing. It would be fair to say that, with certain notable exceptions, life sciences companies have not engaged with the UPC as enthusiastically as other sectors to date. Therefore certain issues which are perennial hot patent topics to that industry have received comparatively little attention in the UPC. However, the recent decision from the Düsseldorf Local Division has tackled one of the thornier issues which has been active in many national courts for several years, namely the infringement of second medical use patents.
For the authors, the key passage from the ruling is paragraph 184 which states:
“The manufacturing of the product and in particular the package insert and the SmPC of a pharmaceutical product can be important. However, they are not always the only decisive factor to be taken into account in assessing whether the alleged infringer is in the end liable for patent infringement. Additionally, the extent to which the alleged infringer knows or should have known that the product will be used for the claimed purpose is of relevance.”
Background
This case is part of the ongoing worldwide dispute relating to proprotein convertase subtilisin/kexin type 9 (“PCSK9”) inhibitors. Sanofi and Regeneron market alirocumab (the active ingredient in Praulent®) whilst Amgen sells the competing product evolocumab (the active ingredient in Repatha®). Since 2014, the parties have been involved in multiple national litigations, including antitrust proceedings in the US for the unlawful bundling of products resulting in a $407 million award of damages to Regeneron on 15 May 2025. This dispute was one of the few life sciences cases which escalated to the UPC very early on in the Court’s infancy, and led to one of the first revocation decisions for Amgen’s patent EP 3 666 797, the appeal for which is scheduled to be heard before the Court of Appeal on 12 August 2025.
In these proceedings, Regeneron was the proprietor, and Sanofi the exclusive licensee, of EP 3 536 712 (“EP 712”) which relates to the use of PCSK9 inhibitors to reduce elevated lipoprotein(a) (Lp(a)) levels in a defined patient group. PCSK9 inhibitors were known to lower low-density lipoprotein (LDL-C) and administered to patients with high cholesterol. EP 712 is a divisional patent, the parent currently being opted out, and the subject of German national proceedings. There are also ongoing EPO opposition proceedings, although the EPO’s preliminary opinion is that EP 712 is valid. Regeneron and Sanofi jointly sued Amgen claiming that Repatha® infringed EP 712. Amgen counterclaimed, arguing EP 712 was invalid and should be revoked.
Claim Construction
Claim 1 of EP 712 is as follows:
“A pharmaceutical composition comprising a PCSK9 inhibitor for use in reducing lipoprotein(a) (Lp(a)) levels in a patient who exhibits a serum Lp(a) level greater than 30 mg/dL and who is diagnosed with or identified as being at risk of developing a cardiovascular disease or disorder prior to or at the time of administration of the composition, or who is diagnosed with or identified as being at risk of developing a thrombotic occlusive disease or disorder prior to or at the time of administration of the composition, wherein the PCSK9 inhibitor is an antibody or antigen-binding fragment thereof that specifically binds PCSK9, wherein the patient is not on a therapeutic statin regimen at the time of administration of the composition.”
The Düsseldorf Local Division construed Claim 1 to mean that the use of PCSK9 inhibitors cannot be solely for the purposes of lowering LDL-C, which was the known use. However, it does not exclude the use of PCSK9 inhibitors to lower LDL-C and also achieve the claimed therapeutic effect of reducing elevated Lp(a) serum levels, the second medical use. It further interpreted the patient group to mean a group that objectively exhibited a serum Lp(a) level above 30 mg/dL. This meant that, without specifying when it is done or how or by whom, patient Lp(a) levels are measured at some point before treatment is started.
Validity
EP 712 was held to be valid. In relation to the novelty attacks, the court rejected the prior art that only disclosed the known prior uses, stressing that known prior use could not deprive a patent of novelty in respect of a claimed second medical use as this would be contrary to the legal fiction that applies to second medical use claims by virtue of Article 54(4) EPC.
Of the three documents relied on to support allegations of obviousness, only one, referred to as “Parhofer 1” was found to provide the skilled person with a motivation to consider PCSK9 inhibitors to lower Lp(a) levels. However, the Court considered that Parhofer 1 would not have given the skilled person a motivation to pursue such a course of action given the prevailing view within the common general knowledge. The Court underlined that context, and motivation, are crucial. In this regard, it seems that the parties’ evidence, given via expert witnesses, factual witnesses or documents, as to the prejudices or assumptions within a given field at the priority date of a patent, will often be highly influential.
Unusually for second medical use claims, the sufficiency objections were swiftly rejected by the Court. There were data in EP 712 that showed the therapeutic effect in the claimed patient population. Questions on how the UPC will handle post-filed data and plausibility therefore still remain open questions for the Court.
Infringement
As a starting point to its assessment, the Court commented that there are no statutory provisions regarding the infringement of second medical use patents, nor is the test harmonised within the UPC member states.
As the claim under consideration was an EPC 2000 claim, it was considered to be a purpose-limited product claim and, as such, it was up to the Claimants to prove that the use feature of the claim was fulfilled. This would be the case if the Defendant offered to place or placed the alleged infringing product on the market in such a way that it knew or ought reasonably to have known that it would be used for the claimed therapeutic purpose. In turn this required an holistic assessment of all the facts and circumstances.
Without wishing to confine itself unduly, the Court set out some potential factors of relevance when assessing infringement including: the extent or significance of the allegedly infringing use; the relevant market including what is customary on that market; the market share of the claimed use compared to other uses; and what actions the alleged infringer had taken to influence the respective market, either ‘positively’ encouraging patented use, or ‘negatively’ by taking measure to prevent the product from being used for patented use.
After setting out the test, the Court then applied it to the facts in this case. At the centre of the dispute was the Claimants’ reliance on the Summary of Product Characteristics (SmPC) and the conclusions that physicians may draw from it to prove both the objective and subjective elements of infringement. Although Repatha® is not stated to be approved for lowering Lp(a) levels in Section 4.1 of its SmPC (therapeutic use), the Claimants sought to rely on Section 5.1 SmPC (pharmacodynamic (PD) properties). This section reported that “in clinical trials, Repatha reduced unbound…Lp(a)” and it was undisputed that in fact, Repatha® lowers the Lp(a) value by at least 25%.
The Court started from the assumption that a physician’s decision to prescribe Repatha® would be based on the approved therapeutic indication (i.e. the stated indication in Section 4.1). The information in Section 5.1 on PD properties in and of itself did not show that Lp(a) levels were addressed independently, let alone that the alleged infringing product was being prescribed to reduce Lp(a) levels. However, for infringement of second medical use claims, it was irrelevant that reducing LDL-C inevitably led to the reduction of Lp(a). The alleged infringer must be responsible for placing the product on the market in a way that leads to the claimed use. Although the SmPC is important in considering the use of a pharmaceutical product, it is not decisive. As there was not sufficient evidence that Amgen had been encouraging physicians to use the contested embodiment to lower Lp(a) levels, neither the objective or subjective elements were satisfied.
The argument that Section 5.1 of the SmPC induces a physician to prescribe the product for lowering Lp(a) (and LDL-C) necessitated that the physician would be prescribing the alleged infringing medicine “off-label” (i.e. for a use not stated on the therapeutic indications section of the SmPC). No evidence was submitted demonstrating off-label use, or that there was a likelihood of this happening. The parties submitted competing expert declarations, and Amgen further provided evidence that the benefit of lowering Lp(a) serum levels was still a matter of debate, and there are regulatory hurdles for the prescriber for off-label use in particular the special need for medical justification and the risk of a refusal of reimbursement by health insurance funds. Although the Court rejected the late filed briefs of the parties which included four letters from patients submitted by the Claimants, it did comment that, in addition to the four letters not showing that any prescription had been made with the direct purpose of lowering Lp(a) levels, it would not have been a sufficient number to establish the likelihood of prescription for the claimed use.
Conclusion
Although only a first instance decision which may well be appealed, this judgment offers the pharmaceutical industry important guidance on how the UPC will approach second medical use claims. Notably, although the label for a given medicine is important, it is not to be regarded as decisive. If the holder of a second medical use patent can demonstrate that the alleged infringer’s product is being used, or is likely to be used, for the patented indication, it may succeed in establishing infringement, even where the patented indication has been carved out from the medicine’s label.
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