How UPC’s first ruling on second medical use infringement reflects German practice

While there has been national case law on the infringement of second medical use claims in Germany, the Unified Patent Court (UPC) only recently issued its first decision dealing with this topic.

The Düsseldorf Local Division delivered ruling UPC_CFI_505/2024 on May 13 2025, which concerned an infringement action and a counterclaim for revocation related to European patent No. EP 3 536 712 B1 (EP’712). The patent pertains to PCSK9 inhibitors for use in reducing lipoprotein(a) (Lp(a)) levels in patients with serum levels of Lp(a) of greater than 30 mg/dL who are at risk of developing cardiovascular or thrombotic occlusive disease.

While it remains to be seen whether the Düsseldorf Local Division’s decision will be upheld on appeal, it offers the first insights into the likely framework for assessing the infringement of second medical use claims before the UPC. This article compares and contrasts the well-established German standards that seem to have inspired the decision with those just beginning to take shape at the UPC.

For a long time, German case law required a ‘purposeful preparation’ (‘sinnfällige Herrichtung’) of the allegedly infringing medical product when asserting a second medical use claim. The purposeful preparation of a medical product presupposes that the medical product is prepared in such a way that use for the patented indication is clearly foreseeable.

This approach had a practical reason: the (directly) infringing commercial activity usually does not take place during the actual use of the medical product (for the patented indication) – e.g., by the physician or patient – but beforehand; i.e., when the medical product is offered on the market.

According to German courts, a purposeful preparation can occur by preparing the medical product prior to its distribution with the patented use specifically in mind; namely, in such a way that the protected therapeutic use can be foreseen. This can, for example, be realised by a certain formulation, dosage, packaging or repackaging, labelling, and/or summary of product characteristics (SmPC) of the medical product, provided that the suitability for use in accordance with the patent is sufficiently clear for the relevant recipient (see Düsseldorf Higher Regional Court, GRUR 2017, 1107, pages 39–40 – Östrogenblocker).

For prescription-only medical products, the specific indications in the SmPC are of crucial importance. In the absence of specific indications – e.g., in the SmPC – case law has for a long time denied a purposeful preparation and thus denied a direct patent infringement.

Due to a perceived insufficient protection of the patentee, there has been a rethinking in recent years as to whether it would be desirable to deviate from the concept of purposeful preparation. In a series of important decisions starting in 2017, the Düsseldorf Higher Regional Court has begun to redefine and concretise the existing liability criteria and to extend them to a ‘preparation-free liability’ (‘herrichtungsfreie Haftung’) in exceptional cases.

In its landmark decision Östrogenblocker, the Düsseldorf Higher Regional Court introduced new liability criteria. It established an additional basis for liability in scenarios lacking a purposeful preparation, focusing on a substantial patented use combined with the infringer’s awareness or negligent ignorance of such use, incorporating a subjective element. The court articulated these new criteria as follows (recital 84 of the decision):

• The product must be (objectively) suitable for the patented purpose.

• The distributor must take advantage of circumstances that, in a manner similar to an active purposeful preparation, make it highly likely that the product being offered or marketed is being, or will be, used for the specified therapeutic purpose. This requires a sufficient and not only occasional use of the medicament according to the patent, as well as the respective knowledge or at least disregard of such knowledge by the supplier acting in bad faith.

According to the Düsseldorf Higher Regional Court, a purposeful preparation may be unnecessary if external conditions, such as those typically found in cross-label use, inherently lead to the patented therapeutic use of the product. While these criteria were primarily developed for cross-label use, they are also applicable to off-label use. Depending on the specifics of a case, it may be justified to hold the supplier liable of patent infringement if they knew, or should have known, about the patent-infringing prescription and substitution practices.

The Düsseldorf Higher Regional Court’s ruling in the Fulvestrant case (GRUR 2019, 279) elaborated on the new liability criteria initially set forth in the Östrogenblocker decision. The Düsseldorf Higher Regional Court addressed, for the first time, the precise requirements to establish liability without a purposeful preparation, emphasising the exceptional nature of such extended liability for distributors.

The Düsseldorf Higher Regional Court clarified that the mere usage of a product exclusively or predominantly for the patented purpose does not automatically establish liability. The critical factor is instead the infringer’s certain knowledge or disregard of knowledge that marketing the medical product will indeed lead to patent-infringing prescriptions and usage. The fundamental requirements for preparation-free liability, as applied by the court, are:

• The probability of a finding that the alleged infringer could not have been unaware of the infringing use would increase with the number of patent-infringing uses that have demonstrably occurred. Merely occasional cases of use could not generally give rise to preparation-free liability.

• A clearly single-digit percentage of use in accordance with the patent is likely insufficient to establish a prescribing practice relevant to liability.

• A further liability scenario could result from the particular outstanding benefits of the patented use compared with other therapeutic uses that would have to almost certainly require use of the medication in accordance with the patent.

• An injunction based on preparation-free liability could only be considered if a prescribing practice relevant to liability could still be established at the time of the oral hearing.

Since the decision in the Fulvestrant case, other German courts have adopted these principles (in particular, the Munich courts). The aforesaid criteria can thus be considered as the predominant German practice in dealing with second medical use claims and ‘skinny label’ products. It follows that if the patentee is able to prove the aforementioned requirements, second medical use claims can also be infringed if no purposeful preparation exists (i.e., if the patented indication is not explicitly mentioned in the SmPC).

Claim 1 of EP’712, owned by Regeneron Pharmaceuticals Inc. (Regeneron), reads 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 […]”.

The Amgen group (Amgen) markets the PCSK9 inhibitor Repatha (evolocumab) as pre-filled pens or mini-dosers in Belgium, France, Germany, Italy, and the Netherlands, where EP’712 is in force. Repatha is approved for lowering low-density lipoprotein cholesterol (LDL-C) and the treatment of mixed hyperlipoidaemia, a condition characterised by elevated levels of cholesterol and triglycerides in the blood. Sanofi Biotechnology SAS (Sanofi), as Regeneron’s exclusive licensee, and Regeneron alleged that Repatha infringes EP’712. Amgen counterclaimed for revocation of EP’712, but the Düsseldorf Local Division found the patent to be valid.

It was undisputed between the parties that Repatha can lower Lp(a), and that data demonstrating this effect is included in the product’s SmPC. It was also undisputed that the therapeutic use of PCSK9 inhibitory antibodies for lowering LDL-C levels was commonly known on the filing date of the patent in suit.

Sanofi and Regeneron argued that the Repatha SmPC is an express pointer to the patented use that encourages physicians to prescribe Repatha for lowering Lp(a) levels (see recitals 27–29). Furthermore, according to Sanofi and Regeneron, prescribing Repatha for an approved use – i.e., for lowering LDL-C and/or the treatment of mixed hyperlipoidaemia – to a patient who also exhibits high Lp(a) levels would fall within the scope of claim 1 (see recital 30) because claim 1 does not require that lowering Lp(a) is the only, or even the main, reason for prescribing Repatha (see recital 17).

Amgen countered that the data included in the SmPC shows only a modest, therapeutically irrelevant lowering of Lp(a) and that the inclusion of the data was required for regulatory reasons pertaining to patient safety (see recital 35). Amgen also argued that the treating physician derives no, let alone substantial, motivation from the data in the SmPC, given that lowering Lp(a) is not an approved indication (see recitals 42–43).

Amgen stressed that, in any case, the fact that claim 1 of EP’712 is a second medical use claim means that the prescription must aim specifically at this medical use (see recital 49); i.e., lowering Lp(a) cannot simply be a by-product of an approved use to infringe the claim. Otherwise, the claim would extend to known uses of PCSK9 inhibitors. For Amgen, off-label uses such as the use of Repatha specifically for lowering Lp(a), however, were, and are not, foreseeable to Amgen.

The Düsseldorf Local Division started its reasoning by providing some general guidance on the basic legal framework for claim interpretation before the UPC (while also noting that no statutory provisions regarding infringement of second medical use claims exist). The court outlined that medical use claims are an exception to the traditional categories of product and process claims, and noted that Article 54(4) and Article 54(5) of the European Patent Convention establish them as ‘purpose-limited product claims’. With respect to the patent in dispute, the court noted that the ‘purpose’ lies in the reduction of Lp(a) levels in a patient group as defined in the claim (see recital 87 and following).

In its claim interpretation, the Düsseldorf Local Division established that the second medical use format of claim 1 excluded from its scope situations in which the prescribing physician only intends to use Repatha for the approved uses but included in its scope situations where lowering Lp(a) is one of several intended uses (see recital 107; emphasis added): “The skilled person will interpret the claim as to exclude the use of PCSK9 antibodies solely for the known purpose of lowering LDL cholesterol. However, different from the Defendants’ position, the claim does not exclude the use of PCSK9 antibodies for other treatments, including the (known) lowering of LDL-C, as long as the PCSK9 inhibitor is also used to achieve the claimed therapeutic effect of reducing (elevated) Lp(a) levels.”

That is, the Düsseldorf Local Division did not accept that situations in which the lowering of Lp(a) in the defined patient group is an unintended by-product of a different, approved use of Repatha. The claimed second medical use must thus be intended by the physician when prescribing – whether alone or alongside other, approved uses – to fall within the scope of a second medical use claim.

The Düsseldorf Local Division then, for the first time, laid out the general principles applying to the infringement of second medical use claims before the UPC (see recital 182; emphasis added): “It is the opinion of the Court that, for a finding of infringement of a second medical use claim, the alleged infringer must offer or place the medical product on the market in such way that it leads or may lead to the claimed therapeutic use of which the alleged infringer knows or reasonably should have known that it does.”

For the case at hand, this means that there must be a prescription to lower Lp(a) levels, or at least circumstances showing that such a use may be expected to occur (objective element), and the infringer must know this, or reasonably should have known (subjective element).

The Düsseldorf Local Division then stressed that the requirements of the alleged infringer’s behaviour cannot be defined in an abstract manner but necessitate an analysis of all the relevant facts and circumstances of the case at hand (see recital 183). The Düsseldorf Local Division provides guidelines for such a balanced assessment at recital 183: “Starting from the construction of the patent claim in question, relevant facts may include

• 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,

• what actions the alleged infringer has taken to influence the respective market,

– either ‘positively’, de facto encouraging the patented use,

– or ‘negatively’ by taking measures to prevent the product from being used for patented use.”

The Düsseldorf Local Division, holding that an alleged infringing product’s SmPC can be important but is not the only decisive factor in the above assessment (see recital 184), found that Sanofi and Regeneron did not conclusively show that:

• Amgen offered Repatha for the off-label second medical use protected by EP’712; and

• Repatha being offered on the market could lead to the claimed second medical use at all.

First, the Düsseldorf Local Division held that Repatha’s SmPC does not report the observed moderate effect of lowering Lp(a) as clinically relevant and consistently presents Repatha as not being approved for lowering Lp(a) (see recital 191; emphasis added): “In the context of infringement of a second medical use claim it is irrelevant that reducing LDL-C may have the windfall effect to reduce an elevated Lp(a) value. As set out above the infringer is held accountable for placing the product on the market in a way that leads or may lead to the claimed use. This requires for example presenting information about the product in a certain way. In the case at hand, the Defendants do not emphasise in any way that the contested embodiment reduces Lp(a) (e.g. by labelling it as recommended for that use). The pharmacodynamic effects in Section 5.1 SmPC are of relevance (and even mandatory) e.g. if the physician has to take account certain side effects as the Defendants presented in this case for diabetes patients. It is the objective report of an outcome effect of a clinical study which is comparable to background information.”

Second, the Düsseldorf Local Division held that an expert opinion outlining an expectation of off-label prescription covered by the second medical use claims of EP’712 do not show actual off-label use, and credible arguments describing hurdles to off-label use were brought forth by Amgen (see recitals 197 and 198). It appears that evidence of actual prescription for the claimed off-label use or a substantial likelihood that such actual prescription will occur (recital 193) would have to be presented to demonstrate that Repatha being offered on the market could lead to the claimed second medical use at all.

Finally, the court also concluded that the claimants did not show that the defendants were aware of an infringing use or that they should have been aware of this. Hence, the subjective element was also denied by the court (recital 199).

Comparing the two legal frameworks

National German practice (preparation-free liability)	UPC practice
Second medical use claim = purpose-limited product claim	Second medical use claim = purpose-limited product claim
Objective element: • The product must be objectively suitable for the patented purpose; and • There is an actual prescription practice for the patented indication.	Objective element: • The alleged infringer must offer or place the medical product on the market in such a way that it leads, or may lead, to the claimed therapeutic use.
Subjective element: • The alleged infringer knows, or could not have been unaware, of the infringing use, whereby the probability of this increases with the number of patent-infringing uses that have occurred; and • A further liability scenario could result from the particular outstanding benefits of the patented use compared with other therapeutic uses that would almost certainly have required use of the medical product in accordance with the patent.	Subjective element: • The alleged infringer knows, or reasonably should have known, that the medical product leads, or may lead, to the patented therapeutic use.
Case-by-case analysis	Case-by-case analysis

The behaviour of the alleged infringer must therefore be assessed in a case-by-case manner, taking into account:

• 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 with other uses; and

• What actions the alleged infringer has taken to influence the respective market.

SmPCs can matter in this analysis, and evidence of an actual prescription practice, or of a substantial likelihood that such actual prescription practice will occur for the alleged infringed second medical use, appears to be required.

The decision of the Düsseldorf Local Division marks a pivotal moment in the landscape of European patent law. As the UPC continues to establish its role in harmonising patent litigation across its member states, the ruling offers highly relevant insights into the court’s interpretation and handling of second medical use claims in the context of skinny label products.

When comparing the German practice with the new approach of the Düsseldorf Local Division, several similarities are immediately evident. Nevertheless, the first instance of the UPC has found its own standard and identified numerous criteria that provide valuable guidance for the assessment of second medical use claims and their enforceability before the UPC.