The Unified Patent Court (UPC) has established a precedent-setting framework for assessing infringement of second medical use patents in a high-stakes dispute between pharmaceutical giants over cholesterol-lowering medications.
In a ruling dated April 10, 2025, the UPC's Düsseldorf Local Division dismissed an infringement action brought by Sanofi and Regeneron against Amgen, while simultaneously upholding the validity of the patent at issue. The case centered on European patent No. EP 3 536 712, owned by Regeneron with Sanofi as exclusive licensee, which covers the use of PCSK9 inhibitors to reduce lipoprotein(a) [Lp(a)] levels in patients.
The Pharmaceutical Context
The dispute involves two competing monoclonal antibody medications: Amgen's evolocumab (marketed as Repatha) and Sanofi/Regeneron's alirocumab (marketed as Praluent). Both drugs target the PCSK9 enzyme to lower low-density lipoprotein cholesterol (LDL-C) levels, particularly in patients who don't respond adequately to statins.
The patent in question relates specifically to using PCSK9 inhibitors for reducing serum Lp(a) levels—a distinct lipoprotein associated with cardiovascular risk. This represents a "second medical use" of these compounds, as their primary approved indication is for lowering LDL-C.
Sanofi and Regeneron alleged that Amgen infringed their patent because Repatha's Summary of Product Characteristics (SmPC) mentions clinical trial data showing effects on Lp(a) levels, which they claimed would induce physicians to prescribe the drug for this purpose. The financial stakes were considerable, with the infringement action valued at €20 million and Amgen's counterclaim for revocation at €25 million.
Landmark Legal Framework for Second Medical Use Patents
In its decision, the Düsseldorf Local Division acknowledged the absence of statutory provisions or established UPC case law regarding infringement of second medical use claims. The court proceeded to establish a two-stage test that will likely influence future cases throughout the UPC territory:
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Objective Element: The alleged infringer must offer or place the medicinal product on the market in such a way that it leads to, or may lead to, the claimed therapeutic use.
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Subjective Element: The alleged infringer must know, or should reasonably have known, of such use.
The court emphasized that assessment requires analysis of all relevant facts and circumstances, including:
- The extent or significance of the allegedly infringing use
- The relevant market context and customary practices
- Market share of the claimed use compared to other uses
- Actions taken by the alleged infringer to either encourage or prevent the patented use
The Court's Analysis
While upholding the validity of Sanofi and Regeneron's patent against Amgen's counterclaim for revocation, the court found no infringement had occurred. The judges determined that Sanofi and Regeneron failed to meet the first part of the two-stage test, as they could not demonstrate that Amgen's placement of Repatha on the market led, or might lead, to the claimed use of lowering Lp(a) levels.
The court noted several key factors in its decision:
- Repatha is not approved for lowering Lp(a) levels, but rather for lowering LDL-C and treating mixed hyperlipidemia
- The mere mention of clinical trial data on Lp(a) reduction in section 5.1 of Repatha's SmPC was deemed insufficient to induce physicians to prescribe it for this purpose
- Sanofi and Regeneron failed to provide convincing evidence that physicians were prescribing or would prescribe Repatha specifically to reduce Lp(a) levels
Expert testimony played a crucial role in the decision. While Sanofi and Regeneron's expert claimed that elevated Lp(a) levels are often considered when prescribing PCSK9 inhibitors primarily for LDL-C reduction, Amgen's experts testified that they and their colleagues did not aim to lower Lp(a) when prescribing PCSK9 inhibitors for LDL-C reduction, even in patients with elevated Lp(a).
Implications for Pharmaceutical Companies
This ruling has significant implications for pharmaceutical companies operating within the UPC territory. It suggests the UPC may take an approach to second medical use claims that shares similarities with some national courts but is developing its own distinct jurisprudence.
For patent holders, the decision underscores the importance of gathering robust evidence of actual or highly likely prescription practices for the patented use. For potential infringers, it highlights the value of taking proactive steps to prevent their products from being used in potentially infringing ways, beyond simply omitting patented indications from product labeling.
Legal experts note that while this decision provides valuable insights into how the UPC may handle second medical use infringement actions, it represents just one ruling from one local division. An appeal is considered likely, and guidance from the UPC's Court of Appeal would provide further clarity on this important area of patent law.
The case also demonstrates that the UPC is not simply adopting the jurisprudence of national courts but is developing its own approach to complex patent issues. Unlike German case law, which distinguishes between liability based on "manifest preparation" and liability without such preparation, the UPC has opted for a multi-factor analysis that, while inspired by national approaches, establishes its own framework for assessing infringement of second medical use claims.
As the UPC continues to develop its case law, pharmaceutical companies will need to carefully consider how their marketing and labeling practices might be interpreted under this emerging legal framework, particularly for products with potential off-label uses that might infringe second medical use patents.
