June 2025 The jurisprudence of the United Patent Court (UPC) is relatively new. Thus, a question of ongoing interest is to what extent the UPC will follow the jurisprudence of the European Patent Office (EPO) and/or one of the UPC member states was not fully known.
The Dusseldorf local division of the UPC has now considered a case in which the infringement of second medical use claims was assessed along with a counterclaim for revocation of those second medical use claims. The result might be considered a framework for assessing infringement of second medical use claims, and this might be used by or persuasive to other UPC courts.
The jurisprudence of the United Patent Court (UPC) is relatively new. Thus, a question of ongoing interest is to what extent the UPC will follow the jurisprudence of the European Patent Office (EPO) and/or one of the UPC member states was not fully known.
The Dusseldorf local division of the UPC has now considered a case in which the infringement of second medical use claims was assessed along with a counter claim for revocation of those second medical use claims. The result might be considered a framework for assessing infringement of second medical use claims, and this might be used by or persuasive to other UPC courts.
This case is part of the international proceedings between Sanofi and Regeneron in relation to the injected monoclonal antibody Repatha (“evolocumab”).
Repatha/evolocumab acts by targeting a protein called PCSK9 which binds to low density lipoprotein (LDL) receptors on the surface of liver cells. The binding of PCSK9 to LDL receptors degrades the LDL receptors and thus reduces the liver’s ability to clear low-density lipoprotein cholesterol (LDL-C) from the bloodstream. Thus, by inhibiting PCSK9, Repatha/evolocumab effectively increases the number of LDL-C receptors that are available, and this allows more LDL-C to be removed from the blood.
Repatha/evolocumab has been approved for use by the US Food and Drug Administration (FDA) and other authorities for, inter alia, reducing LDL-C in adults with primary hyperlipidaemia. However, in slight contrast, Regeneron’s European patent EP3536712 (“the patent”) claims antibody inhibitors against PCSK9 for use in reducing lipoprotein (a) [Lp(a)] in patients with or at risk of cardiovascular disease and elevated Lp(a). As noted above, this contrasts with the clinical indications for which Repatha (Amgen’s product) is authorised.
The results of this case were that the patent was found to be valid but not infringed.
In coming to this decision the Dusseldorf local division of the UPC considered and set out a framework for considering the validity and infringement of second medical use claims that might be persuasive across the UPC. How this relates to this particular case is reviewed below.
Validity
Second medical use claims are claims for known products being used for a novel treatment. Accordingly, while claim 1 of the patent is for a product, its scope is limited to the context of the claimed product being used for the therapeutic use defined in the claim. Accordingly, infringement can only be established if the claimed therapeutic “use” is proven.
Regarding the validity of the patent, the UPC confirmed that claims to new medical uses of known therapeutics, whether these are based on new clinical indications or specific patient subpopulations that might benefit from a known pharmaceutical, are patentable in line with the practice established by the EPO.
Accordingly, the UPC confirmed the validity of the patent and confirmed that its claims were both novel and inventive.
In this vein it was noted that PCSK9 inhibitors being used to reduce Lp(a) levels was not disclosed in the prior art. Furthermore, the UPC confirmed that if Repatha/evolocumab were to be used to reduce LDL-C levels and the reduction of Lp(a) was inherent to such use, this would still be irrelevant to the consideration of the novelty of the second medical use claims of the patent.
Furthermore, the UPC found that the skilled person would not have used a PCSK9 inhibitor to reduce Lp(a) levels because various technical reasons would have deterred the skilled person from pursuing this route. Hence, the claim was inventive.
Thus in terms of validity, the Dusseldorf local division of the UPC has endorsed the validity of second medical use claims and their basis in the technical effect of treatment of a previously unindicated clinical condition.
Infringement
Regarding infringement, the purpose-limited nature of second medical use claims means that infringement can only be demonstrated if the claimed therapeutic use recited in the claim is proved to have been infringed.
The UPC considers that such an analysis requires both objective and subjective elements. That is, to demonstrate infringement “the defendants at least should have known that offering or placing the medical product on the market leads or may lead to the claimed therapeutic use” (decision paragraph 185) and the alleged infringer must reasonably know that this is the case.
The result of this analysis is dependent on the particular facts of the case. In this case, Repatha/evolocumab was acknowledged as being a pharmaceutical product but of equal importance was the extent to which the alleged infringer is, or should be aware of the patented use.
The UPC considered that it was not likely that evolocumab would be prescribed for the use given in the patent. As noted above, the product had been approved for lowering LDL. It might be inferred from the summary of product characteristics and other literature associated with Repatha that its administration might lead to a reduction in Lp(a) levels by at least 25%, but this was considered important rather than decisive in this analysis (decision para. 184). The court therefore looked at hurdles for off-label use of pharmaceuticals (e.g. medical justification and the risk of non-reimbursement of the cost of such off-label drugs) and why this might deter prescribing Repatha/evolocumab for the claimed medical uses.
Thus this is a balanced approach to considering infringement but does place the burden on the patentee to demonstrate that evolocumab was being prescribed for the patented use. This is particularly the case for lowering Lp(a) cholesterol when lowering elevated levels of LDL might be considered to be a more important clinical indication for treatment.
Thus the court considered the evidence that evolocumab was being prescribed for lowering Lp(a) cholesterol and found that Sanofi had not presented sufficient evidence to make out this point. Thus it appears that the court does not consider that off-label use of a drug can be presumed. Even though a drug could be used for a particular clinical purpose it must be shown that the drug is being used for this purpose in clinical practice in order to demonstrate infringement of a second medical use claim.
Functional antibody claims
Cases around the world between Sanofi and Regeneron in relation to Repatha/evolocumab have hinged on a number of different features. One particular aspect of jurisprudence where there is divergence between the US and Europe (for example) is in the scope of claims allowed in relation to antibodies that are defined using functional language.
This UPC case, and other UPC cases, have shown that the UPC is more open to such claims, whereas such broad claims might be invalidated in the US as lacking enablement. Thus broader second medical use claims are obtainable for antibodies in Europe but the jurisprudence relating to enforcing such claims is evolving and the results appear to be highly dependent on the facts and the strength of the evidence being presented.
Conclusion
As noted above, this is the first significant ruling on second medical use claims by the UPC. It appears to present a balanced approach to the consideration of scope of second medical use claims but affirms that a finding of infringement requires demonstration that the claimed therapeutic use is actually occurring. It cannot be presumed that the validity of a patent demonstrating a clinical technical effect necessarily means that drug is being used to achieve that technical effect: convincing evidence is required.
It is possible that an appeal to the UPC Court of Appeal may be filed and this might produce a binding precedent. However, for now, the UPC has affirmed the strength of second medical use claims under European practice and the criteria for their being usefully enforced.
Full Citation:
Sanofi Biotechnologies SAS, Regeneron Pharmaceuticals Inc. v. Amgen Inc. , Amgen GmbH, Amgen Europe B.V., Amgen NV, Amgen S.R.L., Amgen B.V., Amgen S.A.S.LD; Düsseldorf 13 May 2025. Case no. UFC_CFI_505/204
The decision can be read here.
