UPC Local Division Düsseldorf — Sanofi & Regeneron v. Amgen (UPC_CFI_505/2024) — Framework for Infringement of Second Medical-Use Claims and Rejection of “Pleading Ignorance”

Background

Regeneron is the proprietor and Sanofi the exclusive licensee of European patent EP 3 536 712, claiming a pharmaceutical composition comprising a PCSK9 inhibitor for use in reducing lipoprotein(a) levels in patients with serum Lp(a) above 30 mg/dL who are at risk of cardiovascular or thrombotic occlusive disease, where the inhibitor is an antibody or antigen-binding fragment thereof and the patient is not on a therapeutic statin regimen at the time of administration. The claim is in second medical-use format under Art. 54(4)-(5) EPC.

Amgen markets a competing PCSK9-inhibitor antibody product. Sanofi and Regeneron sued Amgen and six European Amgen affiliates in the Düsseldorf Local Division of the UPC, alleging that Amgen’s product is offered and placed on the market in a manner that leads or may lead to its use for the patented Lp(a)-lowering indication. Amgen counterclaimed for revocation. EPO opposition proceedings on the same patent are pending in parallel; the EPO issued a preliminary opinion in August 2024 finding the patent valid.

The Court’s Holding

The Düsseldorf Local Division articulated five headnotes that materially shape UPC second-medical-use jurisprudence and procedure.

1. Definition of “second medical use.” A second medical-use claim under Art. 54(4)-(5) EPC covers a substance or composition used for any specific use not comprised in the state of the art. The new therapeutic use can be a new indication — e.g., a disease not yet treated by the claimed substance — or an indication for a new patient group.

2. Infringement framework. 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 a 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. The court declined to define the precise behavior required in an abstract manner; it requires an analysis of all relevant facts and circumstances of the patent claim in question and the alleged infringing conduct.

3. Notional novelty under Art. 54(5) EPC. To benefit from the notional novelty afforded to second medical-use claims by Art. 54(5) EPC, the claim must relate to a specific use in a method according to Art. 53(c) EPC (a method of treatment of the human or animal body by therapy). The sole reason such claims can be patented despite covering known substances is the novelty (and inventiveness) of the new use. The court signals that medical-use claims will be policed for whether the claimed use is genuinely a specific new method of treatment, not a generic re-labeling.

4. Inventive step and motivation. In assessing inventive step, the claim’s subject matter may be obvious if the skilled person would have been motivated to implement the claimed solution as the next step in solving the technical problem. A motivation may be absent or negated where the skilled person faces many uncertainties or expected difficulties. Where there is no motivation at all, or where motivation is negated, the subject matter involves an inventive step. This dovetails with the Court of Appeal’s same-year framework in Amgen v. Sanofi/Regeneron and Meril v. Edwards (both decided 25 November 2025).

5. Pleading ignorance is not a recognized form of defense. The court ruled that objections based on “pleading ignorance” (e.g., a non-specific defendant declaration that it has no knowledge of certain facts and so cannot meaningfully respond) are in principle disregarded. The UPC Rules of Procedure do not acknowledge this type of pleading. A defendant must engage substantively with the claimant’s factual allegations; non-engagement risks treatment of contested facts as undisputed.

Key Takeaways

• UPC second medical-use infringement requires both an objective element (the product is offered or placed in a way that leads or may lead to the claimed use) and a subjective element (knowledge or constructive knowledge that the off-label use occurs). “Cross-label” enforcement is now a real prospect at the UPC where the originator can prove the generic or competitor knew the product would be used for the patented indication.
• Second medical-use claims need a genuinely new therapeutic indication or patient group. Re-labeling without a new use does not qualify under Art. 54(5) EPC.
• The Düsseldorf inventive-step approach — would the skilled person be motivated to take the next step? — is consistent with the Court of Appeal’s later “would not could” test, providing UPC-wide alignment.
• Defendants cannot use “pleading ignorance” as a shield. The UPC’s Rules of Procedure require substantive engagement with the claimant’s factual allegations. Counsel structuring defensive pleadings should not assume a generic non-knowledge defense will function as it would in some national jurisdictions.
• Parallel EPO opposition proceedings do not stay UPC infringement litigation; the Düsseldorf court proceeded with the merits despite a pending EPO opposition that had issued a preliminary validity opinion.

Why It Matters

Second medical-use claims have been some of the most commercially valuable but doctrinally uncertain claims in European pharmaceutical patent law. National courts in Germany, the UK, and the Netherlands have reached different conclusions on the scope of infringement, particularly on whether the originator must show actual cross-label use of the generic product. The Düsseldorf Local Division’s framework now provides a UPC-wide answer: the originator must show that the generic or competitor offered or placed the product on the market in a way that leads or may lead to the claimed use, with knowledge or constructive knowledge of that fact.

For PCSK9 inhibitors and other antibody therapeutics, this is a direct doctrinal hook for Lp(a)-lowering, lupus-erythematosus, IBD, and other emerging indications where originators are securing second medical-use protection while the underlying compound goes off-patent. Originators should preserve clear evidentiary trails of competitor knowledge of the off-label use; competitors should review labeling, marketing materials, and KOL engagements to ensure they do not generate evidence that they “reasonably should have known” the cross-label use was occurring.

The pleading-ignorance ruling has broader procedural significance. It reinforces that UPC litigation is more demanding on defendants than some national systems — the court will not accept generic non-knowledge defenses, and it expects substantive engagement with the claimant’s factual case. Defendants need to invest more heavily in factual development at the pleadings stage than they may have under prior national-court regimes.