In brief
- The UK Patents Court has upheld the validity of Takeda's supplementary protection certificate (SPC) for lisdexamfetamine (Elvanse), dismissing both invalidity claims brought by Aristo Pharma and Stada.
- The case turned on whether the prodrug LDX, or its active metabolite DEX (which had an earlier marketing authorisation), is the "active ingredient" ("the product") within the meaning of Art. 1(b) of the SPC Regulation.
- The court confirmed that a prodrug can be its own active ingredient and endorsed a simplified approach to identifying it from the marketing authorisation, aligning with the Advocate-General's recent Opinion in the pending Halozyme referral before the European Court of Justice (CJEU).
Background
In Aristo Pharma GmbH v Takeda Pharmaceuticals and the parallel action by Stada Arzneimittal AG, the Patents Court (HHJ Hacon) has upheld the validity of Takeda's supplementary protection certificate (SPC) for lisdexamfetamine ("LDX"), marketed as Elvanse for the treatment of ADHD.
LDX is a prodrug: lysine covalently bound to dexamfetamine ("DEX"), which is pharmacologically inactive until metabolised in the body to release DEX, the active moiety (the specific molecule directly responsible for physiological or pharmacological action of the drug). Because DEX already had an earlier marketing authorisation, the claimants argued that DEX, not LDX, was the true "active ingredient" of Elvanse for SPC purposes under Article 1(b) of the SPC Regulation - meaning the SPC would therefore be invalid under Article 3(d) of the Regulation for relying on an authorisation that was not the first for that product.
Patents Court decision
The court dismissed both claims and held the SPC was validly granted. It found that LDX itself has a metabolic action of its own, distinct from DEX, by reference to its materially different pharmacokinetic profile: LDX permits once-daily dosing, compared with two or three daily doses for DEX, and unchallenged regulatory evidence showed this was a clinically significant advantage sufficient to meet established criteria for a new active substance. The court also considered the marketing authorisation and Public Assessment Report (PAR) as a whole, concluding that a reasonable reader would understand LDX, not DEX, to be the active ingredient, notwithstanding references in the authorisation to LDX being "pharmacologically inactive" in-vitro, a description the court treated as referring only to in-vitro inactivity, not to LDX's status as an active ingredient under the SPC Regulation.
Significantly, the court confirmed that the test for an "active substance" under the Medicinal Products Directive and for an "active ingredient" under the SPC Regulation are one and the same, applying the test adopted in the CJEU's decision in Forsgren (a substance qualifies if it produces a pharmacological, immunological or metabolic action of its own) in the same way to both.
The judge found support for this simplified approach to identifying the active ingredient, looking primarily to the marketing authorisation itself, rather than requiring a fresh substantive scientific reassessment. The judge relied on Advocate-General Emiliou's recent Opinion in the pending Halozyme reference before the CJEU (from the Supreme Administrative Court of Czechia), which proposes that the active ingredient should be determined by its classification in the marketing authorisation.
Key takeaways
Several practical points emerge for prospective SPC strategy. A prodrug can qualify as its own "active ingredient" distinct from its active metabolite, provided a materially different pharmacokinetic profile confers a pharmacological, immunological or metabolic action of its own; in-vitro inactivity is not fatal where conversion produces a clinically significant benefit, such as once-daily versus multiple-daily dosing.
Legal teams should work closely with their regulatory counterparts to ensure the "product" is holistically and clearly identified, since the choice of product must be supported by the wording of the Summary of Product Characteristics itself. Reliance on the PAR, the basic patent, or external scientific papers to establish the active ingredient could be rejected, an issue currently before the CJEU in the pending Halozyme referral.
It is also worth noting that the case was tried under the Shorter Trial Scheme without cross-examination, and the judge found the expert evidence largely unhelpful to the ultimate legal question.
Finally, businesses should plan for continued jurisdictional divergence on this issue: while the UK court has upheld Takeda's SPC (subject to any appeal), Germany's Federal Patent Court invalidated the equivalent German SPC in 2024 (currently under appeal), whereas courts in Denmark, Sweden and Switzerland have all found in Takeda's favour.