A small molecule pharmaceutical patent portfolio typically begins with an application directed to a new chemical entity (NCE). It’s the first ‘flag in the sand’ and getting this application right is crucial. In Europe, there are several landmines to navigate, as well as several opportunities to secure extra protection.
In our article, we set out five strategic tips when handling NCE applications in Europe to help you navigate these early stages and maximise protection.
1. Data and plausibility
The need for experimental data has been a long-debated topic in European case law. Until recently, there was a generally-accepted principal that the attainment of technical effects (e.g. therapeutic effects promised by an NCE) must be rendered ‘plausible’ by an application disclosure as-filed.
The EPO changed this in 2023 with their decision in G2/21, which dispensed with the plausibility requirement (at least in the context of the assessment of inventive step). G2/21 instead reasoned that a technical effect can be relied upon if it is “encompassed by the technical teaching” and “embodied by the same originally disclosed invention”. EPO cases subsequent to G2/21 (see our previous article here for a digest of recent decisions) seem to be applying a low threshold for these criteria and several EPO decisions have indicated that bare assertions of therapeutic activity might be enough (e.g. with a mere statement that a given NCE is therapeutically active, even without data or any technical rationale supporting the statement).
However, law around Europe is not harmonised in this regard. For example, as confirmed in July 2025 by the UK Court of Appeal in Generics (UK) Ltd. & Ors v AstraZeneca AB [2025] (see our article here), an application as-filed must contain experimental data and/or technical rationale to support that a technical effect can be achieved with the claimed subject matter (at least in the UK).
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Practice point 1: Whilst the seemingly more-relaxed EPO approach might suggest that less data is needed, we recommend adopting a cautious approach, being mindful of the stricter standards adopted by courts around Europe (e.g. in the UK). Your application as-filed should provide sufficient data, technical rationale or other evidence (i.e. something beyond a mere assertion) to make it plausible that any key technical effects you intend to rely upon (e.g. therapeutic effects) are provided by the claimed subject matter.
2. EPO added matter and fallback positions
You will most likely use a genus claim (Markush formula) in your initial NCE application to define the scope of protection. However, Markush formulae typically require amendment during prosecution to narrow them in order to navigate around objections and prior art. Generally, the EPO will allow an amendment to restrict a single selected genus moiety; however, multiple combined moiety restrictions are often required during prosecution, and this routinely elicits objections from the EPO due to their typically strict approach to added matter.
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Practice point 2: Give yourself maximum room to manoeuvre by providing basis not just for single moiety restrictions, but also for as many preferred combinations of substituents as you can, at the drafting stage. A particularly useful way of doing this is to include multiple sub-generic formulae (of your Markush formulae) directed to these preferred combinations.
3. Extra term for new lead NCEs: ‘novelty only’ prior art (Article 54(3) EPC)
If you identify a new lead after filing your initial NCE application, don’t forget to consider filing a new application directed to this lead before your initial NCE application publishes. If this can be done, then in Europe your initial NCE application will be citable against the later case for novelty only (not also inventive step, Article 54(3) EPC), while the filing date of your later case means that you’ll secure extra term for your new lead.
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Practice point 3: Keep track of the publication date of your initial NCE application and aim to file any follow-up applications before this date to secure extra term for your new leads. Obtaining grant of a claim directed to specific compounds not disclosed in your earlier filing should be permissible with this approach, and you might be able to obtain a narrow genus as well.
4. Selection inventions
Even if your initial NCE application has published, you can still potentially secure protection for your new lead in the form of a so-called ‘selection invention’ directed to a novel sub-genus of the Markush formula, as compared to your initial NCE application.
A European ‘selection invention’ arises from the selection of a specific sub-genus of compounds which is not directly and unambiguously disclosed in the prior art (e.g. your initial NCE application). At the EPO, your initial NCE application disclosing a Markush formula is not regarded as taking away the novelty of such a sub-genus as long as it is accepted that the skilled person would not have “seriously contemplated” working in the selected areas of the sub-genus overlapping with the broader genus in the prior art. This often occurs if there’s a novel structural motif in your later filing which is not contemplated in the earlier filing, or if there is no pointer to the sub-genus in your initial NCE application.
Your sub-genus will also need to be inventive over your initial NCE application. Specifically, you will need to be able to demonstrate that your sub-genus possesses an unexpected technical effect as compared with the broader genus in your earlier filing (and ideally you will have the data to back this up).
5. The UPC and divisionals
The European patent landscape has changed significantly since the launch of the Unified Patent Court (UPC) in June 2023. The new system provides patentees with an efficient and simplified way of enforcing patents, offering pan-European remedies across multiple participating member states simultaneously. However, this does of course bring the risk of central revocation of a patent across all UPC states in a single action.
Despite predictions of initial hesitance in the pharmaceutical industry of the new UPC system (e.g. that the untested nature of the new court would be too risky for high-value assets), current trends would suggest otherwise (see our recent article here). Notably, the availability of pan-European remedies, and the preliminary injunction in particular, is proving to be a powerful tool in the pharmaceutical patent toolkit. It’s clear that the UPC should be seriously considered in any European pharma patent strategy.
Nonetheless, the risks of central revocation remain. However, there are ways of riding both horses and navigating the pros-and-cons of the UPC through a creative use of your divisional application strategy. Here, you can keep a broad-scope-of-protection ‘parent’ application opted out of the UPC to sidestep the risk of central revocation at the UPC. In parallel, you can keep a narrower-scope-of-protection divisional application (e.g. directed to your lead compound only) opted in to the UPC to give an enforceable right that’s likely less susceptible to central revocation (in view of the narrower breadth).
EPO double patenting rules are very narrow: essentially, as long as there is some difference in scope between each & every claim of your parent and each & every claim of your divisional, you will avoid an objection. This lends itself well to obtaining multiple patents protecting a lead compound.
Overall, navigating patent protection for a brand new compound can be a daunting and potentially complex process with many factors to consider. Adopting a strategic and forward-thinking approach at these early stages can help set you up with a strong foundation for building a robust and valuable pharmaceutical patent portfolio.
If you have any further questions relating to NCE applications, please get in touch with James Snaith, or your usual Kilburn & Strode advisor.