Sufficiency at the priority date: A study protocol is not "the same" as a therapeutic effect invention (T0883/23)
Rose Hughes
Sufficiency at the priority date: A study protocol is not "the same" as a therapeutic effect invention (T0883/23)
Therapeutic inventions are generally not considered sufficiently disclosed absent supporting data. The recent decision in T 0883/23 found that this applies both at the priority date and the filing date of the patent. In this case, the priority document described the dose finding study protocol, whilst the patent claimed and provided data supporting the selection of a particular dosage regimen. The Board of Appeal found that the lack of data in the priority document meant that the "same invention" test for priority was not met and that the priority claim was therefore invalid.
Legal background: Priority and the 'same invention'
The right to claim priority for an invention in Europe is governed by Article 87(1) EPC, which states that a priority right can be claimed for "the same invention" as was disclosed in an earlier application. In G2/98, the EBA established the test for the "same invention" is whether "the skilled person can derive the subject-matter of the claim directly and unambiguously, using common general knowledge, from the previous application as a whole" (G2/98, headnote). A similar test is applied to assess whether an amendment adds matter to the application as filed (IPKat) and whether an invention is disclosed in the prior art for a novelty assessment (IPKat). If a priority claim falls down for claimed subject matter in a patent, any document published between the priority and filing dates becomes citable prior art for both novelty and inventive step.
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| Sufficient data? |
Case background
The patent in T 0883/23 was EP 3337478, owned by Ipsen Biopharm. It was opposed by Sandoz. The patent in question related to a combination therapy for treating metastatic pancreatic cancer in patients who had not received prior chemotherapy. The problem addressed by the invention was finding a treatment that was both effective and tolerable. The claim specified a four-drug cocktail (liposomal irinotecan, oxaliplatin, leucovorin, and 5-fluorouracil) at the specific doses, including 60 mg/m2 of liposomal irinotecan and 60 mg/m2 of oxaliplatin.
The Opposition Division maintained the patent, finding it was entitled to its priority date. The Opponents appealed.
A study protocol is not "the same" as a therapeutic effect
The first issue on appeal was whether the claimed 60/60 dose combination was entitled to priority. The key difference between the patent and the priority document concerned the disclosure of clinical trial results relating to the claimed invention. The priority document outlined the study protocol for a dose-finding study, listing the claimed 60 mg/m2 liposomal irinotecan / 60 mg/m2 oxaliplatin dose as just one of five conditional options. The priority document did not contain the study's results. The patent, by contrast, disclosed the results of this study in which it was demonstrated that the claimed dose was tolerable in human patients, whereas a higher dose also mentioned in the priority document (80 mg/m2 liposomal irinotecan) was not tolerable.
The Opponents argued that the priority document merely listed the claimed combo as one of five options in a proposed study, and didn't contain any results showing that the combination worked. The Patentee argued in response that the combo was described in both the priority document and the patent, and the later-filed results demonstrating the technical effect provided in the patent didn't make the combination "a different invention" for the purposes of claiming priority.
Applying the "direct and unambiguously derivable" test, the Board of Appeal found that the claimed subject-matter did not enjoy priority. The Board of Appeal reasoned that under the established case law, the tolerability of the dose was a "functional technical feature" of the claim and that the tolerability of a treatment is also "a prerequisite for the therapeutic efficacy" (citing T 2506/12, r. 2.8). Given that critical new information of the unique tolerability of the claimed dose was contained in the patent and was not disclosed in the priority document, the Board of Appeal concluded that the invention was "not directly and unambiguously derivable from" the priority document.
Sufficiency at the priority date
Interestingly, the Board of Appeal also observed that whilst according to G 2/98 a condition for priority is "the compliance with the requirement of 'the same invention' that the claimed subject-matter is directly and unambiguously derivable from the earlier application, the Enlarged Board did not conclude that the requirement of 'the same invention' is necessarily satisfied if this condition is fulfilled, irrespective of any technical information associated with the claimed subject-matter, which is only described in the subsequent patent application" (Headnote). On the contrary, for the Board of Appeal in this case, the case law also "confirms the need for sufficient disclosure of the claimed invention in the priority document" (r. 1.5). In other words, the sufficiency requirement must be satisfied at the priority date, and not just at the filing date (Case Law of the Boards of Appeal II.D.4.6). For therapeutic inventions, the Board of Appeal in this case found that this requires some evidence of a technical effect and not just a study protocol.
Inventive step of dose combos
With the loss of the priority claim, the question for the Board of Appeal became one of inventive step (Article 56 EPC). With respect to the priority documents themselves, these could not be cited against inventive step as they were not published before the filing date of the application. The closest prior art was instead identified as the description of various dose regimens for pancreatic cancer. These included the disclosure of a regimen comprising administration of a dose of 180 mg/m2 conventional irinotecan, 85 mg/m2 oxaliplatin, 400 mg/m2 leucovorin, and 400 mg/m2 5-fluorouracil. The subject-matter of claim 1 was thus found to differ from the prior art by the replacement of the 180 mg/m2 conventional non-liposomal irinotecan by 60 mg/m2 liposomal irinotecan and the reduction of the oxaliplatin dosage from 85 mg/m2 to 60 mg/m2.
In view of this prior art, the Board of Appeal found that there was a lack of any "reasonable expectation" of success for the claimed dose regimen. Importantly, the Board of Appeal noted that the preclinical data in mice on tolerability was shown to be "not predictive" of the human clinical setting. As such, the Board of Appeal reasoned, data for 2-drug or 3-drug combinations from the prior art could not be extrapolated to a 4-drug combination. In fact, the patent's own data showed that a dose of liposomal irinotecan known to be tolerable in a 3-drug combo became intolerable when oxaliplatin was added.
The Board of Appeal also found that the cited review articles which suggested swapping in liposomal irinotecan, were purely speculative in their call for "future clinical trials." (r. 3.3.6). For the Board of Appeal, this was an invitation to research, not a path to an obvious solution. The Board of Appeal distinguished the invention from "routine optimisation" cases, noting that the 4-drug combination was known for "problematic side effects" and the prior art gave "no information" on the combined toxicity (r. 3.3.8). The Board of Appeal thus found that the specific, effective, and tolerable dose window was inventive, despite the invalid priority claim.
Final thoughts
When considering how much data you need to support a therapeutic invention, the first thing to consider is to ensure you have sufficient evidence to satisfy the credibility/plausibility of the invention at the filing date. Here the credibility test is used to signify the evidence requirement for therapeutic invention in view of the higher level of underlying substantiated doubt that these types of inventions will work (see IPKat: Plausibility demystified). According to the long-established case law, armchair inventions that speculate about therapeutic effect are not considered sufficiently disclosed, irrespective of whether post-published evidence is provided (IPKat). However, clinical data is not always necessary, and in vitro mechanistic data may be considered sufficient (IPKat).
It is common for applications relating to therapeutic inventions claiming priority to be "topped up" with data that was not present in the priority application. However, the lesson from T 0883/23 is that adding data to the later application cannot rescue the priority date for an invention that was insufficiently disclosed in the priority application. According to T 0883/23 hypothetical examples and study protocols, whilst potentially providing basis for later claims, do not establish priority for an invention relating to a therapeutic effect. The Board of Appeal made clear distinction between the G2/98 test of whether a skilled person can derive the subject-matter of the claim directly and unambiguously from the priority document, and whether the invention is sufficiently disclosed in the priority application. For the Board of Appeal in T 0883/23, both of these requirements need to be met in order to satisfy the "same invention" test of Article 87(1) EPC for claiming priority for therapeutic inventions. G2/21 and its subsequent interpretations by Boards of Appeal, have similarly confirmed that post-published evidence cannot rescue a therapeutic invention that was insufficiently disclosed in the application as filed, irrespective of whether the effect was recited in the application as filed.
The decision in this case is of course also interesting for being another decision to find inventive step for a therapeutic effect based on dose or patient population selection, confirming that the selection of therapeutic doses is often far from straightforward (IPKat). The challenge of these types of invention is also underlined by recent cases in which post-published data actually undermined the sufficiency of the therapeutic invention by showing that the invention did not, in fact, work (IPKat and IPKat).
Further reading
- Second medical use dosage regimen claim successfully traverses both insufficiency and "obvious-to-try" attacks (T 0799/16) (Mar 2021)
- Make no bones about it: The "credibility test" has no place in the novelty assessment of second medical use claims (T 0558/20) (Aug 2023)
- The criteria for the novelty and inventive step of pharmaceutical selection inventions (T 1356/21) (Dec 2023)
- Inventive step of treating a subpopulation of patients in view of prior art reporting a positive phase 3 clinical trial (T 1437/21) (Mar 2024)
- Plausibility as a moving target: Phase III clinical trial results sink second medical use patent (T 0816/22) (Jan 2025)
- The plausibility of diagnostic inventions: No data, no patent (T 0589/22) (April 2025)
- Patentee's own post-published data undermines the credibility of their broad cat antibody patent (T 0709/23) (Oct 2025)