Originally posted on IPKat.
Clinical inventions are highly valuable in the pharma industry. Whilst the composition of matter patent for a drug will often define loss of exclusivity (LoE), patents that capture clinical-stage innovation can provide substantial value by bolstering protection beyond composition of matter expiry, and in some cases may even extend LoE (Evolve Insights). The huge resource that pharma companies need to devote to the clinical stage of drug development is a testament to the fact that navigating a therapeutic candidate through clinical trials is far from straightforward. There is consequently a correspondingly large amount of clinical-stage innovation that may be captured in patent filings. However, given the substantial value that patents for clinical inventions can provide, it is not surprising that these patents are frequently challenged, leading to a substantial amount of case law from the Boards of Appeal.
Clinical trial disclosures and second medical use
T 0136/24: Clinical trial protocols as prior art
A common issue for second medical use patents is the status of clinical trial protocols and summaries as prior art (Evolve Insights). This was the key issue in T 0136/24, involving a Sanofi patent and various generic Opponents. The patent in question related to the use of the taxane cabazitaxel in combination with prednisone for treating metastatic castration-resistant prostate cancer (mCRPC) in patients previously treated with a docetaxel-based regimen.
The Opponents argued that the patent lacked novelty and inventive step in view of documents disclosing the protocol for the Phase III TROPIC study. The key question for the Board of Appeal was whether the mere announcement of the study and its design made the successful therapeutic outcome obvious. The Board of Appeal noted that the prior art disclosed the study protocol but did not reveal any data resulting from this study.
The Board of Appeal was not convinced by the Opponents’ arguments that the initiation of the Phase III trial implied a reasonable expectation of success. For the Board of Appeal, determining whether an expectation of success exists requires a consideration of the specific facts and evidence, rather than a presumption based on the clinical phase. In the case in question, given the lack of effective treatments for this patient group at the time, the Board of Appeal found that proceeding with the study might have been based on “mere hope” rather than a reasonable expectation. Consequently, the appeal was dismissed, and the patent was maintained.
The outcome in T 0136/24 is thus yet further confirmation that, at least in Europe, the mere announcement of a clinical trial does not render obvious a second medical use invention based on data from the trial.
T 0883/23: Priority entitlement requires disclosure of technical effect
From a practical perspective, one of the most important decisions relating to the relationship between clinical trial protocols and second medical use inventions was T 0883/23 (Evolve Insights). This case demonstrated that filing early based on protocols can carry significant risks regarding priority. The patent in this case related to a combination therapy for pancreatic cancer. The priority document contained a study protocol listing the claimed dose as one of several options but did not provide any data. The European patent, filed later and claiming priority from the earlier filing, included data showing the claimed dose was tolerable while others were not.
Significantly, the Board of Appeal found that the priority claim was invalid because the “same invention” requirement was not met. The Board of Appeal reasoned that the tolerability of the dose was a functional technical feature. Because the priority document failed to disclose the technical effect (tolerability) which was central to the invention, the subject matter was found to be not directly and unambiguously derivable from the priority document. This decision underlines that sufficiency must be met at the priority date and that the EPO may not consider a protocol to be “the same” invention as a verified therapeutic effect.
T 0122/23: Protocols combined with earlier data can render success obvious
It is important always to remember that the EPO takes a fact-specific approach to second medical use inventions. In T 0122/23, the patent owned by Salix Pharmaceuticals claimed the use of rifaximin for decreasing the risk of hepatic encephalopathy breakthrough episodes. The closest prior art was identified as the protocol for a Phase III trial. Unlike in the Sanofi decision, in this case the Board of Appeal found that the skilled person did have a reasonable expectation of success in view of this protocol. In its reasoning, the Board of Appeal pointed to earlier open-label study data which, despite limitations, showed efficacy and tolerability. Despite arguments submitted by the Patentee regarding the placebo effect and lack of rigorous evidence in the prior art, the Board of Appeal concluded that the prior results provided enough basis to expect success in the Phase III trial and the patent was revoked.
T 0816/22: Post-published failure of Phase III trials
The dangers of relying on early clinical phase data were further highlighted in T 0816/22. The patent in this case claimed the use of a C1-esterase inhibitor for treating antibody-mediated rejection in transplant patients. While the application was found to render the effect plausible based on Phase II data, a subsequent Phase III trial failed to show any efficacy. The Board of Appeal held that this post-published evidence raised serious doubts about sufficiency that the Patentee could not dispel (Evolve Insights). This case was a reminder that, as confirmed by G 2/21, post-published evidence can be used to undermine as well as support credibility.
Dose and Combinations
Dose patents represent one of the most valuable forms of clinical IP. Unlike most formulations, the dose generally forms part of the label. Generics and biosimilars will therefore usually be required to use the same dose as the innovator. Dose patents which expire later than the composition of matter patent and regulatory exclusivity can therefore provide significant protection against generic and biosimilar market entry. However, this also means that dose patents are frequently challenged, often on the grounds that selection and optimization of the dose would have been obvious to a skilled person in view of prior art mentioning that a therapeutic agent is in clinical trials. The key decisions relating to dose inventions this year confirm the importance of clearly identifying a surprising technical effect associated with a dose invention that is able to counteract the narrative that finding a safe and effective dose of a known drug is a routine and obvious process. However, in this Kat’s view, this shouldn’t be that difficult, given the amount of resources pharma companies need to devote to dose selection. What is critical is capturing the considerable innovation that underlies a dose selection that happens behind the scenes and which is generally not fully elucidated in regulatory submissions.
T 0792/24: The inventive low dose
In T 0792/24, the invention related to the use of plinabulin in combination with docetaxel for reducing neutropenia. The identified closest prior art disclosed a study comparing 30 mg/m2 and 20 mg/m2 doses, but did not reveal the results for the lower dose. The Patentee provided data showing that the lower 20 mg/m2 dose was, surprisingly, at least as effective as the higher dose in reducing grade 3/4 neutropenia. The Board of Appeal accepted that the skilled person would generally expect a lower dose to be less effective. As such, the Board of Appeal considered the finding that the lower dose maintained efficacy whilst presumably offering a better safety profile was non-obvious and the patent was maintained in amended form, limited to the 20 mg/m2 dose.
T 1701/22: Commercial success vs obviousness
T 1701/22 concerned Novo Nordisk’s blockbuster weight-loss drug Wegovy (semaglutide) showed the limits of commercial success arguments compared to arguments based on technical effects. The patent claimed a specific dose and pH for treating obesity. Despite the drug being hailed as a “game changer” in the media, the Board of Appeal found the invention obvious. The prior art was found to have already taught the use of GLP-1 agonists for weight loss and to have suggested overlapping dosage ranges. The Board of Appeal noted that commercial success does not retroactively establish an inventive step if the technical solution was obvious at the filing date (Evolve Insights).
T 0295/22: Mode of administration as a medical use
Another interesting dose-related case this year was the decision in T 0295/22 (Amgen vs Teva), in which the Board of Appeal had to decide if a specific mode of administration (oral) could constitute a new medical use. Deviating from the EPO Guidelines for Examination, the Board of Appeal found that a mode of administration is a limiting feature. However, the patent was revoked because the move to oral administration was considered obvious-to-try given the strong motivation in the field to develop oral dosage forms (Evolve Insights).
Formulation and Polymorphs
T 0722/24: Solving multi-faceted formulation problems
The patent in T 0722/24 covered a solid dispersion of the prostate cancer drug enzalutamide (Xtandi) with the polymer HPMC-AS. The Opponents argued that formulating poorly soluble drugs as solid dispersions was routine. However, the Patentee successfully argued that the specific formulation solved a multi-faceted technical problem: providing convenient dosing, comparable bioavailability to liquid capsules, and “outstanding” physical stability. Remarkably, the Board of Appeal found that the stability effect was so significant that direct comparative data with the prior art was not even necessary.
The Board of Appeal noted that while the prior art suggested HPMC-AS was a useful polymer, the field of amorphous solid dispersions was still reliant on a “tedious trial-and-error approach”. Consequently, the skilled person would not have had a reasonable expectation of success in achieving the combination of properties exhibited by the claimed formulation. The appeals were therefore dismissed.
T 0542/23: Explicit pointers in prior art regarding formulations
The decision in T 0542/23 contrasts with T 0722/24, in which a formulation patent was revoked. The patent claimed an amorphous solid dispersion of the drug ARRY-380 (tucatinib). The Board of Appeal found the invention obvious in view of a prior art poster which explicitly disclosed that amorphous dispersions of the same drug and suggested that it may have improved dissolution and reduced pH variability. Because the prior art explicitly suggested the solution to the technical problem, the Board of Appeal found that it would have been obvious for a skilled person to have arrived at the invention.
T 0243/22: Non-routine salt selection
Similarly, in T 0243/22, Pfizer successfully defended a patent for a crystalline maleate salt of rucaparib. The Board of Appeal agreed that starting from a prior art listing pharmaceutically acceptable salts, finding a specific salt form suitable for solid dosage formulations required non-routine experimentation. The selection of the maleate salt was non-obvious because the prior art preferred phosphate salts, which turned out to be unsuitable.
The contrasting outcomes in T 0542/23 and T 0243/22 compared to T 0722/24 highlight the need for extremely careful drafting in the field of formulation development. It is not enough to merely describe the formulation (as is often seen in US originating drafts). In Europe it is necessary to make it clear what problem or problems the formulation developers had to solve, why this was a particular challenge, and include data demonstrating the surprising technical effect of the lead formulation.
Biomarker and Diagnostics
T 0589/22: Defining the patient population
In T 0589/22 (B.R.A.H.M.S) the patent claimed a method of risk assessment using procalcitonin levels in patients with a non-infectious disease who “did not exhibit any symptoms of a bacterial infection”. The Board of Appeal found the patent insufficient because the examples all involved patients with “shortness of breath”. The Board of Appeal construed shortness of breath as a symptom of bacterial infection (e.g., pneumonia). Consequently, the specific patient group defined in the claims (no symptoms) expressly excluded the only patients tested in the examples. With the supporting data falling outside the claim scope, the invention was insufficiently disclosed. Or put another way, at the EPO, for this type of therapeutic innovation, no data means no patent.
T 0684/23: Routine development of immunoassays
In T 0684/23 (IDEXX Laboratories), the patent at issue concerned an antibody for detecting symmetrical dimethylarginine (SDMA) to determine renal function. The prior art was found to already disclose SDMA as a marker but to use expensive HPLC methods. The Board of Appeal revoked the patent, finding that once the marker was known, developing an immunoassay using a specific antibody was an obvious solution to the problem of finding a cheaper detection method. The Board noted that immunoassays were well-known alternatives to HPLC.
Analysis
It is clear from the decisions this year that having meaningful and relevant data to support your clinical invention remains of paramount importance. While G 2/21 confirmed the admissibility of post-published evidence, decisions like T 0883/23 and T 0816/22 confirm that G 2/21 does not help you if the application as filed (or the priority document) does not provide a credible technical disclosure of a therapeutic invention. As confirmed in the recent Board of Appeal decision to interpret G 1/23, non-enabling speculation is not prior art in the same way as a non-reproducible commercial product (T 1044/23).
However, the need for supporting data to support clinical-stage inventions leaves innovators with a difficult decision when working out when is the best time to file the patent application for such inventions. Filing the application before clinical data is available may render the invention insufficiently disclosed. However, filing after the clinical data has been obtained means that all the required regulatory disclosures relating to the clinical trial, such as the CT.gov summary, may become citable prior art against the application.
The decisions this year also confirm that whilst the EPO is relatively permissible regarding post-published evidence to support an invention, this can be a double-edged sword. As seen in T 0816/22, submitting data to support an inventive step or sufficiency argument can backfire spectacularly if it reveals that the invention as originally conceived does not actually work as broadly as claimed. We saw a similar trend in the 2025 antibody case law review (IPKat). Patentees must thus be extremely cautious about the data they introduce into proceedings.
Finally, for formulation and dosage inventions, the obvious-to-try hurdle remains high in Europe, but is not insurmountable. T 0722/24 and T 0792/24 demonstrated that identifying a dose or a formulation with critical technical properties can secure protection, provided that the prior art depicts a landscape of complexity and trial-and-error rather than a clear path to success. Conversely, as T 0542/23 and T 0684/23 showed, if an opponent can point to prior art showing that the solution and/or the development of a new dose or formulation was routine, the patent may well be in trouble.
So how may this minefield of issues be navigated? As with all IP strategy in the biotech and pharma field, the best approach is to ensure that any patent filing truly captures the considerable technical problem-solving underlying the vast majority of clinical stage inventions. Running successful clinical programs is not easy, but all the problems that had to be overcome in designing the drug product and protocol may well be forgotten by the time a patent is challenged, potentially 10 or more years later. Regulatory documents are also unlikely to fully elucidate all of the considerable challenges that were overcome in order to arrive at the clinical protocol. It is therefore critical that the underlying innovation behind clinical trial design and product development is captured in the patent application if the patent is to be successfully defended.
