The difference between the credibility and the unambiguous disclosure of a therapeutic effect (T 0209/22)

The recent Board of Appeal case T 0209/22 is yet another decision demonstrating the relatively permissive approach in Europe to medical use inventions. The patent related to the medical use of a combination of known drugs. The claim was supported by data described in the application from a phase I clinical trial in healthy volunteers. The patent did not include any patient data for the drug combination. The prior art included a summary of the phase I clinical trial protocol. The questions for the Board of Appeal were: 1) whether the phase I clinical trial and its summary impugned the novelty of the claimed combination,  2) whether the results of the same phase I clinical trial credibly established the claimed treatment effect in patients, and 3) whether there was a novelty/sufficiency squeeze. The Board of Appeal found that there are different evidence standards for novelty and sufficiency and that the claims were both novel and sufficiently disclosed, rejecting the opponents' squeeze argument. 

Legal Background

In Europe methods of treatment are excluded from patentability (Article 53(c) EPC). However, it is possible to patent a known substance or composition for use in a method of treatment (Article 54(5) EP). It is also possible to patent the second medical use of a known drug, e.g. in a different disease or at a different dose (Article 54(4) EP). Importantly, under European patent law, a claim to a substance or composition for use in a method of treatment is construed to include the treatment effect as a functional feature. As demonstrated in the present case, this approach to claim construction has important consequences for novelty and sufficiency. 

Novelty: A clinical trial in healthy volunteers is not a disclosure of a treatment effect

T 0209/22 related to the patent (EP2506844) directed to combination of known drugs for use in the treatment of asthma and COPD. The prior art cited against the patent was the summary of a phase I clinical trial protocol for the drug combination in healthy volunteers on CT.gov (NCT00976144). The clinical trial summary did not disclose the chemical structure of the drugs but did disclose their mechanisms of action. 

The opponents argued that the CT.gov summary anticipated the claimed subject-matter and that the clinical trials itself constituted prior public use of the invention. Whilst the CT.gov summary did not disclose the chemical structure of the drugs, the opponents argued that a skilled person could have derived this information by obtaining and analysing the study drugs. 

The phase I clinical trial described in the CT.gov summary was conducted in healthy volunteers and not patients. In the Board of Appeal's view, neither the trial itself nor the CT.gov summary anticipated the claimed therapeutic use. Critical to this assessment was the construction of the claims, according to established case law, to include the treatment effect in patients as a functional feature. A clinical trial in healthy volunteers could therefore not anticipate such a claim. Therefore, for the Board of Appeal, neither the CT.gov summary nor the clinical trial thus itself impacted the novelty of the claim. 

The Board of Appeal left open the hypothetical question of whether the clinical trial, or the CV.gov summary, would have anticipated the claim if the clinical trial had been conducted in the relevant patient population. However, according to established case law, a clinical trial and/or a clinical trial summary, does not anticipate a claim to a treatment effect assessed in the clinical trial (T 1437/21, IPKat). 

Sufficiency: Is phase I data in healthy volunteers sufficient to render a therapeutic effect in patients credible?

"Hope to succeed" or
"Reasonable expectation of success"?

The sufficiency bar for a medical use European patent is relatively low, at least compared to that required for regulatory approval. Preclinical and/or in vitro data may be sufficient to render a treatment claim credible (T 0966/18, IPKat), whereas a phase III clinical trial is usually needed for regulatory approval of a drug. Credibility for a patent is assessed in view of the data provided in the application as filed and common general knowledge. In the present case, the patent described data showing the treatment effect in patients of the claimed drugs administered as monotherapies. The patent also described data from the aforementioned phase I clinical trial in healthy volunteers, showing that a combination of the drugs was well tolerated. The patent did not provide data showing the efficacy of the combination of drugs in patients. 

For the Board of Appeal, the phase I data for the combo in healthy volunteers, together with the monotherapy data in patients, sufficiently established the credibility of the therapeutic effect of the drug combo in patients. Specifically, the Board of Appeal was not convinced that there was any substantiated doubt over the treatment effect of the combo in view of these data (IPKat) (r. 5.4.4, and 5.4.7). The claimed treatment effect was also supported by post-filed data.  

Novelty-sufficiency squeeze? 

The opponents argued that if the clinical trial summary was found not to impinge the novelty of the patent, then it followed that the results of the clinical trial described in the patent could not be regarded as enabling support of the claimed therapeutic use.

However, the Board noted that different standards should be applied to novelty and sufficiency (r. 5.6). Specifically, "to be novelty-destroying, a prior-art disclosure must meet the standard of direct and unambiguous disclosure of the claimed subject-matter". For the Board, the clinical trial was conducted in healthy volunteers, and therefore did not provide a direct and unambiguous disclosure of a treatment effect. 

In contrast to novelty, for sufficiency it is not always necessary for a claimed technical effect to be disclosed directly and unambiguously in the application as filed, e.g., in the form of results of a clinical phase III trial demonstrating efficacy in the claimed therapeutic use (r. 5.6.4). The test for sufficiency is instead whether it is credible that the treatment effect is attained in view of the disclosure of the patent as a whole and common general knowledge. The data in the patent from the phase I clinical trial in healthy volunteers did not constitute a direct and unambiguous disclosure of a therapeutic effect of the drug combo in patients. However, the Board had already established that the technical effect was credible (i.e. not in substantiated doubt) in view of the clinical trial data for the combo in healthy volunteers and the description in the patent of the clinical efficacy of the drugs as monotherapies in patients. The Board of Appeal therefore rejected the opponents' novelty-squeeze argument. 

Inventive step: "hope to succeed" should not be confused with a "reasonable expectation of success"

For the Board of Appeal, the question to be answered with regard to obviousness of the patent was whether, at the effective date, there was a direct route that would have led to the development of the claimed combination with a reasonable expectation of success. The claimed drugs were disclosed in separate prior art documents as potential treatment suggestions for COPD.  The opponent argued that these disclosures in combination would necessarily have given the skilled person a reasonable expectation of success for the efficacy of a combination of the drugs in patients, absent any prejudice or disincentive to proceed.

The Board of Appeal did not agree. Particularly, according to the Board: 

"while the basis for proceeding with the pharmaceutical development of a compound is favourable preclinical data, this does not necessarily give rise to a well-founded expectation of success, even less in the case of a combination product when neither combination partner has, as yet, progressed to the clinical stage of development". 

Whilst the prior art speculated about the use of each of the drugs in combination as monotherapies, for the Board of Appeal, this would at best:

"have provided the person skilled in the art with the hope to succeed, but that this does not amount to a reasonable expectation of success. Neither agent had been established for the treatment of patients. Each agent's efficacy and safety as well as the duration of action was still to be established. Thus, a high level of uncertainty regarding the potential for successful dual therapy with both agents would have been involved."

The Board of Appeal therefore also concluded that the claimed combination for use in the treatment of asthma and COPD was also inventive. 

Final thoughts 

The Board of Appeal in this case confirms that the data required for a novelty destroying disclosure of a medical use is more than that required to render a claim for that use credible. The decision in T 0209/22 also confirms that the question of inventive step for a medical use claim must be assessed on a case-by-case basis in view of what data is already available and what is already known about the drug product. Furthermore, a hope to succeed should not be confused with a reasonable expectation of success.  T 0209/22 also confirms the broadly favourable approach currently taken by the EPO to medical use inventions, at least in terms of a relatively low novelty and sufficiency bar (see also T 1437/21, T 0799/16).

Further reading

• When does pre-clinical data plausibly support a therapeutic effect? (T 966/18) (Jul 2021)
• Second medical use dosage regimen claim successfully traverses both insufficiency and "obvious-to-try" attacks (T 0799/16) (Mar 2021)
• Plausibility demystified - a review of EPO case law before G 2/21 (Feb 2023)
• 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)