Protecting second medical use inventions in Europe
Second medical use claims protect the use of an already known substance or composition in a new therapeutic application. Given the immense costs that are associated with developing new chemical entities for therapy, the repurposing of already available drugs is an attractive approach for the pharmaceutical industry. The fact that most patent systems provide protection for second medical use inventions encourages and fosters innovation in this area. Given the commercial relevance, this area of patent law has been constantly developing in past years, which is reason enough to keep up to date with developments at the European Patent Office (EPO), which we will explore in this article.
In the EPO, second medical use inventions can generally be protected through purpose-limited product claims. In particular, the allowable format for second medical use claims at the EPO is “substance or composition X for use in a method for the treatment of Y” (see EPO GL G-VI, 7.1.2).
While normally in product claims the expression ‘for use’ is merely interpreted as ‘suitable for use’ (eg, in “substance X for use in fertilising”), in second medical use claims, the mentioned purpose has a truly limiting character. This means that in the case of a second medical use claim, the prior art only anticipates the claim if it discloses the recited medical use (eg, “treatment of Y”). The disclosure in the prior art of substance or composition X alone does not take away novelty from the second medical use claim.
Substances and compositions
To decide whether an invention is amendable for second medical use claim protection, it is necessary to consider whether the therapeutic effect is achieved by a “substance or composition”. Only if it is a substance or a composition is purpose-limited product protection in accordance with Article 54(5) of the European Patent Convention (EPC) available.
Typically, the relevant substance is an active agent that achieves a therapeutic effect by acting pharmacologically, immunologically or metabolically (eg, by binding to a cognate target receptor). However, recent developments at the Boards of Appeal suggest that, in some cases, a broader interpretation can be applied to the term substance or composition.
In decision T 264/17, the claimed lubricant, containing perfluorinated polyethers for replacing synovial fluid, was considered a substance or composition within the meaning of Article 54(5) EPC. In the board’s view, the claimed perfluorinated polyethers achieved the therapeutic effect of acting as a replacement for synovial fluid in diseased joints because of the claimed lubricant’s material properties. The board held that it was secondary whether they were deemed active agents in the traditional sense.
A second medical use of a medical device generally cannot be protected with the indicated purpose-limited product claim format because a device is not a substance or composition. However, if the therapeutic effect can be attributed to a substance or composition, albeit in the context of a medical device, second medical use claim language may be available. For instance, in decision T 2003/08 the substance was a specific ligand for human immunoglobulin, which was immobilised against a column (device). The claimed therapeutic effect of treating cardiomyopathy was achieved extracorporeally, as the claim required that the patient’s plasma pass through the column, thereby removing immunoglobulin from the plasma and achieving the therapeutic effect.
In contrast, filler materials that exert their effect (eg, shielding against radiation) only through their three-dimensional orientation in the patient’s body do not qualify for second medical use protection because the therapeutic effect is not attributed to the chemical properties of the filler material (decision T 1758/15).
How to render a second medical use claim novel?
According to established case law, novelty of second medical use claims can be acknowledged not only in the case of treatment of a new disease in the strict sense, but also in the case of a different treatment for a known disease. A new technical effect in a known treatment, for example an effect identifying a new clinical situation, may also confer novelty, as well as a novel dosage regimen, a novel mode of administration or novel group of subjects to be treated.
Regarding a new group of subjects to be treated, more recently, the Boards of Appeal have held that novelty may also be established for a subgroup of subjects that overlaps with a larger population of previously treated subjects, if the identifying feature of the subgroup was not previously known in the art. The identifying feature may be a biomarker predicting the responsiveness of the subjects to the treatment (decision T 694/16) or the treatment history of the patients (decision T 1491/14). The purposive selection of these subjects is considered a functional technical feature of the claim that renders the claim novel in relation to the prior art.
A mere statement in the prior art that a therapy is explored, without enabling the therapeutic treatment (eg, by disclosing corresponding data), is not considered a novelty-destroying disclosure for a second medical use claim. Rather, for anticipating a second medical use claim, the disclosure in the prior art must make it believable that the therapeutic effect on which the disclosed treatment relies can be achieved.
How much data should be included in the patent application?
A key battleground at the EPO regarding second medical use claims is the so-called plausibility requirement. Is it plausible based on the information provided in the patent application that the claimed therapeutic effect can be achieved? Interestingly enough, the law does not have any such requirement, at least not explicitly.
However, according to established legal practice, the question of whether a technical effect is plausible may be inherent to the sufficiency of disclosure and inventive step requirement, depending on the circumstances. For second medical use claims, plausibility is typically dealt with in the context of sufficiency of disclosure.
In general, the application as filed or common general knowledge must provide some information that makes it technically plausible for a skilled person to use the substance or composition to attain the claimed therapeutic effect. Post-published evidence (ie, evidence filed with the EPO after the date of filing the application) may be taken into account by the EPO to assess plausibility, but only to back up findings in the patent application itself.
In principle, experimental data is not always required for the plausible teaching of a claimed therapeutic effect. However, in most cases it is advisable to include at least some relevant experimental data (eg, relevant in vitro data) in the application. Should circumstances require a patent filing before any data is available, or with only very little data, the following can be considered.
Lack of data on therapeutic effects in a patent application may not be harmful if a functional analogy to a known drug exists and is presented in the patent application. For instance, in decision T 950/13, the claim concerned dasatinib for use in the treatment of chronic myelogenous leukaemia (CML). Despite the absence of any data in the patent for dasatinib, the claim was considered to be sufficiently disclosed in view of a functional analogy to the known CML drug and BCR-ACL inhibitor imatinib. If the therapeutic effect can be argued based on theoretical considerations, such theoretical considerations should be set out in detail in the patent application.
Similarly, in decision T 184/16, plausibility of the therapeutic effect was acknowledged despite the absence of experimental data and based on the fact that “there are no prima facie serious doubts that the effect can be obtained and conversely no a priori reason and indication in the common general knowledge that the effect cannot be obtained”. By this standard, it seems that, in some cases, the absence of evidence to the contrary is already sufficient for plausibility. However, pure speculation with regard to a therapeutic effect is usually not sufficient to acknowledge the sufficiency of disclosure of second medical use claims (decision T 2015/20).
Hence, according to some jurisprudence, the absence of experimental data may not always become a bar to the patentability of second medical use claims. This is particularly important because deciding when to file a patent application can be a difficult decision.
If the patent application is filed too early, it may not contain enough information to plausibly show that the invention will work as envisaged. For example, there may not yet be enough data available from in vitro or animal models, let alone clinical trial results at the date of filing. However, waiting to file the application increases the risk of having to face off critical prior art, jeopardising patentability. For instance, mentioning that a therapeutic compound is undergoing clinical trials can become a bar to an inventive step, even in the absence of the results of the trial (decisions T 239/16 and T 96/20).
Notably, there is currently a referral pending before the Enlarged Board of Appeal, which concerns the plausibility requirement, in particular in the context of post-published evidence (referral number G 2/21, on plausibility). Any decision in this referral may also be of great relevance to the assessment of the plausibility requirement for second medical use claims.
Does it have to work for every patient?
Given that the EPO generally requires that the claimed subject matter is sufficiently disclosed over the whole scope of the claim, one may wonder whether the claimed therapeutic effect has to be achievable in every patient. The Boards of Appeal have made it clear that this is not the case and that the requirements of sufficiency of disclosure are met even if the therapeutic effect is only achieved in a subpopulation of responders and not in the entire patient population. Therefore, it is typically sufficient to show that a proportion of patients benefits from a treatment and that it has acceptable safety. The existence of a proportion of non-responders is considered a common phenomenon that does not prevent the patentability of a second medical use claim. Interestingly, the requirement of sufficiency of disclosure may be fulfilled, even when there is a substantial proportion of non-responders (decision T 799/16).
Summary and outlook
For the pharmaceutical and life science industry, second medical use claims are an important tool to protect intellectual property. There are many ways of establishing a novel and inventive second medical use claim. How much data is necessary before filing the application and when to file the application must be carefully decided based on the individual circumstances of a case.
As we have seen, the case law at the EPO is constantly developing. For instance, currently, we are expecting a crucial decision from the Enlarged Board of Appeal on the plausibility requirement. With many stakeholders involved, a complex legal landscape and significant advances in the pharmaceutical and biopharmaceutical sciences, the area of second medical use claims will keep practitioners on their toes for years to come.
Further, if everything goes according to plan, we may still even see the Unified Patent Court (UPC) system come into force in 2022. There is no way of predicting how the UPC will interpret the validity of second medical use claims, which may yet again require applicants to adapt their practice in the future.