The COVID-19 pandemic has caused severe disruptions to many businesses around the world. Pharmaceutical and biotechnology companies have perhaps felt the impact to a lesser extent than other sectors of the economy because they are often deemed essential businesses. They also have a unique position in aiding the fight against SARS-CoV-2, either by repurposing existing drugs or developing new ones, or by providing new or improved diagnostic assays.
Nevertheless, the pandemic has severely disrupted normal business operations. Social distancing measures mean that research laboratories cannot operate at their usual capacity, and in some facilities shift rotations have been put in place to allow researchers access to their laboratories. Clinical research likewise has been impacted as healthcare providers have focussed their efforts on saving the lives of patients suffering from COVID-19 and have advised patients with non-life threatening conditions to stay away from hospitals. Many sponsors have decided to suspend enrolment or delay initiating trials for new therapies in light of these circumstances. Ongoing clinical trials have been delayed because patients, in particular those who are vulnerable in view of their pre-existing medical condition, may cancel appointments or discontinue treatments to avoid hospital visits.
The pharmaceutical industry is also unique with respect to the pivotal role that intellectual property rights can play in its business success. In many countries, pricing and reimbursement is at least partially linked to patent protection for pharmaceutical products that contain new active ingredients. The disruptions to research and clinical testing will likely have a detrimental effect on acquiring patents to protect inventions, in particular in jurisdictions that require at least some data to support an invention. This article will explore the problems that can arise out of the current situation from a European perspective and will offer some practical solutions.
Consequences of having no data in a European patent application
The European Patent Convention (EPC) requires no experimental proof for patentability. The Boards of Appeal therefore have held that “the disclosure of experimental data or results in the application as filed and/or post-published evidence is not always required to establish that the claimed subject-matter solves the objective technical problem. This is in particular true in the absence of any formulated substantiated doubt […].” (T 1859/08, reason 13). In practice, however, patent applications with experimental data fare better than those without them.
Over the recent years, the case law of the European Patent Office (EPO) and that of national courts such as the UK have placed an ever greater emphasis on the concept of “plausibility”, most obviously when assessing of sufficiency of disclosure and inventive step. A finding by the patent office or a court that it is not “made plausible by the disclosure in the application that its teaching solves indeed the problem it purports to solve” (T 1329/04, reason 12) can have serious consequences. It precludes the applicant from relying on later evidence, e.g., to support an inventive step (T 1329/04). The invention may also be considered insufficiently disclosed, also with the consequence that the applicant cannot remedy such an objection by pointing at post-filing data demonstrating that implementing the claimed invention across its breadth is indeed possible (T 609/02).
Applicants with plans to file a priority application who don’t yet have data to rely on may choose to delay filing and wait for the data, but those who are approaching the end of the priority year and had planned to support an initial filing with further data in a PCT application do not have so much flexibility. For any applications that will ultimately be examined by the EPO, applicants should therefore consider carefully whether the lack of data could negatively impact the chances of success of securing patent protection in Europe.
Addressing gaps in your data with good drafting
Even very limited experimental data may be sufficient to take the plausibility hurdle, as long as the patent application or patent provides a convincing rationale as to why these data can support the claimed invention. Thus, for a patent application that is close to conversion into a PCT application but where COVID-19 disruptions have led to delays and/or reprioritisation of research efforts, and, as a result, to a lack of additional data, it is worth exploring whether even limited existing data can be leveraged more.
Explaining in more detail the inventors’ rationale for conducting experiments and how the results support a broadly applicable technical effect may go a long way towards satisfying the plausibility requirement. Moreover, by carefully considering suitable fall-back options and providing the required written description support, it may be possible to identify commercially valuable intermediate positions in broadly drafted claims to an invention. The EPO typically applies added matter rules strictly, so carving out fall-backs at the drafting stage is important to avoid being pushed back from a broad set of claims to specifically exemplified embodiments. In this context, it may be useful to disclose why certain features may be particularly suitable when practising the invention to demonstrate how a broader rationale can be implemented more specifically.
Particular challenges for second medical use applications
When it comes to new therapeutic applications of known active substances, the requirement for data can be particularly important to support an invention. Under European practice, claims directed to a new therapeutic use of a known substance are typically formulated as purpose-limited product claims. Attaining the claimed therapeutic purpose (“treatment of disease indication Y”) is considered a functional technical feature of the claim. The sufficiency of disclosure requirement must be satisfied at the effective date of the patent, i.e., on the basis of the information in the patent application together with the common general knowledge then available to the skilled person. It is therefore essential that a patent application makes the new therapeutic use at least plausible, i.e. demonstrates the suitability of the active substance to treat the claimed new disease indication.
Supporting therapeutic use claims with in vitro or animal data
Clinical data are not necessarily required to support a therapeutic use claim. In vitro or in vivo data that directly and unambiguously reflect the therapeutic effect on which the claimed therapeutic application relies may be enough to support such a claim. Alternatively, if there is an established relationship between the physiological activities of the compound under consideration and the disease in question, it may even be possible to rely solely on such a rationale, although at least some experimental data will likely be helpful to counter arguments that the invention was obvious in light of prior art. Documents that established the physiological activities of the compound in question may be combinable with prior art that explores the mechanism of the disease indication to be claimed. Therefore, being able to argue that only the additional experiments disclosed in the patent application established a reasonable expectation of success may be important to meet the patentability requirements.
Should a clinical trial have been disrupted because of the COVID-19 pandemic and previously expected data is lacking, looking for unpublished pre-clinical data sets that could be used to fill the void as the PCT conversion deadline is looming could be invaluable.
Very limited clinical data may not be enough to support a therapeutic use claim
If clinical data are disclosed in a patent application, care must be taken that the therapeutic effect can be clearly established. Data from a single patient or data that are not statistically significant are unlikely to be useful to support the suitability of a compound in treating the claimed disease indication. For example, in T 1045/13 the technical Board of Appeal examining the data in an opposed patent had the following misgivings: “The examples do not give rise to statistically significant data. Each example relates to a single patient only, contrary to common practice which requires a certain number of patients to be tested under the same conditions in order to allow statistical analysis of the results. Also, in the absence of a control group, placebo effects cannot be excluded.” Appropriate study populations and controls are required to avoid such objections. Indeed, these considerations also apply to any preclinical data sets.
As clinical studies are typically performed only after extensive preclinical research has taken place, the combination of preclinical data sets with early signs of clinical efficacy may strengthen a claim to a new therapeutic use, in particular if the patent application links the provided experimental evidence with an overarching rationale for the efficacy of the treatment.
Clinical protocols as prior art
The disclosure of a clinical trial set-up can result in particularly tricky situations for medical use patent applications at the EPO. Delays in initiating or completing clinical trials due to the COVID-19 pandemic may cause problems because a filing strategy to capture, e.g., specific dosage regimens, can no longer be executed as planned. Hoped-for results that were expected within a 12-month time period from initiating a study may not be available for inclusion in a planned PCT application.
The disclosure of a clinical trial-set up does not typically take away the novelty of a claim directed to a corresponding medical use (e.g., a claim directed to a specific dosage regimen that had been disclosed as being tested in a clinical trial). For instance, in T 1859/08 the technical Board of Appeal held that “[If] a prior art document discloses clinical investigations such as phase I, II or III studies (or states that these investigations are ongoing), but the document fails to disclose the final result of these studies, this document is not novelty-destroying.” However, although novelty may be acknowledged, the obviousness assessment is often more onerous in such situations.
In general, when drafting a patent application against a prior art background of a clinical trial protocol, it is advisable to include in the claims any features discovered only from the performance of the clinical trial, such as a specific outcome or a safety feature. Any explanation regarding the inventors’ rationale for choosing certain biomarkers/endpoints that may not have been disclosed previously may also be useful. Should COVID-19 disruptions result in delays which means that the clinical data to support these features are now not available in time to complete an application at the PCT stage, it will become challenging to obtain patent protection at the EPO, even for such specific clinical outcomes. In such cases, and particularly where interim results from the clinical trials that might allow some of the tactics discussed above to be deployed are not available, it may be worth considering whether re-filing the application at a later date could be the better choice.
Delaying the filing of an application may mean that a later application will face additional prior art, e.g., in form of press releases or scientific posters commenting on interim results. The disclosure of such prior art interim results is far from ideal, but is not inevitably fatal. For example, if it could be argued that these interim results are not statistically significant, they may be addressable by pointing to a complete data set in a subsequent patent application which includes a full statistical analysis. Giving up on an earlier filing date will always be a difficult decision to make, and a detailed assessment of the facts and balancing of the advantages and disadvantages will be necessary to inform the appropriate strategy.
Experimental data in contentious proceedings to defend existing patents
In some situations, it may not be the generation of new intellectual property in form of patent filings but the defence of existing patents that are affected by resource availability under the current pandemic. For example, it may have been planned to support a patent in European opposition proceedings with additional data which now cannot be generated because research priorities have changed or social distancing measures mean that laboratory capacity had to be reduced.
Depending on the stage of the proceedings, it may be possible to request an extension or to delay the final submissions deadline by requesting a hearing postponement. It will very much depend on the finer details whether such a strategy can be implemented successfully. For patents under attack, having a pending divisional application may help as it leaves open the possibility of obtaining commercially relevant protection at a later date.
Planning a patent filing strategy can be challenging in normal times, especially with limited resources and rapidly changing priorities. The COVID-19 pandemic has disrupted many research organisations and has delayed a large number of clinical trials, adding a further layer of complications. Experimental data in a patent application can be essential in order to establish that a patent application has made a claimed invention plausible. The plausibility requirement must be met before applicants and patentees are able to rely on post-filing evidence to support an inventive step and to confirm sufficiency of disclosure.
Even limited data can be sufficient to establish plausibility, if care is taken when drafting the application to explain how such data can support a broad claim. Explaining the rationale and including multiple fall-backs can be helpful and is good practice in all situations. Therapeutic use claims may be adequately supported by in vitro and animal data, and limited clinical data suggesting therapeutic efficacy may be strengthened by including unpublished preclinical data sets as further support.
There may be situations where postponing the filing of a patent application is the preferred option because the deficiency in experimental support is such that a successful prosecution of the application in the future appears very unlikely to address known prior art disclosures, e.g., the disclosure of a clinical trial set-up. If the procedural rules allow it, delaying tactics may also be appropriate in contentious proceedings where experimental support may strengthen the defence of an existing patent.
We would be interested to hear from readers about the situations they have encountered. Please contact Jens or Anna if there are particular scenarios not covered in this article that could be addressed in future editions.