Dosage regimen claims typically refer to compounds for use in treating a condition at a specific frequency of administration, at a specific dose or within a specific dosage range. Sometimes further features of the formulation or the administration mode are also included, reflecting a dosage regimen of an approved product. Prosecution of these claims at the EPO can be challenging and even following grant they are vulnerable to revocation during opposition proceedings.
This article is in two parts. This first part focusses on pitfalls to be aware of and approaches for success. For a more detailed discussion of the EPO case law which underpins this, see the second part here.
The common hurdles to patentability of a novel dosage regimen claim at the EPO are inventive step and sufficiency (enablement). The EPO’s default position is that specific dosages are ‘obvious to try’ and thus fall within routine experimentation. Further, the existence of a published Phase II clinical trial protocol – even without results – leads to an expectation of success that can nix inventive step of the claims. To meet the requirement of sufficiency, the efficacy of the claimed dosage regimen has to be credible at the filing date of the patent. The arguments put forward by patentees to overcome these objections can be two sides of the same coin and navigating sufficiency and inventive step can involve treading a fine line.
Practice points
To give your dosage regimen patents the best chance for success, firstly take enormous care of the disclosures surrounding you clinical data – whether this is an announcement for investors, or part of the regulatory approval process. If clinical trial data is being published in scientific journals, be mindful of the publication dates and ensure an application is filed before that date.
It is not a bad idea to prepare the framework of the patent specification ahead of time and start considering the detail as soon as a candidate compound has been selected for a Phase I trial – be ready to include data, comparisons to placebo or the standard of care, details of specific patient populations and mechanistic explanations supporting the effect.
Always important for EP applications is to include ‘layering’ in the description to ward off added subject-matter objections – include preferred ranges as well as specific dosages, in combination with specific diseases. These combinations (e.g. a specific dosage for a specific patient group) should be individually called out, to avoid the EPO considering an amendment to these features to be an ‘intermediate generalisation’ that was not disclosed in the application as filed. Consider a pre-filing review of the specification by your European patent counsel to optimise the application in this regard.
Drill into the data from the clinical trial and consider carefully which data to include in the application. Remember that data can be filed during prosecution of the European application to support or corroborate an effect already established by the technical teaching (e.g. made plausible) in the application as filed, for the purposes of inventive step. However, post-filed data cannot remedy a lack of sufficiency, where the efficacy of the claimed dosage regimen was not already made credible in the application. Graphs illustrating the technical effect of the dosage regimen can be helpful and persuasive during prosecution at the EPO.
Consider including not only the preferred dosage regimen (a specific dose or range and frequency of administration) in the claims, but also features of the specific formulation, condition being treated, patient group and administration mode. A narrow claim drawn to your marketed product can be valuable as well as robust.
Where a disease is complex and results are unpredictable between patient populations, or even within the same patient population over time, the Boards of Appeal have upheld dosage regimen claims1. The greater the challenges linked to a particular target, the higher the chances that an inventive step will be acknowledged. Again a thorough analysis of the trial data and the effects observed in vivo can unearth unexpected results of the treatment.
More generally, technical effects that can lead to the allowance of a dosage regimen claim include the speed of results or a longer duration of action compared to known treatment (or placebo if there is no suitable comparison), or if the previous standard of care was not tailored to the specific condition the dosage regimen is directed to. A surprising magnitude of the beneficial effect can also be persuasive. Combinations of benefits, such as reduced side effects or discomfort in addition to an improvement in the pharmacokinetics can also improve the patentability position at the EPO2. Advantages illustrated by the pharmacokinetic profile can play a decisive part in a positive decision on a dosage regimen claim.
During prosecution, take care if arguing sufficiency based on similar results in prior art disclosures – as is seen time and time again in Decisions of the Boards of Appeal, taking this position can often scupper the inventiveness of the claims.
Finally, regarding regulatory submissions in the EU, remember that if dosages are considered to be commercially confidential information3, dose details can be redacted and replaced by digits ‘00’ in the relevant structured data field in the CTIS system. This is in order to prevent disclosure of dose information when the clinical trial application decision is issued by the Member States concerned. Redacted versions of documents can be provided for publication, with the non-redacted, ‘not for publication’ versions provided for Member State assessment. Justification for the redaction of the dose information must be provided in the cover letter of the application, submitting that the specific information constitutes patentable subject matter.
While dosage regimen claims can be challenging to obtain at the EPO, a considered approach to drafting and disclosures, and a detailed analysis of the data can lead to a successful outcome and valuable patent protection.
If you have any questions relating to this topic, please get in touch with Andrea Coles or your usual Kilburn & Strode advisor.
1 T 0799/16
2 T 1356/21
3 Limited redaction is possible, where commercially confidential information is at issue, but justification must be given.