We are now all so used to drafting medical use claims in the “new” style, that it is easy to forgot the fiction of the Swiss type claim that was necessary under EPC 1973. However, every now and then, a claim works its way through the system that makes some of us smile as we remember the good old days.

T 1732/18 is one such case, recently published by the EPO’s Boards of Appeal and relating to the treatment of thromboembolic disorders with rivaroxaban. The patent was granted on 24 April 2015 with two claims to:

1.The use of a rapid-release tablet of the compound 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]- l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide for the manufacture of a medicament for the treatment of a thromboembolic disorder administered no more than once daily for at least five consecutive days, wherein said compound has a plasma concentration half life of 10 hours or less when orally administered to a human patient.

and

2. The use as claimed in Claim 1, wherein the thromboembolic disorder is ST Segment Elevation Myocardial Infarction (STEMI), Non ST Segment Elevation Myocardial Infarction (NSTEMI), unstable angina, reocclusion after angioplasty or aortocoronary bypass, pulmonary embolisms, deep vein thromboses or stroke.

The patent was opposed by 13 parties and was revoked by the opposition division for lack of inventive step. The decision was appealed by the proprietor (appellant) and two further parties filed notices of intervention to join the proceedings (making 15 respondents in total).

In considering these claims, the Board had a number of things to say about claim construction.

Firstly, the feature that ‘the compound has a plasm concentration half life of at least 10 hours or less when orally administered to a human patient’ was considered by the Board to be redundant. The claim therefore did not require any mandatory step of verifying plasma concentration half life in an individual patient being treated. The opponents/respondents had argued that the patent was insufficient as this feature was an absolute criterion that meant that the half life was required to be ten hours or less in all humans or in all patients with thromboembolic disorder under any circumstance. The Board disagreed with this construction on the basis that the feature had been used in the claims as filed to describe a group of compounds envisaged for use in the invention. The claims as granted referred to a specific compound, rivaroxaban, and the prior art and description characterised this particular compound as having a half life of four to six hours. There was therefore no other intended meaning of this feature apparent from the context given. The feature was relevant to the group of compounds in the claims as filed but not rivaroxaban in the claims as granted.

Secondly, the Board confirmed that treatment covered prophylactic and therapeutic treatment and that an implicit feature of this was that the treatment had to have clinical benefits. This meant both efficacy and safety had to be taken into account when considering the prior art. This was important because prior art documents D2 and D11 related to a phase I clinical study of rivaroxaban carried out in healthy volunteers. The opponents/respondents had argued that administration to healthy subjects fell within the definition of prophylactic treatment as everyone is at some risk of suffering from a thromboembolic event. The Board found that the clinical study described in D2/D11 was not designed to test the efficacy and safety of a specific dosage regime in subjects requiring prophylactic or therapeutic anticoagulant treatment and that candidates eligible for prophylactic treatments with anticoagulants did not include healthy subjects – there had to be a reason i.e. some risk factor for thromboembolism, to justify prophylactic treatment with a medicament that had potential to cause major bleeding as a severe adverse effect. The claims were therefore novel over D2 and D11. More generally, the Board commented that:

Clinical efficacy is only determined in phase II and III studies. A phase I study limited to the initial testing of a range of doses on healthy subjects to obtain certain base parameters cannot establish the clinical efficacy of a dosage regime for treating patients with pathology. (reason 5.9.2)

The reading of safety and efficacy into the claims was important, not only for novelty, but also for sufficiency and inventive step.

The claims were sufficient without requiring the inclusion of dosage range because it was implicit that only safe and effective doses would provide clinical treatment:

The person skilled in the art would be well aware that there must be, in practice, a lower dosage limit to ensure efficacy and an upper limit to ensure safety and that these can be determined by appropriate clinical studies within the ordinary scope of ability of a skilled person. (reason 8.3.3)

Inventive step was assessed against D2/D11 as the closest prior art. These documents disclosed oral doses of 5 mg once daily, twice daily or three times daily; or 10 mg, 20 mg, 30 mg twice daily for five days but D2/D11 did not disclose the use of tablets nor did they establish the clinical benefits of any specific dosage regimen of rivaroxaban in the therapy or prophylaxis of thromboembolic disorders. The distinguishing feature was thus found to be the use of tablets and the once daily dosing of rapid release rivaroxaban for at least five consecutive days and the objective technical problem was formulated as the provision of a safe, effective and convenient oral dosage regimen for the prophylactic and therapeutic treatment of thromboembolic disorders.

Some respondents had contested that safety and efficacy should form part of the problem and others argued that the patent did not credibly demonstrate that the claimed treatment was safe. In response the Board repeated its finding that both safety and efficacy were part of the claim, stating that:

The medical indication “for the treatment of a thromboembolic disorder” in claim 1 implies that the treatment provided by the medicament and dosage regimen fulfils its purpose, i.e. that it is safe and effective. Embodiments that do not achieve this are not encompassed by the claim. (reason 9.12)

The claims were ultimately found to be inventive as the prior art contained no pointers that would have prompted the skilled person to combine rapid release with once daily dosing given the narrow therapeutic window open to anticoagulants (i.e. the efficacy of anticoagulation versus the safety concern of bleeding) and the desire to minimise fluctuations in plasma half life.

In this case, the Board was firmly of the view that safety and efficacy were already part of the medical treatment claims without the need for further dose information particularly as a skilled person could routinely work out the therapeutic window from phase II and III clinical trials. This has implications for the drafting of medical use applications as careful consideration will need to be given to the timing of the application vis-à-vis the progress of clinical trials through phases I, II and III and the necessary public disclosures that accompany them.

If you would like any further information about this Decision or other aspects of European patent practice relating to medical treatments please contact Hazel Robson at docketing@secerna.co.uk or 01904 202900.