Second medical use claim: when is a specific subgroup of patients disclosed?

The P did not agree and argued that there was incorrect reading of the press release documents. The prior art disclosed a patient population having mild, moderate or severe renal impairment as a whole and the effective treatment in each of the in each of the subgroups of patients with renal impairment could not be directly derived. This was compounded by a post-published prior art document which indicated a lack of efficiency in patients with severe renal impairment. The P also stated the inference of the positive results in patients with mild renal impairment at a 10 mg empagliflozin dose to that of an effective 25 mg dose to patients with moderate renal impairment was speculative.

The Board of Appeal (the Board) agreed with the P and the decision under appeal was set aside and the patent was maintained as granted.

Background

In the decision under appeal, the decision of the OD to revoke the European Patent 2981271 was appealed by the P. Independent claim 1 of European Patent 2981271 as granted was a second medical use claim for treating prediabetes comprising administering empagliflozin to patients with moderate renal impairment or stage 3 chronic kidney disease or an estimated glomerular filtration rate (eGFR) of ≥30 ml/min/1.73 m2. Eight oppositions were filed against the grant of European Patent 2981271 on the grounds that its subject-matter lacked at least novelty and an inventive step. The OD arrived at the following conclusions:

1. Press release articles (cited as D22/D29) reporting the successful completion of a Phase III clinical trial using 25 mg empagliflozin in the treatment of type 2 diabetes mellitus with patients with mild, moderate or severe renal impairment was novelty destroying for claim 1 of the patent as granted.
2. The Auxiliary requests either did not introduce any distinguishing feature with respect to the prior art or did not support an inventive step.

The Appeal

The decision of the OD to revoke the European Patent 2981271 was appealed by the P. 

[Novelty]
The crucial issue to be decided was whether the skilled person would in view of the prior art have reasonably expected that empagliflozin would show significant efficacy in the treatment of diabetes in patients with moderate renal impairment. 

Document D22/D29 evaluated:

• 25 mg dose of empagliflozin in Type 2 Diabetes patients with mild, moderate or severe renal impairment, and 
• 10 mg dose in those with mild renal impairment

versus placebo for 52 weeks and reported efficient treatment.

The O argued that the skilled person would conclude that within each of the subgroups of patients, the primary efficacy end point compared to placebo was indeed reached. The efficacy of 10 mg empagliflozin in patients in patients with mild renal impairment would suggest efficacy in patients at a 25 mg dose with moderate renal impairment. A post-published document (D53) disclosed a lack of efficacy of empagliflozin in patients with severed renal impairment. The O argued that D53 served to confirm the efficacy in patients with moderate renal impairment and only suggested an issue with treatment of patients with severe kidney disease.  

In contrast, the P argued that the press releases in question presented a generic description of a group of patients with renal impairment ranging from mild to severe. The effective treatment from administration of 25 mg empagliflozin reported in documents (D22/D29) therefore only concerned this patient population as a whole. The effective treatment in each of the subgroups of patients by the mentioned levels of renal impairment was contradicted by the lack of efficacy in patients with severe renal impairment reported in the post-published document (D53). The P did not agree with the inference that the reported efficacy of 10 mg empagliflozin in patients with mild renal impairment indicates that a 25 mg dose must have been effective at least also in patients with moderate renal impairment. 

Other Case Law

The Board considered that it is established case law that the prior disclosure that an investigational product for use in the treatment of a particular condition is undergoing clinical trials may preclude that a subsequently claimed invention involving this product for use in the treatment of that specific condition is considered to involve an inventive step, even where the results of the trial have not been made available to the public (see T2506/12 and T239/16). However, as explained in T2963/19, the approval of a clinical study does not, by way of a heuristic, imply an expected positive outcome of the treatment nor represent a scientific advice on the development programme of the investigational product tested. 

Decision of the Board of Appeal

The Board ruled that the press releases (D22/D29) announced efficacy of treatment with 25 mg of empagliflozin was understood as relating to the patient population having mild, moderate or severe renal impairment as a whole. The skilled person cannot directly derive that the treatment is effective in each of the subgroups of patients defined by the mentioned levels of renal impairment. The ‘Data on file’ does not disclose the number of patients with moderate renal impairment and only presents the total number of participants in the Study. Furthermore, the positive comments on the results from the trial and the reported efficacy of 10 mg empagliflozin in patients with mild renal impairment do not provide any basis for the skilled reader to conclude that as a matter of fact the 25 mg dose must also have been effective in the patients with moderate renal impairment. Thus the Board was of the view that the subject-matter of claim 1 as granted is new over the prior art under an Art. 54(5) EPC format. 

The Board also ruled that in the problem-solution with the press release documents (D22/D29) as the closest prior art, the differences are the efficacy in treatment of the defined forms of diabetes in patients with moderate renal impairment. The objective technical problem was thus be formulated as the provision of effective treatment for diabetic patients with moderate renal impairment. 

Thus, the mere inclusion of diabetic patient with renal impairment beyond the stage of mild renal impairment in Phase III clinical trial does not provide a reasonable expectation of success. The post-published prior art (D53) further confirmed that efficacy of treatment was not expected in patients with severe renal impairment. The Board was of the view that the subject-matter of claim 1 as granted was not obvious to the skilled person in view of the prior art and thus involves an inventive step. 

The Board set the decision under appeal aside and the patent was maintained as granted.