T 1356/21 - dosage regimen - bonus effect


Dosage regimen, novelty, G 2/08, bonus effect

T 1356/21
The appeal was filed by the opponent (appellant) against the interlocutory decision of the opposition division finding that the patent met the requirements of the EPC.
Claim 1 of the main request pertains to an aqueous pharmaceutical formulation characterised in particular in that "the concentration of insulin glargine is 270-330 U/mL".
Claim 11 is identical to claim 1 with the addition of "for use in the treatment of Type I and Type II Diabetes Mellitus in a patient". Claim 23, pertaining to the "aqueous formulation according to any of the foregoing claims for use in the treatment of Type 1 Diabetes Mellitus and Type 2 Diabetes Mellitus", relates to the same subject-matter as claim 11. Thus both claims 11 and 23 are drafted in the format of Article 54(5) EPC, i.e. as claims directed to the same composition as in claim 1 for a specific use in a method referred to in Article 53(c) EPC.
According to the appellant, the subject-matter of claims 11-23 of the main request lacks novelty over D12, because the insulin glargine concentration defined in said claims falls within the broad meaning of the term "dosage regimen" as used in G 2/08, and yet is not characterised by any technical effect that would be particular to said sub-range compared to other concentrations within the range disclosed in D12. The appellant did not, however, object to the novelty of claim 1.
D12 does not disclose a concentration of insulin glargine in the composition in the claimed range of 270-330 U/ml. The claimed range is narrow compared to the range of D12 (criterion (a)) and far removed (criterion (b)) from any example of this document, the concentration of insulin glargine being always 100 U/ml. In this respect, the Board concurs with the most recent decisions, according to which the former criterion of purposive selection (criterion (c)) is relevant for the question of inventive step rather than for novelty. Thus the subject-matter of claim 1 is novel over D12.
Neither decision G 2/08 nor its reference to T 1074/06 (where the claims related to doses, and not concentration) justify reading the word "concentration" of claims 11 and 23 as a dosage regimen. The concentration feature defines the composition itself, i.e. the amount of insulin glargine in the composition, and not the use of the composition, i.e. the dose given to a patient at particular times or time intervals. This concentration feature thus establishes novelty for the subject-matter of claims 11 and 23 for the same reasons as for claim 1.
The appellant's objection must fail for the additional reason that, even if the concentration features of claims 11 and 23 were arguendo seen as a dosage regimen, the former criterion of a purposive selection (criterion (c)) should no longer be regarded as a requirement under G 2/08 for a dosage regimen to represent a novel selection from a broader range known in the prior art.
Accordingly, the claimed subject-matter is novel.
The differentiating feature, namely the increase in insulin glargine concentration, leads to two types of technical effects: reduced discomfort or pain, and flatter PK/PD profile, longer duration of action.
According to the appellant, the reduction in the injection volume is the relevant effect, and was, as acknowledged in the patent, the purpose for increasing insulin glargine concentration in the first place. The additional effect of the concentration-dependent change of the PK/PD profile would be inevitably achieved as the result of increasing the insulin glargine concentration for the purpose of reducing the injection volume, and would thus represent a mere bonus effect.
In the Board's view, the case law on bonus effects cannot be applied to all situations where a given differentiating feature (here: the increase in insulin glargine concentration) leads to (or inevitably achieves) two separable technical effects (here: reduced discomfort/injection volume; and flatter PK/PD profile/longer duration of action), one of which may be expected. For an additional, unexpected effect to be disqualified as a mere bonus effect, it must be shown either that the situation is characterised by a lack of alternatives as regards the means for achieving the first, expected improvement (i.e. a "one-way-street" situation), or that the additional unexpected effect is merely accidental. In situations which do not qualify as a "one-way street", the Board does not consider it appropriate that a crucial and unexpected technical advantage be disregarded in the assessment of inventive step as soon as any additional obvious effect is mentioned in the patent.
The present case does not qualify as a "one-way-street" situation. The skilled person could have addressed the issue of discomfort caused by the injection of larger volumes of the formulation by other means than an increased concentration.
Furthermore, the effects of flatter PK/PD profiles and longer duration of action cannot be regarded as merely accidental, but instead represent crucial advantages in the context of basal insulins.
According to the appellant, this PK/PD effect was discovered only after arriving at the higher concentration formulation, and would thus be nothing but an additional bonus effect. However, in the Board's opinion, it would also not be appropriate to disqualify the effect of flatter PK/PD profiles and longer duration of action as accidental, i.e. as being of lesser technical and practical importance, on account that these effects may be the result of a serendipitous discovery. What matters when deciding if the effect is to be taken into account is not in what circumstances the inventors realised the invention, but what the invention achieves.
It follows from the above that the relevant question is whether the skilled person not only could, but would consider an increase of the insulin glargine concentration in the expectation of solving the problem, and in particular in the expectation of achieving a flatter PK/PD profile and longer duration of action.
The prior art is silent about the effect of a higher concentration on the PK and PD profiles in the context of insulin glargine.
As a consequence, the skilled person had no reasonable expectation that raising the concentration of insulin glargine would lead to flatter PK/PD profiles and a longer duration of action.
Accordingly, the subject-matter of the main request involves an inventive step.
The appeal is dismissed.