T 1356/21 - Limits on the bonus effect rule

Key points

• The bonus effect rule can be used to hold a claim obvious despite the claimed subject matter providing a surprising technical effect. 
• "in the Board's view, the case law on bonus effects cannot be applied to all situations where a given differentiating feature [...] two separable technical effects [...], 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 as explained in T 192/82), or that, considering the relative technical and practical importance of the effects in the circumstances of the case, the additional unexpected effect is merely accidental (following T 227/89 and T 1147/16) [effect was no bonus effect]. 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."
• T227/89: "In determining which effect is crucial and which is merely accidental (so-called "bonus effect"), a realistic approach has to be taken, considering the relative technical and practical importance of those effects in the circumstances of a given case. In the present case, tensile strength, elongation at break and thermal stability are at least as important as the blooming properties for the overall value of the compositions in question, and any improvements thereof cannot therefore be disqualified as being merely accidental."
• "The Board is aware of the view expressed in T 1317/13 (see point 24 of the reasons) that a "one-way-street" situation is not a mandatory prerequisite for the application of the principle established in T 21/81 (see above). However, neither T 1317/13 nor T 21/81 offer a basis for an unqualified application of the bonus effect case law to any situation of plurality of technical effects without regard to their respective technical and practical importance. The Board's view in this regard is in agreement with the statement in decision T 192/82 (see point 16 of the reasons) that the use of means leading to some expected improvements might well be patentable if relying on an additional effect, provided this involves a choice from a multiplicity of possibilities."
• Note that the cited decisions are either old or relatively new.
• In the case at hand, the two effects are reduced discomfort/injection volume (unsurprising); and flatter PK/PD profile/longer duration of action (surprising) as a result of a concentration increase of an injected medicament.
• "The present case does not qualify as a "one-way-street" situation. As argued by the respondent, 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, such as dividing the injection into several smaller volumes, adding further substances that facilitates diffusion at the injection site avoiding the formation of a large depot, heating the injection site to increase diffusion, including an analgesic, ..."
• "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. "
• "this PK/PD effect was discovered only after arriving at the higher concentration formulation [to reduce injection volume], and would thus be nothing but an additional bonus effect [according to the opponent]. 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 pK/PD profile effect is to be taken into account is not in what circumstances the inventors realised the invention, but what the invention achieves."
• "Similarly, the Board is not convinced that the effect of reduced discomfort and injection volume should be regarded as a bonus effect either. For the reasons given above (see 3.4.3), the fact that two technical effects arise from the same distinguishing feature does not mean that one of the two effects must necessarily be regarded as a bonus effect. However, considering that the effect on PK/PD profile and duration of action must be taken into account and already leads to the acknowledgement of an inventive step (see below), the question whether the reduced discomfort and injection volume should be additionally considered may be left unanswered."
• " the subject-matter of the main request involves an inventive step."

EPO 

The link to the decision is provided after the jump, as well as (an extract of) the decision text.

https://www.epo.org/en/boards-of-appeal/decisions/t211356eu1

3.4 Technical problem; bonus effect

The parties differ as to which of the two effects should be taken into account in the assessment of inventive step.

3.4.1 In the Board's view, both effects are mentioned in the patent (see paragraph [0005] for the reduced discomfort, and paragraphs [0017] and [0018] for the flatter PK/PD profile with a longer duration of action) and are credibly achieved by the claimed subject-matter in comparison with the closest prior art embodiment. Accordingly, the technical problem is to be formulated objectively, taking into account both effects, as the provision of an improved aqueous pharmaceutical formulation of insulin glargine, i.e. the improvement being both a flatter exposure and flatter biological profile together with a longer duration of action, and a reduced discomfort.

3.4.2 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.

The Board does not agree, for the following reasons.

3.4.3 According to established case law, an effect which may be said to be unexpected can be regarded as an indication of inventive step. However, certain preconditions have to be met (see Case Law of the Boards of Appeal, 10**(th) edition, 2022, I.D.10.8). In T 21/81 (see Headnote) the board considered that "if having regard to the state of the art it would already have been obvious for a person skilled in the art to arrive at something falling within the terms of a claim, because an advantageous effect could be expected to result from the combination of the teachings of the prior art documents, such claim lacks inventive step, irrespective of the circumstance that an extra effect (possibly unforeseen) is obtained." In line with this decision, in T 506/92 it was affirmed that an additional effect achieved inevitably by the skilled person on the basis of an obvious measure without any effort on his part simply represents a bonus under EPO case law which cannot substantiate inventive step, even as a surprising effect (see point 2.6 of the reasons).

However, 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 as explained in T 192/82), or that, considering the relative technical and practical importance of the effects in the circumstances of the case, the additional unexpected effect is merely accidental (following T 227/89 and T 1147/16). 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 Board is aware of the view expressed in T 1317/13 (see point 24 of the reasons) that a "one-way-street" situation is not a mandatory prerequisite for the application of the principle established in T 21/81 (see above). However, neither T 1317/13 nor T 21/81 offer a basis for an unqualified application of the bonus effect case law to any situation of plurality of technical effects without regard to their respective technical and practical importance. The Board's view in this regard is in agreement with the statement in decision T 192/82 (see point 16 of the reasons) that the use of means leading to some expected improvements might well be patentable if relying on an additional effect, provided this involves a choice from a multiplicity of possibilities.

3.4.4 The present case does not qualify as a "one-way-street" situation. As argued by the respondent, 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, such as dividing the injection into several smaller volumes, adding further substances that facilitates diffusion at the injection site avoiding the formation of a large depot, heating the injection site to increase diffusion, including an analgesic, reducing the speed of injection, using continuous injection or adjusting the depth of injection. D20 (see page 1240; page 1242, right column) and D21 (see page 71, Results) merely express a preference, in the context of regular insulin, for the use of a (concentrated) U-500 formulation with multiple daily injections or continuous subcutaneous (s.c.) infusion. It cannot be concluded from these documents that the present case is characterised by a lack of alternative means for addressing the issue of discomfort associated with the injection of large volumes.

3.4.5 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. As explained in D27 (see page 98, section "Basal Insulin"), basal insulins are meant to provide a constant background level of insulin that controls hepatic plasma glucose production on a diurnal basis. Basal insulins include insulin glargine and NPH insulin. The ideal properties for a basal insulin are the following:

"Its action should be protracted to ensure glycaemic control over long time periods with few injections (i.e. have a long duration of action). The kinetic profile should be flat and smooth (i.e. peakless) with minimal variability between patients and within each patient from day to day to ensure predictability of control and to lower the risk of hypoglycaemia."

The effects of flatter PK/PD profiles and longer duration of action thus correspond to essential properties of basal insulins. These effects cannot be regarded as being technically and practically less important that the reduced discomfort upon injection.

3.4.6 Lastly, the patent explains in paragraphs [0005] and [0006] that the formulation containing 300 U/mL insulin glargine was initially developed for the purpose of reducing the injection volume, and thus to address the issue of discomfort upon injection of larger doses of the U 100 formulation in patients e.g. with increased insulin resistance. The inventors expected both the U 100 and U 300 formulations to provide the same insulin exposure and effectiveness, yet unexpectedly discovered that the U 300 formulation instead led to flatter PK/PD profiles (see paragraph [0017]).

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 pK/PD profile effect is to be taken into account is not in what circumstances the inventors realised the invention, but what the invention achieves.

3.4.7 Thus, in the circumstances of the present case where several alternatives could lead to reduced discomfort upon injection, and owing to their crucial importance, the technical effects of flatter PK/PD profiles and longer duration of action cannot be regarded as accidental and must be taken into account.

Similarly, the Board is not convinced that the effect of reduced discomfort and injection volume should be regarded as a bonus effect either. For the reasons given above (see 3.4.3), the fact that two technical effects arise from the same distinguishing feature does not mean that one of the two effects must necessarily be regarded as a bonus effect. However, considering that the effect on PK/PD profile and duration of action must be taken into account and already leads to the acknowledgement of an inventive step (see below), the question whether the reduced discomfort and injection volume should be additionally considered may be left unanswered.

3.5 Obviousness

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 to 270-330 U/mL 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.