The patent relates to long-acting formulations of insulin.
Brief outline of the case
The opponent appealed the decision of maintenance according to a new MR filed during OP before the OD.
In the summons to OP before the OD, the OD held that claim 1 as granted lacked N over D1=US 2004/048783, the only document of category X,A in the ISR established by the EPO.
The board confirmed the decision of maintenance according to the MR.
The case is interesting as it deals with the following topic: limits to the application of the concept of bonus effect.
Closest prior art – Difference
In the case at hand, the choice of the starting document has no bearing on the assessment of inventive step, because the embodiment chosen as starting point is in all cases a 100 U/mL glargine composition
The board referred to D1, examples; D10, Lantus composition, page 1; D11, U-100 insulin glargine; D12, Lantus composition.
The relevant differentiating feature is the claimed insulin glargine concentration of 270-330 U/mL. It is consequently not necessary to identify precisely the document(s) used as starting point(s), or to decide whether the objection based on D10 should be admitted into the appeal proceedings.
Effect of the difference
The differentiating feature, namely the increase in insulin glargine concentration from 100 U/mL to 270-330 U/mL, leads to two types of technical effects:
Effect 1: reduced discomfort or pain
This claimed formulation does allow patients to inject the same number of units of insulin glargine at one third the volume of injection.
Effect 2: flatter PK/PD profile, longer duration of action
Figures 1-3 of the patent demonstrate that insulin glargine U 300 exhibits flatter PK and PD profiles and longer duration of action than insulin glargine U100.
The opponent’s point of view
The opponent did not contest that both effects 1 and 2 are achieved by the composition with a concentration of 300 U/mL in comparison with the prior art embodiment having a concentration of 100 U/ml.
The opponent however submited that the effects are not specific to the claimed range of 270-330 U/ml, but also arise with other concentrations falling within the broader range disclosed in D12 for insulins in general, such as 500 U/ml.
According to the opponent, 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’s decision
The board did not consider that the opponent’s argument modifies the assessment of the technical effect over the closest prior art. The starting point for the evaluation of inventive step is the 100 U/mL insulin glargine composition, and not a hypothetical 500 U/ml insulin glargine composition which would conceptually fall within the scope of D12.
In the board’s view, both effects are mentioned in the patent for the reduced discomfort, and 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.
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.
The board referred to T 21/81, see Headnote, in which it was held that if 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.
The board also referred to T 506/92, Reasons 2.6, 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.
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 was aware of the view expressed in T 1317/13, Reasons 24, that a “one-way-street” situation is not a mandatory prerequisite for the application of the principle established in T 21/81.
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, Reasons 16, 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.
The present case does not qualify as a “one-way-street” situation. As argued by the proprietor, 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.
Comments
The starting point for the evaluation of inventive step has to be realistic and not relate to some hypothetical value.
It might be easy to consider that, once a given solution has been selected, said solution providing a given effect, any further effect boils down to a mere bonus.
This appears only be possible in a “one-way-street” situation.
In any other situation as a “one-way-street” situation, a differentiated view has to be adopted, and IS acknowledged.
https://www.epo.org/en/boards-of-appeal/decisions/t211356eu1
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