T 0259/15 - Reasonable expectation of succes and clinical trials

Key points

• In this opposition appeal for a patent directed to a buprenorphine patch for use in treating pain with a dosing interval of at least 7 days, the buprenorphine patch as such was known. The main argument of patentee in support of the presence of inventive step was that the skilled person would not have started such clinical tests (with 7 day intervals) in the absence of a reasonable expectation of success.
• The Board notes that the concept of " reasonable expectation of succes" comes from the case law in the field of biotechnology. In connection with pharmaceutical inventions as claimed, the Board notes that " the concept of "reasonable expectation of success" does not apply when the implementation and the testing of an approach suggested by the prior art do not involve any particular technical difficulties. In such situations the skilled person would prefer to verify whether the potential solution that he has conceived works, rather than abandon the project because success is not certain." 
• The fact that human clinical trials are necessary does not change this in the abstract. For the clinical trials necessary in the present case, the Board notes that " the experimentation required to verify whether the patch of D1 can be used effectively for convenient pain therapy is relatively simple and does not involve major risks for the volunteers." 

EPO T 0259/15 -  link

Reasons for the Decision

MAIN REQUEST (PATENT AS GRANTED)

1. Inventive step

The invention underlying the patent in suit relates to a transdermal delivery device for the administration of buprenorphine, an opioid analgesic agent.

Thus, in the Board's opinion, the skilled person would have observed that the device of example 3 of D1 could be used for a dosing interval of at least 7 days by performing tests which simply require applying the patch of D1 and monitoring the level of buprenorphine in the blood.

1.3.4 In line with the appealed decision, the main argument of the respondent [patentee] in support of the presence of inventive step was that the skilled person would not have started such clinical tests in the absence of a reasonable expectation of success.
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1.3.5 According to the established case law of the boards of appeal, the general idea behind the concept of "reasonable expectation of success", which has been developed in particular in the field of biotechnology, is that in certain circumstances the person skilled in the art, on the basis of his common general knowledge or the teaching of the prior art, may be able to theoretically conceive a straightforward approach to solve a given technical problem. However, the practical implementation of that approach and/or the experimentation required to verify whether it does indeed work, may involve, for instance, overcoming technical difficulties ([CLBA 2016 I.D.7.1). In such circumstances, the skilled person would possibly avoid embarking on a troublesome experimentation if he did not have a reasonable expectation of success. On that basis, inventive step may be acknowledged even if the prior art contains a teaching to follow that approach.

However, the concept of "reasonable expectation of success" does not apply when the implementation and the testing of an approach suggested by the prior art do not involve any particular technical difficulties []. In such situations the skilled person would prefer to verify whether the potential solution that he has conceived works, rather than abandon the project because success is not certain.

The Board holds that this is the situation in the present case.

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1.3.7 The respondent has argued that a skilled person would not conduct tests on human subjects in the form of a try-and-see screening approach if he did not have a reasonable expectation of success.

In the Board's opinion this issue cannot be approached in abstract terms but it needs to be considered in relation to the circumstances of each specific case. It is agreed that trials involving experimentation in humans demand, in general terms, a cautious approach. Nevertheless, the technical difficulties involved in such experiments, the risks to the subjects and the ethical concerns are highly variable. In the present case, the experimentation required to verify whether the patch of D1 can be used effectively for convenient pain therapy is relatively simple and does not involve major risks for the volunteers. Furthermore, no relevant argument has been submitted regarding any possible ethical issue.

Thus, in the circumstances of the present case, the Board considers that the skilled person would test the device of D1 on human subjects despite the uncertainties as to the maximum duration of application.

1.3.8 The Board is aware of decisions T 293/07, T 847/07 and T 1545/08 in which a "try-and-see" approach was denied in circumstances in which experiments on human beings were involved.

The invention underlying case T 293/07 related to the use of erythropoietin (Epo) for producing a peripherally applied pharmaceutical for the treatment of stroke in humans. The deciding board came to the conclusion that the skilled person would not have adopted a "try-and-see" approach to verify whether Epo could indeed be used for the treatment of stroke. However, a key aspect of the Board's reasoning was the consideration that carrying out a study on humans, with the objective of developing therapeutic measures for the treatment of stroke, could not be regarded as a well-established routine activity. In addition, it was highly doubtful whether Epo could cross a compromised blood-brain barrier (see point 37 of the Reasons). The present case differs from that of decision T 293/07 at least because the effectiveness of the solution suggested in the prior art (i.e. the patch of D1), can be tested through routine experimentation.

In T 847/07, the Board held that it was "questionable whether the skilled person would adopt a "try and see" attitude at all in cases such as the present one where extensive in vivo animal and ultimately human testing would be necessary in order to determine whether or not a compound has a certain property." The case concerned formulations comprising highly purified recombinant coagulation factor VIII. The decision did not discuss which in vivo testing would have been required for determining the property of factor VIII. The Board notes that the present case concerns a clinically used active ingredient with therapeutic properties that are already known. The patch defined in claim 1 of the patent in suit is the same patch as that described in D1. For the reasons explained above, the Board considers that assessing whether this patch can solve the problem defined in point 1.2.1 above does not involve extensive testing on animals and humans.

In decision T 1545/07 the Board concluded that the skilled person was not in a "try-and-see" situation by referring to the principles discussed in T 293/07 and T 847/07 (see points 93 and 94 of the Reasons).

In the Board's view, the case law does not support the conclusion that the skilled person would systematically avoid a "try-and-see" approach whenever testing on human patients is involved, regardless of the specific circumstances of the case.

1.4 For the above reasons, the Board concludes that the subject-matter of claim 1 of the patent does not meet the requirements of Article 56 EPC.