T 0867/13 - Plausibility, or derived from the patent

Key points

• This opposition appeal clearly was a good fight about a pharmaceutical patent. 
• The CPA D67 "reports that a phase II clinical trial in infantile Pompe patients with recombinant human acid alpha-glucosidase (rhGAA) produced in the milk of transgenic rabbits "has finalised with positive results"" 
•  The subject-matter of claim 1 differs from the disclosure of document D67 in that the human rhGAA used for the treatment of GSD-II is produced in Chinese hamster ovary (CHO) cells.
• The Board concludes that this was an obvious alternative, no improvement being shown in the patent. Some post-published data allegedly showing the improvement is disregarded because " no improvement over the treatment known from document D67 is derivable from the patent". (the opponent had indeed used the term 'plausibility' on this point).
• The Board rejects the argument that the skilled person would not look for further improvements after the success of D67. "it is established case law that it is the normal task of a skilled person working in a certain field not to remain inactive but to seek alternatives, to be constantly occupied with the elimination of deficiencies, with the overcoming of drawbacks and with the achievement of improvements of known devices and/or products " 
• The Board concludes that the use of CHO cells was obvious in view of D73f which teaches  that "although no efficacy data is yet available for the two ongoing clinical trials of rhGAA replacement therapy, "pre-clinical data suggest that enzyme replacement therapy will be successful" (one of these clinical trials using CHO cells, as D73f mentions).

EPO T 0867/13 -  link

Thus, no improvement over the treatment known from document D67 can be derived from paragraphs [0008], [0009] and [0043] of the patent.

8.3 Paragraph [0013] of the patent discloses that CHO-cell-derived rhGAA is preferred and further that it "is assumed that the glycosylation differs from that of GAA that is produced in transgenic mouse and rabbit milk (...)". In the board's judgement, it does not follow directly and unambiguously from this statement that the assumed difference in glycosylation leads to an improved treatment if CHO-cell-derived rhGAA is used rather than transgenic rabbit-milk-produced rhGAA.

8.4 Documents D60a and D103 - both published after the priority date - relate to effects seen in Pompe mice (document D60a; see left-hand column, second paragraph under the heading "Results", and right-hand column, first paragraph under the heading "Conclusions") and GAA knockout mice (see document D103, page 452, right-hand column, fourth and fifth paragraphs, and Figures 3 and 4). However, these results obtained in mice do not establish that CHO-cell-derived rhGAA is better than rabbit-milk-derived rhGAA at effecting glycogen clearance in humans. Moreover, the alleged effect - an improved treatment for GSD-II - could only be taken into account when determining the problem underlying the invention for the purpose of assessing inventive step, if it can be deduced by the skilled person from the patent considered in relation to the closest prior art (see also Case Law of the Boards of Appeal, 8th edition 2016, I.D.4.4.2 and I.D.4.4.6). In the present case, no improvement over the treatment known from document D67 is derivable from the patent (see points 8.1 to 8.3).

8.5 In the board's judgement, the subject-matter of claim 1 can thus not be considered to provide an improved treatment over the treatment disclosed in document D67.

9. Therefore, starting from the closest prior art document, D67, the objective technical problem to be solved is the same as formulated by the opposition division, namely the provision of an alternative treatment for human GSD-II or its associated cardiomyopathy (see decision under appeal, Reasons, point 3.5.12).

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Obviousness

10. The opposition division held that the claimed solution was obvious in light of the teachings of the available prior art documents, in particular document D73f (see decision under appeal, Reasons, points 3.5.18 to 3.5.30).

11. To determine whether the claimed invention, starting from the closest prior art and the objective technical problem, would have been obvious to the skilled person, the boards of appeal apply the "could-would approach". When considering whether or not claimed subject-matter constitutes an obvious solution to an objective technical problem, the question to be answered is whether or not the skilled person, in the expectation of solving the problem, would have modified the teaching in the closest prior art document in the light of other teachings in the prior art so as to arrive at the claimed invention (see Case Law of the Boards of Appeal, 8th edition 2016, I.D.5.). Accordingly, what the skilled person, starting from the closest prior art and faced with the objective technical problem, would or would not do depends not solely on the disclosure of the closest prior art document, but also on the state of the art in the relevant technical field (see also decision T 939/92, OJ EPO 1996, 309, Reasons, point 2.4.3).

Furthermore, in accordance with the case law of the boards of appeal, a course of action can be considered obvious within the meaning of Article 56 EPC if the skilled person would have carried it out in expectation of some improvement or advantage. In other words, obviousness is not only present when the results are clearly predictable but also when there is a reasonable expectation of success (see Case Law of the Boards of Appeal, 8th edition 2016, I.D.7.1).

12. The appellant submitted that, in view of the disclosure of document D67, which reported a successful treatment for a lethal disease for the first time, the skilled person was not motivated to look for an alternative treatment, i.e. the skilled would not have been motivated to modify the treatment disclosed in document D67.

13. However, it is established case law that it is the normal task of a skilled person working in a certain field not to remain inactive but to seek alternatives, to be constantly occupied with the elimination of deficiencies, with the overcoming of drawbacks and with the achievement of improvements of known devices and/or products (cf. inter alia, decisions T 247/11 of 24 February 2017; Reasons, point 25; T 1102/00 of 1 June 2004, Reasons, point 14; T 455/91, OJ EPO 1995, 684, Reasons, point 5.1.3.2). In the board's view, it is not conceivable that in the case of the treatment of a potentially lethal disease the motivation of the skilled person to search for further - or alternative - treatments stops, solely because one treatment exists - even if it is perceived as satisfactory at the time. Indeed, when document D67 was published, alternative treatments were already pursued in clinical trials (see below, point 14) and there is no evidence that these were stopped in view of the success reported in document D67.

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Furthermore document D73f reports that "the observation that rhGAA improves muscle strength (in the quail model) and histopathology and biochemical parameters (in both quail and mouse models) suggests that rhGAA is a promising enzyme replacement therapy for human GSD-II. Based on these results, two clinical trials using different enzyme sources have recently been initiated to investigate the potential of rhGAA to safely treat GSD-II patients. A phase II study is being conducted in the Netherlands (...) using GAA purified from the milk of transgenic rabbits and a Phase I/II study using rhGAA purified from CHO cells is being conducted in the USA (...)" (see page 247, right-hand column, third paragraph).

Document D73f adds that, although no efficacy data is yet available for the two ongoing clinical trials of rhGAA replacement therapy, "pre-clinical data suggest that enzyme replacement therapy will be successful" (see page 249, right-hand column, third paragraph).

14.1 The board considers that the evidential value of document D73f is not lessened because it is authored by the inventor of the patent, as it is co-authored by another expert in Pompe disease who is not an inventor on the patent. Moreover, document D73f is a scientific article, published in an academic journal. In the board's opinion, it is therefore not conceivable that the authors of document D73f were not objective in their assessment of the pre-clinical data in the primary literature they reviewed merely because one of the authors was also an inventor on what, at the time, was a patent application.

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17. The board concludes that the prior art motivated the skilled person to use CHO-cell-derived rhGAA for the manufacture of a medicament for the treatment of human GSD-II or its associated cardiomyopathy and that, based on a scientific evaluation of the facts available (see decision T 207/94, OJ EPO 1999, 273, Reasons, point 31), the skilled person also had a reasonable expectation of success. Therefore, the subject-matter of claim 1 is considered to be obvious and thus to fail to meet the requirements of Article 56 EPC.

Order

For these reasons it is decided that:

The appeal is dismissed.