T 0317/20 - The subgroup attack

Key points

• "The requirements of Article 83 EPC of a medical use claim are complied with if, at the relevant date of the application, the skilled person is able to prepare the claimed product, ... and if the application discloses that the claimed product is suitable for the claimed therapeutic application, ... unless this is already known to the skilled person at the priority date" 
• The key part here is likely " discloses that the claimed product is suitable" - does "discloses"  means that merely a verbal statement is enough? (as it is for Article 123(2) - though see T 2842/18 of the same Board 3.3.04).
• The opponent argues that the compound does not work, i.e. does not provide the medical effect specified in the claim, for a sub-group of patients. The patent does not include data for that sub-group of patients.
• " In the absence of experimental proof of treatment of these patients, comprehensible and plausible arguments can substantiate serious doubts as to whether the skilled person could carry out the invention as claimed, and evidence in the form of experimental data is not necessarily required" 
• " The opponent and the intervener argued that the improvement of physical function observed in Example 9 of the patent was only due to the relief of pain caused by the anti-NGF antagonist antibody. Indeed, Example 9 of the patent relates to a study on the analgesic effects of anti-NGF antibody E3 in patients with moderate to severe pain from osteoarthritis of the knee"
• " The board notes that it was not disputed between the parties that, even if rare, osteoarthritis patients with impaired physical function who did not suffer from pain existed", those patients are the sub-group invoked by the opponent.
• " In view of this interrelation of use-related pain and physical function as assessed by the WOMAC questionnaire, a lower score in the pain-related domain of the WOMAC questionnaire is expected to also result in a lower score for difficulties in physical activities, as was reported in Example 9 of the patent. However, Example 9 of the patent cannot demonstrate the suitability of an anti-NGF antagonist antibody for the improvement of physical function in osteoarthritis patients who do not suffer from pain." 
• " the proprietor submitted that an occasional failure in the treatment of a small patient subgroup did not result in an insufficiency of disclosure. [] However, the disclosure of a patent must allow an invention to be performed in the whole range claimed (see also Case Law of the Boards of Appeal of the European Patent Office, 9th edition, 2019, II.C.5.4). The improvement of physical function of an osteoarthritis patient is a limiting purpose-feature of the claim, and therefore the invention as defined in the claim is only sufficiently disclosed if this improvement is achieved for all osteoarthritis patients." 
• I suppose that this statement when quoted out of context could kill a lot of pharma patents. It should be understood in the more nuanced way as set out by the Board in the next paragraph. 
• " Therefore, the failure of treating an entire patient subgroup, albeit small, which is distinguished from the patient group as a whole by its pathological status, is not equivalent to an occasional failure in treating some patients within the patient group. The size of the patient subgroup is not decisive for the assessment of sufficiency of disclosure of the invention as defined in the claim. This argument [of patentee] therefore does not persuade the board, either." 
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• " in view of the above considerations, it is concluded that the opponent's arguments substantiate serious doubt that the skilled person could carry out the invention as claimed. Neither the teaching in the patent nor the skilled person's common general knowledge at the filing date of the patent discloses the suitability of an anti-NGF antagonist antibody to improve the physical function of an osteoarthritis patient in the absence and independent of pain relief.  Therefore, the invention as defined in claim 1 of the main request is not disclosed in the application such as to meet the requirements of Article 83 EPC." 
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• Turning to the auxiliary requests: " the board could not identify exceptional circumstances which would justify the amendment of the proprietor's case by filing auxiliary requests 11, 17, 18 and 19 after the board had summoned the parties to oral proceedings and issued its preliminary opinion. The board thus decided not to admit auxiliary requests 11, 17, 18 and 19 into the appeal proceedings pursuant to Article 13(2) RPBA 2020." 
• The patent is revoked.

EPO 

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

https://www.epo.org/law-practice/case-law-appeals/recent/t200317eu1.html

Main request

Sufficiency of disclosure (Article 83 EPC) - claim 1

11. The requirements of Article 83 EPC of a medical use claim are complied with if, at the relevant date of the application, the skilled person is able to prepare the claimed product, here an anti-nerve growth factor (NGF) antagonist antibody, and if the application discloses that the claimed product is suitable for the claimed therapeutic application, here for improving physical function in an individual having osteoarthritis, unless this is already known to the skilled person at the priority date (see Case Law of the Boards of Appeal of the European Patent Office, 9th edition, 2019, II.C.7.2., in particular decision T 609/02 discussed there).

12. In the case at hand, the opponent and the intervener considered that the second requirement was not met, i.e. an anti-NGF antagonist antibody was not suitable for the improvement of physical function in osteoarthritis patients who did not experience pain. The proprietor argued that the invention as claimed was supported by Example 9 and Figure 27 of the patent. The burden of proof was therefore on the opponent and the intervener to substantiate their allegation by verifiable facts or evidence, which they had failed to do.

13. The board notes that it was not disputed between the parties that, even if rare, osteoarthritis patients with impaired physical function who did not suffer from pain existed (see, for example, Figure 5.1 of document D39a). It was also not disputed that all osteoarthritis patients treated with an anti-NGF antagonistic antibody in the clinical study disclosed in Example 9 of the patent suffered from pain. The patent therefore does not contain experimental proof that physical function could be improved in osteoarthritis patients who do not suffer from pain.

14. In the absence of experimental proof of treatment of these patients, comprehensible and plausible arguments can substantiate serious doubts as to whether the skilled person could carry out the invention as claimed, and evidence in the form of experimental data is not necessarily required (see, for example, decision T 347/15, Reasons 2.2.2).

15. The opponent and the intervener argued that the improvement of physical function observed in Example 9 of the patent was only due to the relief of pain caused by the anti-NGF antagonist antibody. Indeed, Example 9 of the patent relates to a study on the analgesic effects of anti-NGF antibody E3 in patients with moderate to severe pain from osteoarthritis of the knee (see the title of Example 9 on page 74, lines 6 to 7 and paragraph [0426] of the patent). The Visual Analogue Scale (VAS) and the Western Ontario and MacMaster Universities osteoarthritis (WOMAC) questionnaire were employed to assess arthritis pain after single intravenous doses of anti-NGF antibody E3 (paragraphs [0429] and [0431]).

16. Also, effects on physical function were assessed with the WOMAC questionnaire, which contains separate questions for the three domains of pain, physical function and stiffness (see paragraph [0431] of the patent and documents D5 and D6). Single administration of the anti-NGF antibody reduced pain and improved physical function and stiffness (see paragraph [0436] and Figure 27 of the patent).

17. However, all osteoarthritis patients treated in the study of Example 9 suffered from pain (see points 13. and 15. above), and the observed effects on physical activity were solely based on the WOMAC questionnaire. Four of the five questions in the pain-related domain of the WOMAC questionnaire relate to use-related pain. Difficulties in, inter alia, doing the same physical activities affected by pain are again assessed in the physical-function domain of the WOMAC questionnaire (walking on flat surfaces, going up and down stairs, sitting, lying, and standing upright; see documents D5 and D6 (Table I)).

18. In view of this interrelation of use-related pain and physical function as assessed by the WOMAC questionnaire, a lower score in the pain-related domain of the WOMAC questionnaire is expected to also result in a lower score for difficulties in physical activities, as was reported in Example 9 of the patent. However, Example 9 of the patent cannot demonstrate the suitability of an anti-NGF antagonist antibody for the improvement of physical function in osteoarthritis patients who do not suffer from pain.

19. The suitability of an anti-NGF antagonist antibody for improving physical function in these patients could also be demonstrated by the common general knowledge at the filing date of the patent (see point 11. above).

20. In this context, the proprietor submitted, with reference to documents D19 and D26, that some physical activities in osteoarthritis might be affected and could therefore be treated independently of pain. However, document D19 only discusses that functional disability was an "important additional primary endpoint for symptom modifying drugs" (see page 2/6, section II a)) but does not refer to an anti-NGF antagonist antibody. Document D26 likewise merely discusses that drugs could have an effect on stiffness and physical function without affecting pain but does not disclose that an anti-NGF antagonist antibody would or could have this effect (see section (viii) on page 4). Hence, documents D19 and D26 do not provide the skilled person with the knowledge of whether an anti-NGF antagonist antibody was suitable for a pain-independent improvement of physical activity.

21. The proprietor also argued that, as evident from the background section of the invention on page 3 of the patent, NGF had various other functions unrelated to pain which could also account for its effect on physical function. However, the proprietor did not point to any specific function of NGF, nor could the board identify an NGF function in the cited passages of the patent, that would support the suitability of an anti-NGF antagonist antibody for improving physical function and that was independent of its known activity as an analgesic. This argument therefore also fails to persuade the board.

22. In a further line of argument, the proprietor submitted that an occasional failure in the treatment of a small patient subgroup did not result in an insufficiency of disclosure.

23. However, the disclosure of a patent must allow an invention to be performed in the whole range claimed (see also Case Law of the Boards of Appeal of the European Patent Office, 9th edition, 2019, II.C.5.4). The improvement of physical function of an osteoarthritis patient is a limiting purpose-feature of the claim, and therefore the invention as defined in the claim is only sufficiently disclosed if this improvement is achieved for all osteoarthritis patients.

24. Therefore, the failure of treating an entire patient subgroup, albeit small, which is distinguished from the patient group as a whole by its pathological status, is not equivalent to an occasional failure in treating some patients within the patient group. The size of the patient subgroup is not decisive for the assessment of sufficiency of disclosure of the invention as defined in the claim. This argument therefore does not persuade the board, either.

25. The proprietor further requested the board to consider its submissions in the procedure before the opposition division (documents D35 and D36). Apart from the obligation of the proprietor to present its complete case in appeal (Article 12(3) RPBA 2020), these submissions do not add any relevant argument to the above assessment.

26. Consequently, in view of the above considerations, it is concluded that the opponent's arguments substantiate serious doubt that the skilled person could carry out the invention as claimed. Neither the teaching in the patent nor the skilled person's common general knowledge at the filing date of the patent discloses the suitability of an anti-NGF antagonist antibody to improve the physical function of an osteoarthritis patient in the absence and independent of pain relief.

27. Therefore, the invention as defined in claim 1 of the main request is not disclosed in the application such as to meet the requirements of Article 83 EPC.