T 0792/24 - Fewer side efffects as second medical use

Key points

•  This opposition appeal is about a second medical use claim. 
• Claim 1: "Plinabulin for use in reducing the neutropenia rate of a grade 3 or 4 neutropenia in a subject being administered with 75 mg/m² docetaxel, wherein the plinabulin is administered intravenously ". 
• The compound docetaxel is used for treating cancer and causes neutropenia (lack of white blood cells). It was found that plinabulin mitigates this side effect.
• "The Board considers that present claim 1 indeed defines a purpose limited product claim in the sense of Article 54(5) EPC. As stated in the impugned decision, the Board considers that the skilled person would understand the use of claim 1 as relating to the alleviation of neutropenia as a side effect of docetaxel treatment per se, i.e. in comparison to the treatment with docetaxel alone."
• "preventing the side effects induced by a therapy has a significant clinical value, and there is no justification for excluding this from being regarded as a form of prophylactic treatment." ... "the claimed use is prophylactic to the extent that it is administered before the side effect can be observed and reduces the occurrence thereof"
• "D5 is an abstract reporting the results of a phase II clinical study of docetaxel alone or in combination with plinabulin in patients with non-small cell lung cancer (NSCLC). "
• "the results section of D5 unambiguously discloses the reduction of incidence of docetaxel induced neutropenia in general when administering plinabulin"
• "The Board comes therefore to the conclusion that there is no direct and unambiguous disclosure in D5 that plinabulin indeed reduces the rate of neutropenia of specifically grade 3 and/or 4." (This is the first distinguishing feature)
• D5 also failed to teach a recited feature of the administration. " No particular effect has been brought forward for the administration time (feature (ii)). This feature was therefore arbitrarily chosen and cannot contribute to an inventive step."
• For the first distinguishing feature: "It follows that, while the provided data substantiate that plinabulin is indeed effective to reduce the rate of neutropenia grades 3 and 4 as well as grades 1 and 2, no greater reduction of grades 3 and/or 4 compared to grades 1 and 2 is achieved."
• The Board undertakes an enquiry into the technical effect of the distinguishing feature. However, the feature recites an effect (in my view), so this part of the reasoning is not entirely clear to me. 
• "starting from D5, the objective technical problem can only be formulated as the provision of a further use of plinabulin in docetaxel cancer therapy"
• " The [proprietor] argued that the skilled person would not have had any reasonable expectation of success of using plinabulin to reduce the rate of the clinically more relevant neutropenia grade 3 or 4, in particular to the extent shown in the patent and D16."
• The Board disagrees.
• "In view of the general disclosure of D5, the skilled person would anticipate that administering 30 mg/m**(2) of plinabulin would effectively mitigate the decrease in neutrophil counts in a subject in general, i.e. also in subjects susceptible to have decreased neutrophil counts corresponding to neutropenia grade 3 or 4. The appellant [respondent, I think, i.e. the proprietor] did moreover not provide any evidence that the effect of plinabulin in limiting the reduction of neutrophil count in a subject would be different depending on the level thereof. The skilled person would therefore expect that administering 30 mg/m**(2) of plinabulin would also be effective in reducing the rate of neutropenia grade 3 or 4."
• The subject-matter of claim 1 of the main request is thus not inventive when starting from D5 as the closest prior art.
  
  
• An auxiliary request specifying a dose of the plinabulin is found to be inventive. 
•  "The Board however agrees with the [proprietor], that the data in Figure 5 of the patent and in Table 1 of D16 show that the reduction of the occurrence of docetaxel induced neutropenia of grades 3 or 4 with 20 mg/m**(2) plinabulin is at least as good as with 30 mg/m**(2) plinabulin. That such an effect is achieved with the much reduced dose of 20 mg/m**(2) represents an improvement which is to be taken into account for the assessment of inventive step."
• " starting from D5, the skilled person would not have expected that the 20 mg/m**(2) plinabulin dose would be at least as effective as the significantly higher 30 mg/m**(2) dose in reducing docetaxel induced neutropenia rates of grades 3 and 4. While the skilled person would have expected some effect in reducing docetaxel induced neutropenia grades 3 or 4 also with 20 mg/m**(2) plinabulin, the extent of the reduction obtained compared to the 30 mg/m**(2) dose would not reasonably have been expected."

EPO 

The link to the decision can be found after the jump.

https://www.epo.org/en/boards-of-appeal/decisions/t240792eu1