CABINET CHAILLOT

Independent claim 1 of European patent 3 337 478 ("the patent") as granted related to liposomal irinotecan for use in a method of treating metastatic adenocarcinoma of the pancreas in a human patient who has not previously received chemotherapy to treat the metastatic adenocarcinoma of the pancreas, wherein the liposomal irinotecan is administered in combination with oxaliplatin, leucovorin, and 5-fluorouracil, the method comprising administering an antineoplastic therapy to the patient a total of once every two weeks, the liposomal irinotecan being irinotecan sucrose octasulfate salt liposome injection.
The priority application P1 presents a scheme for carrying out a dose escalation/de-escalation study involving the combined administration of liposomal irinotecan ("Nal-IRI"), oxaliplatin leucovorin and 5-fluorouracil, described as Part 1 of a clinical trial for the assessment of the safety, tolerability and efficacy of liposomal irinotecan in combination with other anticancer agents in patients with metastatic pancreatic adenocarcinoma who have not received prior chemotherapy. The described objectives of Part 1 are (i) the evaluation of the safety and tolerability of the combined administration of liposomal irinotecan, oxaliplatin leucovorin and 5-fluorouracil and (ii) the characterization of dose-limiting toxicities and the determination of the dose to be used in the subsequent stage of the study, Part 2, for the assessment of the efficacy of liposomal irinotecan containing regimens in first-line treatment of metastatic pancreatic cancer patients.
The priority application P1 does not disclose the outcome of this dose escalation/de-escalation study.
The patent and the application from which it derives present in Example 4 the results of the dose escalation/de-escalation study for which the priority application P1 only presents the outline. 
The Board observes that the dose combination as defined in claim 1 of the main request differs from the combination defined in claim 22 of priority application P1 at least in the lower dose for the liposomal irinotecan.
The information from Example 4 of the patent concerning the tolerability of the selected dose combination of claim 1 of the main request, as opposed to the intolerable and thus unsuitable alternative dose combinations defined in priority application P1, was not revealed in the priority application.
The Board does not recognise that this information is in any way provided by the mere outline for the dose escalation/de-escalation study in priority application P1, which the patent proprietor relied on as a pointer to the subject-matter of claim 1 of the main request with reference to the considerations in T 1261/21.
In T 1261/21, the competent Board considered that a "pointer" in an original disclosure is an implicit or explicit indication or hint towards a combination of features, which demonstrates that this combination of features does not represent an arbitrary combination of features only conceptually comprised, but is actually envisaged in the original disclosure. 
In the present case, priority application P1 provides with the outline for the dose escalation/de-escalation study only a conditional proposal for the use of a combination of 60 mg/m2 liposomal irinotecan and 60 mg/m**(2) oxaliplatin as part of a study still to be carried out. This conditional proposal cannot be considered to provide any pointer to the combination of 60 mg/m2 liposomal irinotecan and 60 mg/m2 oxaliplatin uniquely tolerable in first-line treatment of patients with metastatic pancreatic cancer as defined in claim 1 of the main request.
The Board rejects the patent proprietor's argument that the priority application P1 describes the same subject-matter as defined in claim 1 of the main request, which should in accordance with G 2/98 therefore benefit from the priority of P1, regardless of any additional technical effects, such as the results of the dose escalation/de-escalation study, which may have been described only in the subsequent application from which the patent is derived.
According to the established jurisprudence of the boards of appeal, attaining the claimed therapeutic effect is regarded as a functional technical feature of claims in the format of Article 54(5) EPC. Notably, the tolerability of the defined treatment is a prerequisite for the therapeutic efficacy. The tolerability of the dose combination as defined in claim 1 of the main request, as opposed to the intolerability of the alternative combinations with higher doses of claims 5 and 8 and the dose escalation/de-escalation scheme in priority application P1, is thus a functional technical feature of the subject-matter defined in claim 1 of the main request. This feature concerns information which is not directly and unambiguously derivable from priority application P1.
The Board further observes that according to G 2/98, the requirement for claiming priority of "the same invention", referred to in Article 87(1) EPC, means that priority of a previous application in respect of a claim in a European patent application in accordance with Article 88 EPC is to be acknowledged only if the skilled person can derive the subject-matter of the claim directly and unambiguously, using common general knowledge, from the previous application as a whole. The Enlarged Board of Appeal thus determined in G 2/98 that it is a condition for the compliance with the requirement of "the same invention" that the claimed subject-matter is directly and unambiguously derivable from the earlier application. However, the Enlarged Board did not conclude that the requirement of "the same invention" is necessarily satisfied if this condition is fulfilled, irrespective of any technical information associated with the claimed subject-matter, which is only described in the subsequent patent application. Notably, the established jurisprudence confirms the need for sufficient disclosure of the claimed invention in the priority document.
The Board therefore concludes that claim 1 of the main request does not enjoy the claimed priorities. 
The subject-matter of claim 1 of the main request differs from D3 in the replacement of the 180 mg/m**(2) conventional non-liposomal irinotecan by 60 mg/m**(2) liposomal irinotecan and the reduction of the oxaliplatin dosage from 85 mg/m**(2) to 60 mg/m**(2).
Starting from document D3, the objective technical problem may therefore be formulated, at least, as the provision of further first-line chemotherapy for metastatic adenocarcinoma of the pancreas which is effective and tolerable.
Neither document D3 nor the cited documents D29-D33 could therefore have provided the skilled person with any reasonable expectation that the dosage regimen as defined in claim 1 of the main request, which includes the administration of liposomal irinotecan, would be effective and tolerable.
Document D3 discusses only modifications to the FOLFIRINOX regimen involving dose reductions of conventional irinotecan, oxaliplatin and 5-fluorouracil to improve the tolerability of the original FOLFIRINOX regimen. Consequently, document D3 could not provide the skilled person with any reasonable expectation regarding effective and tolerable doses if the conventional irinotecan were to be replaced by liposomal irinotecan. 
The combination of irinotecan with oxaliplatin, 5-fluorouracil, and leucovorin in the FOLFIRINOX regimen was known to cause problematic side effects, which was why the modified FOLFIRINOX regimens discussed in document D3 were developed in the first place. 
Accordingly, the Board concludes that the subject-matter of claim 1 of the main request involves an inventive step.
The appeals are dismissed.