Wanneer anticipeert voorafgaand gebruik op een uitvinding? Een verhaal van twee polymorfen

In the decision under appeal, the OD ruled that the public prior use of Xifaxan tablets was not novelty destroying even though a batch of Xifaxan tablets (batch 13012) purchased prior to the priority date had been shown in document D7 to comprise polymorph forms alpha and delta of rifaximin in the ratio and total amount as defined in claim 1. The acknowledgement of novelty was based on OD’s evaluation that it had not been demonstrated that the batch 13012 could be analysed to comprise the relevant amount of filler as described in claim 1. In the assessment of inventive step, the underlying problem was defined as a provision of a formulation having a decreased bioavailability, while at the time of filing the delta form of rifaximin was known to be considerably more bioavailable than the alpha form. The Proprietor (P) argued that for solving this problem, the batch 13012 should not have been used as the closest prior art as it was defective for the reason that the presence of the rifaximin form delta in the tables was unintended and caused by time-dependent partial conversion of rifaximin form alpha. The OD appeared to agree with this reasoning, and considered that it was not obvious for the skilled person to add the delta form to the alpha form to provide a rifaximin combination that had low bioavailability, since this addition would be expected to increase the bioavailibity of the rifaximin combination. 

The O did not agree and argued that the claimed composition had had been publicly available before the priority date through sales of the batch 13012 tablets that comprised rifaximin in the polymorphic forms alpha and delta in the ratio defined by claim 1 and that the instructions for the preparation of Xifaxan (in document D44) indicated that the amount of filler needed to make a Xifaxan tablet was the same in the tables of the batch as defined in claim 1.

The Board of Appeal (the Board) agreed with the O, the decision under appeal was set aside, and the patent was revoked.

Background

In the decision under appeal, the decision of the OD to maintain the European Patent no. 3294270 was appealed by the O. The claims as granted related to a pharmaceutical composition comprising rifaximin in polymorphic form alpha and polymorphic form delta in a molar ratio of 9:1 to 1:9 and a method for preparing a tablet comprising said composition. In addition, claim 1 stated that the pharmaceutical composition comprised 45 wt% to 75 wt% of form alpha and delta, and 10 wt% to 45 wt% of filler. Rifaximin is a non-absorbable antibiotic used to treat diarrhea. Before the filing date of EP3294270, it was known that the form delta gave rise to higher absorption of rifaximin, whilst the form alpha had lower absorption. Two oppositions were filed against the grant of the patent on the grounds that its subject-matter lacked novelty and inventive step and that the claimed invention was not sufficiently disclosed.

The OD arrived at the following conclusions:

1. The subject-matter of the main request was new over the prior art, including the public prior use of Xifaxan (rifaximin) tablets. A batch of Xifaxan tablets (batch 13012) purchased prior to the priority date had been shown in document D7 to comprise the polymorph forms alpha and delta of rifaximin in the ratio and total amount as defined in claim 1. However, the OD considered that it could not be demonstrated that the batch 13012 comprised the relevant amount of filler as described in claim 1. 
2. The delta form of rifaximin was known before the priority date to be more bioavailable than the alpha form. Therefore, for providing a rifaximin combination that had low bioavailability, in accordance with the purpose of EP3294270, the OD deemed it not obvious for the skilled person to add the more bioavailable delta form to the less bioavailable form alpha since this would be expected to increase the bioavailability of the resulting combination above the bioavailability of the alpha form alone.

The Appeal

The decision of the OD to maintain EP3294270 was appealed by the O, who argued that Xifaxan had been publicly available before the priority date as tablets of batch 13012 that comprised rifaximin in the polymorphic forms alpha and delta in the ratio defined by claim 1. Moreover, the O argued that document D44 containing instructions for the preparation of Xifaxan, indicated the amount of filler needed to make a Xifaxan tablet as defined in claim 1. The O also referred to documents A55-A57 teaching techniques for analysing amount of filler materials (albeit from textile industry)and concluded that the skilled person would face no undue burden to analyse the content of Xifaxan batch 13012 and to find that it contained rifaximin forms alpha and delta and an amount of filler as define in claim 1 

In contrast, the P stated that the document D44 was not publicly available and, furthermore, that it referenced a different Xifaxan batch (no. 15384), for which reasons, it could not be used to anticipate the composition and/or the amount of filler in Xifaxan batch 13012 without undue burden. To support their position, the P cited G1/92 which states that the composition and internal structure of a product is state of the art, when the product as such is available to the public and can be analysed and reproduced by the skilled person without undue burden. Lastly, the P objected to the O’s reliance on documents A55-A57 for the reason that they did not belong to the field of galenics, and concluded that they could not therefore be relied upon for determining the amount of filler in the Xifaxan tablets.

In the problem-solution approach, the P argued that the Xifaxan batch 13012 was defective for the reason that it was not intended to contain the rifaximin form delta, which form only accumulated in the tablet due to storage as a result of partial conversion of rifaximin form alpha. For this reason, P argued that the prior use was not a suitable starting point for the assessment of inventive step. They further argued that even if the skilled person would consider starting from the Xifaxan batch 13012, the provision of rifaximin form alpha and form delta before the compression into tablets was advantageous over the time dependent process in which the Xifaxan batch 13012 was generated. 

Decision of the Board of Appeal

The Board ruled that document D44 should have been admitted, because even though it was not publicly available at the priority date and even though it concerned a method in which a different Xifaxan batch (no. 15384) was produced, the production process as a whole was publicly available before the priority date and therefore the document was representative for all Xifaxan tablets available on the market. The Board also admitted documents A55-A57 because even though they did not belong in the field of galenics, the described therein processes of determining the amount of filler material were seen as applicable to experimentally determine the filler amount in Xifaxan batch 13012. In addition, the Board found the P’s reliance on G1/92 not convincing, because the skilled person in the field of galenics could easily retrieve the documents A55-A57 and because their application to determining the amount of filler in Xifaxan tablets had not been demonstrated to involve undue burden.

The finding under appeal that Xifaxan batch 13012 contained rifaximin forms alpha and delta in the ratios defined in claim 1 was not in dispute, therefore, the assessment of novelty exclusively concerned the filler range of 10-45 wt%. Document D44 disclosed that Xifaxan 13012 did indeed comprise an amount of filler as defined in claim 1.

The Board agreed that the Xifaxan tablets of batch 13012 represented an approved market product. Document D8 described Xifaxan to comprise rifaximin form alpha with a shelf life of 3 years (expiring in April 2017). Document D15 reported that rifaximin form alpha would not convert to other polymorphic forms during storage, however, document D7 established that the tablets of Xifaxan batch 13012 on 17 December 2015, comprised both polymorphic forms alpha and delta as defined in claim 1. Therefore, these tablets had partially converted to form delta, even though the tablets had not expired then. Contrary to the finding by the OD, the Board considered that the prior use of the Xifaxan batch 13012 was a realistic starting point to assess inventive step.

The subject-matter of claim 1 differed from the prior use of Xifaxan batch 13012 because it provided rifaximin in the two forms alpha and delta prior to their compression into a tablet, instead involving the time dependent partial conversion of rifaximin form alpha to form delta. The objective technical problem was therefore defined as a provision of a more convenient method for the production of the tablets. Faced with this problem, the Board considered that the skilled person would find it obvious to mix the two forms alpha and delta prior to their compression to avoid the inconvenience of waiting associated with the time dependent conversion. 

Accordingly, the Board concluded that the subject matter of claim 1 was not novel and lacked an inventive step. Hence, the decision under appeal aside and revoked the patent.