9.9. Inventions dans le domaine de la chimie
9.9.5 Avantages prévisibles des formes cristallines sur les formes amorphes
Dans l'affaire T 777/08 (JO 2011, 633), les revendications en question portaient sur un polymorphe particulier (forme IV) d'hydrate d'atorvastatine sous une forme cristalline. La chambre a fait observer que l'homme du métier dans le domaine du développement des médicaments aurait su que le polymorphisme est un phénomène répandu dans les molécules intéressant l'industrie pharmaceutique, et qu'il était conseillé de rechercher les polymorphes à un stade précoce du développement d'un médicament. Il aurait par ailleurs été bien au courant des procédés habituels de criblage. Par conséquent, en l'absence de préjugé technique et en l'absence de propriété inattendue, le simple fait de fournir une forme cristalline d'un composé pharmaceutique actif connu ne pouvait être considéré comme impliquant une activité inventive (voir aussi T 41/17, T 1831/18). En outre, partant de la forme amorphe d'un composé pharmaceutique actif comme état de la technique le plus proche, l'homme du métier s'attendrait manifestement à ce qu'une forme cristalline de ce composé résolve le problème consistant à fournir un produit ayant des caractéristiques améliorées du point de vue de la filtrabilité et du séchage. Le choix arbitraire d'un polymorphe spécifique dans un groupe de candidats pouvant pareillement convenir ne peut être considéré comme impliquant une activité inventive.
Dans l'affaire T 478/17, la chambre a fait une distinction entre le cas d'espèce et les affaires T 777/08 et T 41/07. L'affaire en cause ne portait pas sur la sélection d'une forme cristalline, mais sur la sélection d'un sel spécifique, à savoir l'hémitartrate d'éliglustate, dont au moins 70% en poids du sel était cristallin. La sélection de ce sel spécifique n'était pas arbitraire. Au contraire, ce sel avait des propriétés inattendues, à savoir une meilleure hydroscopicité (réduite) et une meilleure stabilité chimique. La chambre n'a pas constaté de "situation à sens unique" au vu de D1, comme le prétendait le requérant. L'homme du métier, partant de D1, aurait eu diverses options sur le plan de la stoïchiométrie et du degré de cristallinité. Elle a conclu qu'eu égard à l'antériorité citée, il n'aurait pas été évident pour l'homme du métier d'isoler l'hémitartrate d'éliglustate où au moins 70% en poids du sel était cristallin pour arriver au composé défini dans la revendication 19 de la requête principale.
Dans la décision T 1684/16, la chambre a fait une distinction entre l'affaire en cause et l'affaire T 777/08, à la lumière de laquelle le requérant faisait valoir que la solution dans le cas d'espèce était évidente puisque la détection de polymorphes était une tâche de routine, comme le démontrait l'état de la technique. Contrairement à la décision T 777/08, l'affaire en cause ne portait pas sur la sélection d'une forme cristalline quelconque, mais sur la sélection d'une forme cristalline spécifique (forme I du monohydrate de bosutinib). La chambre a estimé que la sélection de cette forme cristalline spécifique n'était pas arbitraire, mais au contraire que cette forme avait des propriétés inattendues, à savoir une meilleure stabilité que les autres formes cristallines de D1, D2 et D3. Le fait que l'état de la technique enseignait à l'homme du métier d'étudier les polymorphes afin d'isoler la forme cristalline ayant les propriétés les plus souhaitables n'était pas en soi nécessairement suffisant pour considérer comme évidente une forme polymorphique spécifique présentant certaines propriétés souhaitées (voir aussi T 1326/18).
- T 672/21
Résumé
In T 672/21 the appellant (opponent 2) had provided submissions on obviousness based on the assumption that any improved property was absent, so that the objective technical problem was the mere provision of a further polymorph. It relied in this respect on decision T 777/08.
The board, however, defined the objective technical problem in a more ambitious way. For this reason alone, the board held the appellant's submission on obviousness had to fail. The objective technical problem as defined by the board was the provision of a crystalline form of selexipag with a balance of beneficial properties, namely an intermediate stability and at the same time improved industrial processability and improved purity in terms of reduced amounts of residual solvents and residual impurities.
The board noted that according to T 777/08 "in the absence of any technical prejudice and in the absence of any unexpected property, the mere provision of a crystalline form of a known pharmaceutically active compound cannot be regarded as involving an inventive step" (headnote 1) and "the arbitrary selection of a specific polymorph from a group of equally suitable candidates cannot be viewed as involving an inventive step" (headnote 2). However, in the present case there was no absence of unexpected properties and the selection was not arbitrary, since the selected Form I had a balance of beneficial properties in terms of stability, industrial processability and purity in comparison with Form II and Form III. There was nothing in the prior art which pointed to the fact that the claimed Form I would have this balance of beneficial properties and they were thus not expected. The present case thus differed from the situation at issue in decision T 777/08.
The board also distinguished T 41/17, relied upon by the appellant for its further argument that the alleged stability of Form I was not a surprising technical effect because the skilled person always looked for the most thermodynamically stable polymorph in order to avoid the problem of interconversion within the dosage form. In T 41/17 it was concluded that the skilled person would have performed screening of the different polymorphs disclosed in the closest prior art, which could exist in order to isolate and identify the most thermodynamically stable form thereof. By doing so, the skilled person would have arrived at the claimed polymorph, which was the most thermodynamically stable form and which, for this reason, was expected not to convert to other forms under mechanical stress. However, unlike in T 41/17, in the present case the stability was not the only property, but rather part of a balance of beneficial properties. Hence, even if the stability of Form I (which is at an intermediate level) had been expected, the same would not apply to the balance of various beneficial properties.
The board also noted that the mere fact that the skilled person would have carried out routine screening for polymorphs as such did not render the claimed Form I obvious. As set out in T 1684/16, the fact that the skilled person was taught in the prior art to investigate polymorphs in order to isolate the crystalline form having the most desirable properties was in itself not necessarily sufficient to consider a specific polymorphic form having a certain desired property or, as in the present case, balance of properties obvious.
Thus the subject-matter of claim 1 of the main request, and by the same token of claims 2 to 13, which included the subject-matter of claim 1, involved an inventive step in view of D10 as the closest prior art.
- T 1994/22
Résumé
In T 1994/22 the appeal lay from the opposition division's decision to reject the oppositions filed against the European patent. Claim 1 of the main request related to Form II of selexipag, an agonist of the prostaglandin receptor PGI2. The appellant (opponent) objected to the inventive step of the subject-matter of claim 1 of the main request in view of D10 as the closest prior art. The distinguishing feature of claim 1 of the main request in view of example 84 of D10 was the crystalline form, namely Form II of selexipag.
In view of the available experimental results, the board concluded that Form II exhibited the best stability but only intermediate industrial processability, intermediate residual solvent content and an intermediate amount of residual impurities. Contrary to the situation in T 672/21 there was no balance of beneficial properties for Form II according to the main request. The objective technical problem could therefore only be considered that of providing a crystalline form of selexipag which is the best for one property, but only intermediate for all other tested properties.
The respondent submitted that, in line with T 1684/16, there was no reasonable expectation based on the prior art that a suggested investigation in terms of polymorph screening would be successful in finding a form of selexipag having a balance of beneficial properties in terms of stability, industrial processability, solvent content and purity.
The board disagreed. Based on T 1684/16 and in line with T 777/08, an inventive step can be acknowledged if the claimed polymorph has an unexpected property meaning that its selection is non-arbitrary. In the present case, the board saw nothing unexpected in finding a polymorph that was optimum for one property but only intermediate for several other properties. If this were unexpected and thus gave rise to an inventive step being acknowledged, an applicant or proprietor having identified a new polymorph would simply need to carry out tests for long enough to find one single property for which the identified polymorph performed best. This might result in a situation in which almost any polymorph in the world becomes inventive, which would render Art. 56 EPC meaningless.
Therefore, the selection of Form II is an arbitrary selection from the host of alternatives covered by the closest prior art. Such an arbitrary selection without any unexpected balance of properties being produced cannot contribute to inventive step. The subject-matter of claim 1 of the main request therefore does not involve an inventive step in view of D10 as the closest prior art.
- Compilation 2023 “Abstracts of decisions”