9.9. Chemical inventions
9.9.5 Predictable improvements resulting from amorphous forms as compared to crystalline forms
In T 777/08 (OJ 2011, 633) the claims in question related to a particular polymorph (form IV) of crystalline atorvastatin hydrate. The board found that the skilled person in the field of pharmaceutical drug development would have been aware of the fact that instances of polymorphism were commonplace in molecules of interest to the pharmaceutical industry, and would have known it to be advisable to screen for polymorphs early on in the drug development process. Moreover, he would be familiar with routine methods of screening. Consequently, 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 could not be regarded as involving an inventive step (see also T 41/17, T 1831/18). Further, when starting from the amorphous form of a pharmaceutically active compound as closest prior art, the skilled person would have a clear expectation that a crystalline form thereof would provide a solution to the problem of providing a product having improved filterability and drying characteristics. The arbitrary selection of a specific polymorph from a group of equally suitable candidates cannot be viewed as involving an inventive step.
In T 478/17 the board distinguished the case in hand from T 777/08 and T 41/07. The case in hand was not about the selection of any crystalline form but about the selection of one specific salt, namely eliglustat hemitartrate, in which at least 70% by weight of the salt was crystalline. The selection of this specific salt was not arbitrary. Rather, this salt had unexpected properties, namely an improved (reduced) hygroscopicity and an improved chemical stability. The board could not see any "one-way street situation" in view of D1, as claimed by the appellant. The skilled person starting from D1 would have had various choices in terms of stoichiometry and degree of crystallinity. It concluded that, having regard to the cited prior art, it would not have been obvious to the skilled person to isolate eliglustat hemitartrate in which at least 70% by weight of the salt was crystalline and arrive at the compound as defined in claim 19 of the main request.
In T 1684/16 the board distinguished the case in hand from T 777/08, in the light of which the appellant submitted that the solution in the case in hand was obvious since screening of polymorphs was a routine task as demonstrated in the prior art. Unlike T 777/08 the case in hand was not about the selection of any crystalline form but about the selection of one specific crystalline form (Form I of bosutinib monohydrate). The board found that the selection of this specific crystalline form was not arbitrary, but rather this form had unexpected properties, namely an improved stability when compared with the other crystalline forms in D1, D2 and D3. 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 obvious (see also T 1326/18).
- T 672/21
Abstract
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
Abstract
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.
- 2023 compilation “Abstracts of decisions”