Key points
- "claim 1 is directed to second medical uses of a crystalline solvate of [the compound] dapagliflozin with water and (S)-propylene glycol which comprises these three constituents in equimolar amounts (1:1:1 molar ratio) [; for use in treating a disorder selected from diabetes, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, delayed wound healing, insulin resistance, hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, hyperlipidemia, dyslipidemia, obesity, hypertriglyceridemia, Syndrome X, diabetic complications, atherosclerosis or hypertension, or for use in increasing high density lipoprotein levels in a mammal] "
- "In accordance with claim 1, this crystalline solvate is referred to as form SC-3 below. "
- D1 is the CPA.
- "D1 describes the stepwise synthesis of dapagliflozin."
- "The appellant put forward inventive-step objections starting from both forms of dapagliflozin disclosed in D1, i.e. amorphous dapagliflozin and the crystalline complex of dapagliflozin with L-phenylalanine."
- "It can be concluded that form SC-3 has a higher stability, i.e. a lower hygroscopicity, than amorphous dapagliflozin."
- " the objective technical problem can be considered that of providing a pharmaceutical composition comprising a crystalline form of dapagliflozin which is more stable, i.e. less hygroscopic."
- "As regards obviousness, the appellant pointed to D4."
- "D4 relates to PG solvates of APIs and states, quite generally, (on page 4, paragraph 4; page 3, paragraphs 2 and 3) that: (a) the formation of PG solvates makes it possible to obtain crystalline compounds from APIs [active pharmaceutical ingredient] which are difficult to crystallise (b) API PG solvates are more stable and less hygroscopic than the corresponding APIs"
- The Board: "the skilled person, in order to take the teaching of D4 into account, would also have had to have a reasonable expectation of success, i.e. a reasonable expectation that this teaching would solve the objective technical problem. However, this is not the case, as set out in the following."
- "On pages 45 to 296, D4 gives a very long list of APIs whose PG solvates are said to be covered by the invention in D4. Among these compounds is T-1095 (page 267, entry 4), i.e. a compound which is structurally similar to dapagliflozin. In view of points 12.1 (a) and (b) above, this list amounts to D4 pretending to have found an almost universal solution to the problem of providing a crystalline form of an API and in particular to the problem of providing a form of an API which is less hygroscopic. This alone would not have given the skilled person a reasonable expectation of success, i.e. a reasonable expectation of obtaining a crystalline form of the compound dapagliflozin which is less hygroscopic than amorphous dapagliflozin. The reason is that, as agreed by both parties at the oral proceedings, the formation of crystalline forms and their properties such as hygroscopicity is highly unpredictable. So while the board acknowledges that D4 demonstrates that four structurally very different and unrelated APIs can be transformed into crystalline PG solvates, D4 lacks experimental data showing that an API PG solvate is less hygroscopic than the API itself."
- "Furthermore, the examples in D4 cast legitimate doubt on whether the effect of a lower hygroscopicity is actually achieved as universally as suggested. "[follows an analysis of the examples]
- " the skilled person would have considered the effect suggested by D4, namely the universal decrease in hygroscopicity, to be a mere allegation. Given the generally recognised high unpredictability of properties of crystalline forms (see above), the skilled person would not have had a reasonable expectation of obtaining a less hygroscopic form of dapagliflozin."
- " In summary, the subject-matter of claim 1 involves an inventive step over amorphous dapagliflozin as disclosed in D1 in combination with D4 because the skilled person, considering the teaching of D4, would not have had a reasonable expectation of obtaining a form of dapagliflozin which is less hygroscopic than amorphous dapagliflozin."
- The patent is maintained in amended form.
- I use the term 'plausibility' in the blog post title as a generic catchword. The Board does not use it. Possibly, still, the 'technical teaching' requirement of G 2/21, or the credible requirement for second medical use claims in the same decision, can also be operationalized along the lines of this decision: would the skilled person have a reasonable expectation of success on the basis of the application as filed and using common general knowledge at the relevant date?
EPO
The link to the decision is provided after the jump, as well as (an extract of) the text of the decision.
source http://justpatentlaw.blogspot.com/2023/05/t-021520-dapagliflozin-plausibility.html
