The patent relates to a “Pharmaceutical composition comprising ivabradine hydrochloride polymorph IV”
Brief outline of the case
Claim 1 as granted was lacking IS over D2=WO 2013/064307. This document was the first document cited in the ESR and was qualified as X,D,Y. The same applied to AR1.
The OD thus revoked the patent
The proprietor appealed the revocation of its patent.
The board confirmed the revocation for lack of IS over D2.
The case is interesting as the proprietor tried to defend its patent as being the result of a problem invention.
The technical problem underlying the invention
The problem underlying the invention is to provide pharmaceutical compositions comprising ivabradine HCl polymorph IV which are stable and suitable for use on a commercial scale, see paragraphs - of the patent.
This problem is solved, following claim 1, by stabilizing the tablet by a moisture barrier as claimed, created by means of packaging the tablet in blister pack material.
There is no debate that D2 is a suitable starting point for the assessment of inventive step.
The assessment of IS depended on whether or not, the claimed invention qualify as a “problem invention”
The proprietor’s position
According to the proprietor, the objective technical problem is the provision of a stabilized pharmaceutical composition of ivabradine HCl form IV. The proprietor relied on paragraphs - of the patent in support.
Paragraphs - of the patent compare the stability, at 40°C and 75% RH for periods of 2.5 to 6 months, of ivabradine HCl form IV tablets (uncoated and coated) in different blister pack materials. It is found that the use of a cold form foil (CFF, or Alu-Alu foil), which has a WVTR value within the claimed range (see paragraph ), prevents the conversion of form IV into form ß.
In contrast, the use of blister pack materials with lesser moisture barrier properties, i.e. higher WVTR values (PVC, Duplex) leads to partial conversion into form ß.
According to the proprietor, D2 describes form IV as stable.
The problem of instability of ivabradine HCl form IV as part of a pharmaceutical composition would not have been observed as part of the skilled person’s routine and was hitherto not recognized in the art.
The board’s position
The Board was of the opinion that a technical effect of stabilizing form IV against conversion into form ß in tablets under such humid conditions is credibly shown.
The technical problem may be thus formulated as the proprietor suggests, namely as the provision of a stabilized pharmaceutical composition of ivabradine HCl form IV, at least to the extent that the stability refers to this stability against this polymorphic conversion.
The Board did not share the proprietor’s view.
D2 firstly discusses general aspects of polymorphic behaviour of drugs (see page 4, second paragraph). The document differentiates between the most stable polymorphic form and metastable forms, and mentions that the transformation of metastable polymorphs to the stable polymorph may be facilitated by moisture (see page 4).
D2 then emphasizes the need to produce ivabradine HCl Form IV in “a form having constant physical properties”, and indicates that form IV is “a thermodynamically stable polymorphic form under certain experimental conditions of isolation or purification” (see page 5, emphasis added by the Board).
The skilled person would not understand this qualified statement as indicating that form IV is the most stable polymorphic form of ivabradine HCl. The further statement of D2 that ivabradine HCl form IV is “stable and easy to handle” (see page 5, lines 8-14) also does not teach that form IV is perfectly stable.
D2 does not teach either that form IV is perfectly stable when formulated in a tablet. In particular, in example 26 (see page 17), the description of the process for preparing a tablet comprising ivabradine HCl form IV is followed by the conclusion “The absence of any transformation of the crystalline Form IV of ivabradine hydrochloride was confirmed”. This statement does not refer to storage stability or stability upon exposure to moisture, and would rather be read as referring to stability during the preparation steps.
Thus, there is no teaching in D2 that ivabradine HCl form IV is perfectly stable, whether as such or formulated in a tablet.
In the case at hand, D2 neither says whether the stability over time of ivabradine HCl form IV in a tablet formulation may or may not be improved.
However, the skilled person would in any case have had to address the stability issues of formulated form IV as part of routine works towards development of the tablet for commercial use.
As acknowledged by the proprietor, and as explained in D2 (see the paragraph bridging pages 4 and 5), for the purpose of registering a pharmaceutical product, the stability of the active ingredient within the pharmaceutical composition needs to be examined in any case.
It is also part of the common general knowledge that not only the drug substance (here: ivabradine HCl form IV) but also the finished dosage forms (here: immediate release tablets containing it) must be tested for stability and constant physical properties.
Thus the skilled person would in any case have to verify the stability of the immediate-release tablet comprising ivabradine HCl polymorph IV, irrespective of any statements regarding its stability or lack thereof in the prior art D2.
The proprietor did thus not demonstrate that observing the instability of ivabradine HCl form IV in a pharmaceutical composition would have required any undue effort. On the contrary, the post-published evidence D24 (Stability experiment carried out on tablet formulations of ivabradine hydrochloride (Form IV) according to Example 26 of D2) shows that, when subjecting the tablets of example 26 of D2, containing ivabradine HCl form IV, to the standard stress conditions 40°C / 75% RH for a month, a complete loss of form IV is observable.
Contrary to the proprietor’s position, the use of such accelerated stability testing conditions is not uncommon and is recommended in D32, see Annex 5 (“WHO Expert Committee on Specifications for Pharmaceutical Preparations” Thirty-fourth report of 1996, p 1-194.
Special considerations on problem inventions in the decision
An inventive step may, in certain circumstances, be acknowledged on the basis of the discovery of an unrecognised problem, even if the claimed solution is in itself obvious (see also the Case Law of the Boards of Appeal, 10**(th) edition, 2022, I.D.9.12).
However, the posing of a problem which the skilled person would have encountered in the course of routine work cannot represent a contribution to the inventive merit of a claimed subject-matter.
It is therefore not sufficient that the prior art is silent about a problem for the claimed invention to qualify as a problem invention. As explained in T 252/10, cf. point 8 of the reasons, the absence of a hint in the prior art that there might still be a desire for further improvement does not mean that an unrecognized problem has been discovered.
When discussing IS and the solution of the problem, the board used “credible” instead of “plausible”. One wonders if it is not a tribute to G 2/21.
The notion of problem inventions is resurfacing regularly. Rarely with success for the applicant/proprietor. See for instance T 703/18, T 791/92, T 630/92, and T 119/82 among many other decision with the same conclusion.
It is indeed rare that a board concludes that there is a problem invention, i.e. that the invention lay in the formulation of the problem, whereby the solution to this problem appears trivial.
There are very few decisions actually positively dealing with this topic.
Courtesy of T. Debled, Professional Representative, I can show two of those.
In T 2/83, the problem with which the claimed invention was concerned was to provide an improved anti-flatulency effect side by side with an antacid effect in the stomachs of patients. It was standard to avoid a barrier layer isolating the antacid from the simethicone, but here the effect was surprising.
Layered varieties of tablets, which were also obtainable on the market, showed a substantially reduced anti-foaming activity in comparison with a tablet after prolonged storage containing a barrier according to the application under appeal. The modification provides a striking difference in performance, although the presentation of simethicone in a solid adsorbed form on at least 20 to 40 times the quantity of lactose together with starch and other carriers should have been sufficient to prevent migration and inactivation.
In T 2/83, the catchword reads:
The discovery of an unrecognised problem may in certain circumstances give rise to patentable subject-matter in spite of the fact that the claimed solution is retrospectively trivial and in itself obvious (“problem-inventions”).
In a case where the applicant had supplemented a known layered tablet by the provision of a barrier between the layers, the Board held that the proper question to be asked was not whether the skilled man could have provided the barrier but whether he would have done so in expectation of some improvement or advantage.
The tablets claimed in the present application are therefore novel, and show, in consequence of the inserted barrier, an improved performance.
The improved cat flap
If a cat, when trying to go through a cat flap which is top hung, the cat changes its mind and decides to stay on the same side, the paw gets stuck and the cat hurts itself. The harder the cat pulls back its paw, the tighter the flap jams. The solution to this problem is to provide an enlarged clearance for the cat’s paw between the tunnel portion and the bottom edge of the flap when the flap is displaced in at least one direction.
Paw trapping incidents may well have occurred repeatedly but hardly with the same cat since it either would have learnt how to proceed through the door or would have avoided the door in the future.
The succession of incidents would thus have concerned different doors and different cats at different places. In some cases the cat would have freed itself but of course could not report to the owner why the accident had happened, indeed the cat door might not even have been suspected to be the cause.
It cannot be expected that the cat owner is present each time the cat enters or leaves the building because the purpose of a cat flap is precisely to make such presence unnecessary.
The board thus has substantial doubts as to whether the recognition of the paw injury problem was obvious and accordingly gives the benefit of the doubt to the applicant on this point, so that the recognition of this particular problem contributes to the inventive step of the subject-matter of Claim 1.
Problem inventions do exist, but much less frequently as argued by representatives.