In the patent profession, cases have this way of always coming back at us.
You may work hard on a case and complete a difficult action, possibly with some sense of achievement (or relief). But then, a few months or years later, the case is back with a vengeance.
Happy about the way you have drafted your patent application, having navigated through all of the prior art and the inventor’s wishes? Wait until you get the search report. Enjoying your ride or flight back home after having been steam-rollered in opposition oral proceedings? Let’s meet again in 2 years’ time for the appeal. Satisfied that you have managed to digest the other party’s 300-page submissions just in time to file your reply in court? As well you should, although next time you will get 350 pages from them.
And so it is with this blog.
Almost exactly 2 years ago, I published a post on Ethypharm SAS v. Merck Sharp & Dohme Corp.
Now that the appeal judgment has been handed down, it seems like a good time to revisit this litigation.
Most appeal judgments in France confirm the first instance decisions (it is said that the confirmation rate is around 80%). But this one did not confirm, which makes it all the more interesting.
As a reminder, the case pitches Ethypharm as a nullity plaintiff against Merck Sharp & Dohme Corp. (MSD), defendant and owner of the patent in suit, EP 1455756.
The first topic addressed in my previous post was the assessment of whether the action was time-barred. On this aspect, the appeal judges came to the same conclusion as their colleagues below, with a slightly different reasoning.
The TGI had decided that the starting point for the 5-year limitation period was the date of the EPO Board of appeal’s decision (July 7, 2014), announced during the oral proceedings, per which the patent under opposition was to be maintained in amended form.
As noted in my post, this finding was already a deviation from earlier case law.
The Paris Cour d’appel took an even later date as a starting point, namely the day on which the amended patent was published by the EPO (September 23, 2015). Said the court: “this is when the modified patent became opposable to third parties“.
An entirely reasonable finding, but which makes it more difficult than ever to know and predict how this limitation period should be computed in general. Case law keeps going all over the place. Fortunately, the statute has now been amended so as to take away this disastrous limitation period. We will still have to live with this legal mess, but less and less so.
The other notable point in my earlier post was that I felt there may be some contradiction in the TGI’s position regarding sufficiency on the one hand and inventive step on the other hand.
As a reminder which is probably quite necessary (at least for me), claim 1 reads as follows:
A nanoparticulate composition comprising the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine [a.k.a. aprepitant], or a pharmaceutically acceptable salt thereof, the compound having adsorbed on the surface thereof at least one surface stabilizer in an amount sufficient to maintain an effective average particle size of less than about 1000 nm; where “effective average particle size of less than about 1000 nm” means that at least 95% of the particles, by weight, have a particle size of less than about 1000 nm.
Ethypharm’s insufficiency challenge failed at first instance, as the court noted that there was a prior U.S. patent disclosing the so-called “Nanocrystal” method, for making nanoparticles with a surface modifier adsorbed thereon, having an average size of less than 400 nm. This Nanocrystal patent also taught that such nanoparticles improve the bioavailability of poorly water-soluble actives.
Ethypharm also argued lack of inventive step of claim 1 over this Nanocrystal patent, but the attack failed. The lower court held that the teaching of the Nanocrystal patent could not be applied in an obvious manner to aprepitant, and that there were many technical uncertainties.
I was not completely comfortable with the articulation between both positions.
Maybe the appeal judges also had trouble with this approach: while they agreed that the invention was sufficiently disclosed in the patent, they held that it lacked inventive step.
Starting with sufficiency, the court tackled plausibility, an essential phase of most pharma cases. The court repeated the now well-established French criterion per which the patent must “directly and unambiguously reflect the therapeutic effect” at stake. But then they added that “it is not systematically required that the description of the patent should contain tests, this condition is not required in case of a product claim”. A helpful comment, quite in line with the Boards of appeal’s stance on the matter.
The court further remarked that the patent in suit made reference to the U.S. Nanocrystal patent, which made it plausible for the skilled person that nanoparticulate aprepitant had improved bioavailability. Ethypharm did not demonstrate that this was not the case and thus did not discharge its burden of proof. In fact, it appears that some test reports were filed by the plaintiff to support the sufficiency challenge, but they were deemed inconclusive.
Turning then to inventive step, MSD’s case was that increasing bioavailability was a complex problem, and that there were many parameters to be taken into account.
To them, reducing the size of aprepitant particles to less than 1000 nm was not an approach that the skilled person would have used.
But the court relied on expert’s evidence showing that the dissolution rate is often a limiting factor in bioavailability; and that reducing the particle size of a drug makes it possible to increase the contact surface area between the undissolved active and the solvent, which generally increases the dissolution rate. Reference was made in particular to a 1982 textbook.
MSD countered that reducing the particle size to less than 1000 nm was not commonly practiced at the priority date, and had been little explored. The court was not persuaded. Some nanoparticulate drugs were tested already in the 1990s, and it had been proposed in a general manner that a poorly soluble drug could be reduced to a nano size. The Nanocrystal technology of course was also taken into consideration. Not just the patent, but also a press release by Elan Technologies, according to which their process was broadly applicable to many poorly soluble actives.
MSD further relied on a document showing that micronization of aprepitant did not give satisfactory results, so as to show that the skilled person would not have continued with this approach. But the document was an internal one and the skilled person would of course not have been aware of it.
In the end, the court did not deny that there were several possible approaches for the skilled person, but found that the nanoparticulate approach was nevertheless obvious to try:
Even if the skilled person knew of other methods and if the EP’299 patent only showed tests on three different active ingredients, he […] knew that nanonization improved the bioavailability of poorly soluble active substances and was thus incited, based on converging information […], to start research on this pathway in order to improve the bioavailability of aprepitant when used as a drug.
The Board of appeal decision per which the patent was maintained in amended form, namely T 210/11 (Board 3.3.07) reached an opposite conclusion of course:
It results that the skilled person, looking for a solution to the problem as defined above, faces multiple possible solutions to said problem of low bioavailability of aprepitant, and would not be conducted by the teaching of documents (5), (6) or (7) to the use of a nano-particulate composition of aprepitant.
Ethypharm was not a party to the opposition proceedings at the EPO, and the Paris court may have been presented with additional evidence that the Board did not see.
But my overall impression is that this is basically a matter of the court and the board placing the inventive step bar at different heights. This may be one of those grey-area cases, with complex facts to consider, which may very well go one way or the other depending on who looks at them.
This is the end of the story – for now, unless there is a cassation appeal and the case comes back to haunt this blog again.
CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, October 29, 2019, SAS Ethypharm v. Merck Sharp & Dohme Corp., RG No.18/03876.