Posts Tagged ‘pregabalin’
November 21, 2018 by IPAlchemist
I went last night to the IBIL event that discussed last week’s pregabalin decision. There was a stellar lineup in the panel, and an equally august audience in attendance. But there was a major flaw. The panel jumped straight to discussing how the Supreme Court decision compares with the situation in other countries, and whether it was correct, without first establishing what the decision actually says. What now is the standard for plausibility? Has it changed, and if so how?
I am pleased to be in good company in finding it difficult to discern a difference in legal standard for plausibility as set out between the majority decision (Lord Sumption) and the minority dissents (Lord Mance and Lord Hodge) – Lord Hoffmann last night said that he could see little difference in their respective positions. So what is going on?
Lord Hodge clearly states that he disagrees with Lord Sumption, stating at :
Where I differ from Lord Sumption is that, in agreement with Lord Mance, who has analysed the three cases of ALLERGAN, IPSEN and BRISTOL MYERS SQUIBB, I do not interpret those principles as requiring the patentee to demonstrate within its patent a prima facie case of therapeutic efficacy.
Lord Mance similarly disagrees, stating at :
In my view, Lord Sumption’s analysis imposes too high a threshold, and imposes a burden on a patentee which the case law of the Board of Appeal of the European Patent Office does not justify. I prefer the approach advocated by Mr Mitcheson, but rejected by Lord Sumption in para 30 of his judgment.
What is rejected by Lord Sumption in para 30 of his judgment is the argument that
it is necessary for the patentee to disclose reasons for regarding the claimed therapeutic effect as plausible only when the skilled person reading the patent would be sceptical about it in the absence of such disclosure.
Later on at  Lord Sumption states
It must always be necessary for the patentee to demonstrate that he has included in the specification something that makes the claim to therapeutic efficacy plausible.
And at  he summarises:
The fundamental principle which [these judgments from the EPO Boards of Appeal] illustrate is that the patentee cannot claim a monopoly of a new use for an existing compound unless he not only makes but discloses a contribution to the art. None of them casts doubt on the proposition that the disclosure in the patent must demonstrate in the light of the common general knowledge at the priority date that the claimed therapeutic effect is plausible. On the contrary, they affirm it.
Lord Sumption also disagrees with the Court of Appeal – at  he explains:
They [the Court of Appeal judges] considered that the threshold was not only low, but that the test could be satisfied by a “prediction … based on the slimmest of evidence” or one based on material which was “manifestly incomplete”. Consistently with that approach, they considered (paras 40, 130) that the Board’s observations in SALK laid down no general principle. I respectfully disagree. The principle is that the specification must disclose some reason for supposing that the implied assertion of efficacy in the claim is true. Plausibility is not a distinct condition of validity with a life of its own, but a standard against which that must be demonstrated. Its adoption is a mitigation of the principle in favour of patentability. It reflects the practical difficulty of demonstrating therapeutic efficacy to any higher standard at the stage when the patent application must in practice be made. The test is relatively undemanding. But it cannot be deprived of all meaning or reduced, as Floyd LJ’s statement does, to little more than a test of good faith. Indeed, if the threshold were as low as he suggests, it would be unlikely to serve even the limited purpose that he assigns to it of barring speculative or armchair claims.
So what Lord Sumption appears to be expounding, which goes further than the plausibility test as previously understood (at least by me), is that it is not sufficient that it be objectively plausible that the invention works, based on the information in the patent and what was otherwise known at the priority date, but that the patent specification must actively disclose why it is plausible. Thus there appears to be a new disclosure requirement – “the specification must disclose some reason for supposing that the implied assertion of efficacy in the claim is true” (as quoted above from para 36).
There is considerable advocacy in Lord Sumption’s judgment, and reading it alone it is entirely convincing. It is only when trying to work out precisely how it differs from the views of Lord Hodge, Lord Mance, and indeed the Court of Appeal, that it becomes evident that the standard it purports to lay down, and how this standard has evolved from earlier English jurisprudence, is not clearly expressed.
But there is a bigger problem. Having set out a standard, albeit unclearly, Lord Sumption does not then apply it. When reversing the finding of Mr Justice Arnold that the specification satisfied the plausibility requirement for peripheral neuropathic pain, Lord Sumption did so not on the basis of a different applicable legal standard, and “not because there was anything wrong with the judge’s findings, but because those findings do not support his conclusion that the specification makes it plausible to predict that pregabalin will be efficacious for treating neuropathic pain.” 
He goes on at :
The judge’s analysis of the implications for peripheral neuropathic pain of the data presented in the specification was based entirely on the common general knowledge that central sensitisation was “involved” in both inflammatory and peripheral neuropathic pain. The judge concluded from this that it was “possible” that a drug which the specification showed to be effective for the first would also be effective for the second, “although this would not necessarily be the case.” In my opinion this is a logical non-sequitur.
Thus, Lord Sumption seems to be saying that Arnold J’s analysis is not logically sound even on its own terms, and so he is reversing on that basis. Not on the basis that the threshold applied by Arnold J was too low, or that the patent failed to satisfy the new disclosure requirement articulated earlier.
I rather hope that I am wrong, but it seems to me that Lord Sumption has not actually applied in the operative part of his ruling the standard that he appears to have set out earlier. If that is the case, is the earlier standard even ratio decidendi? It is hard to see how this ruling from the Supreme Court can be applied to future cases.
A final comment on infringement. We have three dissenting views of what infringes a second medical use claim. They are all obiter. What we are supposed to do with them seems more a matter of philosophy than the practice of law.
January 19, 2018 by IPAlchemist
The patent litigation on pregabalin has been one of the most important UK patent stories of this century. It has raised important questions about the scope and meaning of second medical use patents, and has led to entirely new forms of court order (the Patents Court ordering NHS England to issue instructions on the prescribing of pregabalin by brand rather than generically). At the time, I wrote about the story extensively on the IPKat blog. (My last post is here; my posts on the main first instance decisions are here and here; links to earlier decisions are here.) I have been looking at the situation again because I am collaborating with Ben Goldacre and Richard Croker at the Department of Primary Care Health Sciences, University of Oxford on a study of the effect of the litigation on pregabalin prescribing and cost.
There was one recurring fact in the litigation that was often referred to but never explained. The Supplementary Protection Certificate (SPC/GB04/034) based on the original product patent for pregabalin (EP0641330) was applied for in October 2004, following the granting of the European marketing authorisation to Pfizer for their Lyrica brand pregabalin, and granted in February 2005. But then in May 2013 the renewal fees required to bring it into force upon expiry of EP0641330 were not paid, so that it lapsed. It is a vanishingly rare occurrence to allow an SPC to lapse in this manner, and it must have been intentional. The question is, why would Pfizer do this? Incidentally, the owner of the patent and SPC is not Pfizer, but Northwestern University. There is no licence recorded on the UK IPO register, but licences are often not recorded and I presume that Pfizer (or one of its subsidiaries) is actually a licensee under the patent.
While looking into the case, I noticed that the US application from which EP0641330 claims priority is a continuation-in-part of an earlier US application. This is often a signpost to a possible self-collision issue, and so I took a closer look.
EP0641330 is based on international patent application WO93/23383, and claims priority from US application number 07/886,080. (“Claiming priority” is a system where you can file an application up to a year later than the earlier application, but it is regarded for the purposes of considering patentability [novelty and inventive step] as having been filed at the earlier date. Such a priority claim is valid only if the subject matter of the claim in question is present in both applications, and also provided that the earlier of the two applications is the first application for that subject matter). However, 07/886,080 is a continuation-in-part of US application 07/618,692, and a PCT application WO92/09560 was also filed claiming priority from that earlier US application.
The timeline is as follows:
27 November 1990 US 07/618,692 filed
20 November 1991 WO92/09560 filed
20 May 1992 US 07/886,080 filed
11 June 1992 WO92/09560 published
18 May 1993 WO93/23383 filed
Now, if we consider the right to priority of the claim to pregabalin in EP0641330, the corresponding subject matter is present in 07/886,080 and therefore on the face of it the first part of the test for a valid priority claim is satisfied – the subject matter is present in both applications. On that basis, WO92/09560 is not available as prior art, because it was published after 20 May 1992. (If this were not the case, I would expect the EPO examiner to have noticed it).
The difference between WO92/09560 and EP0641330 is that in EP0641330 pregabalin is claimed as a single enantiomer – the S-(+) enantiomer. In WO92/09560, by contrast, while the pregabalin molecule is disclosed, it is only made and tested as the racemate. However, WO92/09560 also states:
“The compounds made in accordance with the present invention can contain one or several asymmetric carbon atoms. The invention includes the individual diastereomers or enantiomers, and the mixtures thereof. The individual diastereomers or enantiomers may be prepared or isolated by methods already well known in the art.”
There is a plausible argument that this passage, in combination with the disclosure of the racemic pregabalin, is sufficient to count as a disclosure of the S-(+) enantiomer. In that case, however, WO92/09560 (or its priority application 07/618,692) is the “first” application for that subject matter, and not 07/886,080. That would make the priority claim invalid so that the effective date for considering the patentability of EP0641330 would become the filing date of WO93/23383, namely 18 May 1993. Thus WO92/09560 would become novelty-destroying prior art, because it was published before the filing date of WO93/23383 and thus EP0641330.
Now, all of this is arguable both ways, and it is possible that a court would not accept the argument. It is also a fairly subtle point, and I can imagine an EPO examiner missing it. It does not surprise me that the patent was nevertheless granted – on the face of it if the priority claim of WO93/23383 is valid, then WO92/09560 is not prior art at all since it was never filed at the European Patent Office as a European application. (If WO92/09560 has been filed as a European application, it would have been considered by the EPO examiner as “novelty-only” prior art under Article 54(3) EPC as being filed before, but published after, the priority date of WO93/23383). It is only if the additional criterion, whether 07/886,080 is the “first application” in respect of the subject matter of the S-(+) enantiomer of pregabalin, is considered that a potential problem becomes apparent.
None of this would apply in the USA, where the rules about your own earlier applications counting as prior art against your own application are completely different from the rules in Europe.
Also, a possible reason why the patent might be invalid is not of itself a reason for Pfizer to drop the SPC. Pharmaceutical patents are often found to be invalid by national courts, and although obviously the proprietor then loses the patent case, there is usually no further adverse outcome.
However, in 2009 the EU Commission published the Final Report in its competition inquiry into the pharmaceutical sector, which raised a number of questions about behaviours that had previously been considered unproblematic. Then in July 2010 the General Court upheld a finding of abuse of dominant position against AstraZeneca in relation to Losec (omeprazole), for actions including providing incorrect information about the date of the first marketing authorisation when applying for supplementary protection certificates, and this was upheld by the Court of Justice of the European Union in December 2012.
Moreover, in January 2012, the Italian Competition Authority sanctioned Pfizer for abuse of a dominant position relating to latanoprost consisting of various aspects including basing an SPC on a divisional application. This was quashed by the Regional Administrative Court of Lazio in September 2012, but then reinstated in February 2014 by the Consiglio di Stato.
All of these events together created a perception around 2010-2012 that, at least in respect of an SPC (if not necessarily in respect of a patent), the proprietor might (under competition law if not under any intellectual property law) be under a kind of good faith obligation that was more extensive than had previously been the case in Europe, and that the EU competition authorities might regard breach of such a good faith requirement as constituting an abuse of a dominant position. That perception is perhaps less prominent now, but at the time such views were widely discussed. A person might therefore have had a concern that a patent proprietor applying for an SPC based on a patent that the proprietor knew or should have known to be invalid, because the reason for invalidity was their own prior art, might be found to be an abuse of a dominant position under competition law.
There is no clear authority that it is an abuse of a dominant position to apply for an SPC based on an invalid patent (even where the patentee should know it is invalid, for example because the prior art is their own related application), but it may well have seemed in 2013 that this was the direction in which competition law was heading. The EU Commission can fine an undertaking up to 10% of worldwide turnover, so the risks involved if competition law comes into play are very high.
By not bringing the SPC into force, it was pretty much guaranteed that there would never be any litigation under the patent, since it would expire before the end of the data exclusivity period. On the other hand, if the SPC were brought into force, there would inevitably be litigation with generic companies, and there would be a risk that the patent might be found invalid for this self-collision reason. Once that reason became public by reason of the litigation, there could then arise a concern that this would lead to EU Commission action under competition law.
I do not know why Pfizer decided not to bring the SPC into force. However, this priority issue leading to a potential self-collision provides a plausible reason (and I have not seen any other possible reason suggested) why someone might have decided that it was too risky to bring the SPC into force. I wonder whether anyone can tell me whether it is anywhere close to the real reason.