The patent in suit is Lilly‘s EP 1 313 508 B1; see the EPO Register and Swissreg for further details. In a nutshell, EP’508 relates to combination of pemetrexed disodium and vitamin B12. See this Blog here for a discussion about earlier infringement proceedings concerning the same patent.
Now, nullity is at stake.
An Opposition Division of the EPO had maintained the patent as granted with decision of 27 December 2010; an appeal had initially been lodged but withdrawn later. Related decisions in civil proceedings elsewhere had also addressed the validity of EP’508, e.g. in
USA (Court of Appeals for the Federal Circuit, 2015-2067, decision of 12 January 2017 relating to the corresponding US patent 7,772,209 and maintaining the patent);
Japan (IP High Court, 2015 (Gyo-Ke) 10249 et al., decision of 2 February 2017 relating to the corresponding JP patent 5102928 and maintaining the patent).
Thus, it was an uphill fight for the plaintiff. And even though the FPC took the parallel decision of the German FPC into account, it explicitly disagreed. It is held on p 19 (penultimate and lastparagraph), that the German FPC erred with the finding that
[…] bei einer Pemetrexedgabe durch die Blockierung der drei Schlüsselenzyme Thymidylatsynthase (= TS), Dihydrofolatreduktase (= DHFR) und Glycinamidribonukleotidformyltransferase (= GARFT) im «DNA- Zyklus» nicht nur dieser Zyklus, sondern auch der «Methylierungszyklus» blockiert wird.
Consequently, the FPC did not put much weight (if any) on the parallel decision in Germany.
On the contrary, the decision holds that the claimed subject-matter was novel over Worzalla et al. since mere reference to a diet ‘Purina Chow #5001’ did not implicitly, yet clearly and unambiguously, disclose the presence of vitamin B12 (or folic acid).
EP’181 is meant to protect Lilly‘s low dosage forms of tadalafil, i.e. Cialis® 2.5 mg and Cialis® 5 mg, for the treatment of erectile dysfunction. Cialis at these low dosages is sometimes referred to as the ‘weekend pill’ because it can not only be taken on demand but also once daily, without regard to timing of sexual activity. See drugs.com and Lilly’s prescribing information.
The feature analysis of claim 1 of CH/EP’181 H1 reads as follows:
Pharmaceutical unit dosage composition
comprising a compound having the structural formula [tadalafil]
comprising 1 to 5 mg of this compound
said unit dosage form suitable for oral administration
up to a maximum total dose of 5 mg per day
for use in treating a condition where inhibition of PDE5 is desirable
wherein the condition is sexual dysfunction.
No dosage regime
Note that the claim does not address the frequency of taking of tadalafil. In accordance with feature 1.5, tadalafil could be taken once or several times per day (prophylactic or on demand, as long as the dose of 5 mg per day is not exceeded), and it is not defined that tadalafil is taken each day. Similar to the German FPC (¶ II.1), the decision holds that the claim lacks an essential element of a dosage regime, i.e. the frequency of taking tadalafil.
The decision holds that the claim to priority is presumably valid, both formally (¶ 19) and on the merits (¶¶ 20-22).
Presumably no undue extension of subject-matter
The range of ‘1 to 20 mg’ in EP’181 B1 — with ‘5 to 20 mg’ being preferred — had been limited to ‘1 to 5 mg’ in EP’181 B3.
The decision holds that the plea in defense with respect to an undue extension of subject-matter is presumably unfounded (¶¶ 23-24), because the skilled person would still have seriously contemplated the range of 1 to 5 mg in view of dependent claim 4 (2.5 mg) and example 7 (2 mg).
Novelty acknowleged …
Since the priority claim was held presumably valid, the only remaining document to be considered with respect to novelty was WO 97/03675 A1 (Daugan). The relevant disclosure therein reads as follows (p 5, l 1-11):
For administration to man in the curative or prophylactic treatment of the disorders identified above, oral dosages of [tadalafil] will generally be in the range of from 0.5-800 mg daily for an average adult patient (70kg). Thus for a typical adult patient, individual tablets or capsules contain from 0.2 – 400 mg of active compound, in a suitable pharmaceutically acceptable vehicle or carrier, for administration in single or multiple doses, once or several times per day. […] In practice the physician will determine the actual dosing regimen which will be most suitable for an individual patient and it will wary with the age, weight and response of the particular patient.
Specific examples in Daugan make use of 50 mg of active compound in a tablet (p 12 ff).
Now, is the range of 1-5 mg novel over the broad range disclosed in Daugan?
According to the EPO Guidelines (G-VI, 8, ed. 2018), a sub-range selected from a broader numerical range of the prior art is considered novel, if each of the following three criteria is satisfied (emphasis added):
the selected sub-range is narrow compared to the known range;
the selected sub-range is sufficiently far removed from any specific examples disclosed in the prior art and from the end-points of the known range;
the selected range is not an arbitrary specimen of the prior art, i.e. not a mere embodiment of the prior art, but another invention (purposive selection, new technical teaching).
The decision only applies criteria a. and b. for novelty, while the requirement of a purposive selection / new technical teaching (c.) is said to be related to obviousness only. Note that this criterion is also abolished with in the 2019 edition of the EPO Guidelines, entering into force on 1 November 2019.
Clearly, 1-5 mg is a narrow range compared to 0.2 – 800 mg; criterion a. is thus fulfilled.
But is the range sufficiently removed from the working example of 50 mg in Daugan? The decision holds that even though the absolute difference is only 45 mg, the absolute amounts still differ by a factor of 10. Thus, criterion b. is also considered fulfilled.
On a personal note, I doubt that time was already ripe for changing the Guidelines. The recent 2019 edition of the book ‘Case Law of the Boards of Appeal’ in chapter I.C.6.3.1 correctly holds that there are several decsions that disregard criterion c., but still there are even recent decisions that do apply criterion c. There have been constant rumors for quite a while that this might be sth for the EBoA to finally decide. I would have preferred to await final clarification on BoA level over the uncertainty of an early change in first instance proceedings that might perhaps need to be reversed again in a worst-case scenario. In my view, criterion c. when correctly applied is a test whether there is a ‘new technical teaching’ (not just a formally new numerical value); see emphasis above. I cannot see any fundamental misconception in doing so under the title of novelty. A new technical teaching must not be confused with a non-obvious technical teaching. But be this as it may, I am still hopeful that the EBoA might finally have its say.
… but the low dosage form is obvious
Actually, obviousness is at the heart of this multi-national dispute. Lilly argued that courts in strict application of the problem-solution approach had found that EP’181 B3 was valid (e.g. in DK and FI), whereas only courts that applied a somewhat different approach concluded that EP’181 B3 was invalid (e.g. in the U.K., DE and NL):
Søog Handelsretten, Denmark, with decision A-49-17 of 15 June 2018;
Markkinaoikeus, Finland, with decision 131/19 of 25 March 2019.
Accordingly, Lilly pushed for a strict application of the problem-solution approach in the present proceedings. The FPC indeed applied the problem-solution approach, but still concluded that EP’181 H1 was invalid.
The parties agreed on WO 97/03675 A1 (Daugan) as the closest prior art.
It’s no more than a sideshow for the outcome of the decision, but an interesting one:
The decision holds in ¶ 33 that the skilled person would understand the broad ranges in Daugan as ‘boiler plates’ which are aimed at claiming the broadest possible protection. This implies quite some knowledge of a patent practitioner. The discussion of the broad ranges is in the specification, not in the claims. What is more, the skilled person is defined earlier in the decision as follows (¶ 14):
[A] team consisting of a clinical pharmacologist (with knowledge of the pharmacokinetics of conventional medicines and biological preparations) and a clinician (with knowledge of urology, and in particular of sexual dysfunctions or erectile dysfunctions and available medicinal treatments such as sildenafil).
I wonder where any knowledge of a patent practitioner stems from in this team. When discussing patent literature in litigation, it is constantly assumed that the ‘skilled person’ just knows how to read patents, and that he is even able to understand what the drafting attorney might have had in mind and intended in legal terms when drafting the specification. This is anything but realistic, in my perception. On the contrary, the typical pharmacologist and clinician will be used to read scientific publications, and without any additional training in patent matters he will approach a patent document just like any other piece of scientific literature.
In view of WO 97/03675 A1 (Daugan) as closest prior art, the FPC defined the objective technical problem as to provide a clinically effective and safe dosage of tadalafil for the treatment of sexual dysfunction.
The decision holds that it is credible that the skilled person would always aim to find the lowest possible effective dosage of an active substance, for various reasons. First, because the skilled person knows that a lower dosage will have fewer side effects, and the avoidance of side effects is always a goal in drug research. Second, the skilled person will strive to find the lowest possible effective dosage, because it may well be that the regulatory authority asks for it. Although it is not certain that the approval authority will require this information, it is still reasonably possible. Even this possibility is a sufficient incentive to identify the lowest possible dosage: If the necessary studies would only be done at the request of the authority later on, the market authorisation would be considerably delayed.
Interestingly, the decision also expands on the ‘reasonable expectation of success’ (see this Blog here) — and its irrelevance for the case at hand. A ‘reasonable expectation of success’ is not necessary if the skilled person has an incentive for any other reason (e.g. a potential inquiry from the approval authority to specify the lowest effective dosage in the present case). The skilled person will then just take the necessary steps towards the invention unless he has to assume that this is hopeless right from the outset (¶36):
[E]ine Erfindung [ist] naheliegend, wenn der Stand der Technik […] dem Fachmann einen Anlass (“Motivation”) bietet, den nächstliegenden Stand der Technik so abzuwandeln, dass er zum beanspruchten Gegenstand gelangt. Oft wird den Fachmann eine begründete Erfolgserwartung zu der Weiterentwicklung veranlassen, d.h. wenn er aufgrund wissenschaftlicher Erwägungen annimmt, dass die Abwandung des Standes der Technik mit hoher Wahrscheinlichkeit zur Lösung der Aufgabe führt, wird er diese Abwandlung naheliegenderweise vornehmen. Eine begründete Erfolgserwartung in diesem Sinne ist aber nicht notwendig, wenn der Fachmann bereits aus anderen Gründen einen Anlass hat, den nächstliegenden Stand der Technik zum Gegenstand des geltend gemachten Anspruchs weiterzuentwickeln. Er wird diese Entwicklung dann vornehmen, wenn er nicht geradezu annehmen muss, dass sie aussichtslos ist.
The decision holds that the skilled person would have routinely included a dose of 5 mg of tadalafil in the phase IIb clinical study to determine the dose-response curve, in particular in view of Goldstein et al. (1997) where quite some efficacy of the sildenafil, the first-in-class drug, had been reported for a dosage of as low as 5 mg.
The skilled person would then inevitably have realised that tadalafil at a dose of 5 mg was still clinically effective. Thus, the decision holds that the subject-matter of EP’181 H1 was prima facieobvious.
The decision can still be appealed to the Supreme Court.
1. Use of pemetrexed disodium in the manufacture of a medicament for use in combination therapy for inhibiting tumor growth in mammals wherein said medicament is to be administered in combination with vitamin B12 or a pharmaceutical derivative thereof, said pharmaceutical derivative of vitamin B12 being hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin or cobalamin.
12. A product containing pemetrexed disodium, vitamin B12 or a pharmaceutical derivative thereof said pharmaceutical derivative of vitamin B12 being hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin or cobalamin, and, optionally, a folic binding protein binding agent selected from the group consisting of folic acid, (6R)-5-methyl-5,6,7,8-tetrahydrofolic acid and (6R)-5-formyl-5,6,7,8-tetrahydrofolic acid, or a physiologically available salt or ester thereof, as a combined preparation for the simultaneous, separate or sequential use in inhibiting tumor growth.
It’s all about a combination of the antifolate pemetrexed disodium, vitamin B12 and, optionally, folic acid. Briefly, pemetrexed is an antifolate that inter alia inhibits synthesis of thymidine and thus de novo DNA synthesis. Evidently, antifolates are quite toxic. But according to EP’508, toxicity can be successfully controlled by co-administration of pemetrexed with vitamin B12 and, optionally, folic acid.
EP’508 had already been litigated in infringement proceedings in Switzerland, resulting in a landmark decision of the Supreme Court on the Doctrine of Equivalents and how amendments of the patent during prosecution are to be dealt with in this respect; see this Blog here.
This time, validity of EP’508 is being challenged, based on a lack of novelty or, at least, lack of an inventive step; and added matter. Only inventive step has been pleaded in the hearing. With respect to the other grounds of nullity, the Sandoz merely referred to the written submissions.
It was evident from the pleadings that the opinion of the judge-rapporteur had been in favour of the defendant. This interim opinion is in line with the decision of an EPO opposition division, the Rechtbank Den Haag (Case No. C/09/533354 / HA ZA 17-581; judgment available as Dutch original and inofficial English translation), the IP High Court of Japan and the U.S. CAFC. On the other hand, the German Federal Patent Court had revoked the German part of EP’508; an appeal before the Supreme Court is still pending.
Sandoz started from Jackman as closest prior art in the assessment of inventive step. With reference to Worzalla et al., Jackman describes experiments in which pemetrexed was administered alongside with folic acid. Further, phase I clinical trials had been reported in which pemetrexed was administered together with folic acid (Hammond et al.). In consideration of the biochemical pathways, Sandoz argued that it had been obvious to add vitamin B12 to said known combination.
Eli Lilly of course disagreed. In Lilly’s view, the skilled person would not have pursued a combination of pemetrexed and folic acid, let alone to add vitamin B12. In real life, phase II clinical trials began with pemetrexed alone, irrespective of the experiments of Hammond et al. Toxicity of pemetrexed had intially been deemed controllable. It was only in the course of phase II clinical trials that the therapy scheme was switched because toxicity was found to be too severe.
A significant point of discussion was whether a skilled person would have been motivated to add vitamin B12 in light of some marker experiments. Niyikiza, the main inventor of the patent in suit, had published a report that described a correlation of pemetrexed toxicity with an unspecific marker (homocysteine), but not with the vitamin B12-specific marker MMA (methlymalonic acid). Accordingly, in Lilly’s view, a skilled person would not have been prompted towards the invention.
The basic EP’668 had lapsed already back in 2015; and the SPC has also lapsed meanwhile, on 4 May 2019. But the present decisions relate to an apparent mishap shortly before the SPC finally lapsed.
Sandoz had Swissmedic’s market authorization for its generic ‘Tadalafil Sandoz’ since 7 November 2017, but did not yet put it on the market. Still, the plaintiffs came across database entries for ‘Tadalafil Sandoz’ in HCI Solutions‘ medINDEX (for physicists) and pharmINDEX (for pharmacists). These databases are used by practitioners to order pharmaceuticals. Even though ‘Tadalafil Sandoz’ could not be ordered at that time, the President held that the effect of the database entries was essentially comparable to an inquiry of future needs (see S2014_001). Potential customers are made aware that the launch of a generic is imminent. This may tempt them to postpone orders for the original product and to order the cheaper generic once it becomes available. The generic manufacturer benefits from this advertising effect to the detriment of the supplier of the original product. During the term of the SPC, such advertising constitutes a violation of the exclusive rights of the owner of the SPC.
At the face of it, the situation was apparently so clear that the President granted interim injunctive relief without hearing Sandoz beforehand, and obliged Sandoz to immediately request the database provider to delete the entries.
Decision of 21 March 2019 in case of ICOS Corp, Eli Lilly SA v. Sandoz Pharma AG re SPC for tadalafil: inclusion of product in database of available products infringes patentee’s exclusive rights even if the product cannot be ordered (ex parte injunction), https://t.co/5SLv4kFPKQ
After hearing the defendant, it turned out that Sandoz’ had not made the entries in the databases. The entries had been made the database provider, an independent third party, without Sandoz’s knowledge and intervention. The database entries had meanwhile been deleted on Sandoz’s request, and thus there was no basis anymore for interim injunctive relief. The request was thus denied.
Now, what about the costs?
As a rule, the costs are clapped on the unsuccessful party; Art. 106(1) CPC. But the court may diverge from the general principles and allocate the costs at its own discretion when a party was caused to litigate in good faith; Art. 107(1) lit. b.
The President held that even though the plaintiff’s course of action may be understandable under the given circumstances, this still does not justify that the defendant bears the costs incurred in view of the unlawful conduct of an unrelated third party:
The plaintiffs have refrained from issuing a warning to the defendant before submitting the request for action. The applicants’ action may be understandable in the circumstances, but it does not justify the defendant having to bear the costs of the proceedings. As the defendant credibly demonstrates, it had nothing to do with the unlawful conduct of a third party; it is to be regarded neither as an instigator nor as an accomplice nor as a collaborator. Nor does it exercise any control over the third party. Since the defendant is not responsible for the unlawful conduct and has not created the appearance of being responsible for it, it cannot be ordered to pay the costs.
The court fee and a compensation for legal representation of the defendant are thus to be borne by the plaintiffs.
AZ’s request for interim injunctive relief w/o hearing the defendant beforehand was dismissed with decision of 20 February 2019. Hearing the defendant didn’t change the outcome; the request was also dismissed with decision of 9 April 2019. Both requests failed for lack of urgency, given the fact that Sandoz’s generic has been on the market since 2.5 years.
At the face of it, this appears to be pretty straight forward, in particular in view of the most recent decisions S2018_006 (¶13) and S2019_001 (¶6) emphasizing the 14 months time bar in no uncertain terms.
But the devil is in the detail. Maybe.
This is not the first time that the FPC had to deal with EP’573. The patent had been revoked for lack of inventive step over Howell in view of McLeskey; see this Blog here. But AZ appealed and essentially argued that the FPC erroneously assumed a (concrete) pharmaceutical formulation in Howell, thus incorrectly defined the distinguishing features and the (objective) technical problem, and then wrongly concluded for lack of inventive step.
And, indeed, the Supreme Court agreed and remitted the case for re-assessment of inventive step; see this Blog here. From the reasons of the present decisions, we can now catch a glimpse of what is currently going on in the remitted proceedings (formerly O2015_011, now O2018_009): The judge-rapporteur held on 23 November 2018 that the patent was valid. But it is not only that the wind has changed at the FPC. The Gerechtshof Den Haag also held that the patent was valid, in second instance proceedings. Likewise, a Board of Appeal at the EPO overruled the first instance revocation of an opposition division and finally ruled on 24 January 2019 that the patent was valid.
On the other hand, this is also not the first time that AZ sought injunctive relief for Sandoz’s generic. AZ had asserted a different patent against the same generic already in summary proceedings S2016_007, i.e. EP'138. It becomes clear from the present decisions that these earlier proceedings had been terminated because AZ had withdrawn the requests.
Now, here is a timeline events which is colored to reflect my very personal view on the prima facie validity of EP’573 over time:
One may conclude from the above timeline that there had been some red(-ish) flags concerning the validity of EP’573 for quite a long time.
The decisions note in passing that main infringement proceedings with case no. O2017_004 concerning Sandoz’s generic are pending in parallel, but based on a different patent (EP'195); from the case no. it is clear that this suit has been brought in 2017, but no further information is available to date.
Further, the decision indicates that in some proceedings with case no. O2018_010 the very same EP’573 is at stake as in the present matter, but the defendant is not revealed.
AZ essentially argued that it had been prevented from bringing the request for interim injunctive relief earlier because of the previously negative assessment of validity EP’573 by the EPO, the FPC (O2015_011) and the district court of The Hague (NL), and that the wind has changed only very recently; see timeline above.
The single judge did not buy into that and emphasized that AZ had undoubtedly been aware of Sandoz’s generic since 26 July 2016; AZ could have lodged main proceedings at any time since then. The decision further holds (¶22; inofficial translation):
[T]he decision of the Board of Appeal of the EPO of 24 January 2019 […] may substantiate the claim to which the plaintiff is entitled with regard to the validity of the patent in suit, but in no way justifies urgency. […]
Ultimately, however, all parallel proceedings have no influence on the purely procedural question of urgency in the present summary proceedings. […]
The tactical awaiting of a foreign parallel decision on the patent in suit before an action is lodged does not belong to the subjective but rather to the subjective circumstances.
It surely is a tough exercise to fit the gist of a decision in a single tweet; but the FPC’s tweet on the decision is straight to the point:
A decision of a Board of Appeal of the EPO does not give rise to urgency where the contested product has been on the market for 30 months.
Urteil v. 9. April 2019 i.S. AstraZeneca AB g. Sandoz Pharma AG re vorsorgl. Massnahme (#Fulvestrant): ein Entscheide einer Beschwerdekammer des EPA begründet keine Dringlichkeit, wenn das angegriffene Produkt schon seit 30 Monaten auf dem Markt ist, https://t.co/iinRKiYDWk
The approach taken in the present decisions in my understanding focuses much more on the total time than on the apparent change of prima facie validity of the patent in suit over time. While the 14 months time bar is comparably generous (German courts typically deny urgency after 1-2 months, in my experience), it seems to be a pretty rigid time bar nowadays.
In an earlier case at the FPC, urgency had still been acknowledged for a request that had been filed five months after a BoA of the EPO had maintained the patent in suit which had been revoked in first instance by an opposition division (S2013_004, decision of 12 May 2014, ¶4.8).
It will be interesting to see how the FPC’s approach in the assessment of urgency will develop.
Please see this Blog here for a detailed review of the first instance decision S2018_004 of the FPC in this matter, granting interim injunctive relief against Sandoz’s generic Kivexa®.
An appeal against a decision in summary proceedings is not so easy anymore as it used to be. In former times, a not easily repairable harm had routinely be assumed on appeal against decisions concerning interim injunctive relief (see BGE 134 I 83, ¶3.1, with further reference). However, the more recent case law requires that the appellant is threatened by a not easily repairable harm (in legal terms) in the specific case at hand; see BGE 144 III 475, ¶1.2, with further reference). In the case at hand, the Supreme Court left it undecided whether the loss of the first mover advantage or reputational damages would be sufficient to meet the threshold. But the Supreme Court noted that the interim injunctive relief also prohibited possession and storage, and the defendant would thus have to destroy all products on stock. The Supreme Court held that this constitutes a not easily repairable harm in the sense of Art. 93(1) lit. a SCA, and the appeal was admissible already for this reason. This surely is lawyer’s playground; but I am wondering why the loss of stock was considered a not easily repairable harm? It surely is a harm. But wouldn’t it be one of the kind that is quite easy to repair?
Further, Sandoz had argued that the plaintiff was not actually at risk of a ‘not easily repairable harm’ as required by Art. 261(1) lit. b CPC.
The FPC had held that a not easily repairable harm was sufficiently credible; it was ‘obvious and notorious’ that in such group structures of pharmaceutical companies a disadvantage that cannot be easily repaired arises for the group and thus at least indirectly also for the formal holder of the SPC. The FPC failed to see why / to what extent this should not be the case in the present setup.
Es ist offensichtlich und notorisch, dass in derartigen Gruppenkonstellationen von pharmazeutischen Konzernen ein nicht leicht wiedergutzumachender Nachteil bei der Gruppe anfällt und damit wenigstens indirekt auch bei der formellen Inhaberin des Schutzrechts. Inwiefern dies in der vorliegenden Konstellation nicht der Fall sein sollte, ist nicht ersichtlich.
The Supreme Court essentially confirmed this reasoning.
The decision also discusses the dispatch of the Federal Council on the Civil Procedure Code and holds that any impairment of the execution of absolute rights constitutes a not easily repairable harm; BBl 2006, ¶5.19, p. 7354:
[…], wird in der Botschaft zur ZPO ausgeführt, jede Beeinträchtigung in der Ausübung absoluter Rechte bedeute einen nicht leicht wieder gutzumachenden Nachteil ([…]).
Frankly, I don’t see that in the dispatch. In my reading, the dispatch only holds that any impairment of the execution of absolute rights constitutes a harm, but it does not say that this harm is automatically not easily repairable:
Als Nachteil gilt beispielsweise eine Beeinträchtigung der Ausübung absoluter Rechte (z.B. Störung des Eigentums).
As to the alleged lack of novelty over D1 (WO 96/06844), the Supreme Court held that the FPC did not arbitrarily acknowledge novelty based on multiple selections from lists. In my perception, the Supreme Court suggests that the standard established by the case law of the Boards of Appeal of the EPO in relation to selections from multiple lists of certain length shall be applicable:
Die Beschwerdeführerin stellt zu Recht nicht in Frage, dass auf die Praxis der Beschwerdekammern des EPA abgestellt werden kann.
Thus, let’s do it. Here is the critical paragraph of D1:
[Abacavir] may be administered alone or in combination with […] Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for example zidovudine, zalcitabine, lamivudine, didanosine, stavudine, 5-chloro-2′,3′-dideoxy-3′-fluorouridine and (2R,5S)-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine; non-NRTIs for example nevirapine and α-APA; HIV protease inhibitors for example saquinavir; other anti-HIV agents for example soluble CD4; immune modulators for example interleukin II, erythyropoetin, tucaresol; and interferons for example a-interferon.
Now, does it require a multiple selection from two lists of certain lengths to arrive at the combination of abacavir and lamivudine, in accordance with the established case-law of the Boards of Appeal of the EPO? Does one have to first choose a generic class (NRTIs) and then lamivudine within that class — or does one just have to pick one compound from a single (structured) list of compounds? A decision on that question could have been a very interesting read. But the Supreme Court merely held that the FPC could well assume, without becoming arbitrary, that it would still require a twofold choice and thus a multiple selection from D1.
Selbst wenn daher die Rüge der Beschwerdeführerin begründet wäre (was offen bleiben kann), dass die im angefochtenen Entscheid genannte erste Auswahl keine relevante Wahl im Sinne der Rechtsprechung sein sollte [Anm.: Mono- bzw. Kombinationstherapie], konnte die Vorinstanz ohne in Willkür zu verfallen davon ausgehen, es erfordere immer noch eine zweifache Wahl und damit eine Mehrfachauswahl aus [D1], um zum Gegenstand des Patents der Beschwerdegegnerin zu gelangen.
Now, what? Does any ‘twofold selection’ whatsoever create novelty? I don’t think so. What about the requirement of the Boards of Appeal that the lists have a ‘certain length’? And what about the argument that the above is only a single, yet structured list? While the FPC clearly intended to follow the EPO’s approach, I am not so sure about the Supreme Court’s view on this. Anyway, time will tell …
As to the background of this case, please see the report about the hearing of 10 September 2018 on this Blog here.
Making a long(er) story short: The FPC granted interim injunctive relief to prohibit Sandoz from placing its generic version of Kivexa®, i.e. ‘Abacavir Lamivudine Sandoz®’, on the Swiss market. Noteworthy, Sandoz has apparently already lodged an appeal with the Supreme Court — long before the due date.
The decision is pretty straight-forward, at least at first glance. But still, it comes along with some quite pointed conclusions.
The standard of novelty
D1 (WO 96/06844) is not pre-published prior art, but might be relevant for the assessment of novelty under Art. 54(3) EPC 1973. The timeline is a bit tricky. The FPC holds that the priority claims of the patent in suit are valid, with particular reference to GB 9506490.3, claim 16. Still, D1 might be prior art under Art. 54(3) EPC if i) it had been further prosecuted before the EPO, and ii) the designation fees had been validly paid (R. 23a EPC 1973) — what is actually the case (see EPO Register), but had not been argued by the parties. The FPC thus left this issue undecided and did correctly not investigate this of its own motion. Rather, it moved on to the assessment of novelty vis-à-vis D1 as a matter of precaution, and held that novelty is given.
Interestingly, the German Federal Patent Court had apparently held in an interim assessment (which is not publicly available, to the best of my knowledge) that novelty was not given over D1. Now, how does the FPC explain the different outcome? That’s an interesting read, indeed. In a nutshell, the FPC bluntly notes that the standard of novelty is interpreted differently in Germany and at the European Patent Office — and that the FPC follows the approach taken by the EPO. Noteworthy, the FPC holds that the different standard is taken in particular with selection inventions. I am wondering: With all selection inventions, or only some kind of selection inventions? And what does in particular mean here? Is the different standard not even limited to selection inventions?
Dass das deutsche Bundespatentgericht in seiner vorläufigen Stellungnahme zu einem anderen Schluss gekommen ist, hängt damit zusammen, dass der Neuheitsbegriff in Deutschland anders interpretiert wird als vom Europäischen Patentamt, insbesondere [Anm.: Hervorhebung hinzugefügt] bei Auswahlerfindungen. Während beim europäischen Patentamt ein strenger Massstab angelegt wird hinsichtlich dessen, was im geltend gemachten Dokument des Standes der Technik für Neuheitsschädlichkeit offenbart sein muss (gewissermassen streng fotografischer Ansatz), wird gemäss deutscher Rechtsprechung ein grosszügigerer Massstab angelegt.4 D.h. ein Dokument ist gemäss deutscher Rechtsprechung bei Auswahlerfindungen eher neuheitsschädlich als gemäss Auffassung der Rechtsprechung der Beschwerdekammern des europäischen Patentamts.
Das Schweizer Bundespatentgericht folgt dem Ansatz der Beschwerdekammern des europäischen Patentamts, weswegen wie oben dargelegt Neuheit glaubhaft vorliegt.
4 Vgl. z.B. Moufang in Schulte, PatG, 10. Auflage, §3 Anm. 128 und 129.
The fact that the German Federal Patent Court came to a different conclusion in its provisional statement is due to the fact that the concept of novelty is interpreted differently in Germany than by the European Patent Office, in particular [Note: emphasis added] with regard to selection inventions. While the European Patent Office applies a strict standard with regard to what must be disclosed in the asserted prior art document in order to destroy novelty (to a certain extent a strictly photographic approach), according to German case law a more generous standard is applied.4 I.e. according to German case law a document is more harmful to novelty in selection inventions than according to the case law of the Boards of Appeal of the European Patent Office.
The Swiss Federal Patent Court follows the approach of the Boards of Appeal of the European Patent Office, which is why, as explained above, novelty is plausible.
4 See e.g. Moufang in Schulte, PatG, 10th edition, §3 Notes 128 and 129.
Practitioner may or may not share the FPC’s view in this respect. In any event, I feel that I have never seen this in writing, without any sugarcoat. Even Moufang in Schulte (referred to in fn 4 of the decision) only gives examples of decisions of the EPO and in Germany for closed numerical ranges, but does not draw any conclusions beyond that.
About motivation and expectation (of success)
The decision holds that in the assessment of inventive step the question arises whether there was a motivation for the combination of the two active ingredients and a reasonable expectation that this combination would also show the same or at least comparable effectiveness, i.e. that it is effectively a valid alternative; see ¶4.8. But there is no reference in the decision why it should be done this way.
I have mentioned earlier on this Blog here that I do not readily agree with the cumulative application of both the motivation and reasonable expectation of success criteria. And I still don’t. But this issue is not relevant for the outcome of the present matter; the decision denies a motivation and does not deal at all with the issue of a reasonable expectation.
Defendant firmly insisted in the hearing of 10 September 2018 that this is not the case, with reference to an illustration similar to the one shown on the right. In brief, plaintiff ViiV Healthcare UK Ltd is the holder of the Swiss SPC, and is fully owned by ViiV Healthcare Ltd; cf the right branch of the illustration.
The decision literally recites what has been argued by the defendant in the written reply to plaintiff’s request for injunctive relief (loosely translated below):
Plaintiff has failed to provide prima facie evidence, let alone to state reasons, and to prove that he would suffer any damage which could not easily be remedied if the request for interim injunctive relief was refused. In particular, the defendant contests the allegations in para. 138-141 of the application, namely the allegations (i) that the applicant would suffer damage consisting of a decrease in the number of units sold in Switzerland; (ii) that the applicant would be affected by a price review by the Federal Office of Public Health; (iii) that the applicant would suffer financial losses in the event of a price review; and (iv) that the Federal Office of Public Health would require the applicant either to reduce the ex-works price of Kivexa® or to accept a higher deductible. In any event, the defendant cannot be held liable for any losses resulting from the market entry of a second generic manufacturer (see the allegations in paragraph 1. 139 of the application regarding Art. 38 of the Swiss Care Allowance Ordinance).
Further, defendant had apparently submitted in writing (again, loosely translated):
Paragraph 14 of the request for interim injunctive relief states that ViiV Healthcare GmbH (hereinafter ViiV Switzerland) is a group company and not a subsidiary of the plaintiff. According to the extract from the commercial register (act. 1_5), ViiV Switzerland is 100% owned by ViiV Healthcare Overseas Limited (UK), which is a 100% subsidiary of the parent company of the ViiV Group, ViiV Healthcare Limited. ViiV Healthcare Limited is the sole shareholder of the applicant.
The above had been submitted under the heading ‘Parties’, but apparently not in relation to the (lack of a) not easily repairable harm. The decision holds that the fact that the plaintiff itself does not suffer any damage due to the aforementioned corporate structure, but rather ViiV Switzerland, had not been asserted by the defendant in his written reply to the request for injunctive relief, but only for the first time at the hearing on 10 September 2018 — i.e., after the closure of the file after a single exchange of briefs (see decision 144 III 117 of the Supreme Court, ¶2.2).
But even if these allegations were admitted into the proceedings, the decision holds that a not easily repairable harm would be sufficiently credible. In the FPC’s view, it is ‘obvious and notorious’ that in such group constellations of pharmaceutical companies a disadvantage that cannot be easily repaired arises for the group and thus at least indirectly also for the formal holder of the SPC. The FPC failed to see why / to what extent this should not be the case in the present setup.
Es ist offensichtlich und notorisch, dass in derartigen Gruppenkonstellationen von pharmazeutischen Konzernen ein nicht leicht wiedergutzumachender Nachteil bei der Gruppe anfällt und damit wenigstens indirekt auch bei der formellen Inhaberin des Schutzrechts. Inwiefern dies in der vorliegenden Konstellation nicht der Fall sein sollte, ist nicht ersichtlich.
As noted above, defendant has apparently already appealed the decision.
UPDATE 10 April 2019:
Defendant’s appeal has been dismissed by the Supreme Court with decision 4A_575/2018 of 12 March 2019; published today.
The European public assessment report (EPAR) of the European Medicines Agency (EMA) provides a wealth of further information about this antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection.
Sandoz‘s generic version ‘Abacavir Lamivudine Sandoz®’ had obtained market approval on December 15, 2017, and it has been listed since April 1, 2018; see compendium.ch.
Sandoz contests infringement of the SPC solely on the ground that EP’637 and the SPC are null and void. A lack of novelty and inventive step is alleged, and that the priority claim was not valid. Sandoz had refused to undertake not to put the product on the market before the expiry of the SPC (October 30, 2020); Sandoz rather informed ViiV that it would start marketing in calendar week 21 — and has consequently been sued by ViiV.
The parties dissent about whether or not EP’637 is actually entitled to the priorities claimed; see a compilation of the two priority documents here. Respondent argued that the whole disclosure of the priority documents is about a combination of three active substances, compared to a combination of only ABC and 3TC finally claimed in the patent in suit; plaintiff disagreed.
If priority was not validly claimed, D1 (WO 96/06844) would be pre-published prior art, i.e. relevant for both novelty and inventive step assessment.
Has D1 (WO 96/06844) to be considered in the assessment of novelty?
From the pleadings, I conclude that in the exchange of briefs the plaintiff himself had submitted that D1 (WO 96/06844) forms prior art that is (only) relevant for the assessment of novelty. Respondent had agreed. Only later, in my understanding in the judge-rapporteur’s expert opinion, it has been held that D1 does not form part of the prior art under Art. 54(3) and (4) EPC 1973 or Art. 7(3) lit. a old PatA, respectively. Respondent disagrees on the merits, and further argued that the principle of party disposition was violated.
Respondent argued that the German Federal Patent Court and a Stockholm court had denied novelty. I could not yet spot any such decision; maybe these were only interim assessments of the courts before the respective parties settled(?).
If you know more, I would be grateful if you would let me know.
An ‘optional’ disclaimer in summary infringement proceedings?
In a secondary line of defense, plaintiff offered to limit the patent with a disclaimer, to exclude the disclosure of D1 and to restore novelty if necessary.
Defendant argued that this was not possible and referred to an order of the Zurich Commercial Court (HE070010 of 22 August 2007, issued by Dieter BRÄNDLE, the later President of the FPC) that was upheld by the Zurich Court of Appeal (AA070145/U/Ia of 25 January 2008). At that time, it had been held (emphasis in original; cf ¶3.2):
Im Massnahmeverfahren [kann] sich der Kläger somit nur auf ein Zertifikat bzw. das diesem zugrundeliegende Patent in der aktuellen (d.h. uneingeschränkten) Fassung berufen.
In summary proceedings the plaintiff may thus only rely on the SPC or the basic patent, respectively, in its current (i.e. unamended) version.
Risk of a not easily reparable harm for the plaintiff?
Further, the requirement of a ‘not easily reparable harm’ for interim injunctive relief to be granted has been addressed at length by the parties. Is the plaintiff actually at risk of a ‘not easily reparable harm’ as required by Art. 261(1) lit. b CPC?
Respondent firmly insisted that this is not the case, with reference to an illustration similar to the one shown on the right. In brief, plaintiff ViiV Healthcare UK Ltd is the holder of the Swiss SPC, and is fully owned by ViiV Healthcare Ltd; cf the right branch of the illustration.
Respondent argued that none of the boilerplate arguments like confusion of the market, price erosion, etc can apply here, since this does not affect the plaintiff / SPC holder. Plaintiff inter alia argued in the hearing that the Swiss MA holder has a license under SPC. This was firmly rebutted by the respondent as ‘not true’, or at least not to be a royalty-bearing license — and procedurally belated in any event. In my understanding, it had not been argued in the written exchange of briefs that a license is in place.
Finally, the parties were asked whether they were interested in settlement discussions. I would have loved to hear the answer, but the public has been excluded on request of the plaintiff even before the general (un)willingness to talk settlement has been indicated.
Reported by Martin WILMING
P.S.: After plaintiff’s initial pleadings, the presiding judge asked whether the pleading notes that had obviously at least partially been read out would be handed over to the court (“not necessarily to the other party”), to ease compilation of the minutes. The parties agreed. A pragmatic approach. Still, I strongly feel that whenever pleading notes are handed over to the court, the other party should get a copy, too. Frankly, I would not feel comfortable when the counter-party submits something in writing that I haven’t seen. How would I know that there was no change or omission in the speech vis-à-vis the pleading notes, and how easily might a different message silently sneak into the minds of the judges …