Tag: patent

Another Italian take on the Fulvestrant Saga. The Court of Milan on technical prejudice, plausibility and off-label use.

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AstraZeneca has fought its fulvestrant patent portfolio all across Europe, including Italy, for quite some time (see for instance here, here, here and here). Fulvestrant is an oncological product used for the treatment of breast cancer and is marketed by AstraZenca as Faslodex.

The Court of Milan recently chipped in again with its decision of 3 December 2020 (No. 7930/2020, Judge Rapporteur Ms Alima Zana, AstraZeneca v. Teva, here), delivering a number of interesting points on validity and infringement of second medical use patents.

In particular, the Court argued that the Italian arm of AstraZenca’s European patent No. EP 1 272 195 (“EP195”) lacked inventive step, among other things, as it did not overcome a technical prejudice, that the claimed therapeutic indication was not plausible and that – in any case – AstraZeneca did not offer sufficient evidence of Teva’s off-label infringement.

Photo by Chokniti Khongchum on Pexels.com

Procedural background

In 2018, AstraZeneca filed an action against Teva before the Court of Milan for the alleged infringement of the EP195 patent, titled “use of fulvestrant in the treatment of resistant breast cancer”. Teva counter-claimed arguing that EP195 was invalid.

In May 2020, as Teva was about to launch Fulvestrant Teva into the Italian market, AstraZeneca filed a petition for preliminary injunction based on EP195. The Court refused the PI in August (here) as it deemed that AstraZeneca’s action did not meet the “likelihood of success on the merits” requirement (so-called fumus boni iuris). The Court thus went on to decide the case on the merits.

The patent and the allegedly infringing product

Claim 1 of EP195 reads: “Use of fulvestrant in the preparation of a medicament for the treatment of a patient with breast cancer who previously has been treated with an aromatase inhibitor and tamoxifen and has failed with such previous treatment” – a typical “Swiss-type” claim (for additional information on “Swiss-type” claims, see EPO’s Guidelines, here).

We gather that the patented use of fulvestrant (in “the treatment of a patient with breast cancer who previously has been treated with an aromatase inhibitor and tamoxifen and has failed with such previous treatment”) was not indicated in the SmPC or package leaflet of Fulvestrant Teva. The product’s marketing authorization (“MA”) would confirm this (see the 2016 version of the MA, here, and further updates here, here, here and here).

Expert opinions and foreign decisions

The Court of Milan deemed that EP195 was invalid, going against the opinion of its own Court-appointed expert. This is rather uncommon in Italian patent proceedings since Judges have no technical background and they necessarily rely on their experts’ reports. Here, however, the Court was convinced by the opinion issued by a different expert in the parallel proceedings brought by AstraZeneca against another generic company on EP195 (Docket No. 37181/2018 – this case is referred to in the judgement, but we are not aware of a published decision yet).

Also, the Court relied on the foreign decisions issued on EP195 by the German Bundespatentgericht (here), the Swiss Bundespatentgericht and the Court of Barcelona (order of 18 July 2018, confirmed in 2019, here).

In doing so, the Court stressed that judges can base their decisions also on evidence that is acquired in different proceedings between the same parties, or even different parties. The general rule of Article 116 of the Civil Procedure Code (CPC) – according to which “the judge must assess the evidence according to his or her prudent judgment, unless the law provides otherwise” – fully applies to the Expert Report issued in the parallel proceedings brought by AstraZeneca on EP195. Besides, the “parallel” Expert Report was also filed by the parties to these proceedings and heavily discussed in their briefs, so that there was no surprise argument.

Lack of inventive step

The Court-appointed Expert deemed that the closest prior art to EP195 was the “Gale” article. The Court picked the “Vogel” article instead as the closest prior art and determined the objective technical problem accordingly. Applying the EPO’s “could-would approach”, the Court of Milan concluded that the solution disclosed in EP195 (i.e., to use fulvestrant as a line of treatment for breast cancer after aromatase inhibitors and tamoxifen) lacked inventive step.

According to the Court, the person skilled in the art would have found in “Vogel” an incentive to use fulvestrant as a third line treatment, after tamoxifen and aromatase inhibitors, since (i) “Vogel” mentioned pure anti-estrogens as emerging candidates to be used in the second-to-fourth therapeutic line (ii) fulvestrant was identified as a pure anti-estrogen in a publication (“DeFriend”) referenced in “Vogel” and (iii) “Vogel” specifically taught that pure anti-estrogens inhibit the growth of a tumor already treated with tamoxifen.

The Court also denied that the use of fulvestrant after tamoxifen overcame a technical prejudice. AstraZeneca argued that because tamoxifen and fulvestrant have a similar mechanism of action, the person skilled in the art would have feared that the breast cancer may have formed resistances and mutations to fulvestrant after administration of tamoxifen. The Court, however, found that tamoxifen and fulvestrant have substantial differences, which were known in the art, and therefore no technical prejudice could arise. On this point, the Court directly referenced the German Bundespatentgericht decision (here), which found that there was no technical prejudice against the choice of fulvestrant as a pure anti-estrogen since:

“the person skilled in the art associated the choice of fulvestrant with a reasonable expectation of success because Vogel considers it to be an advantageous example of a pure anti-estrogen, as it does not show any relevant side effects despite its high efficacy and shows fewer side effects than other drugs known to be effective for the endocrine treatment of breast cancer”.

Plausibility (?)

As an additional ground of invalidity, the Court of Milan stressed that the patent would be valid only in relation to a purely palliative treatment (and not as an adjuvant therapy) in a patient affected by breast cancer that was previously treated by an aromatase inhibitor and tamoxifen, where said treatments were unsuccessful. This is because the experimental data provided in the patent and in the “Perey” document – published in 2007, after the filing – allegedly “refer only to a palliative use of fulvestrant”, showing that a “plausible solution to the technical problem was found only in relation to the palliative use” of the active principle. The Court thus held that, in any case, AstraZeneca would have had to submit a limited wording of claim 1 on the palliative use alone.

The Court, however, did not precisely identify which patentability requirement would have been affected by this “plausibility” issue, although novelty, inventive step and sufficiency of disclosure can all be theoretically impacted by a (lack of) plausibility argument (on the “nebulous” plausibility requirement, see a recent article by Rt. Hon. Professor Sir Robin Jacob, here). The Court was arguably hinting at an insufficiency of disclosure in relation to the therapeutic indication. It should be stressed, however, that the EPO does not expect applicants to submit clinical trials for each therapeutic indication. In particular, the EPO Guidelines (here) suggest that:

“Either the application must provide suitable evidence for the claimed therapeutic effect or it must be derivable from the prior art or common general knowledge. The disclosure of experimental results in the application is not always required to establish sufficiency, in particular if the application discloses a plausible technical concept and there are no substantiated doubts that the claimed concept can be put into practice (T 950/13 citing T 578/06). Any kind of experimental data have been accepted by the boards. It has also been repeatedly emphasised that ‘it is not always necessary that results of applying the claimed composition in clinical trials, or at least to animals are reported’ (T 1273/09 citing T 609/02)”.

Besides, in an earlier case on fulvestrant (Decision of 24 July 2019, Actavis v. AstraZeneca, concerning the Italian portion of EP 2 266 573: here), the Court of Milan had rejected an insufficiency/plausibility argument by stating that: “[t]he inclusion of examples in the patent specification is not mandatory nor is it a requirement for the sufficiency of the disclosure the completion of a clinical trial at the date of the filing, as it is possible to rely on subsequent trials (decision T 433/05), provided that the effect was plausible at the date of filing” (for a comment on this case see here). As the argument was not fully developed in the decision by reference to the “Perey” document, it could seem that the Court of Milan is adopting diverging approaches to plausibility, and further clarifications would be welcomed.

Lack of infringement

To seal the deal, the Court of Milan then went on to say that, in any case, Teva’s product would not have infringed EP195. The Court argument goes as follows:

“I. The asserted patent is a patent for a second medical use, the patent being directed at the protection of a known substance, limited to the use claimed;

II. In such a case the infringement cannot be found if the generic medicine in its marketing authorisation contains a clear limitation to uses that do not violate patent rights […]

III. In order for there to be infringement […] it is necessary that the [competitor’s] product is not only abstractly suitable for the claimed use, but that the package leaflet indicates the use of the product for the intended purpose.

This assessment is supported by the numerous proceedings in other jurisdictions that have ruled in favour of non-infringement [e.g. the decision of the Oberlandesgericht Düsseldorf, 9 January 2019, mentioned in the footnote].

The defendant’s argument that Teva’s drug is not ‘suitable’ for the claimed use is therefore correct, as this is not the case from a regulatory (since the product is not authorised for the claimed use) nor from a practical point of view (since the claimed use is not foreseen or included in the oncological practice), nor has the [plaintiff] offered any evidence to the contrary”.

Due to the finding of invalidity of EP195, the Court’s non-infringement argument is ad abundantiam and consequently rather short. However, some passages are worth being discussed.

First, as to point (II), it is not entirely clear what the Court is referring to when it says that the MA of Fulvestrant Teva “contains a clear limitation to uses that do not violate patent rights”. Assuming that the Fulvestrant Teva’s MA does not explicitly include the therapeutic indication covered by EP195, the Court could be referring to the following passage in the authorization (see here and here):

“The holder of the marketing authorization for the generic drug is solely responsible for full compliance with the industrial property rights of the reference medicinal product and of the patent legislation in force.

The holder of the MA of the equivalent medicine is also responsible for ensuring full compliance with the provisions of Article 14(2) of Legislative Decree 219/2006, which requires that those parts of the summary of product characteristics of the reference medicine which refer to indications or dosages still covered by a patent at the time the medicine is placed on the market are not included in the leaflets”.

If this is the case, the Court’s argument on the MA is not particularly convincing. Indeed, this wording – which is boilerplate and often included in MAs – can hardly be read as a “clear limitation to uses that do not violate patent rights”. Infringing uses are technically neither excluded nor forbidden by it, at least under patent law. The Italian Pharmaceutical Authority simply stresses that it is the generics’ responsibility to steer clear of patent rights.

Second, as to point (III), the Court would seem to suggest that patent infringement of a second medical use patent can only occur if the package leaflet “indicates the [claimed] use“. However, the fact that a specific therapeutic indication is missing from the MA, SmPC or package leaflet does not exclude per se that the drug may be used and prescribed for the patented use.

Photo by Pixabay

Besides, the Court’s argument is not fully supported by the case law of the Oberlandesgericht Düsseldorf referred to in the decision (see here and here). Although in the parallel AstraZeneca v. Teva proceedings the Düsseldorf Court found that EP195 was not infringed on the merits of the case, German case law has established that patent infringement can occur also in “off-label” cases, where the pharmaceutical product is (i) suitable to be used according to the patented indication and (ii) the manufacturer or distributor takes advantage of circumstances that ensure that the product is sold and/or is used for the intended purpose. This, in turn, requires a sufficient extent of use in accordance with the patent as well as knowledge (or at least a willful blindness) of this use on the part of the manufacturer or distributor (see Oberlandesgericht Düsseldorf, 5 May 2017, I-2 W 6/17, Estrogen Blocker, § 85, another case on EP195, here).

In any way, the Court of Milan somewhat softens its argument by adding, in the last paragraph, that AstraZeneca did not provide any evidence of the infringement by Teva or that the use of fulvestrant according to EP195 was the current oncological practice in Italy. Conversely – one may wonder – if AstraZeneca had provided sufficient evidence of the off-label use a finding of infringement could have been possible.

For further answers we now look forward to the decision of the Court of Milan in the parallel case (Docket No. 37181/2018) and will report on any interesting development.

Giovanni Trabucco

Court of Milan, 3 December 2020, Decision No. 7930/2020, AstraZeneca v. Teva

The Court of Rome affirms its jurisdiction in a torpedo case

IPlens1 Comment

In a post of some months ago, after noting that none of the torpedoes launched in Italy after the Asclepion ruling [Italian Court of Cassation, 10 June 2013, no. 14508, in Giur. ann. dir. ind., 2013 (for a full English translation, see IIC, 2014, pp. 822 ff.)] had been successful, we envisaged a possible end to the Italian torpedo story. A recent decision of the Court of Rome shows, however, that the end is yet to come. In a non-infringement action brought against an Austrian patentee (and two other defendants, also from Austria) with regard to the Italian part and several foreign parts of a European patent, the Court of Rome firmly stated that

“the Italian courts have jurisdiction … for the French, German, Austrian and UK parts of the patent, on the basis of art. 5.3, EU Council Regulation 44/2001 of 22 December 2000, whereby the courts for the place where the harmful event occurred or may occur have jurisdiction, and on the basis of art. 27 of the Regulation, concerning jurisdiction for related actions”.

The brief reasoning of the decision (full text, in Italian) exclusively stems from a quotation of the Asclepion ruling of the Court of Cassation mentioned above. With regard to this ruling and its impact on torpedo actions (as well as for a review of the most recent decisions issued in Italy on the topic), we refer to the considerations already made here.

Riccardo Perotti

Court of Rome, 5 February 2018, Anki v. Stadlbauer 

A requiem for torpedo actions? A catalogue of the most recent decisions on the issue

IPlens3 Comments

 

Actions

(i) relating to a European Patent

(ii) aimed at obtaining a declaration of non-infringement of different national portions of said European Patent

(iii) brought before Italian Courts

(iv) against a patentee who is not domiciled in Italy

are commonly known as Italian torpedoes (the expression is a fortunate coinage of Mario Franzosi).

These actions are often started to take advantage of the rules concerning lis pendens. Where a non-infringement action is pending before a Court (say an Italian Court) with regard to the national portion of a European Patent (say the German portion), any infringement action subsequently brought before the Court of another country (say a German Court) with regard to the same portion of the same European Patent may be stayed. This stay – and the consequent delay in ascertainment of infringement – is the goal of torpedo-launchers.

Of course, the slower the jurisdiction, the longer the stay. Thus, launching a torpedo is particularly effective in slow jurisdictions, like – at least in the past – that of Italy.

Traditionally Italian Courts have not looked with favor on such actions, seeing them as tools for misusing the (flaws of the Italian) legal system.

This traditional view was authoritatively expressed by a 2003 decision of the Joint Divisions of the Court of Cassation (the Windmöller decision), which deracinated torpedo actions on the grounds that Article 5.3 of the Brussels Convention of 1968 does not apply to non-infringement claims (Italian Court of Cassation, decision no. 19550/2003, in Giur. Ann. Dir. Ind., 2004, pp. 61 ff.). If it is the plaintiff itself which denies the existence of a harmful event, said the Court, then by definition there cannot be jurisdiction under Article 5.3 of the Brussels Convention.

A few years later, in the GAT case (here), the EU Court of Justice struck another blow against torpedoes by stating that the rule of exclusive jurisdiction laid down by Article 16.4 of the Brussels Convention of 1968 [corresponding to Article 22.4 of Regulation 44/2001] concerns all proceedings relating to the registration or validity of a patent

“irrespective of whether the issue is raised by way of an action or a plea in objection” (the principle was later incorporated in Article 24.4 of Regulation 1215/12).

As a result – and even regardless of the restrictive interpretation of Article 5.3 of the Brussels Convention given by the Windmöller ruling -, in order not to fall into the exclusive jurisdiction under Article 16.4 of the Brussels Convention and 22.4 of Regulation 44/2001, torpedo actions had to be based on pure non-infringement arguments.

In this scenario, most certainly not favorable to torpedoes, a decision of the Joint Divisions of the Court of Cassation reopened the discussion on the admissibility of this kind of action (Court of Cassation, 10 June 2013, in Giur. ann. dir. ind., 2013, pp. 60 ff.: the Asclepion case; a full English translation of the decision has been published in IIC, 2014, pp. 822 ff.). In the context of a non-infringement case brought before the Court of Rome by a German company with regard to the Italian and German portions of a European Patent owned by a US company, the Joint Divisions – quoting, word for word, the EUCJ Folien Fischer decision (here) – stated that

(a) “Article 5.3 of Regulation 44/2001 … must be interpreted “as meaning that an action for a negative declaration seeking to establish the absence of liability in tort, delict, or quasi-delict falls within the scope of that provision”

and also that

 (b) “therefore [pertanto, in the original Italian text] with regard to the declaration of non-infringement sought … before the Court of Rome, the Italian Courts must be considered to have jurisdiction, on the grounds that they are the Courts of the place where the harmful event may occur, also with regard to the “German portion” of the European Patent” [my translation].

The 2013 Asclepion ruling certainly lent itself to interpretation as a general permit to launch torpedoes, at least when they do not rely on any arguments of invalidity. This is, indeed, what the Court said. But, looking more closely, a missing step can be seen in the reasoning of the Asclepion ruling, between statements (a) and (b). This significantly limits its practical impact.

If closing the jurisdictional door of Article 5.3 of Regulation 44/2001 to non-infringement actions, as the Windmöller 2003 decision did, fatally blocks any attempt to launch torpedoes, interpreting Article 5.3 as covering both infringement and non-infringement actions does not necessarily mean – in spite of the adverb “therefore” used by the Court of Cassation – that the Italian Courts have jurisdiction under this provision over actions concerning the foreign portions of a European Patent. To this end, something more must exist, and namely a link with Italy.

It is precisely because of the (non-) existence of this link that the torpedo actions brought before Italian Courts after the Asclepion ruling have been stopped.

In Schindler v. Otis, in line with Asclepion, the Court of Milan (Judge Dr. Marina Tavassi; decision of 27 January 2014, published in Giur. ann. dir. Ind., 2014, pp. 741 ff.) admitted that, in itself, a non-infringement action may be brought against a foreign defendant under Article 5.3. Nevertheless, it declined its jurisdiction on the non-infringement claims submitted against a US patentee, insofar as the Spanish portions of the European patent in suit were concerned. According to the Court,

“Italy can be the place where the harmful event occurs or may occur only with regard to the Italian portion of a European patent, because there cannot be harm – actual or potential – caused in Italy by the alleged infringement of the Spanish portions of the patents in suit. Indeed, any national portion of a European patent is effective only in the relevant country and may be infringed only in that country” [my translation].

Therefore, in the opinion of the Court of Milan, when it comes to the infringement/non infringement of foreign portions of European patents owned by foreign patentees, there can never be a link with the country of Italy.

In the more recent Basf v. Bayer case, the Court of Milan (Judge Dr. Alessandra Dal Moro; the decision, dated 14 December 2016, published in Riv. dir. ind., 2017, I, pp. 309 ff. and also available here) fully confirmed the above approach and declared its lack of jurisdiction over the non-infringement of the foreign portion of a European patent (in particular, the German portion). In doing so, the Court explicitly dealt with the reasoning of Asclepion, clarifying why, in its view, the Court of Cassation’s decision could not be read as allowing torpedoes:

“the fact that article 5.3 of Regulation 44/2001 (now replaced by Regulation 1215/2012) may be applied to non-infringement actions in no way changes the stance of the Supreme Court with regard to the existence of jurisdiction in the case of infringement (or non-infringement) of non-Italian portions of European Patents. A claim seeking a declaration whereby certain conduct does not constitute infringement of a patent means that the patent is effective, and this effectiveness is geographically limited to the perimeter of the legal system to which it refers. Outside that perimeter of effectiveness, it is not possible to discuss infringing or non-infringing conduct and it is therefore not even possible to allege an, actual or potential, ‘harmful event’” [my translation].

A further decision was issued on torpedoes in 2014, but on different grounds. In Agilent v. Oerlikon, the Court of Genova (Judge Dr. Rossella Silvestri; the decision, dated 23 April 2014, is available here) declined its jurisdiction because the torpedo-launcher had raised invalidity arguments in support of non-infringement claims concerning the German portion of a European patent and a German utility model. The claims thus fell into the exclusive jurisdiction of the Courts of the place of registration.

Hence, all the torpedoes launched in Italy after the Asclepion ruling have been dismissed on the grounds of lack of jurisdiction. Does this mean that the torpedo saga has finally come to an end?

Riccardo Perotti

Product-by-process patent = product patent??

IPlens1 Comment

Worthy of comment is a recent decision of EPO’s Enlarged Board of Appeal (March 25, 2015) in the cases Tomato II and Broccoli II (respectively, Case Number G2/12 here and Case Number G2/13 here). Both cases relate to the patentability of plants and plant matter under Article 53(b) EPC. The Tomato II case concerns a “method for breeding tomatoes having reduced water content and product of the method”, while the Broccoli II case concerns a “method for selective increase of the anticarcinogenic glucosinolates in brassica species”.

The EPO’s Enlarged Board of Appeal stated that even a product-by-process patent is a “product patent” autonomously protected from the process that describes the former and from which the implementation as product depends.

The EPO’s approach (see, in each decision: Reasons, Legal erosion of the exceptions to patentability,§ 6.(b), p.61) is open to criticism. On the one side it risks paralyzing the competitive dynamics of process innovation, in contrast an interpretation of articles 64(2) EPC and 34 TRIPs whereby third parties are allowed to make the same product with a totally different process—hence,   without any absolute block imposed by pre-existing product patents that are the fruit of a totally different intellectual process. On the other side, EPO’s opinion ‘forgets’ that in absence of that process, the product wouldn’t even exist, as the facts of the cases highlighted that no other processes were available to achieve the same result. The final outcome of said decisions is even more debatable as the process through which the product was described and claimed was essentially biological , thus as such non patentable: with the paradoxical ultimate result of allowing the patenting of a product that could be realized only through a process not patentable by definition!

Gustavo Ghidini

Gianluca De Cristofaro

EPO, Enlarged Board of Appeal, 25 March 2015, Case Number G2/12 and Case Number G 2/13, Tomato II and Broccoli II

updated on 12 November 2015