Study on SPCs for the Dutch Parliament published

The Technopolis group has recently completed a study on SPCs for the Dutch parliament entitled "Effects of supplementary protection mechanisms for pharmaceutical products". A copy of the study is available for downloading here.

Alfred Radauer of the Technopolis Group writes:

"The study investigates the impacts of the interaction of supplementary protection certificates (SPCs), paediatric extensions, data and market exclusivity as well as orphan drug protection on innovation in pharma and on the healthcare system. The 173-page report is in English and builds on a legal analysis as well as an economic analysis involving an interview programme, secondary data analysis as well as case studies for seven drugs that have used the said supplementary protection instruments.

The study was performed by Technopolis in collaboration with experts from the University of Liverpool and University of Amsterdam. It was commissioned by the Dutch Ministries of Health and Economics.

We hope that this study makes for good reading and adds to the debate on SPCs and regulatory protection of pharmaceutical products. We would be delighted to receive comments and suggestions at ips@technopolis-group.com."

Rosuvastatin: is it a “pharmaceutically acceptable salt”?

On 15 July 2015 the District Court for The Hague handed down its decision in Resolution Chemicals v Shionogi and AstraZeneca. This case turned on the validity and scope of protection of Shionogi’s SPC -- in particular, was Resolution Chemicals’ proposed zinc salt of rosuvastatin a “pharmaceutically acceptable salt” as claimed in the basic patent and which would infringe the SPC? The District Court granted a declaration of non-infringement. 

Jan Pot and Mark van Gardingen (both of Brinkhof, which acted for Resolution Chemicals) know how interesting this decision is for our readers and therefore have kindly let us have both the authentic Dutch text of the judgment and an English translation. Their summary of the decision -- without any commentary -- appears below.

Thanks so much, Jan and Mark, for your efforts, which are much appreciated!

Shionogi holds supplementary protection certificate (SPC) 300125 for ‘Rosuvastatinum, if desired in the form of a non-toxic pharmaceutically acceptable salt, in particular the calcium salt’. AstraZeneca is the exclusive licensee for this SPC. The basic patent for the SPC was EP 0 521 471 (“EP 471”), which had expired in 2012. Claim 1 of EP 471 was for “the compound [rosuvastatin, described using its molecular formula] acid or a non-toxic pharmaceutically acceptable salt thereof.” Resolution Chemicals requested the Court to partly nullify the SPC, namely insofar as it extended to more than the calcium and sodium salt of rosuvastatin, and to grant a declaration of non-infringement in relation to its rosuvastatin zinc salt. The case is somewhat unusual in that Resolution Chemicals attacked the validity and scope of protection of the basic patent after its expiration in order to limit (the scope of protection of) the SPC.

The first issue before the court was construction of the term “non-toxic pharmaceutically acceptable salt” as used in claim 1 of EP 471. Resolution Chemicals argued that this term was limited to salts with an alkali metal ion, an alkaline earth metal ion or an ammonium ion by virtue of a definition in paragraph [0007] of the patent, which stated that “the term "a non-toxic pharmaceutically acceptable salt" refers to a salt in which the cation is an alkali metal ion, an alkaline earth metal ion, or an ammonium ion”. As a consequence, rosuvastatin zinc was not within the scope of claim 1. Shionogi and AstraZeneca however contended that para. [0007] should not be considered limiting and that “a non-toxic pharmaceutically acceptable salt” should be understood to include the zinc salt. The Court concluded that the skilled person would read the claim term “non-toxic pharmaceutically acceptable salt” in claim 1 in conjunction with para. [0007], and that the skilled person would construe this paragraph as a limiting definition. The court observed that at other points the specification used non-limiting terms such as “and the like”, whereas para. [0007] used the more restrictive “refers to”. The Court also noted that it was common general knowledge at the priority date that the choice for a particular salt form for a medicinal product matters in terms of therapeutic availability, and that performing a salt screen was for that reason routinely applied. Consequently, the skilled person may presume that the choice for the salts disclosed in paragraph [0007] was a conscious choice by the patentee. The Court therefore ruled that the zinc salt was not within the scope of EP 471.

The second issue was that of added matter. While the patent as granted was limited to rosuvastatin, the original application disclosed and claimed a broad class of compounds using a Markush formula. Resolution contended that the application as filed only offered support for rosuvastatin calcium and rosuvastatin sodium: these were the only salt forms of rosuvastatin disclosed by the examples and it was not permissible to extend this disclosure to other salt forms or to the acid. AstraZeneca and Shionogi claimed that rosuvastatin was the essence of the invention and that it was permissible to claim other salts as well as the acid. After examining the application as filed, the Court came to the conclusion that there was support in the original application not only for sodium and calcium but also for the other salts mentioned in para. [0007]. However, the Court found that there was no direct and unambiguous disclosure in the application for rosuvastatin acid. The Court therefore concluded that the SPC would have to be limited to the salt forms of rosuvastatin in which the cation was an alkali metal ion, an alkaline earth metal ion or an ammonium ion, as there would have been grounds to nullify the basic patent insofar as it had a broader scope.

Having dealt with validity and scope of protection of the basic patent and the SPC, the Court swiftly dealt with infringement. As zinc is neither an alkali metal ion, nor an alkaline earth metal ion, nor an ammonium ion, there was no direct infringement. The Court rejected infringement through equivalence, as zinc would have been a foreseeable alternative at the priority date which are taken into account when construing the claims according to Article 69 EPC. Accordingly, there was no need to discuss whether the zinc salt is “technically” equivalent to the calcium or sodium salt of rosuvastatin (or any of the other salts defined in para. [0007]). Finally, the Court also rejected indirect infringement. Shionogi and AstraZeneca’s indirect infringement argument was based on the premise that the scope of protection extended to rosuvastatin acid, which had already been rejected by the Court on the basis of added matter. The Court did not deal with AstraZeneca’s further argument that the rosuvastatin anions in solution associate with sodium cations present in the gastric fluid, since this argument was raised too late.

Dutch Council of State upholds Syngenta's "wrong date" appeal

Writing on behalf of himself and his Netherlands CMS colleagues Edmon Oude Elferink, Conny Delissen and Willem Hoorneman, Rogier de Vrey brings news of a recent judgment delivered by the Dutch Council of State on 18 February 2015 in what he describes as a very interesting SPC case [so far as this blogger is concerned, all SPC cases are interesting, and he can even find room in his heart for those decisions on the Special Mechanism ...]. The Council of State is the highest general administrative court in the Netherlands, so its pronouncements deserve our attention. Writes Rogier

This case basically concerns the issue whether it is possible to rectify – in this case extend – the term of protection of an SPC, after it has been granted, if the term of protection of the certificate is incorrectly calculated.

In this case, the Netherlands Patent Office ("NPO") granted Syngenta an SPC on 9 December 2005 on the basis of a ('mono') Polish MA. It is now undisputed, after the University of Queensland judgment of the Court of Justice of the European Union (C-630/10), that the SPC was granted on the basis of the wrong MA. The NPO should have used the Finnish "combi-MA" for the calculation of the term of the SPC. As a result, the certificate was valid until 24 March 2014 while, had the Finnish "combi-MA" been used, the term of the certificate would have extended for more than 1½ years. 

On 3 September 2013, about eight years after the grant of the certificate, Syngenta asked the NPO to rectify the duration of the certificate. At the time of this request, the certificate was still in force. This request was denied by the NPO. The NPO also dismissed the notice of objection lodged by Syngenta to the NPO. The Court of The Hague subsequently dismissed the appeal brought by Syngenta against this decision of the NPO. Syngenta appealed this decision with the Administrative Jurisdiction Division of the Council of State, requesting the president to grant an interim injunction. This request for an interim injunction was rejected as well.

Council of State

In the proceedings on the matters before the Council of State, NPO asserted that there is no obligation to reconsider its decision to grant the certificate in 2005. Syngenta could have filed a notice of objection (after 9 December 2005) within the statutory period of 6 weeks, which it had not done. Article 17(2) of Regulation 1610/96 (the Regulation) does not, according to the NPO, lead to another result, as this clause allegedly only refers to the possibility of lodging an objection in accordance with national rules of procedure (the 6 weeks term). There were no new facts or changed circumstances that would require reconsideration of the original decision under administrative law (art. 4:6 of the Dutch Administrative Act). Finally, NPO asserted that rectifying the duration of the certificate could affect the interests of third parties.

Syngenta argued – in brief - that the interpretation of NPO of Article 17(2) of the Regulation does not comply with the mandatory and supranational nature of Regulation 1610/96, the general aim and purpose of this Regulation and the principle of Loyalty in EU Law (Article 4 (3) TEU). The correction mechanism introduced in Article 17(2) would be meaningless if invoking this Article would be subject to a national appeal period of 6 weeks. Article 17(2) was inserted (at a later stage) in the Regulation as an option for appeal, separate from the option provided by Article 17(1). Moreover, Article 17(2) should be interpreted broadly. The fact that in this case the incorrect calculation of the duration of the certificate is not the result of an error in the entry in the application of the date of the first MA, but the result of the use of an incorrect MA, can not preclude application of Article 17 (2).

The Council of State (on the merits) was convinced by the arguments of Syngenta and upheld the appeal lodged by Syngenta. The Council of State ruled that the duration of the certificate granted to Syngenta will be extended in the sense that the expiry date of the certificate will be set at 18 December 2015 and ordered NPO to compensate Syngenta for the costs of the proceedings.

In particular, this broad interpretation of Article 17(2) and the ability to basically at anytime request rectification under Article 17(2), is groundbreaking and has a potential impact on the position of SPC owners. To our knowledge, the judgment is the first of its kind in the European Union. We are very pleased with the spectacular result.

Rogier has helpfully furnished The SPC Blog with an English translation of this decision, which you can read here or download here

"One SPC per patent" again -- this time in the Netherlands

From our friend Martijn de Lange comes news of a fascinating Dutch development. Explains Martijn:

"The Court of Appeal has decided in a case concerning the product irbesartan + HCTZ that the CJEU rulings in Medeva and Georgetown should be read as "one SPC per patent", not "one SPC per product per patent" (see (i) this summary on the IE-Forum blog, and (ii) the full judgment which is reasonably readable with Google Translate). 

The Court notes that, even if this restriction set by the CJEU would not be in agreement with the SPC Regulation, this does not automatically imply that the restriction does not apply. 

The Court points out that the CJEU has on other occasions imposed restrictions on IP rights which cannot (directly) be found in the applicable guidelines or regulations. 

The Court then explains that this restriction may be in agreement with the Regulation if the term 'product' is interpreted narrowly as the ' invented basic substance'.

This all came in on the eve of the oral hearing last week in Luxembourg in the Georgetown, Eli Lilly and Actavis cases.

Most of the parties involved (like most if not all national patent offices in the past) have have rejected the "one SPC per patent" interpretation, but I do agree with the Court of Appeal that this is what the CJEU meant in Medeva and Georgetown and, in my opinion, the Court of Appeal does a most admirable job under the circumstances in explaining how this could be in agreement with the Regulation since the CJEU does not provide any argumentation in their own judgements, hence the mess we're in".

Note that this was a case for injunctive relief, adds Martijn, not a decision on the merits.

Thanks so much, Martijn, for keeping us up to date!

Going Dutch: taking a view post-Medeva in interim proceedings

The SPC Blog is again grateful to its friends Tjibbe Douma, Gertjan Kuipers and Margot Kokke (De Brauw Blackstone Westbroek N.V., Amsterdam) for sharing news of an interesting recent decision from the Netherlands.  This time it's an interim ruling of the District Court The Hague in Sanofi v  Teva c.s., 14 September 2012.  As Tjibbe his colleagues explain:

Further to the  recent posts (here and here) regarding the decision of the Patents Court for England and Wales in  Actavis v Sanofi [2012] EWHC 2545 , the Dutch decision in the somewhat similar Sanofi v Teva case  rendered on 14 September 2012 (cited by the Patents Court in its own decision) gives a rather different perspective on the interpretation of the SPC Regulation post-Medeva.

Where the Patents Court for England and Wales felt (again) that questions should be referred to the Court of Justice before establishing the validity of the SPC, the Dutch Court considered that it was in a position to decide (provisionally) on this issue and actually prohibited Teva from launching a generic version of Sanofi's product. To this end the interim relief judge held in the Dutch case that:

(i)                  The one-SPC-per-patent rule should be interpreted to read "one-SPC-per-product-per-patent"; and

(ii)                 The Medeva test "specified in the wording of the claims of the basic patent relied on" should in practice boil down to determining whether the combination product is part of the subject matter of the patent.

This different approach (and outcome) can in some respects be explained by the difference of the facts and nature of these cases.

Sanofi's patent, SPCs and MAs 

Sanofi has two SPCs, one for irbesartan (the mono SPC) and another for irbesartan in combination with HCTZ (the combination SPC). The SPCs were based on separate Marketing Authorisations (MA) for the mono product and the combination product respectively. Both SPCs were based on (different claims of) the same patent. The mono SPC expired in August 2012, but the combination SPC is valid until October 2012. The combination SPC is based on claim 7 of the patent which claims irbesartan in combination with a diureticum. HCTZ is not mentioned explicitly as an example of a diureticum, neither in the claim nor in the description.

Differences Dutch case and the England and Wales case 

The case in England and Wales was brought forward by Actavis on 26 June 2012. Actavis apparently wanted to clear to road before entering the market and Patents Court to declare the SPC invalid; Sanofi was the defendant in that case. The Patents Court felt that there were reasons to refer questions to the Court of Justice --- and that the nature of the case allowed for that.

In the Dutch case, however, there was no time for referrals. This case was a response by Sanofi to Teva's actions. Teva was preparing a launch at risk on 1 September 2012 (i.e. before the expiry of the SPC for the combination product). To this end, Teva's combination product was listed in the Dutch "G-standard" on 21 August 2012. In the Netherlands, a product needs to be announced on this list about two weeks before it can be marketed.

Sanofi - as could be assumed - did not appreciate this move (enlisting on the G-standard is considered 'offering' and thus an infringing action in the Netherlands) and filed an action with the District Court of The Hague requesting preliminary relief with a writ of summons dated 23 August 2012. On 3 September 2012 the Court already granted Sanofi's initial preliminary relief claim: Teva was ordered to refrain from offering the generic version for the duration of the actual preliminary relief proceedings.

Subsequently, the case was continued and resulted in the decision dated 14 September 2012. Teva argued as a defence that the SPC should be held invalid. Besides incompliance with Article 3(c), Teva also argued that Sanofi's combination SPC was invalid because of incompliance with Article 3(a) SPC Regulation because the product is not protected by the basic patent.

One SPC per patent? 

In the Dutch decision the interim relief judge provisionally ruled that the one-SPC-per-patent rule should be interpreted to read "one-SPC-per-product-per-patent" Teva's reference to a consideration in the Medeva ruling that "only one certificate may be granted for that basic patent" should not be read as meaning that only one SPC per patent could be granted. If the Court of Justice had meant to deviate from its earlier case-law which was widely interpreted to mean one-SPC-per-product-per patent, it would have done so explicitly, according to the judge. The preliminary relief judge also stated that, given Teva's announced launch at risk, there was no time for a referral and that the administrative court of the Hague had proposed to refer questions regarding thereto to the Court of Justice, so this question will already be dealt with by that court.

Specified in the wording of the claims? 

In the same judgment, the judge applied Medeva and Georgetown, interpreting "specified in the wording of the claims of the basic patent relied on" in a broader way than was done before. 

The interim Judge considered that, on the basis of the Dutch Court of Appeal's decision in Lundbeck/generieken, it should be determined whether the combination product was part of the subject matter of the patent. To determine what the subject matter was, she interpreted the claims taking into account not only the description and the drawings, but the general knowledge of the man skilled in the art at the priority date. Sanofi submitted several publications proving that, at the time of the priority, the man skilled in the art would immediately think of HCTZ when reading "a diureticum". This reading was not contested by Teva. . The judge therefore provisionally considered the product specified/identified sufficiently in the wording of the claims of the patent, the requirement of 3(a) met and the SPC valid

Thus, even though one of the active ingredients of the combination product for which an MA was obtained was not mentioned in the patent at all, the preliminary relief judge held that the SPC for the combination product was valid. This is different from the Lundbeck case where the active ingredient of the combination product was in fact mentioned in the (description of the) patent.

Where the Patents Court referred to the Dutch Court of Appeal decision in Lundbeck/ generieken  to point out the difference with Sanofi , the Dutch preliminary relief judge actually used Lundbeck/ Generieken to support her interpretation of the Medeva test,

In  Lundbeck/generieken  (The Hague Court of Appeal 24 January 2012)  the product of the MA was not mentioned literally in the wording of the claim. Claimed were escitalopram and certain salts thereof. The specific salt covered by the MA, escitalopramoxalaat, was mentioned in the description only. The Court of Appeal considered that escitalopramoxalaat "was obviously part of the subject matter of the patent" and was sufficiently 'specified or identified in the wording of the claims" for the SPC to be valid.

The judge's 'new' interpretation of the Medeva test in Sanofi v Teva is interesting and it remains to be seen how this will proceed.

More on that Dutch Advair litigation

Further to The SPC Blog's post earlier today on GSK's loss of its Advair patent and SPC (here), thanks are owed to Peter Burgers (Brinkhof) for providing us with a full 21-page translation of the decision. You can read it here.

Peter has also drawn our attention to a note on this decision that was posted on the Kluwer Patent Blog here last Wednesday by his colleague Rik Lambers.

GSK reverse on Dutch Advair patent and SPC

Reuters reported last week ("GSK says considering appeal to a higher court") that GlaxoSmithKline lost a Dutch patent action last Wednesday which concerned its top-selling lung drug Advair, in what the report describes as "the latest in a series of legal battles across Europe over the inhaled medicine".  Advair, known as Seretide in most of Europe, attracted sales of £5 billion ($7.9 billion) last year, giving GSK 18 percent of group revenue.

GSK said in a statement that a court in The Hague had ruled in favour of joint claimants Novartis units Sandoz BV and Hexal AG, ruling that the Dutch part of the European patent for Advair, as well as its supplementary protection certificate, were invalid.  It is understood that the company is considering an appeal which, given the value of the product in the market, is understandable.  GSK has however previously suffered patent defeats on Advair in Britain, Ireland and Germany.

If any reader has more specific details of the court's decision, we'd love to hear about it.

Escitalopram patent/SPC held invalid in the Hague

The Dutch first instance decision in ratiopharm et al v Lundbeck, concerning the validity of Lundbeck’s escitalopram patent (EP 066) has now been handed down by the Hague District Court. The court held that all the claims of Lundbeck’s escitalopram patent (and Lundbeck’s Dutch Supplementary Protection Certificate which was based upon it) were invalid for lack of inventive step.

Interestingly, the court's decision contains many references in the decision to the 4 May 2007 decision of Mr Justice Kitchin, with which decision the Dutch Court on relevant points “respectfully disagrees” (as the court said, in English, at § 6.39), on the basis of different/further evidence to that put before Kitchin J. You can read the court's decision in full here -- in Dutch.

[Information supplied by Richard Ebbink and Mark van Gardingen, Brinkhof].

More on Menantine - from the Netherlands and Germany

On 26 March 2009, the Netherlands Patent Office handed down its decision on Memantine. Here's a short English summary of the case:

Synthon requested that the Octrooicentrum revoke the certificate or revise the date of the certificate based on the earlier marketing authorisations that were not granted in accordance with directive 65/65. The Netherlands Patent Office denied this request. In their view it follows mainly from the recitals in the preamble that the relevant first marketing authorisation is an authorisation in accordance with directive 65/65, i.e. for a medicinal product which has been tested thoroughly for quality, safety and efficacy.

Thanks to Martijn de Lange from the Netherlands Patent Office for informing us about this decision.

Just in case you missed out on the German Patent Court decision on Memantine of 11 December 2007, you can get it here.

Sitagliptin - NL - negative term

The SPC Blog recently reported the Netherland Patent Office's positive decision to grant an SPC for Sitagliptin. On that occasion, the Blog noted that a zero-term SPC was granted. However, after a more detailed look at the register (and the decision - the Blog isn't fluent in Dutch), it appears that the Netherland Patent Office granted an negative term SPC. So the score is now 2:3:1 (negative term SPC - UK and NL; rejected - PT, SI, DE; zero term SPC - GR) .

Let's see how the other patent offices decide.

Dutch zero-term SPCs: original transcript available

On 28 January this blog posted news that the Dutch had recognised zero-term SPCs in the Sitagliptine application. We now have a copy of the Dutch decision, made on 22 January 2009. You can download it here -- but alas it is at present available to us only in Dutch.

Zero Term SPCs: the Dutch decision

The score is now 3:3 for the grant of an SPC for sitagliptin, now that the Netherlands Patent Office (NPO) has decided to grant a zero-term SPC.

For those of you who don't quite master Ruud van Nistelrooy's native language, here is a summary of the key points the NPO argued:

• First, the grounds for refusal included in the SPC regulation appear to be limited.
  
• Secondly from the proposal of the Paediatric Regulation it is clear that the term extension was meant not only as a reward for carrying out mandatory paediatric studies for new marketing authorizations but also as an incentive for companies with existing marketing authorizations to perform such studies. It is repeatedly stated in the proposal that companies will want to develop new formulations, dosage forms and indications for their existing products in order to access the six-month SPC extension (see the references in our decision). Not granting a zero-term SPC would mean that in this case no such incentive exists. That does not seem in line with the purpose of the Paediatric Regulation which is to increase our knowledge on the safety and efficacy of medicines in the paediatric population. Furthermore applicants could also be tempted to delay granting of the marketing authorization in order to qualify for an SPC with a positive duration. Delayed entry of pharmaceuticals onto the market (and available to patients) is obviously not desirable and this is also explicitly stated in the preamble of the Paediatric Regulation (4th recital).

Thanks to Martijn de Lange from the Netherlands Patent Office for informing us on this decision.