The SPC blog

A niche blog dedicated to the issues that arise when supplementary protection certificates (SPCs) extend patents beyond their normal life -- and to the respective positions of patent owners, investors, competitors and consumers. The blog also addresses wider issues that may be of interest or use to those involved in the extension of patent rights. You can email The SPC Blog here

Monday, 3 August 2015

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.

Tuesday, 7 July 2015

SPCs on the agenda, and a chance to save some money

If you are attending this year's C5 Life Sciences IP Summit (programme here) in Berlin on 22 to 23 October 2015, it has a session on SPCs that looks like this:
4:15 to 5:30 A Case-Law Review of the Jurisprudence on Supplementary Protection Certificates in Europe
  • Matthew Royle
    Partner
    Taylor Wessing (United Kingdom)
  • Lessons learnt from C-493/12 (Lilly-HGS), C-631/13 (Forsgren), E-16/14 (Pharmaq-Intervet)
  • An overview of the pending referrals concerning SPCs before the CJEU
  • Understanding under which circumstances you can obtain an SPC in the context of antibody claims
  • Obtaining an SPC on combinations of active ingredients for new uses
  • Neurim’s, Medeva’s, Georgetown’s, AstraZeneca’s, Merck’s aftermath: an overview of the CJEU’s interpretation on development of a new indication from an old substance
IPKat blog readers can get a 15% reduction on the registration fee: details can be found here.

Thursday, 25 June 2015

Quetiapine in Turin: court-appointed expert's analysis rejected

In an IPKat post back in March 2012 Darren Smyth wrote about what he called the “tigers v lions” quetiapine case; patents for this substance have been litigated in various locations [including Bulgaria, where some vigorous litigation over the SPC was noted by this weblog here back in 2011], and most recently in Italy before the Turin Court. The guest post below comes from Gian Paolo di Santo (Pavia e Ansaldo), who writes as follows:
With its decision n. 4000/15 issued on 1 June in Case 628/2013 [in the original Italian here and in English translation here] between Sandoz and AstraZeneca a Panel of three specialized Judges of the Turin Court has declared the Italian portion of European Patent No. EP 0 907 364, which had as object an extended-release formulation containing a gelling agent and quetiapine as an active principle having an antipsychotic function, to be null and void for lack of inventive step.

This decision is perfectly in line with a long and rather straightforward sequence of European decisions that held this same patent EP 364 to be invalid (similar decisions have indeed been issued in UK, Germany and The Netherlands (with final decisions) as well as in Spain and Belgium (with decisions that are currently under appeal by AstraZeneca).

The patent at stake is a formulation patent applied for in 1997 that was meant to protect the sustained release version of quetiapine, now a blockbuster drug in the antipsychotic field, already patented as such in 1987 and for which AstraZeneca enjoyed exclusivity until 2012 by virtue of an SPC. In a nutshell the patent holder claimed that at the priority date of EP 364 there was not enough information on quetiapine as such in order for an expert in the field to embark him/herself in the realization of a new formulation for such a compound, given also a series of possible downside of sustained release formulation in antipsychotic field and in particular with respect to the quetiapine molecule. The position of Sandoz was that, since the expert was aware of the need for a reduced posology of medicines in general and especially of antipsychotics (in Italy in particular it was proven that at least three other antipsychotics drugs had been formulated in sustained release before the priority date), it would have been obvious to go for a sustained release formulation of quetiapine, which was the perfect candidate both under a commercial point of view and from a pharmacology point of view.

What I consider interesting in the Italian extension of the case is that, when assessing the invalidity the Turin Court has -- rather unusually -- rejected the opinion of the Expert that had been appointed by the same Court to provide technical guidance (the appointment by courts of a technical Expert in patent proceedings is common practice).

The Expert appointed by the Court had analyzed all the alleged problems put forward by AstraZeneca (to name a few among a very very long list: occupancy of D2 receptors; PH-dependent solubility; clinical prejudice against once-a-day formulations) and found them not to be actual “prejudices” but simple “obstacles” that an expert in the field could overcome by means of simple routine activities. Still, however, the Expert suggested in his report to the Court that, given that no medicine based on quetiapine had yet been put into the market at the priority date of EP 364 (the studies on quetiapine were in advanced phase III), an expert in the field would not have had sufficient reasons to try and test a sustained release formulation in order to overcome the problem of reducing the number of daily doses. This, in fact, would have implied the necessity to start lengthy and expensive research. The Expert consideretherefore the patent to be valid since the expert in the field did not have sufficient motivation nor pointers towards the then patented solution.

The Italian Court completely rejected this point by affirming the following: 
the overcoming of those obstacles and the identification of the pharmacokinetics data concerning quetiapine – the latter was not yet marketed at the priority date of the patent –  implied an activity, which can be qualified as a mere routine activity for the expert of the field, consisting of clinical trials. The statement of  the Court Technical Expert who affirmed that those barriers would have discouraged the expert of the field, who could have reached the invention but would have not found a stimulus to do that, is not shareable. After all, the same Court Technical Expert affirmed that the expert of the field could have identified such elements through clinic research and that the long analysis which were necessary may also be qualified as routine ones in the pharmaceutical field, in the sense that they have in any case to be carried out but require the use of a great number of employees and resources as well as a substantial economic disbursement. Moreover, the necessity to make use of employees and resources and the costs of the analysis is an element which is not enough to state the inventive step of the patented technical solution because the expert of the field was not required to carry out any inventive activity but instead merely usual clinic research and tests” (see lines 276, ff. of the English translation).
In the context of such a long and high-value proceeding the aspects scrutinized were many more and a full reading of the decision may provide further valuable insights (almost every aspect such as definition of the technical problem, identification of the expert in the field and so on were discussed). Still, I think this particular aspect is an interesting interpretation of the inventive step requirement in Italy that may come into question in other cases where the patent holder tries to sustain the validity of the patent on the basis of an “economic analysis” of the situation in the prior art, instead than demonstrating the true technical advancement brought by the patented solution (which in this case was held to be minimum or even absent).

To what I said above I should add a couple more pieces of information. On the one side two parallel cases on the merits (involving Accord and TEVA v AstraZeneca) have not been decided yet on this same patent, although preliminary injunctions requests have been submitted by AstraZeneca and refused by the same Court on the basis of the same arguments on which the decision at stake is based. I should also add that AstraZeneca can still appeal this decision in favour of Sandoz before the Court of Appeal.

Friday, 5 June 2015

Forsgren: a new case note

The Bio-Science Law Review (Bio-SLR), published by Lawtext Publishing, carries a note on SPCs on vol.14 issue 4: it's "CJEU rules on the requirements for protecting carrier proteins using Supplementary Protection Certificates (SPCs)" and the author is Jennifer O'Farrell (Boult Wade Tennant, London). According to the abstract:
"Supplementary Protection Certificates (SPCs) extend the duration of protection conferred by a European patent for a medicinal product requiring marketing authorisation. The Court of Justice of the European Union (CJEU) has recently handed down the latest in a series of judgments (C-631/13 [a.k.a. Forsgren, noted briefly on The SPC Blog here]) which seeks to clarify what can, and cannot, be protected under EC Regulation No 469/2009 (the SPC Regulation). Here the CJEU has decided that an SPC may be granted for an active ingredient covalently bound to another substance only if the active ingredient for which supplementary protection is sought has a therapeutic effect covered by the wording of the marketing authorisation".

Friday, 29 May 2015

Reliable information on non-EU and non-US patent term extension: can you help?

I have been approached by a correspondent who has posed the following question:
Can you recommend a reference work or website that can provide reliable information as to the availability and rules surrounding Patent Term Extensions or Supplementary Patent Protection in countries other than the US or Europe?
Offhand, I couldn't think of one, though I'm sure that one must exist somewhere -- and one certainly should if none has yet been compiled.

Can readers of this weblog make any recommendations or point our correspondent to an appropriate source -- in English or in any other language?

Monday, 25 May 2015

MAs and APIs: the Austrian Supreme Court applies Forsgren ruling

Last week our friend Rainer Schultes (Geistwert) posted on his blog this note, which we are happy to reproduce below with his permission, on the Austrian Supreme Court's application of the provisions of the SPC Regulation in the light of a recent ruling of the Court of Justice of the European Union (CJEU) in response to the Austrian court's reference in the Synflorix case.  For the benefit of any first-time readers, API stands for "active pharmaceutical ingredient" and an MA is not a higher degree but a marketing authorisation:
The API of an SPC need not be mentioned in the MA

In Case C-631/13 Forsgren [noted briefly here on The SPC Blog], the CJEU already ruled: Article 3(b) of Regulation 469/2009 must be interpreted as precluding the grant of a supplementary protection certificate for an active ingredient whose effect does not fall within the therapeutic indications covered by the wording of the marketing authorisation.

Article 1(b) of Regulation 469/2009 must be interpreted as meaning that a carrier protein conjugated with a polysaccharide antigen by means of a covalent binding may be categorised as an ‘active ingredient’ within the meaning of that provision only if it is established that it produces a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the marketing authorisation.

GEISTWERT has blogged already (link).

Now, the Austrian Supreme Court shed further light on the SPC Regulation when applying the CJEU's judgment (Austrian Supreme Court, 4Ob20/15t).

In the matter at stake an SPC was requested for a protein D, which is a carrier protein covalently bonded to other active ingredients. Covalent binding does not exclude an SPC.

The Supreme Court analysed the context between the order for reference, the statement of the European Commission and the CJEU’s judgment: The Supreme Patent- and Trademark Senate, which referred the question to the CJEU had individualized the protein D as a carrier for which no pharmaceutical effect was mentioned in the Marketing Authorisation (MA). With regard to that, the Commission meant that the protein’s activity had to be mentioned in the MA, otherwise the request for SPC was not justified. The CJEU did not follow that but referred to the facts, thus to the effectiveness of the protein within Synflorix.

Upon this analysis, the Supreme Court now held that an own pharmacological, immunological or metabolic action of the protein D within the indications covered by the MA has to be established but it is not necessary that the protein D is explicitly mentioned in the Marketing Authorisation.

To verify that, the matter was referred back to the first instance.
Thanks so much, Rainer, for keeping us informed!

Wednesday, 20 May 2015

SPCs for Beginners and a touch of Rembrandt

Room service has definitely improved
since the days of Rembrandt himself
The SPC blog earlier this year, in "SPCS for beginners", drew the attention of readers that, on Tuesday 16 June, a seminar is being arranged on the subject of (yes, you've guessed it) SPCs for Beginners. Speaking in this event is Paul Brady (Abel & Imray), who has just contacted The SPC Blog to tell us that the event's organiser (Sarah Packham at Management Forum) has aske The SPC blog to tell its readers that -- in keeping what seems to be a most agreeable trend* towards more affordable registration fees -- Management Forum is offering a 15% discount for SPC blog readers.

For the mathematically minded, this is effectively the 15% early bird reduction, which has now been extended for SPC Blog readers beyond its original deadline date. It works out at (£508.30 + VAT rather than £598.00+VAT). £508.30 is just a couple of pounds short of three times the price this blogger paid for his first car ...

For the record, the seminar takes place at The Rembrandt Hotel, London (if you're staying there, do check out the attic ...). Paul Inman (Wragge Lawrence Graham LLP) is either in the chair or is actually the chair (everything is so politically correct these days), and the other speakers are Oliver Kingsbury (Elkington & Fife LLP), Andrew Rudge (Pfizer) and regular SPC Blog contributor Mike Snodin (Park Grove IP). For further details and registration, just click here.

* For another instance of this trend see the 25% registration fee reduction offered by CIPA for everyone, even non-blog-readers, for this year's Congress.

Tuesday, 19 May 2015

Pharma Law Academy: a Tale of Downing and Discounts ...

The Pharmaceutical Law Academy 2015 is running from 25 to 27 August 2015, the venue being the very pleasant facilities of Downing College, Cambridge, UK (right). While the programme, as the name suggests, runs a good deal more widely than coverage of SPCs, both patent term extensions and marketing authorisations are among the topics addressed in the first day's programme, chaired by Matthieu Guérineau (Director of the Contract Department, Les Laboratoires Servier). Developments concerning the Paediatric Medicines Regulation are dealt with on day two, while the third day investigates -- among other things -- recent SPC case law.

For further information, you can view the latest agenda and register at the event website here. Readers of The SPC Blog who quote VIP code FKW82574SPC can save 10% on their registration fee.

Friday, 24 April 2015

Questions for the CJEU? No, says court, it's too early even to ask

ViiV Healthcare UK Ltd v Teva UK Ltd [2015] EWHC 1074 (Ch), a ruling yesterday by John Baldwin QC, sitting as a Deputy Judge of the Patents Court, England and Wales, was easy to miss: there was no great fanfare of advance publicity ahead of it and, curiously, BAILII has mis-filed it in its online database under the regular Chancery Division cases and not as a Patents Court case.

Given the propensity of SPC cases to end up with references to the Court of Justice of the European Union (CJEU) for preliminary rulings, it's not surprising that ViiV, the claimant, contemplated the prospect of such a reference in this action.  Viiv however felt that it might be a good idea to start with the preliminary reference, so John Baldwin QC was called up to deal with the application for the reference even before the (in)validity of ViiV's Kivexa/Trizivir patent could be established and before a decision on conditional application to amend that patent was necessary.  Teva opposed the application for a CJEU reference and argued that, first, it was unnecessary since the questions that ViiV wanted to pose were acte clair and there was therefore no basis for referring them, and secondly that it was premature to make such a reference ahead of the making of some essential findings of fact.

Said the Deputy Judge, dismissing the application for a reference to the CJEU, not only was it too early to refer any questions to the CJEU -- it was too early even to ponder over whether the questions were indeed acte clair.  Since the decision is so short, The SPC Blog is reproducing it in full here:


JOHN BALDWIN QC:
  1. This is an application for a reference to the Court of Justice of the European Union (CJEU) in an action in which the Claimant (ViiV) seeks a declaration as to the proper interpretation of Article 3 of Regulation (EC) No 469/2009 (the Regulation) in the context of a Supplementary Protection Certificate (SPC) granted in 2005 in respect of
  2. "A combination comprising abacavir, optionally in the form of a physiologically functional derivative and lamivudine, optionally in the form of a physiologically functional derivative."
    It is sufficient for present purposes if the SPC wording is expressed as
    "A combination comprising A + B."
  1. The application is resisted by the Defendant (Teva) on two main grounds. First it is contended that the answers to the proposed questions are acte clair, and second it is contended that there should be no reference to the CJEU until some important essential facts have been found.

  2. The SPC was granted on the basis of EP (UK) 0817637 (the Patent), which was applied for on 28 March 1996, and a marketing authorisation ("MA") notified on 22 December 2004 for a medicinal product containing abacavir (as a sulphate salt) and lamivudine (i.e. A + B) for the treatment of HIV. The product ViiV market pursuant to this MA is called Kivexa. The language of the SPC is substantially the same as the language of claim 1 of the Patent.

  3. ViiV also market another product for the treatment of HIV. It is called Trizivir and an MA was notified in respect of this on 2 January 2001. Trizivir is a combination of abacavir, lamivudine and AZT, i.e. is a product comprising A + B + C using the short hand nomenclature. As such, Trizivir also falls within claim 1 of the Patent. However, this triple combination is also protected by claim 3 of the Patent, which is in these terms:
  4. "A combination comprising abacavir or a physiologically functional derivative thereof, AZT or a physiologically functional derivative thereof, and lamivudine or a physiologically functional derivative thereof."
  5. An MA for Trizivir was granted within 5 years of filing of the Patent and, accordingly, an SPC with a positive term has never been available based on this MA.

  6. ViiV issued proceedings for a declaration on 26 November 2014 and by Defence and Counterclaim served on 22 December 2014 the Defendant (Teva) sought revocation of the SPC. Sometime in February 2015 Teva indicated its intention to amend its Counterclaim to seek, in addition, an order revoking the patent upon which the SPC is based, and the amended version was filed and served on 8 April 2015.

  7. It is common ground that the patent revocation proceedings should progress to trial whether or not a reference is made and it is anticipated that the trial will take place in March 2016, with a Court of Appeal judgment following about a year later.

  8. The approach to references to the CJEU
  9. Article 267 of the Treaty on the Functioning of the European Union provides:
  10. The Court of Justice of the European Union shall have jurisdiction to give preliminary rulings concerning:
    (a) the interpretation of the Treaties;
    (b) the validity and interpretation of acts of the institutions, bodies, offices or agencies of the Union;
    Where such a question is raised before any court or tribunal of a Member State, that court or tribunal may, if it considers that a decision on the question is necessary to enable it to give judgment, request the Court to give a ruling thereon.
    Where any such question is raised in a case pending before a court or tribunal of a Member State against whose decisions there is no judicial remedy under national law, that court or tribunal shall bring the matter before the Court.
  11. The CJEU's "Recommendations to national courts and tribunals in relation to the initiation of preliminary ruling proceedings" (2012/C 338/01) include the following:
  12. "The appropriate stage at which to make a reference for a preliminary ruling
    18. A national court or tribunal may submit a request for a preliminary ruling to the Court as soon as it finds that a ruling on the interpretation or validity of European Union law is necessary to enable it to give judgment. It is that court or tribunal which is in fact in the best position to decide at what stage of the proceedings such a request should be made.
    19. It is, however, desirable that a decision to make a reference for a preliminary ruling should be taken when the national proceedings have reached a stage at which the referring court or tribunal is able to define the legal and factual context of the case, so that the Court of Justice has available to it all the information necessary to check, where appropriate, that European Union law applies to the main proceedings."
  13. Over 40 years ago Lord Denning MR said in the context of Article 267 (ex Article 177) and in a section of his judgment where he set out a number of guide lines as to whether or not it was appropriate to refer a matter (Bulmer v Bollinger [1975] RPC 321, 341):
  14. "It is to be noticed too, that the word is "necessary". This is much stronger than "desirable" or "convenient". There are some cases where the point, if decided one way, would shorten the trial greatly. But, if decided the other way, it would mean that the trial would have to go to its full length. In such a case it might be "convenient" or desirable to take it as a preliminary point because it might save much time and expense. But it would not be necessary at that stage. When the facts were investigated, it might turn out to have been quite unnecessary. The case would be determined on another ground altogether. As a rule you cannot tell whether it is necessary to decide a point until all the facts are ascertained. So in general it is best to decide the facts first."
    This was said in the context of a sub-heading entitled 'Decide the Facts first' and I found it helpful to be reminded of the whole of Lord Denning's section on The Guide Lines in relation to references to the CJEU.
  1. More recently, Warren J in Eli Lilly v Human Genome Sciences [2012] EWHC 2290 (Pat) said:
  2. "107 In principle, a reference should only be made in the context of facts agreed or determined by the national court. That is, perhaps, not an entirely rigid rule in the sense the ECJ will give answers to questions on the basis of facts contained in the reference even if those facts have not yet been found. But that is an inherently undesirable procedure."
    The application of that approach to the facts
  3. The parties have cooperated in producing drafts of an Agreed Statement of Facts and of Questions To Be Referred To The CJEU. The draft Agreed Statement of Facts is not, to my mind, quite what it purports to be. Thus the last four 'Facts' are:
  4. 18 The Claimant alleges (and the Defendant disputes) that a combination consisting of [A+B] for the treatment of HIV infection was a separate innovation from a combination consisting of [A+B+C] for the treatment of HIV infection, {and/or that the use of a product consisting of A and B for the treatment of said disease constitutes part of the subject matter of the invention covered by the basic patent relied upon for the purposes of the application for an SPC,} and/or that a claim to a combination consisting of [A and B] is independently valid over a claim to a combination comprising [A+B+C].
    19. Further the Claimant has made a conditional application to amend the Patent if the Kivexa SPC would otherwise be invalid, inter alia, to include a claim to a combination consisting of [A+B], or alternatively to include a claim to a combination comprising two compounds selected from [A, B and C] provided that the two compounds are not [B and C]. The Defendant does not accept that the Claimant's proposed amendment is allowable under the relevant provisions of the EPC and national patent law. {The Claimant has also made a further conditional application to amend the Patent if the Kivexa SPC would be otherwise invalid, inter alia, to amend the claims to a combination comprising [A+B] to claims to a combination consisting of [A+B], or alternatively to include a claim to a combination comprising two compounds selected from A, B and C provided that the two compounds are not [B and C], and in each case so as to delete claims to a combination comprising [A, B and C].}
    20. The Claimant contends that, if it is necessary for it to make its application to amend the patent and the amendment is granted, the Patent as amended should be treated as the basic patent on which the Kivexa SPC application is based for the purposes of assessing the validity of the Kivexa SPC, in particular for assessing whether the requirements of Article 3(d) of the SPC Regulation have been met in relation to the Kivexa SPC. The Defendant does not accept the Claimant's contention.
    21. The Claimant contends that [A and B] in Kivexa interact synergistically with each other in the treatment of HIV infection. The Defendant does not accept this contention {and relies, inter alia, upon the facts that (i) the Claimant's predecessor in title, when applying for Kivexa's MAs, represented to the European Medicines Agency that there was no synergistic effect arising from combining [A and B] and (ii) the European Medicines Agency granted the Kivexa MAs with a Summary of Product Characteristics stating that [A and B] were additive in effect (i.e. were not synergistic).}
  5. With respect to Fact 18, Teva did not agree that the matter surrounded by {} should be included. In any event, Fact 18 is not a fact but a matter which will or may be decided at the forthcoming trial. In addition, Teva took issue with the word 'innovation' contending that it was not clear what it meant in the present context.

  6. With respect to Fact 19, Teva did not agree that the matter surrounded by {} should be included. The issue of whether any amendments are allowable on conventional grounds will or may be decided at the forthcoming trial. Moreover, at the time of the hearing before me, ViiV had two different conditional applications to amend in play. Since the hearing I was told that one of these has been abandoned and will be replaced by a further application, the object of which is to make clear beyond doubt that protection for a combination of A+B+C will, if necessary, be excised from the Patent. Teva relies on the additional uncertainty created by this state of affairs as a further reason why it is premature to consider any reference to the CJEU. ViiV contends it is merely a contingency and the CJEU should be asked to give useful guidance upon whether or not it is necessary for ViiV to amend to save its SPC.

  7. Fact 20 is not a fact at all. It relates to a topic addressed by questions 1 and 4 in the reference made in Actavis v Boehringer C-577/13 at [24] (albeit those questions were in the context of Art.3(a) and not Art.3(d)) but which were not answered by the CJEU, even though fully argued, because its answers to other questions rendered these questions academic. This failure to answer fully argued academic questions is a good indication that the CJEU is not interested in questions other than those necessary to resolve any particular case.

  8. With respect to Fact 21, ViiV did not agree that the matter surrounded by {} should be included. Again, Fact 21 is not a fact. It is more an indication of an area which will be explored at trial. In particular, it may well be relevant to explore whether A and B also interact synergistically in the presence of C, or whether C has some (and if so what) influence thereon. And it is impossible to predict now what will be the likely outcome of the debate, or even whether the question is a simple binary one.

  9. I was told that, on references to the CJEU, it was not unusual to include facts in Agreed Statements of Facts which were not actually facts but which were parties' contentions as to the facts. There may be circumstances where that is appropriate but it seems to me that such should not be the norm. The whole idea seems to be contrary to the concept that references are only made when "a decision on the question is necessary to enable [the court] to give judgment" (cf Article 267).

  10. As for the draft questions to be referred, there is presently disagreement over their form and utility but I think it is likely that matters could be resolved if I thought it otherwise appropriate to make a reference. In brief, the questions concern Article 3(d) of the Regulation and address the circumstance where there has been an earlier MA for a product consisting of A+B+C, there is a later MA for A+B and there is an SPC for a product comprising A+B. There are additional questions which depend on whether there is synergy between A and B and/or C and upon whether use of a product consisting of A+B constitutes a separate innovation (perhaps invention is a better word, ViiV was content with either, Teva with neither) from use of a product consisting of A+B+C (for treatment of the same disease). There are also questions relating to the form of the claims of the patent and the content of the SPC as well as questions similar in content (although not form) to questions 1 and 4 of Actavis v Boehringer.

  11. Article 3 of the Regulation is in these terms:

  12. A certificate shall be granted if, in the Member State in which the application referred to in Article 7 is submitted and at the date of that application:
    a) the product is protected by a basic patent in force;
    b) a valid authorisation to place the product on the market as a medicinal product has been granted…;
    c) the product has not already been the subject of a certificate;
    d) the authorisation referred to in point (b) is the first authorisation to place the product on the market as a medicinal product.
  13. With respect to the SPC in relation to Kivexa, a) is satisfied by the Patent, b) is satisfied by the MA notified on 22 December 2004, c) is true as a fact, and that leaves d). Teva contends that the MA granted in respect of Kivexa was not the first authorisation to place the 'product' in question on the market as a medicinal product. It contends that the first such authorisation was that notified in January 2001 in relation to Trizivir. Further, it contends that, in the light of the case law which has already emerged from the CJEU, the matter is acte clair.

  14. ViiV, on the other hand, submits that the matter is not so clear at all, especially in circumstances where there is 'innovation' in a combination of A+B over A+B+C, a scenario which has not previously been before the CJEU, or where there is synergy between A and B and/or C. The questions which it wishes to refer to the CJEU directly address these points and ViiV contends that the sooner this court knows the answer to those questions the better. ViiV also points to the timing benefits which will be gained if a reference is made now. It suggests that, with a reference, the proceedings will conclude at more or less the same time as the UK Court of Appeal will conclude any appeal on patent validity (end of 2016 or so), whereas if no reference is made until then, the proceedings will go on for another two years thereafter, perhaps longer. ViiV submits that the question of whether or not to make a reference is essentially one of case management and that the 'overriding objective' is best served by making a reference now.

  15. ViiV urged upon me that a reference to the CJEU would not be that expensive, that payment of any costs thrown away would not be a problem and that, bearing in mind the commercial value of Kivexa (very substantial, according to ViiV) and the timetable, a reference was justified when there was a potential for answers to the questions to be of real value.

  16. In the context of ViiV's conditional applications to amend, counsel submitted that, if the court were satisfied that the amendments were otherwise allowable (i.e. there were no valid objections on conventional grounds), then ViiV was entitled to take the position that it would amend if it was necessary to preserve the validity of the SPC but not otherwise, and that the judge would not be able to decide upon whether it was necessary for ViiV to amend without a reference to the CJEU. Accordingly, it was appropriate to make a reference now so that the judge would be equipped to deal with any eventualities.

  17. I am far from satisfied that this is the right approach to take. In effect, ViiV wishes for guidance from the CJEU upon a number of hypothetical scenarios so as to be better placed to decide whether to make any application to amend the Patent, the prime objective being to maximise the protection surrounding Kivexa whilst maintaining as wide a patent monopoly as possible.

  18. That, however, seems to me to go to desirability, and what may be desirable from ViiV's point of view may not be so from Teva's point of view (and Teva contends it is not). Moreover, the issue is not desirability from the perspective of the parties (which may or may not coincide with that of the court), but necessity from the perspective of the court.

  19. I am not satisfied that this court should make a reference to the CJEU merely to enable a party to be better informed as to whether to go forward with an application to amend its patent. That seems to me to be way beyond the ambit of Article 267 and my attention was not drawn to any authority which approved this use of the CJEU's resources.

  20. I am satisfied, however, that it is far too early to make a reference in this case, principally for the following reasons. First, if the patent is revoked at the validity trial, all questions relating to the SPC become irrelevant. Second, if ViiV's conditional applications to amend are not allowable for conventional reasons, then all questions relating thereto or contingent thereon become irrelevant. Third, if the combination of A+B is not innovative over the combination of A+B+C, then an important if not the main plank of ViiV's argument that its SPC is valid falls away and the questions in relation thereto become irrelevant. Likewise with respect to whether or not there are any synergistic interactions between A or B or C or any combination of them and if so what significance should be attached thereto. Each of these matters may or will be decided at the trial and a decision as to whether a reference is necessary cannot, in my view, be meaningfully made before that time, at least. Finally, I am not satisfied that the proposed Statement of Facts is sufficiently precise to give the CJEU a firm basis on which to make a decision. There are too many contingencies.

  21. In these circumstances I do not need to decide now whether the points ViiV wish to raise are acte clair or not. Indeed, they may never call for decision. I dismiss the application.

Thursday, 23 April 2015

Pharmaq v Intervet: the story behind the case -- and a helpful explanation of its significance

Earlier this month The SPC Blog broke the news that the EFTA Court had given its ruling in Case E 16/4 Pharmaq v Intervet International BV.  Given the length and complexity of the ruling, this blogger has done his best to hide from it till such time should become available to him as to enable him to read it carefully and write it up for this weblog. Fortunately for him, no less a person than Penny Gilbert of Powell Gilbert LLP has come to his rescue with a note on the case which is agreeably accessible -- not least because Penny, together with Gunnar Meyer and Lars Erik Steinkjer (Wikborg Rein) and Ida Gjessing (Grette), represented Pharmaq in these proceedings and therefore had first-hand knowledge of the case.  This is what Penny writes:
The EFTA Court rules on the application of Articles 2, 3 and 4 of the SPC Regulation in the context of veterinary vaccine products
In a referral of questions from the Oslo District Court relating to the grant of an SPC for a veterinary vaccine the EFTA Court [equivalent to the CJEU for matters referred by the national courts of the three EFTA states (Norway, Iceland and Liechtenstein)] has held that

  • a provisional marketing authorisation properly granted under Art 26 (3) Directive 2001/82 relating to veterinary medicinal products may be the first authorisation to place the product on the market under Art 3(b) and (d) of Council Regulation 1768/92 concerning the creation of a supplementary certificate for medicinal products, so can be the basis for an SPC application.
  • a provisional permission to place a product on the market under Art 8(1) Veterinary Medicines Directive will not amount to an authorisation for the purposes of Art 3(b) and (d) provided that it has been properly granted.  Art 8(1) permissions being strictly limited to the use of immunological veterinary medicinal products , without a marketing authorisation,  in the event of serious epizootic diseases where there is an absence of suitable medicinal products and after informing the Commission /EFTA surveillance authority of the detailed conditions of use.
  • an SPC is invalid as in breach of Art 4 SPC Regulation to the extent it has been granted with wider scope “than that set out in the relevant Marketing Authorisation (“MA”)”. 
The case has been remitted to the Oslo District Court for interpretation of the EFTA Court’s judgment on the specific facts of the case.

Background

The case before the Oslo District Court concerns the validity and scope of an SPC granted to Intervet on a Norwegian patent which broadly claims the F93-125 strain of Salmonid Pancreatic Disease (“PD”) Virus together with all strains which share “similar genotypic and/or phenotypic characteristics and react serologically [with F93-125]”, effectively the entire PD species.  The patent also claims vaccines containing inactivated PD virus.  The strain F93-125 belongs to the PD subtype SAV1, found mainly in Ireland and Scotland.

PD virus affects farmed fish (salmon and trout) and is considered to be one of the most serious fish health problems in the fish farming industry involving high mortality rates, reduced production and significant loss to the industry. PD continues to be a serious problem in Norway, where fish farming is a major industry, and fish farmers have called for better vaccines against PD to be made available to prevent the spread of the disease.

Intervet’s vaccine (Norvax) was granted an MA in 2011 for “Inactivated Salmon Pancreatic Disease Virus Strain F93-125”.  An SPC was granted by the Norwegian Patent Office in the same broad terms as the patent claims rather than reflecting the wording of the MA, in effect granting a general patent term extension. Pharmaq developed its own vaccine based on a different subtype of PD (SAV3) that it isolated from a diseased fish in Norway.  SAV3 is genetically distinct from SAV1 (and also SAV2).   In previous patent litigation before the Norwegian court Pharmaq’s vaccine was held to infringe the broad claims of Intervet’s patent and launch of the product is currently prevented pending expiry of the SPC

These proceedings relate to Pharmaq’s challenge to the validity of Intervet’s SPC on the basis of Art 2, 3 and 4 of the SPC Regulation and the following facts:

  • Between 2003 – 2011 Intervet had sold its vaccine to fish farmers in Norway under “Special Approval Exemptions” (“SAEs”) under sections 2-7 (or 2-6) of the Norwegian Medicines Regulation.
  • During this period the vaccine was also sold in Ireland under a corresponding scheme known as AR16 Licences.
  • A provisional MA was granted in the UK in 2005.
  • A full MA was first granted in the UK and Norway in 2011.
  • Total sales of Norvax in the period 2003 – 2011 amounted to well over 73 Million Euros. 
In essence, the Oslo District Court sought guidance on whether the SPC is invalid on the basis that Norvax was “placed on the market” prior to an administrative authorisation procedure within the meaning of Art 2 SPC Regulation as a result of the prior sales under the SAEs and AR16 Licences.  If not, then to the extent that the SAEs and AR16 Licences were to be considered as an “administrative procedure”, was the SPC granted in breach of Art 3 of the SPC Regulation?

The Oslo Court further asked whether the SPC was granted in breach of Art 4 SPC Regulation, since the broad wording of the granted SPC extends beyond the “product covered by the authorisation to place the corresponding medicinal product on the market”.  If so, is it invalid?

The questions referred by the Oslo District Court are set out at pages 10-11 of the judgment of the EFTA court which can be found here.

The EFTA Court judgment 

Art 2 & 3 SPC Regulation

In summary, the Court decided that the supply of a vaccine without an MA on the basis of Art 8(1) Veterinary Medicines Directive may not amount to a general placing on the market.  Article 8(1) allows the grant of provisional permission, without the same safety and efficacy testing for a full MA, to supply to the extent necessary to combat a “serious epizootic disease”, but does not entitle the producer to market the product.  Consequently, such supply does not generally constitute a placement on the market for the purpose of Art 2 SPC Regulation. 

The Court concluded that, since it does not involve an administrative procedure, a provisional permission to supply under Art 8(1), may not be considered an authorisation to place the product on the market within the meaning of Art 3(b) and (d) of the SPC Regulation. However, the grant of a provisional marketing authorisation in exceptional circumstances, under Art 26(3) Veterinary Medicines Directive does constitute an administrative authorisation for the purposes of Art 3(b) and (d) of the SPC Regulation.  Art 26(3) permits the grant of an MA, for objective, justifiable reasons, in exceptional circumstances.  Such authorisations are subject to specific procedures, including safety reporting, and also subject to annual assessment.

The Court acknowledged the dispute between the parties as to whether, in fact, Intervet had been able to place the Norvax product on the market since it had been supplied in significant quantities prior to the grant of a full MA.  The question of fact as to whether the SAEs, AR16 Licences and UK provisional MA in the present case were based on national provisions correctly implementing Art 8(1), or were based on Art 26(3) Veterinary Medicines Directive, was therefore remitted to the National Court for determination. 

The Court noted that the SPC Regulation is intended to provide an adequate period of effective protection of a basic patent, intended to compensate - at least in part - for the delay to the commercial exploitation of the invention by reason of the time elapsed between the date on which the patent application was filed and the date on which the first marketing authorisation was granted. In this case, however, the patentee was able to sell the product, at the same time as compiling clinical data for over 7 years prior to grant of a full MA.

Art 4 SPC Regulation

Art 4 provides that an SPC “shall only extend to the product covered by the authorisation” and Recital 9 of the SPC Regulation confirms that the protection granted should be “strictly confined” to the authorised product.

The Court nevertheless went on to propose that an SPC can extend to cover a specific strain of virus (included in the basic patent but not mentioned in the MA), but only if the specific strain:
  • Constitutes the “same active ingredient as the approved medicinal product”; and
  • Has “therapeutic effects that fall within the same therapeutic indications for which a MA was granted”.
By its answers to the referred questions the Court appears to have introduced a new requirement for interpreting the scope of Art 4, namely whether the same active ingredient in another, separate product would have “therapeutic effects falling within the therapeutic indication” for which the MA was granted.  This is not a phrase which is found in the SPC Regulation but derives from the CJEU’s decision in Forsgren, C-631/13.  

In Forsgren, the question was whether a patented component, Protein D - an IgD-binding protein of H.Influenzae which functioned as a covalently bound carrier protein in a vaccine, Synflorix, used against S. pneumonia, and was itself mentioned in the relevant MA - could be the subject of its own SPC. The Synflorix MA expressly stated that there was not sufficient evidence that it had any protective effect against H. influenzae. The answer from the CJEU was that an SPC could not be granted unless the patented component found in the combination product had its own “therapeutic effects falling within the same therapeutic indication” of the MA.  Thus, the issues in Forsgren were entirely different to those here: both parties’ vaccines are mono-products, not combination products, containing a single active ingredient (their respective strain of PD virus) which is not bound to any other active ingredient.

Nevertheless, the Court noted that the SPC granted to Intervet is expressly limited to the F93-125 strain. It confirmed that since an SPC can only be granted for the active ingredient  in the product which is the subject of the relevant MA then an SPC is invalid to the extent that it is granted a wider scope than set out in that MA. 
The case now returns to the Oslo District Court to decide the matter on its facts.

What next?

This case is the first occasion on which the EFTA Court has been required to interpret the SPC Regulation.  While giving guidance on the referred questions, the Court has left issues to be determined by the mational court, based on the specific facts of this unusual case. 

The case goes to trial in Oslo during late April, with the District Court having to determine whether the SAEs, AR16 Licences and Provisional MA were properly granted under either Art 8(1) or Art 26(3) Veterinary Medicines Directive and, if not, whether the SPC is therefore invalid under Art 2 or Art 3 SPC, a question of regulatory law and fact. 

Likewise the Oslo District Court must decide whether, in fact, the SPC is invalid on the basis that it extends beyond the scope of the granted MA, which is expressly limited to Intervet’s F93-125 strain.  Since the EFTA Court’s decision is not binding on the referring Court (unlike the position with the CJEU) one might also expect the EFTA Court’s assumptions, based on Forsgren, to be reviewed.

Quite how the EFTA Court’s judgment will apply to other biological products remains uncertain. However, it is expected that future referrals to the CJEU on the scope of protection of Art 4 are almost inevitable, given the importance of the market for biosimilar and biobetter products.