Third time’s not a charm

Welcome to the third and final part of the SPC drama miniseries on Patent my French, still courtesy of guest blogger Lionel Vial.

Spoiler alert: I would never have thought that the fate of an SPC application would be at least partly decided based on a number of bibliographic citations – and yet…

The Easter egg which was missing from the latest post has finally been found again.

The last of the three decisions we discuss today was rendered by the Paris Cour d’appel on February 9, 2021 following an appeal against a decision of the French patent office (INPI) to refuse SPC application No. FR16C1004.

The SPC application was filed by Wyeth and the General Hospital Corporation on the basis of European patent No. EP 1848414 filed on February 2, 2006 and of marketing authorization (MA) No. EU/1/16/1086 granted in 2016 to Astrazeneca for Tagrisso® (osimertinib mesylate).

Tagrisso® is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (i.e. mutations of EGFR which cause cancer), and in particular for treating those patients who harbor a T790M mutation-positive EGFR (i.e. the amino acid threonine (T) in position 790 of the EGFR is substituted by a methionine (M)).

Osimertinib

Osimertinib is a Tyrosine Kinase Inhibitor (TKI) which irreversibly inhibits EGFRs harboring sensitizing-mutations (EGFRm) (i.e. mutations causing cancer) and the TKI-resistance mutation T790M.

Astrazeneca obtained an SPC for osimertinib on the basis of the MA and of European patent No. EP 2736895 filed on July, 25, 2012, which claims osimertinib as such.

The SPC application of Wyeth and the General Hospital Corporation was based on claim 23 of the basic patent which relates to a pharmaceutical composition for use in treating cancer in a subject with a cancer having a mutation in EGFR, wherein the mutation is a substitution of a methionine for a threonine at position 790; and wherein the pharmaceutical composition comprises an irreversible EGFR inhibitor.

Claim 24, which depends from claim 23, further gives a list of irreversible EGFR inhibitors: EKB-569, HKI-272 and HKI-357, which are structurally related to gefitinib, an EGFR inhibitor sensitive to the T790M mutation.

The SPC application was refused by the INPI on August 1, 2019 pursuant to Article 3(a) of Regulation (EC) No. 469/2009 (hereafter the “SPC regulation”). The INPI in particular considered that while the claims of the basic patent did implicitly and necessarily relate to osimertinib, they did not specifically relate to it, since osimertinib was neither mentioned in the specification of the patent nor identifiable as such.

The Cour d’appel essentially based its reasoning on the judgement handed by the CJEU on April 20, 2020 in case C‑650/17 (Royalty Pharma):

1. Article 3(a) of Regulation (EC) No. 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary protection certificate for medicinal products must be interpreted as meaning that a product is protected by a basic patent in force, within the meaning of that provision, if it corresponds to a general functional definition used by one of the claims of the basic patent and necessarily comes within the scope of the invention covered by that patent, but is not otherwise indicated in individualized form as a specific embodiment of the method of that patent, provided that it is specifically identifiable, in the light of all the information disclosed by that patent, by a person skilled in the art, based on that person’s general knowledge in the relevant field at the filing date or priority date of the basic patent and on the prior art at that date.

2. Article 3(a) of Regulation No. 469/2009 must be interpreted as meaning that a product is not protected by a basic patent in force, within the meaning of that provision, if, although it is covered by the functional definition given in the claims of that patent, it was developed after the filing date of the application for the basic patent, following an independent inventive step. (emphasis added by the Cour d’appel).

Regarding the first part of the Royalty Pharma test the Cour d’appel considered that:

To demonstrate that the person skilled in the art could specifically identify osimertinib as an irreversible inhibitor of the EGF receptor, the appellants only put forward allegations, arguing that the skilled person needed only perform standard enzymatic inhibition assays distinguishing EGFR irreversible inhibition from the reversible inhibition of EGFR, said assays being comprised in the basic knowledge of a biochemist […], without submitting any evidence, such as scientific publications or declarations from persons skilled in the art in support of their thesis.

Besides, the court observes that several years of research were necessary to precisely and specifically identify osimertinib as an active product, since osimertinib was only claimed in a patent on July 25, 2012 by Astrazeneca, which confirms that upon reading all the information contained in the [basic] patent in the light of its knowledge, this product was unknown to the person skilled in the art at the filing date in 2006. The skilled person could not directly and unequivocally infer [osimertinib] from said patent, its discovery being the result of several years of complex research.

Regarding the second part of the Royalty Pharma test the Cour d’appel considered that:

The appellants however argue, in the light of the Royalty Pharma judgement, that while osimertinib was developed after the filing date of the basic patent application, the inventive activity which led to the authorized product was not ‘independent’ since the inventors of the Astrazeneca patent relating to osimertinib based their work on the EP’414 basic patent and on scientific publications, in particular a KWAK publication of 2005 (Mr. Eunice KWAK being one of the inventors of the EP’414 basic patent), since an AVIZIENYTE publication of 2008, of which Mr. Richard WARD was a co-author (and also a co-inventor of Astrazeneca’s EP’895 patent in which osimertinib is identified) referred to the KWAK publication of 2005 […].

While these elements demonstrate that the EP’414 basic patent has undoubtedly enriched the state of the art and contributed to research relating to EGFR inhibitors, they do not establish that the active product osimertinib, which has led to the Tagrisso medicinal product, would not be the result of an independent inventive activity.

In this regard, the Cour finds that while Astrazeneca also filed two US patents US 8946235 and US 9732058 on July 25, 2012 and on December 19, 2014, relating to this active product, which mention the basic patent as prior art, fifteen other patents are also cited as prior art, which counterbalances the appellants’ allegations.

Similarly, it should be noted that if the AVIZIENYTE publication of 2008 mentioned the KWAK study of 2005, it also mentions thirty-one other bibliographic references.

Accordingly, the refusal of the SPC application was upheld by the Cour d’appel.

We must say that we are not entirely convinced by the simple quantitative approach adopted by the Cour d’appel for determining if the work underlying Astazeneca’s EP’895 patent is independent from the work which yielded the basic patent EP’414. Indeed, simply counting the total number of references cited by a patent or a scientific publication does not take into account the fact that not all cited references relate to the subject of interest, e.g. some of the cited references may only relate to minor experimental procedures, nor that not all cited references have the same scientific weight. In our opinion, it could be more relevant to establish the influence exerted by a publication/patent on following publications/patents, which can be estimated by counting the number of times the publication/patent has been cited by others, that is to say its impact factor. In this regard, it should be noted that the KWAK 2005 publication was cited more than 1000 times (Google Scholar count) which is a huge number. By comparison the AVIZIENYTE publication of 2008 was cited 93 times (Google Scholar count). We are not sure if this establishes whether the inventive activity leading to osimertinib depends from the work forming the subject-matter of the landmark KWAK 2005 publication and of the EP’414 patent, as the CJEU is rather elusive as to what constitutes an independent inventive activity, but in our opinion it is likely that this seminal work gave birth to a new field of research, i.e. searching for irreversible EGFR inhibitors useful to circumvent the T790M mutation, which eventually led to osimertinib.

With this decision we end our series of three recent decisions of the Paris Cour d’appel rendered on SPC refusals by the INPI. The final score is a spectacular hat trick (3 – 0) in favor of the INPI against SPC applicants.

Strikingly, if we perform a rapid statistical analysis of the decisions of the Paris Cour d’appel rendered on refusals of SPC applications by the INPI and discussed on this blog since 2016, we find that the Paris Cour d’appel upheld 100% (10/10) of the SPC refusals.

The odds of obtaining a reversal of a refusal decision are therefore clearly not in favor of SPC applicants. As such, if this trend were to continue, the best thing that could be expected from an appeal against a refusal of an SPC application by the INPI would be a reference for preliminary ruling by the CJEU, as e.g. in the Santen case (C-673/18). And indeed, all three decisions we discussed attempted to obtain a reference for a preliminary ruling, which the Cour d’appel however refused to pursue.

Thanks again Lionel for making my life easier reporting on this recent SPC case law – and for incidentally teaching me a sports-related idiom (definitely not my forte).

Is it fair to generally consider that, if a second patent filed after the publication of the basic patent gets granted and if it specifically claims an active ingredient which is generally covered by the basic patent, then there is almost no way the basic patent can be validly relied upon for an SPC application on that active ingredient?

Anyway, we will make sure to do something special on this blog next time an SPC refusal is overturned on appeal.


CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, February 9, 2021, Wyeth LLC & The General Hospital Corporation v. Directeur général de l’INPI, RG No. 19/19410.

To be continued

I think it is high time to wish all readers of this blog happy holidays. 2018 was an eventful year in the small world of European patent law, and there is little doubt that 2019 will be as well.

Before you go, here is a short summary of a few things to watch out for in the coming year – so that you can ponder over those and make your own 2019 predictions while indulging in device- or apparatus-shaped chocolates, or while humming typical Christmas songs such as “we wish you a valid patent, we wish you a valid patent, we wish you a valid patent, and a happy new grant“.

Let me start with the topic of last week’s post, the new mandatory web-based filing system implemented by the INPI. Let’s hope that it will improve next year and become more manageable and user-friendly.

Two side notes on this topic. One, the INPI guidelines have now been updated to reflect the new filing procedure. You can download them here. Second, there was an interesting discussion in the comment section of the post. There seems to be a strong argument that the Patent Law Treaty makes it impossible for the patent office to prohibit paper filing. One reader reported that, in one of his cases, the INPI accepted a paper filing when the representative insisted. But there has been no communication from the office on this issue. The updated guidelines no longer mention paper filing, and neither does the decision of the Director of the INPI which sets up the new system.

Hopefully we will get some clarification in the near future.

And while we are talking about the INPI, there is actually a lot going out right now, as reported in one of my previous posts. Will the legislative reform be successfully completed? What will the French opposition proceedings look like? Will there indeed be a full examination of French national applications? If the current expectations are confirmed, this will be an upheaval of French patent practice – but so far the always important practical details have not been forthcoming.

Things are also moving on the SPC battlefront – aren’t they always – with a number of important pending references to the CJEU. Just a few days ago, the opinion of the Advocate General in Abraxis (C-443/17) was issued, and it calls into question Neurim (C-130/11), which is one of SPC applicants’ favorite CJEU rulings. See a full report by Alexa von Uexküll and Oswin Ridderbusch here. We’ll see which way this one goes. And perhaps one day we will finally get to understand what a “product” is – almost a philosophical question.

“A kit for creating an illusion that suggests a Santa Claus visit”. Wait a minute? Is Santa Claus just an illusion?

Turning now to the EPO, no upheaval in sight, but still some interesting developments.

First, the new version of the Rules of procedure of the Boards of appeal will likely be finalized soon. As noted by a number of colleagues, such as Adam Lacy and Thorsten Bausch (here), this will likely make the lives of many parties in appeal proceedings more difficult.

One side remark again: when I reported on T 1914/12 (which by the way does not seem to be very much followed by other Boards, see Peter de Lange’s blog here), I wondered whether the proposed revision of the rules of procedure could potentially be considered as breaching article 114 EPC, if one were to adhere to the reasoning of Board 3.2.05 in this decision. Any thoughts on this?

Next, a new online user consultation has been launched by the EPO regarding the possibility of a postponed examination option (see here). A very recurring subject indeed. We’ll see whether and how it progresses in 2019.

Last but not least, the broccoli / tomato / bell pepper battle is still raging at the EPO. Remember that it was decided in G2/12 and G2/13 that the exclusion of essentially biological processes for the production of plants from patentability does not preclude patents on the plants themselves. But the European Commission subsequently expressed its disagreement with this position, which led to the amendment of R. 28 EPC in July 2017. And then bang! Board 3.3.04 in T 1063/18 decided that amended R 28 EPC violates art. 53 EPC. See Laurent Teyssèdre’s report here. It is quite difficult to predict where things will go from there.

As a consolation, faithful readers of this blog will be satisfied that Lionel Vial correctly anticipated some of the current difficulties with the application of amended Rule 28 EPC one and a half year ago. Are you skeptical? The evidence is here.

This post would not be complete if I did not say a word on the white whale of European patent law: the UPC. Rumor had it that the
German Bundesverfassungsgericht would issue a decision on the constitutional complaint in December, but you know how it is with UPC-related rumors. So I would be surprised if we had a decision under the tree on Christmas morning, and the suspense will likely continue for some time. Come March 29 and the actual Brexit, it is clear that the plan will have to be reworked.

That’s all folks, season’s greetings to all!

Happy birthday

Happy birthday, blog. On October 17, 2015, this blog’s first post was published. I am looking forward to another year of blogging and I do hope to be able to publish a second birthday post – although no promises are made.

Thank you very much Lionel Vial and Aujain Eghbali for your contributions up to now. You are welcome back on this blog any time. Other contributors are also welcome, even for a short message. Anonymous contributions may also be accepted.

A few stats for those who are interested. At this point the blog has a little bit more than 70 email subscribers. Thank you all. The link for subscribing is at the bottom of the left banner. The blog has had approximately 13,500 page views so far. The best score ever was 628 views in a single day when Laurent Teyssèdre kindly mentioned the blog in a post of his own famous blog. Thank you so much for this huge publicity.

The home page and some permanent pages are the most viewed ones. Other than that, the most popular post ever was the April fools’ joke on the UPC. Makes me think that I should quit reading case law decisions and start a career in hoaxes. Then, the next most popular ones are generally in the pharma field, this one being the winner.

Unfortunately, the vast majority of search queries which led visitors to this blog remain unknown to the blogmaster, but a tiny minority are known (this all depends on which search engine is used as far as I understand), and it makes you realize that sometimes the search results must have been quite disappointing for the searchers.

For instance, someone looking for a “patent for poison” was led to this post on poisonous divisionals; another person wanting to translate “the remedy may be worse than the disease” into French landed on a report by Lionel Vial on Merck v. Actavis; last but not least, a reader interested in “nice models” ended up on another (gorgeous) report by Lionel Vial, this time on disease models and their importance for the appraisal of sufficiency of disclosure.

This may also be a good time to ask readers about their thoughts on the blog and their opinion on how it could be improved:

  • Would you like to read more about EPO case law? Or to read only about French case law?
  • Should the posts be more succinct?
  • Should I switch to French because no foreign reader can possibly have any interest in what is discussed here?
  • Are there topics which have not been addressed yet and which should?
  • What about posting frequency?
  • Should my sentences be shorter and contain less passive voice as the blog editor keeps telling me?

Comments and private messages are welcome.

Enough celebrated. Let's extinguish the candles right now.
Enough celebrated. Let’s extinguish the candles right now.