A French revolution

You may have heard that French revolutions have a reputation for violence. But things do not always have to be that way.

Case in point: a groundbreaking SPC ruling recently issued by the Paris Cour d’appel. Contrary to what you would expect, heads did not roll. Quite the opposite in fact: the revolution is precisely that the SPC at stake survived unscathed. Lionel Vial reports.

This is it. It has happened. The Paris Cour d’appel has finally reversed a decision of the French PTO (INPI) to refuse an SPC.

Indeed, as noted here, since we began discussing French SPC case law on this blog in 2016, the Paris Cour d’appel has upheld 100% of the 11 SPC refusals by the INPI that we have commented on.

What prompted the Cour d’appel to change its habit? Avelumab.

Avelumab is an anti-PD-L1 monoclonal antibody. It is the active ingredient of Bavencio® (Pfizer), which is indicated in the treatment of cancers.

Anti-PD-L1 antibodies, like anti-PD-1 antibodies, disrupt the PD-1/PD-L1 interaction in vivo, which accounts for their biological effects.

On November 17, 2017, the Dana-Farber Cancer Institute filed an application for an SPC (FR17C1046) based on European patent EP 1210424 (hereafter EP’424), filed on August 23, 2000, and on marketing authorisation (MA) EU/1/17/1214 for avelumab granted to Merck Europe B.V. on September 20, 2017.

Interestingly, the subject-matter of EP’424 essentially relates to PD-L1, which is claimed as an isolated polypeptide (in claim 12). EP’424 also generally claims “an antibody which selectively binds to a polypeptide of claim 12” (claim 17) and “an antibody which selectively binds to a polypeptide of SEQ ID NO: 2 or 4 [i.e. PD-L1]” (claim 27), but does not claim avelumab in itself. Indeed, avelumab is claimed in itself in a later patent, EP 2785375, filed on November 21, 2012 by Merck Patent GmbH, which forms the basis of SPC application FR20C1068.

On February 3, 2021, the INPI refused the SPC pursuant to Article 3(a) of Regulation (EC) No 469/2009 (hereafter the SPC regulation). Essentially applying the Royalty Pharma judgment of the Court of Justice of the European Union (CJEU) in case C-650/17, the INPI considered that while avelumab was implicitly and necessarily covered by the functional definition used in claims 17 and 27 of the basic patent, avelumab is nonetheless not specifically identifiable from the patent, avelumab having been developed after the filing date of the basic patent following an independent inventive step.

A very similar case was submitted to the Cour d’appel 2 years ago, leading to a decision on January 19, 2021, which we commented on here.

As a brief reminder, the Cour d’appel then sustained the decision of the INPI to reject an SPC application for nivolumab, an anti-PD-1 monoclonal antibody. The Cour d’appel considered that while nivolumab was implicitly and necessarily within the scope of the invention covered by the basic patent, the preparation of monoclonal antibodies required more than routine operations; furthermore, three years after the basic patent was filed were necessary to file a patent specifically relating to nivolumab, which was a sound indication that an independent inventive step was needed from the basic patent to arrive at nivolumab.

It is therefore quite a surprise that in the present case the Cour d’appel decided not to side with the INPI.

What seems to have been key in the new decision of the Cour d’appel was to take into account the criteria for inventive step which result from the European patent convention (EPC), as well as from the Guidelines and case law of the European patent office (EPO), in order to assess the “independent inventive step” criterion of Royalty Pharma.

The Cour d’appel thus considered that:

[…] The methods for generating and identifying an antibody directed against a given antigen are routine techniques for the person skilled in the art at the priority date; as a consequence, when the targeted antigen is already known, the discovery of an antibody binding to this antibody does not involve an inventive step.

Besides, the Cour d’appel did acknowledge that European patent EP 2785375, filed 11 years after the filing date of EP’424, was granted for avelumab but noted that the Examining division had first considered avelumab as lacking an inventive step and that if an inventive step was finally recognized by the EPO, it was due to the inter-species cross-reactivity of avelumab, and not for its capacity to bind to PD-L1.

Accordingly, the Cour d’appel went on to conclude:

It can be deduced from these elements, on the basis of the general knowledge of the person skilled in the art and from the state of the art at the priority date of patent EP464 that the human monoclonal antibody avelumab was specifically identifiable by the person skilled in the art in the light of the teachings of said patent, by known and well mastered routine experiments, which may be long and fastidious, but do not involve an independent inventive step.

The Cour d’appel admittedly also took into consideration the fact that the invention forming the subject-matter of EP’424 was a breakthrough invention which led to the marketing of several antibodies, such as avelumab, having a decisive public health impact in the fight against cancer.

How could the difference in outcome with the earlier case regarding the anti-PD-1 nivolumab then be explained, as the basic patent also contained guidance for manufacturing anti-PD-1 antibodies in this earlier case? Certainly not by the composition of the Cour d’appel, which was identical to the composition in the present case.

One possible explanation would be that, although the invention forming the subject-matter of the basic patent originated from the work of Tasuku Honjo, who won the Nobel prize for the discovery of PD-1, it was less of a breakthrough invention, as the basic patent neither claimed PD-1 (which was discovered several years before its filing) nor anti-PD-1 antibodies in general, and was indeed filed after EP’424. Besides, the SPC in that earlier case was also found by the Cour d’appel not to comply with Article 3(c) of the SPC regulation, which made the assessment of the compliance with Article 3(a) less crucial.

Whatever the reason, the present judgment is in our opinion a landmark decision which could be seen as lowering the bar which had been set by the Medeva (C-322/10) and Eli Lilly (C-493/12) case law to pass the requirements of Article 3(a) of the SPC regulation for monoclonal antibodies in France.

Last year, Renaud promised, perhaps a little too boldly, to do something special on this blog next time an SPC refusal would be overturned on appeal. I therefore leave it to him to surprise you!

What can I say, I should know better than to make reckless promises, especially when SPC law is involved. But I am not one to balk – and so, a surprise it is…

The surprise.

CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, May 25, 2022, Dana-Farber Cancer Institute Inc. v. INPI, RG No.21/08514.

Same player shoot again

Long time no see! I am sure that readers have noticed that PatentMyFrench has been dormant over the past few months. Hopefully, posting can resume in the near future, so as to perhaps tackle the backlog of interesting decisions that have not been commented on – but let’s face it, we are not there yet.

That said, owing to regular contributor and SPC enthusiast Lionel Vial, the blog at least temporarily comes back to life today, for an update on Halozyme’s mishaps with the French patent office. Many thanks Lionel, the floor is yours.

We had a feeling of déjà-vu with this decision of the Paris Cour d’appel, dated January 18, 2022, concerning the rejection by the French patent office (INPI) of Halozyme Inc.’s SPC application No. FR16C0030. This application pertains to a combination of an anti-CD20 monoclonal antibody, Rituximab, and recombinant human hyaluronidase, which is indicated for the treatment of non-Hodgkin lymphoma.

Indeed, last year we discussed the decision of the Paris Cour d’appel to sustain the decision of the INPI to reject Halozyme Inc.’s SPC application No. FR15C0053 pertaining to a combination of an anti-HER2 monoclonal antibody, Trastuzumab, and recombinant human hyaluronidase (here).

Of note, the panel of judges of the Cour d’appel was the same for both decisions.

In the previous case, the Cour d’appel had decided as follows:

[…] it appears from the “summary of the product characteristics” of the MA [marketing authorisation] that the active ingredient of the medicinal product is Trastuzumab, that hyaluronidase is an excipient, and that no other element contained in the MA justifies that hyaluronidase alone, or associated to Trastuzumab, would produce a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the MA. […]

It follows that, in the combination of Trastuzumab and recombinant human hyaluronidase, forming the subject-matter of the SPC at stake, only Trastuzumab is the active ingredient, while a MA has already been granted for Trastuzumab alone. Therefore the invoked MA is not the first MA for the product pursuant to article 3(d) of the regulation. Accordingly, the director of the INPI rightly decided that the SPC application did not comply with the requirements of the regulation and that it had to be rejected.” (emphasis added).

In the present case, Halozyme repeated the previously raised arguments that the fact that hyaluronidase was coined an excipient in the MA did not mean that it was deprived of a physiological action of its own. In fact, hyaluronidase makes room in the subcutaneous space by degrading hyaluronan, which increases the dispersion and absorption of Rituximab upon its injection.

In addition, in order to show that hyaluronidase has a therapeutic effect of its own, Halozyme also provided two publications reporting the results of experiments carried out in mouse models of pancreatic cancer and breast cancer, one of the two publications – presumably Shuster et al. (2002) Int J Cancer 102:192-7 –  indicating that hyaluronidase may itself have intrinsic anti-cancer activity.

So, did Halozyme prevail this time?

Moving up to the next level.

This is what the Cour d’appel decided:

[…] the CJEU ruled [in case C-210/13 Glaxosmithkline] that “(…) just as an adjuvant does not fall within the definition of ‘active ingredient’ (…), a combination of two substances, namely an active ingredient having therapeutic effects on its own, and an adjuvant which, while enhancing those therapeutic effects, has no therapeutic effect on its own, does not fall within the definition of ‘combination of active ingredients’ within the meaning of that provision”.

In the present case, the court noted that on page 14 of the assessment report […] a paragraph entitled “New excipient: recombinant human hyaluronidase (rHuPH20)” states that “rHuPH20 degrades hyaluronan under physiological conditions and acts as a propagation factor in vivo. Thus, when combined or co-formulated with certain injectable drugs, rHuPH20 facilitates their absorption and dispersion by temporarily clearing a pathway through the connective tissue in the subcutaneous space […]”.

It follows from these elements that recombinant human hyaluronidase is an excipient that allows to increase the therapeutic effects of the active ingredient by facilitating its absorption and dispersion through the connective tissue of the subcutaneous space. This does not allow, contrary to the allegations of Halozyme, to qualify the combination of Rituximab and recombinant human hyaluronidase as being a combination of active ingredients within the meaning of article 1(b) of the Regulation as interpreted by the CJEU.

It follows from all the foregoing that the combination of Rituximab and recombinant human hyaluronidase for which the contested SPC application was filed is not a product within the meaning of Article 1(b) of Regulation (EC) No 469/2009, that Rituximab has already been the subject of two previous marketing authorizations, so that the MA invoked is not the first for this product within the meaning of article 3(d) of the regulation, and that the Director of the INPI therefore rightly decided that the [SPC] application does not meet the conditions set forth by the Regulation, so that the appeal against the decision of the Director of the INPI must be rejected. (emphasis added).

Same result then.

In this regard, it should be noted that the two above-mentioned publications cited by Halozyme to establish that hyaluronidase has a therapeutic effect of its own were not taken into account by the Cour d’appel because they relate to the treatment of cancers other than non-Hodgkin lymphoma. One can therefore wonder what the outcome would have been, if results of experiments establishing that hyaluronidase has a therapeutic effect of its own in an animal model of non-Hodgkin lymphoma had been presented to the court.


CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, January 18, 2022, Halozyme Inc. v. Directeur Général de l’INPI, RG No. 20/17731.

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.

Court says no to Ono

Owing to my colleague and excellent friend Lionel Vial, it is SPC month on Patent my French!

After tackling the recent Halozyme judgment a couple of weeks ago, Lionel now goes one-on-one with Ono.

As promised last week, we are back to discuss the second of the third recent supplementary protection certificate (SPC) appeal decisions rendered on refusals of the French patent office (INPI).

This week’s decision, which was rendered by the Paris Cour d’appel on January 19, 2021, discusses not one but two articles (aren’t we lucky) of Regulation (EC) No 469/2009 (the “SPC regulation”): 3(a) and 3(c).

SPC application FR15C0088 was filed on December 15, 2015 by Ono Pharmaceutical Co. Ltd and Professor H., whom we are told in the decision is a Nobel prize winner, on the basis of (i) marketing authorization EU/1/15/1014 in the name of Bristol-Myers Squibb Pharma EEIG and of (ii) European patent EP 1537878 (which will give you the full name of Professor H. if you are curious or if you don’t know the names of all Nobel prize winners by heart). EP 1537878 was filed on July 2, 2003 and granted on September 22, 2010. The product forming the subject-matter of the SPC is nivolumab (Opdivo®), a human monoclonal antibody which blocks the PD-1 receptor and is indicated in the treatment of certain cancers.

Since the decision begins with article 3(c) of the SPC regulation, let’s do the same.

The SPC application was rejected on March 2, 2018 pursuant to article 3(c) of the SPC regulation because a SPC had already been granted to Ono Pharmaceutical Co. Ltd for nivolumab.

The SPC in question is FR15C0087, also filed on December 15, 2015, granted on January 6, 2017, and held by Ono Pharmaceutical Co. Ltd and E. R. SQUIBB & SONS, L.L.C on the basis of European patent EP 2161336.

The INPI based its decision in particular on the judgment of the CJEU of September 3, 2009 in case C‑482/07 (AHP Manufacturing), which notably provides that “it should be pointed out that the first sentence of Article 3(2) [of Regulation (EC) No 1610/96, i.e. the phytosanitary SPC regulation] precludes the grant, to the holder of more than one patent for the same product, of more than one SPC for that product. However, the second sentence of Article 3(2) allows such a grant to two or more holders of different patents for the same product. It is thus apparent that the special condition for the grant of two or more SPCs for the same product is that the relevant applications emanate from different holders of basic patents” (see paragraph 25 of the judgement).

Faithful readers will immediately be reminded of a previous decision discussed here on this blog, in which the Cour d’appel sustained the decision of the INPI to reject a SPC applied by Medivir AB for simeprevir pursuant to article 3(c) in view of a previous SPC for the same product held by Medivir AB and Janssen Sciences Ireland UC.

The INPI therefore appears to be consistent in considering that the different holders of a same SPC or SPC application should not be considered as a single entity but individually.

Is it also the case of the Cour d’appel?

In the appeal proceedings, Ono and Professor H. notably argued that the case law of the General Court of the European Union (EU) allows the EU judge who cannot find elements in the EU law which would allow her/him to specify the content and scope of an EU provision by an autonomous interpretation to rely on national law. In the present case, pursuant to French civil law ruling co-ownership, the “holder” within the meaning of the SPC and phytosanitary SPC regulations would thus refer to all the persons holding property rights on a patent, so that the two basic patents (and the corresponding SPCs) would be held by different holders.

The Cour d’appel ruled as follows:

In this regard, the reference made by the appellants to the rules of civil law relating to co-ownership to argue that the holders of the EP 336 and EP 878 patents are not the same – the co-ownership consisting of the ONO and SQUIBB & SONS companies, holders of the EP 336 patent, being in this regard different from the co-ownership consisting of the ONO company and Pr. H., holders of the EP 878 patent – so that the conditions of Article 3(2) (second sentence) of regulation (EC) 1610/96 are fulfilled, is inoperative. The rules governing patent co-ownership are specifically defined by articles L. 613-29 to L. 613-32 of the Code de la propriété intellectuelle. Article L. 613-30 expressly provides that the ordinary law governing co-ownership resulting from the civil code does not apply to co-ownership of a patent application or a patent. Article L. 613-29 provides that “Each of the co-owners may use the invention for its own benefit, provided the other co-owners are indemnified (…)”. It follows therefrom that ONO, which is a co-owner of both the EP 336 and EP 878 patents and which may use them alone under the conditions set forth in article L. 613-29 of the Code de la propriété intellectuelle, is a “holder” of these patents within the meaning of article 3(2) of previously cited regulation No. 1610/96.

The decision of the INPI was therefore sustained.

Here, we are of the opinion that the reasoning of the Cour d’appel might miss a point. Indeed, article L. 613-32 of the Code de la propriété intellectuelle provides that articles L. 613-29 to L. 613-31 apply in the absence of contractual provisions stating otherwise and that co-owners may decide otherwise at any time through a co-ownership agreement.

As such, before reaching its conclusion, the Cour d’appel should have checked whether co-ownership agreements had been set up between Ono & Squibb on the one hand, and between Ono & Professor H. on the other hand, and if both these agreements allowed Ono to use the patents for its own benefit, without requiring any authorization from the other parties.

Perhaps this missing piece in the reasoning of the Cour d’appel will be addressed by the Cour de cassation (the French Supreme court) in the future.

An Easter egg was supposed to be hidden in this post, but it went missing.

Notwithstanding, this may be irrelevant for the outcome of this case, as the rejection was also based on article 3(a) of the SPC regulation.

Claim 3 of the basic patent was relied on for the purpose of the SPC application:

Anti-PD-1 antibody which inhibits the immunosuppressive signal of PD-1 for the use in cancer treatment.

The INPI considered that while claim 3 did “implicitly” cover nivolumab, it could not be interpreted in the light of the description of the basic patent as relating “necessarily” and “specifically” to this active ingredient within the meaning of the judgement of the CJEU in case C‑493/12 (Eli Lilly), as the description of the patent did not contain any indication, such as a concrete embodiment or any other teaching allowing to specifically individualise nivolumab.

The appellants argued that nivolumab necessarily relates to the invention covered by the patent, because it implements the technical contribution brought by the basic patent. The appellants further argued that nivoluab was specifically identifiable by the person skilled in the art because patent EP 878 teaches all the necessary elements to identify the antibodies forming the subject-matter of claim 1, and describes in detail the steps for producing an anti-PD-1 antibody and how to screen these antibodies to identify those which inhibit the immunosuppressive signal of PD-1; as such, the person skilled in the art could obtain, at the filing date of the EP 878 patent, through routine operations, all the antibodies fulfilling the function recited by the EP 878 patent, including nivolumab.

The Cour d’appel essentially relied on the judgement handed by the CJEU on April 30, 2020 in case C‑650/17 (Royalty Pharma) to reach its decision.

The Royalty Pharma judgement provides:

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 individualised 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).

The Cour d’appel agreed with the appellants that nivolumab is implicitly and necessarily within the scope of the invention covered by the basic patent. However, it came to a different conclusion as to whether nivolumab is specifically identifiable.

The Cour d’appel considered that the preparation of monoclonal antibodies requires more than routine operations. The fact that 3 years were necessary for Ono to file the EP 336 patent which specifically relates to nivolumab was a sound indication that an independent inventive step was needed from the EP 878 patent to arrive at nivolumab.

The decision of the INPI based on article 3(a) of the SPC regulation was therefore also sustained.

For our part, we are not certain that the article 3(a)-test should be applied in the same manner to functionally-defined antibodies on the one hand and small molecules on the other hand.

Indeed, given a protein target, it is generally considered that the level of difficulty for identifying small molecule inhibitors is higher than for antibody inhibitors. As such, this difference should also be reflected in the standard to apply for determining if a product is specifically identifiable from a patent specification. In this regard, it should be noted that the Royalty Pharma judgement arose from a small molecule case (sitagliptin). In contrast, the Eli Lilly judgement arose from a monoclonal antibody case (tabalumab). Accordingly, perhaps monoclonal antibody SPCs should be assessed on the basis of the Eli Lilly judgement, without applying the “independent inventive step” test added by the Royalty Pharma judgment, which should be reserved to small molecules, at least until the CJEU clearly states that this latter test is of universal application for functionally-defined products. In this regard, it should be noted that the UK intellectual property office did grant a SPC for nivolumab based on the EP 878 patent on June 25, 2018 (before the Royalty Pharma judgement was handed).

We will be back soon with the last of the three SPC appeal decisions rendered on refusals of the INPI, with yet another article 3(a)/Royalty Pharma case.

Thank you Lionel. Any decent SPC post is supposed to end with the expression of a wish for – or fear of – a future CJEU referral, and I am quite happy that this one is no exception.


CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, January 19, 2021, Ono Pharmaceutical Co. Ltd. et al. v. Directeur général de l’Institut national de la propriété industrielle, RG No. 18/10522.

Easy as ACD

Even for those who know the ABCs of patent law, mastering the ACDs of SPC law may seem a daunting task. I am talking about article 3(a), 3(c) and 3(d) of the SPC regulation of course, a never-ending source of legal headaches. 

I am happy to once again host a contribution from SPC enthusiast Lionel Vial, reporting on the first of a series of three recent judgments. With his explanations, I am sure everything will look as easy as ACD.

Today we discuss the first of three recent decisions of the Cour d’appel (appeal court) of Paris rendered on appeal against decisions of the French patent office (INPI) to reject three SPC applications in view of Articles 3(a), 3(c) and 3(d) of the SPC Regulation (Regulation (EC) No 469/2009):

Date of the decision Parties SPC Product Article of the SPC regulation applied Main CJEU decisions applied Outcome
15/12/2020 Halozyme Inc. 15C0053 Trastuzumab and recombinant human hyaluronidase 3(d) C-631/13 (Arne Forgsen) SPC rejection sustained
19/01/2021 Ono Pharmaceutical Co. Ltd & Prof. H 15C0088 Nivolumab 3(a) & 3(c) C-482/07 (AHP Manufacturing) & C-650/17 (Royalty Pharma) SPC rejection sustained
09/02/2021 Wyeth LLC & the General Hospital Corporation 16C1004 Osimertinib 3(a) C-650/17 (Royalty Pharma) SPC rejection sustained
The ABC mouse is right: SPC law does feel like the teacher playing a joke on the class.

In the first case, Halozyme Inc. had applied for a SPC (FR15C0053) for a combination product of trastuzumab and recombinant human hyaluronidase on the basis of a marketing authorization (MA) granted on 26 August 2013.

The combination is indicated in the treatment of breast and gastric cancer. Trastuzumab is a monoclonal antibody targeting HER2 thereby inhibiting the proliferation of human tumor cells that overexpress HER2. Recombinant human hyaluronidase increases the dispersion and absorption of co-administered drugs when administered subcutaneously, by catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix.

A previous MA for trastuzumab was granted on 28 August 2000.

Problem: the summary of the product characteristics of the MA of 2013 mentions trastuzumab as the sole active ingredient and hyaluronidase is listed among the excipients.

As a consequence, the INPI rejected the SPC application on 7 March 2018 on the basis of Article 3(d) of the SPC Regulation, considering that recombinant human hyaluronidase was not an active ingredient having a therapeutic action of its own but that it was an excipient, as provided in the summary of the product characteristics of the MA. As such, hyaluronidase did not qualify as a product within the meaning of the SPC regulation, the product being none other than the active ingredient shown in the MA, i.e. trastuzumab, which had already been granted a MA in 2000.

Halozyme appealed the decision of the INPI in particular on the ground that, based on judgement C-631/13 (Arne Forgsen) of the CJEU, it was of no consequence that hyaluronidase was presented as an excipient in the MA, since the SPC regulation does not provide that a SPC should be only granted for active ingredients presented as such in the corresponding MA. Instead, it should be verified, based on all pertinent factual and scientific elements, whether the ingredient at stake could be considered an active ingredient. In this regard, recombinant human hyaluronidase should be considered as an active ingredient, since it has a therapeutic action on the organisms of patients allowing treating breast cancer.

As a reminder, judgement C-631/13 notably provides that:

Article 1(b) of Regulation No 469/2009 must be interpreted as meaning that a carrier protein conjugated with a polysaccharide antigen by means of a covalent binding may be categorized 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 authorization, a matter which it is for the referring court to determine, in the light of all the facts of the dispute in the main proceedings. (emphasis added).

This is what the Court decided:

It results from the foregoing that it appears from the “summary of the product characteristics” of the MA that the active ingredient of the medicinal product is trastuzumab, that hyaluronidase is an excipient, and that no other element contained in the MA justifies that hyaluronidase alone, or associated to trastuzumab, would produce a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the MA (emphasis added).

[…]

It follows that, in the combination of trastuzumab and recombinant human hyaluronidase, forming the subject-matter of the SPC at stake, only trastuzumab is the active ingredient, while a MA has already been granted for trastuzumab alone. Therefore the invoked MA is not the first MA for the product pursuant to article 3(d) of the regulation. Accordingly, the director of the INPI rightly decided that the SPC application did not comply with the requirements of the regulation and that it had to be rejected.

Even though the appeal was eventually rejected, it should be noted that the Cour d’appel did consider other parts of the MA than the summary of the product characteristics to assess the action of hyaluronidase and establish whether it could be considered as an active ingredient.

Accordingly, there is still some hope for combination SPCs in France when one of the ingredients of the combination is not mentioned as an active ingredient in the summary of the product characteristics of the MA, provided, of course, that data showing a therapeutic action of its own within the indications of the MA is available.

To be continued with the second of the three decisions!


CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, December 15, 2020, Halozyme Inc. v. Directeur Général de l’INPI, RG No. 18/14332.