MSD’s ezetimibe-simvastatin SCP revoked by the Paris Court of Appeal

Thanks to Jean-Baptiste Thiénot & Alexandre Ghanty of CMS Francis Lefebvre Avocats for the recent update from France - reproduced below.

In a case involving Merck Sharp and Dohme (MSD) and TEVA, Paris Court of Appeal issued an interesting decision on 25 September 2020 regarding both articles 3(a) and 3(c) of Regulation EU No.469/2009, widely in line with the ruling adopted by the CJEU in Actavis v. Sanofi (CJEU, C-443/12, 12 Dec. 2013). 

Background

MSD obtained two SPCs on the basis of the same patent (EP 0 720 599) entitled “hydroxy-substituted azetidinone compounds effective as hypocholesterolemic agents”. 

• A first SPC had been granted to MSD on 4 February 2005 on the basis of EP 599 for a drug whose API was ezetimibe (EZETROL®). 
• A second SPC had been granted nearly 2 years later, on 21 December 2006, on the basis of the same patent but this time for a combination product ezetimibe + simvastatin (INEGY®). 

The dispute

TEVA launched a revocation action against the second SPC, arguing – among other things - that the combination product at stake was a mere variation of the invention protected by the patent, and not a distinct “product” from ezetimibe alone, in breach of both articles 3(a) and 3(c). 

TEVA’s claims have been dismissed by Paris First instance Court on 25 October 2018. In parallel, a few months later (on 08 February 2019), MSD obtained preliminary injunctions against other generic companies on the basis of this ezetimibe + simvastatin SPC.

This decision has been reversed. Indeed, on appeal, TEVA obtained from the Court of Appeal the revocation of the ezetimibe + simvastatin SPC in a decision dated 25 September 2020. 

Regarding article 3(a), although the patent at stake specifically mentions the combination ezetimibe-simvastatin, the court considered that such combination cannot be deemed as “protected by a basic patent” within the meaning of the Regulation. In other words, the Court considers that patent EP 599 contains only one invention and that the combination with simvastatin cannot be regarded as another invention. Indeed, it emphasizes that the specification uses the singular when designating the invention, presents the combination as “another aspect of the invention”, and makes no distinction in therapeutic effect between the mono and the combination therapies. Besides, it is noted that the skilled person, who was deemed aware of the possibility of combining two anticholesterolemic drugs having different mechanisms of action and who was familiar with simvastatin, would not consider the ezetimibe-simvastatin combination to constitute an innovative product (towards ezetimibe alone). 

Regarding article 3(c), the court recalled, in application of Actavis v. Sanofi, that where the holder of a patent has already obtained a SPC for an active ingredient entitling him to oppose the use of that active ingredient, either alone or in combination with other active ingredients, such article must be interpreted as precluding that patent holder from obtaining a second SPC relating to that combination. 

To the extent that the ezetimibe-simvastatin combination is not deemed to constitute an innovative product, the Court considered that the first SPC granted for the use of ezetimibe should allow, in itself, MSD to oppose to the marketing of a drug containing ezetimibe in combination with simvastatin. 

This decision was predictable since the Court of Appeal used the same reasoning a few months ago (14 February 2020, cases No. 19/03820 (Sandoz) and No. 19/06114 (Mylan) as reported by the SPC blog here) to revoke the preliminary injunctions granted to MSD on the basis of this ezetimibe + simvastatin SPC.

What next?

The battle is not over: an appeal before the Cour de cassation is pending in the above-mentioned preliminary injunction cases and the same is expected in the Teva v. MSD case.

Although the means are quite different here than in the Santen case (CJEU, C-673/18, 9 July 2020), the trend seems to be the same, leading to a stricter approach in the analysis of the conditions of SPCs where the basic patent has already given rise to a first SPC. As it has been observed in Abraxis Bioscience, “the legislature intended, in establishing the SPC regime, to protect not all pharmaceutical research giving rise to the grant of a patent and the marketing of a new medicinal product, but to protect research leading to the first placing on the market of an active ingredient or a combination of active ingredients as a medicinal product” (CJEU, C-443/17, 21 March 2019, §37).

Korean IPTAB Issues Leading Decision on Patent Term Extension (PTE) - Enforceable Scope Related to Medicinal Use

Thanks to Sang Young LEE and Kevin Kyumin LEE of Kim & Chang for some news from Korea - reproduced below.  There is no published decision available yet, and we will post it once it appears. 

"In contrast to some foreign jurisdictions where the patent scope during PTE covers all types of use, Article 95 of the Korean Patent Act stipulates that PTE patent scope should be restricted to the specific use of the approved originator product.  It was generally considered that the use of medical inventions should refer to the target disease of the approved products but there has been no judicial precedent supporting how Article 95 should be interpreted on this issue.

This changed on July 1, 2020 when the Korean Intellectual Property Trial and Appeal Board (IPTAB) rendered a historic decision regarding the type of "use" that is considered within the enforceable patent scope during the PTE of a pharmaceutical compound patent.  Galvus® (API: vildagliptin), a type 2 anti-diabetic drug of Novartis, has five different types of dosage regimens (or efficacy and effect under the Korean translation).  Utilizing the fact that Novartis filed a PTE application based on only one approved efficacy and effect, three Korean generic companies filed scope confirmation actions claiming that their products did not fall within the patent scope because they had carved out the efficacy and effect first filed by Novartis as the basis for the PTE.  They argued that the patent scope during the PTE should be limited to the first approved efficacy and effect only, and that the later approved four efficacies and effects were not covered.

An expanded five-member panel of the IPTAB held that the use (and therapeutic effect) that is within the patent scope of the compound PTE is not limited to the first efficacy and effect, and that the generic's products were within the scope of the patent during PTE ruling in favor of Novartis.

The IPTAB's detailed reasoning was as follows:

l  If the scope of a patent during PTE is restricted to specific items of an approved product underlying the PTE (first approved effect and efficacy in this case), it becomes easy for generic companies to circumvent the patent during PTE when it relied on most of the approval data of the original products in gaining approval of its product.  This violates the purpose of the PTE system which is to compensate the non-practicing period of the patentees.

l  The Supreme Court held in a previous case ("Vesicare® case") that the patent right during the PTE should not be limited to the specific items as approved.  The Vesicare® case involved the issue of whether patent scope during the PTE for a compound patent is limited to specific salt forms of the approved product.  The Supreme Court held that the patent scope during the PTE should be determined based on the active ingredient, therapeutic effect, and use of an approved product underlying the PTE and not limited to the specific items as approved.

l  Compound patents during PTE should be more broadly protected than dosage regimen patents considering the different technical significances (meaning that a dosage regimen as approved as efficacy and effect should not limit the scope of compound patents).

l  The efficacy and effect in a marketing approval is governed by regulatory laws and is dependent on various factors including the type of disease and approval schedule, etc.  Thus, it is unreasonable to confine the scope of a patent based on efficacy and effect, which has a different legislative focus from patent law. 

The IPTAB decision can still be appealed to the Patent Court so is not yet the final say on this issue.  However, we believe this is a significant first step in improving understanding in the patent system of how the use of a medical invention should be defined during PTE, and has the potential to affect many originator pharmaceutical companies that rely on PTE to protect their products.  The IPTAB rejected the generic's efforts to unjustly narrow the PTE scope, and thereby laid the groundwork for originators to protect their legitimate interests from generic challenges as well as preserve the originator drug price after generic entry."

Santen ends Neurim-style SPCs

The wording of Article 3d of the SPC Regulation requires that the SPC application must rely on “the first authorisation to place the product on the market as a medicinal product”. This always suggested that a marketing authorisation granted for a new indication of a previously approved active ingredient could not be relied upon as the basis of an SPC for the patent directed to the new medical use.

However, based on a purposive construction of the Regulation, the CJEU decision in Neurim in 2012 opened the door to just that possibility.

Unusually, the CJEU has now reversed its own Neurim decision in the Santen decision C-673/18 issued on 9 July 2020. A later MA to a new indication cannot be used as the “first MA” supporting an SPC on a new medical use of the same active ingredient. The Santen decision states:

“Article 3(d) of [the SPC Regulation] must be interpreted as meaning that a marketing authorisation cannot be considered to be the first marketing authorisation, for the purpose of that provision, where it covers a new therapeutic application of an active ingredient, or of a combination of active ingredients, and that active ingredient or combination has already been the subject of a marketing authorisation for a different therapeutic application.”

Neurim was always the problem child, out of step with earlier CJEU decisions, and national patent offices struggled to know how broadly to apply it. In Santen, the CJEU expressly now disapproves of the Neurim logic (see paragraph 53 of the decision).

In reaching its decision the CJEU (sitting in Grand Chamber with 13 judges) first concluded that the definition of an active ingredient under Article 1b of the SPC regulation does not import any use-limitation:

"the fact that an active ingredient, or a combination of active ingredients, is used for the purposes of a new therapeutic application does not confer on it the status of a distinct product where the same active ingredient, or the same combination of active ingredients, has been used for the purposes of a different, already known, therapeutic application".

As a result, Article 3d of the regulation must then refer to the first MA for any use of that active ingredient as a medicinal product:

"In addition, in the light of the strict definition of the term ‘product’ within the meaning of Article 1(b) of Regulation No 469/2009, .. the analysis of the wording of Article 3(d) of that regulation presupposes that the first MA for the product as a medicinal product for the purpose of that provision means the first MA for a medicinal product incorporating the active ingredient or the combination of active ingredients at issue (see, to that effect, judgment of 21 March 2019, Abraxis Bioscience, C‑443/17, EU:C:2019:238, paragraph 34), irrespective of the therapeutic application of that active ingredient, or of that combination of active ingredients, in respect of which that MA was obtained."

So, the Neurim logic appears to be dead.

Crucially, any products protected only by SPCs based on second or further medical use patents, and relying on a second, or later, MA for that active, may now be vulnerable to immediate generic competition.

Hold the Front Page: Royalty involved in SPC decision!

The CMS patent litigation team in London have provided a review of the Royalty Pharma decision (C650/17). Many thanks to Gareth Morgan, Natalie Coan and Hannah Rigby for their thoughts.  

On 30 April 2020, the CJEU ruled on the interpretation of Article 3(a) of the SPC Regulation in an action between the Royalty Pharma Collection Trust and the German Patent and Trademark Office (C-650/17) (“Royalty”).  

In its ruling, the CJEU in Royalty held that a product developed after the filing date of a patent following an independent inventive step but falling under the functional definition of said patent was not considered ‘protected’ under Article 3(a) of the SPC Regulation. The case brings greater clarity after an uncertain line of case law following Medeva (C-322/10) in relation to what is ‘specified in the wording of the claim’. The CJEU in the Royalty ruling confirmed the test endorsed by the CJEU in  Gilead (C-121/17) by following the two pronged test but most notably added clarification by confirming that the term “core inventive advance” was not relevant to the interpretation of Article 3(a). Until now the CJEU had failed to offer a clear test for applying Article 3(a) but this decision has the effect of finally placing the interpretation of Article 3(a) on more stable ground.

Article 3(a) of the SPC Regulation requires that a product be protected by a basic patent in force before an SPC may be granted in respect of it. Medeva introduced the concept of ‘specified in the wording of the claim’, although it was unclear what that really meant. A further layer of confusion appeared in the CJEU’s decision in Actavis (C-443/12) which stated that the product had to constitute “the core inventive advance of that patent”. That case related to Article 3(c) but the CJEU referred to the same test in Actavis (C-577/13) which related to Article 3(a). It was then unclear when exactly the core inventive advancement of the patent should be taken into consideration and whether it had replaced the Medeva test.

Arnold J sought some clarity on this point in his referral to the CJEU in Gilead. In his referral, Arnold J suggested that ‘protected by the patent’ should mean that the product must ‘embody the core inventive advance’ of the patent, replacing ‘specified in the wording of the claim’. The CJEU did not explicitly reject this proposal but confirmed that each active ingredient should (1) necessarily fall under the invention covered by the patent; and (2) be specifically identifiable in light of the information disclosed by that patent. Arnold J took this to mean that the patent’s technical contribution was relevant to the assessment. The UK Court of Appeal subsequently overturned Arnold J’s interpretation, replacing this with a simpler test of whether all components of the “product” were necessarily required by the language of the claim.

The confusion caused by pre-Gilead case law has however remained, leading to a number of referrals, including that of the German Federal Court in Royalty.

Royalty Pharma had applied for an SPC protecting sitagliptin on the basis of its patent claiming use of dipeptidylpeptidase IV inhibitors to lower blood glucose levels. Sitagliptin was developed after the filing date of the relevant patent. It is however a dipeptidylpeptidase IV inhibitor and was therefore covered by the functional definition in the patent’s claims.

The German Federal Court requested guidance as to whether a product is protected under Article 3(a) where:

1.       The product is not expressly referred to in the patent’s claims;

2.       The product is not considered the specific embodiment of the patent;

3.       The product was developed after the filing date of the patent; and

4.       The product was covered by a functional definition in the patent’s claims.

The CJEU held that Article 3(a):

“is to be interpreted as meaning that a product is protected by a basic patent in force within the meaning of this provision if it corresponds to a general functional definition used in one of the claims of the basic patent and necessarily relates to the invention protected by this patent, but without being individualized as a specific embodiment from the teaching of the patent, provided that it can be specifically identified, in light of all the information disclosed by said patent, by a person skilled in the art, on the basis of their general knowledge in the field, considered on the filing or priority date of the basic patent and the state of the art on that same date.”

This ruling follows the ruling in Gilead.

The CJEU’s clarification seems to have confirmed that the test for Article 3(a), in effect, equates to a question whether there has been an enabling disclosure of the product. The CJEU held that:

“Article 3(a) must be interpreted as meaning that a product is not protected by a basic patent in force within the meaning of that provision where, although that falling under the functional definition given in the claims of this patent, it was developed after the filing date of the application for the basic patent, at the end of an autonomous inventive step.”

The CJEU has therefore confirmed that the patentee of the basic patent must demonstrate that the skilled person could produce the product which is the subject of the SPC using only the common general knowledge and prior art, with no inventive activity.

The Royalty ruling confirms, and clarifies, the Gilead decision. It represents another nail in the ‘core inventive advance test’ coffin with respect of Article 3(a), and further demarcates the appropriate test for Article 3(a).  Notwithstanding the clarity offered on Article 3(a) new questions arise in respect of the compatibility of this ruling with the earlier Actavis case law on Articles 3(a) and 3(c), and also the extent to which any later independent inventive activity creates a new “product” for the purposes of SPC eligibility. 

Paris Court of Appeal overturns preliminary injunctions against Mylan and Sandoz/ MSD's ezetimibe/simvastatine SPCs

Many thanks to Denis Schertenleib, from Schertenleib Avocats (an old friend of the blog) for the following report on events before the Paris Court of Appeal, in relation to Merck's ezetimibe/simvastatine SPC, in which he was involved: 

On 14 February 2020, the Paris Court of Appeal overturned a series of preliminary injunctions against Mylan and Sandoz based on Merck's ezetimibe/simvastatine SPC. These decisions are of specific interest as they are the first to follow a series of injunctions and substantial awards of provisional damages granted against several generics by the High Court of Paris from 2018 to 2019.  Commentators following such injunctions and awards of provisional damages had argued that this constituted a landmark change of practice at the High Court in pharmaceutical cases. However, these decisions had not been subject to appellate review.  On appeal the court held that, in addition to the relevant SPC being invalid, the measures ordered were disproportionate. The Court of Appeal held that Merck’s SPC suffered from serious grounds of invalidity, thus overturning the previous High Court decision that found this SPC valid and infringed. The Court of Appeal further held that the various product recalls and provisional damages ordered were disproportionate and thus should not have been granted even if the SPC was valid. 

A translation of the Mylan decision is attached here and the Sandoz decision here.

The AG's opinion in Santen

Thanks to Nick Fischer at Marks & Clerk law for being first to alert the blog to the AG Opinion in Santen (C-673/18) which was handed down last week. 

The official English translation isn’t available yet, but it looks like the AG favours a strict literal meaning of Article 3(d) (i.e. going against Neurim). 

Nick comments (and the blog agrees based on Google translate!) that there is also a suggestion that, if the CJEU does want to follow Neurim, it should allow SPCs for new therapeutic indications or for uses of the same active which have a pharmaceutical, immunological or metabolic action of their own. 

The Opinion is available here.