Benjamin Niemeijer

On 11 February 2025, the Court of Appeal of The Hague (“CoA”) rendered its decision in the PI proceedings between Janssen Biotech Inc (“Janssen”) and Samsung Bioepis NL B.V. (“Samsung”). The CoA upholds the decision of the Provisions Judge in first instance and denies the PI claimed by Janssen. Samsung can benefit from the SPC Manufacturing Waiver for production and stockpiling for export of its biosimilar product containing ustekinumab. This case is of particular interest as it is one of the few decisions on the application of the SPC Manufacturing Waiver and, more generally, provides clear answers to various questions raised on when a manufacturer can benefit from said waiver. What preceded In our Pharma Update of 31 January 2024 we have reported on the decision of the Provisions Judge of the District Court of 23 January 2024. In said decision the PI claimed by Janssen was denied as the Provisions Judge was of the preliminary opinion that Samsung could benefit from the production-for-export and stockpiling- for-export exemptions of the SPC Manufacturing Waiver. Facts Janssen holds EP 1 309 692 B1 (“EP 692”) for “ANTI-IL-12 Antibodies, compositions, methods and uses”. The medicinal product of Janssen is marketed under the brand name ‘Stelara’ and contains the active ingredient ustekinumab. EP 692 was granted on 13 May 2009 in, among others, Italy and Denmark. The patent expired on 7 August 2021. After expiration, Janssen was granted an SPC in Italy, Denmark and the United Kingdom (UK – ending on 19 January 2024). Similar Stelara patents in Canada and South Korea have also expired. However, Jansen has filed patent(s) (applications) in these countries that protect the treatment regimen approved for Stelara for ulcerative colitis disease. Samsung has developed a biosimilar of ustekinumab with Stelara as reference called SB17. The Dutch Samsung entity (the defendant) issued a notice to the Danish and Italian authorities respectively that it intended to manufacture and stock its biosimilar in Denmark and Italy for the purpose of exporting it to the UK, Canada and South Korea based on Regulation 2019/933 regarding the SPC Manufacturing Waiver “MW Regulation”) and to market the product in the European Union after expiration of the SPC (stockpile exemption). Samsung mentioned that it would submit the reference numbers of its market authorisations in said countries as soon as publicly available. Samsung additionally undertook towards Janssen that it would not manufacture its biosimilar products for the EU-market until 24 January 2024 in order to avoid discussion on the stockpile exemption in the PI proceedings. Assessment of the CoA In its decision, the CoA considers the full range of arguments put forward by the parties. In general, the CoA considers that the purpose of the SPC Manufacturing Waiver is to create a level playing field for generic and biosimilar manufacturers in the EU vis-à-vis competitors in third countries in order to promote EU competitiveness in global markets where protection expired, while at the same time ensuring protection for SPC holders in the EU. In particular, the CoA answers three legal questions: 1. Does a valid reliance on the production-for-export exemption require that the manufacturer has a MA for the intended country of export at the time of notification, or at least before production commences? The CoA answers this question by first analysing the wording of the MW Regulation and finds that article 5(5)(e) of the MW Regulation only requires that the reference number of an MA is provided in relation to the notice of the SPC Manufacturing Waiver once this is available. There is no obligation for the manufacturer to wait with giving notice or with starting production until the MA for the intended country of export is granted and a reference number is provided. 2. Does a valid reliance on the production-for-export exemption require that at the time of the notification, or at least before the start of production, there are no IP rights in force in the intended exporting countries that could oppose entry into that country’s market? The CoA is of the opinion that the MW Regulation does not contain a requirement that the manufacturer must wait with the production under the waiver until the IP rights have expired in the intended export country. Starting production before those rights have expired is not considered unlawful because manufacturing in the EU under the waiver does not automatically infringe an IP right in the country intended for export. This would only be the case if IP rights still exist when the product is imported into that country’s market. 3. Does a manufacturer have the right to stockpile for the intended export? The CoA considers that under article 5(2)(a)(ii) MW Regulation the EU manufacturer is also entitled to stockpile its products as this is strictly necessary for export to third countries in order to achieve Day 1 entry and for the manufacturer to benefit from the “first mover” effect. The CoA considers that this is in line with the intention of the Union legislator and that Day 1 entry is not only intended for the EU but also for Day 1 entry in third countries, giving the EU manufacturer a first mover effect. The CoA rejects Janssen’s concerns that stockpiling could create a risk that products destined for third countries would eventually enter the EU market. According to the CoA there are sufficient safeguards in the MW Regulation to prevent such products from entering the EU market.

On 22 January 2025, the District Court of The Hague handed down its judgement in the final relief proceedings initiated by Biogen against Sandoz, Polpharm, Neuraxpharm and Mylan (collectively referred to as “the Generics”). It ruled that EP 2653873 (“EP 873”) of Biogen on dimethyl fumerate (DMF, marketed as Tecfidera®), is invalid. EP873 protects the use of an orally administered pharmaceutical composition containing the active ingredient DMF for treating multiple sclerosis (MS) with an effective daily dose of 480 mg DMF. DMF has been known since the 1990s as a drug for treating psoriasis. Inventive step Shortly after the Generics listed their generic 480 mg DMF products in the G-Standard (pricelist) for October 2022 and after health insurers designated some of these products as preferential in NL, Biogen sued  the Generics for infringement of EP 873. The Generics counterclaimed for revocation of Biogen’s patent, inter alia arguing that EP 837 lacked inventive step or sufficiency of disclosure (G2/21). The Generics relied on a clinical study that demonstrated the efficacy of 720 mg DMF per day and the potential for a lower dose to also be effective for the treatment of MS. The clinical study became part of the prior art through two pre-priority date presentations called ‘Kappos I’ and ‘Kappos II’. In the proceedings, both Biogen and the Generics acknowledge that Kappos I and II are full prior art and disclose the use of DMF as an effective drug for the treatment of MS. Starting from Kappos I or II, the Court found that the only difference between Kappos I or II and EP 837 relates to the 480 mg per day dosage set forth in claim 1. During the oral hearing it was established that both parties found that the administration of DMF to treat MS at a dose of 480 mg per day is as effective as administration of 720 mg per day. Therefore, the Court considered that the objective technical problem that the patent tries to resolve is to find an alternative treatment for MS that is as effective as the state of the art, namely the administration of DMF of a dose of 720 mg per day. Biogen argued that the objective problem was to find an improvement in the oral treatment of MS, but the Court rejected this argument and held that – unlike the apixaban case – the patent application (parent patent) of EP 837 did not describe an improved treatment. In addition, the Court found that the purpose of the patent application was not to find the best dose of DMF, but to screen for potentially MS-active substances similar to DMF. Agreeing with the Generics, the Court is of the opinion (5.39) that the skilled person, starting from Kappos I and/or Kappos II, and the general common knowledge,  knows that the efficacy (and therefore the effectiveness) of DMF is dose-dependent and that lower doses are also effective for the treatment of psoriasis. The skilled person would therefore have a reasonable expectation of success that this problem for an alternative dose could be solved in an obvious way by testing lower doses of DMF. Contrary to Biogen’s argument, the skilled person would then carry out those tests. In this way, with routine testing and thus without inventive effort, the skilled person would find that a dose of 480 mg per day has a therapeutic effect. Therefore, claim 1 of EP 837 is obvious. The two auxiliary requests filed by Biogen are also dismissed by the Court. Sufficiency of disclosure The Court also addresses the ‘squeeze’ that the Generics identified, namely that in case EP 873 would be found inventive (quod non), it lacks sufficiency of disclosure and is (also) invalid for that reason. The Court held that the patent or application must sufficiently disclose the subject matter allowing the skilled person to apply the invention over the whole range claimed by the patent without undue burden. Second medical use claims bring about that it must be tested whether the therapeutic effect of the composition and dosage regimen for the claimed medical indication (in this case MS) is disclosed in the application/patent or, in the absence thereof, is credible. In relation to G2/21, the Court states that if the desired technical effect is part of the claim, but the patent does not prove or at least make plausible that this technical effect is achieved by the teachings of the patent, nor does the person skilled in the art assumes this on the basis of the common general knowledge or the cited literature, then there is insufficient disclosure. The Court found that that the application says nothing about the efficacy of the claimed dosage of DMF in treating MS. Since the Court does not consider any experimental data other than Kappos I and II, EP 873 is lacks sufficiency of disclosure. Parallel proceedings  The decision handed down by the District Court of The Hague is the first decision in final relief proceedings to hold (the NL part of) EP 873 invalid. To date, only Sweden has ruled in final relief proceedings on (the validity of) EP 873. The Swedish Court found EP 873 valid and imposed an injunction on the generic companies. Earlier Biogen commenced several PI proceedings in various European countries. In the Czech Republic, Denmark, Latvia, Slovakia, Estonia, Ireland and Sweden, PI’s were granted. In contrast, in Austria, Belgium, Portugal, Slovenia, Italy, France, Spain, Estonia, Germany, Norway and Hungary, PI’s were rejected because the patent was found invalid on a preliminary basis. Conclusion It remains to be seen if the NL judgement on the invalidity of EP 873 is going to be followed by other European jurisdictions.

On 30 October 2024, the District Court of The Hague ruled in two separate final relief proceedings that EP 1 427 415 B1 (“EP 415”) and the SPC of Bristol-Myers Squibb (“BMS”) on apixaban are valid and, in the case of Sandoz infringed (BMS/Sandoz and Teva/BMS). With these rulings, the NL District Court allows post-published evidence. G2/21 (plausibility) and G1/22 and G2/22 (priority) are taken into account. What preceded: interim relief (PI) proceedings The first PI decision on apixaban in the Netherlands goes back to 10 May 2022 when the Provisions Judge of the District Court of The Hague denied a PI, requested by BMS against the sale of generic apixaban by Sandoz. After the decision in G2/21 of 23 March 2023, BMS started new PI proceedings against Sandoz and STADA/Centrafarm, later also against Teva. In separate decisions of 17 May 2023 and 31 May 2023, the Provisions Judge again ruled in favour of the generic companies and denied the requested PI, stating that G2/21 did not change the position regarding the rejection of post-published evidence. The Provisions Judge assessed it as likely that the claims of EP 415 would not be considered inventive due to lack of plausibility in final relief proceedings. All decisions were appealed by BMS. Contrary to the Provisions Judge, the Court of Appeal (CoA) held EP 415 inventive and found that the post-published evidence could be taken into account when assessing inventive step. Reference is made to our Pharma Update of 25 August 2023. Two NL final relief (invalidity) proceedings The final relief proceedings which have now been decided, were initiated well before the PI proceedings, but delayed in view of G2/21. Priority in view of G1/22 and G2/22 The Court first considers the attack on priority. The generic companies argued that BMS cannot rely on priority document US 165 because, at the date of filing of the EP 415 application, the applicant (BMS Company, the predecessor of BMS) was not the holder of priority document US 165. The transfer of US 165 from the holder of the priority document to the applicant of EP 415 did not take place until several years after the filing of the EP 415 application. In its judgment, the District Court refers to G1/22 and G2/22, in which the EBA stated that, under the EPC, the holder claiming priority is presumed to be entitled to rely on the priority document claimed. This presumption also applies where the European patent is derived from an international (PCT) application and/or where the applicants of the priority document are different from the applicant of the subsequent application. The burden of proof to rebut this presumption lies with the party contesting the right to priority. With regard to G1/22 and G2/22, the Court finds that implicit consent to the transfer of priority rights is sufficient. As the EBA considers the possibility of a nunc pro tunc transfer of priority rights, the Court concludes that, in this case, the deed of transfer after the filing date can be relied on to claim priority and the generic companies failed to provide sufficient evidence to rebut the presumption of priority. Plausibility in view of G2/21 In light of the inventive step attack brought by the generic companies, the main issue in the final relief proceedings is whether BMS can rely on a claimed technical effect for inventive step. The Court first applies the PSA as set forth in G2/21 and then analyses if for the skilled person, having the common general knowledge in mind, and based on the application as originally filed, said technical effect is derivable as being encompassed by the technical teaching and embodied by the same originally disclosed invention. Like the CoA, the District Court considers that, in view of the decision in G2/21, there is no obligation that the patent application must always “prove” or make plausible that the claimed technical effect actually occurs. The District Court concludes that the claimed technical effect is disclosed, inter alia, in one of the preferred embodiments mentioned in the patent application. It therefore admits BMS’s post-published evidence and finds that the post-published evidence shows an improvement in the technical effect. Other jurisdictions The Court further notes that also in France, Norway and Sweden EP 415 was held valid, albeit following a different line of reasoning. The English High Court ruled differently because – according to the Dutch Court – it applied a different test (plausibility in the context of sufficiency) as set forth the Supreme Court’s decision in Warner- Lambert. Likewise the Irish Court. Multiple invalidity proceedings on EP 415 are still pending, e.g. in Bulgaria, Czech Republic, Denmark, Finland, Hungary, Italy, Croatia, Poland, Portugal, Slovakia, Spain and Switzerland. Conclusion The decisions show that depending on the circumstances, post-published evidence may be admissible if the technical effect is derivable for the skilled person from the application as filled and is part of its overall technical teaching. Earlier, in Insud Pharma / Galenicum, the Court of Appeal of The Hague had decided that post-published evidence may be rejected if the technical effect is not derivable from the application. The decisions also show that the rebuttal of the presumption of priority as presented in G1- and G2/21, along with the subsequent decisions of the Court of The Hague, remains a very challenging proposition in practice.

On 23 January 2024, the Provisions Judge of the District Court of The Hague handed down a decision in the PI proceedings initiated by Janssen Biotech Inc. (“Janssen”) against Samsung Bioepis NL B.V. (“Samsung NL”). Janssen claimed that Samsung NL infringed its Stelara SPCs granted in Italy and Denmark. The Provisions Judge denied the PI as according to his preliminary assessment Samsung NL can benefit from the SPC Manufacturing Waiver. Janssen’s SPC- Stelara Janssen holds European patent EP 1 309 692 B1 (“EP 692”) for “ANTI-IL-12 Antibodies, compositions, methods and uses“. The medicinal product of Janssen is marketed under the brand name ‘Stelara’ and contains the active ingredient ustekinumab. EP 692 was granted on 13 May 2009 in, among others, Italy and Denmark. The patent expired on 7 August 2021. After expiration, Janssen was granted a SPC in Italy, Denmark and the United Kingdom (UK – ending on 19 January 2024). Similar Stelara patents in Canada and South Korea have also expired. However, Jansen has filed patent(s) (applications) in these countries that protect the treatment regimen approved for Stelara for ulcerative colitis disease. SPC Manufacturing Waiver Samsung has developed a biosimilar of ustekinumab with Stelara as reference called SB17. Samsung NL issued a notice to the Danish and Italian authorities respectively that it intended to manufacture and stock its biosimilar in Denmark and Italy for the purpose of exporting it to the UK, Canada and South Korea based on Regulation 2019/933 regarding the SPC Manufacturing Waiver “MW Regulation”) and to market the product in the European Union after expiration of the SPC (stockpile exemption). Samsung NL mentioned that it would submit the reference numbers of its market authorisations in said countries as soon as publicly available. Samsung NL additionally undertook towards Janssen that it would not manufacture its biosimilar products for the EU-market until 24 January 2024 in order to avoid discussion on the stockpile exemption in the PI proceedings. The PI Judge’s assessment of infringement According to Janssen Samsung NL infringes its SPCs in Denmark and Italy and cannot benefit from the SPC Manufacturing Waiver because Samsung NL (i) did not specify the reference numbers of the marketing authorisations in the exporting countries, (ii) Janssen’s patent rights are in force in the countries to which Samsung NL intends to export its biosimilar, and (iii) Samsung NL is not allowed under the SPC Manufacturing Waiver to store the biosimilar products. The PI Judge finds that according to the text of MW Regulation the manufacturer is obliged to provide the reference number of market authorisation, or the equivalent of such authorisation in each exporting third country, only as soon as it is publicly available. This entails, according to the preliminary view of the Provisions Judge, that if this number is not yet publicly available, the manufacturer has the possibility to supplement the notification with the reference number of the marketing authorisation as soon as it is publicly available, as reflected in Article 5(5)(e) MW Regulation. The Provisions Judge considers that the MW Regulation is sufficiently clear on this item. It is taken into account that the nature and the content of the provisions in question were extensively debated during the revision of the earlier SPC Regulation. The Provisions Judge is therefore of the opinion that it is not necessary to raise preliminary questions to the Court of Justice of the EU on the application of the SPC Manufacturing Waiver, as suggested by Janssen. The fact that the District Court of Munich in the matter Janssen vs Formycon ruled differently on this matter does alter his view, especially because the Provisions Judge finds the reasoning of the District Court of Munich in said decision not convincing. Janssen further argued that Samsung NL may not manufacture a biosimilar under the waiver because in the countries to which Samsung NL intendeds to export its product, patent rights are existing. The Provisions Judge considers that there is no requirement under the MW Regulation that the intended exporting countries are free of patent rights and/or that the manufacturer must prove this in advance. Such requirement would be contrary to the objective of the MW Regulation of ensuring a level playing field with global competition. If EU based manufacturers were only allowed to manufacture for export to countries that are ‘free of patents’ they would be put in a serious disadvantage compared to non-EU based competitors not subject to such restrictions. In relation to the storage of the products the Provisions Judge states that it follows from the wording of Article 5(a)(a)(ii) of the MW Regulation that under the export exemption, ‘temporary storage’ is allowed. The MW Regulation does not specify a maximum period for such ‘temporary storage’ other than that it must be strictly necessary for the actual export. Conclusion The Provisions Judge is of the preliminary opinion that – contrary to the Janssen vs Formycon decision – a manufacturer of a biosimilar can rely on the SPC Manufacturing Waiver a) even if the market authorisation reference number is not yet publicly available, b) there are possible patents rights in the countries to which the product is exported and c) temporary storage of the products is possible when strictly necessary for the actual export.

On 15 August 2023, the Court of Appeal of The Hague (”CoA”) rendered its decision in the PI proceedings between Bristol-Myers Squibb Holdings Ireland Unlimited Company (“BMS’’) and Sandoz B.V. (“Sandoz’’), Centrafarm B.V. et al. (“Centrafarm”) & Teva B.V. et al. (“Teva’’). The CoA is of the preliminary opinion that EP 1 427 415 B1 (“EP 415”) makes the technical effect plausible, allowing post-published evidence to be taken into account. The CoA comes to its finding after the Enlarged Board of Appeal (“EBA’’) handed down its decision in G2/21. The likelihood of EP 415 being held valid in the pending final relief proceedings is high and therefore a PI against the generic companies is granted. Making this case of particular interest is that two out of the three CoA Judges are also Appeal Judges in the UPC. This case may show the position the UPC may take on plausibility. BMS is the owner of EP 415 and of SPC no. 300500 based on this patent (“SPC”). EP 415 was in force in the Netherlands until 16 September 2022. The SPC relates to apixaban or pharmaceutically acceptable salt forms thereof (marketed by BMS as Eliquis®) and is in effect from 17 September 2022 until 19 May 2026. What preceded  The first apixaban case in the Netherlands was the PI proceedings between BMS and Sandoz. The Provisions Judge of the District Court of The Hague (“PI Judge” rendered his decision on 10 May 2022. According to the PI Judge, there is no inventive step due to lack of plausibility and therefore a good chance that the patent (and the SPC) will be held invalid in final relief proceedings. A PI against the sale of generic apixaban by Sandoz was denied. No appeal was filed. On 23 March 2023 the EBA decided case G2/21 on plausibility. It considered three questions about the circumstances in which it is permissible to rely on post-published evidence of a technical effect in support of inventive step. The EBA provides guidelines on whether or not to consider post-filed evidence. The new PI proceedings After the EBA ruling, BMS filed another interim relief proceedings against Sandoz and against Centrafarm. BMS requested the PI Judge to grant a PI against both generic companies, alleging infringement of the NL part of EP 415 and the related SPC. The key question was whether the G2/21 decision changed the position taken in the earlier preliminary judgement given on 10 May 2022 and what the standard of plausibility should be in the Netherlands for taking into account post-published evidence. According to the Provisions Judge, the G2/21 decision does not change the application of the concept of plausibility, as the EBA embraces the consistent line of case law of the Technical Boards of Appeal. Therefore, the PI request of BMS is dismissed. BMS also filed interim relief proceedings against Teva before the same Provisions Judge, requesting a PI against Teva. In this case the Parties agreed that a judgement should be rendered identical to the judgment of 17 May 2023, so that all cases could subsequently be heard in the same appeal proceedings. The Provisions Judge rejected the PI against Teva on the same grounds as expressed in his  decision of 17 May 2023. The main considerations of the CoA The key question in the interim relief appeal proceedings is which criteria should be applied in order to decide whether or not post-published evidence can be accepted to hold a patent claim inventive (ab initio plausibility or ab initio implausibility) in light of the decision of the EBA in G2/21. Unlike the Provisions Judge, the CoA holds the patent inventive. It finds that the post-published evidence can be taken into account. According to the CoA, the sole criterion in G2/21 for taking into account a technical effect when applying the PSA is if for the skilled person, having the common general knowledge in mind, and based on the application as originally filed, said technical effect is derivable as being encompassed by the technical teaching and embodied by the same originally disclosed invention. This entails that it is not obliged that the patent application always needs to provide ‘’proof’’ or needs to make plausible that the technical claimed effect actually occurs. This needs to be filled in on a case-by-case basis. The CoA refers to par. 77 of G2/21 to stress that the admission of post-published evidence is different in assessing inventive step when compared to assessing sufficiency of disclosure. The circumstances of the apixaban case imply that on the priority date the average person skilled in the art could derive from the application, WO 652, that apixaban has the most advantageous effect as an fXa inhibitor. Therefore, the criterion as described in G2/21 has been met. The patent application disclosed more than a mere verbal statement of the technical effect so there is no reason for the skilled person in the art to doubt that the function of apixaban (an improved fXa inhibitor) could not be achieved (ab initio implausibility). There is no requirement that any evidence to that effect should be included in the application. The CoA stated that in the final relief proceedings in France and Norway, the Courts came to a similar conclusion based on the same reasoning. It is remarkable that the CoA explicitly considers the decisions of these countries as highly persuasive to the detriment of the UK High Court and Appeal Court decisions, which it distinguishes as being made on the basis of assessing sufficiency of disclosure. The CoA points out (sections 3.21-3.24) that in many countries invalidity proceedings have been instituted, some of which have been decided, others are pending, two of which in NL.