The Swedish pharma and life sciences litigation newsletter

SEPTEMBER 2024

IN THIS ISSUE

Pharma: Bayer v Sandoz, STADA, Teva, Glenmark, and Viatris over rivaroxaban products
Pharma: Sandoz and STADA v Takeda over lisdexamfetamine product and the validity of lisdexamfetamine SPC
Pharma: Novartis v Zentiva, Glenmark, Mylan, and Teva over fingolimod products
Pharma: Bayer v Mylan over sorafenib product
Pharma: Teva v Bristol-Myers Squibb over the validity of apixaban patent and SPC
Pharma: Vivanta v Sanofi over the validity of teriflunomide SPC

News from the UPC
Nordic-Baltic Regional Division

MedTech: Edwards Lifesciences v Meril Life Sciences, SMIS, and Sormedica over transcatheter heart valves

PHARMA

Bayer v Sandoz, STADA, Teva, Glenmark, and Viatris over rivaroxaban products

There is ongoing intense litigation in Sweden between Bayer and several generic companies concerning Bayer’s blockbuster product Xarelto, an anticoagulant used to prevent and treat blood clots.

The dispute began when Sandoz filed a lawsuit against Bayer in November 2022, seeking the invalidation of Bayer’s patent EP 1 845 961. So far, however, the case has been a setback for Sandoz. In February this year, the Swedish Patent and Market Court (PMC) ruled in favour of Bayer and upheld the patent.

The patent covers a dosing regimen where rivaroxaban is administered orally once daily for at least five days to treat thromboembolic disorders, with a half-life of no more than 10 hours. Sandoz argued that the patent lacked inventive step, citing a Phase I dose-escalation study where participants were given rivaroxaban in varying doses either once, twice, or three times daily. Sandoz contended that the skilled person would have proceeded to a Phase II study, included once-daily dosing, and thus arrived at the claimed regimen.

However, the PMC disagreed. The skilled person would have been cautious to avoid risks such as bleeding and blood clots due to over- or under-dosing. Information in the prior art regarding rivaroxaban’s short half-life would also have been central to the skilled person. The skilled person would also have assumed that the therapeutic window was narrow. Additionally, the skilled person would not have taken into account that an anticoagulant effect might not be needed throughout the entire dosing interval. Furthermore, there was no consensus that once-daily dosing was best for anticoagulants such as rivaroxaban; rather, it was considered an exception. The court therefore found that, for several reasons, the skilled person would have doubted that once-daily dosing would be safe and effective.

Sandoz has appealed the decision, but the Patent and Market Court of Appeal (PMCA) has yet to grant leave to appeal.

Bayer has subsequently sued Sandoz for patent infringement. In July this year, the PMC issued a preliminary injunction (PI) against Sandoz, prohibiting the sale of the product. Around the same time, several other generic companies (STADA, Teva, Glenmark, and Viatris) launched their rivaroxaban products. Each of these companies has initiated proceedings to invalidate the patent. The PMC has consistently issued PIs against them. As far as is known, only STADA (capsule form) and Viatris have not yet had PIs issued against their products. The PI proceedings are still active, with some appeals having been granted leave to appeal by the PMCA, while others have not.

We will continue to monitor and report on further developments.

PHARMA

Sandoz and STADA v Takeda over lisdexamfetamine product and the validity of lisdexamfetamine SPC

Currently, there are several disputes in Sweden concerning the patent protection of Takeda’s product Elvanse (lisdexamfetamine), a medication for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).

Firstly, in November 2022, Sandoz sued Takeda seeking a declaration of non-infringement for their generic lisdexamfetamine product. Sandoz requested that the Swedish Patent and Market Court (PMC) declare that their product, which contains the diadipate form of lisdexamfetamine, does not fall within the scope of protection of Takeda’s supplementary protection certificate (SPC).

However, in a decision issued in May this year, the PMC sided with Takeda, concluding that Sandoz’s product constituted an equivalent infringement of the SPC. The court found, among other things, that certain claim amendments made by Takeda during opposition proceedings before the EPO against the basic patent (EP 1 644 019) did not preclude an equivalence interpretation, as those amendments were made to overcome objections related to added matter rather than to limit the invention against prior art. Therefore, the diadipate form was considered equivalent to the mesylate and hydrochloride forms as per claims 2–3. (The court had previously interpreted lisdexamfetamine in claim 1 as limited to the free base form of the compound.) Sandoz has appealed, but the Patent and Market Court of Appeal has not yet decided whether to grant leave to appeal.

Secondly, in October 2023, STADA sued Takeda seeking to invalidate the SPC. STADA argues, in brief, that the only active ingredient in lisdexamfetamine is dexamfetamine. Therefore, according to the SPC Regulation, the product (the active substance) is dexamfetamine. Marketing authorisations (MAs) for dexamfetamine had already been granted before the MA for Elvanse, which is the MA that formed the basis for the SPC. This means that the MA for Elvanse did not constitute the first authorisation to place the product on the market according to Article 3(d) of the SPC Regulation. Furthermore, the SPC lifetime must be calculated based on the earlier MAs for dexamfetamine. This results in a negative lifetime by such a margin that it is impossible to arrive at a positive lifetime even with a paediatric extension. Therefore, the SPC is invalid. The PMC has yet to issue a decision in the case, but a main hearing is scheduled for the autumn of this year.

We will continue to monitor and report on further developments.

PHARMA

Novartis v Zentiva, Glenmark, Mylan, and Teva over fingolimod products

In a previous report, we covered the disputes between Novartis and Zentiva, Glenmark, Teva, and Mylan, which have been ongoing in the Swedish patent courts since spring-summer 2022. The cases revolve around the launch of generic versions of the original drug Gilenya (fingolimod) for treating multiple sclerosis (MS). The cases have now progressed even further.

This matter has seen several twists. Initially, leave to appeal was denied for preliminary injunction (PI) decisions, only to be later granted. Similarly, requests for PI were first refused, then approved, and subsequently overturned again.

Most of these disputes are now either concluded or stayed pending a decision on the validity of Novartis’s patent (EP 2 959 894). The only remaining active dispute is between Novartis and Glenmark, and it continues to offer interesting insights.

One point of interest is how Swedish courts should apply the principles set out by the Enlarged Board of Appeal of the EPO in the significant G 2/21 case. This concerns when post-published evidence can be used to support patentability. It also relates to the requirements for sufficiency of disclosure of the invention.

In March this year, the Swedish Patent and Market Court (PMC) issued a decision invalidating the patent. The PMC first addressed whether the invention was sufficiently disclosed. The patent concerns a medical use of a known substance, fingolimod, in a 0.5 mg daily oral dose for treating RRMS. As the technical effect, a therapeutic action, is a functional feature of the claim, it must be probable (or credible) for the skilled person that the substance is suitable for the claimed medical use. The court assessed whether a skilled person would find it probable (or credible) that fingolimod at this dose would have a therapeutic effect for treating Relapsing-Remitting Multiple Sclerosis (RRMS).

The PMC followed the principles in G 2/21 and found that it is not always necessary to present results from animal or clinical trials in a patent. What is required is evidence of the therapeutic effect or that the effect can be derived from prior art or common general knowledge. If a reasonable technical concept is presented and no substantial doubts exist about its practical applicability, no experimental results are needed to establish that the description is sufficiently clear for the invention to be carried out. Based on this, the court concluded that a skilled person would have found it probable (or credible) that an oral daily dose of 0.5 mg of fingolimod would be effective for the treatment of RRMS.

However, the PMC took a stricter approach when considering inventive step. The difference between the claimed dosage regimen and the prior art was the lower dose. Novartis relied on a post-published study to demonstrate that the lower dose was at least as effective as certain higher doses. Nevertheless, the court concluded that a skilled person would not have been able to derive such an effect from the patent application, in light of their general knowledge. Despite the earlier conclusion that the skilled person would have found the effectiveness of the lower dose probable (or credible), the court therefore disregarded the study.

The PMC thus framed the objective technical problem as merely providing another method to treat RRMS with fingolimod orally. The court then concluded that the skilled person, when facing this less ambitious task, would have reasonably expected a 0.5 mg daily dose to be effective in treating RRMS. The court further found no discouragement in the prior art against attempting such a dose. Therefore, the skilled person would have arrived at the claimed dosing regimen in an obvious manner.

The decision has been appealed, and the Patent and Market Court of Appeal has confirmed it will re-examine the case. We will continue to monitor and report on further developments.

PHARMA

Bayer v Mylan over sorafenib product

In October 2022, Bayer sued Mylan for infringement of EP 2 305 255, titled “Aryl Urea Compounds in Combination with Other Cytostatic or Cytotoxic Agents for Treating Human Cancers” before the Swedish Patent and Market Court (PMC). This concerned Mylan’s product Nexavar, containing sorafenib, for the treatment of certain types of cancer. Mylan countersued for the invalidation of the patent.

The PMC issued a preliminary injunction (PI) against the sale of Mylan’s product in November 2022. However, this PI expired shortly after, as the patent term ended.

The case thus focused on the validity of the patent and the obligation to pay compensation and damages for any infringement that may have occurred during the patent term. The PMC issued a ruling in January of this year.

The case centred on claim 12 of the patent, which concerned the tosylate salt of sorafenib as such, ie without limitation to the method of administration, indication, or similar. The case also dealt with certain amended claims submitted by Bayer, where Bayer had added the method of administration (oral administration) and indication (cancer treatment).

It was Mylan’s case that the patent was invalid due to both added matter and lack of inventive step.

The PMC began by examining the issue of added matter. Mylan argued, among other things, that the application as filed disclosed the tosylate salt of sorafenib as being intimately linked to combination therapies. The skilled person would understand the combination therapies to be mandatory for all embodiments, and the therapy therefore cannot be omitted. Thus, the tosylate salt of sorafenib cannot be isolated or extracted as in claim 12.

However, the PMC disagreed. The court pointed out that the application as filed did disclose the tosylate salt of sorafenib as such in isolated form, as a powder, without a direct connection to any combination therapy. Therefore, claim 12 did not represent an impermissible intermediate generalisation, according to the court.

The PMC then proceeded to consider the issue of inventive step, leading to a lengthy and detailed analysis.

Mylan cited prior art disclosing sorafenib, although (as the PMC interpreted the matter) in its free base form, not as a tosylate salt.

Bayer submitted post-published evidence, including comparative tests, to demonstrate that the tosylate salt had better bioavailability (and, relatedly, dissolution properties) than the free base form. Following a review of the application as filed and case law from the EPO boards of appeal (T 116/18, the case underlying G2/21), the PMC concluded that Bayer’s claimed effect could indeed be derived from the application.

The PMC therefore considered the post-published evidence and concluded that it demonstrated improved solubility properties and oral bioavailability for the tosylate salt compared to the free base form. However, the improved bioavailability was not considered proven, or even assumed to be achieved, across the entire scope of the claim (as the claim was not limited to oral administration). Thus, the objective technical problem was focused on solubility.

Regarding the question of whether the solution to the problem was obvious, the PMC found that it was common practice to form a salt to influence the solubility properties of an active ingredient. The question then became whether the skilled person in this case would have conducted a salt screening to improve the solubility of sorafenib’s free base, and if so, whether tosylate salt would have been included.

After a long and detailed review of various factors such as the strength (pKa value) of salt-forming acids, stable salt forms, toxicity, common and pharmaceutically acceptable salts at the time, and available quantities of sorafenib, the PMC concluded that a skilled person would have conducted a salt screening and would have chosen to include the tosylate salt. The skilled person would thus have produced the tosylate salt of sorafenib and would have reached the invention according to claim 12.

The PMC also reviewed Bayer’s amended patent claims, but they did not alter the outcome.

Bayer has appealed the decision and has been granted leave to appeal by the Patent and Market Court of Appeal. We will continue to monitor and report on further developments.

PHARMA

Teva v Bristol-Myers Squibb over the validity of apixaban patent and SPC

Since 2021, Teva has been pursuing legal action in Sweden against Bristol-Myers Squibb (BMS) with the aim of invalidating BMS’s patent EP 1 427 415 and the associated supplementary protection certificate (SPC). The patent and SPC protect the product Eliquis (apixaban), which is used to prevent and treat blood clots and to prevent strokes. Teva sought to clear the path for the launch of a generic version of apixaban.

As we reported in a previous issue of our newsletter, in November 2022, the Swedish Patent and Market Court (PMC) delivered a decision upholding the patent.

To briefly recap, Teva had argued, among other things, that the priority claimed by the patent was invalid. As a result, another patent application from BMS (which disclosed apixaban) was, according to Teva, citable as prior art and deprived the patent of novelty. The patent claimed priority from a US application, which was filed in the inventors’ own names. When BMS later claimed priority, the inventors had not assigned the priority rights to BMS. Instead, they had assigned the priority rights to a BMS subsidiary, where the inventors were employed. According to Teva, BMS was therefore not the inventors’ “successor in title” under Article 87 of the European Patent Convention and could not claim priority.

However, the PMC did not share this view, finding that BMS was indeed a “successor in title” because, according to the company’s internal policy, BMS had control over the relevant intellectual property rights, including the priority application, making BMS the actual (“beneficial”, as opposed to “legal”) owner of the priority application under Delaware state law.

The PMC also sided with BMS regarding other arguments put forward by Teva concerning the patent’s validity. One such issue involved the “plausibility” of a technical effect, specifically improved inhibition of apixaban’s target enzyme. The court emphasised that there is no absolute requirement for experimental data to be disclosed in a patent application and that, in certain cases, a mechanistic explanation or the general knowledge of a skilled person may suffice. The court thus concluded that the effect had been made plausible, which in turn led to the conclusion that the invention had inventive step. According to the court, the skilled person would not have altered the molecule disclosed in the closest prior art to arrive at apixaban in an obvious manner.

Teva appealed the decision, and the Swedish Patent and Market Court of Appeal (PMCA) has now issued its ruling.

The PMCA first examined the priority issue in detail. According to the court, Teva was entitled to challenge the priority, as it represented the public interest in ensuring that an invention meets the novelty requirement. The court also analysed decisions G 1-2/22 from the EPO Enlarged Board of Appeal. The parties disagreed, among other things, on how the presumption that the priority is valid established by the Enlarged Board in its decision should be understood. BMS argued that the presumption meant that a priority claim should be considered valid unless proven otherwise by the party challenging it. Teva, on the other hand, submitted that the presumption applied only in EPO proceedings and not in national courts. The court agreed with Teva, noting that the Enlarged Board’s decision explicitly states that priority issues arising in national courts should be assessed according to national rules, and that national courts may consider other factors. However, the court still found that, for reasons aligned with the underlying purpose, the presumption of a valid priority should also apply in Swedish courts.

Thus, the burden of proof was on to Teva to demonstrate that BMS had no right to claim priority. The PMCA emphasised that BMS and the company to which the inventors had assigned the priority rights were part of the same corporate group, and there was no dispute regarding the priority between them. The court also noted that the issue was not whether BMS had engaged in any misconduct or tried to circumvent the novelty requirement to the detriment of third parties. Nor was BMS alleged to have acted in bad faith or otherwise dishonestly in obtaining the benefit of priority from the earlier application. According to the court, the circumstances presented by Teva, which argued that there were no assignments and that BMS was not a so-called beneficial owner of the priority right under US law, did not have the character to overturn the presumption of validity. Therefore, the patent was deemed to have a valid priority, and there was no lack of novelty.

The PMCA then proceeded to examine issues of added matter, sufficiency of disclosure, inventive step, and the validity of the SPC, and made a similar assessment as the PMC.

Thus, the patent was upheld in the second instance as well, and BMS successfully prevented Teva from clearing the path for the launch of a generic version of Eliquis in Sweden.

PHARMA

Vivanta v Sanofi over the validity of teriflunomide SPC

In May this year, Vivanta initiated legal proceedings against Sanofi before the Swedish Patent and Market Court, seeking to invalidate Sanofi’s Swedish supplementary protection certificate (SPC) covering its product Aubagio (teriflunomide), which is indicated for the treatment of multiple sclerosis (MS).

The SPC is based on the underlying patent EP 1 381 356, which pertains to the use of teriflunomide for the production of an orally administered medicine intended to treat MS. Vivanta’s case rests on the argument that the basic patent is invalid due to a lack of novelty and inventive step. In support of its position, Vivanta has cited prior patents which, it argues, describe the use of orally administered teriflunomide in the treatment of MS.

Moreover, Vivanta contends that the SPC is invalid because the marketing authorisation (MA) for Aubagio, upon which the SPC is based, was not the first MA granted for the product. According to Vivanta, an earlier MA for the product Arava should be considered the first MA. Arava contains leflunomide, a prodrug of teriflunomide, and Vivanta argues that its therapeutic effect is exclusively attributable to teriflunomide’s action in the body.

We will continue to follow and report on developments in this case.

News from the UPC
Nordic-Baltic Regional Division

MEDTECH

Edwards Lifesciences v Meril Life Sciences, SMIS, and Sormedica over transcatheter heart valves

As previously reported in this newsletter, Edwards is pursuing proceedings before the UPC Nordic-Baltic Regional Division against Meril and two co-defendants, alleging infringement of its EP 2 628 464, titled “Leaflet Attachment Frame for a Prosthetic Valve”, which protects the Sapien valve delivery system. The defendants have counterclaimed for revocation of the patent.

The proceedings had been stayed pending a written decision from the Boards of Appeal of the EPO in opposition proceedings initiated by Meril against the patent. The Board of Appeal has now issued its decision, setting aside the Opposition Division’s decision to maintain the patent as granted, and instead upholding the patent in an amended form according to an auxiliary request.

In light of this, the court has decided to resume the proceedings and has set a timetable for further actions. We will continue to monitor developments and provide updates in future issues of this newsletter.