The decisions concern the compound apixaban, an anticoagulant marketed by BMS under the name Equilis. The compound was protected by claim 1 of the now expired patent EP 1 427 415 B1 and is still protected by the SPC 300500.
The decisions were handed down after three earlier decisions in preliminary proceedings (including one from the Dutch Court of Appeal). The different court rulings are especially interesting because the first decision (preliminary proceedings) was handed down before the guiding decision on plausibility from the Enlarged Board of Appeal (G2/21), while subsequent decisions, based on the same patent and infringement, came thereafter.
Now, the The Hague District Court ruled on the matter of plausibility and inventive step, applying G2/21 for the first time on the merits. It accepted inventive step and ruled that claim 1 of the patent protecting apixaban is valid. In this note, we will look at the District Court’s views on plausibility and inventive step in detail
The different Dutch proceedings: Pre- and Post-G2/21
Before G2/21 was handed down, BMS had filed a PI against Sandoz and Teva, seeking an injunction on the basis of the same patent. That PI was denied, because the Judge (in short) held that there was a lack of inventive step due to a lack of disclosure of a surprising effect of apixaban in the original application. At that time, the interpretation of the “plausibility test” was still rather unclear, which often resulted in different outcomes at the Dutch District Court and the Court of Appeal. In the pre-G2/21 decision, the PI judge gave its own interpretation of this case law and – in our view - applied a rather strict approach.
After G2/21, BMS returned to the PI judge arguing that the Enlarged Board of Appeal's decision caused a change in the law and an injunction should be granted. The PI Judge disagreed, held that G2/21 did not in fact change the law and denied the injunction for a second time. BMS appealed that decision, the Court of Appeal found the patent valid in light of G2/21, and infringed and issued the injunction (on 15 August 2023). The decisions that we discuss here are in the subsequent proceedings on the merits, filed with the District Court against Sandoz and Teva.
Key points of the decisions on inventive steps
The main question regarding inventive step in both decisions was whether BMS could rely on the improved (unexpected) technical effect of factor Xa inhibition by apixaban, specifically in light of G2/21. The District Court, like the Court of Appeal, concluded that this was indeed the case and provided an extensive analysis.
The analyses of inventive step in the BMS v Teva and BMS v Sandoz decisions are highly similar, as Sandoz en Teva attacked the inventiveness of the patent, substantially on the same grounds.
Inventive step in light of G2/21
To assess inventive step, the court applied the problem-solution approach (PSA), as explained in G2/21. It identified the closest prior art (an application referred to as WO 131) and considered the specific claimed compound (apixaban) to be the distinguishing feature. Then, it examined the technical effect that this feature provided (the third step of the PSA (according to G2/21)).
Parties in both cases agreed that the technical effect of the distinguishing feature was the inhibition of factor Xa. However, Teva and Sandoz argued that BMS could not rely on this technical effect, since the skilled person would allegedly not derive the effect from the application, and therefore it was not made plausible. Based on its interpretation of G2/21, the court did not agree.
The court’s interpretation of the plausibility test from G2/21
The court interpreted G2/21 to mean that a technical effect can be relied upon in the context of inventive step if the skilled person, using their common general knowledge, would:
i. derive this technical effect as encompassed by the technical teaching; and
ii. consider this technical effect embodied by the same originally disclosed invention.
The court considered it relevant to determine what the skilled person understands from the application as the technical teaching at the filing date. According to the court, this technical teaching should be understood as the instruction to the skilled person on how to solve the technical problem with technical means (referring to the CoA decision).
Application of the G2/21 test to the case
The court then systematically examined the following elements to answer the two questions under (i) and (ii):
The court clearly outlined the relevant common general knowledge, referring to a document attached to a 2022 UK judgment on apixaban. This inter alia included the focus on factor Xa as a promising target, the fact that reliable and easy tests were available and problems faced by the skilled person at the time (such as low success rates of factor Xa inhibitors, structural issues, etc.).
- Analysis of the application
This was followed by an extensive analysis of the application and of what the skilled person learns from it (i.e. the “technical teaching”). Before diving deeper into the technical teaching, it is important to note that the court (after determining the technical teaching) clarified that the technical effect does not always need to be explicitly disclosed and that the main concern is whether the effect falls within the “nature” of the invention and that accepting the technical effect does not change the nature of the invention. Here the District Court seems to deviate from the preliminary ruling of the Court of Appeal that concluded that the application should explicitly and specifically name the effect as the primary objective of the patent (paragraph 6.15 of its decision).
The District Court also clarified that in this case the skilled person would not have such doubts about the effect or that there is such a broad teaching that additional requirements should be imposed (as in the TBA AgrEvo case, which concerned a very broad Markush formula). After all, in this case, the application concerns a specific group of compounds, for a specific target, and with a specific application.
Technical teaching
The court established the technical teaching as providing the specifically disclosed compounds as improved factor Xa inhibitors through improved inhibition and selectivity for Xa, as well as improved pharmacological properties.
The court arrived at this conclusion based on the following interpretation of the application:
- The skilled person, with their common general knowledge and a “mind willing to understand”, would understand that the application aims to provide new compounds as factor Xa inhibitors. This was clear, according to the court, from the emphasis on factor Xa in the “field of the invention” and “background of the invention” sections, despite some references to other serine proteases. The court noted that factor Xa was known to be crucial for blood coagulation and that there was an ongoing search for its inhibitors.
- The court also held that the patent not only sought to provide new factor Xa inhibitors but also improved ones compared to the prior art, including WO 131. This was explicitly stated in the “background of the invention” section, which highlighted the need for better inhibition, selectivity for factor Xa, and other pharmacological properties.
Then, the court gave weight to the word “accordingly” in the “summary of the invention” section. This section states that the invention “accordingly” provided new lactam-containing compounds which were useful as factor Xa inhibitors. The word “accordingly”, the court said, links back to the 'background of the invention' section, indicating that the inventors had achieved new lactam-containing compounds with improved factor Xa inhibitory activity, selectivity, and other pharmacological properties.
The court further found that the skilled person would not be discouraged by the mention of some compounds having Ki values of less than 10 micromolar. They would understand that the inventors had sought and found compounds with nanomolar affinity for factor Xa, as confirmed in the description. The skilled person would know that not all compounds exhibit the desired Ki values due to inherent unpredictability, but this would not detract from the patent’s focus on improved factor Xa inhibitors.
Finally, the court concluded that the patent provided specific technical means to solve the problem, including 110 synthesized lactam-containing compounds. These compounds were disclosed with their chemical names, and the skilled person could easily test their affinity for factor Xa. The patent also provided a simple test to determine the Ki value.
- Technical effect (i) encompassed by the technical teaching and (ii) embodied by original invention?
The court subsequently concluded that the skilled person would understand the technical effect to be encompassed by the technical teaching (see under (i) above). The skilled person cannot only derive this from the explicit mention of the effect in the application (as also acknowledged by the CoA) but also from the application as a whole.
According to the court, the effect is also embodied by the same originally disclosed invention in the original application as it does not change the nature of the invention (see under (ii) above). The court considered relevant that the claimed compound is one of the preferred embodiments disclosed in the application and is also claimed in claim 8 of the application.
- Conclusion: BMS can rely on the proposed technical effect and provide further evidence
BMS could therefore rely on this effect and is allowed to provide evidence to support its claim that the effect occurs.
Regarding the evidence in these specific cases, it is relevant that parties agreed that the alleged invention should be considered as a selection invention. For inventive selections, the court acknowledged that it is sufficient that there is an improvement regarding at least one feature compared to the relevant other compounds. BMS relied on the evidence it submitted during prosecution in this respect. This concerned in vitro test results comparing the technical effect of apixaban with other closest compounds disclosed in WO 131. The results showed the improved effect of apixaban.
Teva specifically tried to argue that apixaban should have been compared with other example compounds disclosed in the prior art, such as the ones with better affinity (Ki). The court agreed however with BMS that the compounds from the prior art that are structurally closest should be compared instead (which had been done so). Teva apparently did not (timely) substantiate that the examples Teva referred to are similarly compounds from the prior art that are structurally closest as the compounds tested by BMS.
Formulation of technical problem and solution:
The court then came to the final steps of the PSA and determined that the technical problem should be formulated as providing a compound with improved factor Xa inhibition. It concluded that the skilled person would not arrive at the selection of the claimed compound without inventive effort.
According to BMS, there were no indications for the selection of apixaban in the prior art document (WO 131), and several steps would need to be taken to come to that selection. Sandoz did not dispute this, and the court agreed. Teva apparently did not pursue its initial attack against BMS’ argument (which included a combination of prior art documents).
Patent bargain
Finally, the court briefly addressed Sandoz’ and Teva’s argument that BMS’ monopoly conflicts with the “Patent Bargain”. The court found that this was not the case because the monopoly BMS obtained concerns a very specific compound that contributes to the state of the art in a sufficient manner.
Although the court only briefly addressed this point, it is worth mentioning that this argument reflects a current trend in the Netherlands to attack a patent based on proportionality principles.
Conclusion
It is noteworthy that the District Court seemingly paid minimal attention to decisions of other national judges in parallel proceedings dealing with inventive step attacks on the same patent (also contrary to the Court of Appeal did in the PI proceedings).
Instead, the District Court adopted its own perspective on G2/21, implicitly placing emphasis on the broader question of whether the patent protection is commensurate with the technical contribution to the art. A unified EU approach on the concepts of inventive step and plausibility as explained by G2/21 was not brought closer by this decision.
However, the approach does show the willingness of the Dutch District Court to engage in an in-depth analysis of the application, to establish the technical teaching of the patent.
Also, given the differences between the District Court’s and the Court of Appeal’s positions on considering foreign decisions and on whether the technical effect should be explicitly mentioned in the original application (as discussed in the chapter above), it will be interesting to follow whether the Court of Appeal will adopt a similar approach in the appeal on the merits (assuming the decisions will be appealed). Especially also considering that the Court of Appeal previously seems to have interpreted G2/21 on the merits in the Insud Pharma v Galicium case (on 16 April 2024) more restrictively than the District Court has done now.
