EPLAW PATENT BLOG

NL – Bristol-Myers Squibb v. Sandoz / Apaxiban

Posted: May 19th, 2022

Bristol-Myers Squibb Holdings Ireland Unlimited Company v. Sandoz B.V., District Court The Hague (interlocutory decision), 10 May 2022, Case no.  ECLI:NL:RBDHA:2022:4385

BMS markets the medicine Eliquis®, with apixaban as the active ingredient. Apixaban is a substance that inhibits the action of factor Xa. Inhibiting factor Xa helps prevent blood clots from forming. Eliquis® is used in tablet form as an anticoagulant, or blood thinner, in the treatment of thromboembolic disorders. BMS’ EP 415 claims apixaban, or a pharmaceutically acceptable salt thereof.

As the patent holder of the patent EP 415, BMS is challenging the marketing of the same active ingredient apixaban by Sandoz. In the United Kingdom, BMS has already been unsuccessful in the proceedings. The High Court of England and Wales has decided that the UK part of EP 415 is invalid due to a lack of plausibility and technical contribution.

The Court holds:

“BMS argues – in short – that it could be deduced from the application that apixaban (example 18) was seen by the inventor/applicant as a very interesting compound, after which the beneficial inhibition of factor Xa (advantageous dissociation constant Ka) according to standard techniques is simple. can be found. The preliminary relief judge understands this argument in such a way that the average skilled person, who may use his general professional knowledge in interpreting the application, would have found the beneficial effect of the compound of example 18 (after performing the assay to measure the Ki against factor Xa).”

In the provisional opinion of the Court, there is much to be said to the detriment of this reasoning.

“First, it is one thing that the person skilled in the art can use his common general knowledge in interpreting the application, but it is another thing that he must use research methods of his common general knowledge to find any beneficial effect of the compound at all. […]

“Second, as stated, nowhere in the application is it described in so many words that, let alone why, that compound is interesting. The average skilled person must therefore read this between the lines (i.e. speculate on it and then measure). […]

“Third, the indirect indications that BMS mentions (more than 3 grams yield of apixaban and double recrystallization in Example 18) are by no means clear indications of special interest in the compound of Example 18. […]

“Fourth, even if an average skilled person were to focus on  the compound of Example 18, it would still be unclear to him in what respect that compound would then have an advantageous and surprising effect. […]

“Fifth, if the compound of Example 18 has specific advantages, the person skilled in the art would expect that they would also be described. […]

“Sixth, Sandoz has -unsufficiently refuted- argued that a Ki of 10 µM is far from a desired dissociation constant, which must be at least in the nanomolar range.

“For that reason too, it is uncertain whether the judge on the merits will consider any beneficial or surprising effect plausible after reading the application.”

[…]

“In fact, BMS’s most appealing argument is that its patent does not involve a speculative invention, so that no plausibility requirement should be imposed. That is certainly not an unsympathetic argument. However, it can be immediately objected that there was no reason at all not to include the advantageous results of Ki measurements in the application. After all, they have been available for quite some time.” […]

“It is now all the more likely that that information has been omitted for another reason, for example to essentially (as long as possible) not give any openness about the invention that has been made. Although the eventually granted patent only relates to apixaban, it still does not state in so many words why this connection is so interesting. All this does violence to the so-called quid pro quo or patent bargain in patent law (the applicant acquires his monopoly in exchange for disclosure of the invention).

“This means that also according to the arguments of BMS (writ under 8.22) there is no question of inventive step and there is therefore a reasonable chance that the patent (with the SPC) will be held invalid in the proceedings on the merits, just as in the United Kingdom by Meade J.”

A copy of the decision (in Dutch) can be read here.

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