Advanced Cell Diagnostics v Molecular Instruments (UPC_CFI_187/2024 and UPC_CFI_507/2024)
Decision date:
18 November 2025
Osborne Clarke summary
- This decision related to a claim for infringement of two patents relating to a method for detecting and quantifying single molecules of RNA using in situ hybridisation and a counterclaim for their revocation.
- The claimant patent proprietor, Advanced Cell Diagnostics, develops assays for nucleic acid molecules, including so-called 'RNAscope' technology. The defendant, Molecular Instruments, is a biotech startup developing technology for detecting DNA, RNA and proteins, including HCR RNA fluorescence in situ hybridisation.
- The Hague LD noted that there had been earlier parallel proceedings between the parties in the UK, in which the English High Court had found the UK designations of the patents invalid for obviousness over a combination of prior art (Collins with Kern) that was also cited in the UPC action, but that, if valid, one of the patents would have been infringed. The Hague LD reached the opposite conclusions, finding both patents valid, but not infringed either literally or by equivalence.
- In relation to the interpretation of certain claim features, the Hague LD referred to the principles set out by the Court of Appeal in Nanostring v 10 Genomics. In particular, the claimant argued that a feature relating to "non-overlapping" regions of the label probe should be interpreted 'functionally', rather than requiring no overlap at all. The court noted that, in parallel proceedings in the UK, the English High Court had adopted such a functional interpretation, but concluded that the term should be interpreted literally.
- The defendant alleged that the patent was invalid for lack of novelty, lack of inventive step, added matter and insufficiency. The court noted that the defendant had cited numerous prior art documents, but stated it would only discuss those presented as the most promising.
- For novelty, the court applied the so-called ‘gold standard’. It noted that it is not possible to combine different passages or embodiments of a prior art document unless the skilled person would derive that combination directly and unambiguously. It also stated that it is impermissible to combine separate items of prior art unless there is a specific cross-reference to enable the skilled person to construe them as a single disclosure, such as where a second document is referred to for a specific method of preparation of a component described in the first. Applying these standards, the court rejected the novelty attacks.
- For inventive step, the court noted that the parties had "in theory" agreed that the principles set out by the Munich CD in Sanofi v Amgen should apply, and quoted its statement that “In general, a claimed solution is obvious if, starting from the prior art, the skilled person would be motivated (i.e. have an incentive […]) to consider the claimed solution and to implement it as a next step […] in developing the prior art.” The court noted, however, that in practice the parties appeared to have used the problem-solution approach. Nevertheless, it stated that the result did not depend on the specific test and that it would "apply principles that are common to both tools" in its assessment. The court concluded that the patents were not obvious over any of the prior art citations or combinations.
- Two of the prior art citations (Collins and Urdea) disclosed a particular design of probe (a "cruciform" design) in an in vitro context, but were published nine years before the priority date. The court noted that there was no evidence on file that such a design had been used or suggested in the context of in situ assays, as in the patent, in the meantime. It commented that a time lapse of nine years did not necessarily lead to a conclusion of inventive step. However, given that the field of in situ assays was highly competitive, the time lapse did illustrate that cruciform probe designs were not considered in the in situ context.
- The defendant's insufficiency squeeze did not arise as it was not part of the reasoning on inventive step that the prior art was not enabled or created a prejudice. The defendant had also failed to substantiate its allegation of insufficiency. The attack was therefore rejected.
- The court noted that the test for added matter was the same 'gold standard' as for novelty. It rejected the defendant's added matter attacks on the independent claims. The defendant had failed to respond in its reply to defence to counterclaim to the claimant's rebuttals of its added matter attacks in relation to the dependent claims. Accordingly, the court considered that those attacks were "if not forfeited, then in any case, convincingly rebutted by the Claimant".
- On infringement, the court referred to an undisputed product and process description (PPD) for the defendant's products that had been agreed by the parties in the UK proceedings. However, unlike the English High Court, the Hague LD held that the product did not infringe.
- There was no literal infringement in light of the Hague LD's conclusion that the claim feature relating to "non-overlapping" regions required that there was no overlap at all. Depending on the version, the defendant's products had an overlap of 1, 2, 3 or 4 nucleotides.
- The defendant objected to the claimant's equivalence arguments as late filed. The arguments had been raised only in the reply to the defence, even though equivalence had been introduced in the UK proceedings over 18 months before the claimant's statement of claim. The defendant also argued that it would be prejudiced by the late admission of the arguments, as it would only have one written round to respond. The court rejected these submissions. It held that adding an equivalence argument was not an amendment of a case for which judicial leave is required under Rule 263 RoP. Moreover, the equivalence arguments were in response to the arguments in the statement of defence and in line with the claimant's arguments on literal infringement. The defendant was not unreasonably prejudiced, as it had the opportunity to respond in its written rejoinder and orally at the hearing. It could also rely on the debate on equivalence in the UK. The court noted that it would have been "prudent" for the claimant to have included equivalence in the statement of claim, but declined to strike out the arguments.
- The court went on to reject infringement by equivalence with regard to the "non-overlapping" claim feature. Firstly, considering legal certainty, it was "difficult if not impossible" to construe how much overlap would remain equivalent. Secondly, while the patents were valid, it was "clear that they do not form a very significant step" in the development of in situ assays, as all the features were known, just not in combination. Thus, the fair protection of the patentee did not require a finding of equivalence. Thirdly, the defendant's products' overlap of 1 to 4 nucleotides had a specific technical reason that arguably led to an improvement to the invention that was not envisaged by the patents.
Issue
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