Parallel proceedings were held in the UK High Court in April 2024. In contrast to the UPC ruling, both patents were considered invalid for obviousness. Had the patents been deemed valid, Molecular Instruments would have infringed EP1910572 both literally and by equivalence, but EP2500439 was not infringed.

Background

Advanced Cell Diagnostics’ European patent EP1910572 was granted in December 2015 and relates to methods of in situ detection of nucleic acid targets within an individual cell.

Advanced Cell Diagnostics also filed a divisional from EP1910572 relating to a kit for the detection of nucleic acids in an individual cell. The divisional was granted in August 2014 as EP2500439.

The patents relate to an assay consisting of a multiplex fluorescent and chromogenic in situ hybridisation (ISH), capable of detecting and quantifying single molecules of RNA within an individual cell. The method utilises branched DNA (bDNA) as both probes and amplifiers. The bDNA probes and amplifiers do not bind directly to the nucleic acid target. Instead, separate capture probes bind to the nucleic acid target, then the label probe binds either directly to the capture probe, or to an amplifier or a pre-amplifier.

Difference in validity outcome

Both courts found the patents to be novel. Regarding inventive step, the key document in both proceedings was Collins, a scientific paper published in 1997, which describes a bDNA assay for the quantification of nucleic acid target sequences.

There were two notable differences between Collins and the claimed subject matter. First, Collins relates to in vivo assays instead of in situ assays. Second, Collins did not utilise a cruciform design (two capture probes bind the target to one label probe, creating a so-called cruciform structure that reduces “background noise” due to non-specific binding).

The UK High Court found that the use of a cruciform design was taught in Kern, a research paper from 1996, and this teaching would be combined with Collins.

Validity proceedings in the UK boiled down to whether taking an in vitro method and adapting it for in situ use was part of the common general knowledge of the skilled person.

The High Court stated that, in view of a research article by Player, the prospect of success would be assessed by the skilled person as not only reasonable, but good. The judge stated that, even though Player did not provide an explicit disclosure of the use of a cruciform design in situ, it would nonetheless provide additional confidence that bDNA would work in situ. The judge concluded that Player was CGK, and with it the use of bDNA in situ was also CGK.

The High Court found that both of Advanced Cell Diagnostics’ patents were invalid in view of Collins with Kern.

Conversely, the UPC found that Collins, alone or in combination, did not prejudice the inventiveness of either patent.

The UPC stated that the use of a cruciform design in situ was not part of the CGK: Player, was not discussed at length in the decision of the UPC.

Therefore, it appears that the UK High Court was willing to rely upon a probability of success provided by a combination of documents, rather than requiring a single document that discloses all features of the claim, the approach taken by the UPC.

Difference in infringement outcome

The infringement decision in both proceedings came down to the interpretation of complementarity between the label probes and initiators.

The regions of complementarity between the label probes and initiators of Molecular Instruments’ assays have between 1 to 4 nucleotides overlap.

Both of Advanced Cell Diagnostics’ patents specify: “the L sections are complimentary to nonoverlapping regions of the label probe [or (pre)amplifier]”.

The UPC’s approach to claim interpretation was set out in Nanostring v 10x Genomics (UPC_CoA_335/2023). The approach states that the description and drawings must always be used as explanatory aids for claim interpretation, not only to resolve claim ambiguities. Furthermore, the claim should include all embodiments from the description but not extend beyond that which is supported in the description. This results in a rather literal approach to the claim language with reference to the description and drawings as an “interpretation aid”.

Following this approach, the UPC considered the contents of the patents as a whole and found no teachings or embodiments in the patents to support a non-literal interpretation of the claims. Thus, the UPC held that both of Advanced Cell Diagnostics’ patents require that there is no overlap at all between the respective complementary regions on the label probe.

For this reason, the UPC declared that both patents were found to not be literally infringed.

The UPC also ruled that there was no infringement by equivalence for three reasons:

1. The UPC stated that it was difficult or even impossible to construe how much nucleotide overlap would be deemed equivalent.
2. While the UPC found the patents to be valid, it also stated that they do not form a very significant step forward in the development of in situ assays as “all the ingredients of the claimed inventions were already known, just not in combination”. The UPC ruled that fair protection of the patentee does not require a finding of equivalence. (This point is especially interesting given that it is, in essence, the reasoning for the High Court’s decision to find the patents obvious in view of the prior art).
3. The UPC accepted the defendant’s explanations that the 1 to 4 nucleotide overlap results in an increase in specificity and is therefore not simply a workaround to avoid infringing Advanced Cell Diagnostics’ patents. 
   Accordingly, the UPC found that neither patent was infringed, either literally or by equivalence.

By contrast to the approach taken by the UPC, the UK High Court considered the issue of claim interpretation in detail and applied a purposive claim construction, in accordance with established UK case law.

The purpose of the feature at issue (the complementarity between the label probes and initiators) was identified as increasing specificity by having two probes so that non-specific binding is reduced. The judge considered that a small amount of overlap did not undercut this purpose and therefore found that “non-overlapping” did not mean “completely non-overlapping”. The judge further stated: “the key thing is to form two stable duplexes, and while the simplest way to achieve that is to have no overlap, it may be all right and indeed necessary to have a small overlap if there is a positive reason for it, and the key goal is not lost.”

The judge stated that the specification did not support the requirement for a literal interpretation of the claim and that the skilled person would think that the most straightforward approach was to have no overlap but that some overlap would be all right.

The High Court concluded that Molecular Instruments’ invention achieved substantially the same result in substantially the same way, and that this would have been obvious to the skilled person.

Molecular Instruments assisted customers in the UK to troubleshoot their products. Accordingly, the High Court stated that EP1910572 would have been infringed, if the patent had been found valid. EP2500439 was not found to be infringed as it consisted of method claims.

Summary

These parallel proceedings highlight that diverging decisions can arise through differing interpretations of prior-art documents and the claims.

In this case, the UPC took a narrower, more literal interpretation of the claims and prior art documents, whereas the UK High Court took a more purposive approach, considering how the skilled person would interpret the prior art and claims and whether they would consider there to be a probability of success.

This divergence in approaches and the resulting lack of legal certainty across jurisdictions is an uncomfortable position for any UPC user to deal with.

If you are considering initiating a legal action within the UPC and want more information on how the assessment of inventive step at the UPC may affect such action, please contact your usual D Young & Co representative for further information.  

Case details at a glance

Jurisdiction: UPC
Decision level: The Hague Local Division
Parties:  Advanced Cell Diagnostics Inc v Molecular Instruments Inc 
Date: 18 November 2025
Citations: UPC_CFI_187/2024 and UPC_CFI_507/2024
Decision: dycip.com/upc-cfi-187-2024