Different approaches and conclusions in the case of Advanced Cell Diagnostics vs. Molecular Instruments
1.1 Advanced Cell Diagnostics (ACD) sued Molecular Instruments (MI) for infringement of one of its European patents before both the Unified Patent Court (UPC – Local Chamber in The Hague) and the High Court of Justice of England and Wales (EWHC). Based on the same facts, the two courts handed down divergent judgments (UPC: https://www.unifiedpatentcourt.org/en/node/159761 EWHC: https://caselaw.nationalarchives.gov.uk/ewhc/pat/2024/898).
Hereafter, various aspects of these two judgments will be compared.
1.2 The patent underlying the infringement action, EP1910572B1 (“EP572”), relates to a method for detecting one or more nucleic acid targets within an individual cell (in situ RNA detection); the method having improved detection efficiency.
The invention is based on the principle of interposing in situ at least two capture probes between a nucleic acid target to be detected and a label probe.
1.3 The UPC and the EWHC ruled on validity of claim 1 in presence of the same prior art: Collins et al, “A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml” (hereinafter “Collins”) and Kern et al, “An enhanced-sensitivity branched-DNA assay for quantification of human immunodeficiency virus type 1 RNA in plasma.” (hereinafter “Kern”).
1.4 The closest prior art, Collins discloses an embodiment of an in vitro detection method using a (single) capture probe. In another embodiment, presented as theoretical, Collins discloses the in situ aspect and a plurality of capture probes (cruciform “label extenders”) in combination with other features.
1.5 The table below shows the features of a simplified version of claim 1 in question together with the feature structures adopted by the UPC and the EWHC. The table shows for each feature whether it was considered anticipated by the closest prior art “Collins”:
| Claim 1 | UPC – EWHC | Anticipation by “Collins” / UPC | Anticipation by “Collins” / EWHC |
| A method of detecting one or more nucleic acid targets within an individual cell, the method comprising: | 1(a) – A | No (in vitro and not in situ – item 54 of the judgment) | Yes (in situ – item 358 of the judgment) |
| providing a sample comprising the cell, which cell comprises […] one or more nucleic acid targets; | 1(b) – B | No | Yes (in situ) |
| fixing and permeabilizing the cell; | 1(c) – C | No |
No (item 359 of the judgment) [but: implicit – item 360 of the judgment] |
| for each nucleic acid target, providing | 1(d) – D | Yes | Yes |
| (i) one or more label probes, wherein each label probe comprises one or more labels, […] |
1(d)(i)- D (i) |
Yes | Yes |
| for each nucleic acid target, providing two or more different capture probes, | 1(e) – E | No (only one (single) “Label Extender/Capture Probe” per target nucleic acids) | Yes (cruciform design – item 358 of the judgment) |
| wherein each of the two or more capture probes comprises a section T complementary to a section on the nucleic acid target and a section L complementary to a section on the label probe, […], | 1(f) – E(i) | No (because feature 1(e) is not anticipated) | Yes |
| and the L sections are complementary to nonoverlapping regions of the label probe, […]; |
1(h) – E(ii) Part 2 |
No (because feature 1 (c) is not anticipated) | No (item 359 iii) of the judgment) |
| hybridizing, in the cell, the two or more capture probes to a single copy of the nucleic acid target, when present in the cell; | 1(i) – F | No (because feature 1 (c) is not anticipated) | Yes |
| capturing the label probe to the two or more capture probes, thereby capturing the label probe to the nucleic acid target, | 1(j) – G | No | Yes |
| by simultaneously hybridizing at least two different capture probes to single copy of the label probe, […] |
1(k) (i) – G(i) |
No | Yes |
| detecting a signal from the label. | 1(l) – H | Yes | Yes |
2.1 The UPC shows a strict approach and considers that the “in situ” feature and the plurality of capture probes are not disclosed in the same context as Collins’ embodiment taken as a starting point (UPC: items 55./56. of the judgment). Features 1(e)/E and 1(f)/E(i) are therefore not anticipated.
The EWHC, in contrast, considers that these features are disclosed by Collins and therefore does not distinguish between different embodiments in a single document (EWHC: item 358 of the judgment).
2.2 One novelty attack by MI was based on the combination of Collins and Kern because of a reference by Collins to Kern.
The UPC and the EWHC did not uphold this attack, as Collins’ reference to Kern was not sufficiently specific. Combining Collins and Kern to create a compound prior art was considered not to be possible (UPC: item 58 of the judgment – EWHC: item 364 of the judgment).
3.1 With regard to inventive step, both courts took Collins as their starting point and, in summary, considered that the difference lay in the in situ use and the plurality of capture probes (“label extender” or cruciform probes) (UPC: item 59 of the judgment – EWHC: item 368 of the judgment).
3.2 The UPC considers that the technical teaching of Collins rendered the use of cruciform probes obsolete while achieving the same technical effect of reducing the signal-to-noise ratio (item 59 – phrase between pages 20 and 21).
Consequently, the person skilled in the art would have no motivation to provide for a plurality of capture probes by using cruciform capture probes.
3.3 The EWHC considers that the main question is whether, starting from Collins, the person skilled in the art would have had a prejudice against using cruciform probes in an in situ environment. The EWHC considers that this is not the case, given that the person skilled in the art would expect the task to be empirical in nature, even if some practical but surmountable difficulties were to be encountered (EWHC: item 369 of the judgment).
3.4 In summary, the UPC considers that a person skilled in the art would not look beyond Collins, as the technical effect is already achieved, while the EWHC considers that Collins teaches that the sensitivity of the process is good, but that there is an incentive to improve it further (EWHC: items 370, 375, 376) with a reasonable expectation of success (EWHC: item 382).
3.5 The UPC therefore admits inventive step, while the EWHC does not.
4.1 Beyond the question of validity, the opinions of the two courts also differ on the issue of the reproduction of the characteristics of the alleged infringing product.
4.2 The feature at issue is feature 1(h)/E(ii): “[…] the L sections [of the capture probes] are complementary to non-overlapping regions of the label probe […]”.
The alleged infringing product has regions of the label probe where parts of two capture probes partially overlap.
4.3 The UPC interprets feature 1(h)/E(ii) as being limited to the complete absence of overlapping regions, inter alia because the patent does not disclose any example showing partial overlap, and therefore concludes that the features are not reproduced (UPC: item 101 of the judgment).
4.4 The EWHC interprets this feature as encompassing situations of partial overlap, provided that the invention works and the key advantage of the invention is achieved (EWHC: item 273 of the judgment). Consequently, the EWHC considers the features to be literally reproduced.
5. It can be seen that, faced with the same facts, the UPC and the EWHC render quite divergent judgments.
Before deciding before which court to bring an infringement action, it is advisable to analyse the chances of success based on the approaches of the court in question.
If we generalise the lessons learned from this case, where the prior art is fairly relevant, it is preferable to bring the dispute before the UPC, and where the alleged infringement requires a broad interpretation of the claims, it is preferable to bring the case before the EWHC.