Illumina v TDL (Round 2): Mr Justice Arnold finds NIPT novel, inventive and sufficient

The UK courts last month dealt with another patent dispute concerning non-invasive prenatal blood testing (NIPT). NIPT is a method for genetically screening the unborn fetus. NIPT is performed on the maternal blood and is therefore safer than previous methods for genetically testing the fetus that required fetal cells or amniotic fluid. NIPT allows clinicians to screen the fetus for diseases such as Down's syndrome. The global market for NIPT is growing rapidly, and has been predicted to reach almost $5 Billion by 2025. Commercial NIPT tests available in the UK such as The Harmony Test and the IONA test cost around £350-500 per test. The market for NIPT is currently very competitive, with key players jockeying for position; now being played out as patent disputes in the UK courts.

Testing the fetus - a crowded field

Key players in the NIPT testing market include Roche/Ariosa (The Harmony Test) and Illumina, following their acquisition of Verinata Health (Verifi). Another key player is Sequenom, a San Diego based company that began offering its own NIPT in the US in 2011 (MaterniT21). Sequenom owns what are arguably some of the broadest patents in the NIPT field. For example, EP0994963 (Lo), claims the detection of fetal DNA in maternal blood.

Fetus

In 2014, NIPT patent disputes between Illumina and Sequenom were settled with a patent pool agreement. Illumina and Sequenom have since joined forces in going after other players in the field. In 2017, Illumina and Sequenom sued UK NIPT providers Premaitha and TDL for patent infringement of Lo (EP0994963) ([2017] EWHC 2930 (Pat), IPKat post here). Premaitha subsequently agreed to licence the technology from Illumina.

The most recent UK action concerned another Sequenom patent, EP1524321 (Hahn). This patent relates to a key step in NIPT, the separation of fetal DNA from maternal DNA. EP1524321 (Hahn) is based on the discovery that fetal cell free DNA (cfDNA) in the blood of the mother is, on average, smaller in size than the cfDNA of the mother present in the blood. Fetal and maternal DNA could therefore be easily separated to allow the fetal DNA to be analysed.

The latest UK decision - Illumina v TDL [2019] EWHC 1497 - concerned a patent infringement action brought by Illumina and Sequenom against TDL, the UK provider of Roche's Harmony test, for infringement of EP1524321 (Hahn). Claim 1 of the patent specifies a fraction of a blood sample from a pregnant women that has been enriched for extracellular DNA (i.e. cfDNA) such that it substantially consists of DNA 500 base pairs (bp) or less in length. Claims relating to the use of the method to detect Down's Syndrome were deleted, as the Claimants Sequenom and Illumina accepted that theses claims were invalid for insufficiency.

Last year, Mr Justice Carr ruled in Illumnia v Premaitha [2018] EWHC 615  (IPKat post here) that the infringement action was allowed to proceed against TDL, despite the fact that a previous infringement action has previous been brought based on the earlier patent EP0994963 (Lo).

Novelty

The case concerned the novelty of the claim in view of a Japanese conference abstract. The case primarily rested on how a skilled person would interpret the sketchy results and conclusions presented in the abstract.

An interesting point that arose was whether "the state of the art" was the abstract in Japanese or the English translation of the abstract. It was common ground between the parties that what mattered was how the original Japanese would be understood. Mr Justice Arnold was doubtful of this "since the skilled person is located in the UK" (Generics v Warner Lambert, [2015] EWHC 2548 (Pat)) (para. 118). In the end, however, the point was not influential to case in question.

The parties provided their own translators and translations. Every part of the brief abstract was analysed in detail. The point of contention was whether a skilled person would have understood the abstract as disclosing (without the benefit of hindsight) the discovery on which the invention was based. In particular, did the abstract disclose that there is a size difference between fetal and maternal DNA in the maternal plasma?

Mr Justice Arnold found that a skilled person would not have engaged in the detailed analysis of the abstract required to reach this interpretation of the prior art argued for by TDL, but would take the abstract "at face value". Based on expert evidence, Mr Justice Arnold further concluded that, even if the skilled person did undertake some detailed analysis, they would still not arrive at the Defendant's interpretation. The claim was therefore found to be novel and non-obvious in view of the Japanese abstract.

Insufficiency

Mr Justice Arnold noted that the law on insufficiency had recently been reviewed by the Court of Appeal in Regeneron v Kymab (IPKat post here). Mr Justice Arnold summarised three principles from Regeneron v Kymab:

1) the specification need to necessarily enable a skilled person to perform all embodiments of the invention;
2) an assessment of insufficiency must be sensitive to the nature of the invention and the facts of the particular case; and
3) the protection afforded by the claims must correspond to the technical contribution to the art made by the disclosure of the invention (i.e. no arm chair inventions).

TDL argued that the claims of the patent data reported in the patent have since been shown to be wrong. Particularly, although fetal DNA is on average shorter than maternal DNA, the difference is not as large as that reported in the Patent. TDL submitted that the data in the Patent were confounded by contamination with other sources of maternal DNA in the blood. This was perhaps not a surprising argument on behalf of the TDL, given the history of dodgy data from Sequenom.

TDL also argued that there was a construction-insufficiency squeeze: either the claims required a 2.0-fold enrichment (as shown in the examples) or the claims were insufficient because the scope of the claim was broader than the technical contribution of the patent. However, Mr Justice Arnold did not see the connection between this argument and TDL's contention that the results in the patent were wrong due to contamination (para. 239). In any case, Mr Justice Arnold did not construe the claims as limited to a 2.0-fold enrichment.

Mr Justice Arnold addressed the issue of sufficiency by examining a series of publications relating to the size of maternal and fetal DNA in the maternal plasma, published after the patent priority date. Mr Justice Arnold concluded that these documents showed that fetal DNA could be enriched based on size, although by how much was open to question. Mr Justice Arnold concluded that the patent was therefore sufficient:

"I do not accept that the claims are broader than is justified by the technical contribution made by the Patent. The Patent discloses a general principle of technical utility, namely that the foetal cell-free DNA in maternal plasma or serum can be enriched by size separation at 500 bp. The breadth of the claims is commensurate with that technical contribution. It is immaterial that the extent of the enrichment which can be achieved may vary from case to case and may on average be less than 2.0-fold....The fact that on very rare occasions the invention is of no practical benefit does not detract from the fact that in the vast majority of cases it is of technical utility."

The UK High Court judgment was in line with the decision of the Opposition Board of the EPO on the point of sufficiency.

The patentability of natural products

The judgment includes an interesting end note on the patentability of the subject-matter of the claim, in view of an attempt by the defendants to bring a US-style assessment of patent eligibility into proceedings. In the US, the Sequenom NIPT patents have fallen foul of Section 101. Particularly, the US Court of Appeals for Federal Circuit found Sequenom's diagnostic patents invalid for relating to patent ineligible subject matter, particularly for relating to a natural phenomena (Ariosa v Sequenom). Sequenom were denied permission to appeal to the US Supreme Court (Sequenom v Ariosa Diagnostics, Inc 136 S.Ct. 2511 (2016)).

In an attempt to introduce a similar issue into the UK case, TDL argued that the patent related to a discovery, and was therefore excluded from patentability under Section 1(2)(a) UKPA 1977. TDL  argued that "maternal blood and its contents are naturally occurring products". TDL accepted that, as the law stood, this argument could not succeed. None-the-less they asked the court to come to a finding to enable the issue of law to be argued by a higher court. Mr Justice Arnold declined to make any such finding (para. 245) [Merpel: phew].

This case in the High Court is unlikely to be the last relating to NIPT. The growing commercial importance of this technology, and the crowded market, will undoubtedly give rise to yet more patent disputes.  It is not yet known if TDL will seek to appeal the decision.