Monday, October 31, 2016

Tidying Loose Nanopore Patent Threads

A commenter on my recent piece on Genia made a number of assertions with regard to nanopore patents.  A more general one was a complaint that I had covered the opening salvo of the battle from Illumina and University of Washington  and Oxford's formal response and feinting to the CsgG/R9 pore, but failed to cover the campaign's termination.  It's a fair charge and I'll rectify this here.  My (rather lame) excuse is the news broke while I was on vacation in the Pacific Northwest and trying to avoid any remotely professional activities, other than reading Luke Timmerman's Lee Hood biography.  But, that doesn't excuse not writing something on my return.  If you're going to enjoy flame-broiled steak, one must clear the vegetables from one's plate.

The end of the battle was covered when it happened near the end of August in both GenomeWeb and Science. The anticlimatic result is that Oxford agreed to sell no products bearing pores with 68% or greater sequence identity to the MspA pore.  Oxford agreed it would distribute no products with such pores. Oxford won't dispute the validity of the patents in question. None of the parties will make appeals on the matter to the patent office or trade authority. The plaintiffs can request 5 audits to ensure that Oxford isn't violating the agreement, but these can occur no more frequently than once a year and the auditor can be bound to a non-disclosure agreement preventing them from transmitting any information to the plaintiffs other than concerning Oxford's adherence to the agreement.

So how to interpret all this?  My commenter saw it as an admission of guilt by Oxford.  That's certainly one take, but another equally fitting the data is that Oxford's earlier chemistries may have been based on pores similar to MspA, but perhaps with sequence identity different enough that Oxford thought they had a reasonable odds of winning in a court battle.  But by licensing CsgG for the R9 chemistries, Oxford no longer had anything to gain by litigating over MspA.  Either way, if the goal of Illumina and U Washington was to either torpedo ONT or to at least extract a substantial royalty, they've been thwarted.  Oxford goes on selling MinIONs, PromethIONs and the flowcells for each, all of which were targeted by the legal actions. If any of the plaintiffs or their lawyers are commissioning plaques to celebrate their victory, they should have them made from Norwegian Wood, as this bird has flown

The same correspondent also asserted, with an air of authority, that there are not strong grounds for my suggestion that Genia may have trouble from Oxford's patent estate.  I'll confess my comment was based on just the general suspicion that anyone in this field has been prolific in filing patents; I haven't gone fishing for them.  Since Oxford's exonuclease sequencing concept is conceptually similar to Genia's sequencing concept, in so far as both use the nanopore to analyze a by-product of enzymes working on the target DNA molecule, it seems not impossible that Genia might be treading on ground that Oxford has tried to stake a claim on -- and many others. One patent I found in the space lists over thirty other patents, from a wide range of filers, which reference that patent. However, filing (or even having accepted) a patent is one thing; having it stand up under litigation is another.  I'll plead mercy with regards to a summons for looking through that thicket, though should a patent battle ensue I'll steel myself to the task.

A side complaint in the comment is one I will pledge to abide by: should ONT get tangled up in lawsuits with Roche or another big player, then everyone commenting on it should avoid tired "David vs. Goliath" tropes.  Roche is huge with deep pockets, but Oxford isn't some tiny shop either but a serious company that isn't shy about asserting itself.

My commenter made one other interesting point.  Genia's scheme uses phosphate-linked tags on the nucleotides, with these tags released by the polymerase.  This strays into ground which Pacific Biosciences has worked extensively.  So Genia, now owned by Roche, may be sailing close to patents held by Pacific Biosciences, which has a major strategic relationship with Roche.  Presumably these connected relationships will mean PacBio and Roche will come to some amiable licensing terms, but it isn't impossible to imagine this being an irritant in the PacBio-Roche relationship.

Patent battles are ugly and not terribly interesting science, and worse they are extremely expensive.  Codon was sunk in part by a patent lawsuit, though some would see that as just desserts since Codon had sued a different competitor over another patent.  Patents are an important part of biotech business strategies, but are akin to weapons of mass destruction.  Ideally they are used to steer opponents away from one's business and never actually wielded in anger.  Sometimes that results in mutually assured destruction, but perhaps just as bad from these plaintiffs point-of-view is to display their big guns have them shown to be  Quaker guns.  If your plan was to cow your enemy with a show of force, having that force proven illusory is a bitter result.

1 comment:

Anonymous said...

Perhaps there is also another dimension not currently being explored by all these hardware companies in the beginning of their quest to build something new.

Software companies are waiting in the wings. Waiting, for the first devices to be released. Software algorithms can perform "magic", making slow machines faster, fixing errors or making them unimportant, taking away the need for probes or complex library prep procedures.

Most of these companies do not have strengths around advanced skills in big data, AI, machine learning, distributed architecture etc. They don't know what they don't know - they can't see the software dimension. We are not going to get our hands dirty with blood or circuits, but we know how to manipulate data streams and we are about to land a nuclear bomb of disruption on this space. We are just waiting for a few basic devices to come onto the market, then the fun starts!