[patall]

> (and many competitors not too far behind)

From what I have heart (from someone at a cfDNA start-up), competitors have the solid problem of competing with a monopoly here. Grail is Illumina and Illumina will have a quasi monopoly on diagnostic sequencing until their core patents run out (hopefully around 2025?) and BGI and others will join the field. For a diagnostic test, you would want to integrate a number of preparation steps with the sequencer but cannot when the company whose help you'd need for that is competing with you.

[new299]

> you would want to integrate a number of preparation steps with the sequencer

I think this is unlikely, Grail like everyone else probably just do standard sequencing runs with their own prep.

The issue is that Illumina make something like 10x on sequencing consumables.

So if Illumina were to sell a sequencing based test, they have large margins they can cut into to undercut anyone else.

That said, Illumina's dominance in sequencing is probably ending in ~2024 anyway (when basic patents expire).

Grail is not Illumina, it's a spinout that they want to acquire back in. Most likely this is because Illumina see that:

a) This Grail experiment is working out. b) They're going to lose their dominance in sequencing, and they want to acquire downstream applications.

[xiphias2]

Separating Grail out to be bought again for a much higher price was a strange move from Illumina, or at least a bad financial decision in hindsight.

Still, if the 2025 year that you write is true, other companies may be already able to use the patent in a non-commercial way (just for clinical trials and future potential revenue split)

[new299]

Separating out Grail allowed the company to take on outside investment, much of which I imagine flowed back to Illumina in the form of sequencing instrument and consumable sales.

The IP that Illumina is using the block the sale of MGI instruments expires in 2024, I put together some notes on this here:

https://41j.com/blog/2021/05/the-next-few-years-in-dna-seque...

There will probably be a drop in sequencing costs at that time, as there are a few players set to build on expiring IP. Singular Genomics (recent IPO) is one of these, they could possibly be on the market earlier than this (by avoiding some of the last IP to expire).

There's no non-commercial exception for patents, so I don't believe patented approaches could be used in clinical trials. But on the scale of clinical trials, Illumina sequencing would not be prohibitively expensive...

[axg11]

I agree it was an odd decision at the time. Grail is very much built on Illumina’s platform and I don’t see them building anything otherwise. If Galleri is successful, Grail will become Illumina’s biggest customer and the two could become completely interdependent.

In the medium term, I think there’s an opportunity for a company to build ctDNA screening on a different sequencing platform. That could present unique advantages against Grail which is very much tied to using Illumina.

[MontyCarloHall]

> Grail is very much built on Illumina’s platform

I’m not sure this is true. GRAIL’s technology is (a) a protocol for efficient bisulfite conversion of cfDNA to infer cytosine methylation, and (b) proprietary algorithms for using that methylation information to infer presence of cancer. Both (a) and (b) are agnostic to the actual sequencing machine (e.g. Illumina): the end product of (a), namely cfDNA fragments with non-methyl C’s bisulfite converted to uracils, could be sequenced on any machine[*] capable of reading short DNA fragments, not just Illumina’s machines. (b) just requires methylation information, which again, is sequencer agnostic.

[*] companies making such machines will likely become abundant once Illumina’s patents expire in a few years

[axg11]

Grail will have to end-to-end validate any changes to Galleri, especially any change of sequencer. Given that any Illumina competitors based on the same IP wouldn't hit the market until 2024 (extremely optimistic) I'd be surprised if Grail were able to launch a non-illumina Galleri before 2026. A company that is locked into the Illumina platform for the next 5 years is very much dependent on Illumina in my eyes.