Thread by @antonioregalado

UC Berkeley gets patent dispute with Broad Institute renewed.

I looked at the documents: technically, appears UC is betting everything on fact that their CRISPR invention used a "single" guide RNA, whereas Broad initially used two RNAs.

statnews.com/2019/06/25/cri…

Our original scoop on the CRISPR patent dispute from 2014 still provides a good explainer of the basic situation, and the VERY hard feelings involved. technologyreview.com/s/532796/who-o…

The dispute previously led to an "interference" proceeding, in which USPTO decided that basic CRISPR editing and CRISPR in human cells are different inventions.

And it gave CRISPR in eukaryotes to Broad Institute. technologyreview.com/s/603662/paten…

But now as stat reports there is going to be a new interference, this time just about eukaryotes (i.e. human cells). In an interference, one party can take over the other's patent claims.

At a technical level, I think Berkeley is saying is they want all Broad's patent claims that rely on a "single" guide RNA. (but pls comment if you think different). I will try to explain why I think so.

CRISPR involves a cutting protein (Cas9) and a "guide RNA" molecule to tell it where to cut a genome.

These guides are cheap and available from companies like Synthego. They are how you point CRISPR at a specific place.

Almost all CRISPR experiments use a single guide RNA. And pretty much any therapeutic use of gene editing in humans would as well. So it would be a big deal if Berkeley could grab that part of human editing.

In documents connected to the new case, Berkeley making a big deal of the fact that in 2012, in their famous Science paper, Jennifer Doudna, Emmanuel Charpentier, et al, published the "necessary and sufficient" components to program CRISPR cut DNA in a test tube.

In nature, CRISPR uses two RNAs to guide the cut--a CRISPR array and a tracrRNA. But Doudna et. al showed these could be combined to one easily programmed RNA molecule.

"necessary and sufficient" -- all you need, and nothing you don't.

One RNA, not two.

see this @geochurch paper from 2013 (predating dispute) in which he describes Berkeley system in much the same way.

whereas Broad has said that in its labs, by mid-2012, it was also doing CRISPR editing (but didnt publish). That unpublished claim to have invented CRISPR first is what allowed them to get their patents in the first place.

The fly in the ointment -- maybe -- is that the early Broad experiments involved seperate RNAs (the tracrRNA and the crRNA).

Here is Eric Lander, head of the Broad Institute, saying it himself in his notorious Heroes of CRISPR piece in cell.

[[ The "Heroes" article was notorious for providing a detailed history of CRISPR and priority claims but not mentioning the patent dispute or big financial interests of the author's institution in the outcome. ]] technologyreview.com/s/545741/a-sci…

In summary, as far as I can gather---(and this could definitely be wrong)--Berkeley is now saying "all your single RNA patent claims belong to us."

Also, "keep your stinkin double RNA invention".

/END

PS- Here is a screen cap of Broad Institute statement. Provides a different narrative, that USPTO is challenging Berkeley claims to CRISPR in human cells. I don't see that in the documents but might be missing it.