US PTO rules against Univ of California, argues that Broad Inst invented CRISPR | Hacker News Reader

US PTO rules against Univ of California, argues that Broad Inst invented CRISPR

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217 pointsdluan90 comments

Reminiscent of the polymerase chain reaction (PCR) [1] where there were and are ongoing patent disputes for the last 30 years.

The highly esteemed Eric Lander, founding director of the Broad Institute, who recently got turfed out of the Whitehouse for being an asshole following testimony by 14 different staffers [2], wrote a highly biased reinvention of history around CRISPR published in Cell [3] which was severely criticised [4,5]. To this day, this highly cited 'review' still does not have a conflict of interest statement.

[1] https://en.wikipedia.org/wiki/Polymerase_chain_reaction#Pate... [2] https://en.wikipedia.org/wiki/Eric_Lander#Science_Advisor_to... [3] https://www.cell.com/cell/fulltext/S0092-8674(15)01705-5 [4] https://www.statnews.com/2016/01/25/why-eric-lander-morphed/ [5] https://www.michaeleisen.org/blog/?p=1825

Actually, one of the fascinating facts about the history of PCR is that Kary Mullis didn't optimize to make billions on the patent rights. In his Nobel acceptance speech, he reminisces about how a coworker told him to quit his job and start another company before submitting an invention disclosure on PCR, but he didn't do that.

https://www.nobelprize.org/prizes/chemistry/1993/mullis/lect...

My friend Ron Cook, who had founded Biosearch, and produced the first successful commercial DNA synthesis machine, was the only person I remember during that summer who shared my enthusiasm for the reaction. He knew it would be good for the oligonucleotide business. Maybe that’s why he believed it. Or maybe he’s a rational chemist with an intact brain. He’s one of my best friends now, so I have to disqualify myself from claiming any really objective judgement regarding him. Perhaps I should have followed his advice, but then things would have worked out differently and I probably wouldn’t be here on the beach in La Jolla writing this, which I enjoy. Maybe I would be rich in Tahiti. He suggested one night at his house that since no one at Cetus had taken it seriously, I should resign my job, wait a little while, make it work, write a patent, and get rich.

Oh, wow, that's a great Nobel lecture. Thank you for sharing.

The "Whig History of CRISPR" article [1] by Nathaniel Comfort that Eisen quotes is one of the most jaw-dropping rebuttals I have ever seen of anything ever. When Lander was named by Biden to high office I just sat back and waited for the shoe to drop.

[1] https://genotopia.scienceblog.com/573/a-whig-history-of-cris...

It seems that in determining who first 'invented' CRISPR, the PTO has gone into lab notebooks as far back as 2012.

https://twitter.com/jsherkow/status/1498413788994940928/phot...

When I did some undergrad research, the professor was very careful to specify that lab notebooks were essentially legal records of what you worked on and when. It's interesting to see that actually in use

I've read similar things about lab notebooks at Bell Labs, which certainly makes sense given the value of the IP they were creating there (among other things, the first transistor was invented there).

This is hugely important. It comes up rarely, but when it does, it's essential.

Like millions of dollars, people's careers essential. For things like this, or scientific misconduct cases.

Some ~20 years ago, my professor suggested we not only sign and date the notebook, but hash the contents and publish the hash to the new york times. I'm told this in some way resembles the blockchain.

Just stick a cronjob in to mint an NFT of it nightly.

It is less relevant now for patents after the move from first to invent to first to publish/file (happened after crispr).

Why wasn't this simply based on first to file? I thought the PTO moved away from the conception standard to a disclosure one? Board was also first to file.

The first-to-file provisions apply to applications filed on or after March 16, 2013. These were filed well before that date.

Under the old first-to-invent paradigm, when there is a question of fact concerning who invented first, the USPTO adjudicates with an "interference" proceeding, which is what this is.

Thanks, I knew it had been a while, but I guess not as long as I thought!

that's not too far back, relative to the discovery of Cas9 gene editing...

The Code Breaker by Walter Isaacson attempts to chronicle this in detail. The narrative has UC/Doudna making the fundamental contributions. And that the leap to human cells was "trivial" made by Broad/Zhang. Anyone have any perspective on how they were characterized?

While informative, I think it was mentioned in the book that Doudna was the one who asked him to write it about her, so I think it needs to be taken with a grain of salt. I thought isaacson did a pretty good job in trying to make it objective, but it does read a bit like PR at times which is kind of unfortunate for a topic on science. I guess it's been the same way for other historical discoveries as well, especially given the economic stakes involved. I find self promotion a bit debasing but it seems to be important of society like it or not.

That's a generous way of putting it. Just the first chapter nearly had me putting the book down as it read like a press release written on behalf of the scientist. It gets less painful and I understand that authors choose to write books about subjects that interest them but it feels like there's a definite difference in objectivity from his previous works.

this is the first book by isaacson that i read and i doubt i'd like to read any other. the bias in the narration, while duly acknowledged, forces him to paint other people (aka other side) so monstrously—at times—that it's impossible to take his criticisms seriously. that said i liked quite a few people aside from doudna (for example i think emmanuelle charpentier is badass and quite rightly the sort of hero we need—working with elegance and loads of fun).

It’s very unfortunate to read such a statement - Isaacson’s “The Innovators” is an amazing book that never lost its objectivity throughout my readings.

The chapters on Watson are super interesting. If Isaacson had written the book primarily about Watson, it likely would've been at the same level of Steve Jobs.

If that book is a bit one-sided, it has to be mentioned that (as other comments in this thread have noted) the other side also had their share of one-sided publications highlighting the Broad Institute's contribution and minimizing the merits of the other scientists involved, such as this article by Eric Lander: https://www.cell.com/fulltext/S0092-8674(15)01705-5 (reviewed here: https://genotopia.scienceblog.com/573/a-whig-history-of-cris...).

That book is so annoying. Disjointed towards the end and no doubt rushed out because of COVID. Doudna alone on the cover. A real disappointment and woefully little explanation of how CRISPR works.

She has admitted several times that her team tried and failed to make the leap to human cells.

In light of what seems to be this fairly in depth and data based decision by USPTO, maybe PR? :-)

It's depressing that any entity can have monopolistic ownership over CRISPR.

If someone wins, will they prevent people from using the technique without a hefty licensing fee? How much potential is there for this to slow scientific progress?

Reminds me of FDM 3D printing tech. Stratasys patented it in the 80s and proceeded to do fuck all with it except slow down progress in the field. It's only since 2009 when it expired that it became commercialized and mainstream, revolutionizing prototyping as we know it.

At this point patents need to be replaced with a one time monetary reward system or a stipulation that everyone using the tech needs to pay you 5% royalties for a time duration or something of the sort, but no exclusive rights. With the way the climate is going we can no longer afford these 30 year tech setbacks or we're all screwed.

There are other possibilities. Such as a licensing system based around the idea of Harberger taxation. Basically, you make licensing of patents mandatory, and tax the patents based on the licensing fee. The higher the fee, the higher the tax.

Or just cut the duration of patents. 20 years made sense back in the 1800s. These days it should probably be more like 7 years.

This is why there should be an annual fee to renew a patent that increases exponentially, with the base proportional to the worth of the individual/company filing the patent at the time of filing.

That ties the duration of a patent directly to how much value it provides to the company over time, which is the rationale for having patents in the first place. A company could only afford to hold onto a patent for as long as it causes the company’s revenue to grow exponentially. Once the patented technology matures and growth plateaus, keeping the patent would become prohibitively expensive.

Well, the general argument for patents is that before patent law, people just keep developed techniques secret, which slowed scientific progress even more, while patent process at least requires public disclosure.

Interesting side point though from https://www.mercurynews.com/2022/02/28/uc-berkeley-loses-cri...:

''' But over time, according to one expert, the patents may lose value due to continued innovations.

“By the time that large scale commercialization occurs, there will probably be supplemental or supplanting technologies,” according to the UC attorney, who asked that his name not be used. '''

So if mid and late-stage companies continue to innovate for e.g. the purpose of productionizing CRISPR, the effect of the original patent will lessen in value. A nice note that there continues to be an incentive for progress in this space.

Yeah, the assumption underlying this case — that there's a single entity who discovered it or invented it — is fundamentally flawed. No to mention other problems.There's so much about this that's a textbook example of everything wrong with intellectual property and academic credit in our era.

If they couldn't have ownership over their research, they would probably do something else.

In such case, how much potential is there for this to slow scientific progress?

I’ve become convinced that intellectual property restrictions significantly slow innovation. If no one was allowed to own information we’d still have to get things done and work to make a profit. Only once someone figured something out everyone could adopt it right away. Take a look at the landscape of innovation in 3D printers in the 13 years they were for sale under patent and the following 13 years after the patents expired. Innovation absolutely exploded! Instead of one company happy with $25,000 machines we had hackers, hobbyists, and engineers from all over the world working on solving problems and making the machines cheaper. Ten years after the patent expired the price dropped 100x from $25k to $250.

Imagine how cheap medical care would be if all the patents on medical imaging equipment expired. If there were no patents the market still provides incentive to innovate as first movers and reputable brands stay competitive. Meanwhile patents allow big slow companies to sit on their rewards and charge high prices with little real innovation. Things would change, sure. Instead of few large investments we would see more frequent smaller investments. But market competition would still work and natural rewards to innovation persist. Only innovation propagates way faster.

Intellectual property restrictions are a disaster in my mind. And sadly most people believe some basic fairy tale that we were told without ever caring to research if that story is even remotely true.

To be clear: I'm not saying the current IP system is good. It is evil. But no IP would also be evil.

The fact that when prices go down, consumption increases is just basic microeconomics. This is not evidence that removing IP would increase scientific progress or well-being.

One way to approach this would be comparing countries that don't/can't enforce IP protection to countries who do. Of course would need to control for a lot of variables and it wouldn't be a perfect predictor, but already better than pure speculation.

> The fact that when prices go down, consumption increases is just basic microeconomics. This is not evidence that removing IP would increase scientific progress or well-being.

I think you have misunderstood my intent. I am not saying that increased consumption is evidence that we should eliminate patents. I am saying that reduced price of functional 3D printers is a sign of increased innovation. Actually I saw the innovation first hand in the user groups and mailing lists, and I am using the price as an indicator of what I saw.

My point is that we would see more innovation if we eliminated patents and intellectual property restrictions. This would have the effect of lowering prices for things which I think is great, but my point is that patents don’t even do what we are commonly told they do. We are told they increase innovation but in my opinion there was far more innovation in 3D printing once the patents expired.

And it’s no surprise. The only thing a patent actually does is restrict innovation. That is the single function of a patent. The story we are told is that by allowing a government decree to issue monopolies on ideas, there will be more profit in new ideas, leading to a net increase in innovation. But in my opinion this process so significantly restricts follow on innovation that the whole thing ends up being quite counter productive.

You’d appreciate this on the ground report from the culture of unauthorized but widespread copying in China. https://www.bunniestudios.com/blog/?p=284

I have done plenty of cognitive science (intelligence, curiosity) research and psychology (personality) research that is unpatantable yet contributing to the pace of scientific progress. I have never considered slowing my research because of "ownership" of this work.

Not exactly a steel man.

No, of course. I also don't mean that the parent comment isn't correct. Research velocity would surely slow down, but by how much is pretty unknowable.

It least it's only for another 12 years.

What’s especially irksome here is there use of “but this person got it to work first” as their deciding factor, but at the same time they allow thousands of patents for things with no working example

Only somewhat on-topic, but this is the latest in a long line of cases which transfer IP from universities to corporations on various grounds.

For a particularly representative previous example, see Stanford v Roche [1], in which SCOTUS found that a patent originated with the individual researcher and not his institution, and was therefore transferrable to other private entities with whom the researcher had agreements.

I, for one, believe that we should enact stronger protections to ensure that research partially performed at publicly-funded labs remains in the hands of the public. In particular, I think that the Bayh–Dole Act should be strengthened to vest the patent with the institution directly, and to create a default presumption that the institution owns the IP.

[1] https://en.wikipedia.org/wiki/Stanford_University_v._Roche_M....

I think you may be misunderstanding how the Bayh-Dole act works. The Stanford-Roche case looks like it hinged on a very particular set of circumstances involving a signle researcher working in both academia and industry, and the dispute was basically over who owned his work. The CRISPR case is different because the competing labs claim to have made the invention independently, with zero crossover. Even if Broad Institute were a for-profit corporation and not siphoning up vast amounts of NIH grants, the underlying dispute has nothing to do with Bayh-Dole or university IP policies, it's just a classic case of "who was first".

poster was arguing that things should work differently than they do. for some reason it is common when people argue for change for them to get lectures about how things are. weird stuff.

The poster was arguing that, when a university/corporate partnership invents something, the law should ensure the university doesn't get screwed.

The responder was pointing out, in this case, the law could be infinitely strong in allocating credit to the university but it wouldn't help because this case was about whether they invented the thing at all.

While the Broad institute is private, it is a non-profit that is tightly affiliated with MIT and Harvard. To me, this is different than a patent getting transferred to a multinational pharmaceutical corporate.

I didn't know they were a nonprofit. In that case, my OP is pretty off-topic for this case.

Non-profits can still have patent portfolios that they try to exploit for commercial gain -- though by licensing, rather than producing products directly. When the research was publicly funded, the same conflicts of interest apply.

The Broad also makes enormous bank as a sequencing service for pharma. They are "non profit" but they make a profit.

> I, for one, believe that we should enact stronger protections to ensure that research partially performed at publicly-funded labs remains in the hands of the public.

I agree!

> In particular, I think that the Bayh–Dole Act should be strengthened to vest the patent with the institution directly, and to create a default presumption that the institution owns the IP.

That is not the same thing though. The universities have historically been very exclusive about who can license their patent portfolios, and at high cost. They're the same as a business in that respect.

I once looked into licensing some software from an English university. At the very beginning of the discussion, I was read a long list of domains where the software had already been exclusively licensed. Great! We didn't fall into any of those domains, next question. It turned out I had misunderstood, the list was for domains where THEY thought the software should be each exclusively licensed to a third party.

There were other factors, but it became clear it wasn't worth the effort trying to license from the university.

> I, for one, believe that we should enact stronger protections to ensure that research partially performed at publicly-funded labs remains in the hands of the public.

OK...

> In particular, I think that the Bayh–Dole Act should be strengthened to vest the patent with the institution directly, and to create a default presumption that the institution owns the IP.

What happened to remaining in the hands of the public? How does the public benefit from this? With the patent assigned to Broad, nobody's allowed to use it without permission from Broad. With the patent assigned to the UC system, nobody's allowed to use it without permission from the UC regents. As far as the public is concerned, there's no difference.

The university of California is controlled by and owned by the people of California (at least in a round about way).

The PTO, and the very concept of a patent in the American legal system, are also controlled and owned by the people of California in that sense. It's not a useful way to look at the world.

Who are the "UC regents"? It is a public university, so (at least indirectly) the public. Seems like a big difference.

The regents are a corporation which was granted powers to operate on the behalf of the public.

I strongly disagree.

Universities already utilize government funding for research with potential business applications to the maximum extent with the minimum effort required to seek commercialization. Just ask any Director of Technology Transfer.

Because universities have no insight into what research has merit for business purposes, nor have they made any serious effort to discover it after decades of this funding, they farm graduate students into predatory policies designed to treat them like future lottery tickets (corporations).

Government-funded labs sit open while graduate students cannot conduct their research because of the total control administrations now exert - pretending to be VCs because these facilities are under their control.

There are millions of university patents produced yearly. Millions. Yet the commercialization rate is close to 0, even at the best.

The missing input is founders. The rarest ingredient in inventing businesses are founders. But universities treat them as deposable - including when they are from their own faculty.

The public requires no other return than the jobs (and payroll tax) they create - that was the justification for the bill.

This means that universities are committing fraud by preventing commercialization efforts - which they do by action, policy and neglect.

The ASU Foundation has made some strides in minting “founder friendly” commercialization policies, but we’re a long way off from anything to be proud of.

Seems ripe for "use it or lose it" patent policies. It's good when research is going towards useful things, but having all of those patents locked up is not serving anyone.

I agree that publicly funded research should be easier to get access to. Ironically, you have it backwards. Before the Bayh-Dole Act, there tended not to be any patent filings on publicly funded research at universities because it wasn't clear what claim the federal government had to the patents. Bayh-Dole, by clearly vesting patent rights in the universities, allowed the universities to take title to the patents and license or sell them to private corporations.

The usual story that gets told here is of fantastic success. Look at all the startups that have come out of university research. Look at all the licensing revenue universities have generated from patents that they own thanks to Bayh-Dole.

I'm actually a Bayh-Dole skeptic. Like you, I tend to believe that too much publicly funded research does get concentrated into certain private hands thanks to patent rights on federally funded research. But strengthening the Bayh-Dole Act would only encourage more concentration.

Some startups need exclusive rights to succeed, and pharmaceutical or biotech startups are the prime examples. But most startups don't need exclusive rights to succeed, and I don't see why we should trust university tech transfer offices to make good decisions about who should have access to federally funded technology and on what licensing terms when that is the case, as it is so often. A weaker Bayh-Dole Act would be more helpful than a stronger Bayh-Dole Act in that regard.

But even some biotech inventions like CRISPR-Cas9 or mRNA vaccine tech doesn't seem to me to be stuff that the federal government should allow to be controlled by university tech transfer offices. Some technologies are too important for that. That's why the Bayh-Dole Act includes a provision for "march-in rights." The surprising fact, however, is that they have never been used, even during the pandemic. That to me seems like the easiest and best place to push the federal government if you feel like too much tax payer funded research is being held hostage by tollbooth workers in university tech transfer offices.

I think HN has tried to be helpful by removing the trailing "." from the URL, but doing so has broken the Wikipedia link.

I've seen similar behavior elsewhere like in iMessage.

In many cases, leaving IP at Universities effectively means never employing it. For example, if there were stronger protections in place, I don't think the Oxford/Astrazeneca vaccine would ever have been widely available.

You clearly don't know what the Broad is.

This the first-to-invent rule going out with a bang. Under a change in the law in 2013, the UC Regents never would have had the chance to argue that they were entitled to the claims here because Harvard filed first. Actually, they could still argue that Harvard stole (or "derived") the idea from them. But that doesn't seem to be the case here. Under the current law, this interference proceeding never would have happened.

> Harvard filed first

UC filed seven months earlier:

https://genotopia.scienceblog.com/573/a-whig-history-of-cris...

UC was first to file some other claims. In the claims that were at issue in this decision, Harvard was first to file. Actually the opinion does a good job explaining some of that. But Harvard is labeled the senior party in the opinion because they were the first to file this set of claims.

But this is just the US patent, right?

AFAIK, the European patent office already recognizes Charpentier & Doudna as the patent owners.

Yes, just in the US, and only one of the sets of patents in the US. This one is about use of CRISPR-Cas9 in a eukaryotic environment specifically. Both parties have some other claims, and ultimately will have to cross-license each other for the technology to develop. Too bad such an important decision is being left to such a small group of university administrators who know very little about how best to grow the technology into successful therapies and technologies at scale!

More background— https://www.broadinstitute.org/crispr/journalists-statement-...

Yes, I am certain the background this particular website provides will be super objective and unbiased.....

This decision came on the same day Intelia published positive results with gene editing, the stock would have jumped much higher without this decision:

https://www.youtube.com/watch?v=zl8sRdXFHlM

https://ir.intelliatx.com/news-releases/news-release-details...

Wasn't CRISPR discovered in bacteria rather than invented?

CRISPR is the generic name for a system of proteins and RNA found in bacteria. It was discovered by Francisco Mojica. They all chomp viruses' DNA.

Different bacteria have different proteins.

Among these proteins the most interesting is the CAS-9, isolated "in vitro" by the teams of Jennifer Doudna and Emanuele Charpentier. They also showed it could be programmed to handle different DNA sequences. Feng Zhang then proceeded to do the same in vivo, with eukaryotes, months after.

Doudna and Charpentier filed the application first but the Broad Institute filed it with a express requirement so they were granted first.

It was discovered in bacteria but the invention is about how that technique could be used to target a particular section in the genome of your choice.

Do the researchers who discover/invent ever get a stake in the licensing/patent or do the owners/investors of the lab own the rights to the discovery? Or in a university setting, do the professors/researchers get to own a part of their discovery or are the discoveries owned by universities entirely?

they get whatever they agreed to when they took the job.

which is generally very little, in exchange for a salary not conditioned on patent income.

Many universities have inventor-owns IP policies. This can be a factor when considering job offers.

They don't and it's a huge reason why in my opinion innovation has stopped.

There's not a huge reward in doing that extra work.

What you said is plain wrong in most places.

Unrelated but can anyone recommend a good, more technical introduction to CRISPR? I read Isaacson's book and I really enjoyed his technical discussion but I really wanted more

Wow, so the judge grants CVC invented CRISPR-Cas9 but grants it to Broad for reducing it to practice in eukaryotic cells. This feels really unfair to me. It is an essential step, but it's also a subset of broad application in what could be the most profitable area.

Why wasn't this simply based on first to file? I thought the PTO moved away from the discovery standard to a disclosure one?

These patent applications predate that change. This is an interference proceeding, which was the mechanism for resolving priority before first-to-file

Presumably that law change only applies to patents filed after a certain date and this one precedes that.

Sounds economically big, in terms of who gets to monetize CRISPR ip.

Considering Doudna (one of the labs in question) also started Caribou Biosciences now worth $600M, yes, there is a lot at stake.

https://www.google.com/search?q=NASDAQ:+CRBU

https://www.cariboubio.com/about/#leadership

A big maybe at best. CRISPR might not achieve the humanity changing effect it might have any time soon.

It's still making a ton of money as its an excellent tool in the molecular biology lab.

It will be a slow takeoff like AI. It takes time for business applications to emerge. This is how all new tech works.

The businesses built around them have to grow and many will fail.

anyone remember when RAND Corp got the patents for what essentially is the IPv4, despite every single discovery and patents being at UC as well? is this a regular pattern?

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