Loss of CRISPR Priority in Europe is a Warning to All Patent Applicants

On 17 January 2018, a panel of the European Patent Office (EPO) opposition division wholly revoked a patent co-owned by the Broad Institute (‘Broad’) relating to CRISPR/Cas9 ‘gene editing’ technology.  The European patent in question, number EP2771468, is entitled ‘Engineering of systems, methods and optimized guide compositions for sequence manipulation’, and is a European equivalent to US patent no. 8,906,616, which is one of the key Broad patents involved in the US patent interference dispute with the University of California (UC) – which is currently on appeal to the US Court of Appeals for the Federal Circuit.  As is usual with European opposition proceedings, the ruling was issued immediately at the hearing (which had originally been scheduled to continue for two further days).  A full written decision providing detailed reasons is likely to be a few weeks away.

Technically, the basis for revocation in the final decision is likely to be lack of novelty and/or inventive step of all claims of the Broad patent.  However, the underlying reason for Broad’s failure to defend its patent is a loss of priority.  In particular, the EPO panel determined that Broad was not entitled to claim priority from four of its earlier US provisional applications, including the earliest filing, US provisional application no. 61/736,527, which was filed on 12 December 2012.  This loss of priority was fatal to the patent, as a result of a number of publications – including Broad’s own – that occurred subsequently, but prior to the full application’s filing date of 12 December 2013.

While this decision is obviously pivotal in the ongoing disputes between Broad and UC over ownership of foundational patent rights relating to CRISPR/Cas9 technology, it also provides an object lesson and a timely reminder of essential requirements for valid priority claims for patent applicants around the world, in all fields of technology.  While the circumstances of Broad’s case are somewhat more complex than most patent filings, what has happened to it here is not at all specific to the particular invention at issue.  In a nutshell, the problem was that, at the time of filing international application no. PCT/US2013/074819 (from which the European patent is derived), the named applicants – Broad, MIT and Harvard – did not collectively own all of the rights necessary to claim priority from the earlier provisional applications.  More particularly, the provisional applications named a researcher from Rockefeller University as a co-inventor/applicant, yet neither the researcher nor Rockefeller was named as an applicant on the international application.  Nor had the named applicants received any assignment from Rockefeller of the right to claim priority in the international application.

In fairness to Broad, the US national law relating to ‘internal’ priority (i.e. claiming the benefit of a US provisional application in a subsequent non-provisional application) is less strict, and focusses on the substance of the invention actually claimed in the later application rather than on a distinct right of priority.  But this can hardly be an excuse for ignorance of the international position, especially when the stakes are so high.  Broad has issued a statement, arguing that the EPO decision is based on a technicality, and asserting that it is ‘inconsistent with treaties designed to harmonize the international patent process, including that of the United States and Europe’.  I disagree.  Not only is this not the first time that the EPO has applied these rules in relation to priority claims, but it is not the only adjudicating body to have determined that they are, in fact, required by the international treaties in question.

Broad has vowed to appeal.  In the meantime – and in anticipation of the likelihood that any appeal will fail – all international applicants would be well-advised to ensure that they are clear on the ownership of the right to priority at the time of filing.  At the end of this article, I set out some guidelines for avoiding the troubles that Broad has encountered, not only at the EPO but at any international patent office.

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Tags: CRISPR, Europe, International treaties, Paris Convention, Patent Cooperation Treaty, Priority claim

University of California Unsurprisingly Appeals Decision to Terminate CRISPR Patent Interference

In February, I reported the decision of the US Patent and Trademarks Office (USPTO) Patent Trial and Appeal Board (PTAB) in the patent interference proceedings initiated by the University of California (‘UC’) against the Broad Institute of MIT and Harvard (‘Broad’) in relation to CRISPR/Cas9 gene editing technology.  That decision was that there is ‘no interference in fact’, meaning that Broad’s development of the CRISPR/Cas9 system for use in eukaryotic cells (i.e. complex cells with, among other characteristics, distinct nuclei) was a non-obvious advance over UC’s development of the system for use in simpler prokaryotic cells (specifically, bacteria), and that there is thus scope for both parties to hold distinct patents.  At the time, I noted that the PTAB decision was subject to a possible appeal to a US Federal Court – most likely the specialised Court of Appeals for the Federal Circuit (CAFC) – and predicted that UC would file an appeal, in view of the substantial commercial interests at stake.

I am therefore not at all surprised to now be reporting that UC has indeed appealed to the CAFC.  In a press release announcing the appeal, UC has confirmed that it ‘seeks to have the PTAB reinstate the interference’, and quotes Edward Penhoet, a ‘special adviser on CRISPR to the UC president and UC Berkeley chancellor’ as saying that:

Ultimately, we expect to establish definitively that the team led by Jennifer Doudna and Emmanuelle Charpentier was the first to engineer CRISPR-Cas9 for use in all types of environments, including in non-cellular settings and within plant, animal and even human cells

Broad has responded with its own media statement saying, in relation to the appeal, that:

Given that the facts have not changed, we expect the outcome will once again be the same.
We are confident the Federal Circuit will affirm the PTAB decision and recognize the contribution of the Broad, MIT and Harvard in developing this transformative technology.

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Tags: Biotechnology, CRISPR, Genetic technology, Interference, US

USPTO Board Terminates CRISPR Patent Interference

On Wednesday 15 February 2017, the US Patent and Trademarks Office (USPTO) Patent Trial and Appeal Board (PTAB) handed down its much-anticipated decision in the patent interference proceedings initiated by the University of California (‘UC’) against the Broad Institute of MIT and Harvard (‘Broad’) in relation to CRISPR/Cas9 gene editing technology.  That decision, in short, is that there is ‘no interference in fact’.  That is to say, the three judges making up the PTAB panel have determined that Broad’s development of the CRISPR/Cas9 system for use in eukaryotic cells (i.e. complex cells with, among other characteristics, distinct nuclei) was a non-obvious advance over UC’s development of the system for use in simpler prokaryotic cells (specifically, bacteria), and that there is thus scope for both parties to hold distinct patents.

In its full decision [PDF, 412kB], the PTAB summarises its findings as follows:

Broad has persuaded us that the parties claim patentably distinct subject matter, rebutting the presumption created by declaration of this interference. Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment. Specifically, the evidence shows that the invention of such systems in eukaryotic cells would not have been obvious over the invention of CRISPR-Cas9 systems in any environment, including in prokaryotic cells or in vitro, because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment. This evidence shows that the parties’ claims do not interfere. Accordingly, we terminate the interference.

This is a considerable win for Broad which, subject to a potential appeal, has for now delivered a fatal blow to UC’s hopes of invalidating a number of Broad’s CRISPR-related patents and applications.  Unsurprisingly, Broad has reacted to the decision by declaring its full agreement with the PTAB, while UC maintains its belief that the evidence is on its side.  The stock market also reacted quickly to the news, adding US$200 million to the value of the Broad-connected biotech company Editas Medicine Inc.

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Tags: Biotechnology, CRISPR, Genetic technology, Interference, US

CRISPR Patent Interference Hearing – How to Define an ‘Invention’ and Why It Matters

On 6 December 2016, and for the first time since the University of California (‘UC’) first sought to provoke interference proceedings over CRISPR/Cas9 gene editing technology in April 2015, the parties in dispute over just who has the rightful claim to inventorship appeared at an oral hearing before three judges of the US Patent and Trademark Office (USPTO) Patent Trial and Appeal Board (PTAB).  Remarkably, considering the complexity of the scientific, technical and legal issues involved, UC and opposing claimant the Broad Institute of MIT and Harvard (‘Broad’) each had just 20 minutes to present its arguments, plus an optional five minutes for rebuttal of the other side’s submissions.  According to a journalist present at the hearing, it was all over in 45 minutes total.

It is important to understand, however, that while the judges’ decision here (which is expected within about two-to-three months) could put an end to the interference proceedings at the PTAB, the hearing was not actually about the ultimate question of who was first to invent the CRISPR technology at issue.  It was more about what each party may, or may not, have actually ‘invented’, and whether there is even any interference to be decided.

For any readers coming across this story for the first time, you could go back and read all of my articles on the topic (and the many good sources of information linked therein).  However, the key points may be briefly summarised as follows:

1. UC Berkeley Professor of Chemistry Jennifer Doudna and her collaborator Emmanuelle Charpentier were the lead researchers on a team that, in around 2012, developed CRISPR/Cas9 – a biotechnology system consisting of an engineered RNA and a ‘cutting’ protein that can be used for highly-targeted gene editing;
2. a US patent application is pending (serial no. 13/842,859), which is based on the UC team’s work and a series of filings beginning in May 2012;
3. the UC team’s original work related to the discovery of the CRISPR system in relatively simple bacterial cells (examples of ‘prokaryotes’, or simple cells without distinct nuclei), but in January 2013 they were successful in applying the technology to human cells (examples of ‘eukaryotes’, or more complex cells with, among other characteristics, distinct nuclei);
4. roughly in parallel, a team led by Feng Zhang at the Broad reported similar success using CRISPR to edit human genes;
5. a number of US patent applications were filed, beginning in December 2012, based upon the Broad team’s work (i.e. more than six months later than Doudna’s earliest filing);
6. the Broad requested prioritised examination under the USPTO’s Track One program and, as a result, was awarded the first patent on the basic CRISPR technology – US Patent No. 8,697,359, ‘CRISPR-Cas systems and methods for altering expression of gene products’, issued on 15 April 2015.

The UC applications, and the earliest Broad applications, were filed under the ‘old’ US system, according to which the applicant entitled to receive a patent is the first one to invent the claimed subject matter.  This differs from the ‘first-to-file’ priority system that has long existed throughout the rest of the world, and in the US since 16 March 2013.  Under the first-to-invent system, the administrative procedure used to determine who should receive a patent when there are competing claims is called an ‘interference’.

Therefore, the UC parties suggested that the USPTO should institute interference proceedings, in order to determine who is really entitled to own the patent rights to the CRISPR/Cas9 technology, which it did on 11 January 2016.  However, the purpose of the recent hearing was not to determine who was the first inventor, but rather to decide exactly what is the invention at issue, and whether the interference should proceed any further at all.

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Tags: Biotechnology, CRISPR, Genetic technology, Interference, US

CRISPR Patent Dispute – Is It Just Too Big to Settle?

The proceedings at the US Patent and Trademark Office (USPTO) Patent Trial and Appeal Board (PTAB), to determine who is entitled to foundational patent rights relating to CRISPR/Cas9 ‘gene editing’ technology, have been steadily progressing since my last update back in January.  As a reminder, the parties vying for ownership of these rights are a group led by Berkeley Professor of Chemistry Jennifer Doudna and her collaborator Emmanuelle Charpentier, and a group led by Feng Zhang at the Broad Institute, Inc and MIT.  Although a little reductive, it is convenient for me to refer to these two groups as ‘team Doudna’ and ‘team Zhang’ respectively. 

In a very recent development, on 11 April 2016, the ‘senior party’ in the proceedings (team Doudna) filed a notice stating that ‘in accordance with Standing Order ¶ 126, Senior Party hereby notifies the Board that the parties have discussed settlement, and have made a good faith effort to settle the interference, but no agreement has been reached at this time.’  It was necessary for the notice to be filed on or before this date, because the PTAB encourages parties to settle priority disputes between themselves where possible, and the referenced paragraph of the Standing Order in fact makes it compulsory for settlement discussions to be initiated by the ‘last named party’ (which, again, happens to be team Doudna in this case) within three months of an interference being declared.  The CRISPR interference was declared on 11 January 2016.

Interestingly, however, when the PTAB judges raised the matter of settlement discussions during a telephone conference on 10 March 2016, counsel for team Zhang stated that ‘we have not had that opportunity one way or the other to discuss settlement’ while counsel for team Doudna confirmed his understanding that ‘there has not been any formal discussions between the parties’.

So up until two months after the interference was officially declared there had been no discussions about a possible settlement.  Then, during the final month of the period for commencing mandatory discussions, suddenly ‘a good faith effort’ was made to settle the dispute, but no agreement was reached.  Pardon my cynicism, but if you believe that the timing of these events reflects a genuine effort at settlement, then perhaps I can interest you in the purchase of a nice bridge!  On the contrary, it seems pretty clear that at least team Doudna (whose obligation it was to initiate mandatory settlement discussions, and file the notice) has no desire to settle the interference.  In fact, it is quite likely that neither party has any real interest in settlement.

Although I have previously expressed the opinion that a settlement agreement may provide a better outcome for all concerned, I no longer believe that this is a viable option.  I now think it likely that the technology is just too valuable for either party to give ground, particularly at this early stage.  In all likelihood, these interference proceedings are going to run their full course.  Yes, they will be incredibly expensive, but the cost is just a drop in the ocean compared to what is at stake in the main game of commercialising CRISPR/Cas9 technology.

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Tags: Biotechnology, Commercialisation, CRISPR, Genetic technology, Interference, US

CRISPR Interference Update

Two weeks ago I wrote about the interference proceedings that have been instituted by the US Patent and Trademarks Office (USPTO) in order to determine who is rightfully entitled to fundamental patent rights in relation to CRISPR gene-editing technology, under the former ‘first-to-invent’ priority rules.  The contest is between a team led by Berkeley Professor of Chemistry Jennifer Doudna and her collaborator Emmanuelle Charpentier, and a team at the Broad Institute, Inc and MIT led by Feng Zhang.  In that article, I explained generally how interference proceedings work, the distinction between ‘senior’ and ‘junior’ parties in an interference, and what it means to be ‘first-to-invent’.

Kevin Noonan has now written about the CRISPR interference over at the Patent Docs blog.  Being both a US patent attorney, and having a background in molecular biology, Kevin is far better qualified than I to write about this topic!  Obviously, therefore, you should read his article in full, if this subject is of particular interest to you. 

I was also recently contacted by Lee McGuire, who is the Chief Communications Officer at the Broad Institute, drawing my attention to a CRISPR IP information page that is being maintained on the Broad’s website.  You will appreciate, of course, that this is not a source of unbiased information.  It is, however, a useful resource with a lot of interesting content and links covering the CRISPR ‘story’ from Broad’s perspective.  As far as I have been able to determine, Berkeley is not (at this stage) providing any similar resource.

So, what will you learn if you take the time to read these additional sources?

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Tags: Biotechnology, CRISPR, Genetic technology, Interference, US

Who Will Get the CRISPR Patent?

As has been widely reported, the US Patent and Trademark Office (USPTO) has instituted interference proceedings to determine who is entitled to own foundational patent rights in relation to CRISPR/Cas9 ‘gene editing’ technology.  I wrote about this brewing dispute back in July 2015, when I predicted that this would be ‘the last great US patent interference’, given that the US patent system changed from first-to-invent to first-inventor-to-file on 16 March 2013. 

As the number of applications filed under the former first-to-invent system dwindles, the opportunities for new interference proceedings – which are all about figuring out who invented first when separate applications with competing claims are filed – are becoming scarce.  Even less likely is another interference over a genuinely groundbreaking and immensely valuable invention.

For the full story, you should really go back and read my earlier article.  But if you lack the time or stamina, here is the TL;DR recap:

1. Berkeley Professor of Chemistry Jennifer Doudna and her collaborator Emmanuelle Charpentier were the lead researchers on a team that, in around 2012, developed so-called CRISPR/Cas9 – a biotechnology system consisting of an engineered RNA and a ‘cutting’ protein that can be used for highly-targeted gene editing;
2. Doudna, Charpentier and their co-workers have a US patent application pending (serial no. 13/842,859), which is based on a series of filings beginning in May 2012;
3. Doudna and Charpentier’s original work related to the discovery of the CRISPR system in relatively simple bacterial cells, but in January 2013 they were successful in applying the technology to human cells;
4. roughly in parallel, however, a team led by Feng Zhang at the Broad Institute, Inc and MIT reported similar success using CRISPR to edit human genes;
5. Zhang and his team also filed a US patent application, based on a series of their own filings beginning in December 2012 (i.e. more than six months later than Doudna’s earliest filing);
6. to complicate matters, Zhang requested prioritised examination under the USPTO’s Track One program and, as a result, was awarded the first patent on the basic CRISPR technology – US Patent No. 8,697,359, ‘CRISPR-Cas systems and methods for altering expression of gene products’, issued on 15 April 2015, even though Doudna’s group had been the first-to-file;
7. Doundna and Charpentier subsequently requested the USPTO to institute interference proceedings, in order to determine who is really entitled to own the patent rights to the CRISPR/Cas9 technology.

That request has now been granted.  So who will get the CRISPR patent?  Well, if I knew that I could save the USPTO a whole lot of work, and the parties a great deal of time and money.  Ultimately, only time and the evidence will tell.  But what I can do is to outline the basics of interference proceedings, and make a few tentative predictions.

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Tags: Biotechnology, CRISPR, Genetic technology, Interference, US