University of California/Berkeley Appeals Adverse CRISPR Decision by PTAB

By Kevin E. Noonan --

In February, the Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office rendered judgment that there was no interference-in-fact between the claims in interference between the Regents of the University of California/Berkeley and the Broad Institute.  Yesterday, UC/Berkeley filed a Notice of Appeal at the Federal Circuit, challenging the PTO's decision.

The University's position is set out in a press release posted on-line saying that "[u]ltimately, 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," according to their spokesman, Edward Penhoet, associate dean of biology at Berkeley, professor emeritus of molecular and cell biology, and a special adviser on CRISPR to the University of California president and Berkeley chancellor.  The press release also states that the University will continue to pursue related applications both in the U.S. and abroad, for "CRISPR-Cas9 technology and its application in non-cellular and cellular settings, including eukaryotic cells."  Recently, the European Patent Office announced its intention to grant the University an EP patent on May 10, 2017.

Former Solicitor General Don Verrilli will be lead counsel for the University.

For its part, the Broad also issued a press release setting forth its position:

UCB has filed a Notice of Appeal asking the United States Court of Appeals for the Federal Circuit, based in Washington DC, to review the recent decision by the PTAB (Patent Trial and Appeals Board) that there is no interference between the Broad Institute, MIT and Harvard claims concerning the use of the CRISPR system in eukaryotic cells and the patent application of UCB because the claims are patentably distinct.

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.

Importantly, the Federal Circuit does not independently weigh the facts determined by the PTAB.  To overturn the PTAB decision, the Court would need to decide that the PTAB committed an error of law or lacked substantial evidence to reach its decision.  Given the careful and extensive factual findings in the PTAB's decision, this seems unlikely.

Regardless of the likelihood that the PTAB's decision might be reversed, the matter will not be resolved even if the Federal Circuit sends the case back to the Board.  The Office determined only that there was no interference-in-fact between the parties' claims-in-interference (see "PTAB Decides CRISPR Interference in Favor of Broad Institute -- Their Reasoning"), not the substantive questions of priority and patentability raised by the parties in their preliminary motions.  The PTAB's reasoning was based on the University's failure to establish that the Broad's claims would have been obvious in view of the University's application, because inter alia the University had not established that there would have been a reasonable expectation of success that the CRISPR technology would be effective in eukaryotic cells in view of the University's disclosure of the technology's use in prokaryotic cells.  The Federal Circuit's review of this question under Dickinson v. Zurko would be to give the PTAB's factual determinations deference under the substantial evidence standard, and to review de novo the ultimate legal question of obviousness.

Should the University prevail, the case would be remanded to the PTAB for further proceedings.  These would include a determination of which group of inventors had priority (where the Broad is junior party and would bear the burden of establishing earlier invention).  Any further PTAB action should also include rendering decisions on several motions submitted by both parties (see "CRISPR Interference Motions Set").

Should the University's appeal fail, however the status quo will remain:  the Broad will maintain its extensive CRISPR patent portfolio and the University's patent application (reciting claims broader than the Broad's and encompassing CRISPR without regard to the cells in which it is practiced) should grant as a patent in due course.  Under these circumstances a third party wishing to practice the technology in eukaryotic cells (encompassing everything from yeast to man) would need a license from both the University and the Broad (absent the parties coming to an agreement on how their overlapping technologies will be licensed).  This circumstance cannot fail to retard commercial adoption of the techniques, providing further impetus for some sort of settlement to be forged.

For additional information regarding this topic, please see:

• "PTAB Decides CRISPR Interference in Favor of Broad Institute -- Their Reasoning," February 16, 2017
• "PTAB Decides CRISPR Interference -- No interference-in-fact," February 15, 2017
• "Guest Post -- The Patient Side of the CRISPR Patent Battle," December 19, 2016
• "CRISPR Interference Motions Set," March 23, 2016
• "CRISPR Interference Declared," January 28, 2016

Comments

[skeptical]

Is this a part of the "magic" of "directed to"...?

Did not the AIA incorporate the "not DIRECTED TO" human limitation that CRISPR violates?

[ScottE]

Kevin-Do you think the UC patent claims, if granted, will be susceptible to a reverse doctrine of equivalents argument if and when they are applied to eukaryotic cells? Does lack of a reasonable expectation that this process would work in eukaryotic cells warrant the application of this doctrine to limit the effective scope of UC's claims?

[Paul F. Morgan]

Kevin, you hit the nail on the head with "To overturn the PTAB decision, the Court would need to decide that the PTAB committed an error of law or lacked substantial evidence to reach its decision. Given the careful and extensive factual findings in the PTAB's decision, this seems unlikely."
Furthermore, the Fed. Cir. must be aware that if it were to overturn a no-interference-in-fact determination it would just get an even bigger mess back on appeal after the interference.
Furthermore, this has no effect on the equivalent patents in other countries, which do not have interference proceeding exceptions to first to file.

[Paul F. Morgan]

P.S. Furthermore, modern interferences [maybe as many as 100? left after their slow death from the AIA] are quite often decided on unpatentabilty before even dealing with invention priority.

[Kevin E. Noonan]

ScottE: I was just discussing the reverse doctrine the other day, and here is a quote from Roche v. Apotex (Fed. Cir. 2008):

"The reverse doctrine of equivalents is rarely applied, and this court has never affirmed a finding of non-infringement under the reverse doctrine of equivalents."

I think it more likely that an accused infringer, armed with a license from the Broad, would argue that Berkley's patents would be invalid under Sec. 112 if construed to encompass mammalian cells, because it would have been undue experimentation to apply the technology due to the unpredictability of the art, lack of examples in UC's specification, and undue breadth of the claims.

But r-DOE is a creative argument so it may be in an accused infringer's arsenal.

Thanks for the comment.

[ScottE]

Kevin-Thanks for the response. I agree that a 112 argument may be more likely to win the day, but r-DOE is consistent with this and may be used as a back-up. This fact pattern reminds me of the 1999 Enzo v. Calgene decision in which claims generically covering antisense inhibition of gene expression in all cell types but supported only by evidence of inhibition in E. coli were ruled invalid and not enabled.

[Paul F. Morgan]

P.P.S. For pre-AIA-patents proof of 102(g) prior invention may also be available as a prior art defense to a patent suit, so prior invention assertions here may well arise later in spite of no interference here and with other parties.

[Lawrence Ebert]

As to reverse DOE, was Medicines v. Mylan, in effect, a reverse doctrine of equivalents case?

[Kevin E Noonan]

Lawrence: not at the Federal Circuit (http://www.patentdocs.org/2017/04/the-medicines-company-v-mylan-inc-fed-cir-2017.html) or the district court (The Medicines Co. v. Mylan Inc., Civ. No. 1:11-cv-1285, 2014 U.S. Dist. LEXIS 152433 (N.D. Ill. Oct. 27, 2014) (St. Eve, J.)) but I haven't dug any deeper. Let me know if you come up with something and we can discuss

[Lawrence Ebert]

In Medicines, the CAFC read the limitations of an example into a claim term; whether this was justified is open to question. From Alloc:

**
In this respect, this court looks to whether the specification refers to a limitation only as a part of less than all possible embodiments or whether the specification read as a whole suggests that the very character of the invention requires the limitation be a part of every embodiment. For example, it is impermissible to read the one and only disclosed embodiment into a claim without other indicia that the patentee so intended to limit the invention. Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1327 (Fed. Cir. 2002). On the other hand, where the specification makes clear at various points that the claimed invention is narrower than the claim language might imply, it is entirely permissible and proper to limit the claims. SciMed Life Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d 1337, 1345 (Fed. Cir. 2001).

**

In Medicines, there were no indicia that Medicines intended to limit; in fact, quite the opposite.

Apart from the language of the decision, it might appear that the rationale for the decision was that the accused infringer operated in a way distinct from that disclosed by patentee, even though the accused infringer's acts did fall within the literal scope of the claim (which may in fact have been invalid as written). As to noninfringement, this sounds like reverse doctrine of equivalents, as described in Graver Tank, even if not labelled as such.

[Page Korben]

The decisive lack of "Reasonable Expectation of Success" finding whereby inventive skill would have been required to transition the disclosed Doudna CRISPR technology platform from prokaryotes (e.g. bacteria) to eukaryotes (e.g. mammalian cells) seems doubtful when considering the course of the scientific literature that parallels the numerous patent filings.

The technical aspects of Doudna's CRISPR discoveries are embodied in a Science article (Jinek et al) e-published on June 28, 2012.

The BROAD/MIT group filed their "eukaryotic" CRISPR application on December 12, 2012. The counterpart scientific paper was published on January 3, 2013 (Cong et al).

To my knowledge, Science requires a peer review process prior to publication, usually requiring 1-2 months.

Consequently, the incredibly quick turnaround from Jinek to Cong, where Zhang managed to develop and execute extensive lab protocols that produced new, verifiable results in just a matter of weeks suggests that Doudna's findings indeed provided Zhang with a RES that the eukaryotic system would be amenable in supporting Doudna's CRISPR platform, as Doudna suggests in the Jinek article.

This, especially since Zhang merely applied known technologies (NLS sequences, used since the 1980s) in order to guide the CRISPR system into the eukaryotic cell compartments.

Accordingly, it is apparent that the PTAB might have erred in their findings by being dismissive of the science itself.

[Lawrence Ebert]

For completeness, the 2012 Jinek paper was discussed in the interference proceedings related to US 8,945,839. At page 14 of the interference decision, PTAB notes that Jinek said in 2013 that it was not known whether such bacterial system would function in eukaryotic cells. Page 15 includes similar expressions of doubt made by Doudna after Jinek 2012. Page 17 illustrates a strategic error by the UC lawyers, who argued that Jinek and Doudna were not workers of ordinary skill, which PTAB turned on its head in observing that if extraordinary workers manifested doubt, there would be LESS expectation of success for those of ORDINARY skill. The immediacy of later success (argued by Korben) is discussed on page 23, and analysis is made in the next 23 pages. Not clear that PTAB was being dismissive of the science.

As to the 2012 Jinek work, recall also the Zhang work was already patented over Jinek. See for example the 2015 post on IPBiz:
CRISPR is high profile in science, patents; competitor labeled a mere second comer