Sunday, April 23, 2017

Was the CRISPR interference outcome foreseeable?

A comment about the CRISPR patent interference battle appeared on Patent Docs on 20 April 2017:

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.


More than two years earlier, in a post in March 2015, IPBiz noted that the USPTO had passed the patent application of Zhang et al. to allowance over Jinek, which made the outcome of the interference foreseeable [i.e., Zhang work NOT obvious over that of Jinek and Doudna):

** US 8,945,839 issued on February 3, 2015. A "Track I" request had been made on 18 April 2014. A final rejection was issued on 18 Nov. 2014, with claims 1-28 rejected as anticipated over Jinek, WO'772 (later identified as Doudna). There was an issue of whether or not the priority documents to WO 2013/176772 supported the later disclosure. In this, there was an issue that the patent applicant had presented only arguments of counsel, with the examiner citing to In re Huang, 100 F.3d 136, 139 (CAFC 1996 ) and In re De Blauwe, 736 F.2d 699, 705 (CAFC 1984 ). Applicant brought up arguments made to the EPO about a Jinek journal publication, which were not of interest to the USPTO.
In a response filed 1 Dec. 2014, applicant was especially harsh to the Doudna application: "Doudna is nothing more than a mere 'second comer' and had no CRISPR-Cas invention prior to Feng Zhang."


CRISPR is high profile in science, patents; competitor labeled a mere second comer

Also, in an evaluation of patentability of Zhang's claims, the full scope of disclosure of the Jinek/Doudna reference was considered, but in an interference one compares only the claims. It was unlikely that the PTO would have altered its position of Doudna v. Zhang in the later (interference) proceeding. Whether this was the correct scientific outcome can be debated.

UPDATE on 28 April 2017:

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


As to the text -- that CRISPR basically uses the same process for viruses and eukaryotic cells, --, CRISPR-Cas systems protect prokaryotes FROM viruses. The legal determination of "no interference-in-fact" stemmed from the conclusion that Zhang's claims were patentable over Doudna's because one of ordinary skill did not have a reasonable expectation of success in going from Doudna's prokaryotes to Zhang's eukaryotes. Supporting facts arose from statements made by Jinek and Doudna expressing doubt about the transition. As to the future of UC's patent claims, there may be some issues as to enablement of the full scope of the claims, especially in light of BOTH the issuance of the Zhang patent AND the interference result.


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