Negation of Motivation To Combine Defeats Obviousness - Institut Pasteur & Universite Pierre Et Marie Curie v. Focarino

by McDermott Will & Emery

Addressing a finding of obviousness by the U.S. Patent and Trademark Office Board of Patent Appeals and Interferences (now the Patent Trial and Appeal Board) (Board) following inter partes reexamination, the U.S. Court of Appeals for the Federal Circuit reversed the Board’s finding, determining that the Board had failed to give proper consideration to clear teachings of both negative and positive prior art in determining if a person of ordinary skill in the art would have reasonably expected to succeed in achieving what was claimed.  Institut Pasteur & Universite Pierre Et Marie Curie v. Focarino, Case No. 12-1485 (Fed. Cir., Dec. 30, 2013) (Taranto, C.J.).

Pasteur’s claims were directed to a method of targeted gene transfer into the chromosomal DNA of eukaryotic cells.  The claims resulted from Pasteur’s discovery of a class of enzymes -group I intron-encoded (GIIE) endonucleases-that were capable of cleaving chromosomal DNA at specific recognition sites.  The broken DNA could be repaired by the cell’s own DNA repair mechanism known as homologous recombination so long as a template DNA with two regions homologous to either side of the break was available to the cell.  Pasteur had established that by supplying a live eukaryotic cell with a GIIE endonuclease and a plasmid carrying a template DNA, it could successfully transfer a new piece of DNA from the plasmid to the cell’s chromosome. 

During inter partes reexamination, Pasteur’s claims were rejected as obvious over Quirk and Bell-Pedersen prior art references that disclosed using a GIIE endonuclease to transfer DNA from plasmid to a non-chromosomal DNA in bacterial (i.e., prokaryotic) cells.  In affirming this rejection, the Board relied on two other references Frey and Dujon and characterized both as disclosing cleavage of chromosomal DNA in yeast (i.e., eukaryotic) cells using a GIIE endonuclease.  The Board ignored a sole negative prior-art reference teaching that targeting a GIIE endonuclease to chromosomal DNA in a living cell could be highly toxic to the cell, which might not be able to repair double-stranded breaks in the chromosome using homologous recombination.  Instead, the Board relied on the interest stated by the prior art reference Old, which stated “[i]t would be a great advance if such alterations could be engineered into copies of a chosen gene in situ within the chromosomes of a living animal cell.”  The Board concluded that “one of ordinary skill in the art [had] a reasonable expectation that the teachings of Quirk and Bell-Pedersen could be successfully applied to [chromosomal DNA in] yeast cells.”

The Federal Circuit reversed the Board, concluding that the Board’s decision was based on factual findings unsupported by substantial evidence.  The Court stated that the key issue in this case was whether the relevant skilled artisan, after reading Quirk’s and Bell-Pedersen’s disclosure that a GIIE endonuclease can promote targeted gene transfer into non-chromosomal DNA in prokaryotic cells, would have expected that a GIIE endonuclease would successfully promote targeted gene transfer into the chromosomal DNA of eukaryotic cells, and thus had good reason to pursue that possibility.

The Federal Circuit reasoned that neither of Frey and Dujon disclosed a GIIE endonuclease cleaving yeast chromosomes while those chromosomes were in yeast cells.  Frey taught cleaving extracted chromosomes.  Dujon was silent about what type of DNA was cleaved in yeast.  It taught GIIE when expressed in yeast could cleave DNA within the nucleus.  Moreover, the Court criticized the Board for ignoring the negative prior art teachings that targeting a GIIE endonuclease to chromosomal DNA in a living cell could be highly toxic to the cell and for not offering any reason at all that a skilled artisan would have pursued a method that was toxic to cells.  Instead, the Federal Circuit reasoned that such a negative teaching counts significantly against finding a motivation to take the claimed steps with a reasonable expectation of success. 

The Federal Circuit stated that the prior art presented in this case, at best, confirmed the great potential payoff of a method that produced a particular result.  The desire for that payoff could motivate pursuit of the method, but “knowledge of the goal does not render its achievement obvious,” and obviousness generally requires that a skilled artisan have reasonably expected success in achieving that goal, which was not present here.  Thus, the Court reversed the Board’s decision in favor of Pasteur.

Practice Note:  The Court had previously established that the reasonable-expectation-of-success test requires a skilled artisan to be “motivated to do more than merely to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful [In re O’Farrell].”  This decision further shows that negative references that negate motivation can be used in favor of non-obviousness via the reasonable-expectation-of-success test.

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

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