Yoshiya Nakamura | January 22, 2014
Institute Pasteur v. Focarino (Fed. Cir. 2013)
Decided December 30, 2013
Before NEWMAN, CLEVENGER, and TARANTO, Circuit Judges. TARANTO, Circuit Judge.
Key Words: non-obviousness, biotechnology, enzyme, reasonable expectation of success
Institute Pasteur (Pasteur) owned patents claiming inventions related to a group of enzymes, i.e., Group I intron-encoded (GIIE) endonucleases. The enzymes are useful as laboratory tools to cut a DNA sequence at a particular site of the sequence in vitro or in situ. In reexamination of the patents, the Board of Appeals rejected the claims as being obvious over cited references. Pasteur appealed to the CAFC. The CAFC vacated the Board decision and remanded for consideration of what would constitute motivation for one skilled in the art to pursue the claimed invention because the Board misread the teachings in prior art and failed to weigh properly substantive evidence of non-obviousness.
1. Patented claims
Three patents were at issue in this case. Representative claims are claims 1 and 10 from U.S.P. 6,610,545 (’545 patent):
Claim 7: A method for in vivo site directed genetic recombination in an organism comprising:
(a) providing a transgenic cell having at least one Group I intron encoded endonuclease recognition site inserted at a unique location in a chromosome;
(b) providing an expression vector that expresses said endonuclease in said transgenic cell;
(c) providing a plasmid comprising a gene of interest and a DNA sequence homologous to the sequence of the chromosome, allowing homologous recombination;
(d) transfecting said transgenic cell with said plasmid of step (c);
(e) expressing said endonuclease from said expression vector in said cell; and
(f) cleaving said at least one Group I intron encoded endonuclease recognition site with said endonuclease, whereby said cleavage promotes the insertion of said gene of interest into said chromosome of said organism at a specific site by homologous recombination.
Claim 10: The method of claim 7, wherein said organism is yeast.
The patented invention was made based on Pasteur’s discovery that when a small artificial DNA molecule (a vector) designed to express the GIIE endonucleases and a foreign DNA with specific sites to be cleaved are introduced in a living cell, the enzyme successfully cleaves the vector at the sites and the foreign DNA is inserted into the chromosomes of the cell. This technique is particularly useful to design a method to introduce a foreign DNA into the chromosomes in a living eukaryotic cell such as yeast.
2. PTO’s Decision
The primary prior art references disclosed a general method using the GIIE endonuclease in bacterial (prokaryotic) cells, but was silent about an application of the method to chromosomal DNA of a eukaryotic cell such as yeast. The Board then relied on other references, Frey and Dujon, and found a reasonable expectation of success to use the gene transferring with GIIE endonuclease in yeast so as to achieve the claimed invention because the references disclose cleavage of chromosomal DNA with such enzyme expressed in yeast cells.
3. CAFC’s Decision
The CAFC framed the issues as:
– whether the Board properly determined that there was a reasonable expectation of success to apply the gene transfer technique with GIIE endonucleases known for prokaryotic cells (which lack chromosomes) to a gene transferring into the chromosomes in eukaryotic cells; and
– whether “the Board gave proper consideration to at least two categories of evidence–(1) teachings in the prior art that targeting a cell’s chromosomal DNA could be toxic to the cell and (2) industry praise and licensing of Pasteur’s invention– that are important to the obviousness evaluation.” Then, the CAFC held that the factual determinations made by the Board were not supported by substantial evidence.
Regarding the interpretation of the prior art, the CAFC found that the Board misread the cited references as disclosing “GIIE endonuclease cleaving yeast chromosomes while those chromosomes are in yeast cells,” even though the references disclose “only that a GIIE endonuclease could cleave yeast chromosomes extracted from yeast cells.”
The CAFC found that the Board had ignored teachings in another prior art reference that “targeting a GIIE endonuclease to chromosomal DNA in a living cell could be highly toxic to the cell” and that “such a teaching counts significantly against finding a motivation to take the claimed steps with a reasonable expectation of success.” One of the Board’s arguments was that there was another prior art reference showing an interest in introducing copies of a chosen gene in situ within the chromosomes of a living animal cell.” However, the CAFC weighed the teaching of toxicity that “would bear heavily on whether a skilled artisan would have a reasonable expectation of success in achieving that objective.” Citing one of the KSR questions regarding “a design need or market pressure to solve a problem” and “identified, predictable solutions,” the CAFC stated:
In short, the prior art 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. Importantly, without a sound explanation for doing otherwise, which is not present here, the expectation-of-success analysis must match the highly desired goal, not switch to a different goal that may be a less challenging but also less worth- while pursuit.
Regarding this objective evidence, the CAFC found that “Pasteur’s licensing activities provide ‘probative and cogent evidence’ of non-obviousness of the claims at issue,” but “[t]he Board did not properly weigh this evidence.” The CAFC also recognized industry praise of Pasteur’s invention. After the publication of Pasteur’s method, many scientists followed the same method, while the CAFC added that the evidence would only support the non-obviousness conclusion decided here independently of such evidence.
Where, as here, there is strong evidence of non-obviousness it overcomes a weak prima facie obviousness in the absence of contradicting evidence. In the field of biotech engineering, the mere fact that ultimate goals have been known cannot be a per se reason that a claimed invention is obvious, although most of such goals or directions would have appeared in the art.