Addressing a decision out of the U.S. Patent and Trademark Office (PTO) Board of Patent Appeals and Interferences (Board), the U.S. Court of Appeals for the Federal Circuit affirmed the Board’s ruling that there was substantial evidence supporting a determination that a person of ordinary skill in the art would have a reasonable expectation of success when combining prior art references.    In re Droge et al., Case No. 11-1600 (Fed. Cir., Sept. 21, 2012) (Moore, J.).

Droge et al. filed an application having a representative independent claim directed to a “method of sequence specific recombination of DNA in a eukaryotic cell” and including steps of “providing said eukaryotic cell” and “providing to said cell a modified bacteriophage lambda integrase Int, wherein said modified Int is Int-h or Int-h/218 which induces sequence specific recombination through said attB and attP or attR and attL sequences.” 

The Board affirmed the rejection of the claim as obvious over a patent to Crouzet and an article by Christ and Droge, two of the three inventors of the instant application.  The Board found that Crouzet disclosed a method that used bacteriophage lambda and wild-type Int protein to insert foreign DNA into a host cell using the attB and attP recognition sites and that this method may be carried out in any type of cell host, whether eukaryotic or not.  Although the Board found that Crouzet did not disclose the use of modified integrases, it determined that the article by Christ and Droge teaches Int-h and Int-h/218 can function even in the absence of the integration host factor (IHF) that is absent in eukaryotic cells. 

In an attempt to rebut the assertion of obviousness, Droge supplied a declaration setting out reasons why a person of ordinary skill in the art would not have had a reasonable expectation of success in using the claimed modified integrases in eukaryotic cells.  However, the Board found that an article written by Lange-Gustafson et al. refuted the assertions made in the declaration, and thus found that the independent claim would have been obvious over Crouzet in view of the Christ and Droge article.

Droge challenged the Board’s decision, arguing that a person having ordinary skill in the art would not have had a reasonable expectation of success in combining the teachings of the references.  In particular, Droge argued that because the Christ and Droge article stated recombinant activity of the modified integrases decreases in the absence of IHF, which is present in prokaryotic but not in eukaryotic cells, that the Christ and Droge article teaches away from the claimed invention.  In addition, Droge argued that its declaration provided evidence that at the time of the invention, it was unclear whether the modified integrases would work in mammalian (eukaryotic) cells. 

Acknowledging that Droge did not dispute that the references, taken together, teach every limitation of the claimed method, the Federal Circuit found the Board’s determination to be supported by substantial evidence, holding that obviousness does not require absolute predictability of success, all that is required is a reasonable expectation of success.  The Court found that the Lange-Gustafson article directly contradicted Droge’s arguments because it stated that Int-h recombines DNA “identically” regardless of whether its three-dimensional structure is super coiled (prokaryotic DNA) or is topologically relaxed (eukaryotic DNA), and further found that the Christ and Droge article similarly stated that neither supercoiling nor IHF are necessary.