On September 21, 2012, the Federal Circuit affirmed a Board of Patent Appeals and Interferences (BPAI) decision that the claims of U.S. Patent Application No. 10/082,772 (’772 application) was obvious over the prior art. The decision relates to an obviousness rejection that reaffirms the “reasonable expectation of success” standard in combining references, as well as the need for patent practitioners to objectively determine the state of the art.
The ’772 application is directed to methods and compositions for recombining DNA in a eukaryotic cell. In particular, the ’772 patent relates to making DNA molecules via sequence-specific recombination with enzymes involved in the lysogenic lifecycle of bacteriophage lambda. Basically, bacteriophage lambda either infects a bacterial cell, replicates and ultimately lyses the cell concurrently with the release of bacteriophage particles (lytic phase) or integrates into the bacterial chromosome (lysogenic phase) until a stimulus triggers the lytic phase.
The ’772 claims relate to the ezymes involved in lysogeny. Specifically, the DNA sequences that are recognized by bacteriophage enzymes (specifically, integrases) involved integrating bacteriophage DNA into bacterial DNA. Representative claim 29 of the ’772 application relates to a method of sequence-specific recombination of DNA in a eukaryotic cell comprising providing a eukaryotic cell with a DNA sequence recognized by an integrase, introducing a DNA segment and providing a mutant integrase.
The cited prior art includes a primary reference that discloses methods of making therapeutic DNA molecules using sequence-specific recombination either in a host cell or in vitro and that specifically disclosed embodiments using bacteriophage lambda and wild-type integrase for integration of exogenous DNA into a mammalian host cell using integrase recognition sites. The primary reference did not disclose the mutant integrase of the ’772 claims.
The secondary reference disclosed that the mutant integrases of the ’772 claims were active in prokaryotic (such as bacterial cells). The applicants of the ’772 application conceded that both the primary and secondary references disclosed the elements of the claims; however, the applicants argued that a person skilled in the art would not have had a reasonable expectation of success that the mutant enzymes that worked in prokaryotic cells would also work in eukaryotic cells and thus their claims were non-obvious. The assertion was supported in a declaration, but the allegations were rebutted by other references.
The Federal Circuit recognized that the question was whether a person skilled in the art would have had a reasonable expectation of success in substituting the wild-type integrase disclosed in the primary reference with the mutant integrases disclosed in the secondary reference for sequence-specific integration of exogenous DNA into eukaryotic chromosomal DNA. The Federal Circuit found substantial evidence that a person skilled in the art would have had a reasonable expectation of success when combining the references. Furthermore, the references that directly rebut the assertion in the applicants’ declaration were also considered by the court. The Federal Circuit also reiterated that absolute predictability was not the standard for obviousness and “all that is required is a reasonable expectation of success.” In re Kubin , 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O’Farrell , 853 F.2d 894, 903-04 (Fed. Cir. 1988)).
It seems that both the Federal Circuit and the BPAI consider a person skilled in the art to be an expert in DNA recombination. Furthermore, it seems the Federal Circuit and the BPAI also consider the state of the art of DNA recombination to be quite high. Thus, it is important for patent practitioners to work with patent applicants to objectively ascertain the state of the art.