Appeal No. 1996-1085 Application No. 08/097,621 U.S. 1052 (1987). The initial burden of presenting a prima facie case of obviousness rests on the examiner. In re Oetiker, 977 F.2d 1443, 1445, 24 USPQ2d 1443, 1444 (Fed. Cir. 1992). The combination of Bowden and Gilbert: The examiner applies Bowden (Answer, page 4) to teach “‘the permeability of the outer membrane of E. coli … the redox potential, pH, and ionic composition of the periplasmic space varies [sic] depending on the extracellular environment.’” The examiner then applies Gilbert (Answer, page 4) to teach “protein conformation is in part dependent on the thiol-disulfide redox state of the immediate environment.” From these teachings, the examiner reasons (Answer, page 5) that given the teachings of Bowden and Gilbert it “would have been obvious to one of ordinary skill in the art to use oxidizing thiol-reagents (i[.]e. GSH and GSSH) in the extracellular environment (i[.]e. the culture medium) to alter the redox potential of the periplasmic space, thus optimizing the conditions for correct folding of secreted proteins.” We note that neither Bowden nor Gilbert teach the addition of thiol-reagents to culture medium to adjust the redox potential of the periplasmic space. Further, assuming arguendo that the prior art suggested adding a thiol-reagent to the culture medium, the examiner has not identified, and we do not find, where the prior art discloses or suggests that the external membrane of the E. coli cell is sufficiently permeable to provide a sufficient amount of the thiol reagent in its periplasmic space. It is well established that to establish a prima facie case of obviousness, there must be both (1) a suggestion or motivation to modify the references or 4Page: Previous 1 2 3 4 5 6 7 NextLast modified: November 3, 2007