Appeal No. 2001-1580 Page 5 Application No. 08/955,090 The examiner concluded that [i]t would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the fusion proteins of Pastan et al. . . . by substituting for the cytokines disclosed therein the soluble flt3 ligand disclosed by Lyman et al. One of ordinary skill in the art would have been motivated to make circularly permuted forms of the soluble flt3 ligand disclosed by Lyman et al. by the disclosure of Pastan et al. that such circularly permuted proteins are expected to retain or have improved binding properties to the receptor to which they bind, as compared to the non- permuted forms. The particular termini recited in claim 1 are considered to be obvious in view of Hannum et al., which discloses . . . that such sites occur in regions between alpha helices, given that Pastan et al. teach that regions that do not show a highly regular three-dimensional structure are desirable for introducing the new termini to the circularly permuted protein. Id., page 6. Appellants argue that the examiner has not shown prima facie obviousness, because, inter alia, the cited references at best would have made the claimed invention “obvious to try.” See the Appeal Brief, pages 12-17. Appellants argue that the cited references would not have led those of skill in the art to reasonably expect that a circularly permuted flt3 ligand would retain the binding activity of the native ligand, much less have improved binding properties, because the record shows that circular permutation produces unpredictable effects. In support, Appellants refer to the prior art cited in the present specification (pages 3-7), which lists sixteen proteins which have been circularly permuted, and which concludes that [t]he results of these studies have been highly variable. In many cases substantially lower activity, solubility or thermodynamic stability were observed [listing seven proteins]. . . . In other cases, the sequence rearranged protein appeared to have many nearly identical properties as its natural counterpart [listing eightPage: Previous 1 2 3 4 5 6 7 8 9 10 11 NextLast modified: November 3, 2007