Appeal No. 2001-1580 Page 8
Application No. 08/955,090
Pseudomonas exotoxin). Pastan provides additional prophetic examples, but no
further evidence to support the position that, for all proteins, circular permutation
would be expected to result in “circularly permuted ligands which possess
specificity and binding affinity comparable to or greater than the specificity and
binding affinity of the native (unpermuted) ligand.”
On the other hand, the present specification provides evidence that the
effect of circular permutation is unpredictable. The specification lists sixteen
examples of proteins in which circular permutation has been attempted. See
pages 4-6. These examples include the IL-4-Pseudomonas exotoxin fusion
protein exemplified by Pastan. Page 6, lines 15-18. The specification notes that
Pastan’s fusion protein was one of only two examples in which circular
permutation resulted in a protein having improved properties compared to the
native protein. See page 6, line 32 to page 7, line 2. In the vast majority of
cases, the best result that could be expected from circular permutation was that
the permuted protein would behave basically the same as the native protein.
And, in many cases, “substantially lower activity, solubility or thermodynamic
stability were observed.” Specification, page 6, lines 21-22.
While structural similarity is enough, in some cases, to show prima facie
obviousness, in such cases, the claimed and known compounds share a
similarity of structure that provides an expectation that the compounds will also
share similar properties. That is, the structural similarity itself would provide
motivation to modify the known compound with a reasonable expectation of
producing a similar compound having similar properties. See In re Payne, 606
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