Appeal No. 2003-0395 Page 4
Application No. 09/374,704
group” required by the claims on appeal.
Feng describes the structure of the 52-amino acid DNA-binding domain of the
prokaryotic Hin recombinase, which binds to the hixL and hixR sites on the Salmonella
chromosome, catalyzing a site-specific DNA recombination reaction. The binding
domain of Hin “consists of a compact bundle of three "-helices, with [an] extended
amino-terminal arm and [a] carboxyl-terminal tail. "-Helix 1 [ ] lies parallel to the axis of
the DNA, "-helix 2 [ ] is nearly antiparallel to helix 1 . . . and "-helix 3 [ ] is inserted in
the major DNA groove parallel to the base pairs . . . The HTH [helix-turn-helix] motif
formed by helices 2 and 3 is similar to those found in other prokaryotic regulatory DNA-
binding proteins” (page 350, left-hand column). According to Feng, “"-helix 3 is the
DNA recognition helix for the Hin protein” (id.), but the six carboxy-terminal amino acids
(Ile185-Lys186-Lys187-Arg188-Met189-Asn190) also interact with the minor groove of hixL and
hixR (pages 351-352); as do four residues on the amino terminal arm (Gly139-Arg140-
Pro141-Arg142) (page 351). Among other things, Feng notes that “contacts made by the
amino-terminal arm of the Hin DNA-binding domain are at least as critical to DNA
recognition as those of helix 3” since “merely deleting Gly139 and Arg140 from the Hin
DNA-binding peptide is sufficient to abolish specificity of binding to hixL” (page 351). As
Feng summarizes it, “the recognition element of the [hixL and hixR sites] appears to
involve two A•T base pairs [ ] recognized by amino acid residues Gly139 and Arg140 in the
minor groove, two non-specific base pairs [ ], and then a five base sequence [ ]
recognized by helix 3 and the carboxyl-terminal tail in major and minor grooves,
respectively” (page 354, center column).
According to the examiner, it would have been obvious to modify the polyamides
described by Swalley, Parks and Trauger “with a sequence comprising Arg-Pro-Arg,
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