Appeal 2007-2956
Application 10/677,733
For example, heme binding by the PAS domains of FixL . . . allows bacteria
to sense oxygen levels” (Spec. 1). “However, for most PAS domains there
is no evidence for such a cofactor. In fact, structurally characterized PAS
domains without bound cofactors (Amezcua et al., 2002; Erbel et al., 2003;
Morais Cabral et al., 1998) show tightly packed cores with no pre-formed
cavities that would suggest a cofactor or ligand binding site” (Spec. 2).
According to the Specification, “the invention provides methods of detecting
binding of a PAS domain with a foreign core ligand of the PAS domain,
wherein the PAS domain is predetermined, prefolded in its native state, and
comprises a hydrophobic core that has no NMR-apparent a priori formed
ligand cavity” (Spec. 2).
Claims 1 and 2 are pending (App. Br. 1). Claim 1 is rejected under 35
U.S.C. § 103 as obvious over Fesik (WO 97/18471, May 27, 1997) in view
of Edery (US 5,843,683, Dec. 1, 1998), Takahaski (US 6,291,429 B1, Sep.
18, 2001), or Berkenstam (US 6,436,654 B1, Aug. 20, 2002) (Answer 3).
Claim 2 is objected to because it is dependent on rejected claim 1, but the
Examiner states it would be allowed if rewritten in independent form
(Answer 3). Claim 1 reads as follows:
1. A method of detecting binding of a PAS (Per-ARNT-Sim)
domain with a foreign core ligand of the PAS domain, wherein
the PAS domain is predetermined, prefolded in its native state,
and comprises a hydrophobic core that has no NMR-apparent a
priori formed ligand cavity, the method comprising the steps of:
detecting a first NMR spectrum of the PAS domain in the
presence of a foreign ligand; and
comparing the first NMR spectrum with a second NMR
spectrum of the PAS domain in the absence of the ligand to
infer the presence of the ligand specifically bound within the
hydrophobic core of the PAS domain.
2
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