Appeal No. 2005-2207 Page 3
Application No. 09/548,933
existence of a family of hyperpolarization-activated cation channels” (id., page 587),
“members of which are characterized by six membrane-spanning segments (S1-S6),
including a voltage-sensing S4 segment, and an ion-conducting pore between S5 and
S6” (id.), as well as a putative cyclic nucleotide-binding domain (id.). According to
Ludwig, the identification of HAC2 and HAC3 “is consistent with the diversity of Ih
currents detected in different types of neurons” (id., page 590).
Similarly, Santoro3 reports the cloning and functional expression of murine
BCNG-1 (HAC2), as well as the isolation and characterization of human BCNG-2
(HAC1) and human BCNG-1 (HAC2). Santoro, pages 718 and 722-723. Santoro
teaches that “[t]he distinct sequences and tissue distributions of the identified BCNG
[(HAC)] genes reveal[ ] that the BCNG products represent a family of ion channel
proteins, with characteristic motifs for voltage sensing and cyclic nucleotide binding . . .
predominantly located in brain and in heart” (id., page 725). Santoro further teaches
that the properties of mBCNG-1 (mHAC2) “closely correspond to those of the brain
channel (Ih or Iq)” and “these properties are quite similar to those of the pacemaker
current in the heart (If)” (id.). Thus, mBCNG-1 (mHAC2) “may well code for the cardiac
channel” (id.). Santoro also teaches that defects in pacemaker activity can lead to both
inherited and acquired cardiac arrhythmias, and that defects in pacemaker activity may
3 Santoro et al., “Identification of a Gene Encoding a Hyperpolarization-Activated Pacemaker Channel of
Brain,” Cell, Vol. 93, pp. 717-729 (May 29, 1998), especially page 717. Santoro refers to the HAC family
of cyclic nucleotide and hyperpolarization-gated pacemaker channels as the BCNG family.
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