Appeal No. 2005-1516
Application No. 09/182,645
DISCUSSION
Background
Poly(ADP-ribose) glucohydrolase inhibitors are also known as PARG inhibitors.
Specification, page 1. The DNA repair enzyme, poly (ADP-ribose) polymerase2 or
PARP “has emerged as a major player along the continuum of cell death. Cleavage of
PARP by caspase-3 is a defining characteristic of apoptosis, and PARP also plays a
pivotal role in classical necrotic cell death.” Specification, page 3. “Nuclear PARP is
selectively activated by DNA strand breaks to catalyze the addition of long, branched
chains of poly(ADP-ribose) from its substrate nicotinamide adenine dinucleotide (NAD)
to a variety of nuclear proteins, most notably PARP itself. Massive DNA damage, such
as that typically resulting from necrotic stimuli, elicits a major augmentation of PARP
activity which rapidly depletes cellular levels of NAD. Depletion of NAD, an important
co-enzyme in energy metabolism, results in lower ATP production. Furthermore, the
cell consumes ATP in efforts to re-synthesize NAD, and this energy crisis culminates in
cell death.” Specification, page 3.
2 PARP is also known as poly (ADP-ribose) synthetase or poly (ADP-ribose)
transferase.
3
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Last modified: November 3, 2007