Appeal No. 2005-1516
Application No. 09/182,645
“Upon binding to breaks in DNA, PARP activity is increased as much as 500 fold
as it catalyzes the transfer and polymerization of ADP-ribose units onto both itself and
other nuclear proteins.” Specification, pages 4-5. The activation of PARG “promotes
the PARP-induced depletion of cellular energy, increased cell damage and cell death
associated with disease and disorders linked to PARP activity.” Specification, page 6.
“The rapid activation of PARG in response to PAR synthesis and PARP
activation indicates that PAR degradation via PARG should promote disorders and
diseases associated with PARP activity. Accordingly, PARG inhibitors should be useful
in down-regulating PARP by decreasing substrate and targets for PARP activity, and
thus PARG inhibitors are useful for treating disorders and diseases associated with
PARP activity...”. Specification, page 9.
According to the specification, “[i]t has been reported that PARP activation plays
a key role in both NMDA- and NO-induced neurotoxicity.... The potential role of PARP
inhibitors in treating neurodegenerative diseases and head trauma has thus been
known.” Specification, pages 9-10. “PARG inhibitors should influence PARP-
associated NMDA- and NO-induced neurotoxicity by downregulating PARP activity and
thus PARG inhibitors are useful for treating neurodegenerative diseases, head trauma
and cerebral ischemia.” Specification, page 10.
“Neural damage following stroke and other neurodegenerative processes are
thought to result from a massive release of the excitatory neurotransmitter glutamate,
which acts upon the N-methyl-D-aspartate (NMDA) receptors... Neurons release
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