Appeal 2007-0628
Application 10/225,082
cerebral event” (col. 5, ll. 12-14). Jackowski teaches that all three proteins
are found in CSF after release from brain cells (col. 5, ll. 34-37, 64-66; col.
6, ll. 19-22).
However, Jackowski teaches that S100β has about a two-hour half-life
when released in serum (col. 5, ll. 61-62) and that its level in “fluid collected
from brain,” presumably CSF, peaked about 180 minutes after an ischemic
event (col. 7, ll. 8-20). Phanithi, by contrast, teaches that caspase-3 was not
detectable, even intracellularly, until three hours after reperfusion (p. 280,
left-hand column).
If caspase-3 were detectable in CSF at all, it would only be after the
cells expressing it had completed the apoptotic process, died, and released
their cellular contents into the extracellular space. Phanithi teaches that the
TUNEL detects cells undergoing apoptosis, that no TUNEL-positive cells
were detected until five hours after reperfusion, and that the number of
TUNEL-positive cells peaked twenty-four hours after reperfusion (page 280,
paragraph bridging the columns). Phanithi does not suggest whether the
apoptotic cells would release their contents into the CSF, or whether they
would do so in a detectable amount, but it does suggest that, if they did, the
release would be unlikely to coincide with the presence of S100β in CSF.
Finally, Härter7 teaches that “the presence of active caspase-3 is a
good indicator of apoptosis. To date it is unknown whether active caspase-3
can be released from cells dying by apoptosis into CSF” following traumatic
7 Härter et al., “Caspase-3 activity is present in cerebrospinal fluid from
patients with traumatic brain injury,” Journal of Neuroimmunology, Vol.
121, pp. 76-78 (2001). Härter was cited on the Form PTO-892 mailed July
25, 2005.
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