Appeal No. 09/975,899 Page 6
Application No. 2006-0292
P-selectin in endothelial cells. Reviewing the teachings of the Hallahan II
reference, Hallahan II teaches that in using a CAM-based therapy to induce the
expression of a CAM within a tumor, the CAM should meet the requirements of
being readily inducible, having no basal cell surface expression in unirradiated
tissue, and being inducible by radiation. See id. at 15. With respect to P-
selectin, Hallahan II teaches that, upon exposure to ionizing radiation, it is
translocated from WPBs (Weibel Palade organelles) to the blood-tissue interface
of the endothelium, i.e., the lumen of the vasculature. See id. at 3-5. P selectin
is constitutively expressed in WPBs, from where it moves to the vascular lumen
within 30 minutes of irradiation, but is not detected in the pulmonary endothelium
at 6 hours after irradiation. See id. at 16. The radiation dose required for
increased P-selectin expression within the pulmonary vascular endothelium is 2-
Gy, and thus the inventors concluded that P-selectin is a viable target for tumor-
directed therapy. See id. at 16. Thus, in the Summary of the Invention, the
inventors state that the invention is drawn to methods for delivering an agent to
the vasculature of a subject comprising inducing P-selectin translocation to the
lumen of vascular endothelial cells through the use of ionizing radiation and
administering a P-selectin targeting component. See id. at 6-7.
With respect to ICAM-1, Hallahan II teaches that it is not expressed at x-
ray doses below 5 Gy, but shows an increase at 24 hours when higher x-ray
doses were used; thus ICAM-1 induction requires high radiation doses, while
expression is more prolonged. See id. at 16. ICAM-1 is expressed in the
pulmonary capillary endothelium, and minimally within the endothelium of larger
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