Appeal No. 94-4009 Paper No. 32
Application No. 07/953,716 Page 9
As the onset mechanism, the atherosclerotic
intimal thickening of coronary artery is believed to
be one of the main causes for myocardial infarction
and angina pectoris. This atherosclerotic intimal
thickening is considered to be initiated by adhesion
of monocytes or platelets to endothelial cells with
secretion of cytokines and lipid accumulation and to
be progressed by migration of [aortic medial smooth
muscle cells] from the media to the intima and
proliferation of the smooth muscle cells in the
intima and increase of extracellular matrix, due to
pathological and proliferative activation or
modulation of smooth muscle cells. These
activation[s] of the cells are promoted by risk
factors such as hyperlipidemia. Heretofore, it has
been reported that [3-hydroxy-3-methylglutaryl-
coenzyme A] reductase inhibitors suppress the
atherosclerotic intimal thickening by a strong
effect to reduce serum cholesterol in an animal
model..., but the effect in a clinical trial has
been found inadequate.
Nothing in the preceding quote requires treatment before
the initiation of intimal thickening. The quoted paragraph
does, however, identify hyperlipidemia as a risk factor
associated with activating smooth muscle cell proliferation
and migration (second underlined sentence). The paragraph
also associates the proliferation of aortic smooth muscle
cells and their migration into the intima with atherosclerotic
intimal thickening (first underlined sentence). We understand
the specification to teach that hyperlipidemia, among other
risk factors, may precede smooth muscle cell proliferation and
migration, and thus precedes atherosclerotic intimal
thickening.
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