Appeal No. 1997-2182
Application 08/137,443
At page 2 of his Answer, the examiner has listed various
prior art references which serve as the evidence which
supports his rejection. Of all the listed prior art the
examiner has proffered as evidence in support of his
rejection, we find the article by Han et al. in the European
Journal of Medical Chemistry to be the most relevant reference
to the issues presented for our determination. Han et al.
acknowledges on page 673 that:
One of the more promising palliative approaches relates
to potentiating the activity of the central cholinergic
system. A decrease in central nervous system cholinergic
markers is the most consistent and well-documented
neurochemical change in Alzheimer's disease. Accordingly,
several pharmacological strategies to enhance central
cholinergic function are being explored: muscarinic
agonists, acetylcholine releasing agents and
cholinesterase inhibitors. [cites to the bibliography
omitted]
Thereafter in the paragraph bridging pages 673 and 674, the
authors observe that:
Galanthamine (1, scheme 1), a long-acting, centrally-
active competitive cholinesterase inhibitor, has shown
considerable promise. This natural product, an alkaloid
of the Amaryllidaceae family, is hydrolysis-resistant,
only moderately toxic, and more readily absorbed than
physostigmine. The animal data suggest that this compound
might be effective in treating the central cholinergic
deficits in Alzheimer's disease. A recent clinical trial
found that 1 was a well-tolerated drug during long term
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