Appeal No. 1999-0494
Application 08/482,768
intracerebral injection of DMS. DMS is an acronym for "dense microspheres."
Specification, page 4. As explained:
A microscopic structure referred to as the dense microsphere is known to
exist in normal brain and in brain affected by Alzheimer's disease. See
Averback, Acta Neuropathol. 61: 148-52 (1983); results confirmed by Hara, J.
Neuropath. Exp. Neurol. (1986). Evidence for the existence of dense
microspheres (DMS) comes from microscopic histological section studies of fixed
whole brain tissue, where the dense microspheres are seen to have a
proteinaceous central region ("DMS protein") surrounded by continuous
membrane ("DMS membrane"). The dense microspheres are observed as
randomly dispersed, very infrequent structures which occupy an estimated 10-9 or
less of total brain volume, at a unit frequency roughly estimated at
10-16 or less, relative to other definable brain structures such as mitochondria.
Id. Appellant believes that development of amyloid fibrils associated with a number of
conditions including Alzheimer's disease is tied to the unchecked disruption of DMS
in vivo. Specification, page 8. Appellant describes a screening procedure for identifying
compounds which inhibit the disruption of DMS in vivo. As explained:
It has also been discovered that compounds which are effective, at a in-
tissue concentration of about 10-5 M or less, in impeding the formation of amyloid
fibrils in test animals which receive DMS via intracerebral injection can be used
to treat cerebral amyloidosis, including Alzheimer's disease. Particularly effective
in this regard are compounds that act on DMS protein or DMS membrane, for
example, via intracellular or extracellular binding, so as to prevent a structural
transition of DMS protein in the brain to a β-pleated sheet conformation.
Specification, page 8, lines 15-26.
Example 2 of the specification describes use of this assay to identify compounds
meeting the requirements of claim 13. Of the seven compounds tested in Example 2,
appellant states that only three compounds, pyrimethamine, cromolyn sodium, and
erythromycin were found to inhibit amyloid formation in vivo at in-tissue levels in the
range of 10-5 to 10-6 M. On the basis of those results, appellant states that those three
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