Appeal No. 2004-2202 Page 10
Application No. 10/016,324
lengthening the time of liposome circulation in the bloodstream. The skilled artisan
would have been aware that liposomes function by fusing with the membranes of a
target cell, thereby delivering the contents of the liposome to the cytoplasm of the cell
and adding the lipophilic component of the liposome to the lipid bilayer of the
membrane. See, e.g., Marshall, column 33, lines 33-41 (“One type of structure that can
be formed by amphiphiles is the liposome, a vesicle formed into a more or less
spherical bilayer, that is stable in biological fluids and can entrap biological molecules
targeted for intracellular delivery. By fusing with cell membranes, such liposomal
compositions permit biologically active molecules carried therewith to gain access to the
interior of a cell through one or more cell processes including endocytosis and
pinocytosis.”).
Those skilled in the art would also have recognized that breathing is not simply a
process of air being breathed in and taken up directly by red blood cells. Rather,
oxygen must diffuse across the “blood-gas barrier” before it can be taken up by red
blood cells. The same would be expected for any other agent administered by
inhalation – it would have to traverse the various cell membranes that make up the
blood-gas barrier in order to enter the circulatory system.
Thus, those skilled in the art would expect that the liposomes administered by
inhalation by Mihalko would deliver the entrapped therapeutic agent by fusing with the
membranes of the cells lining the lung, and therefore, that only the entrapped drug
would be taken up by the cell and passed through to the systemic circulation. Mihalko
provides evidence that those skilled in the art would have expected the lipid bilayer of
the liposome to remain associated with the lipid bilayer of the lung cells. See page 31,
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