Appeal No. 2001-1436 Page 11
Application No. 08/422,612
receptor, when expressed in yeast cells, would not function to cause dissociation
of the yeast G protein or transduce a signal into the yeast cell.
Dull’s system relies on transduction of a signal by the heterologous
receptor, in order to assay for ligand binding. See column 3, lines 9-13: “The
hybrid receptor of this invention is useful in screening methods for identifying
receptor-active agonistic drugs. One incubates the hybrid receptor with the
candidate drug and assays for the generation of a signal by the heterologous
reporter polypeptide.” The assayable signal can be the activity of an enzymatic
effector protein (column 3, lines 13-16) or activation of G protein by the receptor
(column 11, lines 21-28). In any case, however, Dull’s method depends on
generation of an intracellular signal in response to ligand binding by the
heterologous receptor.
This requirement for functional signal transduction would have led those
skilled in the art to expect that a mammalian G protein-coupled receptor,
expressed in yeast, could not be used in Dull’s assay method. Dietzel teaches
that mammalian G protein α subunit does not interact with a yeast receptor,
which would have led those skilled in the art to also expect the converse: that a
yeast G protein α subunit would not interact with a mammalian receptor. Since
the mammalian receptor would not be expected to interact with the yeast G
protein, those skilled in the art would have expected that a mammalian G protein-
coupled receptor would not produce a signal, even induction of G protein
dissociation, if expressed in yeast cells. Therefore, those skilled in the art would
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