Appeal No. 2001-1378
Application No. 08/832,571
must be localized to a membrane to work efficiently.... Aronheim et al.
teach methods for localizing proteins to membranes by addition of
myristoylation, farnesylation and palmitoylation signal sequences....
The examiner summarizes (Answer, pages 4-5):
It would have been obvious to one of ordinary skill in the art at the
time the invention was made to modify the p110* construct of Hu et al. by
adding DNA encoding membrane localization sequences as taught by
Aronheim et al. Kapeller et al. and Varticovski et al. provide both
motivation to make this modification and a reasonable expectation of
success, in that they each indicate that one of ordinary skill in the art
expected that PI 3-kinase activity would be increased by targeting the
enzyme to membranes, where the enzyme substrates are located. Even
for a constitutively active p110* mutant, one of ordinary skill in the art
would still be motivated to localize it to the cell membranes where its
substrates are, such that optimal production of its phosphorylated lipid
products and maximal physiological responses mediated by these lipid
products could be obtained.
We agree that the examiner has presented sufficient evidence to support a prima
facie case of obviousness. In particular, Hu describes a constitutively active PI 3-
kinase linked to the iSH2 portion of the p85 subunit. Kapellar indicates that PtdIns-3-
kinase substrate is localized at the plasma membrane. Kapeller, page 571, col. 1.
Varticovski suggests that amino terminal myristoylation is needed to place an abl
protein/PI 3 kinase complex at a membrane location where lipid phosphorylation can
occur efficiently. Varticovski, page 1112, col. 1. Similarly, Aronheim generally
describes the binding “of growth factors to cell surface receptors results in receptor
dimerization and activation of their intrinsic tyrosine kinase, leading to intermole-
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