Appeal No. 1999-1245
Application No. 08/245,282
subunit of the PI 3-kinase; that tyrosine phosphorylation of numerous substrates occurs
rapidly following CD28 receptor ligation.” Id.
Vandenberghe is relied on for the disclosure that when CD28+ cells are activated
with antigen, for example, costimulation with CD28 monoclonal antibodies leads to
enhanced production of several lymphokines such as IL-2 and increased cellular
proliferation and further discloses that use of the B7/BB1 ligands gives results similar to
those above obtained with CD28 monoclonal antibodies. Id. The examiner finds that
the results presented in Vandenberghe teach that stimulation of Jurkat T cells and
normal T cells with anti-CD28 mAb induces tyrosine phosphorylation of several
substrates, and that the intracellular action of herbamycin A inhibits the CD28 induced
proliferation and cytokine production by T-cells. Id.
Finally, Ward 1992 discloses that PI 3-kinase produces the D-3 phospho-
inositides and that the D-3 phosphoinositides and the PI 3-kinase may play a role in
cell activation. Answer, page 9.
The examiner summarizes (Answer, page 10):
Therefore, it would have been obvious to one of ordinary skill in the
art at the time the invention was made to modify the methods of Ward
(EJI, 1993) by using specific intracellular inhibitors of PI 3-kinase, such as
herbimycin A as taught by Vandenberghe, in view of the teachings of both
Vandenbergh and Ward (EJI, 1992) (page 45, column 2, top paragraph)
that the lipid products of PI 3-kinase may play an important role in cell
activation and that the D-3 phosphoinositides and PI 3-kinase have
recently been discovered in activated T cells (page 45, column 1, first
paragraph). One of ordinary skill in the art would have had a reasonable
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