Appeal No. 1998-0350
Application No. 08/453,937
because whole blood plasma contains antithrombin. Brief, page 7. Appellant
has submitted a declaration by George J. Broze, Jr., one of the authors of the
Broze reference, which supports Appellant’s position on how the Broze reference
would have been viewed by those skilled in the art.
The examiner addresses this argument as follows:
In spite of the well-known fact that normal plasma or whole blood
by definition would contain a high concentration of antithrombin III
(AT III) and in spite of the fact that Broze teaches that AT III with
heparin abrogated the TF [tissue factor] inhibition by LACI or in
other words, abrogated the anticoagulant effects of LACI, . . . th[e]
reference by Sandset et al. taken together with Broze et al.
establishes that one of ordinary skill in the art would have
recognized that in vitro results of the anticoagulant activity of
compositions are generally predictive of in vivo efficacy and
therefore, it would have been obvious to one of ordinary skill in the
art at the time the invention was made, that administering LACI and
heparin to animals in vivo, . . . would result in an effective
synergistic form of anticoagulant therapy.
Examiner’s Answer, pages 5-6.
We find that the weight of the evidence in the record supports Appellant’s
reading of the prior art. Broze discloses that, in vitro, the presence of
antithrombin III interferes with the anticoagulant activity of LACI and heparin, so
that in the presence of antithrombin III, LACI and heparin together have lower
anticoagulant activity than LACI alone. See Figure 3 of Broze and the Broze
declaration, page 3, second paragraph (“LACI-mediated inhibition of factor
VIIa/tissue factor was reduced by heparin when antithrombin III, a normal plasma
component, was present.”).
The examiner has conceded that “normal plasma or whole blood by
definition would contain a high concentration of antithrombin III.” Nevertheless,
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