Appeal No. 1998-0053
Application 08/444,628
Claims 1 and 4 stand rejected as unpatentable over the combined disclosures of
Goldberg, O’Connell, Murphy and Liotta. According to the examiner:
It would have been obvious to one of ordinary skill in the art using the 92 kDa
gelatinase of [Goldberg] at the time of the invention, to make truncations in it
to delete the carboxyl terminal collagen-like and hemopexin-like domains, as
taught by [O’Connell] in order to reduce sensitivity to the TIMP-1 inhibitor; to
delete the internal fibronectin domain, as taught by [Murphy] in order to
reduce binding to collagen; and to delete the amino terminal at least up to
88
Phe as taught by [O’Connell] and [Liotta] in order to reduce intrinsic
inhibition. Motivation to make a multiply truncated 92 kDa gelatinase is
provided by the teachings of [Goldberg, O’Connell, Murphy and Liotta], who
teach the various improvements in gelatinase activity as described above.
(Examiner’s Answer, page 6, emphasis added).
We disagree. The reason proposed by the examiner for deleting the amino- and
carboxy-terminal regions of the 92 kDa gelatinase is plausible as far as it goes: to
minimize inhibition of enzyme’s ability to degrade gelatin (i.e., denatured collagen).
Indeed, O’Connell discloses a truncated mutant with both of these deletions. The reason
given for the further deletion of the internal fibronectin-like domains, however, is an entirely
different matter. To the extent that manipulation of the 72 kDa gelatinase is relevant to the
92 kDa gelatinase, Murphy shows that deletion of the fibronectin-like domains, by
eliminating the ability of the mutant to bind collagen, markedly impairs the ability of the
truncated mutant to degrade gelatin. Thus, the combination of deletions proposed by the
examiner would seem, based on the references cited, to operate at cross-purposes.
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