Appeal No. 1997-2140
Application 08/357,820
also discloses activation of the carboxy-terminal truncated protein to delete various
portions of the amino-terminal, including a deletion corresponding to amino acids 1-105.
Murphy assesses the role of the fibronectin-like domain of the 72 kDa gelatinase.
A deletion mutant lacking the fibronectin-like domain was unable to bind collagen or
gelatin; once activated, the deletion mutant exhibited markedly impaired ability to degrade
gelatin. Page 6634, left-hand column, and page 6635, left-hand column.
Liotta teaches that a region of the amino terminus of the 72 kDa gelatinase acts as
an intrinsic enzyme inhibitor when the enzyme is in a latent state.
Claim 3 stands 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
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