Appeal No. 1997-2140
Application 08/357,820
catalytic domain of the parent enzyme. The protein encoded by the claimed cDNA
consists of amino acid residues 106-216 fused to residues 391-443 of the parent
molecule. In other words, the truncated protein is distinguished from the parent enzyme by
three separate deletions: amino-terminal residues 1-105, internal residues 217-390, and
carboxy-terminal residues 444-707. According to the specification, the protein encoded
by the claimed cDNA is catalytically active against gelatin, but, unlike the parent enzyme,
inactive against insoluble elastin. Specification, page 3.
Goldberg discloses the full length 92 kDa gelatinase proenzyme, and cDNA
encoding it. The 92 kDa gelatinase is structurally related to the 72 kDa gelatinase, but is
unique among matrix metalloproteinases in having a 54 amino acid proline-rich domain
homologous to the "-2 chain of type V collagen. Figure 6 shows the structural domains
shared by the 92 kDa and 72 kDa gelatinases in alignment; the two enzymes share some
sequence similarity but the 92 kDa gelatinase contains three potential N-glycosylation
sites not found in the 72 kDa gelatinase and is fully glycosylated.
O’Connell assesses the role of the carboxyl-terminal collagen- and hemopexin-like
domains of the 92 kDa gelatinase. Deletion of these domains, which correspond to
carboxy-terminal amino acids 444-707, does not affect the catalytic activity of the enzyme,
4
but does affect the rate of activation in the presence of the inhibitor TIMP-1. O’Connell
4Tissue Inhibitor of Metalloproteinase-1.
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