Pregnancy-associated plasma protein-a2 (papp-a2) polynucleotides

An isolated polynucleotide encoding a polypeptide that is

• (a) a fragment of mature PAPP-A2 (residues 234-1791 of SEQ ID NO:2) at least 5 amino acids in length, wherein said fragment
• (i) has a proteolytic activity against Insulin Like Growth Factor Binding Protein 5 (IGFBP-5);
• and/or
• (ii) is recognized by an antibody, or a binding fragment thereof, that recognizes mature PAPP-A2;
• and/or
• (iii) competes with a polypeptide having the amino acid sequence as shown in SEQ ID NO:2 for binding to a cell surface receptor having an affinity for said polypeptide;
• and
• wherein said fragment comprises at least one of the following regions of SEQ ID NO:2:
• Cys-403 to Cys-499, Cys-828 to Cys-881, Cys-1048 to Cys-1115, Cys-1390 to Cys-1396, Cys-1459 to Cys-1464, Cys-1521 to Cys-1525, Cys-1590 to Cys-1595, Cys-1646 to Cys-1653, Cys-1729 to Cys-1733;
• or
• (b) a fusion of the polypeptide of (a) with an immunogenic carrier protein, or with a tag that facilitates the detection or purification of the fusion.

An isolated polynucleotide encoding a polypeptide comprising

• (a) amino acids 1-22 of SEQ ID NO:2, and
• (b) an amino acid sequence selected from the group consisting of
• (i) an amino acid sequence consisting of residues 234-1791 of SEQ ID NO:2, and
• (ii) an amino acid sequence at least 95% identical to (a);
• wherein said polypeptide, or a cleavable fragment of said polypeptide comprising sequence (b), has a proteolytic activity against Insulin Like Growth Factor Binding Protein 5 (IGFBP-5).

An isolated polynucleotide encoding a polypeptide comprising

• (a) amino acids 23-233 of SEQ ID NO:2, and
• (b) an amino acid sequence selected from the group consisting of
• (i) an amino acid sequence consisting of residues 234-1791 of SEQ ID NO:2, and
• (ii) an amino acid sequence at least 95% identical to (a);
• wherein said polypeptide, or a cleavable fragment of said polypeptide comprising sequence (b), has a proteolytic activity against Insulin Like Growth Factor Binding Protein 5 (IGFBP-5).

An isolated polynucleotide encoding a polypeptide comprising

• (a) amino acids 1-233 of SEQ ID NO:2 and
• (b) an amino acid sequence selected from the group consisting of
• (i) an amino acid sequence consisting of residues 234-1791 of SEQ ID NO:2, and
• (ii) a sequence that is at least 95% identical to (a) above
• wherein said polypeptide, or a cleavable fragment of said polypeptide comprising sequence (b), has a proteolytic activity against Insulin Like Growth Factor Binding Protein 5 (IGFBP-5).

A polynucleotide according to any of the preceding claims operably linked to a further polynucleotide, wherein the further polynucleotide comprises

• (a) nucleotides 5377 to 8527 of SEQ ID NO:
• 1, corresponding to a 3′ untranslated region, and/or
• (b) a fragment of(a), and/or
• (c) SEQ ID NO:1.