Pregnancy-associated plasma protein-A2 (PAPP-A2) polypeptides
AssigneeComo Biotech ApS
InventorsClaus Oxvig, Michael Toft Overgaard
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Abstract
The present invention provides pregnancy associated plasma protein A2 (PAPP-A2), its nucleotide and amino acid sequences, antisense molecules to the nucleotide sequences which encode PAPP-A2, expression vectors for the production of purified PAPP-A2, antibodies capable of binding specifically to PAPP-A2, hybridization probes or oligonucleotides for the detection of PAPP-A2-encoding nucleotide sequences, genetically engineered host cells for the expression of PAPP-A2, and methods for screening for pathologies in pregnant and non-pregnant patients. Methods for screening for altered focal proliferation states in pregnant and/or non-pregnant patients, which include detecting levels of PAPP-A2, are also described.
Claims26
An isolated polypeptide which comprises an amino acid sequence that differs from residues 234-1791 of SEQ ID NO:2 solely by
- (a) addition of 1-10 residues to the amino terminal;
- and/or
- (b) addition of 1-10 residues to the carboxy terminal;
- and/or
- (c) one or more conservative substitutions;
- wherein said polypeptide has a proteolytic activity against Insulin Like Growth Factor Binding Protein 5 (IGFBP-5), and wherein said amino acid sequence is at least 95%, but not 100%, identical to residues 234-1791 of SEQ ID NO:2.
An isolated polypeptide which comprises an amino acid sequence that differs by at least one but not more than 16 insertions and/or substitutions from residues 234-1791 of SEQ ID NO:2;
- wherein said polypeptide has a proteolytic activity against Insulin Like Growth Factor Binding Protein 5 (IGFBP-5).
An isolated polypeptide consisting of:
- (a) a modified fragment, at least 5 amino acids in length, of mature PAPP-A2 wherein said mature PAPP-A2 consists of residues 234-1791 of SEQ ID NO:2, and wherein said modified fragment differs from a fragment of mature PAPP-A2 solely by one conservative substitution, wherein said modified 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, which recognizes mature PAPP-A2;
- and
- 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, or Cys-1729 to Cys-1733;
- or
- (b) a fusion of the polypeptide of (a) with
- (i) an immunogenic carrier protein;
- or
- (ii) a tag which may be used to facilitate the detection or purification of the fusion.
Dependencies are inferred from the claim text.