Assays, methods and means
AssigneeIsis Innovation Limited
InventorsPatrick Henry Maxwell, Christopher William Pugh, Peter John Ratcliffe, Christopher Joseph Schofield
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Abstract
A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the IIIF hydroxylase with a substrate. Modulators of IIIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.
Claims25
1-55. (canceled)
A pharmaceutical composition comprising
- a substance that has been identified as inhibiting the activity of a HIF hydroxylase in mediating the hydroxylation of one or more proline residues of a HIF-α protein by means of an assay method in which
- a HIF prolyl hydroxylase and a substrate of the hydroxylase are contacted under conditions in which the hydroxylase interacts with the substrate, in the presence or absence of a test substance;
- and
- the interaction, or lack of interaction of, the hydroxylase and the substrate is determined by measuring the hydroxylase activity of the hydroxylase;
- wherein the HIF prolyl hydroxylase has the amino acid sequence SEQ ID NO:
- 4;
- and
- a pharmaceutically acceptable excipient.
Dependencies are inferred from the claim text.