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US 11,372,002 B2Granted
Assays for determining plasma kallikrein system biomarkers
AssigneeTakeda Pharmaceutical Company Limited
InventorsDaniel J. Sexton, Ryan Faucette, Jon A. Kenniston, Gregory P. Conley, Andrew Nixon, Christopher TenHoor, Burt Adelman
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Abstract
Methods and assays for determining the activation level of the plasma kallikrein (pKal) system and the uses thereof for assessing the activity of pKal modulators on the pKal system.
Claims15
An ex vivo activation method, comprising:
- placing an activator of the plasma kallikrein (pKal) system in a plasma sample obtained from a subject to produce a mixture, wherein the activator is Factor XIIa (FXIIa);
- incubating the mixture;
- measuring levels of intact high molecular weight kininogen (HMWK), cleaved HMWK, or both, in the plasma sample before and after the incubation;
- determining a reduction of intact HMWK in the sample after the activation and/or an elevated level of the cleaved HMWK in the sample after the activation;
- and
- administering a therapeutic agent to the subject if the plasma sample obtained from the subject has an elevated level of the cleaved HMWK as compared to a predetermined value;
- wherein the therapeutic agent is DX-2930, DX-2922, DX-88, or EpiKal-2.
4 more elements
An ex vivo assay for determining plasma kallikrein (pKal) activity in a sample, comprising:
- placing a pKal system activator and a labeled synthetic peptide substrate of pKal in a plasma sample obtained from a subject to produce a mixture, wherein the activator is Factor XIIa (FXIIa), and wherein the peptide substrate comprises a motif of PFR;
- incubating the mixture;
- measuring the activity of pKal in the mixture based on a cleavage rate of the substrate;
- and
- administering a therapeutic agent to the subject if the plasma sample obtained from the subject has an elevated level of pKal activity compared to a predetermined value;
- wherein the therapeutic agent is DX-2930, DX-2922, DX-88, or EpiKal-2.
3 more elements
Dependencies are inferred from the claim text.