Assays for determining plasma kallikrein system biomarkers

Patent metadata

Field	Value
Publication number	US-12442824-B2
Application number	US-202117555636-A
Country	US
Kind code	B2
Filing date	Dec 20, 2021
Priority date	Oct 21, 2013
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

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.

First claim

What is claimed is:

1. A method for assessing plasma activation, comprising:
providing a plasma sample from a subject;
incubating the plasma sample with an activator of plasma kallikrein (pKal), wherein the activator is Factor XIIa (FXIIa) and wherein the activator is added ex vivo; and
measuring the level of cleaved high molecular weight kininogen (HMWK) in the plasma sample after ex vivo activation;
wherein the subject has been treated with a pKal inhibitor.

2. The method of claim 1 , wherein the level of cleaved HMWK is measured by Western blot analysis.

3. The method of claim 1 , wherein the subject has or is suspected of having a disease associated with the plasma kallikrein (pKal) system.

4. The method of claim 1 , further comprising evaluating the efficacy of the pKal inhibitor, wherein a reduced level of cleaved HMWK after the treatment as compared with the level of cleaved HMWK in a sample obtained from the subject before the treatment indicates that the pKal inhibitor is effective.

5. The method of claim 3 , wherein the disease is hereditary angioedema (HAE).

6. The method of claim 1 , wherein the subject is a human patient having a disease associated with plasma kallikrein (pKal); and wherein the plasma sample is obtained after the treatment or during the course of the treatment.

7. The method of claim 6 , further comprising evaluating the efficacy of the treatment; wherein a reduced level of cleaved HMWK as compared with the level of cleaved HMWK in a sample obtained from the subject before the treatment or a reduced level of cleaved HMWK during the course of the treatment indicates that the treatment is effective.

8. The method of claim 6 , wherein the patient has hereditary angioedema (HAE).

9. The method of claim 1 , wherein the pKal inhibitor is DX-2930, DX-2922, DX-88, or EpiKal-2.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Sexton Daniel J
• Faucette Ryan
• Kenniston Jon A
• Conley Gregory P
• Nixon Andrew
• Tenhoor Christopher
• Adelman Burt

Classifications

• G01N2800/50

  Determining the risk of developing a disease · CPC title

• G01N2500/20

  cell-free systems · CPC title

• G01N2500/02

  Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) · CPC title

• G01N2333/96458

  Factor XII (3.4.21.38) · CPC title

• G01N2333/96455

  Kallikrein (3.4.21.34; 3.4.21.35) · CPC title