Protein biomarkers for diseases associated with the contact activation system

Patent metadata

Field	Value
Publication number	US-11815516-B2
Application number	US-201716333155-A
Country	US
Kind code	B2
Filing date	Sep 15, 2017
Priority date	Sep 16, 2016
Publication date	Nov 14, 2023
Grant date	Nov 14, 2023

Abstract

Provided herein are methods and kits for analyzing a biological sample obtained from a subject having, suspected of having, or being at risk for a disease associated with the contact activation system.

First claim

What is claimed is:

1. A method, comprising:
(i) providing a biological sample obtained from a subject having or suspected of having hereditary angioedema (HAE); and
(ii) measuring the level of a protein biomarker set, which comprises Interleukin-36 alpha (IL-1F6);
(iii) identifying the subject as a patient having HAE if the level of IL-1F6 in the biological sample obtained from the subject is at least 1.1-fold lower than the level of IL-1F6 of a control subject, wherein the control subject is a subject not having HAE; and
(iv) administering to the subject identified as having HAE an effective amount of a therapeutic agent for treating HAE; wherein therapeutic agent is a plasma kallikrein (pKal) inhibitor, a bradykinin 2 receptor (B2R) inhibitor, and/or a C1 esterase inhibitor.

2. The method of claim 1 , wherein the protein biomarker set consists of 2-10 proteins.

3. The method of claim 1 , wherein the biological sample is a serum sample or a plasma sample.

4. The method of claim 1 , wherein the HAE is type I HAE or type II HAE.

5. The method of claim 1 , wherein step (i) comprises collecting the biological sample into an evacuated blood collection tube, which comprises one or more protease inhibitors.

6. The method of claim 1 , wherein step (ii) is performed using an enzyme-linked immunosorbent assay (ELISA), an immunoblotting assay, or a lateral flow assay.

7. The method of claim 1 , wherein the subject is a human patient.

8. The method of claim 1 , wherein the pKal inhibitor is an anti-pKal antibody or an inhibitory peptide.

9. The method of claim 8 , wherein the pKal inhibitor is lanadelumab or ecallantide.

10. The method of claim 1 , wherein the B2R inhibitor is an inhibitory peptide, optionally wherein the inhibitory peptide is icatibant.

11. The method of claim 1 , wherein the therapeutic agent is a C1 esterase inhibitor, which is a human plasma-derived C1 esterase inhibitor.

12. The method of claim 1 , wherein the protein biomarker set further comprises
a mitochondrial protein selected from the group consisting of ATP synthase subunit 0 (ATPO), cyclophilin F, and mitochondrial heat shock protein 60 (HSP60).

13. The method of claim 1 , wherein the protein biomarker set further comprises 14-3-3 zeta/delta or 14-3-3 beta/alpha.

14. The method of claim 1 , wherein the protein biomarker set further comprises a protein kinase selected from the group consisting of protein kinase YES, protein kinase LYN, and mitogen-activated protein kinase 14 (MAPK14).

15. The method of claim 1 , wherein the protein biomarker set further comprises a protein selected from the group consisting of glycogen synthase kinase 3 alpha/beta, ATP-dependent RNA helicase DDX19B, and eukaryotic translation initiation factor 5A-1.

16. The method of claim 1 , wherein the level of IL-1F6 in the biological sample obtained from the subject is at least 1.5-fold lower than the level of IL-1F6 of the control subject.

17. The method of claim 1 , wherein the level of IL-1F6 in the biological sample obtained from the subject is at least 2.0-fold lower than the level of IL-1F6 of the control subject.

18. The method of claim 1 , wherein the level of IL-1F6 in the biological sample obtained from the subject is at least 5-fold lower than the level of IL-1F6 of the control subject.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Sexton Daniel J
• Viswanathan Malini
• Faucette Ryan
• Gaur Tripti

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2800/224

  Haemostasis or coagulation · CPC title

• G01N33/54366

  Apparatus specially adapted for solid-phase testing · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title

• A61P7/10

  Antioedematous agents; Diuretics · CPC title