Rna biomarkers for hereditary angioedema

Patent metadata

Field	Value
Publication number	US-2024271211-A1
Application number	US-202318537204-A
Country	US
Kind code	A1
Filing date	Dec 12, 2023
Priority date	Sep 16, 2016
Publication date	Aug 15, 2024
Grant date	—

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

1 . A method for analyzing a sample, comprising:
(i) providing a biological sample obtained from a subject having, suspected of having, or being at risk for a disease associated with the contact activation system; and (ii) measuring the level of a RNA biomarker set, wherein the RNA biomarker set comprises a messenger RNA encoding mitochondrially-encoded NADH:ubiquinone oxidoreductase core subunit 3 (MT-ND3).

2 . The method of claim 1 , wherein the biomarker set consists of 2-10 RNA biomarkers.

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 disease associated with the contact activation system is hereditary angioedema (HAE).

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

6 . The method claim 1 , wherein the RNA biomarker set further comprises a messenger RNA encoding mitochondrially-encoded cytochrome C oxidase III (MT-CO3).

7 . (canceled)

8 . The method of claim 1 , wherein the RNA biomarker set further comprises a microRNA, optionally wherein the microRNA is selected from the group consisting of hsa-miR-16-5p, hsa-miR-19a-3p, hsa-miR-20a-5p, hsa-miR-17-5p, hsa-miR-28-5p, hsa-miR-423-3p, hsa-miR-26a-5p, hsa-miR-1307-3p, hsa-miR-335-3p, hsa-miR-139-5p, hsa-miR-485-5p, hsa-miR-26b-5p, hsa-miR-885-5p, hsa-miR-361-3p, hsa-miR-769-5p, hsa-miR-140-5p, hsa-miR-485-3p, hsa-miR-889-3p, hsa-miR-941, RPL23, hsa-miR-328-3p, and hsa-miR-484.

9 . The method of claim 1 , wherein step (ii) involves polymerase chain reaction and/or nucleic acid hybridization.

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

11 . The method of claim 1 , further comprising:
(iii) identifying the subject as having the disease associated with the contact system, if the level of the RNA biomarker set of the subject deviates from the level of the same RNA biomarker set of a control subject; and, (iv) administering to the subject an effective amount of a therapeutic agent for treating the disease, if the subject is identified as having the disease.

12 . (canceled)

13 . The method of claim 11 , wherein therapeutic agent is a plasma kallikrein (pKal) inhibitor, optionally wherein the pKal inhibitor is an anti-pKal antibody or an inhibitory peptide, a bradykinin 2 receptor (B2R) inhibitor, and/or a C1 esterase inhibitor.

14 . (canceled)

15 . The method of claim 13 , wherein the therapeutic agent is lanadelumab, ecallantide, icatibant, or human plasma-derived C1 esterase inhibitor.

16 . The method of claim 1 , wherein the subject is a human patient who is on a treatment for the disease, and wherein the method further comprises assessing the efficacy of the treatment based on the level of the RNA biomarker set, a deviation of the RNA biomarker set level of the subject from that of a control subject being indicative of the treatment efficacy.

17 . The method of claim 1 , further comprising identifying a suitable treatment for the subject based on the level of the RNA biomarker set and/or identifying the subject as a candidate for treatment of the disease based on the level of the RNA biomarker set.

18 . (canceled)

19 . The method of claim 17 , wherein the subject has a history of the disease.

20 - 21 . (canceled)

22 . The method of claim 19 , further comprising assessing the risk of disease attack in the subject based on the level of the RNA biomarker set, a deviation of the RNA biomarker set level of the subject from that of a control subject being indicative of the risk of a disease attack.

23 . The method of claim 22 , further comprising administering a therapeutic agent to the subject, if the subject is identified as at risk of a disease attack, optionally wherein the therapeutic agent is for prophylactic treatment.

24 . (canceled)

25 . A kit for analyzing a sample of a subject having, suspected of having, or at risk for a disease associated with the contact system, the kit comprising:
(i) a first binding agent specific to a first RNA biomarker, wherein the first RNA biomarker is a messenger RNA encoding mitochondrially-encoded NADH:ubiquinone oxidoreductase core subunit 3 (MT-ND3); and (ii) a second binding agent specific to a second RNA biomarker selected from the group consisting of mitochondrially-encoded cytochrome C oxidase III (MT-CO3), hsa-miR-423-3p, hsa-miR-1307-3p, hsa-miR-485-5p, hsa-miR-16-5p, hsa-19a-3p, hsa-miR-20a-5p, hsa-miR-17-5p, hsa-miR-885-5p, hsa-miR-335-3p, and hsa-miR-485-5p.

26 . The kit of claim 25 , wherein the first binding agent is an oligonucleotide complementary to the first RNA biomarker or a fragment thereof, and/or the second binding agent is an oligonucleotide complementary to the second RNA biomarker or a fragment thereof.

27 . The kit of claim 25 , wherein the first binding agent, the second binding agent, or both are conjugated to a label and/or wherein the first binding agent and the second binding agent are immobilized on a support member.

28 . (canceled)

Assignees

• Takeda Pharmaceuticals Co

Inventors

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

Classifications

• C12Q2600/158

  Expression markers · CPC title

• C12Q2600/178

  miRNA, siRNA or ncRNA · CPC title

• C12Q1/6876

  Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes · CPC title

• G01N2800/224

  Haemostasis or coagulation · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title