US 12,188,948 B2
Metabolite biomarkers for diseases associated with the contact activation system
Daniel J. Sexton, Melrose, MA (US); Malini Viswanathan, Acton, MA (US); Ryan Faucette, Melrose, MA (US); and Tripti Gaur, South Grafton, MA (US)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed by Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed on Apr. 25, 2022, as Appl. No. 17/728,285.
Application 17/728,285 is a continuation of application No. 16/333,101, granted, now 11,340,237, previously published as PCT/US2017/051755, filed on Sep. 15, 2017.
Claims priority of provisional application 62/518,367, filed on Jun. 12, 2017.
Claims priority of provisional application 62/395,770, filed on Sep. 16, 2016.
Prior Publication US 2022/0365101 A1, Nov. 17, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 33/68 (2006.01); G01N 33/74 (2006.01); G01N 33/82 (2006.01); G01N 33/92 (2006.01); G01N 33/94 (2006.01)
CPC G01N 33/6893 (2013.01) [G01N 33/6806 (2013.01); G01N 33/743 (2013.01); G01N 33/82 (2013.01); G01N 33/92 (2013.01); G01N 33/942 (2013.01); G01N 2800/224 (2013.01); G01N 2800/50 (2013.01); G01N 2800/52 (2013.01); G01N 2800/7095 (2013.01)] 18 Claims
 
1. A method comprising:
(i) providing a biological sample obtained from a subject after a treatment or during a course of treatment for hereditary angioedema (HAE);
(ii) measuring the level of a metabolite biomarker set in the biological sample, wherein the metabolite biomarker set comprises at least one metabolite biomarker selected from the group consisting of serotonin; tryptophan; indolelactate; indolepropionate; gamma-/beta -tocopherol; ascorbate; palmitic amide; oleamide; linoleamide; 9-hydroxyoctadecadienoic acid (9-HODE); 13-hydroxyoctadecadienoic acid (13-HODE); 9,10-di-hydroxy-12Z-octadecenoic acid (9,10-DiHOME); 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME); 19,20-dihydroxy -4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20 DiHDPA); N-acetylmethionine; methionine sulfone; S-adenosylhomocysteine; cysteine; cysteine sulfinic acid, pregnenolone sulfate; 5 alpha -pregnan-3beta,20beta-diol monosulfate; pregnen-diol disulfate; pregn steroid monosulfate; pregnanediol-3-glucuronide; corticosterone; cortisone; dehydroisoandrosterone sulfate (DHEA -S); 16a-hydroxy DHEA 3-sulfate; epiandrosterone sulfate; androsterone sulfate; 4-androsten -3beta, 17beta-diol monosulfate; 4-androsten-3alpha, 17alpha-diol monosulfate; 4-androsten -3beta, 17beta-diol disulfate; 5alpha-androstan-3alpha, 17alpha-diol monosulfate; 5alpha -androstan-3beta, 17-betadiol disulfate; andro steroid monosulfate; etiocholanolone glucuronide; pregnanolone/alloprenanolone sulfate; eicosapentaenoate; mead acid; stearidonate; nicotinamide; and pantothenate;
(iii) identifying the subject as not responsive to the treatment if the level of the metabolite biomarker set deviates from the level of a corresponding metabolite biomarker set in a control sample; and
(iv) administering to the subject identified in (iii) a therapeutic agent for treating HAE.