Vasoactive hormone-based stratification of patients suffering from diseases related to endothelial function/dysfunction

Patent metadata

Field	Value
Publication number	US-9229013-B2
Application number	US-201013318488-A
Country	US
Kind code	B2
Filing date	May 5, 2010
Priority date	May 5, 2009
Publication date	Jan 5, 2016
Grant date	Jan 5, 2016

Abstract

The present invention relates to a method for the stratification of a subject having an acute or a chronic disease, wherein the disease affects endothelial function/dysfunction, comprising the steps of (i) taking a sample of bodily fluid from the subject; (ii) determining in the sample of bodily fluid the concentration of a vasoactive hormone or fragments thereof or precursors or fragments thereof having a length of at least 12 amino acid residues; (iii) stratifying the subjects into either of the categories: (a) responder to a medication for treatment of the disease, (b) non-responder to a medication for treatment of the disease not showing an unfavorable effect after having received the medication; (c) subjects showing an unfavorable effect after having received the medication. The invention also relates to the use of an antibody or a functional fragment thereof in the method according to the invention.

First claim

The invention claimed is:

1. A method for the stratification of a subject having an acute or a chronic disease for response to or risk of unfavorable effect from administration of a medication, wherein said disease affects endothelial function, comprising:
(i) detecting and quantitating in a sample of bodily fluid from said subject the concentration of a vasoactive hormone, a precursor of said vasoactive hormone, or a fragment of said hormone or precursor, selected from the group consisting of
a. a peptide hormone a precursor of said peptide hormone, and a fragment of said peptide hormone or precursor of said peptide hormone, selected from the group consisting of Adrenomedullin (ADM), proADM, Midregional proADM (MR-proADM), Atrial Natriuretic Peptide (ANP), proANP, Midregional proANP (MR-proANP), Brain natriuretic peptide (BNP), proBNP, N-Terminal proBNP (NT-proBNP), C-type natriuretic peptide (CNP), proCNP, Endothelin-1 (ET-1), proET-1, C-Terminal proET-1 (CT-proET-1), Endothelin-2 (ET-2), proET-2, Endothelin-3 (ET-3), proET-3, Arginine-Vasopressin (AVP), proAVP, C-Terminal-proAVP (CT-proAVP or Copeptin), Dendroaspis natriuretic peptide (DNP), proDNP, Urodilatin, proUrodilatin, Angiotensin II, pro-Angiotensin-II, Urocortin, proUrocortin, Urocortin-2 (Stresscopin-related peptide), proUrocortin-2, Urocortin-3 (Stresscopin), proUrocortin-3, Urotensin-II, proUrotensin-II, Urotensin II-related protein (URP), proURP, Neuropeptide Y (NPY), proNPY, Vasoactive intestinal peptide (VIP), proVIP, Calcitonin gene-related peptide I (CGRP I), proCGRP I, Calcitonin gene-related peptide II (CGRP II), proCGRP II, Relaxin, proRelaxin, Endokinin A, and proEndokinin A;
b. a small peptide hormone selected from the group consisting of Bradykinin, proBradykinin, Apelin, proApelin, Neurotensin, proNeurotensin, Substance P, Neurokinin A (Substance K), proTachykinin A, N-terminal proTachykinin A (NT-proPTA), Endokinin A/B, proEndokinin A/B, Endokinin C, proEndokinin C, Methionine-Enkephalin, Leucine-Enkephalin, proenkephalin (PENK), and Mid-Regional-PENK (MR-PENK); or
c. a hormone selected from the group consisting of Serotonin, Prostaglandins and Thromboxane;
wherein said detection and quantitation comprises a diagnostic assay, said assay comprising
a′. contacting the sample with a diagnostic assay reagent comprising a capture probe that specifically binds to vasoactive hormone, precursor of said vasoactive hormone or fragment of said hormone or precursor, and
b′. detecting and quantitating thus-formed complexes of capture probe and vasoactive hormone, precursor of said vasoactive hormone or fragment of said hormone or precursor, and;

(ii) stratifying said subject based on the thus-determined concentration of the vasoactive hormone, precursor of said vasoactive hormone or fragment of said hormone or precursor into one of the following categories by comparison to pre-determined threshold concentration values correlated to the categories:
(a) a responder to a medication for treatment of said disease;
(b) a non-responder to a medication for treatment of said disease not showing an unfavorable effect after having received said medication;
(c) a subject showing an unfavorable effect after having received said medication,
wherein the vasoactive hormone is ADM, pro-ADM or MR-proADM,
wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease (COPD), post stroke condition and post myocardial infarct condition, and
wherein the medication is selected from the group consisting of an anti-coagulant, warfarin, a thrombolytic drug, a platelet aggregation inhibitor, a β-blocker, a lipid lowering substance, a statin, a diuretic, an Angiotensin-Converting Enzyme (ACE) inhibitor, a calcium channel blocker, a prostacyclin derivative, a hormone therapeutic agent, a steroid, a nitrate, acetylsalicylic acid and an antibiotic;

(d) a subject showing an unfavorable effect after having received said medication,
wherein the vasoactive hormone is ANP, pro-ANP, or MR-proANP),
wherein the disease is selected from the group consisting of COPD, post stroke condition and post myocardial infarct condition, and
wherein the medication is selected from the group consisting of an anti-coagulant, warfarin, a thrombolytic drug, a platelet aggregation inhibitor, a β-blocker, a lipid lowering substance, a statin, a diuretic, an ACE inhibitor, a calcium channel blocker, a prostacyclin derivative, a hormone therapeutic agent, a steroid, a nitrate, acetylsalicylic acid and antibiotic;

(e) a subject showing an unfavorable effect after having received said medication,
wherein the vasoactive hormone is Endothelin-1, proET-1 or CT-proET-1,
wherein the disease is selected from the group consisting of COPD, post stroke condition and post myocardial infarct condition, and
wherein the medication is selected from the group consisting of an anti-coagulant, warfarin, a thrombolytic drug, a platelet aggregation inhibitor, a β-blocker, an anti-oxidant, a lipid lowering substance, a statin, a diuretic, an ACE inhibitor, a calcium channel blocker, an endothelin-receptor antagonist, a prostacyclin derivative, a hormone therapeutic agent, a steroid, a nitrate, acetylsalicylic acid, and an antibiotic; or

(f) a subject showing an unfavorable effect after having received said medication,
wherein the vasoactive hormone is AVP, proAVP, or CT-proAVP (Copeptin),
wherein the disease is selected from the group consisting of COPD, post stroke condition and post myocardial infarct condition, and
wherein the medication is selected from the group consisting of an anti-coagulant, warfarin, a thrombolytic drug, a platelet aggregation inhibitor, a β-blocker, an anti-oxidant, a lipid lowering substance, a statin, a diuretic, an ACE inhibitor, a calcium channel blocker, a prostacyclin derivative, a hormone therapeutic agent, a steroid, a nitrate, acetylsalicylic acid and an antibiotic.

2. The method of claim 1 , wherein categories (a) and (b) are considered as a single category.

3. A method for the stratification of a subject having an acute or a chronic disease for risk of an unfavourable effect from administration of a medication, wherein said disease affects endothelial function, comprising:
(i) detecting and quantitating in a sample of bodily fluid from said subject the concentration of a vasoactive hormone, a precursor of said vasoactive hormone, or a fragment of said hormone or precursor, selected from the group consisting of
a. a peptide hormone a precursor of said peptide hormone, and a fragment of said peptide hormone or precursor of said peptide hormone, selected from the group consisting of Adrenomedullin (ADM), proADM, Midregional pro-ADM (MR-proADM), Atrial Natriuretic Peptide (ANP), proANP, Midregional proANP (MR-proANP), Brain natriuretic peptide (BNP), proBNP, N-Terminal proBNP (NT-proBNP), C-type natriuretic peptide (CNP), proCNP, Endothelin-1 (ET-1), proET-1, C-Terminal proET-1 (CT-proET-1), Endothelin-2 (ET-2), proET-2, Endothelin-3 (ET-3), proET-3, Arginine-Vasopressin (AVP), proAVP, C-Terminal-proAVP (CT-proAVP or Copeptin), Dendroaspis natriuretic peptide (DNP), proDNP, Urodilatin, proUrodilatin, Angiotensin II, pro-Angiotensin-II, Urocortin, proUrocortin, Urocortin-2 (Stresscopin-related peptide), proUrocortin-2, Urocortin-3 (Stresscopin), proUrocortin-3, Urotensin-II, proUrotensin-II, Urotensin II-related protein (URP), proURP, Neuropeptide Y (NPY), proNPY, Vasoactive intestinal peptide (VIP), proVIP, Calcitonin gene-related peptide I (CGRP I), proCGRP I, Calcitonin gene-related peptide II (CGRP II), proCGRP II, Relaxin, proRelaxin, Endokinin A, and proEndokinin A;
b. a small peptide hormone selected from the group consisting of Bradykinin, proBradykinin, Apelin, proApelin, Neurotensin, proNeurotensin, Substance P, Neurokinin A (Substance K), proTachykinin A, N-terminal pr

Assignees

• Bergmann Andreas
• Struck Joachim
• Hartmann Oliver
• Ng Leong Loke
• Brahms Gmbh

Inventors

• Bergmann Andreas
• Struck Joachim
• Hartmann Oliver
• Ng Leong Loke

Classifications

• G01N2333/5757

  Vasoactive intestinal peptide [VIP] or related peptides · CPC title

• G01N33/74 Primary

  involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} · CPC title

• G01N2333/5754

  Endothelin, vasoactive intestinal contractor [VIC] · CPC title

• G01N2333/58

  Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin · CPC title

• 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