US 2007/0190586 A1 · Detection and determination of the stages of coronary artery disease

Abstract

A method having clinically sufficient degree of diagnostic accuracy for detecting the presence of coronary artery disease in a human patient from the general population and for distinguishing between the stages of the disease in that patient is disclosed. The stages are, first, the non-acute stage, which is either asymptomatic coronary artery disease or stable angina, second, the acute stage known as unstable angina, and, third, the acute stage known as acute myocardial infarction. The diseased state (as opposed to the non-diseased state) is indicated by the clinically significant presence of a first marker in a sample from the patient. The presence of one of the two acute stages, unstable angina or acute myocardial infarction, is indicated by the clinically significant presence of a second marker in a sample from the patient. The presence of the more severe acute stage known as acute myocardial infarction is indicated by the clinically significant presence of a third marker in a sample from the patient. Preferably the first marker comprises OxLDL, the second marker comprises MDA-modified LDL, and the third marker is a troponin. Preferably the OxLDL and MDA-modified LDL are detected using monoclonal antibodies that can detect the presence of those markers in undiluted human plasma at concentrations as low as 0.02 milligrams/deciliter.

Claims27

Dependent claims

1-58. (canceled)

A method for diagnosing coronary artery disease comprising performing steps (a), (c), and (e) and at least one of steps (b) and (d):

(a) obtaining one or more human samples comprising whole blood or a fluid derived from whole blood;
(b) comparing or having compared a level of oxidized low density lipoprotein (OxLDL) having at least 60 aldehyde-modified lysine residues per apolipoprotein B-100 (apo B-100) moiety in one of the one or more human samples to the level of OxLDL in a control;
(c) comparing or having compared a level of malondialdehyde-modified low density lipoprotein (MDA-modified LDL) having at least 60 aldehyde-modified lysine residues per apolipoprotein B-100 (apo B-100) moiety in one of the one or more human samples to the level of MDA-modified LDL in a control;
(d) comparing or having compared a level of a heart protein in one of the one or more human samples to the level of heart protein in a control;
and
(e) making a diagnosis based on results from step (c) and at least one of steps (b) and (d) from the following matrix if steps (b), (c), and (d) are all performed:
Indication
(b)
(c)
(d)
the individual does not have coronary artery disease
−
−
−
the individual has chronic coronary artery disease
+
−
−
the individual has unstable angina
+
+
−
the individual has acute myocardial infarction of
+
+
+
atherosclerotic origin
the individual has acute myocardial infarction of
−
−
+
non-atherosclerotic origin
or making a diagnosis based on results from step (c) and at least one of steps (b) and (d) from the following matrix if steps (b) and (c) are performed:
Indication
(b)
(c)
the individual does not have coronary artery disease
−
−
the individual has chronic coronary artery disease
+
−
the individual has acute coronary artery disease
+
+
or making a diagnosis based on results from step (c) and at least one of steps (b) and (d) from the following matrix if steps (c) and (d) are performed:
Indication
(c)
(d)
the individual does not have acute coronary artery disease
−
−
the individual has unstable angina
+
−
the individual has acute myocardial infarction of
−
+
non-atherosclerotic origin
the individual has acute myocardial infarction of
+
+
atherosclerotic origin
wherein “+” indicates that the level of the OxLDL, MDA-modified LDL, and heart protein in the human sample is higher compared to the level of the OxLDL, MDA-modified LDL, and heart protein in the control and “−” indicates that the level of the OxLDL, MDA-modified LDL, and heart protein in the human sample is not higher compared to the level of the OxLDL, MDA-modified LDL, and heart protein in the control, the control providing results based on those of a control population.

61 more elements

A method for diagnosing coronary artery disease comprising performing steps (a), (c), and (e) and at least one of steps (b) and (d):

(a) obtaining one or more human samples comprising whole blood or a fluid derived from whole blood;
(b) performing or having performed an immunological assay using mAb4E6 on one of the one or more human samples and comparing a level of oxidized LDL (OxLDL) having at least 60 aldehyde-modified lysine residues per apolipoprotein B-100 (apo B-100) moiety in the human sample from the assay to the level of OxLDL in a control;
the monoclonal antibody mAb4E6 being produced by hybridoma Hyb4E6, which was deposited on Apr. 24, 1997 at the Belgian Coordinated Collections Of Microorganisms under accession number LMBP 1660 CB;
(c) performing or having performed an immunological assay using mAb-1H11 on one of the one or more human samples and comparing a level of malondialdehyde-modified low density lipoprotein (MDA-modified LDL) having at least 60 aldehyde-modified lysine residues per apolipoprotein B-100 (apo B-100) moiety in the human sample from the assay to the level of MDA-modified LDL in a control;
the monoclonal antibody mAb-1H11 being produced by hybridoma Hyb1H11, which was deposited on Apr. 24, 1997 at the Belgian Coordinated Collections Of Microorganisms under accession number LMBP 1659 CB;
(d) performing or having performed an assay for a heart protein on one of the one or more human samples and comparing a level of a heart protein in the human sample from the assay to the level of heart protein in a control;
and
(e) making a diagnosis based on results from step (c) and at least one of steps (b) and (d) from the following matrix if steps (b), (c), and (d) are all performed:
Indication
(b)
(c)
(d)
the individual does not have coronary artery disease
−
−
−
the individual has chronic coronary artery disease
+
−
−
the individual has unstable angina
+
+
−
the individual has acute myocardial infarction of
+
+
+
atherosclerotic origin
the individual has acute myocardial infarction of
−
−
+
non-atherosclerotic origin
or making a diagnosis based on results from step (c) and at least one of steps (b) and (d) from the following matrix if steps (b) and (c) are performed:
Indication
(b)
(c)
the individual does not have coronary artery disease
−
−
the individual has chronic coronary artery disease
+
−
the individual has acute coronary artery disease
+
+
or making a diagnosis based on results from step (c) and at least one of steps (b) and (d) from the following matrix if steps (c) and (d) are performed:
Indication
(c)
(d)
the individual does not have acute coronary artery disease
−
−
the individual has unstable angina
+
−
the individual has acute myocardial infarction of
−
+
non-atherosclerotic origin
the individual has acute myocardial infarction of
+
+
atherosclerotic origin
wherein “+” indicates that the level of the OxLDL, MDA-modified LDL, and heart protein in the human sample is higher compared to the level of the OxLDL, MDA-modified LDL, and heart protein in the control and “−” indicates that the level of the OxLDL, MDA-modified LDL, and heart protein in the human sample is not higher compared to the level of the OxLDL, MDA-modified LDL, and heart protein in the control, the control providing results based on those of a control population.

63 more elements

Dependencies are inferred from the claim text.

Facts

Application

11/654,097Filed 16 Jan 2007

Priority

4 Sep 1998

Published

16 Aug 2007

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

G01N 33/721
Involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood: haemoglobin
G01N 33/6893
Involving proteins, peptides or amino acids: related to diseases not provided for elsewhere
G01N 33/92
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing:…
G01N 2800/32
Detection or diagnosis of diseases: cardiovascular disorders

Family

Application09/148,158Continuation · filed 4 Sep 1998

Application09/906,560Continuation · filed 16 Jul 2001

Application10/174,797Division · filed 18 Jun 2002

Application10/174,797Continuation · filed 18 Jun 2002

Application11/654,097Division · filed 16 Jan 2007

US 2001/0049112 A1Published application

US 2003/0013127 A1Published application

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