Biomarkers
AssigneeOtage Innovation Limited
InventorsChristopher Joseph Pemberton, Arthur Mark Richards, Michael Gary Nicholls, Timothy Grant Yandle
Life of this patent
Estimating the term…
Abstract
The invention provides methods for predicting, diagnosing or monitoring acute cardiac disorders, cardiac transplant rejection, or distinguishing acute cardiac disorders from pulmonary disorders, by measuring ANP signal peptide levels in a sample taken from a subject shortly after onset of, or presentation with the disorder or transplant rejection. Also provided are antibodies useful in the methods of the invention.
Claims67
An antibody or antigen fragment binding thereof which binds
- (a) ANP-SP amino acid sequence 16-25 (SEQ ID NO:12) or 1-10 (SEQ ID NO:16);
- (b) an amino acid sequence encoded by a nucleotide sequence selected from SEQ ID NO:13 or SEQ ID NO:17;
- or
- (c) a variant or fragment of (a) or (b).
A method for predicting, diagnosing or monitoring an acute cardiac disorder (ACD) in a subject, the method comprising:
- measuring the level of ANP-SP in a biological sample obtained from the subject within four hours of onset of the ACD, or within four hours of presentation with ACD;
- and
- comparing the level of said ANP-SP with the ANP-SP level from a control wherein a measured level of ANP-SP higher than the control level is indicative of ACD.
A method for monitoring a response to treatment of an acute cardiac disorder (ACD) in a subject, the method comprising measuring the level of ANP-SP in a biological sample obtained from the subject within four hours of onset of the ACD, or within four hours of presentation with the ACD;
- and comparing the level of said ANP-SP with the ANP-SP level from a control, wherein a change in the measured level of ANP-SP from the control level is indicative of a response to the treatment.
A method for predicting, diagnosing or monitoring a cardiac transplant rejection episode in a subject, the method comprising measuring the level of ANP-SP in a biological sample obtained from a subject within four hours of heart transplant and comparing the level of said ANP-SP with the ANP-SP level from a control, wherein a measured level of ANP-SP higher than the control level is indicative of transplant rejection.
A method of distinguishing between a pulmonary disorder and an acute cardiac disorder (ACD) in a subject, the method comprising measuring the level of ANP-SP in a biological sample obtained from a subject within four hours of presentation with the disorder;
- and comparing the level of said ANP-SP with the ANP-SP level from a control wherein a measured ANP-SP level higher than the control level is indicative of ACD.
A method for predicting, diagnosing or monitoring an acute cardiac disorder (ACD), cardiac transplant rejection, or ACD/pulmonary disorder in a subject, the method comprising measuring the level of ANP-SP in a biological sample obtained from the subject within the first four hours of onset of, or clinical presentation with ACD, cardiac transplant rejection or ACD/pulmonary disorder, wherein the measured level of ANP-SP is compared with the ANP-SP level from a control wherein a measured level of ANP-SP higher than the control level is indicative of ACD or transplant rejection.
An assay for ANP-SP in a biological sample obtained from a subject within four hours from onset of ACD, cardiac transplant rejection, or ACD/pulmonary disorder or within four hours of clinical presentation with ACD, cardiac transplant rejection, or ACD/pulmonary disorder, the assay comprising detecting and measuring the level of ANP-SP in the sample using any known methods.
An assay for ANP-SP comprising:
- (a) binding one or more ANP-SP polypeptides from a biological sample, wherein the ANP-SP polypeptide is selected from the group ANP-SP (1-10) (SEQ ID NO:16), and ANP-SP 16-25 (SEQ ID NO:12), or a variant or fragment thereof;
- and
- (b) measuring the level of bound ANP-SP polypeptide.
An ANP-SP binding agent that binds ANP-SP (SEQ ID NO:14) or a fragment or variant thereof for use in predicting, diagnosing or monitoring an acute cardiac disorder (ACD), cardiac transplant rejection or ACD/pulmonary disorder in a subject, wherein the ACD, cardiac transplant rejection or ACD/pulmonary disorder is characterised by the appearance of ANP-SP in a biological sample obtained from the subject within four hours of onset of, or within four hours of clinical presentation with ACD, cardiac transplant rejection or ACD/pulmonary disorder.
A use of ANP-SP binding agent in the manufacture of a prognostic, diagnostic or monitoring tool for assessing an acute cardiac disorder (ACD), cardiac transplant rejection or ACD/pulmonary disorder in a subject, wherein assessment is carried out within four hours of onset of, or within four hours of clinical presentation with ACD, cardiac transplant rejection or ACD/pulmonary disorder.
A use of ANP-SP binding agent for the prediction, diagnosis or monitoring of acute cardiac disorder (ACD), cardiac transplant rejection or ACD/pulmonary disorder in a subject, wherein the prognosis, diagnosis or monitoring is carried out within four hours of onset of or within four hours of clinical presentation with ACD, cardiac transplant rejection or ACD/pulmonary disorder.
A nucleic acid molecule encoding ANP-SP (16-25) (SEQ ID NO:12) or ANP-SP (1-10) (SEQ ID NO:16) or a fragment or variant thereof wherein said nucleic acid is
- (a) SEQ ID NO:13 or SEQ ID NO:17 or a variant or fragment thereof;
- (b) a sequence which has 70%, 75%, 80%, 90%, 95% or 99% sequence identity to SEQ ID NO:13 or SEQ ID NO:17;
- (c) a sequence which hybridises under stringent conditions to SEQ ID NO:13 or SEQ ID NO:17 or a fragment or variant thereof;
- (d) a sequence of at least 10 nucleotides in length, capable of hybridising to the sequence of any one of (a) to (c) under stringent conditions;
- (e) a complement of any one of (a) to (d);
- with the proviso that the sequence is not SEQ ID NO:
- 15.
An ANP-SP polypeptide or a variant or fragment thereof selected from:
- (a) ANP-SP (16-25) (SEQ ID NO:12) or a variant or fragment thereof;
- (b) ANP-SP (1-10) (SEQ ID NO:
- 16) or a variant or fragment thereof;
- or
- (c) an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95% or 99% amino acid identity to the polypeptide of SEQ ID NO:12 or SEQ ID NO:16.
Dependencies are inferred from the claim text.