Nitroprotein biomarkers for copd
AssigneeChiesi Farmaceutici S.p.A.
InventorsDominic M. DESIDERIO, Xianquan Zhan
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Abstract
Specific nitroprotein biomarkers may be used as prognostic and diagnostic tools for COPD. Identification of certain specific nitroprotein biomarkers allows the development of targeted therapies aimed at prevention and treatment of COPD.
Claims34
A method for identifying a patient at risk of developing COPD, comprising:
- (i) obtaining a biological sample from a patient;
- (ii) selectively identifying the presence or absence of one or more individual nitroproteins in the sample;
- and
- (iii) identifying the patient as being at risk of developing COPD if one or more said nitroproteins is present in the sample.
A method for identifying a patient at risk of developing COPD, comprising:
- (i) obtaining a sample of bronchoalveolar lavage fluid (BALF) from a patient;
- (ii) immunoprecipitating one or more nitroproteins from the BALF sample with anti nitrotyrosine antibodies;
- (iii) digesting said immunoprecipitated one or more nitroproteins with a suitable protease to generate at least one nitropeptide;
- (iv) analysing said at least one nitropeptide by mass spectrometry and determining its sequence;
- and
- (v) identifying said patient as being at risk of developing COPD if one or more of said at least one nitropeptide matches a fragment of the amino acid sequence of proteins selected from the group consisting of:
- progestin and adipoQ receptor family member III, zinc finger protein 432, proteasome subunit alpha type 2, NADH-ubiquinone oxidoreductase B14, slit homolog 1 protein, and lysozyme.
A method for diagnosing early stage COPD in a patient, comprising:
- (i) obtaining a biological sample from a patient;
- (ii) selectively identifying the presence or absence of one or more individual nitroproteins in the sample;
- and
- (iii) identifying said patient as having early stage COPD if one or more said nitroproteins is present in the sample.
A method for monitoring the progression of COPD in a patient, comprising:
- (i) obtaining a first biological sample from a patient with COPD;
- (ii) selectively identifying the presence or absence of one or more individual nitroproteins in said first sample, and optionally quantifying them;
- (iii) obtaining a second biological sample from said patient at a later time point;
- (iv) selectively identifying the presence or absence of one or more individual nitroproteins in said second sample, and optionally quantifying them;
- and
- (v) diagnosing a progression in COPD in said patient if there is a significant increase in the number or quantities of any individual nitroproteins in said second sample relative to said first sample.
A COPD biomarker, which comprises the amino acid sequence of any of the peptides of SEQ ID NO:
- 1-8, or a homologue or subfragment thereof.
A COPD biomarker, which is selected from the group consisting of:
- progestin and adipoQ receptor family member III, zinc finger protein 432, proteasome subunit alpha type 2, NADH-ubiquinone oxidoreductase B14, slit homolog 1 protein, lysozyme, aldose 1-epimerase, PTS system lactose-specific EIICB component, and peptide fragments thereof.
A diagnostic kit for identifying individuals susceptible to developing COPD, comprising an antibody capable of specifically recognising and binding to a nitroprotein or nitropeptide from a biological sample, said nitroprotein or nitropeptide being selected from the group consisting of progestin and adipoQ receptor family member III, zinc finger protein 432, proteasome subunit alpha type 2, NADH-ubiquinone oxidoreductase B14, slit homolog 1 protein, lysozyme, aldose 1-epimerase;
- PTS system lactose-specific EIICB component, and peptide fragments thereof.
A method for assessing the efficacy of potential therapeutic agent for COPD in a subject who has been diagnosed with COPD, comprising:
- (i) obtaining a first biological sample from said subject before administering said potential therapeutic agent;
- (ii) then administering said potential therapeutic agent to the subject;
- (iii) obtaining a second biological sample from said subject after administering said potential therapeutic agent;
- (iv) selectively identifying the presence or absence of one or more individual nitroproteins in said first and in said second sample, and optionally quantifying them;
- and
- (v) confirming the efficacy of said potential therapeutic agent in said patient if there is a significant decrease in the number or quantities of any individual nitroproteins in said second sample relative to said first sample.
A method for assessing the harmful potential of a substance in causing COPD, comprising:
- (i) obtaining a first biological sample from an animal before administering said substance;
- (ii) then administering said potentially harmful substance;
- (iii) obtaining a second biological sample from said animal after administering said substance;
- (iv) selectively identifying the presence or absence of one or more individual nitroproteins in said first and in said second sample, and optionally quantifying them;
- and
- (v) confirming the harmful effect of said substance in said animal if there is a significant increase in the number or quantities of any individual nitroproteins in said second sample relative to said first sample.
A ligand, capable of binding specifically and selectively to a nitroprotein selected from the group consisting of progestin and adipoQ receptor family member III, zinc finger protein 432, proteasome subunit alpha type 2, NADH-ubiquinone oxidoreductase B14, slit homolog 1 protein, and lysozyme.
A ligand, capable of binding specifically and selectively to a nitropeptide selected from the group consisting of SEQ ID NOS:1-5.
An isolated peptide sequence, consisting of any of SEQ ID NOS:
- 1-8, or a homologue or subfragment of any of SEQ ID NOS:1-8.
An isolated nitroprotein, which is selected from the group consisting of:
- progestin and adipoQ receptor family member III;
- zinc finger protein 432;
- proteasome subunit alpha type 2;
- NADH-ubiquinone oxidoreductase B14;
- slit homolog 1 protein;
- lysozyme;
- aldose 1-epimerase;
- and PTS system lactose-specific EIICB component.
Dependencies are inferred from the claim text.