# US 10,768,183 B2 · Metabolite panel for improved screening and diagnostic testing of cystic fibrosis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,768,183 B2 - Document ID: US10768183B2 - Status: Granted - Kind: B2 - Application number: 15/361,216 - Filed: 2016-11-25 - Published: 2017-07-13 - Granted: 2020-09-08 - Earliest claimed: 2014-05-26 - Assignees: McMaster University - Applicants: McMaster University - Inventors: Philip Britz-McKibbin - Web page: https://patentgrep.com/patent/US10768183B2 ## CPC - G01N 33/6893: {related to diseases not provided for elsewhere} - A23L 33/10: using additives (addition of substantially indigestible substances A23L33/21) - A23L 33/40: {Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula} - G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) - G01N 33/6806: {Determination of free amino acids} - G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems - A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs - G01N 27/4473: {by electric means} - G01N 2560/00: Chemical aspects of mass spectrometric analysis of biological material - G01N 2570/00: Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes - G01N 2800/382: Cystic fibrosis - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G16H 50/30: for calculating health indices; for individual health risk assessment - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA - A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION ## Abstract A method of diagnosing cystic fibrosis in a human subject is provided. The method includes the steps of: i) determining in a biological sample from the subject the level of one or more metabolic biomarkers; ii) comparing the level of the biomarker to a control level and determining the difference between the biomarker level and the control level; and iii) determining that the subject has cystic fibrosis or a related disorder when the difference in the level of the biomarker in the sample is statistically different from the control level. ## Claims ### Claim 1 A method of diagnosing and treating cystic fibrosis or CFTR (cystic fibrosis transmembrane conductor regulator)-related metabolic syndrome in a human infant subject comprising: i) detecting in a biological sample from the subject a level of each metabolic biomarker including L-glutamine (Gln), L-tyrosine (Tyr), L-serine, glycine and a metabolite having a m/z of 290.1347 and RMT of 1.2247, and/or L-glutamine, pilocarpic acid and mono(2-ethylhexyl)phthalate (MEHP); ii) comparing the level of each of the biomarkers to a corresponding control level for each biomarker; iii) determining that the infant subject has cystic fibrosis when the levels of L-glutamine, glycine, L-serine, L-tyrosine and a metabolite having a m/z of 290.1347 and RMT of 1.2247 are statistically significantly reduced from their corresponding control levels when the sample is a blood, serum or plasma sample, and/or the level of L-glutamine is increased, and the levels of MEHP and pilocarpic acid are reduced, in comparison to their corresponding control levels when the sample is a sweat sample; iv) treating the infant subject determined to have cystic fibrosis with one or more of nutritional supplementation, a CFTR potentiator, a CFTR corrector, an antibiotic, an anti-inflammatory agent, a mucus-thinning drug, a bronchodilator and a pancreatic enzyme. ### Claim 2 (depends on 1) The method of claim 1, wherein the biological sample is a blood, serum or plasma sample, and the levels of each of the biomarkers L-glutamine, glycine, L-serine, L-tyrosine and a metabolite having a m/z of 290.1347 and RMT of 1.2247 are reduced in comparison to their corresponding control levels. ### Claim 3 (depends on 2) The method of claim 2, wherein the sample is a dried blood sample. ### Claim 4 (depends on 2) The method of claim 2, wherein biomarkers, L-threonine and L-ornithine, are additionally detected, and reduced levels of L-threonine and L-ornithine in comparison to their corresponding control levels are indicative of CF in the infant. ### Claim 5 (depends on 1) The method of claim 1, comprising an additional step of determining a ratio of the levels of two biomarkers, comparing the ratio to a corresponding control ratio, determining the difference between the ratio and the corresponding control ratio, and determining that the subject has cystic fibrosis when the difference in the ratio is statistically different from the corresponding control ratio. ### Claim 6 (depends on 1) The method of claim 1, wherein the corresponding control level is the level of the biomarker in a sample from a healthy infant or healthy infant population that do not have cystic fibrosis. ### Claim 7 (depends on 1) The method of claim 1, wherein the corresponding control level is the level of the biomarker in a sample or samples from one or more infants that are carriers that do not have cystic fibrosis. ### Claim 8 (depends on 1) The method of claim 1, wherein the detection of the level of one or more biomarkers is by a mass spectrometry (MS)-based method selected from direct infusion-mass spectrometry, electrospray ionization (ESI)-MS, desorption electrospray ionization (DESI)-MS, direct analysis in real-time (DART)-MS, atmospheric pressure chemical ionization (APCI)-MS, liquid chromatography-mass spectrometry (LC-MS), gas chromatography- mass spectrometry (GC-MS), or capillary electrophoresis-mass spectrometry (CE-MS). ### Claim 9 (depends on 1) The method of claim 1, wherein the biological sample is a sweat sample and the level of L-glutamine is increased, and the levels of MEHP and pilocarpic acid are reduced, in comparison to their corresponding control levels. ### Claim 10 A method of confirming that a human infant subject is affected with cystic fibrosis and treating the subject for cystic fibrosis comprising the steps of: i) detecting in a biological sample from the subject a level of each metabolic biomarker including L-glutamine (Gln), L-tyrosine (Tyr), L-serine (Ser), glycine and a metabolite having a m/z:RMT of 290.1347:12247, or L-glutamine, pilocarpic acid and MEHP; ii) comparing the level of each of the biomarkers to a corresponding control level for each biomarker, and iii) confirming that the infant subject has cystic fibrosis when the levels of L-glutamine, glycine, L-serine, L-tyrosine and a metabolite having a m/z of 290.1347 and RMT of 1.2247 are reduced in comparison to their corresponding control levels in a blood, serum or plasma sample, or the level of L-glutamine is increased, and the levels of MEHP and pilocarpic acid are reduced, in comparison to their corresponding control levels in a sweat sample and treating the infant subject with one or more of a CFTR potentiator, a CFTR corrector, an antibiotic, an anti-inflammatory agent, a mucus-thinning drug, a bronchodilator and a pancreatic enzyme. ### Claim 11 (depends on 10) The method of claim 10, wherein the biological sample is a blood, serum or plasma sample, and the levels of each of the biomarkers L-glutamine, glycine, L-serine, L-tyrosine and a metabolite having a m/z:RMT of 290.1347:12247 are reduced in comparison to their corresponding control levels. ### Claim 12 (depends on 11) The method of claim 11, wherein the sample is a dried blood sample. ### Claim 13 (depends on 11) The method of claim 11, wherein biomarkers, L-threonine and L-ornithine, are additionally detected, and reduced levels of L-threonine and L-ornithine in comparison to their corresponding control levels are indicative of CF in the infant. ### Claim 14 (depends on 10) The method of claim 10, wherein the biological sample is a sweat sample and the level of L-glutamine is increased and the levels of MEHP and pilocarpic acid are reduced in comparison to their corresponding control levels.