Spectographic Metabolite-Signature for Identifying a Subject's Susceptibility to Drugs

Abstract

A method of predicting the responsiveness of a patient to a pharmaceutical drug by measuring metabolites in a biological sample from the patient is disclosed. Specific drug metabolites in blood from breast cancer patients are analyzed using NMR spectroscopy whereby responsiveness of the human cancer patients before, during and after treatment with a cancer drug is assessed by measuring the change in clinical outcomes. Data obtained is used to identify particular NMR resonances that are strongly correlated with whether the patient is responsive or resistant to each drug. As such, models for predicting the responsiveness of a patient to each drug based on metabolites from the patient are provided.

1 .- 22 . (canceled) 
     
     
         23 . A method of treating a patient, comprising:
 obtaining a sample from a patient wherein the sample is selected from the group consisting of blood, urine, feces, cerebral fluid, saliva and tissue extract;   analyzing a component of the sample using NMR spectroscopy;   obtaining an array of data on the sample from the NMR spectroscopy;   comparing the array of data to data of a statistically significant number of patients administered palbociclib;   determining a Biomarker of Response in patients based on patient response to the palbociclib;   counseling the patient regarding medical options based on determining the Biomarker of Response;   administering palbociclib to the patient wherein the patient has been predetermined as a responder to palbociclib based on having the Biomarker of Response.   
     
     
         24 . The method of  claim 23 , wherein the spectroscopy is carried out by using 2D  1 H- 13 C HSQC NMR spectroscopy. 
     
     
         25 . The method of  claim 23 , wherein the palbociclib has been approved for use only when the patient has been predetermined as a responder to the drug based on the Biomarker of Response. 
     
     
         26 . A method of selecting a population of patients, comprising:
 (a) administering to a group of patients palbociclib over a period of time;   (b) analyzing a metabolite in a biological sample obtained from the patients, wherein the sample is selected from the group consisting of blood, urine, feces, cerebral fluid, saliva and tissue extract of the group of patients at a first point in time;   (c) analyzing the metabolite in the sample of the group of patients at a second point in time different from the first point in time;   (d) comparing results of the analyzing in (b) with the analyzing in (c) to obtain a differential; and   (e) relating the differential to how a patient responds to palbociclib thereby determining responders to palbociclib, which are selected for treatment with palbociclib.   
     
     
         27 . The method as claimed in  claim 26 , further comprising:
 (f) counseling a patient on how the differential obtained in (d) relates to a patient's likely response to palbociclib.   
     
     
         28 . A method of selecting a population of patients, comprising:
 (a) analyzing a metabolite in a biological sample selected from the group consisting of blood, urine, feces, cerebral fluid, saliva and tissue extract of a group of patients taking palbociclib at a first point in time;   (b) continuing to administer to the group of patients the palbociclib over a period of time;   (c) analyzing the metabolite in the sample of the group of patients at a second point in time different from the first point in time;   (d) comparing results of the analyzing in (a) with the analyzing in (c) to obtain a differential;   (e) relating the differential to how a patient responds to palbociclib thereby determining responders to palbociclib, which are selected for further treatment with palbociclib.   
     
     
         29 . The method of  claim 28 , further comprising:
 (f) counseling a patient regarding likelihood of responding to palbociclib.   
     
     
         30 . The method of determining a point at which a patient develops resistance to palbociclib, comprising:
 (a) analyzing a metabolite in a human biological sample of a patient at a first point in time wherein the patient is being treated with a palbociclib;   (b) continuing to treat the patient over time with palbociclib;   (c) analyzing the sample of the patient at a point in time different from the analyzing in step (a);   (d) comparing the analyzing of (a) with the analyzing of (c) to obtain a differential; and   (e) relating to the differential to a standard in order to determine if the patient has developed a resistance to palbociclib.   
     
     
         31 . The method of  claim 30 , further comprising:
 counseling the patient regarding developing resistance to palbociclib; and   discontinuing administration of the palbociclib to the patient when it is determined by comparison of the differential to a standard that the patient has developed resistance to palbociclib.   
     
     
         32 . The method of  claim 30 , wherein the analyzing steps (a) and (c) are begun within 4 hours or less after extraction of the sample from the patient. 
     
     
         33 . The method of  claim 30 , wherein the analyzing step is begun within 15 minutes or less after extraction of the sample from the patient. 
     
     
         34 . The method of  claim 30 , further comprising:
 preserving the sample after extraction from a patient and before the analyzing step (a) or (c).   
     
     
         35 . The method of  claim 34 , wherein the preserving step comprises contacting the sample with a preservative. 
     
     
         36 . The method of  claim 34 , wherein the sample is blood, and the preserving step comprises putting blood into a tube that contains a preservative. 
     
     
         37 . The method of  claim 34 , wherein the preserving step comprises reducing the temperature of the sample. 
     
     
         38 . The method of  claim 34 , wherein the preserving step comprises freezing the sample. 
     
     
         39 . A method of treating a patient, comprising:
 (a) analyzing a sample obtained from a patient being treated with palbociclib using spectroscopy;   (b) obtaining data from the spectroscopy;   (c) comparing the data obtained in (b) with data obtained from a statistically significant sample of patients treated with palbociclib in order to determine a differential;   (d) continuing to treat the patient with palbociclib overtime while periodically repeating steps (a), (b), and (c); and   (e) counseling the patient with respect to the significance of the differential obtained; and   (f) modifying treatment of the patient based on the differential.   
     
     
         40 . The method as claimed in  claim 39 , wherein the patient is a cancer patient, and the spectroscopy is nuclear magnetic residence (NMR) spectroscopy. cations.