Methods for assessing efficacy of a drug in vivo by monitoring adme proteins in extracellular vesicles
OwnerWeiguo Tao, Xiaofeng Wuinventors
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Abstract
Materials and non-invasive methods are provided for determining a subject's present drug metabolic capacity by assessing a biofluid sample taken from the subject following administration of a compound and identifying phenotypic variations in activity of one or more drug absorption, distribution, metabolism and excretion (ADME) enzymes extracted from extracellular vesicles (EVs) in the biofluid sample. Additional materials and methods are provided for determining compound (e.g., drug) efficacy and dose ranging, either in a subject or in a treatment cohort, by quantifying level of expression of such ADME enzymes EVs selectively isolated from biofluid.
Claims20
A method for determining efficacy or dosing range of a compound comprising:
- selectively isolating a population of extracellular vehicles (EVs) in a biofluid sample of a subject having received at least one dose of a compound;
- extracting EV proteins from the isolated population of EVs;
- enriching the extracted EV proteins or peptides generated from the extracted EV proteins;
- and
- identifying and quantifying a level of expression of one or more targeted absorption, distribution, metabolism, and excretion (ADME) proteins in the enriched EV proteins or peptides;
- wherein:
- upregulated expression of the targeted one or more ADME proteins in the subject as compared to a baseline expression of the targeted one or more ADME proteins is indicative of metabolism by the subject of the compound and the at least one dose of the compound being within the therapeutic index of the compound for the subject, and
- baseline expression of the targeted one or more ADME proteins in the subject is indicative of the at least one dose of the compound being outside of the therapeutic index of the compound for the subject.
A method for profiling a subject's present drug response phenotype comprising:
- selectively isolating a population of extracellular vehicles (EVs) in a biofluid sample of a subject that has received at least one dose of a first compound;
- extracting EV proteins from the isolated population of EVs;
- enriching the extracted EV proteins or peptides generated from the extracted EV proteins;
- and
- identifying and quantifying a level of expression, using parallel reaction monitoring, of one or more targeted drug absorption, distribution, metabolism, and excretion (ADME) proteins in the enriched EV proteins or peptides;
- and
- assigning the subject a phenotype for drug metabolism of poor, intermediate, extensive or ultra-rapid based on the level of expression of the targeted one or more ADME proteins.
A method for determining drug efficacy comprising:
- isolating a population of extracellular vehicles (EVs) in a biofluid sample of a subject having received at least one dose of a compound;
- extracting EV proteins from the isolated population of EVs;
- enriching the extracted EV proteins or peptides generated from the extracted EV proteins;
- and
- identifying and quantifying a level of expression of one or more targeted drug absorption, distribution, metabolism, and excretion (ADME) proteins in the enriched EV proteins or peptides;
- wherein:
- upregulated expression of the targeted one or more ADME proteins in the subject as compared to a baseline expression of the targeted one or more ADME proteins is indicative of the at least one dose of the compound being within the therapeutic index of the compound for the subject, and
- baseline expression of the targeted one or more ADME proteins in the subject is indicative of the at least one dose of the compound being outside of the therapeutic index for the subject;
- and
- wherein the step of isolating is performed via lipid affinity-based capture using a device comprising a plurality of microspheres having surfaces coated or modified with a combination of at least one hydrophilic group and at least one hydrophobic group.
Dependencies are inferred from the claim text.