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US 10,473,640 B2Granted
Drug selection for gastric cancer therapy using antibody-based arrays
AssigneeSociete des Produits Nestle S.A.
InventorsSharat Singh, Phillip Kim, Xinjun Liu, Belen Ybarrondo
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Abstract
The present invention provides methods for selecting a suitable anticancer therapy, and for identifying and predicting response for the treatment of a gastric cancer.
Claims18
A method for selecting a suitable anticancer drug for the treatment of a subject with gastric cancer, the method comprising:
- (a) isolating a cancer cell from a subject with gastric cancer after administration of an anticancer drug, or prior to incubation with an anticancer drug;
- (b) determining the activation level of at least each of the following analytes in a cellular extract produced from the isolated cancer cell:
- HER1, HER2, HER3, c-Met, IGF1R, and PI3K,
- wherein determining the activation level of each of said analytes comprises:
- (i) incubating the cellular extract with a dilution series of capture antibodies specific for each of said analytes to form a plurality of captured analytes, wherein the capture antibodies are restrained on a solid support;
- (ii) washing and then incubating the plurality of captured analytes with detection antibodies comprising activation state-independent antibodies and activation state-dependent antibodies specific for each of said analytes to form a plurality of detectable captured analytes,
- wherein the activation state-independent antibodies are labeled with glucose oxidase, wherein the glucose oxidase and the activation state-independent antibodies are conjugated to a sulfhydryl-activated dextran molecule, wherein the activation state-dependent antibodies are labeled with a first member of a signal amplification pair, and wherein the glucose oxidase generates an oxidizing agent which channels to and reacts with the first member of the signal amplification pair;
- (iii) washing and then incubating the plurality of detectable captured analytes with a second member of the signal amplification pair to generate an amplified signal;
- and
- (iv) detecting the amplified signal generated from the first and second members of the signal amplification pair;
- (c) comparing the activation level of each of said analytes in the cellular extract to a reference activation level of each of said analytes that is generated in the absence of the anticancer drug;
- and
- (d) selecting the anticancer drug as suitable for the treatment of the subject with gastric cancer when each of said analytes in the cellular extract is substantially less activated than in the absence of the anticancer drug.
10 more elements
Dependencies are inferred from the claim text.