Molecular profiling of tumors
Inventors
Von Hoff, Daniel D. • Loesch, David M. • Alarcon, Arlet • Penny, Robert J. • Wright, Alan • McGinniss, Matthew J. • Bender, Ryan P. • Pawlowski, Traci
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9322067-B2
Publication Date
2016-04-26
Expiration Date
Abstract
Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.
Core Innovation
The invention provides a method of identifying at least one candidate treatment for a subject in need of treatment for a cancer. The method performs immunohistochemistry (IHC) analysis on a sample from the subject on a plurality of IHC molecular targets, performs in situ hybridization (ISH) analysis on the sample on a plurality of ISH molecular targets, and performs DNA sequencing analysis on the sample on a plurality of sequencing molecular targets.
The plurality of IHC molecular targets comprises at least TOP1, TYMS, MGMT, PTEN, and HER2, and may include at least EGFR, PGP, RRM1, and TLE3. The plurality of ISH molecular targets comprises at least HER2 and cMET. The plurality of sequencing molecular targets comprises at least PIK3CA, KRAS, and BRAF.
A computer accesses a rules database comprising at least one biomarker-drug association rule for each of the molecular targets analyzed in the IHC, ISH, and DNA sequencing steps. A computer generated report is produced based on a comparison of the analysis against the rules in the rules database, and the report identifies the at least one candidate treatment.
The disclosed framework compares biomarker profiles derived from IHC, ISH, and DNA sequencing to biomarker-drug association rules, including positive efficacy and negative contraindications. The document further describes profiling-selected therapy outcomes using progression-free survival (PFS), disease-free survival (DFS), and response measures including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Claims Coverage
The document includes one independent claim directed to multi-modal biomarker profiling and rules/database comparison that produces a computer-generated report identifying at least one candidate treatment. The inventive features span IHC, ISH, DNA sequencing, rules database access, and report generation.
Multi-modal biomarker profiling with IHC, ISH, and sequencing
Perform an immunohistochemistry (IHC) analysis on a sample from the subject on a plurality of IHC molecular targets comprising at least TOP1, TYMS, MGMT, PTEN, and HER2; perform an in situ hybridization (ISH) analysis on the sample on a plurality of ISH molecular targets comprising at least HER2 and cMET; and perform DNA sequencing analysis on the sample on a plurality of sequencing molecular targets comprising at least PIK3CA, KRAS, and BRAF.
Rules database access with biomarker-drug association rules
Using a computer to access a rules database comprising at least one biomarker-drug association rule for each of the molecular targets analyzed in the IHC, ISH, and DNA sequencing analyses.
Computer-generated report identifying candidate treatment based on comparison
Produce a computer generated report based on a comparison of analysis in the IHC, ISH, and DNA sequencing against the rules accessed in the rules database, wherein the report identifies the at least one candidate treatment.
Across the independent claim, the inventive concept centers on performing IHC, ISH, and DNA sequencing on a subject sample, accessing biomarker-drug association rules in a rules database for the analyzed molecular targets, and generating a computer-generated report that identifies candidate treatments based on comparing the analyses to the rules.
Stated Advantages
Provides prioritized treatment recommendations based on biomarker-treatment mappings including positive efficacy and negative contraindications.
Enables identification of at least one candidate treatment for a subject in need of treatment for a cancer.
Provides profiling-selected therapy outcome assessment using progression-free survival (PFS), disease-free survival (DFS), and response measures including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Documented Applications
Generating candidate treatment recommendations for cancer using molecular profiling outputs and biomarker-drug association rules, including for refractory/metastatic cancers [procedural detail omitted for safety].
Profiling-selected therapy outcomes are discussed using progression-free survival (PFS), disease-free survival (DFS), and response measures including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Interested in licensing this patent?