Method or system using biomarkers for the monitoring of a treatment
AssigneeBoehringer Ingelheim International GmbH
InventorsTokuzo Arao, Kanae Kudo, Kazuhiko Nakagawa, Kazuto Nishio
Life of this patent
Estimating the term…
Abstract
The present invention relates to biomarkers to monitor the activity of the compound 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone or a pharmaceutically acceptable salt thereof, and especially its monoethanesulphonate salt form, when used alone or optionally in combination with further pharmaceutically active ingredients and/or further treatments, such as for example radiotherapy.
Claims9
A method for the monitoring of the treatment of an individual with the compound 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone or a pharmaceutically acceptable salt thereof, said method comprising
- determining whether a sample of blood from said individual comprises at least one pharmacodynamic biomarker in an amount that is indicative for said treatment,
- wherein said biomarker is the number of biomarker cells selected from the group consisting of CD34+CD45dimCD133+CD117− cells, CD34+CD45dimCD133−CD117+ cells, CD34+CD45dimCD133+ cells, CD34+CD45dimCD117+ cells and CD34+CD45dimCD133+CD117+ cells,
- wherein determining whether the sample comprises the number of said pharmacodynamic biomarker cells that is indicative for said treatment comprises isolating said cells from the sample and measuring the number of said cells,
- wherein
- when the biomarker is CD34+CD45dimCD133+CD117− cells or CD34+CD45dimCD133+ cells, an increase in the number of cells in a treated patient when compared with pre-treatment is indicative of a pharmacological response to said treatment;
- when the biomarker is CD34+CD45dimCD133+CD117+ cells or CD34+CD45dimCD117+ cells, a decrease in the number of cells in a treated patient when compared with pre-treatment is indicative of a pharmacological response to said treatment;
- and
- when the biomarker is CD34+CD45dimCD133+CD117+ cells, a decrease in the number of cells after treatment is a predictive biomarker indicative of stable disease, and
- wherein an indication of pharmacological response or stable disease is correlated with less risk from or lack of progression of the disease, or that the disease is susceptible to the given treatment.
A method to determine whether treatment of a patient with the compound 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone or a pharmaceutically acceptable salt thereof, is effective, comprising:
- a patient or doctor requesting such a determination;
- acquisition of a blood sample from the patient;
- analysis of the sample using a method comprising determining whether a sample from said individual comprises at least one biomarker in an amount that is indicative for said treatment;
- and communication of the tests results back to the patient or doctor,
- wherein said biomarker is the number of biomarker cells selected from the group consisting of CD34+CD45dimCD133+CD117− cells, CD34+CD45dimCD133−CD117+ cells, CD34+CD45dimCD133+ cells, CD34+CD45dimCD117+ cells and CD34+CD45dimCD133+CD117+ cells,
- wherein determining whether the sample comprises the number of said biomarker cells that is indicative for said treatment comprises isolating said cells from the sample and measuring the amount of said cells,
- wherein
- when the biomarker is CD34+CD45dimCD133+CD117− cells or CD34+CD45dimCD133+ cells, an increase in the number of cells in a treated patient when compared with pre-treatment is indicative of an effective pharmacological response to said treatment;
- when the biomarker is CD34+CD45dimCD133+CD117+ cells or CD34+CD45dimCD117+ cells, a decrease in the number of cells in a treated patient when compared with pre-treatment is indicative of an effective pharmacological response to said treatment;
- and
- when the biomarker is CD34+CD45dimCD133+CD117+ cells, a decrease in the number of cells in responders when compared to non-responders after treatment is indicative of the treatment being effective to maintain stable disease.
Dependencies are inferred from the claim text.