Assays for BTK inhibitors

Patent metadata

Field	Value
Publication number	US-10012650-B2
Application number	US-201514964945-A
Country	US
Kind code	B2
Filing date	Dec 10, 2015
Priority date	Dec 11, 2014
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

The present invention relates to BTK occupancy assays.

First claim

We claim:

1. A method for determining drug target occupancy of a BTK inhibitor compound, comprising:
(a) contacting a sample comprising a mixture of BTK kinase and a BTK inhibitor compound, with a probe to form a probe-bound kinase;
(b) detecting the amount of probe-bound kinase in the sample; and
(c) determining the occupancy of the BTK inhibitor compound based on the amount of probe-bound kinase detected in the sample;

wherein the probe is:

2. The method of claim 1 , wherein the step of determining target occupancy comprises determining the number of binding sites not occupied by the BTK kinase inhibitor based on the amount of probe-bound kinase detected in the sample.

3. The method of claim 1 , further comprising a step of determining or modifying a therapeutic regimen based on the target occupancy of the BTK kinase.

4. The method of claim 1 , further comprising a step of performing the method at two or more time points.

Assignees

• Merck Patent Gmbh

Inventors

• Bender Andrew
• Liu-Bujalski Lesley
• Pereira Albertina
• Caldwell richard d
• Grenningloh Roland
• Xu Daigen

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• G01N33/53 Primary

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• G01N33/58

  involving labelled substances (G01N33/53 takes precedence) · CPC title

• G01N2500/02

  Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) · CPC title

• G01N2333/912

  transferring phosphorus containing groups, e.g. kinases (2.7) · CPC title