ROS kinase in lung cancer

Patent metadata

Field	Value
Publication number	US-11099188-B2
Application number	US-201815994165-A
Country	US
Kind code	B2
Filing date	May 31, 2018
Priority date	Jan 20, 2006
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

The invention provides the identification of the presence of polypeptides with ROS kinase activity in mammalian lung cancer. In some embodiments, the polypeptide with ROS kinase activity is the result of a fusion between a ROS-encoding polynucleotide and a polynucleotide encoding a second (non-ROS) polypeptide. Three different fusion partners of ROS are described, namely proteins encoded by the FIG gene, the SLC34A2 gene, and the CD74 gene. The invention enables new methods for determining the presence of a polypeptide with ROS kinase activity in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer (e.g., an lung cancer).

First claim

The invention claimed is:

1. A method, comprising:
performing a PCR assay using a biological sample from primary human lung cancer, wherein
(i) said PCR assay utilizes a pair of primers which hybridize to a polynucleotide encoding a FIG-ROS fusion polypeptide,
(ii) said polynucleotide comprises a coding nucleotide sequence selected from the group consisting of SEQ ID NO: 57, SEQ ID NO: 55, and SEQ ID NO: 59,
(iii) said primers comprise a forward primer which hybridizes under stringent conditions to the 5′ side of the fusion junction of said polynucleotide, and a reverse primer which hybridizes under said stringent conditions to the 3′ side of the fusion junction of said polynucleotide, and
(iv) said stringent conditions comprise hybridization at 42° C. in a solution containing 50% formamide, 5×SSC, 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 micrograms/ml denatured, sheared salmon sperm DNA, followed by washing in 0.1×SSC at about 65° C.;
detecting an amplification product; and
determining the presence of a FIG-ROS fusion polynucleotide in said sample based on detection of the presence of the amplification product.

2. The method of claim 1 , wherein the PCR assay is RT-PCR and utilizes mRNA in said sample as template.

3. The method of claim 1 , wherein the lung cancer is non-small cell lung carcinoma (NSCLC).

4. The method of claim 1 , wherein the biological sample is selected from the group consisting of lung cancer tissue biopsy, pleural effusion, and bronchioalveolar lavage.

Assignees

• Cell Signaling Technology Inc

Inventors

• Rimkunas Victoria Mcguinness
• Haack Herbert
• Gu Ting-Lei
• Guo Ailan
• Possemato Anthony Paul
• Crosby Katherine Eleanor
• Tucker Meghan Ann
• Beaudet Cynthia

Classifications

• G01N33/5752 Primary

  of the lungs · CPC title

• G01N33/575 Primary

  for cancer · CPC title

• C12Q1/68

  involving nucleic acids · CPC title

• C07K19/00

  Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title