US2012208824A1PendingUtilityA1

ROS Kinase in Lung Cancer

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Assignee: RIMKUNAS VICTORIA MCGUINNESSPriority: Jan 20, 2006Filed: May 23, 2011Published: Aug 16, 2012
Est. expiryJan 20, 2026(expired)· nominal 20-yr term from priority
Inventors:Victoria Mcguinness RimkunasHerbert HaackTing-Lei GuAilan GuoAnthony PossematoKatherine Eleanor CrosbyMeghan Ann TuckerCynthia Reeves
A61P 43/00A61P 35/00A61P 11/00G01N 33/5752G01N 33/575G01N 2333/912C12Q 2600/106C12Q 2600/156C12Q 1/6886C12Q 1/68C07K 19/00
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Claims

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).

Claims

exact text as granted — not AI-modified
1 . A method for detecting the presence of a polypeptide with ROS kinase activity in a biological sample from a mammalian lung cancer or a suspected mammalian lung cancer, said method comprising the steps of: (a) obtaining a biological sample from a mammalian lung cancer or suspected mammalian lung cancer; and
 (b) utilizing at least one reagent that specifically binds to said polypeptide with ROS kinase activity to determine whether said polypeptide is present in said biological sample, wherein detection of specific binding of said reagent to said biological sample indicates said polypeptide is present in said biological sample.   
     
     
         2 . The method of  claim 1 , wherein said mammalian lung cancer is human lung cancer. 
     
     
         3 . The method of  claim 1 , wherein the biological sample is selected from the group consisting of a lung biopsy, a bronchoalveolar lavage, a circulating tumor cell, a lung biopsy, a bronchoalveolar lavage, a circulating tumor cell, a tumor resection, a fine needle aspirate, and a pleural effusion. 
     
     
         4 . The method of  claim 1 , wherein said polypeptide is a full-length ROS polypeptide. 
     
     
         5 . The method of  claim 1 , wherein said polypeptide is a ROS fusion polypeptide. 
     
     
         6 . The method of  claim 5 , wherein said ROS fusion polypeptide is selected from the group consisting of a CD74-ROS fusion polypeptide, an SLC34A2-ROS(S) polypeptide, an SLC34A2-ROS(L) polypeptide, an SLC34A2-ROS(VS) polypeptide, a FIG-ROS (L) polypeptide, a FIG-ROS(S) polypeptide, and a FIG-ROS(VL) polypeptide. 
     
     
         7 . The method of  claim 1 , wherein the reagent is an antibody. 
     
     
         8 . The method of  claim 7 , wherein the antibody specifically binds to a full length ROS polypeptide. 
     
     
         9 . The method of  claim 7 , wherein the antibody specifically binds to a ROS kinase domain. 
     
     
         10 . The method of  claim 1 , wherein said method is implemented in a format selected from the group consisting of a flow cytometry assay, an in vitro kinase assay, an immunohistochemistry (IHC) assay, an immunofluorescence (IF) assay, an Enzyme-linked immunosorbent assay (ELISA) assay, and a Western blotting analysis assay. 
     
     
         11 . A method for detecting the presence of a polynucleotide encoding a polypeptide with ROS kinase activity in a biological sample from a mammalian lung cancer or suspected mammalian lung cancer, said method comprising the steps of: (a) obtaining a biological sample from a mammalian lung cancer or suspected mammalian lung cancer and (b) utilizing a reagent that specifically binds to said polynucleotide encoding said polypeptide with ROS kinase activity to determine whether said polynucleotide is present in said biological sample, wherein detection of specific binding of said reagent to said biological sample indicates said polynucleotide encoding said polypeptide with ROS kinase activity is present in said biological sample. 
     
     
         12 . The method of  claim 11 , wherein said mammalian lung cancer is human lung cancer. 
     
     
         13 . The method of  claim 11 , wherein the biological sample is selected from the group consisting of a lung biopsy, a bronchoalveolar lavage, a circulating tumor cell, a lung biopsy, a bronchoalveolar lavage, a circulating tumor cell, a tumor resection, a fine needle aspirate, and a pleural effusion. 
     
     
         14 . The method of  claim 11 , wherein said polypeptide is a full-length ROS kinase polypeptide. 
     
     
         15 . The method of  claim 11 , wherein said polypeptide is a ROS fusion polypeptide. 
     
     
         16 . The method of  claim 15 , wherein said ROS fusion polypeptide is selected from the group consisting of a CD74-ROS fusion polypeptide, an SLC34A2-ROS(S) polypeptide, an SLC34A2-ROS(L) polypeptide, an SLC34A2-ROS(VL) polypeptide, a FIG-ROS (L) polypeptide, a FIG-ROS(S) polypeptide, and a FIG-ROS(VL) polypeptide. 
     
     
         17 . The method of  claim 11 , wherein said polynucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 2, 6, 8, 23, 29, 55, 57, and 59. 
     
     
         18 . The method of  claim 11 , wherein said reagent is a nucleic acid probe. 
     
     
         19 . The method of  claim 18 , wherein said nucleic acid probe is a fluorescence in-situ hybridization (FISH) probe and said method is implemented in a FISH assay. 
     
     
         20 . The method of  claim 18 , wherein said nucleic acid probe is a polymerase chain reaction (PCR) primer and said method is implemented in a PCR assay. 
     
     
         21 . The method of  claim 1  or  11 , wherein said reagent is detectably labeled. 
     
     
         22 . The method of  claim 1  or  11 , wherein the biological sample is diagnosed as being from a mammalian lung cancer or suspected mammalian lung cancer driven by ROS kinase activity. 
     
     
         23 . The method of  claim 1  or  11 , wherein said mammalian lung cancer or suspected mammalian lung cancer is diagnosed as being likely to respond to a ROS-inhibiting therapeutic. 
     
     
         24 . The method of  claim 23 , wherein said therapeutic is selected from the group consisting of PF-02341066, NVT TAE-684, and AP26113. 
     
     
         25 . A method for inhibiting the progression of a lung cancer or suspected lung cancer that expresses a polypeptide having ROS kinase activity, said method comprising the step of inhibiting the expression and/or activity of said polypeptide in said cancer or suspected lung cancer. 
     
     
         26 . A method for inhibiting the progression of a lung cancer or suspected lung cancer comprising a polynucleotide encoding a polypeptide having ROS kinase activity, said method comprising the step of inhibiting the expression of said polynucleotide in said cancer or suspected lung cancer. 
     
     
         27 . The method of  claim 25  or  26 , wherein said mammalian lung cancer is from a human. 
     
     
         28 . The method of  claim 25  or  26 , wherein expression and/or activity of said polypeptide is inhibited with a composition comprising a therapeutic selected from the group consisting of PF-02341066, NVT TAE-684, and AP26113. 
     
     
         29 . A method of identifying a patient with lung cancer or suspected of having lung cancer as a patient likely to respond to a ROS-inhibiting therapeutic, comprising:
 contacting a biological sample from a lung of said patient with a reagent that specifically binds a polypeptide having ROS kinase activity,   detecting whether the reagent specifically binds to the biological sample, wherein detection of binding of the reagent to the biological sample identifies the patient as a patient likely to respond to a ROS-inhibiting therapeutic.   
     
     
         30 . The method of  claim 29 , wherein the ROS-inhibiting therapeutic is PF-02341066, NVT TAE-684, or AP26113. 
     
     
         32 . The method of  claim 1 , wherein the biological sample is selected from the group consisting of a lung biopsy, a bronchoalveolar lavage, a circulating tumor cell, a tumor resection, a fine needle aspirate, and a pleural effusion. 
     
     
         33 . A method of treating a patient for lung cancer, comprising:
 detecting the presence of a polypeptide having ROS kinase activity in a biological sample from a lung of a patient having or suspected of having lung cancer; and   administering an effective amount of a ROS-inhibiting therapeutic to the patient, thereby treating the subject for lung cancer.   
     
     
         34 . A method of treating a patient for lung cancer, comprising:
 detecting the presence in a biological sample from a lung of a patient having or suspected of having lung cancer of a polypeptide selected from the group consisting of a polypeptide having ROS kinase activity and a polypeptide having ALK kinase activity; and   administering an effective amount of an ALK/ROS-inhibiting therapeutic to the patient, thereby treating the subject for lung cancer.   
     
     
         35 . The method of  claim 33  or  34 , wherein the therapeutic is PF-02341066, NVT TAE-684, or AP26113. 
     
     
         36 . A method of identifying a patient with lung cancer or suspected of having lung cancer as a patient likely to respond to a ROS-inhibiting therapeutic, comprising:
 contacting a biological sample from a lung of said patient with a first reagent that specifically binds a polypeptide having ROS kinase activity and a second reagent that specifically binds to a polypeptide having ALK kinase activity and   detecting whether the first reagent or the second reagent specifically binds to the biological sample, wherein detection of binding of either the first reagent or the second reagent to the biological sample identifies the patient as a patient likely to respond to a ROS-inhibiting therapeutic.   
     
     
         37 . The method of  claim 37 , wherein the first reagent specifically binds to full length ROS kinase protein or a kinase domain of ROS kinase protein. 
     
     
         38 . The method of  claim 37 , wherein the second reagent specifically binds to full length ALK kinase protein or the kinase domain of ALK kinase protein. 
     
     
         39 . The method of  claim 34  or  36 , wherein the biological sample is selected from the group consisting of a lung biopsy, a bronchoalveolar lavage, a circulating tumor cell, a tumor resection, a fine needle aspirate, and a pleural effusion. 
     
     
         40 . The method of  claim 29 ,  33 ,  34 , or  36 , wherein the patient is human.

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