US2021285950A1PendingUtilityA1

Compositions, methods and kits for diagnosis of lung cancer

66
Assignee: BIODESIX INCPriority: May 5, 2016Filed: Oct 13, 2020Published: Sep 16, 2021
Est. expiryMay 5, 2036(~9.8 yrs left)· nominal 20-yr term from priority
G01N 33/5752G06N 7/01G01N 2560/00G16H 40/63G16B 20/00G16H 50/20G16H 30/20G16H 50/30G01N 33/6848G01N 2800/00G06N 7/005G01N 33/57423
66
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Claims

Abstract

Methods are provided for identifying biomarker proteins that exhibit differential expression in subjects with a first lung condition versus healthy subjects or subjects with a second lung condition. Also provided are compositions comprising these biomarker proteins and methods of using these biomarker proteins or panels thereof to diagnose, classify, and monitor various lung conditions. The methods and compositions provided herein may be used to diagnose or classify a subject as having lung cancer or a non-cancerous condition, and to distinguish between different types of cancer (e.g., malignant versus benign, SCLC versus NSCLC).

Claims

exact text as granted — not AI-modified
1 . A method of treating a pulmonary nodule in a subject, comprising:
 (a) performing an immunoassay to measure expression levels of a panel of proteins present in a blood sample obtained from the subject, wherein the panel of proteins comprises LG3BP and C163A;   (b) calculating a probability of lung cancer score based on the measurements of step (a) and clinical risk factors comprising age, smoking status, nodule diameter, nodule spiculation status and nodule location;   (c) ruling out lung cancer for the subject if the score in step (b) is lower than a pre-determined score, and ruling in lung cancer for the subject if the score in step (b) is equal to or higher than a pre-determined score; and   (d) if the lung cancer is ruled out in step (c), then monitoring the subject periodically, and if the lung cancer is ruled in in step (c), then performing a treatment protocol on the subject.   
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the subject has low to moderate cancer risk. 
     
     
         5 . The method of  claim 1 , further comprising a physician's assessment of cancer risk. 
     
     
         6 . The method of  claim 5 , wherein the subject is assigned a physician's assessment of cancer risk from between 0 to 1. 
     
     
         7 . The method of  claim 6 , wherein the cancer risk is determined by a cancer risk predictor C i (k) determined as 
       
         
           
             
               
                 Ci 
                 ⁡ 
                 
                   ( 
                   k 
                   ) 
                 
               
               = 
               
                 { 
                 
                   
                     
                       
                         0 
                         , 
                         
                           
                             if 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             
                               pCA 
                               ⁡ 
                               
                                 ( 
                                 k 
                                 ) 
                               
                             
                           
                           ≤ 
                           
                             T 
                             ⁢ 
                             i 
                           
                         
                       
                     
                   
                   
                     
                       
                         
                           pCA 
                           ⁡ 
                           
                             ( 
                             k 
                             ) 
                           
                         
                         ⁢ 
                         
                             
                         
                         , 
                         otherwise 
                       
                     
                   
                 
               
             
           
         
         where the decision threshold T i  is the median value of {Si(k)} of patients with nodules no larger than 15 mm. 
       
     
     
         8 . The method of  claim 1 , wherein the periodic monitoring is a pulmonary function test (PFT), pulmonary imaging, a biopsy or any combination thereof. 
     
     
         9 . The method of  claim 8 , where said pulmonary imaging is an x-ray, a chest computed tomography (CT) scan, or a positron emission tomography (PET) scan. 
     
     
         10 . The method of  claim 1 , wherein said pulmonary nodule has a diameter of less than or equal to 3 cm. 
     
     
         11 . The method of  claim 1 , wherein said pulmonary nodule has a diameter of about 0.8 cm up to 3.0 cm. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , the panel comprises LG3BP and C163A and the reversal ratio is 0.07. 
     
     
         14 .- 30 . (canceled) 
     
     
         31 . The method of  claim 1 , wherein the immunoassay is enzyme-linked immunosorbent assay (ELISA). 
     
     
         32 . The method of  claim 1 , wherein the step (a) comprises contacting the blood sample with a LG3BP antibody and a C163A antibody. 
     
     
         33 . The method of  claim 1 , wherein the score in step (b) is determined as XL_2(k), for a subject k, wherein 
       
         
           
             
               
                   
               
               ⁢ 
               
                 
                   XL_ 
                   ⁢ 
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                     ( 
                     k 
                     ) 
                   
                 
                 = 
                 
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                                 max 
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                                     0 
                                     , 
                                     
                                       
                                         p 
                                         ⁡ 
                                         
                                           ( 
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                                       - 
                                       
                                         0 
                                         ⁢ 
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                                   ) 
                                 
                               
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                                   2 
                                 
                                 ⁡ 
                                 
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                               ≤ 
                               .38 
                             
                           
                         
                         
                           
                             
                               
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                               > 
                               .38 
                             
                           
                         
                       
                       ⁢ 
                       
                         
 
                       
                       ⁢ 
                       
                           
                       
                       ⁢ 
                       
                         p 
                         ⁡ 
                         
                           ( 
                           k 
                           ) 
                         
                       
                     
                     = 
                     
                       
                         
                           
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                             1 
                             + 
                             
                               e 
                               X 
                             
                           
                         
                         ⁢ 
                         
                           
 
                         
                         ⁢ 
                         X 
                       
                       = 
                       
                         
                           - 
                           6.8272 
                         
                         + 
                         
                           0.0391 
                           * 
                           Age 
                         
                         + 
                         
                           0.7917 
                           * 
                           Smoker 
                         
                         + 
                         
                           0.1274 
                           * 
                           Diameter 
                         
                         + 
                         
                           1.0407 
                           * 
                           Spiculation 
                         
                         + 
                         
                           0.7838 
                           * 
                           Location 
                         
                       
                     
                   
                 
               
             
           
         
         wherein Age is the age of the subject in years, Smoker is 1 if the subject is a former or current smoker otherwise 0, Diameter is the size of the lung nodule in mm, Spiculation is 1 if the lung nodule is spiculated otherwise 0 and Location is 1 if the lung nodule is located in an upper lung lobe otherwise 0. 
       
     
     
         34 . The method of  claim 1 , wherein the treatment protocol is a pulmonary function test (PFT), pulmonary imaging, a biopsy, a surgery, a chemotherapy, a radiotherapy, or any combination thereof. 
     
     
         35 . The method of  claim 34 , wherein the imaging is an x-ray, a chest computed tomography (CT) scan, or a positron emission tomography (PET) scan. 
     
     
         36 . The method of  claim 1 , wherein when lung cancer is ruled out, the subject avoids an invasive procedure. 
     
     
         37 . The method of  claim 36 , wherein the invasive procedure is a biopsy and/or a surgery.

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