Granted Patent
B2
US 12,247,980 · App. 17/470,462 · Granted Mar 11, 2025
Compositions, methods and kits for diagnosis of lung cancer
Inventors:
Paul Edward Kearney (Seattle, WA); Kenneth C. Fang (San Francisco, CA); Xiao-Jun Li (Bellevue, WA); Clive Hayward (Seattle, WA); Douglas Spicer (Enumclaw, WA)
Assignee:
Biodesix, Inc.
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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 (11)
1. A method of analyzing a biological sample of a subject having a pulmonary nodule, comprising:
determining expression levels of a panel of proteins present in a blood sample obtained from the subject by an immunoassay, wherein the panel of proteins comprises LG3BP and C163A.
2. The method of claim 1 , wherein the immunoassay is enzyme-linked immunosorbent assay (ELISA).
3. The method of claim 1 , wherein the panel of proteins further comprises at least one of ALDOA, FRIL, TSP1, COIA1, PEDF, MASP1, GELS, LUM, PTPRJ, IBP3, LRP1, ISLR, GRP78, TETN, PRDX1, CD14, BGH3, FIBA, and GSLG1.
4. The method of claim 1 , wherein the pulmonary nodule of the subject has a diameter of less than or equal to 3 cm.
5. The method of claim 1 , wherein the pulmonary nodule of the subject has a diameter of about 0.8 cm to 3.0 cm.
6. The method of claim 1 , wherein the subject is at risk of developing lung cancer.
7. The method of claim 1 , wherein the subject is 40 years or older.
8. The method of claim 1 , wherein the immunoassay comprises contacting the blood sample with a LG3BP antibody and a C163A antibody.
9. The method of claim 1 , wherein the panel of proteins consists of LG3BP and C163A.
10. The method of claim 1 , wherein the subject has a smoking history.
Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 31, 2023
From: HAYWARD, CLIVE
To: INTEGRATED DIAGNOSTICS, INC.
Reel/Frame 064435/0628 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 31, 2023
From: KEARNEY, PAUL EDWARD; SPICER, DOUGLAS
To: INTEGRATED DIAGNOSTICS, INC.
Reel/Frame 064435/0635 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 31, 2023
From: INTEGRATED DIAGNOSTICS, INC.
To: BIODESIX, INC.
Reel/Frame 064435/0644 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 31, 2023
From: KEARNEY, PAUL EDWARD; FANG, KENNETH CHARLES; LI, XIAO-JUN; HAYWARD, CLIVE
To: INTEGRATED DIAGNOSTICS, INC.
Reel/Frame 064435/0977 →
SECURITY AGREEMENT
Recorded Nov 22, 2022
From: BIODESIX, INC.
To: PERCEPTIVE CREDIT HOLDINGS IV, LP
Reel/Frame 061977/0919 →
Continuity (9)
Provisional Application
61725153
· Nov 12, 2012
Provisional Application
61676859
· Jul 27, 2012
Provisional Application
61589920
· Jan 24, 2012
Provisional Application
61578712
· Dec 21, 2011
References Cited (113)
US 7183188B2
· Kronke et al.
· 2007
[cited by applicant]
US 8124722B2
· Furusako
· 2012
[cited by examiner]
US 9201044B2
· Kearney et al.
· 2015
[cited by applicant]
US 9297805B2
· Kearney et al.
· 2016
[cited by applicant]
US 9297895B2
· Kashi et al.
· 2016
[cited by applicant]
US 9304137B2
· Kearney et al.
· 2016
[cited by applicant]
US 9588127B2
· Kearney et al.
· 2017
[cited by applicant]
US 9594085B2
· Li et al.
· 2017
[cited by applicant]
US 20010041177A1
· Guyre et al.
· 2001
[cited by applicant]
US 20060257857A1
· Keene et al.
· 2006
[cited by applicant]
US 20070099251A1
· Zhang et al.
· 2007
[cited by applicant]
US 20070111322A1
· Yang
· 2007
[cited by applicant]
US 20070128598A1
· Boender
· 2007
[cited by applicant]
US 20070202539A1
· Aebersold et al.
· 2007
[cited by applicant]
US 20070269895A1
· Aebersold et al.
· 2007
[cited by applicant]
US 20090221444A1
· Borlak et al.
· 2009
[cited by applicant]
US 20090317392A1
· Nakamura et al.
· 2009
[cited by applicant]
US 20100093108A1
· Khattar et al.
· 2010
[cited by applicant]
US 20100184034A1
· Bankaitis-Davis et al.
· 2010
[cited by applicant]
US 20100279382A1
· Aebersold et al.
· 2010
[cited by applicant]
US 20110021750A1
· Yu et al.
· 2011
[cited by applicant]
US 20130020396A1
· Mullen et al.
· 2013
[cited by applicant]
US 20170269090A1
· Kearney et al.
· 2017
[cited by applicant]
WO WO2009067546A2
· 2009
[cited by applicant]
WO WO2010030697A1
· 2010
[cited by applicant]
WO WO2011085163A2
· 2011
[cited by applicant]
WO WO2012075042A1
· 2012
[cited by applicant]
WO WO2013096845A2
· 2013
[cited by applicant]
WO WO2013152989A2
· 2013
[cited by applicant]
WO WO2014100717A2
· 2014
[cited by applicant]
WO WO2015013654A1
· 2015
[cited by applicant]
WO WO2015042454A1
· 2015
[cited by applicant]
WO WO2019079635A1
· 2019
[cited by applicant]
Zhang et al., Clin. J Cancer Res 2014, 26(6):647-652.
[cited by examiner]
Addona et al., “A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate makers for cardiovascular disease,” Nat Biotechnol, 29(7):635-643 (2011).
[cited by applicant]
Addona et al., “Multi-site assessment of the preision and reproductibility of multiple reaction monitoring-based measurements of preoteins in plasma,” Nat Biotechnol, 27(7):633-641 (2009).
[cited by applicant]
Albert et al., “Evaluation of the solitary pulmonary nodule,” Am Fam Physician, 80(8):827-831 (2009).
[cited by applicant]
Bigbee et al., “A multiplexed serum biomarker immunoassay panel discriminates clinical lung cancer patients from high-risk individuals found to be cancer-free by CT scanning,” J Thorac Oncol, 7(4):698-708 (2012).
[cited by applicant]
Bouchal et al., “Biomarker discovery in low-grade breast cancer using isoaric stable isotope tags and two-dimensional liquid chromatography-tandem mass spcetrometry (iTRAQ-2DLC-MS/MS) based quantitative proteomic analys…
[cited by applicant]
Brusniak et al., “Corra: computational framework and tools for LC-MS discovery and targeted mass spectrometry-based proteomics,” BMC Bioinformatics, 9:542 (2008).
[cited by applicant]
Carozzi et al., “Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis,” Lung Cancer, 68(2):216-221 (2010).
[cited by applicant]
Chapman et al., “EarlyCDT-Lung Test: Improved clinical utility through additional autoantibody assays,” Tumor Biol, 33(5):1319-1326 (2012).
[cited by applicant]
Cima et al., “Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer,” PNAS, 108(8):3342-3347 (2011).
[cited by applicant]
Desiere et al., “The PeptideAtlas Project,” Nucleic Acids Res, 34:D655-D658 (2006).
[cited by applicant]
Extended European Search Report for EP Application No. 18868355.1 dated Jun. 16, 2021.
[cited by applicant]
Farrah et al., “A high-confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas,” Mol Cell Proteomics, 10(9):M110.006353 (2011).
[cited by applicant]
Fracchia et al., “A comparative study on ferritin concentration in serum and bilateral bronchoalveolar lavage fluid of patients with peripheral lung cancer versus control subjects,” Oncology, 56:181-188 (1999).
[cited by applicant]
Gould et al., “Evaluation of patients with pulmonary nodules: When is it lung cancer?” Chest, 132(S3):108S-130S (2007).
[cited by applicant]
Halliwell et al., “Oxidative stress and cancer: Have we moved forward>” Biochem J, 401(1):1-11 (2007).
[cited by applicant]
Hanash et al., “Emerging molecular biomarkers—Blood-based strategies to detect and monitor cancer,” Nat Rev Clin Oncol, 8(3):142-150 (2011).
[cited by applicant]
Hassanein et al., “Advances in proteomic strategies toward the early detection of lung cancer,” Proc Am Thorac Soc, 8(2):183-188 (2011).
[cited by applicant]
Hennessey et al., “Serum microRNA biomarkers for detection of non-small cell lung cancer,” PLoS One, 7(2):e32307 (2012).
[cited by applicant]
Henschke et al., “CT screening for lung cancer: suspiciousness of nodules according to size on baseline scans,” Radiology, 231(1):164-168 (2004).
[cited by applicant]
Henschke et al., “Early lung cancer action project: Overall design and findings from baseline screenings,” Lancet, 354(9173):99-105 (1999).
[cited by applicant]
Huttenhain et al., “Reproducible quantification of cancer-associated proteins in body fluids using targetd proteomics,” Sci Transl Med, 4(142):149-194 (2012).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2012/071387 mailed Jul. 19, 2013.
[cited by applicant]
International Search Report and Written Opinion for International application No. PCT/US2013/077225 mailed Sep. 8, 2014.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2018/056570 dated Feb. 14, 2019.
[cited by applicant]
Kearney et al., “An integrated risk predictor for pulmonary nodules,” PloS one, 12(5):e0177635 (2017).
[cited by applicant]
Kearney et al., “Protein Identification and peptide expression resolver: Harmonizing protein identification with protein expression data,” J Proteome Res, 7(1):234-244 (2008).
[cited by applicant]
Kitada et al., “Role of treatment for solitary pulmonary nodule in breast cancer patients,” World Journal of Surgical Oncology, 9(124):1-5 (2011).
[cited by applicant]
Kitteringham et al., “Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics,” J Chromatogr B, 877(13):1229-1239 (2009).
[cited by applicant]
Lacovazzi et al., “Serum 9OKIMac-2 Binding Protein (Mac-2BP) as a Response Predictor to Peginterferon and Ribavirin,” Immunopharmacology and Immunotoxicology, 30:687-700 (2008).
[cited by applicant]
Lam et al., “Early CDT-Lung: An immunbiomarker test as an aid to earl detection of lung cancer,” Cancer Prev Res, 4(7):1126-1134 (2011).
[cited by applicant]
Lange et al., “Selected reaction monitoring for quantitative proteomics: A tutorial,” Mol Sys Biol, 4(222):1-14 (2008).
[cited by applicant]
Lehtio et al., “Lung cancer proteomics, clinical and technological considerations,” J Proteomics, 73(10):1851-1863 (2010).
[cited by applicant]
Lombardi et al., “Clinical significance of a multiple biomarker assay in patients with lung cancer,” Chest, 97(3):639-644 (1990).
[cited by applicant]
MacMahon et al., “Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society,” Radiology, 237(2):395-400 (2005).
[cited by applicant]
Makawita et al., “The bottleneck in the cancer biomarker pipeline and protein quantification through mass spectrometry-based approaches: current strategies for candidate verification,” Clin Chem, 56(2):212-222 (2010).
[cited by applicant]
McClish, “Analyzing a portion of the ROC curve,” Med Decis Making, 9(3):190-195 (1989).
[cited by applicant]
Micheel et al., “Evolution of Translational Omics: Lessons Learned and the Path Forward,” Committee on the Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials, XV-338 (2012).
[cited by applicant]
Miller et al., “Minimizing unintended consequences of detecting lung nodules by computed tomography,” Am J Resp Crit Care Med, 178(9):891-892 (2008).
[cited by applicant]
Milman et al., “The serum ferritin concentration is a significant prognostic indicator of survival in primary lung cancer,” Oncol Rep, 9(1):193-198 (2002).
[cited by applicant]
Ocak et al., “Mass spectrometry-based proteomic profiling of lung cancer,” Proc Am Thorac Soc, 6(2):159-170 (2009).
[cited by applicant]
Omenn et al., “Overview of the HUPO plasma proteome project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-avai…
[cited by applicant]
Ost et al., “Decision making in patients with pulmonary nodules,” Am J Respir Crit Care Med, 185(4):363-372 (2012).
[cited by applicant]
Ostroff et al., “Unlocking biomarker discovery: large cale application of aptamer proteomic technology for early detection of lung cancer,” PLoS One, 5(12):e15003 (2010).
[cited by applicant]
Ozaki et al., “Expression and immunogenicity of tumor-associated antigen, 90K/Mac-2 binding protein, in lung carcinoma,” Cancer, 95:1954-1962 (2002).
[cited by applicant]
Pecot et al., “Added value of a serum proteomic signature in the diagnostic evaluation of lung nodules,” Cancer Epidemiol Biomarkers Prev, 21(5):786-792 (2012).
[cited by applicant]
Perkins et al., “Probability-based protein identification by searching sequence databases using mass spectrometry data,” Electrophoresis, 20(18):2551-3567 (1999).
[cited by applicant]
Picotti et al., “High-throughput generation of selected reaction-monitoring assays for proteins and proteomes,” Nat Meth, 7(1):43-46 (2010).
[cited by applicant]
Polanski et al., “A list of candidate canceer biomarkers for targeted proteomics,” Biomarker insights, 1:1-48 (2007).
[cited by applicant]
Price et al., “Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas,” PNAS, 104(9):3414-3419 (2007).
[cited by applicant]
Qin et al., “SRM targeted proteomics in search for biomarkers of HCV-induced progerssion of fibrosis to cirrhosis in HALT-C patients,” Proteomics, 12(8):1244-1252 (2012).
[cited by applicant]
Radulovic et al., “Informatics platform for global proteomic profiling and biomarker discovery using liquid chromatography-tandem mass spectrometry,” Moll Cell Proteins, 3(10):984-997 (2004).
[cited by applicant]
Reiter et al., “mProphet: Automated date processing and statistical validation for large-scale SRM experiments,” Nat Meth, 8(5):430-435 (2011).
[cited by applicant]
Rho et al., “Glycoproteomics analysis of human lung adenocarcinomas using glycoarrays and tandem mass spectrometry: Differential expression and glycosylation patterns of vimentin and fetuin A isoforms,” Protein J, 38(3-…
[cited by applicant]
Rom et al., “Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers,” BMC Cancer, 10:234 (2010).
[cited by applicant]
Schauer et al., “National council on radiation protection and measurements report shows substntial medical exposure increase,” Radiol, 253(2):293-296 (2009).
[cited by applicant]
States et al., “Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasmaproteome collaborative study,” Nat Biotechnol, 24(3):333-338 (2006).
[cited by applicant]
Stern et al., “Nationwide evaluation of X-ray trends (NEXT) Jan. 2000 survey patient radiation exposure from computed tomographic (CT) examinations in the United States,” 87th Scientific Assembly and Annual Meeting of t…
[cited by applicant]
Swensen et al., “Lung cancer screening with CT: Mayo Clinic experience,” Radiology, 226(3):756-761 (2003).
[cited by applicant]
Taguchi et al., “Unleashing the power of proteomics to develop blood-based cancer markers,” Cling Chem, 59:1 (2013).
[cited by applicant]
Teutsch et al., “The evaluation of genomic applications in practice and prevention (EGAPP) initiative: Methods of the EGAPP working group,” Genet Med, 11(1):3-14 (2009).
[cited by applicant]
Tockman et al., “Considerations in bringing a cancer biomarker to clinical applications,” Cancer Research, 52:2711a-2718s (1992).
[cited by applicant]
Ueda et al., “A comprehensive peptidome profiling technology for the identification of early detection biomarkers for lung adenocarcinoma,” PLoS One, 6(4):1-12 (2011).
[cited by applicant]
Vachani et al., “Validation of a Multiprotein Plasma Classifier to Identity Benign Lung Nodules,” Journal of Thoracic Oncology, 10(4): 629-637 (2015).
[cited by applicant]
Walser et al., “Smoking and lung cancer: the role of inflammation,” Proc Am Thorac Soc, 5(8):811-815 (2008).
[cited by applicant]
Wang et al., “The evolving role of mass spectrometry in cancer biomarker discovery,” Cancer Biology and Therapy, 8:1083-1094 (2009).
[cited by applicant]
Wei et al., “Primary tumor xenografts of human lung adeno and squamous cell carcinoma express distinct proteomic signatures,” Journal of Proteome Research, 10:161-174 (2011).
[cited by applicant]
Whiteaker et al., “A targeted proteomics-based pipeline for verification of biomarkers in plasma,” Nat Biotechnol, 29(7):625-634 (2011).
[cited by applicant]
Wiener et al., “Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records,” Ann Int Med, 155(3):137-144 (2011).
[cited by applicant]
Yildiz et al., “Diagnostic accuracy of MALDI mass spectrometic analysis of unfractionated serum in lung cancer,” J Thorac Oncol, 2(10):893-901 (2007).
[cited by applicant]
Zeng et al., “Lung cancer serum biomarker discovery using glycoprotein capture and liquid chromatography mass spectrometry,” J Proteome Res, 9(12):6440-6449 (2010).
[cited by applicant]