IP Library Granted Patent US 12,590,965
Granted Patent B2
US 12,590,965 · App. 16/921,646 · Granted Mar 31, 2026

Palmitoyl protein biomarkers in purified extracellular vesicles for early identification of clinically significant prostate cancer

Inventors: Dolores Di Vizio (Los Angeles, CA); Wei Yang (Studio City, CA); Javier Mariscal Avila (Los Angeles, CA); Tatyana Vagner (Los Angeles, CA); Sungyong You (Los Angeles, CA); Andries Zijlstra (Nashville, TN)
Assignees: Cedars-Sinai Medical Center; Vanderbilt University
G01N33/57434G01N33/6848
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Quick Facts
Patent No.
US 12,590,965
App. No.
16/921,646
Granted
Mar 31, 2026
Kind
B2
Abstract

The invention provides for methods for isolating large EVs and detecting palmitoyl proteins in the large EVs, as well as methods for detecting clinically significant prostate cancer based on the presence of palmitoyl proteins in the isolated large EVs in a subject in need thereof. The method further comprises administering cancer therapy to the subject.

Claims (20)

1 . A method of detecting one or more palmitoyl proteins, comprising:

obtaining a biological sample from a subject having prostate cancer or suspected of having prostate cancer;

isolating large extracellular vesicles (EVs) from the biological sample;

assaying the large EVs for palmitoyl proteins GNAQ, CD9, TLN1, STX11, ITGB3, LYN, SLC4A1, CANX, FLOT2, FLOT1, ABHD16A, MYADM, ATP2A3, TMX1, RAP2B, ATP2A2, SLC2A3, RTN4, LTBP1, and ABCC4; and

detecting the palmitoyl proteins GNAQ, CD9, TLN1, STX11, ITGB3, LYN, SLC4A1, CANX, FLOT2, FLOT1, ABHD16A, MYADM, ATP2A3, TMX1, RAP2B, ATP2A2, SLC2A3, RTN4, LTBP1, and ABCC4.

2 . The method of claim 1 , further comprising assaying for one or more additional palmitoyl proteins other than GNAQ, CD9, TLN1, STX11, ITGB3, LYN, SLC4A1, CANX, FLOT2, FLOT1, ABHD16A, MYADM, ATP2A3, TMX1, RAP2B, ATP2A2, SLC2A3, RTN4, LTBP1, and ABCC4.

3 . The method of claim 1 , wherein the biological sample is blood plasma.

4 . The method of claim 1 , wherein the subject has prostate cancer.

5 . The method of claim 1 , wherein the subject has metastatic prostate cancer.

6 . The method of claim 1 , wherein assaying for palmitoyl proteins comprises using mass spectrometry to detect the palmitoyl proteins.

7 . The method of claim 1 , further comprising administering a prostate cancer therapy to the subject.

8 . A method of detecting clinically significant prostate cancer, comprising:

obtaining a biological sample from a subject having prostate cancer or suspected of having prostate cancer;

isolating large extracellular vesicles (EVs) from the biological sample;

assaying the large EVs for palmitoyl proteins GNAQ, CD9, TLN1, STX11, ITGB3, LYN, SLC4A1, CANX, FLOT2, FLOT1, ABHD16A, MYADM, ATP2A3, TMX1, RAP2B, ATP2A2, SLC2A3, RTN4, LTBP1, and ABCC4; and

detecting the palmitoyl proteins GNAQ, CD9, TLN1, STX11, ITGB3, LYN, SLC4A1, CANX, FLOT2, FLOT1, ABHD16A, MYADM, ATP2A3, TMX1, RAP2B, ATP2A2, SLC2A3, RTN4, LTBP1, and ABCC4,

wherein the detection of the palmitoyl proteins indicates the presence of clinically significant prostate cancer.

9 . The method of claim 8 , further comprising administering a therapy other than androgen deprivation therapy when the one or more palmitoyl proteins are detected, or continuing to administer androgen deprivation therapy when the one or more palmitoyl proteins are not detected, or continuing active surveillance when the one or more palmitoyl proteins are not detected.

10 . The method of claim 8 , wherein assaying the large EVs for palmitoyl proteins comprises using mass spectrometry to assay for the palmitoyl proteins.

11 . The method of claim 8 , further comprising administering a prostate cancer therapy to the subject.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2021
From: DI VIZIO, DOLORES; YANG, WEI; MARISCAL AVILA, JAVIER; VAGNER, TATYANA; YOU, SUNGYONG
To: CEDARS-SINAI MEDICAL CENTER
Reel/Frame 055895/0927 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2021
From: ZIJLSTRA, ANDRIES
To: VANDERBILT UNIVERSITY
Reel/Frame 055896/0043 →
Continuity (3)
Continuation In Part 13975059 · Aug 23, 2013
Provisional Application 61692591 · Aug 23, 2012
Related Publication 20200408766A1 · Dec 31, 2020
References Cited (61)
US 6258540B1 · Lo et al. · 2001 [cited by applicant]
US 6355623B2 · Seidman et al. · 2002 [cited by applicant]
US 6812023B1 · Lamparski et al. · 2004 [cited by applicant]
US 10254285B2 · Di Vizio et al. · 2019 [cited by applicant]
US 11274349B2 · Di Vizio et al. · 2022 [cited by applicant]
US 20060019256A1 · Clarke et al. · 2006 [cited by applicant]
US 20080199890A1 · Letai · 2008 [cited by applicant]
US 20100184046A1 · Klas et al. · 2010 [cited by applicant]
US 20100196426A1 · Skog et al. · 2010 [cited by applicant]
US 20100304989A1 · Von Hoff et al. · 2010 [cited by applicant]
US 20110200998A1 · Weichselbaum et al. · 2011 [cited by applicant]
US 20140038901A1 · Lyden et al. · 2014 [cited by applicant]
US 20140045915A1 · Skog et al. · 2014 [cited by applicant]
US 20140056807A1 · Di Vizio · 2014 [cited by examiner]
US 20140148350A1 · Spetzler et al. · 2014 [cited by applicant]
US 20150301055A1 · Spetzler · 2015 [cited by applicant]
US 20160061842A1 · Di Vizio et al. · 2016 [cited by applicant]
US 20190300966A1 · Di Vizio et al. · 2019 [cited by applicant]
EP 2986326A2 · 2014 [cited by applicant]
EP 2986326B1 · 2018 [cited by applicant]
WO WO2012115885A1 · 2012 [cited by applicant]
WO WO2014172390A2 · 2014 [cited by applicant]
WO WO2018089541A1 · 2018 [cited by applicant]
WO WO2019008414A1 · 2019 [cited by examiner]
International Search Report and Written Opinion of PCT/US2017/60707, dated Mar. 29, 2018, 11 Pages. [cited by applicant]
International Preliminary Report on Patentability of PCT/US2014/034245 dated Oct. 20, 2015; 8 pages. [cited by applicant]
International Search Report and Written Opinion of PCT/US2014/034245 dated Nov. 7, 2014; 13 pages. [cited by applicant]
Extended Search Report of EP Application No. 14785880.7 dated Dec. 19, 2016; 13 pages. [cited by applicant]
Adlard et al.. Prediction of the Response of Colorectal Cancer to Systemic Therapy, The Lancet Oncology, 2002, vol. 3, pp. 75-82. [cited by applicant]
Bhardwaj et al. Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone. International Journal of Pharmaceutics (2010). 388:181-189. [cited by applicant]
Chambers et al. Microvesicle-mediated release of soluble LH/hCG receptor (LHCGR) from transfected cells and placenta explants. Reproductive Biology and Endocrinology (2011). 9:64 (15 pages). [cited by applicant]
Cheruvanky et al. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol (2007). 292:F1657-F1661. [cited by applicant]
Conley et al., High-Throughput Sequencing of Two Populations of Extracellular Vesicles Provides an mRNA Signature that can be Detected in the Circulation of Breast Cancer Patients, 2017, RNA Biology, vol. 14(3), pp. 305… [cited by applicant]
D'Asti et al. Oncogenic extracellular vesicles in brain tumor progression. Frontiers in Physiology (2012). 3:Article 294 (15 pages). [cited by applicant]
Di Vizio et al. Large Oncosomes in Human Prostate Cancer Tissues and in the Circulation of Mice with Metastatic Disease. The American Journal of Pathology (2012). 181(5):1573-1584. [cited by applicant]
Di Vizio et al. Oncosome Formation in Prostate Cancer: Association with a Region of Frequent Chromosomal Deletion in Metastatic Disease. Cancer Research (2009). 69:5601-5609. [cited by applicant]
Dragovic et al. Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis. Nanomedicine: Nanotechnology, Biology, and Medicine (2011). 7:780-788. [cited by applicant]
D'Souza-Schorey et al. Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes & Development (2012). 1287-1299. [cited by applicant]
Fiskaa et al., Distinct Small RNA Signatures in Extracellular Vesicles Derived from Breast Cancer Cell Lines, 2016, PLoS One, vol. 11(8), e0161824, 18 Pages. [cited by applicant]
Floryan et al. Intraoperative use of autologous platelet-rich and platelet-poor plasma for orthopedic surgery patients. AORN Journal (2004). 80:668-674. [cited by applicant]
Freshney, Culture of Animal Cells, A Manual of Basic Technique, 1983, pp. 1-4. [cited by applicant]
Fujita et al., Extracellular Vesicle Transfer of Cancer Pathogenic Components, 2016, Cancer Science, vol. 107(4), pp. 385-390. [cited by applicant]
Gerdes et al., Emerging Understanding of Multiscale Tumor Heterogeneity, Frontiers in Oncology, 2014, 4(Article 366), pp. 1-12. [cited by applicant]
Kaiser, First Pass at Cancer Genome Reveals Complex Landscape, Science, 2006, vol. 313, p. 1370. [cited by applicant]
Morello et al. Abstract 430: MiRNA profiling of prostate cancer cell-derived large oncosomes identifies a signature of invasion and metastasis. Cancer Research (2012). 72(5): Suppl 1 (1 page). [cited by applicant]
Morello et al. Large oncosomes mediate intercellular transfer of functional microRNA. Cell Cycle (2013). 12(22):3526-3536. [cited by applicant]
Muralidharan-Chari et al. Microvesicles: mediators of extracellular communication during cancer progression. Journal of Cell Science (2010). 123:1603-1611. [cited by applicant]
Myers et al. Successful Treatment of Advanced Metastatic Prostate Cancer following Chemotherapy Based on Molecular Profiling. Case Reports in Oncology (2012). 5(1):154-158. [cited by applicant]
Peinado et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med (2012). 18(6):883-891. [cited by applicant]
Pritzker. K., Cancer Biomarkers: Easier Said Than Done, Clinical Chemistry, 2002, vol. 48(8), pp. 1147-1150. [cited by applicant]
Response to Office Action (issued Jul. 9, 2018) of U.S. Appl. No. 14/883,421, filed Sep. 28, 2018, 5 Pages. [cited by applicant]
Shao et al. Protein typing of circulating microvesicles allows real-time monitoring of gliobastoma therapy. Nat Med (2012). 18(12):1835-1840. [cited by applicant]
Tian et al., The Expression of Native and Cultured RPE Grown on Different Matrices, Physiol Genomics, 2004, vol. 17, pp. 170-182. [cited by applicant]
Xiao et al. Effect of 5-Aza-2′ deoxycytidine on immune-associated proteins in exosomes from hepatoma. World Journal of Gastroenterology (2010). 16(19):2371-2377. [cited by applicant]
Zips et al., New Anticancer Agents: In Vitro and In Vivo Evaluation, In Vivo, 2005, vol. 19, pp. 1-8. [cited by applicant]
Haynes et al., Proteome analysis: Biological assay or data archive?, Electrophoresis, 1998, vol. 19, pp. 1862-1871. [cited by applicant]
Chen et al., Discordant Protein and mRNA Expression in Lung Adenocarcinomas, 2002, Molecular & Cellular Proteomics, vol. 1, pp. 304-313. [cited by applicant]
Vogel et al., Nature Reviews Genetics, 2012, vol. 13(4), pp. 227-232. [cited by applicant]
Conley et al., Abstracts from the fourth International Meeting of ISEV, ISEV2015, Washington, D.C., USA, Apr. 23-26, 2015, Journal of Extracellular Vesicles, 2015, vol. 4(10). [cited by applicant]
Spinelli et al., J Extracell Vesicles, 2015, vol. 4(10). [cited by applicant]
Conley et al., Supplementary Tables, retrieved from: https://www.tandfonline.com/doi/full/10.1080/15476286.2016.1259061#supplemental-material-section, RNA Biology, 2017, vol. 14(3), pp. 1-890. [cited by applicant]