IP Library Granted Patent US 12,692,533
Granted Patent B2
US 12,692,533 · App. 17/574,947 · Granted Jul 28, 2026

Methods and compositions for noninvasive detection of organ transplant rejection

Inventors: Gabriel A. Kwong (Atlanta, GA); Andrew B. Adams (Atlanta, GA); Quoc Mac (Atlanta, GA); David V. Mathews (Atlanta, GA)
Assignees: Georgia Tech Research Corporation; Emory University
C12Q1/37C07K5/00C07K7/00C07K14/00G01N2800/245
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,692,533
App. No.
17/574,947
Granted
Jul 28, 2026
Kind
B2
Abstract

An activity-based nanosensor composition for detecting protease activity comprising a cleavable detectable substrate and methods of use are disclosed.

Claims (13)

1 . A method of detecting a T cell cytotoxicity driven immune condition and/or the likelihood thereof in a subject, the method comprising:

i) administering a nanosensor to the subject, said nanosensor comprising:

a) a scaffold;

b) a peptide substrate coupled to the scaffold, wherein the peptide substrate is capable of being cleaved by Granzyme B; and

c) a detectable reporter coupled to the scaffold by the peptide substrate, wherein in vivo cleavage of said peptide substrate releases said detectable reporter from the scaffold;

ii) detecting a level of said detectable reporter in a blood or urine sample collected from the subject; wherein the presence of detectable reporter indicates the subject has or is likely to have a T cell cytotoxicity driven immune condition; and

iii) treating the subject for a T cell cytotoxicity driven immune condition when the detectable reporter is detected.

2 . The method of claim 1 , wherein said nanosensor comprises said detectable reporter selected from a group consisting of a fluorophore, a luminescent reporter, a ligand encoded reporter, a mass spectrometry tag, a contrast agent for imaging, a PET-detectable domain, and a nucleic acid tag.

3 . The method of claim 2 , wherein said detectable reporter further comprises a quencher.

4 . The method of claim 1 , wherein said peptide substrate comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 2-136.

5 . The method of claim 1 , wherein ii) further comprises comparing said level of said detectable reporter to a reference level of detectable reporter in a subject without a T cell cytotoxicity driven immune condition.

6 . The method of claim 1 , wherein i) comprises intravenously administering the nanosensor to the subject.

7 . The method of claim 1 , wherein the scaffold comprises a protein scaffold, a polymer scaffold, a DNA scaffold, a sugar scaffold, or a nanoparticle.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 26, 2022
From: ADAMS, ANDREW B.; MATHEWS, DAVID V.
To: EMORY UNIVERSITY
Reel/Frame 058769/0494 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 26, 2022
From: KWONG, GABRIEL A.; MAC, QUOC
To: GEORGIA TECH RESEARCH CORPORATION
Reel/Frame 058769/0477 →
Continuity (3)
Continuation 16337886 · Sep 28, 2017
Provisional Application 62400656 · Sep 28, 2016
Related Publication 20220186285A1 · Jun 16, 2022
References Cited (199)
US 5013556A · Woodle et al. · 1991 [cited by applicant]
US 6592847B1 · Weissleder et al. · 2003 [cited by applicant]
US 7179655B2 · Patricelli · 2007 [cited by applicant]
US 7329506B2 · Ward et al. · 2008 [cited by applicant]
US 7833728B2 · Pastorek et al. · 2010 [cited by applicant]
US 8209130B1 · Kennedy et al. · 2012 [cited by applicant]
US 8519115B2 · Webster et al. · 2013 [cited by applicant]
US 8551727B2 · Kwon et al. · 2013 [cited by applicant]
US 8673267B2 · Bhatia et al. · 2014 [cited by applicant]
US 8858987B2 · Cullen et al. · 2014 [cited by applicant]
US 9999687B2 · Rajopadhye et al. · 2018 [cited by applicant]
US 10006916B2 · Kwong et al. · 2018 [cited by applicant]
US 20040091943A1 · Schneider · 2004 [cited by applicant]
US 20050191680A1 · Bruno et al. · 2005 [cited by applicant]
US 20090304719A1 · Daugherty et al. · 2009 [cited by applicant]
US 20100015607A1 · Geiss et al. · 2010 [cited by applicant]
US 20100047924A1 · Webster et al. · 2010 [cited by applicant]
US 20100124757A1 · Kwon et al. · 2010 [cited by applicant]
US 20100131432A1 · Kennedy et al. · 2010 [cited by applicant]
US 20100240050A1 · Bhatia et al. · 2010 [cited by applicant]
US 20110189680A1 · Keown et al. · 2011 [cited by applicant]
US 20110229888A1 · Hengen et al. · 2011 [cited by applicant]
US 20110244483A1 · Leeming et al. · 2011 [cited by applicant]
US 20110256567A1 · Berthelot et al. · 2011 [cited by applicant]
US 20130017223A1 · Hope et al. · 2013 [cited by applicant]
US 20130017971A1 · Geiss et al. · 2013 [cited by applicant]
US 20130116405A1 · Yu et al. · 2013 [cited by applicant]
US 20140242612A1 · Wang et al. · 2014 [cited by applicant]
US 20140363833A1 · Bhatia · 2014 [cited by examiner]
US 20150018517A1 · Rajopadhye et al. · 2015 [cited by applicant]
US 20150065420A1 · Soliman et al. · 2015 [cited by applicant]
US 20150132230A1 · Bossmann et al. · 2015 [cited by applicant]
US 20150132785A1 · Bossmann et al. · 2015 [cited by applicant]
US 20150133752A1 · Iverson et al. · 2015 [cited by applicant]
US 20150247149A1 · Feldstein et al. · 2015 [cited by applicant]
US 20160206726A1 · Cobbold et al. · 2016 [cited by applicant]
US 20170049904A1 · Lin et al. · 2017 [cited by applicant]
US 20170176458A1 · Veidal et al. · 2017 [cited by applicant]
US 20170369843A1 · Kahvejian et al. · 2017 [cited by applicant]
US 20180023114A1 · Morin et al. · 2018 [cited by applicant]
US 20180085466A1 · Bradley et al. · 2018 [cited by applicant]
US 20180335429A1 · Bhatia et al. · 2018 [cited by applicant]
US 20190256833A1 · Chung et al. · 2019 [cited by applicant]
US 20190345534A1 · Kwong et al. · 2019 [cited by applicant]
US 20190375796A1 · Touti et al. · 2019 [cited by applicant]
US 20220249369A1 · Holt et al. · 2022 [cited by applicant]
CN 1281346A · 2001 [cited by examiner]
JP 2009518446A · 2009 [cited by applicant]
JP 2010536370A · 2010 [cited by applicant]
JP 2012514982A · 2012 [cited by applicant]
JP 2016505138A · 2016 [cited by applicant]
JP 2017509594A · 2017 [cited by applicant]
KR 20150129908A · 2015 [cited by applicant]
WO 2002014867A2 · 2002 [cited by applicant]
WO 2004005348A1 · 2004 [cited by applicant]
WO 2007011660A2 · 2007 [cited by applicant]
WO 2007076129A2 · 2007 [cited by applicant]
WO 2008018933A2 · 2008 [cited by applicant]
WO 2008127019A1 · 2008 [cited by applicant]
WO 2009025846A2 · 2009 [cited by applicant]
WO WO2009111470A2 · 2009 [cited by applicant]
WO 2010019826A1 · 2010 [cited by applicant]
WO 2010101628A2 · 2010 [cited by applicant]
WO 2011116088A2 · 2011 [cited by applicant]
WO 2012125808A1 · 2012 [cited by applicant]
WO 2012178046A2 · 2012 [cited by applicant]
WO 2014028861A1 · 2014 [cited by applicant]
WO 2014079802A2 · 2014 [cited by applicant]
WO 2014197816A1 · 2014 [cited by applicant]
WO 2014197840A1 · 2014 [cited by applicant]
WO 2015154006A1 · 2015 [cited by applicant]
WO WO2015148622A1 · 2015 [cited by applicant]
WO 2017177115A1 · 2017 [cited by applicant]
WO 2017180587A2 · 2017 [cited by applicant]
WO 2017193070A1 · 2017 [cited by applicant]
WO 2018068135A1 · 2018 [cited by applicant]
WO WO2018064383A1 · 2018 [cited by applicant]
WO 2019236989A1 · 2019 [cited by applicant]
WO 2019236991A1 · 2019 [cited by applicant]
WO 2019236992A1 · 2019 [cited by applicant]
WO 2019237066A1 · 2019 [cited by applicant]
WO 2020160227A1 · 2020 [cited by applicant]
WO 2020160232A1 · 2020 [cited by applicant]
Lin et al., ACSNano, 7:10, 9001-9009, 2013 (Year: 2013). [cited by examiner]
Venner et al., American Journal of Transplantation 2015; 15: 1336-1348 (Year: 2015). [cited by examiner]
Chowdhury and Lieberman, Annu Rev Immunol. 2008 ; 26: 389-420 (Year: 2008). [cited by examiner]
Chen et al., Adv Drug Deliv Rev. Oct. 15, 2013; 65(10): 1357-1369 (Year: 2013). [cited by examiner]
Adessi and Soto, Current Medicinal Chemistry, 2002, 9, 963-978 (Year: 2002). [cited by examiner]
Trapani and Sutton, Current Opinion in Immunology 2003, 15:533-543 (Year: 2003). [cited by examiner]
Rao et al., RSC Adv., 2014, 4, 45625-45634 (Year: 2014). [cited by examiner]
Davalos et al., Ann Neurol 2014;75:303-308 (Year: 2014). [cited by examiner]
Casciola-Rosen et al., J. Exp. Med., vol. 190, No. 6, Sep. 20, 1999 815-825 (Year: 1999). [cited by examiner]
Gallwitz et al., PLoS One, Feb. 2012 | vol. 7, Issue 2, e31756 (Year: 2012). [cited by examiner]
Ludwicka-Bradley et al, Semin Arthritis Rheum 41:212-222 (2011) (Year: 2011). [cited by examiner]
Boivin et al., Laboratory Investigation (2009) 89, 1195-1220 (Year: 2009). [cited by examiner]
Ling et al., Acc. Chem. Res. 2015, 48, 1276-1285 (Year: 2015). [cited by examiner]
Dudani et al., ACSNano, vol. 9, No. 12, pp. 11708-11717, 2015 (Year: 2015). [cited by examiner]
Konishi et al., Circ Res. 2015;117:502-512 (Year: 2015). [cited by examiner]
“Barchetta, et al. “Circulating dipeptidyl peptidase-4 is independently associated with the presence and severtiy of NAFLD/NASH in individuals with and without obesity and metabolic disease” Journal of Endocrinological … [cited by applicant]
“International Search Report and Written Opinion for PCT Application No. PCT/US2017/054105, dated Jan. 18, 2018”. [cited by applicant]
“Kalubowilage, et al., “Early detection of pancreatic cancewrs in liquid biopsies by ultrasensitive fluorescence nanobiosensors” Nanomedicine: Nanotechnology, Biology, and Medicine 14 (2018) 1823-1832”. [cited by applicant]
“Matheeussen, et al., “Method comparison of dipeptidyl peptidase IV activity assays and their applications in biological samples containing reversible inhibitors” Clinica Chimica Acta 413 (212) 456-462”. [cited by applicant]
“Udukala, et al. “Early detection of non-small cell lung cancer in liquid biopsies by ultrasensitive protease activity analysis” J Cancer Metastasis Treat (2020); 6;25”. [cited by applicant]
Li, “Functionalization of gold nanoparticles for biomedical and catalyic applications”, The University of Bordeaux, Hal Open Science, pp. 1-140 (2014). [cited by applicant]
Abudayyeh O.O., “Nanoparticle-Chaperoned Urinary 'Synthetic Biomarkers' for Profiling Proteases in Cancer,” MIT Thesis, 2012, 63 Pages. [cited by applicant]
Allard B., et al., “The Ectonucleotidases CD 39 and CD 73: Novel Checkpoint Inhibitor Targets,” Immunological reviews, Mar. 2017, vol. 276, No. 1, 47 pages. [cited by applicant]
Arias M., et al., “The Untold Story of Granzymes in Oncoimmunology: Novel Opportunities with Old Acquaintances,” Trends in Cancer, Jun. 2017, vol. 3, No. 6, pp. 407-422. [cited by applicant]
Aungier S., et al., “The Extracellular Matrix: A New Dimension in Disease Diagnosis and Treatment,” Biochemist, Aug. 2016, vol. 38, No. 4, pp. 10-15. [cited by applicant]
Bonnans C., et al., “Remodelling the Extracellular Matrix in Development and Disease,” Nature Reviews Molecular Cell Biology, Dec. 2014, vol. 15, No. 12, pp. 786-801. [cited by applicant]
Breiman L., “Random Forests,” Machine Learning, Oct. 2001, vol. 45, No. 1, pp. 5-32. [cited by applicant]
Buss C.G., et al., “Protease Activity Sensors Noninvasively Classify Bacterial Infections and Antibiotic Responses,” EBiomedicine, 2018, vol. 38, pp. 248-256, Retrieved from URL: https://doi.Org/10.1016/j.ebiom.2018.11.… [cited by applicant]
Chikuma S., et al., “Suppressors of Cytokine Signaling: Potential Immune Checkpoint Molecules for Cancer Immunotherapy,” Cancer Science, Apr. 2017, vol. 108, No. 4, pp. 574-580. [cited by applicant]
Cohen J. D., et al., “Detection and Localization of Surgically Resectable Cancers with a Multi-analyte Blood Test,” Science, Jan. 18, 2018, vol. 359, No. 6378, pp. 926-930. [cited by applicant]
Cyll K., et al., “Tumour Heterogeneity Poses a Significant Challenge to Cancer Biomarker Research,” British Journal of Cancer, 2017, vol. 117, No. 3, pp. 367-375. [cited by applicant]
Deshpande P. P., et al., “Current Trends in the Use of Liposomes for Tumor Targeting,” Nanomedicine (London, England), Sep. 2013, vol. 8, No. 9, pp. 1509-1528 (32 Pages). [cited by applicant]
Dudani J.S., et al., “Classification of Prostate Cancer using a Protease Activity Nanosensor Library,” PNAS, Sep. 4, 2018, vol. 115, No. 36, pp. 8954-8959. [cited by applicant]
Dudani J.S., et al., “Harnessing Protease Activity to Improve Cancer Care,” Annual Review of Cancer Biology, 2018, vol. 2, pp. 353-376 (26 Pages). [cited by applicant]
Dudani J.S., “Sustained-Release Synthetic Biomarkers for Monitoring Thrombosis and Inflammation using Point-of-Care Compatible Readouts,” Advanced Functional Materials, May 3, 2016, vol. 26, No. 17, pp. 2919-2928 (20 Pa… [cited by applicant]
Egeblad M., et al., “New Functions for the Matrix Metalloproteinases in Cancer Progression,” Nature Reviews Cancer, Mar. 2002, vol. 2, No. 3, pp. 161-174 (15 Pages). [cited by applicant]
Elion J., et al., “Proteolytic Derivatives of Thrombin,” Annals of the New York Academy of Sciences, 1986, pp. 16-26. [cited by applicant]
Evers T.H., et al., “Quantitative Understanding of the Energy Transfer Between Fluorescent Proteins Connected via Flexible Peptide Linkers,” Biochemistry, 2006, vol. 45, No. 44, pp. 13183-13192. [cited by applicant]
Extended European Search Report for European Application No. 17857448.9, dated May 7, 2020, 10 Pages. [cited by applicant]
Extended European Search Report for European Application No. 19860757.4, dated May 17, 2022, 8 Pages. [cited by applicant]
Extended European Search Report for European Application No. 20772887.4, dated Mar. 28, 2023, 10 Pages. [cited by applicant]
Friedman A.D., et al., “The Smart Targeting of Nanoparticles,” Current Pharmaceutical Design, 2013, vol. 19, No. 35, pp. 6315-6329 (28 Pages). [cited by applicant]
Galati R., et al., “Increased Resistance of Peptides to Serum Proteases by Modification of their Amino Groups,” Zeitschrift fur Naturforschung, 2003, vol. 58c, pp. 558-561. [cited by applicant]
Gang D., et al., “Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals,” Genes, 2018, vol. 9(11), No. 557, 15 Pages. [cited by applicant]
Gentleman R C., et al., “Bioconductor: open software development for computational biology and bioinformatics,” Genome Biology, 2024, vol. 5, No. 10 R80, 16 pages. [cited by applicant]
Gootenberg U.S., et al., “Multiplexed and Portable Nucleic Acid Detection Platform with Cas13, Cas12a, and Csm6,” Science, 2018, vol. 360, No. 6387, pp. 439-444 (10 Pages). [cited by applicant]
Gootenberg U.S., et al., “Nucleic Acid Detection with CRISPRCasl3a/C2c2,” Science, Apr. 28, 2017, vol. 356, No. 6336, pp. 438-442(12 Pages). [cited by applicant]
Gural N., et al., “Engineered Livers for Infection Diseases,” Cellular and Molecular Gastroenterology and Hepatology, 2018, vol. 5, No. 2, pp. 131-144. [cited by applicant]
Hailfinger S., et al., “Adapter and Enzymatic Functions of Proteases in T-Cell Activation,” ImmuNological Reviews, 2009, vol. 232, pp. 334-347. [cited by applicant]
Haines J., et al., “A Quantitative Volumetric Micro-Computed Tomography Method to Analyze Lung Tumors in Genetically Engineered Mouse Models,” Neoplasia, 2009, vol. 11, No. 1, pp. 39-47. [cited by applicant]
Hann J., et al., “Usefulness of Highly Sensitive AFP-L3 and DCP in Surveillance for Hepatocellular Carcinoma in Patients with a Normal Alpha-Fetoprotein,” Jefferson Digital Commons, 2014, 8 pages. [cited by applicant]
Harris T.J., et al., “Protease-Triggered Unveiling of Bioactive Nanoparticles,” Small, 2008, vol. 4, No. 9, pp. 1307-1312. [cited by applicant]
Holt B.A., et al., “Nanosensors to Detect Protease Activity in Vivo for Noninvasive Diagnostics,” Journal of Visualized Experiments, Jul. 16, 2018, vol. 137 No. e57937, pp. 1-6. [cited by applicant]
Holt B.A., et al., “Protease Circuits for Processing Biological Information,” Nature Communications, Oct. 6, 2020, vol. 11, No. 1, DOI: 10.1038/s41467-020-18840-8, XP093032562, Retrieved from URL: https://www.ncbi.nlm.n… [cited by applicant]
Holt B.A., et al., “Proteases as Biological Bits for Programmable Medicine,” bioRxiv, Apr. 12, 2019, pp. 1-43 (42 Pages), [Retrieved on 2022-06-03] Retrieved from URL: https://www.biorxiv.org/content/10.1101/607895vl.fu… [cited by applicant]
Hori S.S., et al., “Mathematical Model Identifies Blood Biomarker-Based Early Cancer Detection Strategies and Limitations,” Science Translational Medicine, Nov. 16, 2011, vol. 3, No. 109, 109ra116, 19 Pages. [cited by applicant]
Hoshyar N., et al., “The Effect of Nanoparticle Size on in Vivo Pharmacokinetics and Cellular Interaction,” Nanomedicine (Lond.), 2016, vol. 11, No. 6, pp. 673-692. [cited by applicant]
Huber W., et al., “Orchestrating high-throughput genomic analysis with Bioconductor,” Nature Methods, 2015, vol. 12, pp. 115-121. [cited by applicant]
Hughes C.J.R., et al., “Dissecting the Role of the Extracellular Matrix in Heart Disease: Lessons from the Drosophila Genetic Model,” Veterinary Sciences, 2017, vol. 4, No. 24, pp. 1-28. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/036036, dated Sep. 12, 2019, 9 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/036039, dated Oct. 24, 2019, 11 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/036041, dated Sep. 19, 2019, 8 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/036155, dated Sep. 4, 2019, 8 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/050530, dated Dec. 19, 2019, 9 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2020/015823, dated Apr. 28, 2020, 10 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2020/015828, dated Jun. 18, 2020, 8 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2020/30132, dated Oct. 22, 2020, 37 Pages. [cited by applicant]
Jia L., et al., “An Attempt to Understand Kidney's Protein Handling Function by Comparing Plasma and Urine Proteomes,” PLoS One, Apr. 2009, vol. 4, Issue. 4, e5146, 9 Pages. [cited by applicant]
Josephson L., et al., “Near-Infrared Fluorescent NaNoparticles as Combined MR/Optical Imaging Probes,” Bioconjugate Chemistry, American Chemical Society, US, May 1, 2002, vol. 13, No. 3, pp. 554-560, DOI: 10.1021/BC0155… [cited by applicant]
Kappelhoff R., et al., “Overview of Transcriptomic Analysis of All Human Proteases, Non-Proteolytic Homologs and Inhibitors: Organ, Tissue and Ovarian Cancer Cell Line Expression Profiling of the Human Protease Degradom… [cited by applicant]
Khair D.O., et al., “Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma,” Frontiers in Immunology, Mar. 19, 2019, vol. 10, Article. 453, 20 Pages. [cited by applicant]
Kircher M.F., et al., “A Dual Fluorochrome Probe for Imaging Proteases,” Bioconjugate Chemistry, 2004, vol. 15, No. 2, pp. 242-248. [cited by applicant]
Klingler D., et al., “Profiling Protease Activities with Dynamic Proteomics Workflows,” Proteomics, Feb. 2012, vol. 12, No. 4-5, pp. 587-596 (17 Pages). [cited by applicant]
Kristensen M., et al., “Cell-Penetrating Peptides as Tools to Enhance Non-Injectable Delivery of Biopharmaceuticals,” Tissue Barriers, 2016, vol. 4, No. 2, e1178369, 15 Pages. [cited by applicant]
Kulkarni A., et al., “Reporter Nanoparticle that Monitors its Anticancer Efficacy in Real Time,” PNAS Early Edition, 2016, 10 Pages. [cited by applicant]
Kutlu O., et al., “Molecular Pathogenesis of Nonalcoholic Steatohepatitis-(NASH-) Related Hepatocellular Carcinoma,” Canadian Journal of Gastroenterology and Hepatology, vol. 2018, Article ID. 8543763, 10 p. 2018. [cited by applicant]
Kwon E.J., et al., “Ultrasensitive Tumor-Penetrating Nanosensors of Protease Activity,” Nature Biomedical Engineering, Apr. 10, 2017, vol. 1, Article No. 0054, 10 Pages. [cited by applicant]
Kwong G.A., et al., “Mass-Encoded Synthetic Biomarkers for Multiplexed Urinary Monitoring of Disease,” Nature Biotechnology, Jan. 2013, vol. 31, No. 1, pp. 63-70 (29 Pages), DOI: 10.1038/nbt.2464, ISSN: 1087-0156, XP055… [cited by applicant]
Kwong G.A., et al., “Mathematical Framework for Activity-Based Cancer Biomarkers,” PNAS, Oct. 13, 2015, vol. 112, No. 41, p. 12627-12632 (12 Pages). [cited by applicant]
Larimer B.M., et al., “Granzyme B Pet Imaging as a Predictive Biomarker of Immunotherapy Response,” Cancer Research, May 1, 2017, vol. 77, No. 9, pp. 2318-2327 (20 Pages). [cited by applicant]
Lau J.L., et al., “Therapeutic Peptides: Historical Perspectives, Current Development Trends, and Future Directions,” Bioorganic & Medicinal Chemistry, 2018, vol. 26, pp. 2700-2707. [cited by applicant]
Lee J., et al., “Implementation of a Multiplex and Quantitative Proteomics Platform for Assessing Protein Lysates using DNA-Barcoded Antibodies,” Molecular & Cellular Proteomics, 2018, vol. 17, No. 6, pp. 1245-1258. [cited by applicant]
Lin C-C., et al., “PEG Hydrogels for the Controlled Release of Biomolecules in Regenerative Medicine,” Pharmaceutical Research, Mar. 2009, vol. 26, No. 3, pp. 631-643. [cited by applicant]
Lin C-C., et al., “The Biodegradation of Biodegradable Polymeric Biomaterials,” Chapter II.4.3 in Biomaterials Science 3d Edition, Ratner et al., Eds Academic Press, 2013, pp. 716-728. [cited by applicant]
Lo J.H., et al., “iRGD-Guided Tumor-Penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer,” Molecular Cancer Therapeutics, Nov. 2018, vol. 17, No. 11, pp. 2377-2388 (13 Pages). [cited by applicant]
Luther J., et al., “Hepatic Connexin 32 Associates with Nonalcoholic Fatty Liver Disease Severity,” Hepatology Communications, Jul. 2018, vol. 2, No. 7, pp. 786-797. [cited by applicant]
Mallinckrodt C.H., et al., “Assessing and Interpreting Treatment Effects in Longitudinal Clinical Trials with Missing Data,” Biological Psychiatry, 2003, vol. 53, pp. 754-760. [cited by applicant]
Mason S.D., et al., “Proteolytic Networks in Cancer,” Trends in Cell Biology, Apr. 2011, vol. 21, No. 4, pp. 228-237 (18 Pages). [cited by applicant]
Mauiyyedip S., et al., “Chronic Humoral Rejection: Identification of Antibody-Mediated Chronic Renal Allograft Rejection by C4d Deposits in Peritubular Capillaries,” Journal of the American Society of Nephrology (JASN),… [cited by applicant]
Metz C.E., “Basic Principles of ROC Analysis,” Seminars in Nuclear Medicine, Oct. 1978, vol. 8, No. 4, pp. 283-298. [cited by applicant]
Milletti F., “Cell-Penetrating Peptides: Classes, Origin, and Current Landscape,” Drug Discovery Today, Aug. 1, 2012, vol. 17, No. 15/16, pp. 850-860. [cited by applicant]
Nagrath S., et al., “Isolation of Rare Circulating Tumour Cells in Cancer Patients by Microchip Technology,” Nature, Dec. 20, 2007, vol. 450, No. 7173, pp. 1235-1239 (11 Pages). [cited by applicant]
Nam C. et al., “CT and MRI Improve Detection of Hepatocellular Carcinoma, Compared With Ultrasound Alone, in Patients With Cirrhosis,” Clinical Gastroenterology and Hepatology, 2011, vol. 9, pp. 161-167. [cited by applicant]
Ncbi Genbank: “Fe-S Oxidoreductase [Serpentinimonas Maccroryi],” NCBI Reference Sequence No. BAO83571.1, Nov. 27, 2018, 2 Pages, 2014, Downloaded via the Worldwide Web/Internet from www.ncbi.com During a BLAST Sequence … [cited by applicant]
Nguyen A. T., et al., “The Prototype HIV-1 Maturation Inhibitor, Bevirimat, Binds to the CA-SP1 Cleavage Site in Immature Gag Particles,” Retrovirology, 2011, vol. 8, No. 101, 13 Pages. [cited by applicant]
Zegarska J., et al., “Extracellular Matrix Proteins, Proteolytic Enzymes, and TGF-Beta1 in the Renal Arterial Wall of Chronically Rejected Renal Allografts,” Transplant Proceedings, 2003, vol. 35, pp. 2193-2195, DOI: 10… [cited by applicant]
Raagel H., et al., “Peptide-Mediated Protein Delivery-Which Pathways are Penetrable?,” Biochimica et Biophysica Acta, 2010, vol. 1798, No. 12, pp. 2240-2248. [cited by applicant]
Robinson C.R., et al., “Optimizing the Stability of Single-chain Proteins by Linker Length and Composition Mutagenesis,” Proceedings of the National Academy of Sciences, May 1998, vol. 95, No. 11, pp. 5929-5934. [cited by applicant]
Sanchez-Martin D., et al., “Selection Strategies for Anti-Cancer Antibody Discovery: Searching off the Beaten Path,” Trends in Biotechnology, May 2015, vol. 33, No. 5, pp. 292-301 (20 Pages), 2017. [cited by applicant]
Schuerle S., et al., “Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling,” Nano Letters, 2016, vol. 16, No. 10, pp. 6303-6310 (22 Pages). [cited by applicant]
Simard B., et al., “Site-Specific Conjugation of the Quencher on Peptide's N-Terminal for the Synthesis of a Targeted Non-Spreading Activatable Optical Probe,” Journal of Peptide Science, 2016, vol. 22, No. 6, pp. 415-4… [cited by applicant]
Singal A., et al., “Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis,” Alimentary Pharmacology & Therapeutics, 2009, vol. 30, pp. 37-47. [cited by applicant]
Sjoblom T., et al., “The Consensus Coding Sequences of Human Breast and Colorectal Cancers,” Science, Oct. 13, 2006, vol. 314, No. 5797, pp. 268-274. [cited by applicant]
Song J., et al., “Prosper: An Integrated Feature-Based Tool for Predicting Protease Substrate Cleavage Sites,” PLoS One, Nov. 2012, vol. 7, Issue. 11, e50300, 23 Pages. [cited by applicant]
Sorenson., “Selection of antibodies against a single rare cell present in a heterogeneous population using phage display”, Nature Protocols, 2011, vol. 6,No. 4, pp. 509-522. [cited by applicant]
Stegall M.D., et al., “The Role of Complement in Antibody-Mediated Rejection in Kidney Transplantation,” Nature Reviews Nephrology, 2012, vol. 8, pp. 670-678, DOI:10.1038/nrneph.2012.212, XP055293015. [cited by applicant]
Tascilar M., et al., “Role of Tumor Markers and Mutations in Cells and Pancreatic Juice in the Diagnosis of Pancreatic Cancer,” Annals of Oncology, 1999, vol. 10, Supplement. 4, pp. s107-s110. [cited by applicant]
Tockman M.S., et al., “Considerations in Bringing a Cancer Biomarker to Clinical Application,” Cancer Research, May 1, 1992, vol. 52, pp. 2711s-2718s. [cited by applicant]
Van Lehn R.C., et al., “Penetration of Lipid Bilayers by Nanoparticles with Environmentally-Responsive Surfaces,” Soft Matter, 2011, vol. 7, pp. 11392-11404. [cited by applicant]
Voskoboink I., et al., “Perforin and Granzymes: Function, Dysfunction and Human Pathology,” Nature Reviews Immunology, Jun. 2015, vol. 15, No. 6, pp. 388-400. [cited by applicant]
Wang M., et al., “Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC,” Cancer Epidemiology, Biomarkers & Prevention, 2017, vol. 26, No. 5, 9 pages. [cited by applicant]
Wang P., et al., “Mass Spectrometry-Based Protein Identification by Integrating De Novo Sequencing with Database Searching,” BMC Bioinformatics, 2013, vol. 14, Supplement. 2, No. S24, 9 Pages. [cited by applicant]
Wang Z., et al., “RNA-Seq: a revolutionary tool for transcriptomics,” Nature Reviews Genetics, 2009, vol. 10, No. 1, 16 pages. [cited by applicant]
Warren A.D., et al., “Disease Detection by Ultrasensitive Quantification of Microdosed Synthetic Urinary Biomarkers,” JACS, 2014, vol. 136, p. 13709-13714 (14 Pages). [cited by applicant]
Warren A.D., et al., “Point-of-Care Diagnostics for Noncommunicable Diseases using Synthetic Urinary Biomarkers and Paper Microfluidics,” PNAS, Mar. 11, 2014, vol. 111, No. 10, pp. 3671-3676 (12 Pages). [cited by applicant]
Wong W., et al., “Chronic Humoral Rejection of Human Kidney Allografts is Associated with MMP-2 Accumulation in Podocytes and Its Release in the Urine,” American Journal of Transplantation, 2010, vol. 10, pp. 2463-2471. [cited by applicant]