IP Library › Granted Patent US 12,360,103
Granted Patent B2
US 12,360,103 · App. 15/733,755 · Granted Jul 15, 2025

Blood biomarker for eosinophilic gastrointestinal disorders

Inventors: Marc E. Rothenberg (Cincinnati, OH); Ting Wen (Cincinnati, OH); Yrina Rochman (Cincinnati, OH)
Assignee: Children's Hospital Medical Center
G01N33/505G01N33/6893G01N2333/5409G01N2333/5437G01N2800/06
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 12,360,103
App. No.
15/733,755
Granted
Jul 15, 2025
Kind
B2
Abstract

The disclosure provides a simple and rapid blood-based bioassay useful in the diagnosis, treatment and monitoring of eosinophilic gastrointestinal disorders, and related compositions and methods.

Claims (30)

1. A method for treating eosinophilic gastrointestinal disorder (EGID) in a human subject in need thereof, the method comprising

detecting thymic stromal lymphopoietin (TSLP) responsive cells in a sample of whole blood obtained from the subject by

contacting cells in vitro with TSLP without stimulation of the cells with anti-CD3 or anti-CD28 antibodies, wherein the cells are selected from PBMC, CD4+ T cells, or memory CD4+ T cells, and

detecting one or more analytes in the cells or secreted by the cells, the one or more analytes selected from phosphorylated signal transducer and activator of transcription 5 (pSTAT5), interleukin-5 (IL-5), and interleukin-13 (IL-13),

wherein the detection of the one or more of the analytes indicates TSLP responsive cells in the blood of the human subject,

determining whether an amount of the one or more analytes is above or below a predetermined diagnostic threshold, wherein an amount above the threshold indicates an EGID status of active disease for the subject and an amount below the threshold indicates that an EGID status of managed, and

administering an EGID therapy to the subject having an EGID status of active disease, wherein the EGID therapy is selected from proton pump inhibitor therapy, dietary therapy, anti-cytokine therapy, anti-ALOX15 therapy, anti-TSLP therapy, anti-eosinophil therapy, glucocorticoid therapy, and esophageal dilation; or

re-administering current therapy to the subject having an EGID status of managed.

2. The method of claim 1 , for use in a method for diagnosing or monitoring EGID in a human subject in need thereof.

3. The method of claim 1 , wherein the method further comprises a step of isolating a fraction of cells from the whole blood enriched for PBMC, CD4+ T cells, or memory CD4+ T cells.

4. The method of claim 1 , wherein the analyte is pSTAT5.

5. The method of claim 1 , wherein the analyte is IL-5 or IL-13 gene or protein expression.

6. The method of claim 4 , wherein the pSTAT5 is detected by a method comprising flow cytometry.

7. The method of claim 5 , wherein the IL-5 or IL-13 gene expression is detected by a method comprising a polymerase chain reaction (PCR), flow cytometry, or a chromatographic technique.

8. The method of claim 5 , wherein the IL-5 or IL-13 protein expression is detected by a method comprising one or more of flow cytometry, immunoassay, and a chromatographic technique.

9. The method of claim 1 , wherein the EGID is eosinophilic esophagitis (EoE) or eosinophilic gastritis (EG).

10. The method of claim 1 , wherein the subject in need is characterized as presenting with one or more clinical features selected from dysphagia, food impaction, vomiting, abdominal pain, refractory reflux symptoms, failure to thrive in young children, a diagnosis of an atopic allergic disorder, and a family member having an EGID diagnosis.

11. The method of claim 10 , wherein the atopic allergic disorder is selected from food allergy, asthma, atopic dermatitis, allergic rhinitis and allergic conjunctivitis.

12. The method of claim 1 , wherein the EGID therapy comprises anti-TSLP therapy.

13. The method of claim 12 , wherein the anti-TSLP therapy is an immunotherapy.

14. The method of claim 13 , wherein the anti-TSLP therapy comprises anti-TSLP monoclonal antibody therapy.

15. An assay for detecting a thymic stromal lymphopoietin (TSLP) responsive population of cells in human blood, wherein the method is performed within 1-6 hours, the method comprising

contacting cells in vitro with TSLP, wherein the cells are previously isolated from a sample of whole blood obtained from a human subject in need of treatment for an eosinophilic gastrointestinal disorder (EGID), and

detecting phosphorylated signal transducer and activator of transcription 5 (pSTAT5) in the cells by a method comprising one or more of flow cytometry, immunoassay, and a chromatographic technique,

wherein the presence of pSTAT5 indicates a TSLP responsive population of cells in the blood of the human subject,

wherein the cells are selected from PBMC, CD4+ T cells, or memory CD4+ T cells, and

wherein the method does not include stimulation of the cells with anti-CD3 or anti-CD28 antibodies.

16. The assay of claim 15 , wherein the assay is performed by a method comprising flow cytometric analysis of pSTAT5.

17. The assay of claim 15 , wherein the method comprises isolating PBMC, CD4+ T cells, or memory CD4+ T cells from the sample of whole blood.

18. The assay of claim 15 , wherein the assay is performed in 2-4 hours.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 12, 2022
From: ROTHENBERG, MARC E.; WEN, TING; ROCHMAN, YRINA
To: CHILDREN'S HOSPITAL MEDICAL CENTER
Reel/Frame 059966/0488 →
Continuity (2)
Provisional Application 62660308 · Apr 20, 2018
Related Publication 20210080453A1 · Mar 18, 2021
References Cited (400)
US 4376110A · David et al. · 1983 [cited by applicant]
US 4522811A · Eppstein et al. · 1985 [cited by applicant]
US 4675604A · Moyer et al. · 1987 [cited by applicant]
US 4675904A · Silverman · 1987 [cited by applicant]
US 5015627A · Lindsey · 1991 [cited by applicant]
US 5148483A · Silverman · 1992 [cited by applicant]
US 5288644A · Beavis et al. · 1994 [cited by applicant]
US 5412073A · Kalsheker · 1995 [cited by applicant]
US 5445934A · Fodor et al. · 1995 [cited by applicant]
US 5530101A · Queen et al. · 1996 [cited by applicant]
US 5700637A · Southern · 1997 [cited by applicant]
US 5744305A · Fodor et al. · 1998 [cited by applicant]
US 5888510A · Kishimoto et al. · 1999 [cited by applicant]
US 5945334A · Besemer et al. · 1999 [cited by applicant]
US 5976081A · Silverman · 1999 [cited by applicant]
US 6054270A · Southern · 2000 [cited by applicant]
US 6300063B1 · Lipshutz et al. · 2001 [cited by applicant]
US 6403782B1 · Luster et al. · 2002 [cited by applicant]
US 6429027B1 · Chee et al. · 2002 [cited by applicant]
US 6733977B2 · Besemer et al. · 2004 [cited by applicant]
US 6780973B1 · Luster et al. · 2004 [cited by applicant]
US 6825350B2 · Crooks et al. · 2004 [cited by applicant]
US 6858394B1 · Chee et al. · 2005 [cited by applicant]
US 7364858B2 · Barany et al. · 2008 [cited by applicant]
US 7514209B2 · Dai et al. · 2009 [cited by applicant]
US 7582620B2 · Lew · 2009 [cited by applicant]
US 7592326B2 · Karaolis · 2009 [cited by applicant]
US 7879547B2 · Rothenberg et al. · 2011 [cited by applicant]
US 8030003B2 · Rothenberg · 2011 [cited by applicant]
US 8409565B2 · Levi-schaffer et al. · 2013 [cited by applicant]
US 9260756B2 · Rothenberg et al. · 2016 [cited by applicant]
US 9345763B2 · Rothenberg et al. · 2016 [cited by applicant]
US 9517238B2 · Rochman et al. · 2016 [cited by applicant]
US 9624545B2 · Rothenberg et al. · 2017 [cited by applicant]
US 9691411B2 · Scherer et al. · 2017 [cited by applicant]
US 9803244B2 · Rothenberg et al. · 2017 [cited by applicant]
US 9928344B2 · Rothenberg et al. · 2018 [cited by applicant]
US 9982303B2 · Rothenberg · 2018 [cited by applicant]
US 10155985B2 · Rothenberg et al. · 2018 [cited by applicant]
US 10294517B2 · Rothenberg et al. · 2019 [cited by applicant]
US 10422004B2 · Rothenberg et al. · 2019 [cited by applicant]
US 10821094B2 · Azouz et al. · 2020 [cited by applicant]
US 11564905B2 · Azouz · 2023 [cited by applicant]
US 20020077825A1 · Silverman et al. · 2002 [cited by applicant]
US 20030078768A1 · Silverman et al. · 2003 [cited by applicant]
US 20030157479A1 · Bachmann et al. · 2003 [cited by applicant]
US 20030167189A1 · Lutgen et al. · 2003 [cited by applicant]
US 20030194404A1 · Greenfeder et al. · 2003 [cited by applicant]
US 20040033502A1 · Williams et al. · 2004 [cited by applicant]
US 20040141951A1 · Rothenberg et al. · 2004 [cited by applicant]
US 20050163764A1 · Medzhitov et al. · 2005 [cited by applicant]
US 20070059720A9 · Fuqua et al. · 2007 [cited by applicant]
US 20070233468A1 · Ozdas et al. · 2007 [cited by applicant]
US 20070233498A1 · Silverman et al. · 2007 [cited by applicant]
US 20080187908A1 · Adra · 2008 [cited by applicant]
US 20080201280A1 · Martin et al. · 2008 [cited by applicant]
US 20090233275A1 · Rothenberg · 2009 [cited by applicant]
US 20090269774A1 · Rothenberg et al. · 2009 [cited by applicant]
US 20100151472A1 · Nolan · 2010 [cited by examiner]
US 20100240965A1 · Furuta et al. · 2010 [cited by applicant]
US 20100262603A1 · Odom et al. · 2010 [cited by applicant]
US 20110123530A1 · Arron et al. · 2011 [cited by applicant]
US 20110144183A1 · Paquet et al. · 2011 [cited by applicant]
US 20110195500A1 · Rothenberg · 2011 [cited by applicant]
US 20110301046A1 · Rothenberg et al. · 2011 [cited by applicant]
US 20120004205A1 · Rothenberg · 2012 [cited by applicant]
US 20120041911A1 · Pestian et al. · 2012 [cited by applicant]
US 20120283117A1 · Rothenberg · 2012 [cited by applicant]
US 20120288068A1 · Jaiswal et al. · 2012 [cited by applicant]
US 20130035961A1 · Yegnanarayanan · 2013 [cited by applicant]
US 20130065972A1 · Dent et al. · 2013 [cited by applicant]
US 20130324435A1 · Rothenberg et al. · 2013 [cited by applicant]
US 20140073801A1 · Storer et al. · 2014 [cited by applicant]
US 20140113372A1 · Haque et al. · 2014 [cited by applicant]
US 20140228301A1 · Meade et al. · 2014 [cited by applicant]
US 20140228315A1 · Rothenberg et al. · 2014 [cited by applicant]
US 20140286896A1 · Rothenberg et al. · 2014 [cited by applicant]
US 20140328861A1 · Payton et al. · 2014 [cited by applicant]
US 20140343255A1 · Gonzalez et al. · 2014 [cited by applicant]
US 20150038552A1 · Rothenberg et al. · 2015 [cited by applicant]
US 20150045334A1 · Rothenberg · 2015 [cited by examiner]
US 20150182499A1 · Reboud-ravaux et al. · 2015 [cited by applicant]
US 20150355180A1 · Resnick et al. · 2015 [cited by applicant]
US 20160129012A1 · Rochman et al. · 2016 [cited by applicant]
US 20160177394A1 · Rothenberg et al. · 2016 [cited by applicant]
US 20160180041A1 · Pestian et al. · 2016 [cited by applicant]
US 20160213681A1 · Santus et al. · 2016 [cited by applicant]
US 20160264658A1 · Ahmed · 2016 [cited by examiner]
US 20160304960A1 · Rothenberg · 2016 [cited by applicant]
US 20160312282A1 · Rothenberg et al. · 2016 [cited by applicant]
US 20170002021A1 · Wagberg · 2017 [cited by applicant]
US 20170061073A1 · Sadhasivam · 2017 [cited by applicant]
US 20170067111A1 · Rothenberg et al. · 2017 [cited by applicant]
US 20170183719A1 · Rothenberg et al. · 2017 [cited by applicant]
US 20170199191A1 · Fulkerson · 2017 [cited by applicant]
US 20170233813A1 · Rothenberg et al. · 2017 [cited by applicant]
US 20170281716A1 · Martin · 2017 [cited by applicant]
US 20190000799A1 · Azouz et al. · 2019 [cited by applicant]
US 20190046444A1 · Konduri et al. · 2019 [cited by applicant]
US 20200338043A1 · Azouz et al. · 2020 [cited by applicant]
CN 101275941A · 2008 [cited by applicant]
EP 0619321A1 · 1994 [cited by applicant]
EP 0619321B1 · 1999 [cited by applicant]
EP 0949271A1 · 1999 [cited by applicant]
GB 2450780A · 2009 [cited by applicant]
WO 8910977A1 · 1989 [cited by applicant]
WO 9937319A1 · 1999 [cited by applicant]
WO 2005007175A2 · 2005 [cited by applicant]
WO 2005033134A2 · 2005 [cited by applicant]
WO 2005106492A2 · 2005 [cited by applicant]
WO 2005106492A3 · 2006 [cited by applicant]
WO 2006083390A2 · 2006 [cited by applicant]
WO 2006119343A1 · 2006 [cited by applicant]
WO 2006083390A3 · 2006 [cited by applicant]
WO 2009015434A1 · 2009 [cited by applicant]
WO 2009018493A1 · 2009 [cited by applicant]
WO 2009061819A1 · 2009 [cited by applicant]
WO 2009089062A2 · 2009 [cited by applicant]
WO 2009089062A3 · 2009 [cited by applicant]
WO 2009089062A8 · 2010 [cited by applicant]
WO 2010126867A1 · 2010 [cited by applicant]
WO 2012025765A1 · 2012 [cited by applicant]
WO 2012094643A2 · 2012 [cited by applicant]
WO 2012094643A3 · 2012 [cited by applicant]
WO 2012174549A2 · 2012 [cited by applicant]
WO 2012177945A2 · 2012 [cited by applicant]
WO 2012178188A2 · 2012 [cited by applicant]
WO 2012174549A9 · 2013 [cited by applicant]
WO 2012177945A3 · 2013 [cited by applicant]
WO 2013082308A1 · 2013 [cited by applicant]
WO 2012178188A3 · 2013 [cited by applicant]
WO 2013126834A1 · 2013 [cited by applicant]
WO 2013155010A1 · 2013 [cited by applicant]
WO 2014059178A1 · 2014 [cited by applicant]
WO 2014190269A1 · 2014 [cited by applicant]
WO 2015017731A1 · 2015 [cited by applicant]
WO 2015127379A1 · 2015 [cited by applicant]
WO 2015142739A1 · 2015 [cited by applicant]
WO 2016023026A1 · 2016 [cited by applicant]
WO 2016196146A1 · 2016 [cited by applicant]
WO 2017048860A1 · 2017 [cited by applicant]
WO 2017123401A1 · 2017 [cited by applicant]
WO 2019204580A1 · 2019 [cited by applicant]
Rochman et al (Science Signaling, 2023, 16.eadg6360, pp. 1-16) (Year: 2023). [cited by examiner]
R&D systems (2024, 6 pages) (Year: 2024). [cited by examiner]
Khan, S. (Best Practice & Research Clin. Gastroent., 2005, 19(2): 177-198) (Year: 2005). [cited by examiner]
Lu et al. (Sep. 15, 2011) “MicroRNA-21 Limits in Vivo Immune Response-mediated Activation of the IL-12/IFN-gamma Pathway, Th1 Polarization, and the Severity of Delayed-type Hypersensitivity”, Journal of Immunology, 187 … [cited by applicant]
Lu et al. (Feb. 15, 2013) “miR-223 Deficiency Increases Eosinophil Progenitor Proliferation”, Journal of Immunology, 190(4):1576-1582. [cited by applicant]
Lu et al. (Jul. 2012) “MiR-375 is Downregulated in Epithelial Cells after IL-13 Stimulation and Regulates an IL-13-Induced Epithelial Transcriptome”, Mucosal Immunology, 5(4):388-396. [cited by applicant]
Lu et al. (Mar. 22, 2013) “Targeted Ablation of miR-21 Decreases Murine Eosinophil Progenitor Cell Growth”, PLoS One, e59397, 8(3):8 pages. [cited by applicant]
Lucendo et al. (Jun. 15, 2011) “Montelukast Was Inefficient in Maintaining Steroid-Induced Remission in Adult Eosinophilic Esophagitis”, Digestive Diseases and Sciences, 56(12):3551-3558. [cited by applicant]
Lucendo et al. (Sep. 2008) “Treatment with Topical Steroids Downregulates IL-5, Eotaxin-1/CCL11, and Eotaxin-3/CCL26 Gene Expression in Eosinophilic Esophagitis”, The American Journal of Gastroenterology, 103 (9):2184-2… [cited by applicant]
Zhang et al. (Dec. 2009) “Effects of Endogenous Glucocorticoids on Allergic Inflammation and T(H)1/T(H)2 Balance in Airway Allergic Disease”, Annals of Allergy, Asthma & Immunology, 103(6):525-534. [cited by applicant]
Markowitz et al. (Apr. 2003) “Elemental Diet Is an Effective Treatment for Eosinophilic Esophagitis in Children and Adolescents”, The American Journal of Gastroenterology, 98(4):777-782. [cited by applicant]
Martin et al. (May 2003) “Role of Innate Immune Factors in the Adjuvant Activity of Monophosphoryl Lipid A”, Infection and Immunity, 71(5):2498-2507. [cited by applicant]
Martinez-Nunez et al. (Jan. 21, 2011) “The Interleukin 13 (IL-13) Pathway in Human Macrophages is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor Alpha1 (IL13Ralpha1)”, Journal of Biological Ch… [cited by applicant]
Matsushima (2010) “MicroRNAs and Esophageal Squamous Cell Carcinoma”, Digestion, 82(3):38-144,. [cited by applicant]
Mattes et al. (Nov. 3, 2009) “Antagonism of microRNA-126 Suppresses the Effector Function of TH2 Cells and the Development of Allergic Airways Disease”, Proceedings of the National Academy of Sciences of the United Stat… [cited by applicant]
Mayer et al. (Apr. 27, 2001) “Identification of Receptor Binding and Activation Determinants in the N-Terminal and N-loop Regions of the CC Chemokine Eotaxin”, Journal of Biological Chemistry, 276(17):13911-13916. [cited by applicant]
Mayoral et al. (Jan. 1, 2009) “MicroRNA-221-222 Regulate the Cell-Cycle in Mast Cells”, Journal of Immunology, 182(1):433-445. [cited by applicant]
McGettrick et al. (Sep. 25, 2007) “Toll-like Receptors: Key Activators of Leucocytes and Regulator of Hematopoiesis”, British Journal of Haematology, 139(2):185-193. [cited by applicant]
Medina et al. (Sep. 2, 2010) “OncomiR Addiction in an in Vivo Model of microRNA-21-induced Pre-β-cell Lymphoma”, Nature, 467(7311):86-90. [cited by applicant]
Meineke et al. (Dec. 2002) “Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine”, Br… [cited by applicant]
Menard-Katcher et al. (2012) “MicroRNAs are Altered in Eosinophilic Esophagitis”, Gastroenterology, 142(5) 8440. [cited by applicant]
Menzies-Gow et al. (Apr. 2003) “Anti-IL-5 (Mepolizumab) Therapy Induces Bone Marrow Eosinophil Maturational Arrest and Decreases Eosinophil Progenitors in the Bronchial Mucosa of Atopic Asthmatics”, The Journal of Aller… [cited by applicant]
Meyer et al. (Jan. 2013) “The UCSC Genome Browser database: Extensions and Updates 2013”, Nucleic Acids Research, 41:D64-D69. [cited by applicant]
Michael et al. (2005) “Biochemical and Enzymatic Characterization of Human Kallikrein 5 (hK5), a Novel Serine Protease Potentially Involved in Cancer Progression”, Journal of Biological Chemistry, 280(15):14628-35. [cited by applicant]
Michaels et al. (Feb. 5-11, 2005) “Prediction of Cancer Outcome with Microarrays: A Multiple Random Validation Strategy”, Lancet, 365(9458):488-492. [cited by applicant]
Milbrandt J. (Nov. 6, 1987) “A Nerve Growth Factor-induced Gene Encodes a Possible Transcriptional Regulatory Factor”, Science, 238(4828):797-799. [cited by applicant]
Milgrom et al. (Dec. 23, 1999) “Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody”, The New England Journal of Medicine, 341(26):1966-1973. [cited by applicant]
Mishra et al. (Jan. 1, 2001) “An Etiological Role for Aeroallergens and Eosinophils in Experimental Esophagitis”, Journal of Clinical Investigation, 107(1):83-90. [cited by applicant]
Mishra et al. (Jan. 2008) “Esophageal Remodeling Develops as a Consequence of Tissue Specific IL-5-induced Eosinophilia”, Gastroenterology, 134(1):204-214. [cited by applicant]
Mishra et al. (Mar. 1, 2002) “IL-5 Promotes Eosinophil Trafficking to the Esophagus”, The Journal of Immunology, 168(5):2464-2469. [cited by applicant]
Mishra et al. (Nov. 2003) “Intratracheal IL-13 Induces Eosinophilic Esophagitis by an IL-5, Eotaxin-1, and STAT6-Dependent Mechanism”, Gastroenterology, 125(5)1419-1427. [cited by applicant]
Mitchell et al. (Jul. 29, 2008) “Circulating microRNAs as Stable Blood-based Markers for Cancer Detection”, Proceedings of the National Academy of Sciences of the United States of America, 105(30):10513-10518. [cited by applicant]
Mizuno et al. (2013) “Genotype of Abcc3-211c > T Influences the Pharmacokinetics of Morphine Glucuronide in Children”, Clinical Pharmacology & Therapeutics, 93:S63. [cited by applicant]
Mogil et al. (Jul. 6, 1999) “The genetic mediation of individual differences in sensitivity to pain and its inhibition”, PNAS, 96(14):7744-7751. [cited by applicant]
Molina-Infante et al. (May 7, 2008) “Overlap of Reflux and Eosinophilic Esophagitis in Two Patients Requiring Different Therapies: A Review of the Literature”, World Journal of Gastroenterology, 14(9):1463-1466. [cited by applicant]
Mori et al. (Jan. 16, 2009) “Identification of the Human Eosinophil Lineage-committed Progenitor: Revision of Phenotypic Definition of the Human Common Myeloid Progenitor”, Journal of Experimental Medicine, 206(1):183-1… [cited by applicant]
Mukhopadhyay et al. (Jul. 2010) “Matrix Metalloproteinase-12 is a Therapeutic Target for Asthma in Children and Young Adults”, The Journal of Allergy and Clinical Immunology, 126(1):70-76. [cited by applicant]
Mulder et al. (Jan. 12, 2011) “Understanding Eosinophilic Esophagitis: The Cellular and Molecular Mechanisms of an Emerging Disease”, Mucosal Immunology, 4(2):139-147. [cited by applicant]
Murata et al. (Jul. 2008) “Activation of Toll-like Receptor 2 by a Novel Preparation of Cell Wall Skeleton from Mycobacterium Bovis BCG Tokyo (SMP-105) Sufficiently Enhances Immune Responses Against Tumors”, Cancer Scie… [cited by applicant]
Nagai et al. (Jun. 2006) “Toll-like Receptors on Hematopoietic Progenitor Cells Stimulate Innate Immune System Replenishment”, Immunity, 24(6):801-812. [cited by applicant]
Nagase et al. (Oct. 15, 2003) “Expression and Function of Toll-like Receptors in Eosinophils: Activation by Toll-like Receptor 7 Ligand”, Journal of Immunology, 171(8):3977-3982. [cited by applicant]
Navarro et al. (Jun. 1, 2010) “Small RNAs Guide Hematopoietic Cell Differentiation and Function”, Journal of Immunology, 184(11):5939-5947. [cited by applicant]
Naya et al. (May 7, 2001) “Discovery of a Novel CCR3 Selective Antagonist”, Bioorganic & Medicinal Chemistry Letters, 11(9):1219-1223. [cited by applicant]
Naya et al. (Jun. 2003) “Structure-Activity Relationships of 2-(Benzothiazolylthio)acetamide Class of CCR3 Selective Antagonist”, Chemical and Pharmaceutical Bulletin, 51(6):697-701. [cited by applicant]
Newberry et al. (Nov. 2005) “Strongyloides Hyperinfection Presenting as Acute Respiratory Failure And Gram-negative Sepsis”, Chest, 128(5):3681-3684. [cited by applicant]
Noel et al. (Jul. 2004) “Clinical and Immunopathologic Effects of Swallowed Fluticasone for Eosinophilic Esophagitis”, Clinical Gastroenterology and Hepatology, 2(7):568-575. [cited by applicant]
Notterman et al. (2002) “Tumor Biology and Microarray Analysis of Solid Tumors: Colorectal Cancer as a Model System”, Microarrays and Cancer Research, 81-111. [cited by applicant]
Novak et al. (Apr. 1, 2007) “CCL23 Expression is Induced by IL-4 in a STAT6-Dependent Fashion”, Journal of Immunology, 178(7):4335-4341. [cited by applicant]
Ogbogu et al. (Dec. 2009) “Hypereosinophilic Syndromes: A Multicenter, Retrospective Analysis of Clinical Characteristics and Response to Therapy”, The Journal of Allergy and Clinical Immunology, 124(6):1319-1325. [cited by applicant]
Ordoñez et al. (Dec. 2000) “Epithelial Desquamation in Asthma”, American Journal of Respiratory and Critical Care Medicine, 162(6):2324-2329. [cited by applicant]
Ozawa et al. (Oct. 2009) “BRAK/CXCL14 Expression Oral Carcinoma Cells Completely Suppresses Tumor Cell Xenografts in SCID Mouse”, Biomedical Research, 30(5):315-318. [cited by applicant]
Ozawa et al. (Oct. 11, 2009) “Restoration of BRAK/CXCL14 Gene Expression by Gefitinib is Associated with Antitumor Efficacy of the Drug in Head and Neck Squamous Cell Carcinoma”, Cancer Science, 100(11):2202-2209. [cited by applicant]
Yousefi et al. 2008. Nature Medicine, 14(9):949-953. [cited by applicant]
Chen et al. Jiepoukexue Jinzhan (2007), 13(4), 388-391. [cited by applicant]
Chu et al. 2011. Nature Immuno, 12(2):151-159. [cited by applicant]
Elsner et al. 1997. Euro. J. of Immuno. vol. 27, pp. 2892-2898. [cited by applicant]
Sinicropi et al., BioMEMS and biomedical nanotechnology. Springer US, 2006. 23-46. [cited by applicant]
Lu et al., 2011. J. Immuno. pp. 3362-3373, vol. 187(16). [cited by applicant]
Sonkoly et al. 2010. J. of Aller and Clin. Immuno, 126(3):581-589. [cited by applicant]
Kalinin et al. Future Medicine, vol. 19, pp. 629-650, 2018. [cited by applicant]
Caldwell. J. Allergy. Clin. Immuno. 134:1114-24 (2014). [cited by applicant]
Eisen et al. 1998. Proc. Natl. Acad. Sci. USA (25)95, p. 14863-14868. [cited by applicant]
Shoda et al. Lancet. Gastroenterology Hepatol. Jul. 2018; 3(7):477-488; Epub 2018. [cited by applicant]
Sato et al. J. Allergy Clin. Immuno. Pract. 2017, 5(6):1639-1649. [cited by applicant]
Descamps et al., Cancer Res. 61, 4337-4340 (2001). [cited by applicant]
Madhusudan et al. Resent Results Cancer Res. 172:25-44. [cited by applicant]
Prakash et al. Expert Rev. Resp. Med. 4(3), 395-411 (2010). [cited by applicant]
Oyoshi Current Opinion in Pediatrics, 2015, 27(6), 741-747. [cited by applicant]
Rochlitzer et al. Biochem Soc. Trans (2006), 34(4), 594-599. [cited by applicant]
Nassenstein et al. J. Allergy Clin. Immuno. 2006; 118:597-605. [cited by applicant]
Weber et al. Experimental Dermatology, 2014. vol. 23, pp. 1-52. [cited by applicant]
Valeska et al. 2019. Gastroenterology. 156(6, Suppl. 1) S619. 1 page. [cited by applicant]
Wang et al. 1994. J. Immuno. 152(10):5014-5021. [cited by applicant]
European Search Report and Written Opinion for Application No. 12732079.4 Apr. 22, 2014, 11 pages. [cited by applicant]
Sato et al. (May 2011) “MicroRNAs and Epigenetics”, The FEBS Journal, 278(10):1598-1609. [cited by applicant]
Sayed et al. (Jul. 2011) “MicroRNAs in Development and Disease”, Physiological Reviews, 91(3):827-887. [cited by applicant]
Scherer et al. (2013) “Investigating the Speech Characteristics of Suicidal Adolescents”, International Conference on Acoustics, Speech and Signal Processing, 5 pages. [cited by applicant]
Schmid-Grendelmeier et al. (Jul. 15, 2002) “Eosinophils Express Functional IL-13 in Eosinophilic Inflammatory Diseases”, Journal of Immunology, 169(2):1021-1027. [cited by applicant]
Schoneberg et al. (Mar. 2, 2018) “Structural Basis of G Protein-coupled Receptor Function”, Molecular and Cellular Endocrinology, 151(1-2):181-193. [cited by applicant]
Schultz et al. (May 26, 1998) “Smart, A Simple Modular Architecture Research Tool: Identification of Signaling Domains”, Proceedings of the National Academy of Sciences of the United States of America, 95(11):5857-5864. [cited by applicant]
Sehmi et al. (Nov. 15, 1997) “Allergen-induced Increases in IL-5 Receptor Alpha-subunit Expression on Bone Marrow-derived CD34+ Cells from Asthmatic Subjects. A Novel Marker of Progenitor Cell Commitment Towards Eosinop… [cited by applicant]
Sexton et al. (Sep. 2009) “Recent Advances in our Understanding of Peptide Hormone Receptors and Ramps”, Current Opinion in Drug Discovery & Development, 2(5):440-448. [cited by applicant]
Shaaban et al. (Dec. 2010) “Eosinopenia: Is it a Good Marker of Sepsis in Comparison to Procalcitonin and C-reactive Protein Levels for Patients Admitted to a Critical Care Unit in an Urban Hospital?”, Journal of Critic… [cited by applicant]
Shah et al. (Mar. 2009) “Histopathologic Variability in Children with Eosinophilic Esophagitis”, The American Journal of Gastroenterology, 104(3):716-721. [cited by applicant]
Sharma et al. (Aug. 5, 2011) “Protein Kinase R as Mediator of the Effects of Interferon (IFN) Gamma and Tumor Necrosis Factor (TNF) Alpha on Normal and Dysplastic Hematopoiesis”, Journal of Biological Chemistry, 286 (31… [cited by applicant]
Shen et al. (Apr. 2011) “Plasma MicroRNAs as Potential Biomarkers for Non-small-cell Lung Cancer”, Laboratory Investigation, 91(4):579-587. [cited by applicant]
Sheng et al. (Jun. 2011) “The MUC13 Cell Surface Mucin Protects Against Intestinal Inflammation by Inhibiting Epithelial Cell Apoptosis”, Gut, 60(12):1661-1670. [cited by applicant]
Sherrill et al. (Jul. 2011) “Genetic Dissection of Eosinophilic Esophagitis Provides Insight into Disease Pathogenesis and Treatment Strategies”, The Journal of Allergy and Clinical Immunology, 128(1):23-32. [cited by applicant]
Sherrill et al. (Jul. 1, 2010) “Variants of Thymic Stromal Lymphopoietin and its Receptor Associate with Eosinophilic Esophagitis”, Journal of Allergy and Clinical Immunology, 126(1):160-165. [cited by applicant]
Shinkai et al. (Aug. 1, 1999) “A Novel Human CC Chemokine, Eotaxin-3, Which Is Expressed in IL-4-Stimulated Vascular Endothelial Cells, Exhibits Potent Activity Toward Eosinophils”, The Journal of Immunology, 163 (3):16… [cited by applicant]
Shinkai et al. (Nov. 2002) “N-terminal Domain of Eotaxin-3 is Important for Activation of CC Chemokine Receptor 3”, Protein Engineering, Design and Selection, 15(11):923-929. [cited by applicant]
Shoda et al. (Jan. 2020) “Molecular, Endoscopic, Histologic, and Circulating Biomarker-based Diagnosis of Eosinophilic Gastritis: Multi-site Study”, The Journal of Allergy and Clinical Immunology, 145(1):255-269. [cited by applicant]
Zahm et al. (Jul. 2011) “Circulating MicroRNA is a Biomarker of Pediatric Crohn Disease”, Journal of Pediatric Gastroenterology and Nutrition, 53(1):26-33. [cited by applicant]
Simon et al. (Oct. 10, 2005) “Roadmap for Developing and Validating Therapeutically Relevant Genomic Classifiers”, Journal of Clinical Oncology, 23(29):7332-7341. [cited by applicant]
Simonini et al. (Nov. 15, 2010) “Epigenetically Deregulated Microrna-375 is Involved in a Positive Feedback Loop with Estrogen Receptor Alpha in Breast Cancer Cells”, Cancer Research, 70(22):9175-9184. [cited by applicant]
Sin et al. (Sep. 2011) “Nerve Growth Factor or IL-3 Induces more IL-13 Production from Basophils of Allergic Subjects than from Basophils of Nonallergic Subjects”, The Journal of Allergy and Clinical Immunology, 108 (3)… [cited by applicant]
Yuan et al. (Feb. 7, 2011) “Microrna-203 Inhibits Cell Proliferation by Repressing Anp63 Expression in Human Esophageal Squamous Cell Carcinoma”, BMC Cancer, 11:10 pages. [cited by applicant]
Slonim Donnak. (Dec. 2002) “From Patterns to Pathways: Gene Expression Data Analysis Comes of Age”, Nature Genetics, 32:502-508. [cited by applicant]
Smith et al. (Jun. 2010) “Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases?”, Pharmacological Reviews, 62(2):199-236. [cited by applicant]
Smith et al. (Feb. 7, 2010) “MicroRNAs, Development of Barrett's Esophagus, and Progression to Esophageal Adenocarcinoma”, World Journal of Gastroenterology, 16(5):531-537. [cited by applicant]
Smith et al. (Dec. 2006) “Serine Proteases, their Inhibitors and Allergy”, Allergy, 61(12):1441-1447. [cited by applicant]
Sonkoly et al. (Jul. 2007) “MicroRNAs: Novel Regulators Involved in the Pathogenesis of Psoriasis?”, PLoS One, e610, 2(7):8 pages. [cited by applicant]
Sonkoly et al. (Dec. 2010) “MIR-155 is Overexpressed in Patients with Atopic Dermatitis and Modulates T-cell Proliferative Responses by Targeting Cytotoxic T Lymphocyte-associated Antigen 4”, The Journal of Allergy and … [cited by applicant]
Spergel et al. (Oct. 2005) “Treatment of Eosinophilic Esophagitis with Specific Food Elimination Diet Directed by a Combination of Skin Prick and Patch Tests”, Annals of Allergy, Asthma & Immunology, 95(4):336-343. [cited by applicant]
Sprenger et al. (Jan. 2009) “Eosinophilic Oesophagitis: An Enigmatic, Emerging Disease”, The Netherlands Journal of Medicine, 67(1):8-12. [cited by applicant]
Spry C. (Sep. 1976) “Eosinophilia in Addison's Disease”, Yale Journal of Biology and Medicine, 49(4):411-413. [cited by applicant]
Stansfield et al. (Dec. 2009) “Periostin is a Novel Factor in Cardiac Remodeling After Experimental and Clinical Unloading of the Failing Heart”, The Annals of Thoracic Surgery, 88(6):1916-1921. [cited by applicant]
Stappert et al. (Aug. 1994) “A Short Core Region of E-cadherin is Essential for Catenin Binding and is Highly Phosphorylated”, Cell Communication & Adhesion, 2(4):319-327. [cited by applicant]
Stein et al. (Jun. 2008) “Anti-IL-5 (Mepolizumab) Therapy Reduces Eosinophil Activation Ex Vivo and Increases IL-5 and IL-5 Receptor Levels”, The Journal of Allergy and Clinical Immunology, 121(6):1473-1483. [cited by applicant]
Stein et al. (Nov. 2010) “Targeting Interleukin (IL) 5 for Asthma and Hypereosinophilic Diseases”, Recent Patents on Inflammation & Allergy Drug Discovery, 4(3):201-209. [cited by applicant]
Stothard P. (Jun. 2000) “Javascript Programs for Analyzing and Formatting Protein and DNA Sequences”, BioTechniques, 28(6);1102, 1104. [cited by applicant]
Straumann et al. (Nov. 2010) “Budesonide is Effective in Adolescent and Adult Patients With Active Eosinophilic Esophagitis”, Gastroenterology, 139(5):1526-1537. [cited by applicant]
Straumann et al. (Feb. 2005) “Eosinophilic esophagitis: escalating epidemiology?”, The Journal of Allergy and Clinical Immunology, 115(2):418-419. [cited by applicant]
Straumann Alex (Feb. 3, 2012) “Eosinophilic Esophagitis: Rapidly Emerging Disorder”, Swiss Medical Weekly, w13513, 142:8 pages. [cited by applicant]
Straumann et al. (Dec. 2001) “Idiopathic Eosinophilic Esophagitis is Associated with a T(H)2-type Allergic Inflammatory Response”, The Journal of Allergy and Clinical Immunology, 108(6):954-961. [cited by applicant]
Straumann et al. (May 2011) “Long-term Budesonide Maintenance Treatment is Partially Effective for Patients with Eosinophilic Esophagitis”, Clinical Gastroenterology and Hepatology, 9(5):370-372. [cited by applicant]
Straumann et al. (Apr. 2012) “Pediatric and Adult Eosinophilic Esophagitis: Similarities and Differences”, Allergy, 67(4):477-490. [cited by applicant]
Strausberg et al. (2002) “Reading the Molecular Signatures of Cancer”, Microarrays and Cancer Research, 11-16. [cited by applicant]
Suire et al. (Apr. 2005) “p84, a New Gβγ-activated Regulatory Subunit of the Type IB Phosphoinositide 3-kinase b110γ”, Current Biology, 15(6):566-570. [cited by applicant]
Svensson et al. (Apr. 2005) “Human Eosinophils Selectively Recognize and Become Activated by Bacteria Belonging to Different Taxonomic Groups”, Microbes and Infection, 7(4):720-728. [cited by applicant]
Talley et al. (Jan. 1990) “Eosinophilic Gastroenteritis: A Clinicopathological Study of Patients with Disease of the Mucosa, Muscle Layer, and Subserosal Tissues”, Gut, 31(1):54-58. [cited by applicant]
Tan et al. (Mar. 15, 2011) “HYAL1 Overexpression is Correlated with the Malignant Behavior of Human Breast Cancer”, International Journal of Cancer, 128(6):1303-1315. [cited by applicant]
Teitelbaum et al. (May 2002) “Eosinophilic Esophagitis in Children: Immunopathological Analysis and Response to Fluticasone Propionate”, Gastroenterology, 122(5):1216-1225. [cited by applicant]
Tezza et al. (Jun. 2013) “Epigenetics of Allergy”, Early Human Development, 89(Suppl 1):S20-S21. [cited by applicant]
Tian et al. (Oct. 1, 2010) “Visualizing of the Cellular Uptake and Intracellular Trafficking of Exosomes by Live-cell Microscopy”, Journal of Cellular Biochemistry, 111(2):488-496. [cited by applicant]
Tkachuk et al. (Nov. 19, 1996) “Regulation and Role of Urokinase Plasminogen Activator in Vascular Remodelling”, Clinical and Experimental Pharmacology and Physiology, 23(9):759-765. [cited by applicant]
Todorov et al. (2018) “Principal Components Analysis: Theory and Applicaiton to Gene Expression Data Analysis”, Genomics and Computational Biology, e100041, 4(2):7 pages. [cited by applicant]
Trapnell et al. (Apr. 2009) “TopHat: Discovering Splice Junctions with RNA-Seq”, Bioinformatics, 25(9):1105-1111. [cited by applicant]
Trapnell et al. (May 2010) “Transcript Assembly and Quantification By RNA-seq Reveals Unannotated Transcripts and Isoform Switching During Cell Differentiation”, Nature Biotechnology, 28(5):511-515. [cited by applicant]
Tsang et al. (Mar. 2010) “Oncofetal H19-derived MIR-675 Regulates Tumor Suppressor RB in Human Colorectal Cance”, Carcinogenesis, 31(3):350-358. [cited by applicant]
Tsuchiya et al. (Jan. 7, 2011) “MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRLI)”, Journal of Biological Chemistry, 286(1):420-428. [cited by applicant]
Tsukamoto et al. (Mar. 15, 2010) “MicroRNA-375 is Downregulated in Gastric Carcinomas and Regulates Cell Survival by Targeting PDK1 and 14-3-3ζ”, Cancer Research, 70(6):2339-2349. [cited by applicant]
Tzvetkov et al. (Jul. 5, 2013) “Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration”, Biochemical Pharmacology, 86(… [cited by applicant]
Ueda et al. (Jun. 6, 2005) “Inflammation and the Reciprocal Production of Granulocytes and Lymphocytes in Bone Marrow”, Journal of Experimental Medicine, 201(11):1771-1780. [cited by applicant]
Vaishnavi et al. (2013) “Oncogenic and Drug-Sensitive NTRK1 Rearrangements in Lung Cancer”, Nature Medicine, 19(11):1469-1472. [cited by applicant]
Valadi et al. (Jun. 2007) “Exosome-Mediated Transfer of mRNA and microRNA is a Novel Mechanism of Genetic Exchange Between Cells”, Nature Cell Biology, 9(6):654-659. [cited by applicant]
Van Rooij et al. (Feb. 3, 2012) “Developing microRNA Therapeutics”, Circulation Research, 110(3):496-507. [cited by applicant]
Vandepapeliere et al. (Jan. 14, 2008) “Vaccine Adjuvant Systems Containing Monophosphoryl Lipid A and QS21 Induce Strong C63 and Persistent Humoral and T Cell Responses Against Hepatitis B Surface Antigen in Healthy Adu… [cited by applicant]
Varnes et al. (Apr. 5, 2004) “Discovery of N-propylurea 3-benzylpiperidines as Selective CC Chemokine Receptor-3 (CCR3) Antagonists”, Bioorganic & Medicinal Chemistry Letters, 14(7):1645-1649. [cited by applicant]
Velasco et al. (Mar. 2005) “Toll-like Receptor 4 or 2 Agonists Decrease Allergic Inflammation”, American Journal of Respiratory Cell and Molecular Biology, 32(3):218-224. [cited by applicant]
Velu et al. (May 7, 2009) “Gfi1 Regulates miR-21 and miR-196b to Control Myelopoiesis”, Blood, 113(19):4720-4728. [cited by applicant]
Venek et al. (2014) “Adolescent Suicidal Risk Assessment in Clinician-Patient Interaction: A Study of Verbal and Acoustic Behaviors”, Spoken Language Technology Workshop, 6 pages. [cited by applicant]
Venge Per (May 2010) “The Eosinophil and Airway Remodelling in Asthma”, The Clinical Respiratory Journal, 4 (Suppl 1):15-19. [cited by applicant]
Venkatasubramanian et al. (Jul. 2014) “ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children”, Pharmacogenomics, 15(10):1297-1309. [cited by applicant]
Verspoor et al. (Jun. 15, 2009) “The textual characteristics of traditional and Open Access scientific journals are similar”, BMC Bioinformatics, 10:183. [cited by applicant]
Vicario et al. (Jan. 2010) “Local B Cells and IgE Production in the Oesophageal Mucosa in Eosinophilic Oesophagitis”, Gut, 59(1):12-20. [cited by applicant]
Vincent et al. (Dec. 2, 2009) “International Study of the Prevalence and Outcomes of Infection in Intensive Care Units”, JAMA 302(21):2323-2329. [cited by applicant]
Von Ahlfen et al. (2007) “Determinants of RNA Quality from FFPE Samples”, PLoS One, e1261, 2(12): 7 pages. [cited by applicant]
Von Arnim et al. (2014) “Eosinophilic Esophagitis—Treatment of Eosinophilic Esophagitis with Drugs: Corticosteroids”, Digestive Diseases, 32(1-2):126-129. [cited by applicant]
Wacker et al. (Jul. 8, 2002) “CCR3 Antagonists: A Potential New Therapy for the Treatment of Asthma. Discovery and Structure-activity Relationships”, Bioorganic & Medicinal Chemistry Letters, 12(13):1785-1789. [cited by applicant]
Wan et al. (Feb. 2004) “Foxa2 Regulates Alveolarization and Goblet Cell Hyperplasia”, Development, 131(4):953-964. [cited by applicant]
Wang et al. (May 2010) “Differential Functions of Growth Factor Receptor-Bound Protein 7 (GRB7) and Its Variant GRB7v in Ovarian Carcinogenesis”, Clinical Cancer Research, 16(9):2529-2539. [cited by applicant]
Yousefi et al. (Aug. 10, 2008) “Catapult-like Release of Mitochondrial DNA by Eosinophils Contributes to Antibacterial Defense”, Nature Medicine, 14(9):949-953. [cited by applicant]
Wen et al. (Oct. 19, 2014) “Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation”, Journal of Allergy and Clinical Immunology,… [cited by applicant]
White (Nov. 24, 2000) “Identification of Potent, Selective Non-peptide CC Chemokine Receptor-3 Antagonist that Inhibits Eotaxin-, Eotaxin-2-, and Monocyte Chemotactic Protein-4-induced Eosinophil Migration”, The Journal… [cited by applicant]
Wills-Karp Marsha (Dec. 2004) “Interleukin-13 in Asthma Pathogenesis”, Immunological Reviews, 202:175-190. [cited by applicant]
Winter et al. (Mar. 2009) “Many Roads to Maturity: microRNA Biogenesis Pathways and their Regulation”, Nature Cell Biology, 11(3):228-234. [cited by applicant]
Wolska et al. (Apr. 2009) “The Role of Toll-Like Receptors in Hematopoietic Malignancies”, Current Molecular Medicine, 9(3):324-335. [cited by applicant]
Wong et al. (Jul. 2007) “Intracellular Signaling Mechanisms Regulating Toll-like Receptor-mediated Activation of Eosinophils”, American Journal of Respiratory Cell and Molecular Biology, 37(1):85-96. [cited by applicant]
Wong et al. (Feb. 2013) “Microrna-21 Regulates the Prosurvival Effect of GM-CSF on Human Eosinophils”, Immunobiology, 218(2):255-262. [cited by applicant]
Woodruff et al. (Oct. 2, 2007) “Genome-wide Profiling Identifies Epithelial Cell Genes Associated with Asthma and With Treatment Response to Corticosteroids”, Proceedings of the National Academy of Sciences of the Unite… [cited by applicant]
Wu et al. (Nov. 2008) “MicroRNAs are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α”, Gastroenterology, e24, 135(5):1624-1635. [cited by applicant]
Xanthou Marietta (Sep. 2008) “Leucocyte Blood Picture in Ill Newborn Babies”, Archives of Disease in Childhood, 47(255):741-746. [cited by applicant]
Xiang et al. (Feb. 15, 2008) “Wound Repair and Proliferation of Bronchial Epithelial Cells Regulated by CTNNAL 1”, Journal of Cellular Biochemistry, 103(3):920-930. [cited by applicant]
Xing et al. (Aug. 23, 2011) “Protease Phenotype of Constitutive Connective Tissue and of Induced Mucosal Mast Cells in Mice is Regulated by the Tissue”, Proceedings of the National Academy of Sciences of the United Stat… [cited by applicant]
Yamazaki et al. (Nov. 2006) “Allergen-specific In Vitro Cytokine Production in Adult Patients with Eosinophilic Esophagitis”, Digestive Diseases and Sciences, 51(11):1934-1941. [cited by applicant]
Yang et al. (Oct. 15, 2006) “Inhibition of Arginase | Activity by RNA Interference Attenuates IL-13-Induced Airways Hyperresponsiveness”, The Journal of Immunology, 177(8):5595-5603. [cited by applicant]
Yang et al. (May 2009) “Th17 and Natural Treg Cell Population Dynamics in Systemic Lupus Erythematosus”, Arthritis & Rheumatology, 60(5);1472-1483. [cited by applicant]
Yee et al. (Jul. 3, 2012) “Insulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater?”, Journal of the National Cancer Institute, 104(13):975-981. [cited by applicant]
Yi et al. (Mar. 13, 2008) “A Skin MicroRNA Promotes Differentiation by Repressing ‘Stemness’”, Nature, 452(7184):225-229. [cited by applicant]
Yin et al. (Jan. 2010) “Targeting the Insulin-like Growth Factor-1 Receptor by Picropodophyllin as a Treatment Option for Glioblastoma”, Neuro-Oncology, 12(1):19-27. [cited by applicant]
European Search Report for Application No. 19787916.6, dated Mar. 1, 2022 (nine (9) pages. [cited by applicant]
Ferguson et al., “Pediatric Eosinophilic Esophagitis Endotypes: Are we closer to predicting treatment response?” Clin Rev Allergy Immunol 55(1):43-55 (2018). doi:10.1007/s12016-017-8658-8. [cited by applicant]
Ochiai et al., “Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells”, Proceedings of the National Academy of Sciences115(5):1033-1038 (2018). [cited by applicant]
Butz et al., “Efficacy, Dose Reduction, and Resistance to High-Dose Fluticasone in Patients With Eosinophilic Esophagitis” Gastroenterology 2014; 147:324-333. [cited by applicant]
Siddique et al., “Clinicopathologic and gene expression analysis of initial biopsies from patients with eosinophilic esophagitis refractory to therapy” Human Pathology (2017) 68, 79-86. [cited by applicant]
Kalinin et al., “Deep learning in pharmacogenomics: from gene regulation to patient stratification” Pharmacogenomics (2018) 19(7), 629-650. [cited by applicant]
Azouz, et al. (May 27, 2020) Supplemental Materials for Functional Role of Kallikrein 5 and Proteinase-activated 9 Receptor 2 in Eosinophilic Esophagitis, Sci. Transl. Med. 12 eaaz773, sciencemag.org/cgi/contenVfull/12/… [cited by applicant]
Fulkerson et al. (Oct. 31, 2006) “A Central Regulatory Role for Eosinophils and the Eotaxin/CCR3 Axis in Chronic Experimental Allergic Airway Inflammation”, Proceedings of the National Academy of Sciences of the United … [cited by applicant]
Fulkerson et al. (Feb. 2013) “Targeting Eosinophils in Allergy, Inflammation and Beyond”, Nature Reviews Drug Discovery, 12(2):117-129. [cited by applicant]
Furuta et al. (Oct. 2007) “Eosinophilic Esophagitis in Children and Adults: A Systematic Review and Consensus Recommendations for Diagnosis and Treatment”, Gastroenterology, 133(4):1342-1363. [cited by applicant]
Garbacki et al. (Jan. 28, 2011) “MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma: A Relationship with mRNAs Targets”, PLoS One, e16509, 6(1):23 pages. [cited by applicant]
Garcia-Echeverria et al. (Apr. 2004) “In Vivo Antitumor Activity of NVP-AEW541-A Novel, Potent, and Selective Inhibitor of the IGF-IR Kinase”, Cancer Cell, 5(3):231-239. [cited by applicant]
Garçon et al. (Aug. 1, 2011) “Development of an AS04-adjuvanted HPV Vaccine with the Adjuvant System Approach”, BioDrugs, 25(4):217-226. [cited by applicant]
Garrett et al. (Jan. 2004) “Anti-interleukin-5 (Mepolizumab) Therapy for Hypereosinophilic Syndrome”, Journal of Allergy and Clinical Immunology, 113(1):115-119. [cited by applicant]
Zimmerman et al. (Feb. 2003) “Chemokines in Asthma: Cooperative Interaction between Chemokines and IL-13”, The Journal of Allergy and Clinical Immunology, 111(2):227-242. [cited by applicant]
Zheng et al. (Mar. 2009) “Transgenic Expression of Interleukin-13 in the Skin Induces a Pruritic Dermatitis and Skin Remodeling”, Journal of Investigative Dermatology, 129(3):742-751. [cited by applicant]
Zhen et al. (Feb. 2007) “IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct Roles in Epithelial Cell Mucin Production”, American Journal of Respiratory Cell and Molecular Biology, 36(2):244-253. [cited by applicant]
Georgantas et al. (Feb. 20, 2007) “CD34+ Hematopoietic Stem-progenitor Cell MicroRNA Expression and Function: A Circuit Diagram of Differentiation Control”, Proceedings of the National Academy of Sciences of the United … [cited by applicant]
Gilbert et al. (Aug. 1978) “Effects of Acute Endotoxemia and Glucose Administration on Circulating Leukocyte Populations in Normal and Diabetic Subjects”, Metabolism, 27(8):889-899. [cited by applicant]
Goettig et al. (2010) “Natural and Synthetic Inhibitors of Kallikrein-Related Peptidases (KLKs)”, Biochimie, 92(11):1546-67. [cited by applicant]
Gong et al. (May 30, 2013) “Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain”, Asian Pacific Journal of Cancer Prevention, 14(5):2937-2943. [cited by applicant]
Gonsalves et al. (Jan. 2020) “Diagnosis and Treatment of Eosinophilic Esophagitis”, The Journal of Allergy and Clinical Immunology, 145(1):1-7. [cited by applicant]
Gonsalves et al. (Sep. 2006) “Histopathologic Variability and Endoscopic Correlates in Adults with Eosinophilic Esophagitis”, Gastrointestinal Endoscopy, 64(3):313-319. [cited by applicant]
Griffiths-Jones et al. (2006) “miRBase: MicroRNA Sequences, Targets and Gene Nomenclature”, Nucleic Acids Research, 34:D140-D144. [cited by applicant]
Griffiths-Jones et al. (Jan. 2008) “miRBase: Tools for Micro RNA Genomics”, Nucleic Acids Research, 36 (Database issue):D154-D158. [cited by applicant]
Gupta et al. (Jan. 2006) “Cytokine Expression in Normal and Inflamed Esophageal Mucosa: A Study into the Pathogenesis of Allergic Eosinophilic Esophagitis”, Journal of Pediatric Gastroenterology and Nutrition: , 42(1):2… [cited by applicant]
Gupta et al. (May 1998) “Expression of Inducible Nitric Oxide Synthase (iNOS) mRNA in Inflamed Esophageal and Colonic Mucosa in a Pediatric Population”, American Journal of Gastroenterology, 93(5):795-798. [cited by applicant]
Guyon et al. (Jan. 2002) “Gene Selection for Cancer Classification using Support Vector Machines”, Machine Learning, 46:389-422. [cited by applicant]
Hahn et al. (Apr. 2006) “Airway Epithelial Cells Produce Neurotrophins and Promote the Survival of Eosinophils During Allergic Airway Inflammation”, Journal of Allergy and Clinical Immunology, 117(4):787-794. [cited by applicant]
Hamilton et al. (1980) “Regulation of The Plasminogen Activator Activity of Macrophage Tumor Cell Lines”, International Journal of Immunopharmacology, 2(4):353-362. [cited by applicant]
Hamoui et al. (Aug. 2004) “Increased Acid Exposure in Patients With Gastroesophageal Reflux Disease Influences Cyclooxygenase-2 Gene Expression in the Squamous Epithelium of the Lower Esophagus”, Archives of Surgery, 13… [cited by applicant]
Hardiman Gary (Nov. 5, 2004) “Microarray Platforms—Comparisons and Contrasts”, Pharmacogenomics, 5 (5):487-502. [cited by applicant]
Hatley et al. (Sep. 14, 2010) “Modulation of K-Ras-dependent Lung Tumorigenesis by MicroRNA-21”, Cancer Cell, 18(3):282-293. [cited by applicant]
Heib et al. (May 2019) “Wheat Amylase/Trypsin Inhibitors Aggravate Eosinophilic Esophagitis”, Gastroenterology, 6 (Suppl. 1):1 page. [cited by applicant]
Hennessy et al. (Apr. 2010) “Targeting Toll-Like Receptors: Emerging Therapeutics?”, Nature Reviews Drug Discovery, 9(4):293-307. [cited by applicant]
Himes et al. (Mar. 4, 2009) “Prediction of Chronic Obstructive Pulmonary Disease (COPD) in Asthma Patients Using Electronic Medical Records”, Journal of the American Medical Informatics Association, 16(3):371-379. [cited by applicant]
Hogan et al. (May 2008) “Eosinophils: Biological Properties and Role in Health and Disease”, Clinical & Experimental Allergy, 38(5):709-750. [cited by applicant]
Hogan et al. (Dec. 2004) “The Eosinophil as a Therapeutic Target in Gastrointestinal Disease”, Alimentary Pharmacology and Therapeutics, 20(11-12):1231-1240. [cited by applicant]
Hotchkiss et al. (Jun. 1, 2001) “Sepsis-induced Apoptosis Causes Progressive Profound Depletion of B and CD4+ T Lymphocytes in Humans”, Journal of Immunology, 166(11):6952-6963. [cited by applicant]
Huang et al. (Jul. 1, 2006) “RegRNA: An Integrated Web Server for Identifying Regulatory RNA Motifs and Elements”, Nucleic Acids Research, 34:W429-W434. [cited by applicant]
Hwang et al. (Apr. 30, 2005) “Expression of IL-17 Homologs and their Receptors in the Synovial Cells of Rheumatoid Arthritis Patients”, Molecular Cell, 19(2):180-184. [cited by applicant]
Indo Y. (Dec. 2001) “Molecular Basis of Congenital Insensitivity to Pain with Anhidrosis (CIPA): Mutations and Polymorphisms in TRKA (NTRK1) Gene Encoding the Receptor Tyrosine Kinase for Nerve Qrowth Factor”, Human Mut… [cited by applicant]
Indo et al. (Aug. 1996) “Mutations in the TRKA/NGF Receptor Gene in Patients with Congenital Insensitivity to Pain with Anhidrosis”, Nature Genetics, 13(4):485-488. [cited by applicant]
Indo Y. (Oct. 2012) “Nerve Growth Factor and the Physiology of Pain: Lessons from Congenital Insensitivity to Pain with Anhidrosis”, Clinical Genetics, 82(4):341-350. [cited by applicant]
IP et al. (Dec. 2007) “Interleukin-31 Induces Cytokine and Chemokine Production from Human Bronchial Epithelial Cells through Activation of Mitogen-activated Protein Kinase Signalling Pathways: Implications for the Alle… [cited by applicant]
Iwasaki et al. (Jun. 20, 2005) “Identification of Eosinophil Lineage-committed Progenitors in the Murine Bone Marrow”, Journal of Experimental Medicine, 201(12):1891-1897. [cited by applicant]
Jacobsen et al. (Jun. 2007) “Eosinophils: Singularly Destructive Effector Cells or Purveyors of Immunoregulation?”, The Journal of Allergy and Clinical Immunology, 119(6):1313-1320. [cited by applicant]
Jakiela et al. (Oct. 2009) “Intrinsic Pathway of Apoptosis in Peripheral Blood Eosinophils of Churg-strauss Syndrome”, Rheumatology (Oxford), 48(10):1202-1207. [cited by applicant]
Jia et al. (Nov. 2008) “Mist1 Regulates Pancreatic Acinar Cell Proliferation through p21 CIP1/WAF1”, Gastroenterology, 135(5):1687-1697. [cited by applicant]
Jiang et al. (Jul. 2011) “The Emerging Role of MicroRNAs in Asthma”, Molecular and Cellular Biochemistry, 353(1-2):35-40. [cited by applicant]
Johnnidis et al. (Feb. 28, 2008) “Regulation of Progenitor Cell Proliferation and Granulocyte Function by MicroRNA-223”, Nature, 451:1125-1129. [cited by applicant]
Juffali et al. (2010) “The WiNAM project: Neural data analysis with applications to epilespy”, Biomedical Circuits and Systems Conference, 45-48. [cited by applicant]
Junttila et al. (Oct. 27, 2008) “Tuning Sensitivity to IL-4 and IL-13: Differential Expression of IL-4Ralpha, L-13Ralpha1, and Gammac Regulates Relative Cytokine Sensitivity”, Journal of Experimental Medicine, 205 (11):… [cited by applicant]
Kaiko et al. (Feb. 2011) “New Insights into the Generation of Th2 Immunity and Potential Therapeutic Targets for the Treatment of Asthma”, Current Opinion in Allergy and Clinical Immunology, 11(1):39-45. [cited by applicant]
Kaimal et al. (Jul. 2010) “Toppcluster: A Multiple Gene List Feature Analyzer for Comparative Enrichment Clustering and Network-based Dissection of Biological System”, Nucleic Acids Research, 38:W96-W102. [cited by applicant]
Kanzler et al. (May 3, 2007) “Therapeutic Targeting of Innate Immunity with Toll-like Receptor Agonists and Antagonists”, Nature Medicine, 13(5):552-559. [cited by applicant]
Kariyawasam et al. (Sep. 2009) “Activin and Transforming Growth Factor-β Signaling Pathways are Activated after Allergen Challenge in Mild Asthma”, The Journal of Allergy and Clinical Immunology, 124(3):454-462. [cited by applicant]
Ozdas et al. (Sep. 2004) “Investigation of Vocal Jitter and Glottal Flow Spectrum as Possible Cues for Depression and Near-Term Suicidal Risk”, Transactions on Biomedical Engineering, 51(9):1530-1540. [cited by applicant]
Papagiannakopoulos et al. (Oct. 1, 2008) “MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells”, Cancer Research, 68(19):8164-8172. [cited by applicant]
Park et al. (Dec. 27, 2006) “Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans”, Clinical Pharmacology & Therapeutics, 81(4):539-546. [cited by applicant]
Patent Cooperation Treaty, “International Preliminary Report on Patentability and Written Opinion in corresponding International application No. PCT/US2012/044061”, mailed on Dec. 23, 2013, 7 pages. [cited by applicant]
PCTUS2015044461,“International Search Report mailed on Nov. 9, 2015 for International Application No. PCT/US2015/044461”, 11 pages. [cited by applicant]
Peeters et al. (Apr. 8, 2005) “Real-time RT-PCR Quantification of mRNA Encoding Cytokines and Chemokines in Histologically Normal Canine Nasal, Bronchial and Pulmonary Tissue”, Veterinary Immunology and Immunopathology,… [cited by applicant]
Persson et al. (Jun. 2001) “Bactericidal Activity of Human Eosinophilic Granulocytes Against [cited by applicant]
Petriv et al. (Aug. 31, 2010) “Comprehensive MicroRNA Expression Profiling of the Hematopoietic Hierarchy”, Proceedings of the National Academy of Sciences of the United States of America, 107(35):15443-15448. [cited by applicant]
Phipps et al. (Sep. 1, 2007) “Eosinophils Contribute to Innate Antiviral Immunity and Promote Clearance of Respiratory Syncytial Virus”, Blood, 110(5):1578-1586. [cited by applicant]
Plötz et al. (Jan. 1, 2001) “The Interaction of Human Peripheral Blood Eosinophils with Bacterial Lipopolysaccharide is CD14 Dependent”, Blood, 97(1):235-241. [cited by applicant]
Polikepahad et al. (Sep. 24, 2010) “Proinflammatory Role for let-7 MicroRNAs in Experimental Asthma”, Journal of Biological Chemistry, 285(39):30139-30149. [cited by applicant]
Pouladi et al. (Jan. 2004) “Interleukin-13-dependent Expression of Matrix Metalloproteinase-12 is Required for the Development of Airway Eosinophilia in Mice”, American Journal of Respiratory Cell and Molecular Biology,… [cited by applicant]
Proudfoot et al. (Nov. 5, 1999) “Amino-terminally Modified Rantes Analogues Demonstrate Differential Effects on Rantes Receptors”, Journal of Biological Chemistry, 274(45):32478-32485. [cited by applicant]
Prows et al. (Nov. 13, 2013) “Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study”, Laryngoscope, 124(5):1242-1250. [cited by applicant]
Prussin et al. (Dec. 2009) “Eosinophilic Gastrointestinal Disease and Peanut Allergy are Alternatively Associated with IL-5+ and IL-5(-) T(H)2 Responses”, The Journal of Allergy and Clinical Immunology, 124(6):1326-1332. [cited by applicant]
Zeng et al. (Feb. 2006) “Extracting Principal Diagnosis, Co-morbidity and Smoking Status for Asthma Research: Evaluation of a Natural Language Processing System”, BMC Medical Informatics and Decision Making, 6(1):9 page… [cited by applicant]
Zediak et al. (Mar. 1, 2011) “Cutting Edge: Persistently Open Chromatin at Effector Gene Loci in Resting Memory CD8+ T Cells Independent of Transcriptional Status”, Journal of Immunology, 186(5):2705-2709. [cited by applicant]
Raap et al. (Feb. 2010) “The Role of Neurotrophins in the Pathophysiology of Allergic Rhinitis”, Current Opinion in Allergy and Clinical Immunology, 10(1):8-13. [cited by applicant]
Rabinowits et al. (Jan. 2009) “Exosomal microRNA: a Diagnostic Marker for Lung Cancer”, Clinical Lung Cancer, 10(1):42-46. [cited by applicant]
Rahaghi et al. ( 2017) “Long-term Clinical Outcomes Following Treatment with Alpha 1-Proteinase Inhibitor for COPD associated with alpha-1 Antitrypsin Deficiency: A Look at the Evidence”, Respiratory Researc, 18(1):9 Pa… [cited by applicant]
Wechsler et al. (Jul. 2018) “Esophagitis Reference Score Accurately Identifies Disease Activity and Treatment Effects in Children”, Clinical Gastroenterology and Hepatology, 16(7):1056-1063. [cited by applicant]
Ramirez et al. (Dec. 15, 2004) “Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins”, Cancer Research, 64(24):9027-9034. [cited by applicant]
Ramirez et al. (Aug. 2006) “Transcriptional Regulation of the Human α2(I) Collagen Gene (COL1A2), an Informative Model System to Study Fibrotic Diseases”, Matrix Biology, 25(6):365-372. [cited by applicant]
Rank et al. (May 2020) “Technical Review on the Management of Eosinophilic Esophagitis: A Report from the AGA Institute and the Joint Task Force on Allergy-immunology Practice Parameters”, Annals of Allergy, Asthma & Im… [cited by applicant]
Ray et al. (May 16, 2011) “Human Mu Opioid Receptor (OPRM1 A 118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers”, PNAS, 108(22):9268-9273. [cited by applicant]
Raychaudhuri et al. (2000) “Principal Components Analysis to Summarize Microarray Experiments: Application to Sporulation Time Series”, Pacific Symposium on Biocomputing, 5:452-463. [cited by applicant]
Robinson et al. (Jan. 1999) “CD34(+)/Interleukin-5Ralpha Messenger RNA+ Cells in the Bronchial Mucosa in Asthma: Potential Airway Eosinophil Progenitors”, American Journal of Respiratory Cell and Molecular Biology, 20(1… [cited by applicant]
Collins et al. (Mar. 2017) “Newly Developed and Validated Eosinophilic Esophagitis Histology Scoring System and Evidence that it Outperforms Peak Eosinophil Count for Disease Diagnosis and Monitoring”, Diseases of the E… [cited by applicant]
Rochman et al. (Jul. 2015) “Neurotrophic Tyrosine Kinase Receptor 1 is a Direct Transcriptional and Epigenetic Target of IL-13 Involved in Allergic Inflammation”, Immunology, 8(4):785-798. [cited by applicant]