IP Library › Granted Patent US 12,384,841
Granted Patent B2
US 12,384,841 · App. 18/338,946 · Granted Aug 12, 2025

Anti-PAR-2 antibodies and methods of use thereof

Inventors: Anna Mikaela Bracken (Lane Cove, AU); Adam Clarke (Riverstone, AU); Bridget A. Cooksey (Curl Curl, AU); Anthony Gerard Doyle (Macquarie Park, AU); Mark Terence Liddament (Victoria, AU); Matthew Pollard (Pullenvale, AU); Lynn Poulton (Macquarie Park, AU); Anna Maria Matilda Quigley (Macquarie Park, AU); Julia Rozenfeld (Macquarie Park, AU); Marta Szabat (Vancouver, CA)
Assignee: Cephalon LLC
C07K16/28A61P17/10A61P29/00A61P35/04C07K2317/24C07K2317/33C07K2317/52C07K2317/565C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,384,841
App. No.
18/338,946
Granted
Aug 12, 2025
Kind
B2
Abstract

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human PAR-2 and compositions comprising such antibodies or antigen-binding fragments thereof. In a particular aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human PAR-2 block the interaction between a PAR-2 activating ligand and an extracellular domain of PAR-2, and/or blocks PAR-2 activation by a PAR-2 activating ligand, In further aspects, the antibodies or antigen-binding fragments can be used to treat diseases or conditions associated with increased expression of PAR-2 and/or diseases or conditions that can be alleviated by antagonizing activation of PAR-2 by a PAR-2 activating ligand (e.g., airway diseases, skin diseases, cancer, orofacial granulomatosis, inflammatory conditions, and pain associated with various diseases or conditions).

Claims (8)

1. A method for detecting PAR-2 in a sample comprising contacting the sample with an isolated antibody or antigen-binding fragment thereof that specifically binds to human protease activated receptor 2 (PAR-2) and comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and the light chain variable region (VL) CDR1, VL CDR2, and VL CDR3 amino acid sequences of:

(a) SEQ ID NOs: 10, 11, 12, 16, 17, and 18, respectively;

(b) SEQ ID NOs: 7, 8, 9, 13, 14, and 15, respectively;

(c) SEQ ID NOs: 10, 11, 12, 16, 19, and 18, respectively;

(d) SEQ ID NOs: 10, 11, 12, 16, 29, and 18, respectively; or

(e) SEQ ID NOs: 10, 11, 12, 16, 22, and 18, respectively.

2. The method of claim 1 , wherein the sample is obtained from a human subject, optionally wherein the sample is a cancer sample.

3. The method of claim 1 , wherein the sample is an in vitro sample.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 30, 2023
From: SZABAT, MARTA
To: ABCELLERA BIOLOGICS INC.
Reel/Frame 065392/0461 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 30, 2023
From: ABCELLERA BIOLOGICS INC.
To: TEVA PHARMACEUTICALS AUSTRALIA PTY LTD.
Reel/Frame 065392/0472 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 30, 2023
From: TEVA PHARMACEUTICALS AUSTRALIA PTY LTD.
To: CEPHALON LLC
Reel/Frame 065392/0494 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 30, 2023
From: BRACKEN, ANNA MIKAELA; CLARKE, ADAM; COOKSEY, BRIDGET A.; DOYLE, ANTHONY GERARD; LIDDAMENT, MARK TERENCE; POLLARD, MATTHEW; POULTON, LYNN; QUIGLEY, ANNA MARIA MATILDA; ROZENFELD, JULIA
To: TEVA PHARMACEUTICALS AUSTRALIA PTY LTD.
Reel/Frame 065395/0768 →
Continuity (3)
Division 17405275 · Aug 18, 2021
Provisional Application 63067259 · Aug 18, 2020
Related Publication 20240150457A1 · May 9, 2024
References Cited (282)
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 5122464A · Wilson et al. · 1992 [cited by applicant]
US 5223409A · Ladner et al. · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5403484A · Ladner et al. · 1995 [cited by applicant]
US 5427908A · Dower et al. · 1995 [cited by applicant]
US 5516637A · Huang et al. · 1996 [cited by applicant]
US 5571698A · Ladner et al. · 1996 [cited by applicant]
US 5580717A · Dower et al. · 1996 [cited by applicant]
US 5658727A · Barbas et al. · 1997 [cited by applicant]
US 5693780A · Newman et al. · 1997 [cited by applicant]
US 5698426A · Huse · 1997 [cited by applicant]
US 5733743A · Johnson et al. · 1998 [cited by applicant]
US 5750753A · Kimae et al. · 1998 [cited by applicant]
US 5780225A · Wigler et al. · 1998 [cited by applicant]
US 5821047A · Garrard et al. · 1998 [cited by applicant]
US 5837242A · Holliger et al. · 1998 [cited by applicant]
US 5869620A · Whitlow et al. · 1999 [cited by applicant]
US 5965726A · Pavlakis et al. · 1999 [cited by applicant]
US 5969108A · McCafferty et al. · 1999 [cited by applicant]
US 5989830A · Davis et al. · 1999 [cited by applicant]
US 6132992A · Ledbetter et al. · 2000 [cited by applicant]
US 6174666B1 · Pavlakis et al. · 2001 [cited by applicant]
US 6291664B1 · Pavlakis et al. · 2001 [cited by applicant]
US 6414132B1 · Pavlakis et al. · 2002 [cited by applicant]
US 6794498B2 · Pavlakis et al. · 2004 [cited by applicant]
US 7083784B2 · Dall'Acqua et al. · 2006 [cited by applicant]
US 7183076B2 · Arathoon et al. · 2007 [cited by applicant]
US 7217797B2 · Hinton et al. · 2007 [cited by applicant]
US 7888482B2 · Virca et al. · 2011 [cited by applicant]
US 7951917B1 · Arathoon et al. · 2011 [cited by applicant]
US 8101724B2 · Macdonald et al. · 2012 [cited by applicant]
US 8227577B2 · Klein et al. · 2012 [cited by applicant]
US 8357367B2 · Virca et al. · 2013 [cited by applicant]
US 8586713B2 · Davis et al. · 2013 [cited by applicant]
US 8927503B2 · Fairlie et al. · 2015 [cited by applicant]
US 9188593B2 · Singhal et al. · 2015 [cited by applicant]
US 10087408B2 · Hansen et al. · 2018 [cited by applicant]
US 11725052B2 · Bracken · 2023 [cited by examiner]
US 20040014194A1 · Beyer et al. · 2004 [cited by applicant]
US 20090068175A1 · Lazar et al. · 2009 [cited by applicant]
US 20090092599A1 · Lazar et al. · 2009 [cited by applicant]
US 20090142340A1 · Lazar et al. · 2009 [cited by applicant]
US 20110059095A1 · MacDonald et al. · 2011 [cited by applicant]
US 20120100140A1 · Reyes et al. · 2012 [cited by applicant]
US 20130122086A1 · Paterson et al. · 2013 [cited by applicant]
US 20160252495A1 · Ricicova et al. · 2016 [cited by applicant]
US 20180305450A1 · Dobson et al. · 2018 [cited by applicant]
US 20190292258A1 · Lippincott et al. · 2019 [cited by applicant]
WO WO8605807A1 · 1986 [cited by applicant]
WO WO8901036A1 · 1989 [cited by applicant]
WO WO9002809A1 · 1990 [cited by applicant]
WO WO9110737A1 · 1991 [cited by applicant]
WO WO9201047A1 · 1992 [cited by applicant]
WO WO9218619A1 · 1992 [cited by applicant]
WO WO9311236A1 · 1993 [cited by applicant]
WO WO9515982A2 · 1995 [cited by applicant]
WO WO9520401A1 · 1995 [cited by applicant]
WO WO9713844A1 · 1997 [cited by applicant]
WO WO0042072A2 · 2000 [cited by applicant]
WO WO2006127379A2 · 2006 [cited by applicant]
WO WO2006127396A1 · 2006 [cited by applicant]
WO WO2009036379A2 · 2009 [cited by applicant]
WO WO2010017086A1 · 2010 [cited by applicant]
WO WO2010105256A1 · 2010 [cited by applicant]
WO WO2010132954A1 · 2010 [cited by applicant]
WO WO2011031695A1 · 2011 [cited by applicant]
WO WO2012009568A2 · 2012 [cited by applicant]
WO WO2012010453A1 · 2012 [cited by applicant]
WO WO2014020350A1 · 2014 [cited by applicant]
WO WO2016005369A1 · 2016 [cited by applicant]
WO WO2016154075A1 · 2016 [cited by applicant]
WO WO2018167322A1 · 2018 [cited by applicant]
WO WO2019157358A1 · 2019 [cited by applicant]
Akers, I. A., et al., “Mast Cell Tryptase Stimulates Human Lung Fibroblast Proliferation via Protease-activated Receptor-2,” American Journal of Physiology Lung Cellular and Molecular Physiology 278(1):L193-L201, Americ… [cited by applicant]
Akiyama, T., et al., “Protease-activated Receptors and Itch,” Handbook of Experimental Pharmacology 226:219-235, Springer-Verlag, Germany (2015). [cited by applicant]
Akiyama, T., et al., “Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch,” Pain 151(2):378-383, Elsevier, Netherlands (Nov. 2010). [cited by applicant]
Altschul, S. F., et al., “Basic Local Alignment Search Tool,” Journal of Molecular Biology 215(3):403-410, Elsevier, United Kingdom (Oct. 1990). [cited by applicant]
Altschul, S. F., et al., “Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs,” Nucleic Acids Research 25(17):3389-3402, Oxford University Press, United Kingdom (Sep. 1997). [cited by applicant]
Ames, R. S., et al., “Conversion of Murine Fabs Isolated From a Combinatorial Phage Display Library to Full Length Immunoglobulins,” Journal of Immunological Methods 184(2):177-186, Elsevier, Netherlands (Aug. 1995). [cited by applicant]
Amiable, N., et al., “Proteinase-Activated Receptor-2 Gene Disruption Limits the Effect of Osteoarthritis on Cartilage in Mice: A Novel Target in Joint Degradation,” The Journal of Rheumatology 38(5):911-920, Journal Of… [cited by applicant]
An, Z., et al., “IgG2m4, an Engineered Antibody Isotype with Reduced Fc Function,” Mabs 1(6):572-579, Taylor & Francis, United States (Nov.-Dec. 2009). [cited by applicant]
Andersen, H. H., et al., “Nonhistaminergic and Mechanical Itch Sensitization in Atopic Dermatitis,” Pain 158(9):1780-1791, Lippincott Williams & Wilkins, United States (Sep. 2017). [cited by applicant]
Asaduzzaman, M., et al., “Functional Inhibition of Par2 Alleviates Allergen-induced Airway Hyperresponsiveness and Inflammation,” Clin Exp Allergy 45(12):1844-1855, Blackwell Scientific Publications, United Kingdom (Dec… [cited by applicant]
Asosingh, K., et al., “Endothelial Cells in the Innate Response to Allergens and Initiation of Atopic Asthma,” The Journal of Clinical Investigation, 128(7):3116-3128, American Society for Clinical Investigation, United… [cited by applicant]
Aubier, M., et al., “Airway Smooth Muscle Enlargement Is Associated With Protease-activated Receptor 2/ligand Overexpression in Patients With Difficult-to-control Severe Asthma,” J Allergy Clin Immunol 138(3):729-739, M… [cited by applicant]
Bagher, M., et al., “Mast Cells and Mast Cell Tryptase Enhance Migration of Human Lung Fibroblasts Through Protease-activated Receptor 2,” Cell Commun Signal 16(1):59, BioMed Central, United Kingdom (Sep. 2018). [cited by applicant]
Bao, Y., et al., “Protease-Activated Receptor 2 Antagonist Potentiates Analgesic Effects of Systemic Morphine in a Rat Model of Bone Cancer Pain,” Regional Anesthesia and Pain Medicine 40(2):158-165, BMJ, United Kingdom… [cited by applicant]
Barratt, S. L., et al., “Idiopathic Pulmonary Fibrosis (IPF): An Overview,” Journal of Clinical Medicine 7(8):201, MDPI AG, Switzerland (Aug. 2018). [cited by applicant]
Berger, P., et al., “Tryptase and Agonists of Par-2 Induce the Proliferation of Human Airway Smooth Muscle Cells,” J Appl Physiol 91(3):1372-1379, American Physiological Society, United States (Sep. 2001). [cited by applicant]
Bird, R. E., et al., “Single-chain Antigen-binding Proteins,” Science 242(4877):423-426, Association for the Advancement of Science, United States (Oct. 1988). [cited by applicant]
Borensztajn, K., et al., “Protease-Activated Receptor-2 Induces Myofibroblast Differentiation and Tissue Factor Up-regulation During Bleomycin-induced Lung Injury: Potential Role in Pulmonary Fibrosis,” The American Jou… [cited by applicant]
Brennan, M., et al., “Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G1 Fragments,” Science 229(4708):81-83, American Association for the Advancement of Science, United State… [cited by applicant]
Bricogne, G., “Direct phase determination by entropy maximization and likelihood ranking: status report and perspectives,” Acta Crystallogr D Biol Crystallogr 49(Pt 1): 37-60, John Wiley and Sons Inc., United States (Ja… [cited by applicant]
Bricogne, G., “Bayesian Statistical Viewpoint on Structure Determination: Basic Concepts and Examples,” Methods in Enzymology 276:361-423, Academic Press, United States (1997). [cited by applicant]
Brinkmann, U., et al., “Phage Display of Disulfide-stabilized Fv Fragments,” Journal of Immunological Methods 182(1):41-50, Elsevier, Netherlands (May 1995). [cited by applicant]
Briot, A., et al., “Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model,” Journal of Investigative Dermatology 130(12): 2736-2742, Elsevier, Unite… [cited by applicant]
Brummell, D. A., et al., “Probing the Combining Site of an Anti-Carbohydrate Antibody by Saturation-Mutagenesis: Role of the Heavy-Chain CDR3 Residues,” Biochemistry 32(4):1180-1187, American Chemical Society, United St… [cited by applicant]
Burks, E. A., et al., “In vitro Scanning Saturation Mutagenesis of an Antibody Binding Pocket,” Proceedings of the National Academy of Sciences USA 94(2):412-417, Plenum Publishing Corporation, United States (Jan. 1997). [cited by applicant]
Burton, D. R., and Barbas, C. F., 3rd., “Human Antibodies From Combinatorial Libraries,” Advances in Immunology 57:191-280, Academic Press, United States (1994). [cited by applicant]
Busso, N., et al., “Evaluation of protease-activated receptor 2 in murine models of arthritis,” Arthritis & Rheumatology 56(1):101-107, John Wiley and Sons Ltd., United Kingdom (Jan. 2007). [cited by applicant]
Camateros, P., et al., “Toll-Like Receptor 7/8 Ligand, S28463, Suppresses Ascaris suum-induced Allergic Asthma in Nonhuman Primates,” American Journal of Respiratory Cell and Molecular Biology 58(1):55-65, American Thor… [cited by applicant]
Cenac, N., et al., “Role for protease activity in visceral pain in irritable bowel syndrome,” Journal of Clinical Investigation 117(3):636-647, American Society for Clinical Investigation, United States (Mar. 2007). [cited by applicant]
Cenac, N., “Protease-activated receptors as therapeutic targets in visceral pain,” Current Neuropharmacology 11(6):598-605, Bentham Science Publishers, United Arab Emirates (Dec. 2013). [cited by applicant]
Cevikbas, F., et al., “Role of protease-activated receptors in human skin fibrosis and scleroderma,” Experimental Dermatology 20(1):69-71, John Wiley and Sons Inc., United States (Jan. 2011). [cited by applicant]
Chayen, N. E., “The role of oil in macromolecular crystallization,” Structure 5(10):1269-1274, Cell Press, United States (Oct. 1997). [cited by applicant]
Chen, Y., et al., “Proteinase-activated receptor 2 sensitizes transient receptor potential vanilloid 1, transient receptor potential vanilloid 4, and transient receptor potential ankyrin 1 in paclitaxel-induced neuropat… [cited by applicant]
Chen, K., et al., “Blocking PAR2 attenuates oxaliplatin-induced neuropathic pain via TRPVI and releases of substance P and CGRP in superficial dorsal horn of spinal cord,” Journal of the Neurological Sciences 352(1-2):6… [cited by applicant]
Chen, D., et al., “Blocking PAR2 Alleviates Bladder Pain and Hyperactivity via TRPA1 Signal,” Translational Neuroscience 7(1):133-138, Walter de Gruyter GmbH, Germany (Nov. 2016). [cited by applicant]
Cheng, R. K. Y., et al., “Structural insight into allosteric modulation of protease-activated receptor 2,” Nature 545(7652):112-115, Nature Publishing Group, United Kingdom (May 2017). [cited by applicant]
Cheung, R. C., et al., “Epitope-specific antibody response to the surface antigen of duck hepatitis B virus in infected ducks,” Virology 176(2):546-552, Academic Press, United States (Jun. 1990). [cited by applicant]
Chien, Y. H., et al., “The genetics of atopic dermatitis,” Clinical Reviews in Allergy & Immunology 33(3):178-190, Humana Press, United States (Dec. 2007). [cited by applicant]
Cho, Y. M., et al., “The IRE1α-XBP1s pathway promotes insulin-stimulated glucose uptake in adipocytes by increasing PPARγ activity,” Experimental & Molecular Medicine 50(8):102, 15 pages, Nature Publishing Group, United… [cited by applicant]
Choi, J., E., and Nardo, A.D., “Skin Neurogenic Inflammation,” Review Seminars Immunopathology 40(3):249-259, Springer, Germany (May 2018). [cited by applicant]
Cockett, M. I., et al., “High Level Expression of Tissue Inhibitor of Metalloproteinases in Chinese Hamster Ovary Cells Using Glutamine Synthetase Gene Amplification,” Biotechnology 8(7):662-667, Nature Publishing Compa… [cited by applicant]
Cocks, T. M., et al., “A Protective Role for Protease-activated Receptors in the Airways,” Nature 398(6723):156-160, Nature Publishing Group, United Kingdom (Mar. 1999). [cited by applicant]
Cocks, T. M., et al., “Protease-activated Receptor-2 (PAR2) in the Airways,” Pulmonary Pharmacology & Therapeutics, 14(3):183-191, Academic Press, United Kingdom (2001). [cited by applicant]
Crilly, A., et al., “PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis,” Annals of the Rheumatic Diseases 71(6):1049-1054, BMJ, United Kingdom (Jun. 2012). [cited by applicant]
Cunningham, B. C., and Wells, J. A., “High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis,” Science 244(4908):1081-1085, American Association for the Advancement of Science, Unit… [cited by applicant]
D'Andrea, M. R., et al., “Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues,” The Journal of Histochemistry and Cytochemistry 46(2):157-164, SAGE Publications, United States (Feb… [cited by applicant]
Davidson, E., and Doranz, B. J., “A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes,” Immunology 143(1):13-20, John Wiley & Sons Ltd., United States (Sep. 2014). [cited by applicant]
De Boer, J. D., “Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation,” Innate Immunity 20(6):618-625, Sage Publications, United States (Aug. 2014). [cited by applicant]
Demir, I. E., et al., “Perineural mast cells are specifically enriched in pancreatic neuritis and neuropathic pain in pancreatic cancer and chronic pancreatitis,” PLoS One 8(3):e60529, Public Library of Science, United … [cited by applicant]
Devine, J. F., “Chronic obstructive pulmonary disease: an overview,” American Health & Drug Benefits 1(7):34-42, Engage Healthcare Communications, Inc., United States (Sep. 2008). [cited by applicant]
Ducroc, R., et al., “Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: evidence for new autocrine loop,” Life Sciences 70(12):1359-1367, Elsevier, Netherlands (Feb. 2012). [cited by applicant]
Dumet, C., et al., “Insights into the IgG heavy chain engineering patent landscape as applied to IgG4 antibody development,” MAbs 11(8):1341-1350, Taylor & Francis, United States (Dec. 2019). [cited by applicant]
Dutra-Oliveira, A., et al., “Protease-activated receptor-2 (PAR2) mediates VEGF production through the ERK1/2 pathway in human glioblastoma cell lines,” Biochemical and Biophysical Research Communications 421(2):221-227… [cited by applicant]
Dux, M., et al., “Involvement of capsaicin-sensitive afferent nerves in the proteinase-activated receptor 2-mediated vasodilatation in the rat dura mater,” Neuroscience 161(3):887-894, Elsevier Science, United States (J… [cited by applicant]
Edelman, G. M., et al., “The covalent structure of an entire gammaG immunoglobulin molecule,” Proceedings of the National Academy of Sciences USA 63(1):78-85, National Academy of Sciences, United States (May 1969). [cited by applicant]
Elmariah, S. B., et al., “Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist,” PLoS One 9(6):e99702, Public Library of Science, United States (Jun. 2014). [cited by applicant]
Ferrell, W. R., et al., “Essential role for proteinase-activated receptor-2 in arthritis,” The Journal of Clinical Investigation 111(1): 35-41, American Society for Clinical Investigation, United States (Jan. 2017). [cited by applicant]
Flatters, S. J. L., et al., “Clinical and preclinical perspectives on Chemotherapy-Induced Peripheral Neuropathy (CIPN): a narrative review,” British Journal of Anaesthesia 119(4):737-749, Elsevier, United Kingdom (Oct.… [cited by applicant]
Foecking, M. K., et al., “Powerful and versatile enhancer-promoter unit for mammalian expression vectors,” Gene 45(1):101-105, Elsevier, Netherlands (1986). [cited by applicant]
Frateschi, S., et al., “PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin,” Nature Communications 18(2):161, Nature Publishing Group, United Kingdom (Jan. … [cited by applicant]
Gatheral, T. L., et al., “Personalised asthma action plans for adults with asthma,” The Cochrane Database of Systematic Reviews 4(4):CD011859, Cochrane Library, United Kingdom (Apr. 2017). [cited by applicant]
Ge, L., et al., “Constitutive protease-activated receptor-2-mediated migration of MDA MB-231 breast cancer cells requires both beta-arrestin-1 and -2,” The Journal of Biological Chemistry 279(53):55419-55424, Elsevier, … [cited by applicant]
Gessler, F., et al., “Inhibition of tissue factor/protease-activated receptor-2 signaling limits proliferation, migration and invasion of malignant glioma cells,” Neuroscience 165(4):1312-1322, Elsevier Science, United … [cited by applicant]
Gieger, R., et al., “Crystallogenesis of biological macromolecules: facts and perspectives,” Acta Crystallographica. Section D, Biological Crystallography 50(Pt4):339-350, Wiley-Blackwell, United States (Jul. 1994). [cited by applicant]
Glennie, M. J., et al., “Preparation and performance of bispecific F(ab′ gamma)2 antibody containing thioether-linked Fab′ gamma fragments,” Journal of Immunology 139(7):2367-2375, American Association of Immunologists,… [cited by applicant]
Hachem, J. P., et al., “Serine protease signaling of epidermal permeability barrier homeostasis,” Journal Of Investigative Dermatology 126(9):2074-2086, Elsevier, United States (Sep. 2006). [cited by applicant]
Hammerling, G. J., et al., eds., “Appendix: Production of Antibody-Producing Hybridomas in the RodentSystems” in Monoclonal Antibodies and T-Cell Hybridomas: Perspectives and Technical Advances, pp. 563-587, Elsevier, N… [cited by applicant]
Hassler, S. N., et al., “Protease activated receptor 2 (PAR2) activation causes migraine-like pain behaviors in mice,” Cephalalgia: An International Journal of Headache 39(1):111-122, SAGE Journals, United Kingdom (Jan.… [cited by applicant]
Henehan, M., et al., “Update on protease-activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases,” Experimental Dermatology 28(8):877-885… [cited by applicant]
Hollenberg, M. D., and Compton, S. J., “Proteinase-Activated Receptor Domains and Signaling,” Drug Development Research, 59(4):344-349, Wiley-Liss, Inc., United States (2003). [cited by applicant]
Hoogerwerf, W. A., “Trypsin Mediates Nociception via the Proteinase-Activated Receptor 2: A Potentially Novel Role in Pancreatic Pain,” Gastroenterology 127(3):883-891, W.B. Saunders, United States (Sep. 2004). [cited by applicant]
Hovnanian, A., “Netherton Syndrome: Skin Inflammation and Allergy by Loss of Protease Inhibition,” Cell And Tissue Research 351(2):289-300, Springer-Verlag, Germany (Feb. 2013). [cited by applicant]
Howells, G. L., “Proteinase-Activated Receptor-2: Expression by Human Neutrophils,” Journal of Cell Science 110 (Pt 7):881-887, Company of Biologists, United Kingdom (Apr. 1997). [cited by applicant]
Huesa, C., et al., “Proteinase-Activated Receptor 2 Modulates OA-Related Pain, Cartilage and Bone Pathology,” Annals of the Rheumatic Diseases, 75(11): 1989-1997, BMJ, United Kingdom (Nov. 2016). [cited by applicant]
Huston, J. S., et al., “Protein Engineering of Antibody Binding Sites: Recovery of Specific Activity in an Anti-digoxin Single-chain Fv Analogue Produced in [cited by applicant]
International Search Report and Written Opinion for International Application PCT/US2021/046552, European Patent Office, Munich, mailed Dec. 21, 2021, 13 pages. [cited by applicant]
Ito, M., “Prostanoid-Dependent Spontaneous Pain and PAR2-Dependent Mechanical Allodynia Following Oral Mucosal Trauma: Involvement of TRPV1, TRPA1, and TRPV4,” Molecular Pain 13:1-17, Sage Publications, United Kingdom (… [cited by applicant]
Iwaki, K., et al., “A Small Interfering RNA Targeting Proteinase-Activated Receptor-2 Is Effective in Suppression of Tumor Growth in a Pancl Xenograft Model,” International Journal of Cancer 122:658-663, Wiley-Liss, Uni… [cited by applicant]
Jefferis, R., and Lefranc, M. P., “Human Immunoglobulin Allotypes: Possible Implications for Immunogenicity,” MAbs 1(4):332-338, Taylor & Francis, United States (Jul.-Aug. 2009). [cited by applicant]
Jimenez-Vargas, N. N., et al., “Protease-Activated Receptor-2 in Endosomes Signals Persistent Pain of Irritable Bowel Syndrome,” Proceedings of the National Academy of Sciences of the United States of America 115(31):E7… [cited by applicant]
Jones, P. T., et al., “Replacing The Complementarity-Determining Regions In A Human Antibody With Those From a Mouse,” Nature 321(6069):522-525, Nature Publishing Group, United Kingdom (May 1986). [cited by applicant]
Kabat, E. A., and Wu, T. T., “Attempts to Locate Complementarity-Determining Residues in the Variable Positions of Light and Heavy Chains,” Annals of the New York Academy of Sciences 190:382-393, Blackwell, United State… [cited by applicant]
Kaplanski, G., “Interleukin-18: Biological Properties and Role in Disease Pathogenesis,” Immunological Reviews 281(1):138-153, Blackwell, United Kingdom (Jan. 2018). [cited by applicant]
Karpovsky, B., et al., “Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies,” The Journal of Experimental Medicine 160(6):1… [cited by applicant]
Kaufmann, R., et al., “Met Receptor Tyrosine Kinase Transactivation Is Involved in Proteinase-Activated Receptor-2-mediated Hepatocellular Carcinoma Cell Invasion,” Carcinogenesis 30:1487-1496, IRL Press At Oxford Unive… [cited by applicant]
Kawabata, A., and Kawao, N., “Physiology and pathophysiology of proteinase-activated receptors (PARs): PARs in the respiratory system: cellular signaling and physiological/pathological roles,” Journal of Pharmacological… [cited by applicant]
Kawagoe, K., et al., “Effect of Protease-Activated Receptor-2 Deficiency on Allergic Dermatitis in the Mouse Ear,” Japanese Journal of Pharmacology, 88(1):77-84, Japanese Pharmacological Society, Japan (Jan. 2002). [cited by applicant]
Kelso, E. B., et al., “Expression and proinflammatory role of proteinase-activated receptor 2 in rheumatoid synovium: ex vivo studies using a novel proteinase-activated receptor 2 antagonist,” Arthritis & Rheumatology 5… [cited by applicant]
Kempkes, C., et al., “Proteinase-activated receptors 1 and 2 regulate invasive behavior of human melanoma cells via activation of protein kinase D1,” The Journal of Investigative Dermatology 132:375-384, Elsevier, Unite… [cited by applicant]
Ketabchi, S., et al., “Expression of Protease-Activated Receptor-1 and -2 in Orofacial Granulomatosis,” Oral Diseases 13(4):419-425, Copenhagen, Denmark (Jul. 2007). [cited by applicant]
Kettleborough, C. A., et al., “Isolation of Tumor Cell-specific Single-chain Fv From Immunized Mice Using Phage-antibody Libraries and the Re-construction of Whole Antibodies From These Antibody Fragments,” European Jou… [cited by applicant]
Kirkland, T. N., et al., “Analysis of the Fine Specificity and Cross-reactivity of Monoclonal Anti-lipid A Antibodies,” Journal of Microbiology 137(11):3614-3619, Microbiological Society of Korea, Korea (Dec. 1986). [cited by applicant]
Knight, D. A., et al., “Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma,” Allergy Clin Immunol 108(5):797-803, Mosby, United States (Nov. 2001). [cited by applicant]
Knight, V., et al., “Protease-activated receptor 2 promotes experimental liver fibrosis in mice and activates human hepatic stellate cells,” Hepatology 55(3):879-887, Williams & Wilkins, United States (Mar. 2012). [cited by applicant]
Kobayashi, H., et al., “Tryptophan H33 Plays an Important Role in Pyrimidine (6-4) Pyrimidone Photoproduct Binding by a High-Affinity Antibody,” Protein Engineering Design and Selection 12(10):879-884, Oxford University… [cited by applicant]
Kohler, G., and Milstein, C., “Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity,” Nature 256(5517):495-497, Nature Publishing Group, United Kingdom (Aug. 1975). [cited by applicant]
Kostelny, S. A., et al., “Formation of a Bispecific Antibody by the Use of Leucine Zippers,” The Journal of Immunology 148(5):1547-1553, American Association of Immunologists, United States (Mar. 1992). [cited by applicant]
Kouzaki, H., et al., “Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2,” J Immunol 183(2):1427-1434, American Association of Immunologists, Uni… [cited by applicant]
Kwapiszewska, G., et al., “PAR-2 Inhibition Reverses Experimental Pulmonary Hypertension,” Circulation Research 110(9):1179-1191, Lippincott Williams & Wilkins, United States (Apr. 2012). [cited by applicant]
Labrijn, A. F., et al., “Therapeutic IgG4 Antibodies Engage in Fab-Arm Exchange with Endogenous Human IgG4 in Vivo,” Nature Biotechnology 27(8):767-771, Nature America Publishing, United States (Aug. 2009). [cited by applicant]
Lam, D. K., and Schmidt, B. L., “Serine Proteases and Protease-Activated Receptor 2-Dependent Allodynia: A Novel Cancer Pain Pathway,” Pain 149(2):263-272, Lippincott Williams & Wilkins, United States (May 2010). [cited by applicant]
Lam, D. K., et al., “Novel Animal Models of Acute and Chronic Cancer Pain: A Pivotal Role for PAR2,” The Journal of Neuroscience 32(41):14178-14183, Society for Neuroscience, United States (Oct. 2012). [cited by applicant]
Lam, D., et al., “TMPRSS2, A Novel Membrane-Anchored Mediator in Cancer Pain,” Pain 156(5):923-930, Lippincott Williams & Wilkins, United States (May 2015). [cited by applicant]
Larsen, K. S., et al., “Engineering of substrate selectivity for tissue factor.factor VIIa complex signaling through protease-activated receptor 2,” The Journal of Biological Chemistry, 285(26):19959-19966, Elsevier Inc… [cited by applicant]
Lau, C., et al., “Chimeric anti-CD14 IGG2/4 Hybrid antibodies for therapeutic intervention in pig and human models of inflammation,” Journal of Immunology 91(9):4769-4777, American Association of Immunologists, United S… [cited by applicant]
Lee, S. E., et al., “Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis,” Yonsei Medical Journal 51(6):808-822, Yonsei University, Korea (Nov. 2010). [cited by applicant]
Lee, J. H., et al., “A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children,” The Journal of Allergy and Clinical Immunology 128(6):1326-1334, Mosby, United States (Dec. 2011… [cited by applicant]
Lee, H. J., et al., “Protease-activated receptor 2 mediates mucus secretion in the airway submucosal gland,” PLoS One 7(8):e43188, Public Library of Science, United States (2012). [cited by applicant]
Lee, K. H., et al., “Cigarette smoke extract enhances neutrophil elastase-induced IL-8 production via proteinase-activated receptor-2 upregulation in human bronchial epithelial cells,” Experimental & Molecular Medicine … [cited by applicant]
Li, W., et al., “Simultaneous Generation and Germline Transmission of Multiple Gene Mutations in Rat Using CRISPR-Cas systems,” Nature Biotechnology 31(8):684-6, Nature America Publishing, United States (Aug. 2013). [cited by applicant]
Liang, G., et al., “Naive T cells sense the cysteine protease allergen papain through protease-activated receptor 2 and propel TH2 immunity,” The Journal of Allergy and Clinical Immunology, 129(5):1377-1386, Mosby, Unit… [cited by applicant]
Liang, W. J., et al., “Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome,” Gut Liver 10(3):382-390, Editorial Office of Gut and Liver, Korea (May 2016). [cited by applicant]
Lin, K. W., et al., “Protease-activated receptor-2 (PAR-2) is a weak enhancer of mucin secretion by human bronchial epithelial cells in vitro,” Int J Biochem Cell Biol 40(6-7):1379-1388, Elsevier, Netherlands (2008). [cited by applicant]
Lin, C., et al., “Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis,” Molecular Medicine 21(1):576-583, BioMed Central, United Kingdom (Jun. 2015). [cited by applicant]
Linder, J. R., et al., “Delayed Onset of Inflammation in Protease-Activated Receptor-2-Deficient Mice,” Journal of Immunology, 165(11):6504-6510, American Association of Immunologists, United States (Dec. 2000). [cited by applicant]
Liu, M. A., et al., “Heteroantibody duplexes target cells for lysis by cytotoxic T lymphocytes,” Proceedings of the National Academy of Sciences of the United States of America 82(24):8648-8652, National Academy of Scie… [cited by applicant]
Liu, H., et al., “Role of mast cells, stem cell factor and protease-activated receptor-2 in tubulointerstitial lesions in IgA nephropathy,” Inflammation Research Journal 59(7):551-559, Basel, Switzerland (Jul. 2010). [cited by applicant]
Liu, S., et al., “Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain,” European Journal of Pain 18(3):326-337, Wiley, United Kingdom (Mar. 2014). [cited by applicant]
Lonberg, N., “Human Antibodies From Transgenic Animals,” Nature Biotechnology, 23(9):1117-1125, Nature America Publishing, United States (Sep. 2005). [cited by applicant]
Lourbakos, A., et al., “Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis,” FEBS Letters 435(1):45-48, John Wiley & Sons Ltd, United Kingdom (Se… [cited by applicant]
Matej, R., et al., “Proteinase-activated receptor-2 expression in breast cancer and the role of trypsin on growth and metabolism of breast cancer cell line MDA MB-231,” Physiological Research 56:475-484, Institute of Ph… [cited by applicant]
McCulloch, K., et al., “Rheumatic Disease: Protease-Activated Receptor-2 in Synovial Joint Pathobiology,” Frontiers in Endocrinology 9:257, Lausanne, Switzerland (May 2018). [cited by applicant]
McPherson, A., “Current Approaches to Macromolecular Crystallization,” European Journal of Biochemistry 189(1):1-23, Blackwell Science Ltd, United Kingdom (Apr. 1990). [cited by applicant]
Miike, S., et al., “Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2,” J Immunol 167(11):6615-6622, American Association of Immunologists, United … [cited by applicant]
Milner, J. M., et al., “Matriptase Is a Novel Initiator of Cartilage Matrix Degradation in Osteoarthritis,” Arthritis and Rheumatism 62(7):1955-1966, Wiley-Blackwell, United States (Jul. 2010). [cited by applicant]
Miotto, D. M., et al., “Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers,” Thorax 57(2):146-151, British Medical Assn, United Kingdom (Feb. 2002). [cited by applicant]
Miyata, S., et al., “Trypsin stimulates integrin alpha(5)beta(1)-dependent adhesion to fibronectin and proliferation of human gastric carcinoma cells through activation of proteinase-activated receptor-2,” The Journal o… [cited by applicant]
Moldenhauer, G., et al., “Identity of HML-1 antigen on intestinal intraepithelial T cells and of B-ly7 antigen on hairy cell leukaemia,” Scandinavian Journal of Immunology 32(2):77-82, Blackwell Scientific Publications,… [cited by applicant]
Morel, G. A., et al., “Monoclonal Antibodies to Bovine Serum Albumin: Affinity and Specificity Determinations,” Molecular Immunology 25(1):7-15, Pergamon Press, United Kingdom (Jan. 1988). [cited by applicant]
Morgan, C. R., “Changes in Proteinase-Activated Receptor 2 Expression in the Human Tooth Pulp in Relation to Caries and Pain,” Journal of Orofacial Pain 3(3): 265-274, Quintessence Pub. Co, United States (2009). [cited by applicant]
Moussa, L., et al., “Protease-activated receptor-2 augments experimental crescentic glomerulonephritis,” The American Journal of Pathology 171(3):800-808, Elsevier, United States (Sep. 2007). [cited by applicant]
Mrozkova, P., et al., “The Role of Protease-Activated Receptor Type 2 in Nociceptive Signaling and Pain,” Physiological Research 65(3):357-367, Institute of Physiology of the Czechoslovak Academy of Sciences by Academia… [cited by applicant]
Mußbach, F., et al., “Proteinase-activated receptor 2 (PAR [cited by applicant]
Muley, M., et al., “Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice,” Journal of Neuroinflammation 14:168, BioMed Central, United Kingdom (Aug. … [cited by applicant]
Murray, D. B., et al., “Tryptase Activates Isolated Adult Cardiac Fibroblasts via Protease Activated Receptor-2 (PAR-2),” Journal of Cell Communication and Signalling 6(1):45-51, Springer, Germany (Mar. 2012). [cited by applicant]
Myers, E. W., and Miller, W., “Optical Alignments in linear space,” Computer Applications in the Biosciences 4(1):11-17, Oxford University Press, United Kingdom (Mar. 1988). [cited by applicant]
Nadeem, A., et al., “Proteinase activated receptor-2-mediated dual oxidase-2 up-regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma,” Immunology 145(3):391-403, Blac… [cited by applicant]
Nadeem, A., et al., “Protease activated receptor-2 mediated upregulation of IL-17 receptor signaling on airway epithelial cells is responsible for neutrophilic infiltration during acute exposure of house dust mite aller… [cited by applicant]
Namkung, W., et al., “Protease-activated receptor 2 exerts local protection and mediates some systemic complications in acute pancreatitis,” Gastroenterology 126(7):1844-1859, W.B. Saunders, United States (Jun. 2004). [cited by applicant]
Needleman, S. B., and Wunsch, C. D., “A General Method Applicable to the Search for Similarities in the Amino Acid Sequence of Two Proteins,” Journal of Molecular Biology 48(3):443-453, Academic Press, United Kingdom (M… [cited by applicant]
Nichols, H. L., et al., “β-Arrestin-2 Mediates the Proinflammatory Effects of Proteinase-activated Receptor-2 in the Airway,” Proc Natl Acad Sci USA 109(41):16660-16665, National Academy of Sciences, United States (Oct.… [cited by applicant]
Nishimura, S., et al., “The proteinase/proteinase-activated receptor-2/transient receptor potential vanilloid-1 cascade impacts pancreatic pain in mice,” Life Science 87(19-22):643-650, Elsevier, Netherlands (Nov. 2010). [cited by applicant]
O'Brien, P. J., et al., “Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1,” J Biol Chem 275(18):13502-13509, Elsevi… [cited by applicant]
Pal, K., et al., “Divergent β-Arrestin-dependent Signaling Events Are Dependent Upon Sequences Within G-protein-coupled Receptor C Termini,” J Biol Chem 288(5):3265-3274, Biochemistry and Molecular Biology, United State… [cited by applicant]
Palikhe, N. S., et al., “Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma,” PLoS One 10(12):e0144500, Public Library of Science, United … [cited by applicant]
Park, Y. S., et al., “Clinical Implication of Protease-activated Receptor-2 in Idiopathic Pulmonary Fibrosis,” Respiratory Medicine 107(2):256-262, Oxford University Press, United Kingdom (Feb. 2013). [cited by applicant]
Paulus, H., et al., “Preparation and biomedical applications of bispecific antibodies,” Behring Institute Mitteilungen 78:118-132, Behringwerke AG, Germany (Dec. 1985). [cited by applicant]
Persic, L., et al., “An Integrated Vector System for the Eukaryotic Expression of Antibodies or Their Fragments After Selection From Phage Display Libraries,” Gene 187(1):9-18, Elsevier/North-Holland, Netherlands (Mar. … [cited by applicant]
Portenoy, R. K., et al., “Breakthrough Pain: Characteristics and Impact in Patients with Cancer Pain,” Pain 81(1-2):129-134, Lippincott Williams & Wilkins, United States (May 1999). [cited by applicant]
Quirt, J., et al., “Asthma,” Allergy Asthma Clin Immunol, 12:14(Suppl 2):50, BioMed Central, United Kingdom (Sep. 2018). [cited by applicant]
Rabe, K. F., et al., “Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary,” American Journal of Respiratory and Critical Care Medicine 176(6):53… [cited by applicant]
Ramachandran, R., et al., “Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2),” J Biol Chem 286(28):24638-24648, Elsevier Inc. on behalf of American Society for Biochemistry and Mole… [cited by applicant]
Riechmann, L., et al., “Reshaping Human Antibodies for Therapy,” Nature 332(6162):323-327, Nature Publishing Group, United States (Mar. 1988). [cited by applicant]
Roguska, M. A., et al., “Humanization of Murine Monoclonal Antibodies through Variable Domain Resurfacing,” Proceedings of the National Academy of Sciences USA 91(3):969-973, National Academy of Sciences, United States … [cited by applicant]
Roguska, M. A., et al., “A Comparison of Two Murine Monoclonal Antibodies Humanized by CDR-grafting and Variable Domain Resurfacing,” Protein Engineering 9(10):895-904, Oxford University Press, United Kingdom (1996). [cited by applicant]
Rothmeier, A. S., and Ruf, W., “Protease-activated receptor 2 signaling in inflammation,” Semin Immunopathol 34(1):133-149, Springer, Germany (Jan. 2012). [cited by applicant]
Roux, K. H., et al., “Comparisons of the ability of human IgG3 hinge mutants, IgM, IgE, and IgA2, to form small immune complexes: a role for flexibility and geometry,” J Immunol 161(8):4083-4090, American Association of… [cited by applicant]
Roversi, P., et al., “Modelling Prior Distributions of Atoms for Macromolecular Refinement and Completion,” Acta Crystallographica. Section D, Biological Crystallography 56(Pt10):1316-1323, International Union of Crysta… [cited by applicant]
Sakamoto, A., et al., “Involvement of Mast Cells and Proteinase-Activated Receptor 2 in Oxaliplatin-Induced Mechanical Allodynia in Mice,” Pharmacological Research 105:84-92, Elsevier, Netherlands (Mar. 2016). [cited by applicant]
Schaffner, F., & Ruf, W., “Tissue factor and PAR2 signaling in the tumor microenvironment,” Arteriosclerosis, Thrombosis, and Vascular Biology 29(12): 1999-2004, Lippincott Williams & Wilkins, United States (Aug. 2009). [cited by applicant]
Schaffner, F., et al., “Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development,” Blood 116:6106-6113, American Society of Hematology, United States (Dec. 2010). [cited by applicant]
Schmidlin, F., et al., “Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway”, Journal of Immunology 169(9):5315-5321, American Association of Immunol… [cited by applicant]
Sharma, A., et al., “Protection against acute pancreatitis by activation of protease-activated receptor-2,” American Journal of Physiology. Gastrointestinal and Liver Physiology 288(2):G388-395, American Physiological S… [cited by applicant]
Silva, J. P., et al., “The S228P mutation prevents in vivo and in vitro IgG4 Fab-arm exchange as demonstrated using a combination of novel quantitative immunoassays and physiological matrix preparation,” J Biol Chem 290… [cited by applicant]
Songsivilai, S., and Lachmann, P. J., “Bispecific Antibody: A Tool for Diagnosis and Treatment of Disease,” Clinical and Experimental Immunology 79(3):315-321, Blackwell Scientific Publications, United Kingdom (Mar. 199… [cited by applicant]
Stahli, C., et al., “Distinction of Epitopes by Monoclonal Antibodies,” Methods in Enzymology 92:242-253, Academic Press, United States (1983). [cited by applicant]
Steinhoff, M., et al., “Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase,” Experimental Dermatology 8:282-294, Munksgaard, Denmark (Aug. 1999). [cited by applicant]
Suckow, K. S., et al., “NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity,” Molecular Pain 5:54, Sage Publications,… [cited by applicant]
Tam, S. H., et al., “Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality,” Antibodies (Basel) 6(3):12, MDPI, Switzerland (Sep. 2017). [cited by applicant]
Terada, Y., et al., “Contribution of TRPA1 as a downstream signal of proteinase-activated receptor-2 to pancreatic pain,” Journal of Pharmacological Sciences 123(3):284-287, Japanese Pharmacological Society, Japan (2013… [cited by applicant]
Tian, L., et al., “Role of PAR2 in regulating oxaliplatin-induced neuropathic pain via TRPA1,” Translational Neuroscience 6(1):111-116, Walter de Gruyter GmbH, Germany (Mar. 2015). [cited by applicant]
Tindell, A. G., et al., “Correlation of protease-activated receptor-2 expression and synovitis in rheumatoid and osteoarthritis,” Rheumatology International 32(10):3077-3086, Springer International, Germany (Oct. 2012). [cited by applicant]
Tsai, M. C., et al., “The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy,” Medicina (Kaunas) 57(6):574, MDPI, Switzerland (Jun. 2021). [cited by applicant]
Tsubota, M., et al., “Prostanoid-dependent bladder pain caused by proteinase-activated receptor-2 activation in mice: Involvement of TRPVI and T-type Ca 2+ channels,” Journal Of Pharmacological Sciences 136(1):46-49, Ja… [cited by applicant]
UniProt, “PERV-A receptor-2,” UniProt.org, Accession No. E5FAJ7, accessed at URL:[https://www.uniprot.org/uniprot/E5FAJ7] on Nov. 3, 2021, 4 pages. [cited by applicant]
UniProt, “Immunoglobulin heavy constant gamma 2,” UniProt.org, Accession No. P01859, accessed at URL:[https://www.uniprot.org/uniprot/P01859] on Nov. 3, 2021, 8 pages. [cited by applicant]
UniProt, “Immunoglobulin heavy constant gamma 4,” UniProt.org, Accession No. P01861, accessed at URL:[https://www.uniprot.org/uniprot/P01861] on Nov. 3, 2021, 7 pages. [cited by applicant]
UniProt, “Proteinase-activated receptor 2,” UniProt.org, Accession No. P55085-1, accessed at URL:[https://www.uniprot.org/uniprot/Q63645] on Nov. 3, 2021, 7 pages. [cited by applicant]
UniProt, “Proteinase-activated receptor 2,” UniProt.org, Accession No. Q63645, accessed at URL:[https://www.uniprot.org/uniprot/P55085] on Nov. 3, 2021, 10 pages. [cited by applicant]
Vafa, O., et al., “An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations,” Methods 65(1):114-126, Academic Press, United States (Jan. 2014). [cited by applicant]
Vasilopoulos, Y., et al., “Genetic association between an AACC insertion in the 3′UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis,” Journal of Investigative Dermatology 123(1):62-66, Nature Pub… [cited by applicant]
Vergnolle, N., et al., “Proteinase-activated Receptor-2 and Hyperalgesia: a Novel Pain Pathway,” Nat Med 7(7):821-826, Nature Publishing Company, United States (Jul. 2001). [cited by applicant]
Vergnolle, N., “Modulation of Visceral Pain and Inflammation by Protease-Activated Receptors,” British Journal of Pharmacology 141(8):1264-1274, Wiley, United Kingdom (Apr. 2004). [cited by applicant]
Verhoeyen, M., et al., “Reshaping Human Antibodies: Grafting an Antilysozyme Activity,” Science 239(4847):1534-1536, American Association for the Advancement of Science, United States (Mar. 1988). [cited by applicant]
Vidarsson, G., et al., “IgG subclasses and allotypes: from structure to effector functions,” Front Immunology 5:520, Frontiers Research Foundation, Switzerland (Oct. 2014). [cited by applicant]
Wang, Q., et al., “Inhibition of PAR2 and TRPA1 signals alleviates neuropathic pain evoked by chemotherapeutic bortezomib,” Journal of Biological Regulators and Homeostatic Agents 31(4):977-983, Biolif, Italy (Oct.-Dec.… [cited by applicant]
Wang, X., et al., “IgG Fc engineering to modulate antibody effector functions,” Protein Cell 9(1):63-73, Higher Education Press, Germany (Jan. 2018). [cited by applicant]
Ward, E. S., et al., “Binding Activities of a Repertoire of Single Immunoglobulin Variable Domains Secreted from [cited by applicant]
Weiszer, I., et al., “Ascaris Hypersensitivity in the Rhesus Monkey. I. A Model for the Study of Immediate Type Thypersensitity in the Primate,” Journal of Allergy 41(1):14-22, Mosby, United States (Jan. 1968). [cited by applicant]
Wilson, S. R., et al., “Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptors,” Prostate 60:168-174, Wiley-Liss, United States (Jul. 2004). [cited by applicant]
Wojtukiewicz, M. Z., et al., “Protease-activated Receptors (PARs)—biology and Role in Cancer Invasion and Metastasis,” Cancer Metastasis Reviews 34:775-796, Kluwer Academic, Netherlands (Dec. 2015). [cited by applicant]
Wyckoff, H. W., “Diffractometry,” Methods in Enzymology 114:330-386, Academic Press, United States (1985). [cited by applicant]
Wygrecka, M., et al., “Role of Protease-Activated Receptor-2 in Idiopathic Pulmonary Fibrosis,” American Journal of Respiratory and Critical Care Medicine 183(12):1703-1714, American Thoracic Society, United States (Jun… [cited by applicant]
Xiang, Y., et al., “Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta,” Osteoarthritis Cartilage 14(11):1163-1173, W. B. Saunders for the Ost… [cited by applicant]
Xu, W., et al., “Electroacupuncture Relieves Visceral Hypersensitivity by Inactivating Protease-Activated Receptor 2 in a Rat Model of Postinfectious Irritable Bowel Syndrome,” Evidence-Based Complementary and Alternati… [cited by applicant]
Yau, M-K., et al., “Protease activated receptor 2 (PAR2) modulators: a patent review (2010-2015),” Expert Opinion on Therapeutic Patents 26(4):471-483, Informa UK Limited, United Kingdom (2016). [cited by applicant]
Yoon, H., et al., “Protease Activated Receptor 2 Controls Myelin Development, Resiliency and Repair,” Glia 65(12):2070-2086, Wiley-Liss, United States (Dec. 2017). [cited by applicant]
Younger, J., et al., “Pain Outcomes: A Brief Review of Instruments and Techniques,” Current Pain and Headache Reports 13(1):39-43, Current Science Inc., United States (Feb. 2009). [cited by applicant]
Zhang, W., et al., “Proteinase-activated receptor 2 mediates thermal hyperalgesia and is upregulated in a rat model of chronic pancreatitis,” Pancreas 40(2):300-307, Lippincott Williams & Wilkins, United States (Mar. 20… [cited by applicant]
Zhou, B., et al., “Activation of PAR2 or/and TLR4 promotes SW620 cell proliferation and migration via phosphorylation of ERK1/2,” Oncology Reports 25:503-511, Spandidos, Greece (Feb. 2013). [cited by applicant]
Zhou, J., et al., “Neutrophil elastase induces MUC5AC secretion via protease-activated receptor 2,” Molecular and Cellular Biochemistry 377(1-2):75-85, Springer, Netherlands (May 2013). [cited by applicant]
Zhu, J., et al., “Trypsin-protease activated receptor-2 signaling contributes to pancreatic cancer pain,” Oncotarget 8(37):61810-61823, Impact Journals, United States (Jun. 2017). [cited by applicant]
Edwards, B.M., et al., “The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS,” J Mol Biol 334(1):103-118, Elsevier, Netherlands (Nov.… [cited by applicant]
Lloyd, C., et al., “Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Eng Des Sel 22(3):159-168, Oxford University … [cited by applicant]
Goel, M., et al., “Plasticity within the antigen-combining site may manifest as molecular mimicry in the humoral immune response,” J Immunol 173(12):7358-7367, American Association of Immunologists, United States (Dec. … [cited by applicant]
Kanyavuz, A., et al., “Breaking the law: unconventional strategies for antibody diversification,” Nat Rev Immunol 19(6):355-368, Nature Portfolio, Germany (Jun. 2019). [cited by applicant]
Damiano, B.P., “Increased expression of protease activated receptor-2 (PAR-2) in balloon-injured rat carotid artery,” Thromb Haemost 81(5):808-814, Wiley, United States (May 1999). [cited by applicant]
Kopruszinski, C.M., et al., “Characterization and preclinical evaluation of a protease activated receptor 2 (PAR2) monoclonal antibody as a preventive therapy for migraine,” Cephalalgia 40(14):1535-1550, Sage Publishing… [cited by applicant]