IP Library › Granted Patent US 12,195,557
Granted Patent B2
US 12,195,557 · App. 16/768,341 · Granted Jan 14, 2025

Optimised compounds

Inventors: David Jackson (Melbourne, AU); Ian Holmes (Melbourne, AU); Weiguang Zeng (Melbourne, AU); Christophe Demaison (Melbourne, AU)
Assignee: AXELIA ONCOLOGY PTY LTD
C07K5/0606A61K47/542A61K47/60A61P11/00C07C317/48C07C323/60A61K38/00
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Quick Facts
Patent No.
US 12,195,557
App. No.
16/768,341
Granted
Jan 14, 2025
Kind
B2
Abstract

The present invention relates to TLR2 agonist compounds and their compositions, and the use of such compounds and compositions in the prevention and/or treatment of respiratory infections, or diseases or conditions associated with viral or bacterial infections.

Claims (10)

1. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

4. A compound:

or a pharmaceutically acceptable salt thereof.

5. A compound:

or a pharmaceutically acceptable salt thereof.

Assignments (7)
CHANGE OF NAME Recorded Apr 11, 2023
From: INNAVAC PTY LTD
To: ENA THERAPEUTICS PTY LTD
Reel/Frame 063295/0371 →
CHANGE OF NAME Recorded Apr 11, 2023
From: ENA THERAPEUTICS PTY LTD
To: AXELIA ONCOLOGY PTY LTD
Reel/Frame 063295/0373 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2020
From: ZENG, WEIGUANG, DR.
To: THE UNIVERSITY OF MELBOURNE
Reel/Frame 052797/0220 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2020
From: DEMAISON, CHRISTOPHE; JACKSON, DAVID
To: ENA THERAPEUTICS PTY LTD
Reel/Frame 052797/0695 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2020
From: BCP3 PTY LIMITED
To: ENA THERAPEUTICS PTY LTD
Reel/Frame 052797/0720 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2020
From: THE UNIVERSITY OF MELBOURNE
To: ENA THERAPEUTICS PTY LTD
Reel/Frame 052798/0078 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2020
From: HOLMES, IAN
To: BCP3 PTY LIMITED
Reel/Frame 053548/0596 →
Priority Claims (3)
AU 2017905128 · Dec 21, 2017 · national
AU 2018901056 · Mar 29, 2018 · national
AU 2018903597 · Sep 25, 2018 · national
Continuity (1)
Related Publication 20210230217A1 · Jul 29, 2021
References Cited (210)
US 7316996B2 · Muhlradt et al. · 2008 [cited by applicant]
US 8883174B2 · Dickey et al. · 2014 [cited by applicant]
US 8986700B2 · Jackson et al. · 2015 [cited by applicant]
US 9089508B2 · Jackson et al. · 2015 [cited by applicant]
US 9676819B2 · Jackson et al. · 2017 [cited by applicant]
US 9889195B2 · Jackson et al. · 2018 [cited by applicant]
US 10406100B2 · Jackson et al. · 2019 [cited by applicant]
US 11351114B2 · Jackson et al. · 2022 [cited by applicant]
US 20040191270A1 · Drane et al. · 2004 [cited by applicant]
US 20070066534A1 · Jackson et al. · 2007 [cited by applicant]
US 20080069831A1 · Duke et al. · 2008 [cited by applicant]
US 20080069832A1 · Chomez et al. · 2008 [cited by applicant]
US 20090257980A1 · Davies et al. · 2009 [cited by applicant]
US 20100129385A1 · Jackson et al. · 2010 [cited by applicant]
US 20100310595A1 · Jackson et al. · 2010 [cited by applicant]
US 20110280899A1 · Jackson et al. · 2011 [cited by applicant]
US 20120064109A1 · Jackson et al. · 2012 [cited by applicant]
US 20130230544A1 · Jackson et al. · 2013 [cited by applicant]
US 20150150966A1 · Jackson et al. · 2015 [cited by applicant]
US 20190380952A1 · Jackson et al. · 2019 [cited by applicant]
US 20200147028A1 · Bartlett · 2020 [cited by examiner]
US 20210177795A1 · Jackson · 2021 [cited by examiner]
US 20220347146A1 · Demaison et al. · 2022 [cited by applicant]
US 20220388950A1 · Holmes et al. · 2022 [cited by applicant]
US 20230043518A1 · Demaison et al. · 2023 [cited by applicant]
US 20230226004A1 · Tsitoura et al. · 2023 [cited by applicant]
US 20230257345A1 · Holmes et al. · 2023 [cited by applicant]
US 20230278954A1 · McLachlan · 2023 [cited by applicant]
AU 2014202674A1 · 2014 [cited by applicant]
EP 1550458A1 · 2005 [cited by applicant]
EP 1666056A1 · 2006 [cited by applicant]
EP 3728289A1 · 2020 [cited by applicant]
JP 2016216593A · 2016 [cited by applicant]
WO WO2001037869A1 · 2001 [cited by applicant]
WO WO2001090129A2 · 2001 [cited by applicant]
WO WO2004014956A1 · 2004 [cited by applicant]
WO WO2004014957A1 · 2004 [cited by applicant]
WO WO2005070959A2 · 2005 [cited by applicant]
WO 2005079419A2 · 2005 [cited by applicant]
WO WO2005112991A2 · 2005 [cited by applicant]
WO WO2006069262A2 · 2006 [cited by applicant]
WO WO2006084319A1 · 2006 [cited by applicant]
WO WO2006091591A1 · 2006 [cited by applicant]
WO 2007059931A1 · 2007 [cited by applicant]
WO WO2007103322A2 · 2007 [cited by applicant]
WO WO2008085549A2 · 2008 [cited by applicant]
WO WO2009046498A1 · 2009 [cited by applicant]
WO 2009137103A2 · 2009 [cited by applicant]
WO WO2009155332A1 · 2009 [cited by applicant]
WO WO2010028246A2 · 2010 [cited by applicant]
WO WO2010093436A2 · 2010 [cited by applicant]
WO WO2010111485A1 · 2010 [cited by applicant]
WO WO2010115229A1 · 2010 [cited by applicant]
WO WO2010115230A1 · 2010 [cited by applicant]
WO WO2010128303A1 · 2010 [cited by applicant]
WO WO2011080259A1 · 2011 [cited by applicant]
WO WO2011119759A1 · 2011 [cited by examiner]
WO 2012037612A1 · 2012 [cited by applicant]
WO WO2013049941A1 · 2013 [cited by applicant]
WO WO2014207708A2 · 2014 [cited by applicant]
WO 2016037240A1 · 2016 [cited by applicant]
WO WO2016044839A2 · 2016 [cited by applicant]
WO WO2017019896A1 · 2017 [cited by applicant]
WO WO2017145097A2 · 2017 [cited by applicant]
WO 2018176099A1 · 2018 [cited by applicant]
WO 2018197582A1 · 2018 [cited by applicant]
WO WO2019043604A1 · 2019 [cited by applicant]
WO 2019119069A1 · 2019 [cited by applicant]
WO 2021042171A1 · 2021 [cited by applicant]
Tan et al. “Intranasal Administration of the TLR2 Agonist Pam2Cys Provides Rapid Protection against Influenza in Mice” Molecular Pharmaceutics 9:2710-2718 (Year: 2012). [cited by examiner]
Beaumont et al. “Design of Ester Prodrugs to Enhance Oral Absorption of Poorly Permeable Compounds: Challenges to the Discovery Scientist” Current Drug Metabolism 4:461-485. (Year: 2003). [cited by examiner]
Ettmayer et al. “Lessons Learned from Marketed and Investigational Prodrugs” J. Med. Chem. 47:2393-2404. (Year: 2004). [cited by examiner]
Han H “Targeted Prodrug Design to Optimize Drug Delivery” AAPS Pharmsci 2:Article 6 (Year: 2000). [cited by examiner]
Muller C “Prodrug Approaches for Enhancing the Bioavailability of Drugs with Low Solubility” Chemistry & Biodiversity 6:2071-2083 (Year: 2009). [cited by examiner]
Singh et al. “Recent Trends in Targeted Anticancer Prodrug and Conjugate Design” Curr. Med. Chem. 15:1802-1826. (Year: 2008). [cited by examiner]
Testa B “Prodrug research: futile or fertile?” Biochem. Pharmacol. 68:2097-2106. (Year: 2004). [cited by examiner]
Contoli et al., Viral infections in exacerbations of asthma and chronic obstructive pulmonary disease. Minerva Med. Dec. 2009;100(6):467-78. [cited by applicant]
Richard et al., TLR2 signaling decreases transmission of [cited by applicant]
Tan et al., Intranasal administration of the TLR2 agonist Pam2Cys provides rapid protection against influenza in mice. Mol Pharm. 2012;9(9):2710-2718. [cited by applicant]
Voss et al., The activity of lipopeptide TLR2 agonists critically depends on the presence of solubilizers. Eur J Immunol. Dec. 2007;37(12):3489-98. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/AU2018/050295, dated May 23, 2018, 10 pages. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/AU2018/051397, dated Feb. 28, 2019, 16 pages. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/AU2018/051401, dated Feb. 12, 2019, 13 pages. [cited by applicant]
Akazawa, Development of a Functionally Designed Artificial Adjuvant. Research Report of the Uehara Memorial Foundation 23. 12 pages, (2009). [cited by applicant]
Alexopoulou et al., Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. Oct. 18, 2001;413(6857):732-8. [cited by applicant]
Alphs et al., Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2. Proc Natl Acad Sci U S A. Apr. 15, 2008;105(15):5850… [cited by applicant]
Amigorena, Fc gamma receptors and cross-presentation in dendritic cells. J Exp Med. Jan. 7, 2002;195(1):F1-3. [cited by applicant]
Andra et al., Enhancement of endotoxin neutralization by coupling of a C12-alkyl chain to a lactoferricin-derived peptide. Biochem J. Jan. 1, 2005;385(Pt 1):135-43. [cited by applicant]
Archer et al., MyD88-dependent responses involving toll-like receptor 2 are important for protection and clearance of Legionella pneumophila in a mouse model of Legionnaires' disease. Infect Immun. Jun. 2006;74(6):3325-… [cited by applicant]
Asea et al., Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem. Apr. 26, 2002;277(17):15028-34. [cited by applicant]
Azuma et al., The peptide sequence of diacyl lipopeptides determines dendritic cell TLR2- mediated NK activation. PLoS One. Sep. 2, 2010;5(9):e12550, 12 pages. [cited by applicant]
Basto et al., Targeting TLR2 for vaccine development. J Immunol Res. 2014;2014:619410, 22 pages. [cited by applicant]
Baz et al., Branched and linear lipopeptide vaccines have different effects on primary CD4+ and CD8+ T-cell activation but induce similar tumor-protective memory CD8+ T-cell responses. Vaccine. May 19, 2008;26(21):2570-… [cited by applicant]
Belz et al., A previously unrecognized H-2D(b)-restricted peptide prominent in the primary influenza A virus-specific CD8(+) T-cell response is much less apparent following secondary challenge. J Virol. Apr. 2000;74(8):… [cited by applicant]
Bodmer et al., Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein. Cell. Jan. 29, 1988;52(2): 3486-3493. [cited by applicant]
Brown et al., Immune recognition. A new receptor for beta-glucans. Nature. Sep. 6, 2001;413(6851):36-7. [cited by applicant]
Bulut et al., Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol. Feb. 1, 2002;168(3):1435-40. [cited by applicant]
Buwitt-Beckmann et al., TLR1- and TLR6-independent recognition of bacterial lipopeptides. J Biol Chem. Apr. 7, 2006;281(14):9049-57. [cited by applicant]
Buwitt-Beckmann et al., Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol. Jan. 2005;35(1):282-9. [cited by applicant]
Chaturvedi et al., A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res. Oct. 2011;2(4):215-22. [cited by applicant]
Cheng et al., Characterization of nasal spray pumps and deposition pattern in a replica of the human nasal airway. J Aerosol Med. 2001 Summer; 14(2):267-80. [cited by applicant]
Chow et al., Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem. Apr. 16, 1999;274(16):10689-92. [cited by applicant]
Chua et al., A Self-adjuvanting Lipopeptide Vaccine for Immunotherapy of Hepatitis C Virus Infection Activates Dendritic Cells and Induces Antigen-Specific T Cell Responses. J Hepat. 2008;48:S236-S237, Abstract 635. [cited by applicant]
Chua et al., Comparison of lipopeptide-based immunocontraceptive vaccines containing different lipid groups. Vaccine. Jan. 2, 2007;25(1):92-101. [cited by applicant]
Chua et al., Dendritic cell acquisition of epitope cargo mediated by simple cationic peptide structures. Peptides. Jun. 2008;29(6):881-90. [cited by applicant]
Chua et al., Soluble proteins induce strong CD8+ T cell and antibody responses through electrostatic association with simple cationic or anionic lipopeptides that target TLR2. J Immunol. Aug. 15, 2011;187(4):1692-701. [cited by applicant]
Chua et al., The use of a TLR2 agonist-based adjuvant for enhancing effector and memory CD8 T-cell responses. Immunol Cell Biol. Apr. 2014;92(4):377-83. [cited by applicant]
Cleret et al., Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route. J Immunol. Jun. 15, 2007;178(12):7994-8001. [cited by applicant]
Cluff et al., Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious challenge. Infect Immun. May 2005;73(5):3044-52. [cited by applicant]
Deliyannis et al., Intranasal lipopeptide primes lung-resident memory CD8+ T cells for long-term pulmonary protection against influenza. Eur J Immunol. Mar. 2006;36(3):770-780. [cited by applicant]
Dikopoulos et al., Novel peptide-based vaccines efficiently prime murine “help”—independent CD8+ T cell responses in the liver. Hepatology. Aug. 2004;40(2):300-9. [cited by applicant]
Djupesland, Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res. Feb. 2013;3(1):42-62. [cited by applicant]
Duggan et al., Synergistic interactions of TLR2/6 and TLR9 induce a high level of resistance to lung infection in mice. J Immunol. May 15, 2011;186(10):5916-26. [cited by applicant]
Engering et al., The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells. Eur J Immunol. Sep. 1997;27(9):2417-25. [cited by applicant]
Farley et al., Lipopolysaccharide structure determines ionic and hydrophobic binding of a cationic antimicrobial neutrophil granule protein. Infect Immun. Jun. 1988;56(6):1589-92. [cited by applicant]
Feinberg et al., Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. Dec. 7, 2001;294(5549):2163-6. [cited by applicant]
Firat et al., H-2 class I knockout, HLA-A2.1-transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies. Eur J Immunol. Oct. 1999;29(10):3112-21. [cited by applicant]
Frison et al., Oligolysine-based oligosaccharide clusters: selective recognition and endocytosis by the mannose receptor and dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin. J Bio… [cited by applicant]
Fujimoto et al., Virus clearance through apoptosis-dependent phagocytosis of influenza A virus-infected cells by macrophages. J Virol. Apr. 2000;74(7):3399-403. [cited by applicant]
Fuse et al., Role of Toll-like receptor 2 in recognition of Legionella pneumophila in a murine pneumonia model. J Med Microbiol. Mar. 2007;56(Pt 3):305-312. [cited by applicant]
Futaki et al., Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem. Feb. 23, 2001;276(8):5836-40. [cited by applicant]
Gariepy et al., Vectorial delivery of macromolecules into cells using peptide-based vehicles. Trends Biotechnol. Jan. 2001;19(1):21-8. [cited by applicant]
Ghielmetti et al., Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses. Eur J Immunol. Aug. 2005;35(8):2434-42. [cited by applicant]
Gianfrani et al., Human memory CTL response specific for influenza A virus is broad and Multispecific. Hum Immunol. May 2000;61(5):438-52. [cited by applicant]
Gonzalez-Juarrero et al., Dynamics of macrophage cell populations during murine pulmonary tuberculosis. J Immunol. Sep. 15, 2003;171(6):3128-35. [cited by applicant]
Gotch et al., Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. Nature. Apr. 30, 1987-May 6;326(6116):881-2. [cited by applicant]
Gratton et al., Cell-permeable peptides improve cellular uptake and therapeutic gene delivery of replication-deficient viruses in cells and in vivo. Nat Med. Mar. 2003;9(3):357-62. [cited by applicant]
Gros et al., A non-covalent peptide-based strategy for protein and peptide nucleic acid transduction. Biochim Biophys Acta. Mar. 2006;1758(3):384-93. [cited by applicant]
Guo et al., The Novel Toll-Like Receptor 2 Agonist SUP3 Enhances Antigen Presentation and T Cell Activation by Dendritic Cells. Front Immunol. Feb. 21, 2017;8:158, 15 pages. [cited by applicant]
Hayashi et al., The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. Apr. 26, 2001;419(6832):1099-103. [cited by applicant]
Heil et al., pecies-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. Mar. 5, 2004;303(5663):1526-9. [cited by applicant]
Hemmi et al., A Toll-like receptor recognizes bacterial DNA. Nature. Dec. 7, 2000;408(6813):740-5. [cited by applicant]
Hemmi et al., Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. Feb. 2002;3(2):196-200. [cited by applicant]
Heuking et al., Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers. J Drug Target. Sep. 2009;17(8):662-70. [cited by applicant]
Hoffmann et al., Induction of tumor cytotoxicity in murine bone marrow-derived macrophages by two synthetic lipopeptide analogues. Biol Chem Hoppe Seyler. Jun. 1989;370(6):575-82. [cited by applicant]
Huynh et al., Novel toll-like receptor 2 ligands for targeted pancreatic cancer imaging and immunotherapy. J Med Chem. Nov. 26, 2012;55(22):9751-62. [cited by applicant]
Ismaili et al., Monophosphoryl lipid A activates both human dendritic cells and T cells. J Immunol. Jan. 15, 2002;168(2):926-32. [cited by applicant]
Iwabuchi et al., Effects of intranasal administration of Bifidobacterium longum BB536 on mucosal immune system in respiratory tract and influenza virus infection in mice. Milk Science. 2009;58(3):129-133. [cited by applicant]
Jackson et al., A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc Natl Acad Sci U S A. Oct. 26, 2004;101(43):… [cited by applicant]
Jameson et al., Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species. J Immunol. Jun. 15, 1999;162(12):7578-83. [cited by applicant]
Kang et al., Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity. Dec. 18, 2009;31(6):873-84. [cited by applicant]
Kawamura et al., Probing the impact of valency on the routing of arginine-rich peptides into eukaryotic cells. Biochemistry. Jan. 31, 2006;45(4):1116-27. [cited by applicant]
Kery et al., Ligand recognition by purified human mannose receptor. Arch Biochem Biophys. Oct. 1992;298(1):49-55. [cited by applicant]
Khong et al., Adjuvants for peptide-based cancer vaccines. J Immunother Cancer. Sep. 20, 2016;4:56, 11 pages. [cited by applicant]
Kutzler et al., Developing DNA vaccines that call to dendritic cells. J Clin Invest. Nov. 2004;114(9):1241-4. [cited by applicant]
Landsman et al., Lung macrophages serve as obligatory intermediate between blood monocytes and alveolar macrophages. J Immunol. Sep. 15, 2007;179(6):3488-94. [cited by applicant]
Lau et al., Lipid-containing mimetics of natural triggers of innate immunity as CTL-inducing influenza vaccines. Int Immunol. Dec. 2006;18(12):1801-13. [cited by applicant]
Licalsi et al., Dry powder inhalation as a potential delivery method for vaccines. Vaccine. Mar. 26, 1999;17(13-14):1796-803. [cited by applicant]
Martinez et al., Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection. PLoS Pathog. Mar. 12, 2010;6(3):e1000811, 13 pages. [cited by applicant]
Medical Dictionary, admixture. retrieved online at: https://medical-dictionary.thefreedictionary.com/admixture. 1 page, (2012). [cited by applicant]
Meng et al., Cellular recognition of tri-/di-palmitoylated peptides is independent from a domain encompassing the N-terminal seven leucine-rich repeat (LRR)/LRR-like motifs of TLR2. J Biol Chem. Oct. 10, 2003;278(41):39… [cited by applicant]
Metzger et al., Synthesis of novel immunologically active tripalmitoyl-S-glycerylcysteinyl lipopeptides as useful intermediates for immunogen preparations. Int J Pept Protein Res. Jan. 1991;37(1):46-57. [cited by applicant]
Morr et al., Differential recognition of structural details of bacterial lipopeptides by toll-like receptors. Eur J Immunol. Dec. 2002;32(12):3337-47. [cited by applicant]
Muhlradt et al., Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration. J Exp Med. Jun. 2, 1997;185(11):1951-8. [cited by applicant]
Muhlradt et al., Structure and specific activity of macrophage-stimulating lipopeptides from Mycoplasma hyorhinis. Infect Immun. Oct. 1998;66(10):4804-10. [cited by applicant]
Okusawa et al., Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6. Infect Immun. Mar. 2004;72(3):1657-65. [cited by applicant]
Olive et al., A lipid core peptide construct containing a conserved region determinant of the group A streptococcal M protein elicits heterologous opsonic antibodies. Infect Immun. May 2002;70(5):2734-8. [cited by applicant]
Olive et al., Enhanced protection against [cited by applicant]
Ozinsky et al., The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci U S A. Dec. 5, 2000;97(25):13766-71. [cited by applicant]
Palma et al., The toll-like receptor 2/6 ligand MALP-2 reduces the viability of [cited by applicant]
Pascolo et al., HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med. Jun. 16, 1997;18… [cited by applicant]
Pina et al., Shiga toxin B-subunit sequential binding to its natural receptor in lipid membranes. Biochim Biophys Acta. Mar. 2007;1768(3):628-36. [cited by applicant]
Poltorak et al., Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. Dec. 11, 1998;282(5396):2085-8. [cited by applicant]
Raffai et al., Binding of an antibody mimetic of the human low density lipoprotein receptor to apolipoprotein E is governed through electrostatic forces. Studies using site-directed mutagenesis and molecular modeling. J… [cited by applicant]
Raffai et al., Molecular characterization of two monoclonal antibodies specific for the LDL receptor-binding site of human apolipoprotein E. J Lipid Res. Sep. 1995;36(9):1905-18. [cited by applicant]
Reppe et al., Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia. Am J Respir Cell Mol Biol. Apr. 2009;40(4):474-81. [cited by applicant]
Riedl et al., Complexes of DNA vaccines with cationic, antigenic peptides are potent, polyvalent CD8(+) T-cell-stimulating immunogens. Methods Mol Med. 2006;127:159-69. [cited by applicant]
Rose et al., FSL-1, a bacterial-derived toll-like receptor 2/6 agonist, enhances resistance to experimental HSV-2 infection. Virol J. Nov. 10, 2009;6:195, 11 pages. [cited by applicant]
Rothbard et al., A sequence pattern common to T cell epitopes. EMBO J. Jan. 1988;7(1):93-100. [cited by applicant]
Schirmbeck et al., Antigenic epitopes fused to cationic peptide bound to oligonucleotides facilitate Toll-like receptor 9-dependent, but CD4+ T cell help-independent, priming of CD8+ T cells. J Immunol. Nov. 15, 2003;17… [cited by applicant]
Schwandner et al., Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem. Jun. 18, 1999;274(25):17406-9. [cited by applicant]
Seifert et al., Activation of superoxide formation and lysozyme release in human neutrophils by the synthetic lipopeptide Pam3Cys-Ser-(Lys)4. Involvement of guanine-nucleotide-binding proteins and synergism with chemota… [cited by applicant]
Sekiya et al., PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitude of ensuing antibody and CD8+ T cell responses. Biomaterials. Aug. 2017;137:61-72. [cited by applicant]
Sherman et al., Extracellular processing of peptide antigens that bind class I major histocompatibility molecules. J Exp Med. May 1, 1992;175(5): 1221-6. [cited by applicant]
Shiratsuchi et al., Elimination of influenza virus-infected cells by phagocytosis. Yakugaku Zasshi. Dec. 2006;126(12):1245-51. [cited by applicant]
Stambach et al., Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells. Glycobiology. May 2003;13(5):401-10. [cited by applicant]
Takeuchi et al., Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pa… [cited by applicant]
Takeuchi et al., Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. Jul. 1, 2002;169(1):10-4. [cited by applicant]
Tannock et al., Relative immunogenicity of the cold-adapted influenza virus A/Ann Arbor/6/60 (A/AA/6/60-ca), recombinants of A/AA/6/60-ca, and parental strains with similar surface antigens. Infect Immun. Feb. 1984;43(2… [cited by applicant]
Tansey et al., Synthesis and characterization of branched poly(L-glutamic acid) as a biodegradable drug carrier. J Control Release. Jan. 8, 2004;64(10):39-51. [cited by applicant]
Tighe et al., Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur J Immunol. Jul. 2000;30(7):1939-47. [cited by applicant]
Wallace et al., The cytotoxic T-cell response to herpes simplex virus type 1 infection of C57BL/6 mice is almost entirely directed against a single immunodominant determinant. J Virol. Sep. 1999;73(9):7619-26. [cited by applicant]
Wikipedia, TLR-2. Retrieved online at: https://en.wikipedia.org/wiki/TLR2. 14 pages, (2021). [cited by applicant]
Zeng et al., Characterisation of the antibody response to a totally synthetic immunocontraceptive peptide vaccine based on LHRH. Vaccine. Aug. 15, 2005;23(35):4427-35. [cited by applicant]
Zeng et al., Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines. J Immunol. Nov. 1, 2002;169(9):4905-12. [cited by applicant]
Zeng et al., Synthesis of a new template with a built-in adjuvant and its use in constructing peptide vaccine candidates through polyoxime chemistry. J Pept Sci. Jan. 1996-Feb.;2(1):66- 72. [cited by applicant]
Zeng et al., Totally synthetic lipid-containing polyoxime peptide constructs are potent immunogens. Vaccine. Jan. 6, 2000;18(11-12):1031-9. [cited by applicant]
Bartlett et al., Upper Airway TLR2 Immune Modulators Prime Broad Respiratory Immunity Against Rhinovirus and Influenza Infection and Inhibit Subsequent Lung Inflammation. American Journal of Respiratory and Critical Car… [cited by applicant]
Batzloff et al., Intranasal vaccination with a lipopeptide containing a conformationally constrained conserved minimal peptide, a universal T cell epitope, and a self-adjuvanting lipid protects mice from group A [cited by applicant]
Bogoch et al., Diagnosis of influenza from lower respiratory tract sampling after negative upper respiratory tract sampling. Virulence. Jan. 1, 2013;4(1):82-4. [cited by applicant]
Boiardi et al., Reducing transmission of SARS-COV-2 with intranasal prophylaxis. EBioMedicine. Jan. 2021;63:103170, 2 pages. [cited by applicant]
Chua et al., Enhancing immunogenicity of HCV DNA vaccines by targeted delivery to dendritic cells. Journal of Hepatology. 2008;48:S236, Abstract 634. [cited by applicant]
Duggan et al., Broad Resistance Against Pneumonia Induced By Synergistic TLR2/6 And TLR9 Stimulation. American Journal of Respiratory and Critical Care Medicine. 2010;181:Abstract A1799, 3 pages. [cited by applicant]
Ernest et al., The Toll-Like Receptor 2 agonist PEG-Pam2Cys as an immunochemoprophylactic and Immunochemotherapeutic against the liver and transmission stages of malaria parasites. Int J Parasitol Drugs Drug Resist. Dec… [cited by applicant]
Feng et al., A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages. Nat Commun. May 22, 2019;10(1):2272, 14 pages. [cited by applicant]
Jaiswal et al., Innate Immune Response Modulation and Resistance to SARS-COV-2 infection: A Prospective Comparative Cohort Study in High Risk Healthcare Workers. medRxiv. Retrieved online at: https://www.medrxiv.org/con… [cited by applicant]
Proud et al., Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding In a SARS-COV-2 challenge ferret model. EBioMedicine. Jan. 2021;63:103153, 9 pages. [cited by applicant]
Rathananand et al., Preparation of mucoadhesive microspheres for nasal delivery by spray drying. Indian J Pharm Sci. 2007;69(5):651-657. [cited by applicant]
Riedl et al., Peptides containing antigenic and cationic domains have enhanced, multivalent immunogenicity when bound to DNA vaccines. J Mol Med (Berl). Feb. 2004;82(2):144-52. [cited by applicant]
Sharma et al., Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs. Mol Immunol. Apr. 2020;120:52-60. [cited by applicant]
Wali et al., Immune Modulation to Improve Survival of Viral Pneumonia in Mice. Am J Respir Cell Mol Biol. Dec. 2020;63(6):758-766. [cited by applicant]
You et al., Induced Resistance to Influenza A Infection By Cooperative TLR2/6 and TLR9 Activation. American Journal of Respiratory and Critical Care Medicine. 2010;181:Abstract A2629, 3 pages. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/AU2020/050660, dated Sep. 3, 2020, 10 pages. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/AU2021/050506, dated Jul. 13, 2021, 14 pages. [cited by applicant]
Agnihotri et al., Structure-activity relationships in toll-like receptor 2-agonists leading to simplified monoacyl lipopeptides. J Med Chem. Dec. 8, 2011;54(23):8148-60. [cited by applicant]
Li et al., Relationship of Toll like receptor-2 and some virus infectious diseases. Chemistry of Life. 2009;4:568-571. [cited by applicant]
Lu et al., Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines. J Med Chem. Mar. 12, 2020;63(5):2282-2291. [cited by applicant]
Sasidharan Nair et al., Immune checkpoint inhibitors in cancer therapy: a focus on T-regulatory cells. Immunol Cell Biol. Jan. 2018; 96(1):21-33. [cited by applicant]
Wang et al., Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice. Proc Natl Acad Sci U S A. Sep. 11, 2018;115(37):E8698-E8706. [cited by applicant]
Alfredo et al., Pathophysiology of viral-induced exacerbations of COPD. International Journal of COPD. 2007;2 (4):477-483. [cited by applicant]
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