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Treatment of respiratory infection with a tlr2 agonist

An agonist, respiratory technology, applied in the field of prevention or treatment of respiratory diseases, can solve the problems of morbidity, mortality and high burden of health care costs

Pending Publication Date: 2019-11-15
艾娜呼吸私人有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Rhinovirus is the most common viral infection associated with asthma exacerbations, and thus poses the greatest burden in terms of morbidity, mortality, and health care costs

Method used

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  • Treatment of respiratory infection with a tlr2 agonist
  • Treatment of respiratory infection with a tlr2 agonist
  • Treatment of respiratory infection with a tlr2 agonist

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0551] Inhibition of rhinovirus infection in a mouse model

[0552] This study was performed to determine whether activation of the innate immune system by TLR2 agonists reduces viral load and virus-induced inflammation during rhinovirus infection in mice.

[0553] animal

[0554] Female 6-8 week old BALB / c mice were used for all studies. Each group contained 5 mice. Following treatment or challenge procedures, mice were monitored daily for body weight changes and behavioral or physical changes, as specified in the Animal Ethics Approval for Project A-2016-605. At the time of sample collection, all mice were sacrificed by intraperitoneal administration of sodium pentobarbital. All mice were housed in individually ventilated cages at the HMRI Bioresources facility with no more than four mice per cage. Observe mice daily and maintain a health checklist from the beginning of each study.

[0555] Mouse Surgery and Treatment

[0556] Rhinovirus serotype 1B was initially purif...

example 2

[0613] Protective and therapeutic effects of TLR2 agonists against rhinovirus infection in primary asthmatic bronchial epithelial cells

[0614] This study was performed to determine whether TLR2 agonist treatment or prevention reduces viral load and virus-induced immune mediators in air-liquid interface (ALI)-differentiated human asthmatic bronchial epithelial cells during rhinovirus infection.

[0615] Air-liquid interface differentiation of primary bronchial epithelial cells from COPD patients

[0616] Primary bronchial epithelial cells obtained from 6 patients with mild to moderate persistent asthma ( Figure 12 a) Grown to confluence (passage 3) in T75 flasks and differentiated at the air-liquid interface (ALI). Briefly, primary cells were grown in submerged monolayer cultures in complete BEGM (Lonza) with growth factor supplements and then in 12-well plates with ALI-initial medium Seed until confluence (at least three days in both top and bottom compartments) with 2×10 ...

example 3

[0656] Synthesis of INNA-003 and INNA-006

[0657] Synthesis of INNA-003 and INNA-006

[0658] Reagents: Solid support: TentaGel S RAM resin (substitution factor 0.24 mmol / g; Rapp Polymere, Tübingen, Germany). Amino acid derivatives: Fmoc-Gly-OH, Fmoc-Ser(tBu)-OH, Fmoc-homo-Ser(tBu)-OH, Fmoc-homo-Ser(tBu)-OH from Merck, Darmstadt, Germany -Ser(PO(OBzl)OH)-OH, Fmoc-Thr(tBu)-OH, Fmoc-NH-(PEG) 3 -COOH, Fmoc-NH-(PEG) 5 -COOH, Fmoc-NH-(PEG) 11 -COOH, Fmoc-NH-(PEG) 27 -COOH.

[0659]

[0660] NOTE: Merck Cat. No. 851024 was used to generate the following as "INNA-003" (also referred to herein as Pam2Cys-SS-PEG) and "INNA-006" (also referred to herein as Pam2Cys-S-PEG) PEG) structure.

[0661] INNA-003:

[0662]

[0663] INNA-006 or Compound (1):

[0664]

[0665] Acylation: Use 4-fold molar excess of Fmoc amino acid, O-benzotriazole-N,N,N',N'-tetramethyl-uronium hexafluorophosphate (HBTU) and 6-fold molar excess in all acylation steps Molar excess of diisoprop...

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Abstract

The present invention relates to methods, compositions and kits for the treatment or prevention of respiratory conditions. In particular, the methods, compositions and kits are particularly useful, but not limited to, the prevention and / or treatment of rhinovirus infection and the prevention and / or treatment of asthma exacerbation. The invention provides a method inhibiting a rhinovirus infectionin a subject comprising administering a composition consisting of a compound comprising a TLR2 agonist and a pharmaceutically acceptable carrier.

Description

[0001] Cross References to Prior Applications [0002] This application claims priority from Australian provisional applications AU 2017901180, AU 2017905124, AU 2017905128 and AU 2018900409, the entire contents of each provisional application being incorporated herein by reference in its entirety. technical field [0003] The present invention relates to methods, compounds, compositions and kits for preventing or treating respiratory disorders. In particular, these methods, compounds, compositions and kits are particularly useful for, but not limited to, the prevention and / or treatment of rhinovirus infection and the prevention and / or treatment of respiratory exacerbations. Background technique [0004] Respiratory tract infections are the most common cause of human illness worldwide and are usually caused by viruses. Rhinoviruses (RV) are one of the most common types of viruses to infect humans and are known to cause the common cold. Unlike sporadic and seasonal influenz...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/10A61K39/39A61P31/16A61P11/00
CPCA61K38/10A61K39/39A61P11/00A61P31/16A61K39/12A61K2039/543A61K2039/55516A61K2039/58C12N2770/32734A61K9/0043A61K9/0075A61K31/20A61K31/23A61K31/573A61K47/42
Inventor N·巴特利特J·吉尔金D·杰克逊W·曾I·霍尔姆斯C·德迈松
Owner 艾娜呼吸私人有限公司
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