GUT FLORA-DERIVED EXTRACELLULAR VESICLES, AND METHOD FOR SEARCHING FOR A DISEASE MODEL, VACCINE, AND CANDIDATE DRUG AND FOR DIAGNOSIS USING THE SAME

• US 20120222142A1
• Filed: 07/20/2010
• Published: 08/30/2012
• Est. Priority Date: 09/01/2009
• Status: Active Grant

• Current Assignee: Aeon Medix Inc.
• Original Assignee: Aeon Medix Inc.
• Inventors: Kim, Yoon Keun, Gho, Yong Song, Hong, Bok Sil, Kim, Jung Wook, Park, Kyoung Su, Kim, Ji Hyun, Kim, You Sun, Lee, Won Hee, Kim, Dae-Kyum
• Granted Patent: US 9,201,072 B2
• Time in Patent Office: Days
• US Class Current: 800/10
• CPC Class Codes: A01K 2207/20 Animals treated with compounds which are neither proteins nor nucleic acids
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0337 Animal models for infectious diseases
• CPC Class Codes: A01K 2267/035 Animal model for multifactorial diseases
• CPC Class Codes: A01K 67/027 New or modified breeds of vertebrates
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C12Q 1/025 : for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics antimicrobial activity C12Q1/18
• CPC Class Codes: C12Q 1/37 : involving peptidase or proteinase
• CPC Class Codes: G01N 33/56916 : Enterobacteria, e.g. shigella, salmonella, klebsiella, serratia

Abstract

The present application relates to a composition including gut flora-derived extracellular vesicles, and to an animal disease model using same. In addition, the present application relates to a method for using the gut flora-derived extracellular vesicles to efficiently search for a candidate drug which may prevent or treat diseases that occur due to gut flora-derived extracellular vesicles, and to a vaccine which can efficiently prevent or treat infections caused by gut flora or diseases that occur due to gut flora-derived extracellular vesicles. Further, the development of diagnostic technology to discover, using the gut flora-derived extracellular vesicles of the present application, the etiology of diseases that occur due to gut flora-derived extracellular vesicles, can be achieved.

Claims

1. A composition, comprising extracellular vesicles derived from gut flora.

2. The composition of claim 1, wherein the gut flora comprises Gram-negative bacteria.

5. The composition of claim 1, wherein the extracellular vesicles are those that are spontaneously or artificially secreted.

7. The composition of claim 1, wherein the extracellular vesicles are isolated from at least one selected from the group consisting of mammal feces, mammal large intestinal fluid, mammal gastric fluid, mammal small intestinal fluid, and mammal oral fluid.

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12. A disease model, established by administering gut flora-derived extracellular vesicles to an animal.

24. The disease model of claim 12, wherein the extracellular vesicles are administered intraperitoneally, intravenously, orally, rectally, intranasally, or intratracheally.

30. The disease model of claim 12, wherein the disease is selected from the group consisting of sepsis, arteriosclerosis, acute coronary syndrome, stroke, emphysema, acute respiratory distress syndrome, osteoporosis, hypertension, obesity, diabetes, arthritis, and a cerebral disease.

31. The disease model of claim 12, wherein the disease is selected from the group consisting of mouth ulcer, oral cancer, esophagitis, esophageal cancer, gastritis, duodenal ulcer, stomach cancer, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, cholangitis, cholecystitis, pancreatitis, cholangiocarcinoma, and pancreatic cancer.

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32. A method for screening a drug candidate preventive or therapeutic of a disease, using gut flora-derived extracellular vesicles.

45. The method of claim 32, comprising treating cells with the gut flora-derived extracellular vesicles.

57. The method of claim 32, comprising administering the gut flora-derived extracellular vesicles in combination with a drug candidate, and quantitatively analyzing an inflammation-related mediator.

59. The method of claim 32, comprising administering the gut flora-derived extracellular vesicles in combination with a drug candidate and analyzing an inflammation-related signal transduction pathway.

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60. A vaccine for preventing or treating a gut flora-derived extracellular vesicle-caused disease, comprising gut flora-derived extracellular vesicles.

61. The vaccine of claim 60, wherein the disease is selected from the group consisting of sepsis, arteriosclerosis, acute coronary syndrome, stroke, emphysema, acute respiratory distress syndrome, osteoporosis, hypertension, obesity, diabetes, arthritis, and a cerebral disease.

62. The vaccine of claim 60, wherein the disease is selected from the group consisting of mouth ulcer, oral cancer, esophagitis, esophageal cancer, gastritis, duodenal ulcer, stomach cancer, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, cholangitis, cholecystitis, pancreatitis, cholangiocarcinoma, and pancreatic cancer.

66. The vaccine of claim 60, wherein the vaccine is modified using transformed bacteria or by treating bacteria with a compound.

71. The vaccine of claim 60, wherein the vaccine is intended to be used in combination with a drug so as to enhance its efficacy or decrease its side effect.

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69. The vaccine of claim 65, wherein the vaccine is modified by treating the extracellular vesicles with a compound.

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73. A vaccine for preventing a gut-flora infection, comprising gut flora-derived extracellular vesicles.

75. The vaccine of claim 73, being derived from Gram-negative bacteria, which is selected from the group consisting of E. coli, Klebsiella spp., Pseudomonas spp. and Bacteoides spp.

78. The vaccine of claim 73, wherein the vaccine is modified by using transformed bacteria or by treating bacteria with a compound.

83. The vaccine of claim 73, wherein the vaccine is intended to be used in combination with a drug so as to enhance its efficacy or decrease its side effect.

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85. A method for preventing or treating a disease, comprising administering gut flora-derived extracellular vesicles at a sublethal dose to a mammal.

86. The method of claim 85, wherein the gut flora is Gram-negative bacteria, which is selected from the group consisting of E. coli, Klebsiella spp. Pseudomonas spp. and Bacteroides spp.

97. The method of claim 85, wherein the extracellular vesicles are modified using transformed bacteria or by treating bacteria with a compound.

102. The method of claim 85, wherein the extracellular vesicles are administered in combination with a drug so as to enhance their efficacy or decrease there side effect.

105. The method of claim 85, wherein the disease is selected from the group consisting of sepsis, arteriosclerosis, acute coronary syndrome, stroke, emphysema, acute respiratory distress syndrome, osteoporosis, hypertension, obesity, diabetes, arthritis, a cerebral disease, mouth ulcer, oral cancer, esophagitis, esophageal cancer, gastritis, duodenal ulcer, stomach cancer, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, cholangitis, cholecystitis, pancreatitis, cholangiocarcinoma, pancreatic cancer, peritonitis, sepsis, pneumonia, urinary tract infection, bone infection, and central nervous system infection.

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116. A pharmaceutical composition for preventing or treating a disease, comprising a substance selected by a screening method using gut flora-derived extracellular vesicles.

117. The pharmaceutical composition of claim 116, wherein the substance is a kinase inhibitor.

124. The pharmaceutical composition of claim 116, wherein the disease is selected from the group consisting of sepsis, arteriosclerosis, acute coronary syndrome, stroke, emphysema, acute respiratory distress syndrome, osteoporosis, hypertension, obesity, diabetes, arthritis, a cerebral disease, mouth ulcer, oral cancer, esophagitis, esophageal cancer, gastritis, duodenal ulcer, stomach cancer, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, cholangitis, cholecystitis, pancreatitis, cholangiocarcinoma, and pancreatic cancer.

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126. A method for diagnosis of a pathogenic factor through application of gut flora-derived extracellular vesicles.

129. The method of claim 126, wherein the disease is selected from the group consisting of sepsis, arteriosclerosis, acute coronary syndrome, stroke, emphysema, acute respiratory distress syndrome, osteoporosis, hypertension, obesity, diabetes, arthritis, a cerebral disease, mouth ulcer, oral cancer, esophagitis, esophageal cancer, gastritis, duodenal ulcer, stomach cancer, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, cholangitis, cholecystitis, pancreatitis, cholangiocarcinoma, and pancreatic cancer.

131. The method of claim 126, wherein the application comprises base sequencing a genetic material contained within the gut flora-derived extracellular vesicles.

133. The method of claim 126, wherein the application comprises quantitatively analyzing a protein contained within the gut flora-derived extracellular vesicles.

134. The method of claim 126, wherein the application comprises analyzing an immune response to gut flora-derived extracellular vesicles.

136. The method of claim 126, wherein the diagnosis is performed with at least one which is selected from the group consisting of feces, blood, urine, ascites, pleural fluid, synovial fluid, and cerebrospinal fluid.

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