CA2394856A1 - Enzyme treatment for infection - Google Patents
Enzyme treatment for infection Download PDFInfo
- Publication number
- CA2394856A1 CA2394856A1 CA002394856A CA2394856A CA2394856A1 CA 2394856 A1 CA2394856 A1 CA 2394856A1 CA 002394856 A CA002394856 A CA 002394856A CA 2394856 A CA2394856 A CA 2394856A CA 2394856 A1 CA2394856 A1 CA 2394856A1
- Authority
- CA
- Canada
- Prior art keywords
- enzyme
- composition according
- infection
- carbohydrate
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000004190 Enzymes Human genes 0.000 title claims abstract 42
- 108090000790 Enzymes Proteins 0.000 title claims abstract 42
- 208000015181 infectious disease Diseases 0.000 title claims abstract 18
- 150000001720 carbohydrates Chemical class 0.000 claims abstract 19
- 230000000694 effects Effects 0.000 claims abstract 16
- 102000018697 Membrane Proteins Human genes 0.000 claims abstract 15
- 108010052285 Membrane Proteins Proteins 0.000 claims abstract 15
- 230000002924 anti-infective effect Effects 0.000 claims abstract 8
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract 7
- 241001465754 Metazoa Species 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims 49
- 229940088598 enzyme Drugs 0.000 claims 39
- 238000000034 method Methods 0.000 claims 33
- 108010064785 Phospholipases Proteins 0.000 claims 16
- 102000015439 Phospholipases Human genes 0.000 claims 16
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 claims 12
- 108090000371 Esterases Proteins 0.000 claims 8
- 241000193755 Bacillus cereus Species 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 6
- 244000079416 protozoan pathogen Species 0.000 claims 6
- 102100032487 Beta-mannosidase Human genes 0.000 claims 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 4
- 102000006486 Phosphoinositide Phospholipase C Human genes 0.000 claims 4
- 108010044302 Phosphoinositide phospholipase C Proteins 0.000 claims 4
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 claims 4
- 102000011971 Sphingomyelin Phosphodiesterase Human genes 0.000 claims 4
- 244000052616 bacterial pathogen Species 0.000 claims 4
- 108010055059 beta-Mannosidase Proteins 0.000 claims 4
- 108010089934 carbohydrase Proteins 0.000 claims 4
- 235000013339 cereals Nutrition 0.000 claims 4
- -1 cerebrosidases Proteins 0.000 claims 4
- 229940059442 hemicellulase Drugs 0.000 claims 4
- 108010002430 hemicellulase Proteins 0.000 claims 4
- 239000000463 material Substances 0.000 claims 4
- 239000006186 oral dosage form Substances 0.000 claims 4
- 239000003755 preservative agent Substances 0.000 claims 4
- 230000002335 preservative effect Effects 0.000 claims 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims 4
- 102000004169 proteins and genes Human genes 0.000 claims 4
- 108090000623 proteins and genes Proteins 0.000 claims 4
- 239000003381 stabilizer Substances 0.000 claims 4
- 241000194107 Bacillus megaterium Species 0.000 claims 3
- 108020004511 Recombinant DNA Proteins 0.000 claims 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims 2
- DBTMGCOVALSLOR-UHFFFAOYSA-N 32-alpha-galactosyl-3-alpha-galactosyl-galactose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(OC2C(C(CO)OC(O)C2O)O)OC(CO)C1O DBTMGCOVALSLOR-UHFFFAOYSA-N 0.000 claims 2
- 235000007319 Avena orientalis Nutrition 0.000 claims 2
- 244000075850 Avena orientalis Species 0.000 claims 2
- 241000193422 Bacillus lentus Species 0.000 claims 2
- 241000193403 Clostridium Species 0.000 claims 2
- 241000223935 Cryptosporidium Species 0.000 claims 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 2
- RXVWSYJTUUKTEA-UHFFFAOYSA-N D-maltotriose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 RXVWSYJTUUKTEA-UHFFFAOYSA-N 0.000 claims 2
- 241000223924 Eimeria Species 0.000 claims 2
- 229930091371 Fructose Natural products 0.000 claims 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims 2
- 239000005715 Fructose Substances 0.000 claims 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 2
- 240000005979 Hordeum vulgare Species 0.000 claims 2
- 235000007340 Hordeum vulgare Nutrition 0.000 claims 2
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims 2
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims 2
- 244000046052 Phaseolus vulgaris Species 0.000 claims 2
- 235000010627 Phaseolus vulgaris Nutrition 0.000 claims 2
- 240000004713 Pisum sativum Species 0.000 claims 2
- 235000010582 Pisum sativum Nutrition 0.000 claims 2
- 239000004283 Sodium sorbate Substances 0.000 claims 2
- 240000006394 Sorghum bicolor Species 0.000 claims 2
- 235000011684 Sorghum saccharatum Nutrition 0.000 claims 2
- 101100041681 Takifugu rubripes sand gene Proteins 0.000 claims 2
- 241000209140 Triticum Species 0.000 claims 2
- 235000021307 Triticum Nutrition 0.000 claims 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N Xylose Natural products O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims 2
- 240000008042 Zea mays Species 0.000 claims 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims 2
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 2
- 235000005822 corn Nutrition 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 244000053095 fungal pathogen Species 0.000 claims 2
- 239000007903 gelatin capsule Substances 0.000 claims 2
- 239000008103 glucose Substances 0.000 claims 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 2
- 239000012669 liquid formulation Substances 0.000 claims 2
- FYGDTMLNYKFZSV-UHFFFAOYSA-N mannotriose Natural products OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(OC2C(OC(O)C(O)C2O)CO)C(O)C1O FYGDTMLNYKFZSV-UHFFFAOYSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000011707 mineral Substances 0.000 claims 2
- 235000010241 potassium sorbate Nutrition 0.000 claims 2
- 239000004302 potassium sorbate Substances 0.000 claims 2
- 229940069338 potassium sorbate Drugs 0.000 claims 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims 2
- 229960003415 propylparaben Drugs 0.000 claims 2
- 239000004576 sand Substances 0.000 claims 2
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 claims 2
- 235000019250 sodium sorbate Nutrition 0.000 claims 2
- 239000000600 sorbitol Substances 0.000 claims 2
- 239000011782 vitamin Substances 0.000 claims 2
- 229940088594 vitamin Drugs 0.000 claims 2
- 229930003231 vitamin Natural products 0.000 claims 2
- 235000013343 vitamin Nutrition 0.000 claims 2
- 125000000969 xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 claims 2
- 244000000190 yeast pathogen Species 0.000 claims 2
- FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H](CO)O[C@@H](O[C@@H]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 1
- 235000014347 soups Nutrition 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/189—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/04—Phosphoric diester hydrolases (3.1.4)
- C12Y301/04011—Phosphoinositide phospholipase C (3.1.4.11)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01078—Mannan endo-1,4-beta-mannosidase (3.2.1.78), i.e. endo-beta-mannanase
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- Animal Husbandry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fodder In General (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Enzymes of a particular class, characterized by the ability to cleave a linkage that effects release of a cell-surface protein or carbohydrate, which does not contain an anti-infection agent, display significant anti-infectious activity. Upon oral administration, these enzymes are effective, for example, in the treatment of digestive tract infections in humans and in animals. In the latter, there are benefits of significantly improved growth rate, feed efficiency, and overall health.
Claims (76)
1. A composition comprising (I) an enzyme that cleaves a linkage that effects release of a cell-surface protein or carbohydrate, said enzyme being other than an endo-1,4-.beta.-D-mannanase, and (ii) a physiologically acceptable carrier for said enzyme, wherein said composition is in a form suitable for oral administration.
2. The composition according to claim 1, wherein said composition is a feed.
3. The composition according to claims 1 or 2, wherein said composition contains no anti-infection agent other than said enzyme.
4. The composition according to any one of claims 1-3, wherein said enzyme cleaves a linkage that effects release of a cell-surface protein.
5. The composition according to claim 1, wherein said enzyme is selected from the group consisting of esterases, cerebrosidases, and carbohydrases that cleave a linkage that effects release of a cell-surface protein or carbohydrate.
6. The composition according to claim 5, wherein said esterases are selected from the group consisting of sphingomyelinases and phospholipases.
7. The composition according to claim 6, wherein said phospholipase is a type C
or type D phospholipase.
or type D phospholipase.
8. The composition according to claim 6, wherein said phospholipase is a phosphatidylinositol-specific phospholipase C.
9. The composition according to anyone of claims 1-8, wherein said composition further comprises a stabilizer, a carbohydrate carrier or a preservative.
10. The composition according to claim 9, wherein said stabilizer is a buffer, a carbohydrate or a glycol.
11. The composition according to claim 9, wherein said carbohydrate carrier is selected from the group consisting of xylose, fructose, glucose, sorbitol, and maltotriose.
12. The composition according to claim 9, wherein said preservative is selected from the group consisting of propylparaben, sodium sorbate, potassium sorbate, and ascorbyl palmitate.
13. The composition according to anyone of claims 1-12, wherein said carrier is a foodstuff into which said enzyme is incorporated.
14. The composition according to anyone of claims 1-12, wherein said foodstuff is an animal feed comprised of grain material, a source of protein, vitamins, amino acids, and minerals.
15. The composition according to claim 14, wherein said grain material is corn, sorghum, wheat, barley or oats.
16. The composition according to claim 14, wherein the source of protein is beans or peas.
17. The composition according to anyone of claims 1-12, wherein said composition is in a solid or a liquid formulation.
18. The composition according to anyone of claims 1-12, wherein said enzyme is contained in a tablet or a gelatin capsule shell.
19. The composition according to claim 1, wherein said enzyme is prepared from a Bacillus cereus strain.
20. The composition according to claim 19, wherein said Bacillus cereus strain is ATCC 7004 or ATCC 6464.
21. The composition according to claim 1, wherein said enzyme is obtained by expression of a recombinant DNA in a host organism.
22. The composition according to claim 21, wherein said host organism is from a Bacillus megaterium strain.
23. The composition according to claim 1, wherein said enzyme is present at 200 IU/Kg -4000 UI/Kg feed.
24. A method of treating or ameliorating the risk of a digestive tract infection, comprising orally administering, to a subject suffering from or at risk for suffering said infection, an effective amount of enzyme that cleaves a linkage that effects release of a cell-surface protein or carbohydrate, said enzyme is other than an endo-1,4-.beta.-D-mannanase.
25. The method according to claim 24, wherein said enzyme cleaves a linkage that effects release of a cell-surface protein.
26. The method according to claim 24, wherein said method does not include administering an anti-infection agent other than said enzyme.
27. The method according to claim 24, wherein said infection is caused by a protozoan, bacterial, yeast or fungal pathogen.
28. The method according to claim 27, wherein said infection is caused by a protozoan pathogen of the genus Eimeria.
29. The method according to claim 27, wherein said infection is caused by a protozoan pathogen of the genus Cryptosporidium
30. The method according to claim 27, wherein said infection is caused by a bacterial pathogen of the genus Clostridium.
31. The method according to claim 24, comprising administering orally, to said subject, an extracellular enzyme preparation from a Bacillus cereus strain.
32. The method according to claim 31, wherein said Bacillus cereus strain is ATCC 7004 ar ATCC 6464.
33. The method according to claim 24, wherein said enzyme is obtained by expression of a recombinant DNA in a host organism.
34. The method according to claim 33, wherein said host organism is from a Bacillus megaterium strain.
35. The method according to claims 24, wherein said enzyme is selected from the group consisting of esterases, cerebrosidases, and carbohydrases that cleave a linkage that effects release of a cell-surface protein or carbohydrate.
36. The method according to claim 35, wherein said esterases are selected from the group consisting of sphingomyelinases and phospholipases.
37. The method according to claim 36, wherein said phospholipase is a type C
or type D phospholipase.
or type D phospholipase.
38. The method according to claim 36, wherein said phospholipase is a phosphatidylinositol-specific phospholipase C.
39. A composition comprising (i) an enzyme that cleaves a linkage that effects release of a cell-surface protein or carbohydrate and (ii) a physiologically acceptable carrier for said enzyme, wherein said composition is in a form suitable for oral administration and does not contain an anti-infection agent other than said enzyme.
40. The composition according to claim 39, wherein sand carrier is a foodstuff into which said enzyme is incorporated.
41. The composition according to claim 40, wherein said foodstuff is an animal feed comprised of grain material, a source of protein, vitamins, amino acids, and minerals.
42. The composition according to claim 41, wherein said grain material is corn, sorghum, wheat, barley or oats.
43. The composition according to claim 41, wherein said some of protein is beans or peas.
44. The composition according to claim 39, wherein said composition is in a soled or a liquid formulation.
45. The composition according to claim 39, wherein said enzyme is contained in a tablet or gelatin capsule shell.
46. The composition according to claim 39, wherein said enzyme is a hemicellulase.
47. The composition according to claim 46, wherein said hemicellulase is a mannanase.
48. The composition according to claim 47, wherein said mannanase is the endo-1,4-B-D-mamnanase produced by Bacillus lentus designated as ATCC 55045.
49. The composition according to claim 39, wherein said enzyme is selected from the group consisting of esterases, cerebrosidases, and carbohydrases that cleave a linkage that effects release of a cell-surface protein or carbohydrate.
50. The composition according to claim 49, wherein said esterases are selected from the group consisting of sphingomyelinases and phospholipases.
51. The composition according to claim 50, wherein said phospholipase is a type C or a type D phospholipase.
52. The composition according to claim 50, wherein said phospholipase is a phosphatidylinositol-specific phospholipase C.
53. The composition according to claim 39, wherein said composition further comprises a stabilizer, a carbohydrate carrier or a preservative.
54. The composition according to claim 53, wherein said stabilizer is a buffer, a carbohydrate or a glycol
55. The composition according to claim 53, wherein said carbohydrate carrier is selected from the group consisting of xylose, fructose, glucose, sorbitol and maltotriose.
56. The composition according to claim 53, wherein said preservative is selected from the group consisting of propylparaben, sodium sorbate, potassium sorbate, and ascorbyl palmitate.
57. A, method of treating or ameliorating the risk of a digestive tract infection, comprising orally administering, to a subject suffering from or at risk for suffering said infection, an effective amount of enzyme that cleaves a linkage that effects release of a cell-surface protein or carbohydrate, wherein said method does not include administering, with said enzyme, an antimicrobially effective amount of another anti-infection agent.
58. The method according to claim 57, wherein said infection is caused by a protozoan, bacterial, yeast, or fungal pathogen.
59. The method according to claim 58, wherein said infection is caused by a protozoan pathogen of the genus Eimeria.
60. The method according to claim 58, wherein said infection is caused by a protozoan pathogen of the genus Cryptosporidium.
61. The method according to claim 58, wherein said infection is caused by a bacterial pathogen of the genus Clostridium.
62. The method according to claim 57, comprising administering orally, to said subject, an extracellular enzyme preparation from a Bacillus cereus strain.
63. The method according to claim 62, wherein said Bacillus cereus strain is ATCC 7004 or ATCC 6464.
64. The method according to claim 57, wherein sand enzyme is obtained by expression of a recombinant DNA in a host organism.
65. The method according to claim 64, wherein said host organism is from a Bacillus megaterium strain.
66. The method according to claim 57, wherein said enzyme is a hemicellulase.
67. The method according to claim 66, wherein said hemicellulase is a mannanase.
68. The method according to claim 67, wherein said mannanase is the endo-1,4-B-D-mannanase produced by Bacillus lentus designated as ATCC 55045.
69. The method according to claim 57, wherein said enzyme is selected from the soup consisting of esterases, cerebrosidases, and carbohydrases that cleave a linkage that effects release of a cell-surface protein or carbohydrate.
70. The method according to claim 69, wherein said esterases are selected from the group consisting of sphingomyelinases and phospholipases.
71. The method according to claim 70, wherein said phospholipase is a type C
or type D phospholipase.
or type D phospholipase.
72. The method according to Claim 70, wherein said phospholipase is a phosphatidylinositol-specific phospholipase C.
73. Use of an oral dosage form of an enzyme that cleaves a linkage that effects the release of a cell-surface protein or carbohydrate, wherein said enzyme is other than an endo-1,4-.beta.-D-mannanase, for treating or ameliorating the risk of a digestive tract infection.
74. Use of an enzyme that cleaves a linkage that effects the release of a cell-surface protein or carbohydrate, wherein said enzyme is other than an endo-1,4-.beta.-D-mannanase, for the manufacture of an oral dosage form of a medicament, for treating or ameliorating the risk of a digestive tract infection.
75. Use of an oral dosage form of an enzyme that cleaves a linkage that effects the release of a cell-surface protein or carbohydrate, wherein said enzyme is not administered with an antimicrobially effective amount of another anti-infection agent, for treating or ameliorating the risk of a digestive tract infection.
76. Use of an enzyme that cleaves a linkage that effects the release of a cell-surface protein or carbohydrate, wherein said enzyme is not administered with an antimicrobially effective amount of another anti-infection agent, for the manufacture of an oral dosage form of a medicament, for treating or ameliorating the risk of a digestive tract infection.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16993599P | 1999-12-10 | 1999-12-10 | |
| US60/169,935 | 1999-12-10 | ||
| PCT/US2000/033466 WO2001041785A2 (en) | 1999-12-10 | 2000-12-08 | Enzyme treatment for infection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2394856A1 true CA2394856A1 (en) | 2001-06-14 |
| CA2394856C CA2394856C (en) | 2011-05-10 |
Family
ID=22617824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2394856A Expired - Lifetime CA2394856C (en) | 1999-12-10 | 2000-12-08 | Enzyme treatment for infection |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US6780628B2 (en) |
| EP (1) | EP1239872B1 (en) |
| JP (1) | JP4871473B2 (en) |
| KR (1) | KR100639746B1 (en) |
| CN (3) | CN101327320A (en) |
| AR (2) | AR026764A1 (en) |
| AT (1) | ATE481981T1 (en) |
| AU (1) | AU782831B2 (en) |
| BR (1) | BRPI0016231B8 (en) |
| CA (1) | CA2394856C (en) |
| CL (1) | CL2008000057A1 (en) |
| CO (1) | CO5280226A1 (en) |
| CR (1) | CR6674A (en) |
| CZ (1) | CZ304925B6 (en) |
| DE (1) | DE60045010D1 (en) |
| DK (1) | DK1239872T3 (en) |
| ES (1) | ES2353371T3 (en) |
| HU (1) | HU230301B1 (en) |
| IL (2) | IL150048A0 (en) |
| IN (1) | IN247731B (en) |
| MX (1) | MX264033B (en) |
| MY (1) | MY124714A (en) |
| NZ (1) | NZ519404A (en) |
| PH (1) | PH12000003381B1 (en) |
| PL (1) | PL203054B1 (en) |
| PT (1) | PT1239872E (en) |
| RU (1) | RU2272419C2 (en) |
| SK (1) | SK287956B6 (en) |
| TW (1) | TWI255189B (en) |
| UA (1) | UA78486C2 (en) |
| WO (1) | WO2001041785A2 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008066403A1 (en) | 2006-11-28 | 2008-06-05 | Dmitry Dmitrievich Genkin | Method for treating human diseases associated with an increased deoxyribonucleic acid content in extracellular spaces of tissues and a medicinal preparation for carrying out said method |
| US8388951B2 (en) | 2003-07-14 | 2013-03-05 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
| US8431123B2 (en) | 2003-07-14 | 2013-04-30 | Cls Therapeutics Limited | Method for treating systemic bacterial, fungal and protozoan infection |
| US8710012B2 (en) | 2003-07-14 | 2014-04-29 | Cls Therapeutics Limited | Method for treating oncological diseases |
| US8916151B2 (en) | 2005-04-25 | 2014-12-23 | Cls Therapeutics Limited | Method for treating a reduction of fertility |
| US10617743B2 (en) | 2014-06-19 | 2020-04-14 | Cls Therapeutics Limited | Method to improve safety and efficacy of anti-cancer therapy |
| US11701410B2 (en) | 2015-05-22 | 2023-07-18 | Cls Therapeutics Limited | Extracellular DNA as a therapeutic target in neurodegeneration |
| US11905522B2 (en) | 2018-01-16 | 2024-02-20 | Cls Therapeutics Limited | Treatment of diseases by liver expression of an enzyme which has a deoxyribonuclease (DNase) activity |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA78486C2 (en) | 1999-12-10 | 2007-04-10 | Хемджен Корпорейшн | Formulation for oral use in fowls and animals for treating or decreasing risk of infections of digestive tract (variants), use of composition (variants), method for treating or decreasing risk of infections of digestive tract (variants) |
| US7247299B2 (en) * | 2002-11-27 | 2007-07-24 | Kemin Industries, Inc. | Antimicrobial compounds from Bacillus subtilis for use against animal and human pathogens |
| US7566447B2 (en) * | 2003-05-15 | 2009-07-28 | Iogenetics, Llc | Biocides |
| US8703134B2 (en) | 2003-05-15 | 2014-04-22 | Iogenetics, Llc | Targeted cryptosporidium biocides |
| US8394379B2 (en) * | 2003-05-15 | 2013-03-12 | Iogenetics, Llc | Targeted cryptosporidium biocides |
| US20050014932A1 (en) * | 2003-05-15 | 2005-01-20 | Iogenetics, Llc | Targeted biocides |
| US20080274095A1 (en) * | 2004-10-20 | 2008-11-06 | Jane Homan | Biocides |
| MY145870A (en) * | 2005-12-15 | 2012-05-15 | Lilly Co Eli | Enzymes for reduced immunological stress |
| PL2164862T3 (en) * | 2007-06-08 | 2015-12-31 | Australian Poultry Crc Pty Ltd | Clostridial toxin netb |
| NZ585453A (en) * | 2007-12-20 | 2011-12-22 | Danisco Us Inc | A composition comprising a perhydrolase enzyme an a removal enzyme mixture |
| NO2254591T3 (en) | 2008-02-08 | 2017-12-23 | ||
| EA029906B1 (en) | 2012-02-16 | 2018-05-31 | Эланко Юэс Инк. | Methods and compositions for reducing the environmental impact of animal waste |
| TWI656872B (en) | 2014-11-13 | 2019-04-21 | 美商益農美國公司 | Antiviral effects of narasin in swine feed |
| CN106119221A (en) * | 2016-06-28 | 2016-11-16 | 浙江省农业科学院 | Phosphatidylinositol-specific phospholipase C gene, carrier, engineering bacteria and application |
| CN106318925B (en) * | 2016-08-19 | 2021-04-02 | 浙江省农业科学院 | Method for efficiently expressing PI-PLC gene by using bacillus subtilis |
| CN106615691B (en) * | 2016-10-11 | 2019-07-02 | 上海国龙生物技术集团有限公司 | A kind of anti-infective Enzyme reactors and its application in feed |
| US10501730B2 (en) * | 2017-05-30 | 2019-12-10 | Ab Enzymes Oy | Mannanase variants |
| US12031991B2 (en) * | 2018-03-02 | 2024-07-09 | Evonik Operations Gmbh | In vitro method for detecting intestinal barrier failure in animals |
| RU2720471C1 (en) * | 2019-03-21 | 2020-04-30 | Федеральное Государственное бюджетное научное учреждение "Федеральный научный центр биологических систем и агротехнологий российской академии наук" | Fodder additive for broiler chickens |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1509866A (en) | 1975-06-10 | 1978-05-04 | Johnson & Johnson | Enteric coated digestive enzyme compositions |
| JPS5534039A (en) | 1978-08-30 | 1980-03-10 | Hiroo Ikezawa | Preparation of phsophatidylinositol phospholipase c from bacillus thuringiensis |
| US4891319A (en) | 1985-07-09 | 1990-01-02 | Quadrant Bioresources Limited | Protection of proteins and the like |
| US4877738A (en) | 1986-07-25 | 1989-10-31 | Wisconsin Alumni Research Foundation | Biological control of damping off and root rot and inoculum preparation therefor |
| US5049379A (en) | 1987-07-27 | 1991-09-17 | Wisconsin Alumni Research Foundation | Fungicidal toxin and method and inoculum for controlling root rot and damping off |
| JPH0338530A (en) * | 1989-07-03 | 1991-02-19 | Ajinomoto Co Inc | Antifungal agent |
| US5487897A (en) * | 1989-07-24 | 1996-01-30 | Atrix Laboratories, Inc. | Biodegradable implant precursor |
| ATE161395T1 (en) * | 1990-05-29 | 1998-01-15 | Chemgen Corp | HEMICELLULAS ADDITIONAL SUITABLE FOR INCREASING THE ENERGY EFFICIENCY OF FOODS AND ANIMAL FEED CONTAINING HEMICELLULOSE |
| EP0477739A3 (en) * | 1990-09-27 | 1992-12-09 | F. Hoffmann-La Roche Ag | Glycosyl-phosphatidylinositol-specific phospholipase d |
| JPH07184642A (en) * | 1993-12-27 | 1995-07-25 | Toagosei Co Ltd | Production of phospholipase c |
| EP0743017B1 (en) * | 1995-05-15 | 2004-09-29 | DSM IP Assets B.V. | Application of phospholipases in animal feed |
| NL1003096C2 (en) | 1995-05-15 | 1996-11-19 | Gist Brocades Bv | Application of phospholipases in animal feed. |
| JPH08332032A (en) * | 1995-06-12 | 1996-12-17 | Showa Denko Kk | Peroral enzyme preparation for animal and its use |
| JP3914585B2 (en) * | 1995-10-19 | 2007-05-16 | イーエヌ大塚製薬株式会社 | Macrophage nitric oxide production enhancer |
| CN1092495C (en) * | 1996-05-03 | 2002-10-16 | 开姆根有限公司 | Hemicellulase use in feeds with low caloric content |
| US6162473A (en) * | 1996-05-03 | 2000-12-19 | Chemgen Corporation | Hemicellulase use in feeds with low caloric content |
| JPH1045581A (en) * | 1996-07-29 | 1998-02-17 | Hideyo Yamaguchi | Agent for suppressing lowering of neutrophilic function or infection protecting agent |
| CN1235636A (en) * | 1996-10-31 | 1999-11-17 | 诺沃挪第克公司 | Phospholipase, production and use thereof |
| NL1013308C2 (en) | 1998-10-15 | 2000-06-30 | Dsm Nv | Antimicrobial enzymes in animal feed. |
| UA78486C2 (en) | 1999-12-10 | 2007-04-10 | Хемджен Корпорейшн | Formulation for oral use in fowls and animals for treating or decreasing risk of infections of digestive tract (variants), use of composition (variants), method for treating or decreasing risk of infections of digestive tract (variants) |
| US20020116029A1 (en) * | 2001-02-20 | 2002-08-22 | Victor Miller | MRI-compatible pacemaker with power carrying photonic catheter and isolated pulse generating electronics providing VOO functionality |
-
2000
- 2000-08-12 UA UA2002075677A patent/UA78486C2/en unknown
- 2000-12-07 CO CO00093684A patent/CO5280226A1/en not_active Application Discontinuation
- 2000-12-07 AR ARP000106541A patent/AR026764A1/en not_active Application Discontinuation
- 2000-12-08 PT PT00989240T patent/PT1239872E/en unknown
- 2000-12-08 AT AT00989240T patent/ATE481981T1/en active
- 2000-12-08 PL PL356175A patent/PL203054B1/en unknown
- 2000-12-08 PH PH12000003381A patent/PH12000003381B1/en unknown
- 2000-12-08 SK SK826-2002A patent/SK287956B6/en not_active IP Right Cessation
- 2000-12-08 KR KR1020027007363A patent/KR100639746B1/en active IP Right Review Request
- 2000-12-08 MY MYPI20005779A patent/MY124714A/en unknown
- 2000-12-08 EP EP00989240A patent/EP1239872B1/en not_active Expired - Lifetime
- 2000-12-08 IL IL15004800A patent/IL150048A0/en unknown
- 2000-12-08 AU AU25776/01A patent/AU782831B2/en not_active Expired
- 2000-12-08 CZ CZ2002-2007A patent/CZ304925B6/en not_active IP Right Cessation
- 2000-12-08 HU HU0203402A patent/HU230301B1/en unknown
- 2000-12-08 MX MXPA02005735 patent/MX264033B/en active IP Right Grant
- 2000-12-08 CN CNA2008101259037A patent/CN101327320A/en active Pending
- 2000-12-08 NZ NZ519404A patent/NZ519404A/en not_active IP Right Cessation
- 2000-12-08 BR BRPI0016231A patent/BRPI0016231B8/en not_active IP Right Cessation
- 2000-12-08 WO PCT/US2000/033466 patent/WO2001041785A2/en not_active Application Discontinuation
- 2000-12-08 RU RU2002118694/13A patent/RU2272419C2/en active
- 2000-12-08 CN CN00818851A patent/CN1433319A/en active Pending
- 2000-12-08 DE DE60045010T patent/DE60045010D1/en not_active Expired - Lifetime
- 2000-12-08 ES ES00989240T patent/ES2353371T3/en not_active Expired - Lifetime
- 2000-12-08 US US09/731,971 patent/US6780628B2/en not_active Expired - Lifetime
- 2000-12-08 CA CA2394856A patent/CA2394856C/en not_active Expired - Lifetime
- 2000-12-08 JP JP2001543129A patent/JP4871473B2/en not_active Expired - Lifetime
- 2000-12-08 CN CN201110076924.6A patent/CN102172262B/en not_active Expired - Lifetime
- 2000-12-08 DK DK00989240.7T patent/DK1239872T3/en active
-
2001
- 2001-03-07 TW TW089126252A patent/TWI255189B/en not_active IP Right Cessation
-
2002
- 2002-06-05 IL IL150048A patent/IL150048A/en active IP Right Grant
- 2002-06-06 IN IN585DE2002 patent/IN247731B/en unknown
- 2002-06-07 CR CR6674A patent/CR6674A/en unknown
-
2004
- 2004-05-28 US US10/855,416 patent/US7723091B2/en not_active Expired - Lifetime
-
2008
- 2008-01-09 CL CL200800057A patent/CL2008000057A1/en unknown
-
2013
- 2013-01-24 AR ARP130100218A patent/AR089799A2/en not_active Application Discontinuation
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9072733B2 (en) | 2003-07-14 | 2015-07-07 | Cls Therapeutics Limited | Method for treating systemic bacterial, fungal and protozoan infection |
| US9770492B2 (en) | 2003-07-14 | 2017-09-26 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
| US8431123B2 (en) | 2003-07-14 | 2013-04-30 | Cls Therapeutics Limited | Method for treating systemic bacterial, fungal and protozoan infection |
| US8535663B2 (en) | 2003-07-14 | 2013-09-17 | Cls Therapeutics Limited | Method for treating delayed-type hypersensitivity |
| US8796004B2 (en) | 2003-07-14 | 2014-08-05 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
| US8388951B2 (en) | 2003-07-14 | 2013-03-05 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
| US9845461B2 (en) | 2003-07-14 | 2017-12-19 | Cls Therapeutics Limited | Method for treating oncological diseases |
| US8710012B2 (en) | 2003-07-14 | 2014-04-29 | Cls Therapeutics Limited | Method for treating oncological diseases |
| US9248166B2 (en) | 2003-07-14 | 2016-02-02 | Cls Therapeutics Limited | Method for treating oncological diseases |
| US9463223B2 (en) | 2003-07-14 | 2016-10-11 | Cls Therapeutics Limited | Method for monitoring development of somatic mosaicism |
| US8916151B2 (en) | 2005-04-25 | 2014-12-23 | Cls Therapeutics Limited | Method for treating a reduction of fertility |
| WO2008066403A1 (en) | 2006-11-28 | 2008-06-05 | Dmitry Dmitrievich Genkin | Method for treating human diseases associated with an increased deoxyribonucleic acid content in extracellular spaces of tissues and a medicinal preparation for carrying out said method |
| US8871200B2 (en) | 2006-11-28 | 2014-10-28 | Cls Therapeutics Limited | Method for treating human diseases associated with an increased deoxyribonucleic acid content in extracellular spaces of tissues and a medicinal preparation for carrying out said method |
| US10617743B2 (en) | 2014-06-19 | 2020-04-14 | Cls Therapeutics Limited | Method to improve safety and efficacy of anti-cancer therapy |
| US11701410B2 (en) | 2015-05-22 | 2023-07-18 | Cls Therapeutics Limited | Extracellular DNA as a therapeutic target in neurodegeneration |
| US11905522B2 (en) | 2018-01-16 | 2024-02-20 | Cls Therapeutics Limited | Treatment of diseases by liver expression of an enzyme which has a deoxyribonuclease (DNase) activity |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2394856A1 (en) | Enzyme treatment for infection | |
| JP2003520207A5 (en) | ||
| CN1236817C (en) | Novel mixtures of microbial enzymes | |
| WO2007053619A2 (en) | A composition with a fungal (yeast) lipase and method for treating lipid malabsorption in cystic fibrous as well as people suffering from pancreatic lipase insufficiency | |
| AU2014266266B2 (en) | Preventive or therapeutic agent for ruminant animal mastitis | |
| EP2422804A1 (en) | Controlled release formulations of enzymes, microorganisms, and antibodies with mucoadhesive polymers | |
| ES2204740T3 (en) | Feed Additive for Animals. | |
| KR20030061102A (en) | Composition for reducing somatic cell and preventing or treating mastitis of dairy cattle | |
| US5624678A (en) | Method and composition for treatment and/or prophylaxis of coccidiosis | |
| CN1376519A (en) | Multi-enzyme complex capsule | |
| CN107467670B (en) | Probiotic preparation and preparation method and application thereof | |
| US20020016307A1 (en) | Pharmaceutical composition with both a lipase inhibitor and a lipophilic polysaccharide and an improved method for treating adiposity | |
| JPS6114124B2 (en) | ||
| EP0086774A1 (en) | Treatment of coccidial infections with amidinourea or amidinothiourea derivatives | |
| NL7905345A (en) | PREPARATION AND METHOD FOR THE PROPHYLAXIC OR TREATMENT OF DYSENERY IN PIGS. | |
| WO2014035961A1 (en) | Composition and use for increasing t cells | |
| RU2004135538A (en) | NEW BACTERIA FOR TREATMENT OF DISEASE | |
| US20130164275A1 (en) | Method for treating acidosis in ruminants | |
| JPS6112891B2 (en) | ||
| JP2623324B2 (en) | Manufacturing method of livestock feed for electrolyte solution | |
| WO2021202363A1 (en) | Combined animal-derived and synthetically produced pancreatic enzyme replacement therapy | |
| JPH0984528A (en) | Feed for pisciculture | |
| JP2000038349A (en) | Gastric emptying ability enhancer composition containing lipase as active ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20201208 |