JP7507560B2 - コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート - Google Patents
コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート Download PDFInfo
- Publication number
- JP7507560B2 JP7507560B2 JP2019536071A JP2019536071A JP7507560B2 JP 7507560 B2 JP7507560 B2 JP 7507560B2 JP 2019536071 A JP2019536071 A JP 2019536071A JP 2019536071 A JP2019536071 A JP 2019536071A JP 7507560 B2 JP7507560 B2 JP 7507560B2
- Authority
- JP
- Japan
- Prior art keywords
- lal
- coagulogen
- clarified
- endotoxin
- kda
- 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.)
- Active
Links
- 239000012480 LAL reagent Substances 0.000 title claims description 259
- 239000002158 endotoxin Substances 0.000 claims description 128
- 108010045487 coagulogen Proteins 0.000 claims description 92
- 238000000034 method Methods 0.000 claims description 78
- 238000009295 crossflow filtration Methods 0.000 claims description 75
- 239000003593 chromogenic compound Substances 0.000 claims description 71
- 239000000203 mixture Substances 0.000 claims description 65
- 239000000523 sample Substances 0.000 claims description 55
- 239000012465 retentate Substances 0.000 claims description 49
- 238000003556 assay Methods 0.000 claims description 47
- 102000004169 proteins and genes Human genes 0.000 claims description 42
- 108090000623 proteins and genes Proteins 0.000 claims description 42
- 239000006228 supernatant Substances 0.000 claims description 34
- 239000000872 buffer Substances 0.000 claims description 33
- 239000003153 chemical reaction reagent Substances 0.000 claims description 29
- 230000008859 change Effects 0.000 claims description 25
- 238000002835 absorbance Methods 0.000 claims description 22
- 239000012528 membrane Substances 0.000 claims description 21
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 claims description 20
- 241000239218 Limulus Species 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 14
- 230000035945 sensitivity Effects 0.000 claims description 12
- 239000012472 biological sample Substances 0.000 claims description 11
- 238000010186 staining Methods 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 10
- 238000003776 cleavage reaction Methods 0.000 claims description 8
- 230000007017 scission Effects 0.000 claims description 8
- 239000003599 detergent Substances 0.000 claims description 6
- 230000002255 enzymatic effect Effects 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 5
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 3
- 108020004707 nucleic acids Proteins 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 3
- 239000006201 parenteral dosage form Substances 0.000 claims description 3
- 229960005486 vaccine Drugs 0.000 claims description 3
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 63
- 230000035484 reaction time Effects 0.000 description 31
- 238000005119 centrifugation Methods 0.000 description 27
- 229920006008 lipopolysaccharide Polymers 0.000 description 23
- 238000011026 diafiltration Methods 0.000 description 21
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- 238000000926 separation method Methods 0.000 description 21
- 239000000758 substrate Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 108090000790 Enzymes Proteins 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 15
- 229940088598 enzyme Drugs 0.000 description 15
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical group NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 239000000499 gel Substances 0.000 description 13
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 10
- 239000007983 Tris buffer Substances 0.000 description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical group OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
- 206010053567 Coagulopathies Diseases 0.000 description 8
- 102000010911 Enzyme Precursors Human genes 0.000 description 8
- 230000035602 clotting Effects 0.000 description 8
- 230000003287 optical effect Effects 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 5
- 108010062466 Enzyme Precursors Proteins 0.000 description 5
- 102000002262 Thromboplastin Human genes 0.000 description 5
- 108010000499 Thromboplastin Proteins 0.000 description 5
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 5
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- LOHQECMUTAPWAC-UHFFFAOYSA-N coagulin Natural products C1C(C)=C(CO)C(=O)OC1C1(C)C(C2(C)CCC3C4(C(=O)CC=CC4=CCC43)C)(O)CCC24O1 LOHQECMUTAPWAC-UHFFFAOYSA-N 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 150000002632 lipids Chemical group 0.000 description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 description 5
- 239000012466 permeate Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000004611 spectroscopical analysis Methods 0.000 description 5
- -1 vaccines Substances 0.000 description 5
- 238000011050 LAL assay Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000004695 Polyether sulfone Substances 0.000 description 4
- 238000006911 enzymatic reaction Methods 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 238000012454 limulus amebocyte lysate test Methods 0.000 description 4
- 229920006393 polyether sulfone Polymers 0.000 description 4
- 239000002510 pyrogen Substances 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 241001529572 Chaceon affinis Species 0.000 description 3
- 102000003712 Complement factor B Human genes 0.000 description 3
- 108090000056 Complement factor B Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 241000239220 Limulus polyphemus Species 0.000 description 3
- 239000007987 MES buffer Substances 0.000 description 3
- 241000607142 Salmonella Species 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 210000002421 cell wall Anatomy 0.000 description 3
- 108010055222 clotting enzyme Proteins 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 150000002482 oligosaccharides Chemical class 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 102000003390 tumor necrosis factor Human genes 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 101710112984 20 kDa protein Proteins 0.000 description 2
- KZZWQCKYLNIOBT-UHFFFAOYSA-N 5-amino-2-nitrobenzoic acid Chemical compound NC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 KZZWQCKYLNIOBT-UHFFFAOYSA-N 0.000 description 2
- AKASINKCIWHQEP-UHFFFAOYSA-N 7-amino-4-methoxychromen-2-one Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2OC AKASINKCIWHQEP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 231100000699 Bacterial toxin Toxicity 0.000 description 2
- 241000588807 Bordetella Species 0.000 description 2
- 241000588722 Escherichia Species 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 101710159910 Movement protein Proteins 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 241000607768 Shigella Species 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 101710090398 Viral interleukin-10 homolog Proteins 0.000 description 2
- BHATUINFZWUDIX-UHFFFAOYSA-N Zwittergent 3-14 Chemical group CCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O BHATUINFZWUDIX-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 238000002820 assay format Methods 0.000 description 2
- 239000000688 bacterial toxin Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 238000010924 continuous production Methods 0.000 description 2
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000012471 diafiltration solution Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- DEKPYXUDJRABNK-UHFFFAOYSA-N dimethyl 5-aminobenzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(N)=CC(C(=O)OC)=C1 DEKPYXUDJRABNK-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000002095 exotoxin Substances 0.000 description 2
- 231100000776 exotoxin Toxicity 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 210000003677 hemocyte Anatomy 0.000 description 2
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- IZWSFJTYBVKZNK-UHFFFAOYSA-N lauryl sulfobetaine Chemical compound CCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O IZWSFJTYBVKZNK-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000006225 natural substrate Substances 0.000 description 2
- 229920002492 poly(sulfone) Polymers 0.000 description 2
- 108010005636 polypeptide C Proteins 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- NNLZBVFSCVTSLA-XMABDTGBSA-N (4r,5r,6r)-6-[(1r)-1,2-dihydroxyethyl]-2,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound OC[C@@H](O)[C@H]1OC(O)(C(O)=O)C[C@@H](O)[C@H]1O NNLZBVFSCVTSLA-XMABDTGBSA-N 0.000 description 1
- CWRWJDAEKWYUJT-CGKXPTHNSA-N 1-(9S,13S,12-oxophytodienoyl)-2-(7Z,10Z,13Z)-hexadecatrienoyl-3-(beta-D-galactosyl)-sn-glycerol Chemical compound C([C@H](OC(=O)CCCCC\C=C/C\C=C/C\C=C/CC)COC(=O)CCCCCCC[C@@H]1[C@@H](C(=O)C=C1)C\C=C/CC)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O CWRWJDAEKWYUJT-CGKXPTHNSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
- UJVBZCCNLAAMOV-UHFFFAOYSA-N 2h-1,2-benzothiazine Chemical compound C1=CC=C2C=CNSC2=C1 UJVBZCCNLAAMOV-UHFFFAOYSA-N 0.000 description 1
- YUDPTGPSBJVHCN-DZQJYWQESA-N 4-methylumbelliferyl beta-D-galactoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-DZQJYWQESA-N 0.000 description 1
- QULZFZMEBOATFS-DISONHOPSA-N 7-[(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenoxazin-3-one Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(N=C2C(=CC(=O)C=C2)O2)C2=C1 QULZFZMEBOATFS-DISONHOPSA-N 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000035404 Autolysis Diseases 0.000 description 1
- 241000606126 Bacteroidaceae Species 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 101710140962 Capsid scaffolding protein Proteins 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 241001183186 Fusobacteriaceae Species 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000239205 Merostomata Species 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241000588656 Neisseriaceae Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000606752 Pasteurellaceae Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 229920012266 Poly(ether sulfone) PES Polymers 0.000 description 1
- 241000947836 Pseudomonadaceae Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 241001430183 Veillonellaceae Species 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 241000607493 Vibrionaceae Species 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- NFIKTSWJXJTUBZ-ZEQRLZLVSA-N benzyl n-[2-[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]carbamate Chemical compound C([C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC2=CC=3OC(=O)C=C(C=3C=C2)C)CCN1C(=O)CNC(=O)OCC1=CC=CC=C1 NFIKTSWJXJTUBZ-ZEQRLZLVSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 150000004775 coumarins Chemical class 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 230000007893 endotoxin activity Effects 0.000 description 1
- 108010072542 endotoxin binding proteins Proteins 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 210000000087 hemolymph Anatomy 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 150000002386 heptoses Chemical class 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- KYQCXUMVJGMDNG-SHUUEZRQSA-N keto-3-deoxy-D-manno-octulosonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CC(=O)C(O)=O KYQCXUMVJGMDNG-SHUUEZRQSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000028043 self proteolysis Effects 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000001429 visible spectrum Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
- C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/579—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving limulus lysate
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2400/00—Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
- G01N2400/10—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- G01N2400/50—Lipopolysaccharides; LPS
-
- 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
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022166858A JP7724762B2 (ja) | 2017-01-11 | 2022-10-18 | コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762445136P | 2017-01-11 | 2017-01-11 | |
| US62/445,136 | 2017-01-11 | ||
| PCT/US2018/013310 WO2018132562A1 (en) | 2017-01-11 | 2018-01-11 | Coagulogen-free clarified limulus amebocyte lysate |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022166858A Division JP7724762B2 (ja) | 2017-01-11 | 2022-10-18 | コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020505007A JP2020505007A (ja) | 2020-02-20 |
| JP2020505007A5 JP2020505007A5 (enExample) | 2021-02-12 |
| JP7507560B2 true JP7507560B2 (ja) | 2024-06-28 |
Family
ID=61249697
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019536071A Active JP7507560B2 (ja) | 2017-01-11 | 2018-01-11 | コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート |
| JP2022166858A Active JP7724762B2 (ja) | 2017-01-11 | 2022-10-18 | コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022166858A Active JP7724762B2 (ja) | 2017-01-11 | 2022-10-18 | コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US11352656B2 (enExample) |
| EP (1) | EP3552021B1 (enExample) |
| JP (2) | JP7507560B2 (enExample) |
| KR (1) | KR102545029B1 (enExample) |
| CN (1) | CN110192110B (enExample) |
| IL (1) | IL267593B2 (enExample) |
| WO (1) | WO2018132562A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL264464B2 (en) | 2016-08-03 | 2024-02-01 | Lonza Walkersville Inc | A method for detecting endotoxin using Limulus extract of amoeba, which is mainly free of coagulogen |
| US11352656B2 (en) | 2017-01-11 | 2022-06-07 | Lonza Walkersville, Inc. | Coagulogen-free clarified limulus amebocyte lysate and chromogenic assay of endotoxin |
| WO2025090132A2 (en) * | 2023-05-12 | 2025-05-01 | Life Technolohgies Corporation | Methods and kits for detecting endotoxin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012057609A1 (en) | 2010-10-29 | 2012-05-03 | Universiti Malaysia Terengganu | Process for the preparation of amoebocyte lysate from the haemolymph of the horseshoe crab |
| JP2019526052A (ja) | 2016-08-03 | 2019-09-12 | ロンザ ウォーカーズヴィル，インコーポレーテッド | 実質的にコアギュローゲンを含まないリムルスアメボサイトライセートを使用してエンドトキシンを検出する方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0141685B1 (ko) * | 1988-09-01 | 1998-07-01 | 야마따니 와따루 | 참게 아메보사이트 라이세이트 g 인자 활성화 저해제 |
| ATE148230T1 (de) * | 1989-10-30 | 1997-02-15 | Biowhittaker Inc | Kinetische bestimmungsmethode für endotoxin unter verwendung von limulus-amoebocyten-lysat und chromogenem substrat |
| JP3122454B2 (ja) * | 1990-09-27 | 2001-01-09 | 生化学工業株式会社 | カブトガニ・アメボサイト・ライセートの調製法 |
| US5208148A (en) | 1990-12-07 | 1993-05-04 | Molecular Probes, Inc. | Lipophilic fluorescent glycosidase substrates |
| ATE180018T1 (de) | 1991-08-23 | 1999-05-15 | Molecular Probes Inc | Verwendung von haloalkylderivaten von reportermolekülen zur analyse der metabolischen aktivität in zellen |
| US5242805A (en) | 1991-08-23 | 1993-09-07 | Molecular Probes, Inc. | Long wavelength lipophilic fluorogenic glycosidase substrates |
| US5576424A (en) | 1991-08-23 | 1996-11-19 | Molecular Probes, Inc. | Haloalkyl derivatives of reporter molecules used to analyze metabolic activity in cells |
| JP3242733B2 (ja) * | 1993-02-26 | 2001-12-25 | 生化学工業株式会社 | エンドトキシン特異的測定剤 |
| US5830912A (en) | 1996-11-15 | 1998-11-03 | Molecular Probes, Inc. | Derivatives of 6,8-difluoro-7-hydroxycoumarin |
| US5773236A (en) | 1997-04-25 | 1998-06-30 | Molecule Probes, Inc. | Assay for glutathiane transferase using polyhaloaryl-substituted reporter molecules |
| US20100203071A1 (en) * | 2007-03-21 | 2010-08-12 | Norman Blais | Chimeric antigens |
| CN101855539B (zh) | 2007-11-12 | 2012-08-22 | 国立大学法人广岛大学 | 内毒素浓度测定方法及浓度测定用试剂盒 |
| US7846678B2 (en) | 2008-08-18 | 2010-12-07 | BioDtech, Inc. | Enhancing endotoxin detection |
| CN102305788A (zh) * | 2010-11-22 | 2012-01-04 | 天津市一瑞生物工程有限公司 | 革兰阴性菌脂多糖(内毒素)比色检测试剂盒的制备及其使用方法 |
| US11352656B2 (en) | 2017-01-11 | 2022-06-07 | Lonza Walkersville, Inc. | Coagulogen-free clarified limulus amebocyte lysate and chromogenic assay of endotoxin |
| US20190001330A1 (en) | 2017-06-28 | 2019-01-03 | Lonza Walkersville, Inc. | Cartridge for endotoxin detection |
-
2018
- 2018-01-11 US US15/868,318 patent/US11352656B2/en active Active
- 2018-01-11 JP JP2019536071A patent/JP7507560B2/ja active Active
- 2018-01-11 WO PCT/US2018/013310 patent/WO2018132562A1/en not_active Ceased
- 2018-01-11 KR KR1020197023341A patent/KR102545029B1/ko active Active
- 2018-01-11 IL IL267593A patent/IL267593B2/en unknown
- 2018-01-11 CN CN201880006683.8A patent/CN110192110B/zh active Active
- 2018-01-11 EP EP18706328.4A patent/EP3552021B1/en active Active
-
2022
- 2022-05-05 US US17/737,578 patent/US12359241B2/en active Active
- 2022-10-18 JP JP2022166858A patent/JP7724762B2/ja active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012057609A1 (en) | 2010-10-29 | 2012-05-03 | Universiti Malaysia Terengganu | Process for the preparation of amoebocyte lysate from the haemolymph of the horseshoe crab |
| JP2019526052A (ja) | 2016-08-03 | 2019-09-12 | ロンザ ウォーカーズヴィル，インコーポレーテッド | 実質的にコアギュローゲンを含まないリムルスアメボサイトライセートを使用してエンドトキシンを検出する方法 |
Non-Patent Citations (1)
| Title |
|---|
| Ｃｌｉｎ Ｃｈｉｍ Ａｃｔａ．１９８５，ｖｏｌ．１４９，ｎｏ．１，ｐｐ．５５－６５ |
Also Published As
| Publication number | Publication date |
|---|---|
| US12359241B2 (en) | 2025-07-15 |
| JP2020505007A (ja) | 2020-02-20 |
| KR20190104387A (ko) | 2019-09-09 |
| EP3552021B1 (en) | 2022-10-26 |
| KR102545029B1 (ko) | 2023-06-19 |
| JP2023002669A (ja) | 2023-01-10 |
| IL267593A (en) | 2019-08-29 |
| IL267593B1 (en) | 2024-12-01 |
| CN110192110A (zh) | 2019-08-30 |
| JP7724762B2 (ja) | 2025-08-18 |
| US11352656B2 (en) | 2022-06-07 |
| IL267593B2 (en) | 2025-04-01 |
| WO2018132562A1 (en) | 2018-07-19 |
| EP3552021A1 (en) | 2019-10-16 |
| US20220267824A1 (en) | 2022-08-25 |
| CN110192110B (zh) | 2023-01-10 |
| US20180208964A1 (en) | 2018-07-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7044222B2 (ja) | 実質的にコアギュローゲンを含まないリムルスアメボサイトライセートを使用してエンドトキシンを検出する方法 | |
| JP7724762B2 (ja) | コアギュローゲンを含まない、清澄化リムルスアメボサイトライセート | |
| US10119969B2 (en) | Compositions for the detection of microbial contaminants | |
| US6270982B1 (en) | Methods and compositions for the detection of bacterial endotoxins | |
| Sheraba et al. | Advanced approaches for endotoxin detection and removal from snake antivenoms | |
| HK40007693A (en) | Coagulogen-free clarified limulus amebocyte lysate | |
| HK40007693B (en) | Coagulogen-free clarified limulus amebocyte lysate | |
| HK40006346A (en) | Method of detecting an endotoxin using limulus amebocyte lysate substantially free of coagulogen | |
| US20060183181A1 (en) | Methods and compositions for the detection and/or quantification of gram positive bacterial contaminants | |
| HK40006346B (zh) | 利用基本上不含凝固蛋白原的鲎阿米巴样细胞溶解物检测内毒素的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20190705 |
|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20190705 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20190920 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201224 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201224 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220104 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220331 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220802 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221018 |
|
| C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20221018 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20221025 |
|
| C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20221101 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20221209 |
|
| C211 | Notice of termination of reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C211 Effective date: 20221213 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240411 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240618 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7507560 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |