JP5758291B2 - Ｓｔａｐｈｙｌｏｃｏｃｃｉｂａｃｔｅｒｉａに対する活性を有するキメラバクテリオファージ溶解素 - Google Patents
Ｓｔａｐｈｙｌｏｃｏｃｃｉｂａｃｔｅｒｉａに対する活性を有するキメラバクテリオファージ溶解素 Download PDFInfo
- Publication number
- JP5758291B2 JP5758291B2 JP2011516843A JP2011516843A JP5758291B2 JP 5758291 B2 JP5758291 B2 JP 5758291B2 JP 2011516843 A JP2011516843 A JP 2011516843A JP 2011516843 A JP2011516843 A JP 2011516843A JP 5758291 B2 JP5758291 B2 JP 5758291B2
- Authority
- JP
- Japan
- Prior art keywords
- lysin
- bacteriophage lysin
- seq
- chimeric
- chimeric bacteriophage
- 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.)
- Expired - Fee Related
Links
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 title claims description 148
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 title claims description 148
- 241001515965 unidentified phage Species 0.000 title claims description 59
- 230000000694 effects Effects 0.000 title description 40
- 238000009739 binding Methods 0.000 claims description 55
- 230000027455 binding Effects 0.000 claims description 54
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 53
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 39
- 229920001184 polypeptide Polymers 0.000 claims description 38
- 208000015181 infectious disease Diseases 0.000 claims description 32
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 29
- 241000894006 Bacteria Species 0.000 claims description 28
- 230000003197 catalytic effect Effects 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 27
- 241000191967 Staphylococcus aureus Species 0.000 claims description 26
- 241000295644 Staphylococcaceae Species 0.000 claims description 22
- 150000001413 amino acids Chemical group 0.000 claims description 22
- 210000002421 cell wall Anatomy 0.000 claims description 21
- 108010059378 Endopeptidases Proteins 0.000 claims description 18
- 102000005593 Endopeptidases Human genes 0.000 claims description 18
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 15
- 239000002953 phosphate buffered saline Substances 0.000 claims description 15
- 241000191963 Staphylococcus epidermidis Species 0.000 claims description 14
- 230000002147 killing effect Effects 0.000 claims description 14
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims description 11
- 229960003085 meticillin Drugs 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 9
- 241000894007 species Species 0.000 claims description 8
- 239000004599 antimicrobial Substances 0.000 claims description 7
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000000845 anti-microbial effect Effects 0.000 claims description 5
- 229940088710 antibiotic agent Drugs 0.000 claims description 5
- 230000002458 infectious effect Effects 0.000 claims description 5
- 230000008685 targeting Effects 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 206010041925 Staphylococcal infections Diseases 0.000 claims description 3
- 230000003385 bacteriostatic effect Effects 0.000 claims description 3
- 238000011012 sanitization Methods 0.000 claims description 3
- 239000003899 bactericide agent Substances 0.000 claims description 2
- 239000000022 bacteriostatic agent Substances 0.000 claims description 2
- 238000004140 cleaning Methods 0.000 claims description 2
- 101710126949 Lysin Proteins 0.000 description 107
- 108090000623 proteins and genes Proteins 0.000 description 30
- 102000004190 Enzymes Human genes 0.000 description 28
- 108090000790 Enzymes Proteins 0.000 description 28
- 229940088598 enzyme Drugs 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 25
- 102000004169 proteins and genes Human genes 0.000 description 25
- 230000001580 bacterial effect Effects 0.000 description 22
- 125000003275 alpha amino acid group Chemical group 0.000 description 18
- 230000004083 survival effect Effects 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 108090000988 Lysostaphin Proteins 0.000 description 16
- 239000008363 phosphate buffer Substances 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000000872 buffer Substances 0.000 description 14
- 239000000499 gel Substances 0.000 description 14
- 230000002101 lytic effect Effects 0.000 description 13
- 229960001019 oxacillin Drugs 0.000 description 13
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 13
- 108700023418 Amidases Proteins 0.000 description 12
- 101000925662 Enterobacteria phage PRD1 Endolysin Proteins 0.000 description 12
- 102000005922 amidase Human genes 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 241000588724 Escherichia coli Species 0.000 description 10
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000011144 upstream manufacturing Methods 0.000 description 10
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 9
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000005090 green fluorescent protein Substances 0.000 description 9
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 8
- 241000543700 Staphylococcus virus Twort Species 0.000 description 8
- 230000009089 cytolysis Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 241000193830 Bacillus <bacterium> Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 108010059993 Vancomycin Proteins 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 229960003165 vancomycin Drugs 0.000 description 7
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 7
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 108091006116 chimeric peptides Proteins 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000013207 serial dilution Methods 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- 239000004472 Lysine Substances 0.000 description 5
- 208000037942 Methicillin-resistant Staphylococcus aureus infection Diseases 0.000 description 5
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 5
- 108010013639 Peptidoglycan Proteins 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 241000193755 Bacillus cereus Species 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 244000000059 gram-positive pathogen Species 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 108010013198 Daptomycin Proteins 0.000 description 3
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241001505901 Streptococcus sp. 'group A' Species 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 102000023732 binding proteins Human genes 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000005277 cation exchange chromatography Methods 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 description 3
- 229960005484 daptomycin Drugs 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 108091093088 Amplicon Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000193738 Bacillus anthracis Species 0.000 description 2
- 206010011409 Cross infection Diseases 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 241000554957 Staphylococcus phage phiNM3 Species 0.000 description 2
- 241000191978 Staphylococcus simulans Species 0.000 description 2
- 241000193998 Streptococcus pneumoniae Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 229940065181 bacillus anthracis Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000005757 colony formation Effects 0.000 description 2
- 239000006781 columbia blood agar Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 238000003113 dilution method Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 2
- 229960003907 linezolid Drugs 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 125000006853 reporter group Chemical group 0.000 description 2
- 239000008279 sol Substances 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000009044 synergistic interaction Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000607 toxicokinetics Toxicity 0.000 description 2
- 239000001974 tryptic soy broth Substances 0.000 description 2
- 108010050327 trypticase-soy broth Proteins 0.000 description 2
- 231100000747 viability assay Toxicity 0.000 description 2
- 238000003026 viability measurement method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000004092 Amidohydrolases Human genes 0.000 description 1
- 108090000531 Amidohydrolases Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000034309 Bacterial disease carrier Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006563 Bullous impetigo Diseases 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 108010072454 CTGCAG-specific type II deoxyribonucleases Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 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 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 101710198774 Envelope protein US9 Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical group C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 241001492308 Lactococcus phage Tuc2009 Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 101710097941 N-acetylmuramoyl-L-alanine amidase CwlA Proteins 0.000 description 1
- 206010029803 Nosocomial infection Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000256215 Spongomorpha aeruginosa Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 201000005008 bacterial sepsis Diseases 0.000 description 1
- 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 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- PPKJUHVNTMYXOD-PZGPJMECSA-N c49ws9n75l Chemical compound O=C([C@@H]1N(C2=O)CC[C@H]1S(=O)(=O)CCN(CC)CC)O[C@H](C(C)C)[C@H](C)\C=C\C(=O)NC\C=C\C(\C)=C\[C@@H](O)CC(=O)CC1=NC2=CO1.N([C@@H]1C(=O)N[C@@H](C(N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(=CC=2)N(C)C)C(=O)N2C[C@@H](CS[C@H]3C4CCN(CC4)C3)C(=O)C[C@H]2C(=O)N[C@H](C(=O)O[C@@H]1C)C=1C=CC=CC=1)=O)CC)C(=O)C1=NC=CC=C1O PPKJUHVNTMYXOD-PZGPJMECSA-N 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000004046 cell surface extension Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 239000010436 fluorite Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960004675 fusidic acid Drugs 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002337 glycosamines Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 244000039328 opportunistic pathogen Species 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- MXHCPCSDRGLRER-UHFFFAOYSA-N pentaglycine Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(O)=O MXHCPCSDRGLRER-UHFFFAOYSA-N 0.000 description 1
- 230000016446 peptide cross-linking Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 108010071077 quinupristin-dalfopristin Proteins 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- -1 rhodamine isothiocyanate Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940037648 staphylococcus simulans Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FPZLLRFZJZRHSY-HJYUBDRYSA-N tigecycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CNC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O FPZLLRFZJZRHSY-HJYUBDRYSA-N 0.000 description 1
- 229960004089 tigecycline Drugs 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2462—Lysozyme (3.2.1.17)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
- A01N63/50—Isolated enzymes; Isolated proteins
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2795/00—Bacteriophages
- C12N2795/00011—Details
- C12N2795/10011—Details dsDNA Bacteriophages
- C12N2795/10311—Siphoviridae
- C12N2795/10322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Environmental Sciences (AREA)
- Dentistry (AREA)
- Plant Pathology (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7827708P | 2008-07-03 | 2008-07-03 | |
| US61/078,277 | 2008-07-03 | ||
| PCT/US2009/049349 WO2010002959A2 (en) | 2008-07-03 | 2009-07-01 | A chimeric bacteriophage lysin with activity against staphylococci bacteria |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015033626A Division JP6169632B2 (ja) | 2008-07-03 | 2015-02-24 | Ｓｔａｐｈｙｌｏｃｏｃｃｉｂａｃｔｅｒｉａに対する活性を有するキメラバクテリオファージ溶解素 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011526920A JP2011526920A (ja) | 2011-10-20 |
| JP2011526920A5 JP2011526920A5 (https=) | 2012-08-16 |
| JP5758291B2 true JP5758291B2 (ja) | 2015-08-05 |
Family
ID=41466590
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011516843A Expired - Fee Related JP5758291B2 (ja) | 2008-07-03 | 2009-07-01 | Ｓｔａｐｈｙｌｏｃｏｃｃｉｂａｃｔｅｒｉａに対する活性を有するキメラバクテリオファージ溶解素 |
| JP2015033626A Expired - Fee Related JP6169632B2 (ja) | 2008-07-03 | 2015-02-24 | Ｓｔａｐｈｙｌｏｃｏｃｃｉｂａｃｔｅｒｉａに対する活性を有するキメラバクテリオファージ溶解素 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015033626A Expired - Fee Related JP6169632B2 (ja) | 2008-07-03 | 2015-02-24 | Ｓｔａｐｈｙｌｏｃｏｃｃｉｂａｃｔｅｒｉａに対する活性を有するキメラバクテリオファージ溶解素 |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US8840900B2 (https=) |
| EP (2) | EP2307557B1 (https=) |
| JP (2) | JP5758291B2 (https=) |
| AU (2) | AU2009266982B2 (https=) |
| CA (2) | CA2729160C (https=) |
| ES (1) | ES2627321T3 (https=) |
| HK (1) | HK1248722A1 (https=) |
| WO (1) | WO2010002959A2 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8389469B2 (en) | 2005-06-06 | 2013-03-05 | The Rockefeller University | Bacteriophage lysins for Bacillus anthracis |
| EP2360248A1 (en) | 2005-08-24 | 2011-08-24 | The Rockefeller University | Ply-GBS mutant lysins |
| DK2699253T3 (en) | 2011-04-21 | 2018-07-16 | Univ Rockefeller | STREPTOCOCCUS BACTERYPHAGIC LYSINES FOR THE DETECTION AND TREATMENT OF GRAM POSITIVE BACTERIES |
| DK3085777T3 (da) * | 2011-05-04 | 2020-02-03 | Micreos Human Health Bv | Polypeptid |
| US9279118B2 (en) | 2011-10-05 | 2016-03-08 | The Rockefeller University | Dimeric bacteriophage lysins |
| RU2018121290A (ru) | 2012-05-09 | 2019-03-06 | Контрафект Корпорейшн | Комбинации лизина бактериофага и антибиотика против грам-положительных бактерий |
| BR112014027818B1 (pt) * | 2012-05-09 | 2023-03-28 | Contrafect Corporation | Usos de composições compreendendo polipeptídeo de lisina para prevenção, ruptura ou tratamento de um biofilme bacteriano |
| CN103122347B (zh) * | 2013-02-01 | 2015-04-22 | 中国科学院武汉病毒研究所 | 一种杀灭葡萄球菌的裂解酶及其应用 |
| ES2525954B1 (es) * | 2013-05-28 | 2015-10-23 | Consejo Superior De Investigaciones Científicas (Csic) | Enzibióticos bactericidas mejorados frente a neumococo y otras bacterias |
| CN104762285B (zh) * | 2015-04-23 | 2017-10-27 | 武汉菲吉乐科生物科技有限公司 | 一种自内裂解大肠杆菌的裂解酶及其应用 |
| CN104805066B (zh) * | 2015-05-18 | 2018-04-24 | 武汉菲吉乐科生物科技有限公司 | 一种葡萄球菌裂解酶及其应用 |
| EP3454888B1 (en) | 2016-05-12 | 2021-02-24 | Contrafect Corporation | Broth microdilution method for evaluating and determining minimal inhibitory concentration of antibacterial polypeptides |
| BR112020026267A2 (pt) * | 2018-06-22 | 2021-04-06 | Contrafect Corporation | Lisinas e seus derivados resensibilizam novamente staphylococcus aureus e bactérias gram-positivas aos antibióticos |
| WO2020032232A1 (ja) * | 2018-08-10 | 2020-02-13 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | バクテリオファージ剤 |
| CN109666667A (zh) * | 2019-01-22 | 2019-04-23 | 上海交通大学 | 杀灭金黄色葡萄球菌的嵌合酶抗生素及其制备和应用 |
| WO2021084558A2 (en) * | 2019-10-31 | 2021-05-06 | Bactoclear Holdings Pte. Ltd | Chimeric proteins for selective lysis of bacteria |
| WO2021178968A1 (en) * | 2020-03-06 | 2021-09-10 | Endolytix Technology, Inc. | Compositions and methods for the treatment of intracellular bacterial infections |
| WO2021180892A1 (en) * | 2020-03-11 | 2021-09-16 | Telum Therapeutics S.L. | New recombinant lysin and its use in the treatment of gram-negative bacterial infections |
| CN111808837A (zh) * | 2020-07-17 | 2020-10-23 | 青岛诺安百特生物技术有限公司 | 一种金黄色葡萄球菌噬菌体裂解酶及其制备方法和应用 |
| CN115820616A (zh) * | 2022-07-22 | 2023-03-21 | 昆明理工大学 | 一种带荧光标记的噬菌体裂解酶及其应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997008553A1 (en) * | 1995-08-22 | 1997-03-06 | The Regents Of The University Of California | Targeting of proteins to the cell wall of gram-positive bacteria |
| US6056954A (en) * | 1997-10-31 | 2000-05-02 | New Horizons Diagnostics Corp | Use of bacterial phage associated lysing enzymers for the prophylactic and therapeutic treatment of various illnesses |
| US6703025B1 (en) * | 1998-08-31 | 2004-03-09 | Inhibitex, Inc. | Multicomponent vaccines |
| US20020127215A1 (en) * | 1999-09-14 | 2002-09-12 | Lawrence Loomis | Parenteral use of bacterial phage associated lysing enzymes for the therapeutic treatment of bacterial infections |
| GB0107661D0 (en) * | 2001-03-27 | 2001-05-16 | Chiron Spa | Staphylococcus aureus |
| US20040213765A1 (en) * | 2001-07-13 | 2004-10-28 | Vincent Fischetti | Use of bacterial phage associated lytic enzymes to prevent food poisoning |
| EP1504088B1 (en) * | 2002-03-25 | 2007-08-15 | University Of Warwick | Bacteriophages useful for therapy and prophylaxis of bacterial infections |
| JPWO2004020635A1 (ja) * | 2002-08-28 | 2005-12-15 | 株式会社テクノネットワーク四国 | バクテリオファージおよび細菌感染症治療剤 |
| EP2360248A1 (en) * | 2005-08-24 | 2011-08-24 | The Rockefeller University | Ply-GBS mutant lysins |
| WO2009024327A2 (en) | 2007-08-22 | 2009-02-26 | Profos Ag | New proteins for use in human and animal staphylococcus infections |
| US8563504B2 (en) * | 2008-10-10 | 2013-10-22 | Lusomedicamenta, S.A. | Antibacterial phage peptides and methods of use thereof |
| AU2010211456B2 (en) * | 2009-02-06 | 2016-05-26 | Technophage, Investigação E Desenvolvimento Em Biotecnologia, S.A. | Antibacterial phage, phage peptides and methods of use thereof |
-
2009
- 2009-07-01 WO PCT/US2009/049349 patent/WO2010002959A2/en not_active Ceased
- 2009-07-01 CA CA2729160A patent/CA2729160C/en active Active
- 2009-07-01 JP JP2011516843A patent/JP5758291B2/ja not_active Expired - Fee Related
- 2009-07-01 EP EP09774409.8A patent/EP2307557B1/en active Active
- 2009-07-01 CA CA2984933A patent/CA2984933C/en active Active
- 2009-07-01 US US13/502,912 patent/US8840900B2/en active Active
- 2009-07-01 AU AU2009266982A patent/AU2009266982B2/en not_active Ceased
- 2009-07-01 ES ES09774409.8T patent/ES2627321T3/es active Active
- 2009-07-01 EP EP17158578.9A patent/EP3263588A1/en not_active Withdrawn
-
2014
- 2014-09-09 US US14/480,822 patent/US10053681B2/en active Active
-
2015
- 2015-02-24 JP JP2015033626A patent/JP6169632B2/ja not_active Expired - Fee Related
- 2015-09-25 AU AU2015230807A patent/AU2015230807B2/en not_active Ceased
-
2018
- 2018-06-27 HK HK18108284.8A patent/HK1248722A1/en unknown
- 2018-08-20 US US16/105,155 patent/US11015182B2/en active Active
-
2021
- 2021-05-24 US US17/328,299 patent/US11827911B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2009266982B2 (en) | 2015-06-25 |
| EP2307557A4 (en) | 2012-04-11 |
| US8840900B2 (en) | 2014-09-23 |
| AU2009266982A1 (en) | 2010-01-07 |
| AU2015230807B2 (en) | 2017-07-27 |
| CA2729160A1 (en) | 2010-01-07 |
| US11015182B2 (en) | 2021-05-25 |
| WO2010002959A2 (en) | 2010-01-07 |
| EP3263588A1 (en) | 2018-01-03 |
| US20190055533A1 (en) | 2019-02-21 |
| JP2011526920A (ja) | 2011-10-20 |
| US10053681B2 (en) | 2018-08-21 |
| US20150064156A1 (en) | 2015-03-05 |
| ES2627321T3 (es) | 2017-07-27 |
| CA2729160C (en) | 2017-11-14 |
| JP2015126738A (ja) | 2015-07-09 |
| US20120258088A1 (en) | 2012-10-11 |
| JP6169632B2 (ja) | 2017-07-26 |
| CA2984933C (en) | 2020-07-07 |
| US11827911B2 (en) | 2023-11-28 |
| EP2307557B1 (en) | 2017-03-01 |
| HK1248722A1 (en) | 2018-10-19 |
| WO2010002959A3 (en) | 2010-05-06 |
| AU2015230807A1 (en) | 2015-10-15 |
| CA2984933A1 (en) | 2010-01-07 |
| EP2307557A2 (en) | 2011-04-13 |
| US20210348146A1 (en) | 2021-11-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11827911B2 (en) | Chimeric bacteriophage lysin with activity against Staphylococci bacteria | |
| Hermoso et al. | Taking aim on bacterial pathogens: from phage therapy to enzybiotics | |
| Borysowski et al. | Bacteriophage endolysins as a novel class of antibacterial agents | |
| HK1244503A1 (zh) | 用於革兰氏阳性菌检测和治疗的链球菌属细菌噬菌体溶素 | |
| JP2023103347A (ja) | 血液成分による溶菌タンパク質の抗菌活性の強化、並びにその方法及び使用 | |
| AU2018203076B2 (en) | Dimeric bacteriophage lysins | |
| US20180353575A1 (en) | Clostridium difficile bacteriophage lysins for detection and treatment of clostridium difficile bacteria infection | |
| Borysowski et al. | Enzybiotics and their potential applications in medicine | |
| Shang | Structure-Guided Engineering of a Multimeric Bacteriophage-Encoded Endolysin PlyC | |
| HK1259718A1 (zh) | 用於革兰氏阳性菌检测和治疗的链球菌属细菌噬菌体溶素 | |
| HK1259586A1 (en) | Dimeric bacteriophage lysins | |
| HK1260296A1 (en) | Dimeric bacteriophage lysins | |
| HK1260296B (en) | Dimeric bacteriophage lysins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120628 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120628 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131126 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140224 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140303 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140325 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140401 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140409 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141024 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150123 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150224 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150507 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150603 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5758291 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |