TWI626307B - 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 - Google Patents
重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 Download PDFInfo
- Publication number
- TWI626307B TWI626307B TW102139558A TW102139558A TWI626307B TW I626307 B TWI626307 B TW I626307B TW 102139558 A TW102139558 A TW 102139558A TW 102139558 A TW102139558 A TW 102139558A TW I626307 B TWI626307 B TW I626307B
- Authority
- TW
- Taiwan
- Prior art keywords
- bont
- protein
- sequence
- amino acid
- acid sequence
- Prior art date
Links
- 108030001720 Bontoxilysin Proteins 0.000 title claims abstract description 197
- 231100001103 botulinum neurotoxin Toxicity 0.000 title description 13
- 241000193155 Clostridium botulinum Species 0.000 title description 5
- 101710185720 Putative ethidium bromide resistance protein Proteins 0.000 claims abstract description 105
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 77
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 68
- 241000588724 Escherichia coli Species 0.000 claims abstract description 24
- 239000002773 nucleotide Substances 0.000 claims abstract description 19
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 claims abstract description 18
- 108020004705 Codon Proteins 0.000 claims description 93
- 102000004142 Trypsin Human genes 0.000 claims description 91
- 108090000631 Trypsin Proteins 0.000 claims description 91
- 239000012588 trypsin Substances 0.000 claims description 90
- 150000001413 amino acids Chemical class 0.000 claims description 64
- 235000001014 amino acid Nutrition 0.000 claims description 59
- 229940024606 amino acid Drugs 0.000 claims description 54
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 40
- 235000004279 alanine Nutrition 0.000 claims description 29
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 29
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 26
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 239000007788 liquid Substances 0.000 claims description 23
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 15
- 239000004471 Glycine Substances 0.000 claims description 15
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 15
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 15
- 235000018417 cysteine Nutrition 0.000 claims description 15
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 15
- 235000003704 aspartic acid Nutrition 0.000 claims description 14
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 14
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 14
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 13
- 235000013922 glutamic acid Nutrition 0.000 claims description 13
- 239000004220 glutamic acid Substances 0.000 claims description 13
- 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 12
- 230000005661 hydrophobic surface Effects 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 229940124272 protein stabilizer Drugs 0.000 claims description 9
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 8
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 8
- 239000003446 ligand Substances 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000006172 buffering agent Substances 0.000 claims description 6
- 150000002016 disaccharides Chemical class 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 6
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- 229940009098 aspartate Drugs 0.000 claims description 2
- 239000008223 sterile water Substances 0.000 claims description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 description 39
- 108020004414 DNA Proteins 0.000 description 34
- 235000018102 proteins Nutrition 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 31
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 27
- 238000003776 cleavage reaction Methods 0.000 description 26
- 230000007017 scission Effects 0.000 description 25
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 23
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 23
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 20
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 20
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 20
- 125000003275 alpha amino acid group Chemical group 0.000 description 18
- 102000035195 Peptidases Human genes 0.000 description 17
- 108091005804 Peptidases Proteins 0.000 description 17
- 239000004365 Protease Substances 0.000 description 17
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 14
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 11
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 238000013519 translation Methods 0.000 description 11
- 229930195712 glutamate Natural products 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 108700012359 toxins Proteins 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- -1 SNAP-25 Proteins 0.000 description 5
- 102000000583 SNARE Proteins Human genes 0.000 description 5
- 108010041948 SNARE Proteins Proteins 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 238000005342 ion exchange Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 4
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 231100000065 noncytotoxic Toxicity 0.000 description 4
- 230000002020 noncytotoxic effect Effects 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000005917 R-SNARE Proteins Human genes 0.000 description 3
- 108010005730 R-SNARE Proteins Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 238000005349 anion exchange Methods 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000012145 high-salt buffer Substances 0.000 description 3
- 229960001340 histamine Drugs 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229930027917 kanamycin Natural products 0.000 description 3
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 3
- 229960000318 kanamycin Drugs 0.000 description 3
- 229930182823 kanamycin A Natural products 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- 101710081722 Antitrypsin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 101710138657 Neurotoxin Proteins 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 102000015799 Qa-SNARE Proteins Human genes 0.000 description 2
- 108010010469 Qa-SNARE Proteins Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 206010040954 Skin wrinkling Diseases 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000001475 anti-trypsic effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 230000002934 lysing effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000001640 nerve ending Anatomy 0.000 description 2
- 239000002581 neurotoxin Substances 0.000 description 2
- 231100000618 neurotoxin Toxicity 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 210000002706 plastid Anatomy 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000012772 sequence design Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 230000037303 wrinkles Effects 0.000 description 2
- 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 1
- GUPXYSSGJWIURR-UHFFFAOYSA-N 3-octoxypropane-1,2-diol Chemical compound CCCCCCCCOCC(O)CO GUPXYSSGJWIURR-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 244000003416 Asparagus officinalis Species 0.000 description 1
- 235000005340 Asparagus officinalis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000012619 Butyl Sepharose® Substances 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108700010070 Codon Usage Proteins 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
- 229920002271 DEAE-Sepharose Polymers 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 101710204837 Envelope small membrane protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 231100000111 LD50 Toxicity 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
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 101710145006 Lysis protein Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000004390 N-Ethylmaleimide-Sensitive Proteins Human genes 0.000 description 1
- 108010081735 N-Ethylmaleimide-Sensitive Proteins Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000012614 Q-Sepharose Substances 0.000 description 1
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
- 102000006384 Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins Human genes 0.000 description 1
- 108010019040 Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 101150057615 Syn gene Proteins 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 0.000 description 1
- 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 1
- 102100035054 Vesicle-fusing ATPase Human genes 0.000 description 1
- 102000036861 Zinc-dependent endopeptidases Human genes 0.000 description 1
- 108091006982 Zinc-dependent endopeptidases Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 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 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000013882 gravy Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000004237 neck muscle Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 235000013311 vegetables Nutrition 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)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
-
- 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
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- 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)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- 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)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A61K38/4893—Botulinum neurotoxin (3.4.24.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24069—Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Dermatology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB201219602A GB201219602D0 (en) | 2012-10-31 | 2012-10-31 | Recombinant clostridium botulinum neurotoxins |
| ??1219602.8 | 2012-10-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201435084A TW201435084A (zh) | 2014-09-16 |
| TWI626307B true TWI626307B (zh) | 2018-06-11 |
Family
ID=47358958
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102139558A TWI626307B (zh) | 2012-10-31 | 2013-10-31 | 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 |
| TW108125708A TW202012622A (zh) | 2012-10-31 | 2013-10-31 | 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 |
| TW107110108A TWI673361B (zh) | 2012-10-31 | 2013-10-31 | 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108125708A TW202012622A (zh) | 2012-10-31 | 2013-10-31 | 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 |
| TW107110108A TWI673361B (zh) | 2012-10-31 | 2013-10-31 | 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 |
Country Status (26)
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201219602D0 (en) * | 2012-10-31 | 2012-12-12 | Syntaxin Ltd | Recombinant clostridium botulinum neurotoxins |
| RU2746736C2 (ru) * | 2015-03-26 | 2021-04-20 | Президент Энд Феллоуз Оф Гарвард Колледж | Сконструированный ботулинический нейротоксин |
| WO2017063743A1 (en) | 2015-10-14 | 2017-04-20 | Merz Pharma Gmbh & Co. Kgaa | Improvements to ultrasound-based therapy of photoaged tissue |
| KR20180114891A (ko) | 2016-03-02 | 2018-10-19 | 메르츠 파마 게엠베하 운트 코. 카가아 | 보툴리눔 독소를 포함하는 조성물 |
| EP3263710A1 (en) * | 2016-07-01 | 2018-01-03 | Ipsen Biopharm Limited | Production of activated clostridial neurotoxins |
| EP3504226A1 (en) | 2016-08-24 | 2019-07-03 | President and Fellows of Harvard College | Engineered botulinum neurotoxin |
| US10369190B2 (en) | 2016-09-13 | 2019-08-06 | Allergan, Inc. | Non-protein clostridial toxin compositions |
| WO2018233813A1 (en) | 2017-06-20 | 2018-12-27 | Merz Pharma Gmbh & Co. Kgaa | Novel recombinant botulinum toxin with increased duration of effect |
| US11155802B2 (en) | 2017-07-06 | 2021-10-26 | Merz Pharma Gmbh & Co. Kgaa | Recombinant botulinum neurotoxins with increased duration of effect |
| EP3694489A4 (en) | 2017-10-11 | 2021-06-30 | Illustris Pharmaceuticals, Inc. | METHOD AND COMPOSITION OF TOPICAL ADMINISTRATION |
| US11634460B2 (en) * | 2018-01-29 | 2023-04-25 | Ipsen Biopharm Limited | Non-neuronal snare-cleaving botulinum neurotoxins |
| EP3752128B1 (de) * | 2018-02-16 | 2025-01-15 | preclinics discovery GmbH | Nukleinsäure-basiertes botulinum neurotoxin zur therapeutischen anwendung |
| GB201815844D0 (en) * | 2018-09-28 | 2018-11-14 | Ipsen Biopharm Ltd | Therapeutic & comestic uses of botulinum neurotoxin serotype e |
| GB202011055D0 (en) | 2020-07-17 | 2020-09-02 | Ipsen Bioinnovation Ltd | Treatment of post-operative pain |
| GB202015618D0 (en) * | 2020-10-01 | 2020-11-18 | Ipsen Biopharm Ltd | Method for producing beta-trypsin |
| CN115819526A (zh) * | 2022-12-02 | 2023-03-21 | 海雅美生物技术(珠海)有限公司 | 一种重组肉毒杆菌神经毒素及其制备方法和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006011966A1 (en) * | 2004-06-30 | 2006-02-02 | Allergan, Inc. | Optimizing expression of active botulinum toxin type e |
| WO2008008805A2 (en) * | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for non-clostridial toxin target cells |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6967088B1 (en) * | 1995-03-16 | 2005-11-22 | Allergan, Inc. | Soluble recombinant botulinum toxin proteins |
| NZ308772A (en) * | 1995-05-17 | 1999-04-29 | Du Pont | Recombinant baculovirus insecticides |
| EP1119626B1 (en) | 1998-07-10 | 2008-01-02 | U.S. Army Medical Research Institute of Infectious Diseases | Botulinum neurotoxin vaccine |
| KR100876060B1 (ko) * | 1999-08-25 | 2008-12-26 | 알러간, 인코포레이티드 | 활성화가능한 재조합 신경독 |
| US7374896B2 (en) | 2001-08-28 | 2008-05-20 | Allergan, Inc. | GFP-SNAP25 fluorescence release assay for botulinum neurotoxin protease activity |
| AU2005327457B2 (en) * | 2003-09-25 | 2012-08-23 | Allergan, Inc. | Media for clostridium bacterium and processes for obtaining a clostridial toxin |
| US20110111483A1 (en) * | 2004-06-30 | 2011-05-12 | Allergan, Inc. | Optimizing Expression of Active Botulinum Toxin Type E |
| US7514088B2 (en) * | 2005-03-15 | 2009-04-07 | Allergan, Inc. | Multivalent Clostridial toxin derivatives and methods of their use |
| GB2416122A (en) * | 2004-07-12 | 2006-01-18 | Ipsen Ltd | Botulinum neurotoxin composition |
| DE102004043009A1 (de) * | 2004-09-06 | 2006-03-23 | Toxogen Gmbh | Transportprotein zum Einbringen chemischer Verbindungen in Nervenzellen |
| DE102005002978B4 (de) * | 2005-01-21 | 2013-04-25 | Merz Pharma Gmbh & Co. Kgaa | Rekombinante Expression von Proteinen in einer disulfidverbrückten, zweikettigen Form |
| JP5134540B2 (ja) * | 2005-09-19 | 2013-01-30 | アラーガン、インコーポレイテッド | クロストリジウム毒素活性化クロストリジウム毒素 |
| US20070218084A1 (en) * | 2005-12-30 | 2007-09-20 | Fondazione Pierfranco E Luisa Mariani- Onlus | Method for the Mapping of the Epileptogenic Focus in the Pre-Surgical Evaluation of Patients with Intractable Epilepsy |
| WO2009014854A1 (en) * | 2007-07-26 | 2009-01-29 | Allergan, Inc. | Methods of activiting clostridial toxins |
| KR20110106346A (ko) | 2008-12-10 | 2011-09-28 | 알러간, 인코포레이티드 | 클로스트리디움 독소 약제학적 조성물 |
| GB0903006D0 (en) * | 2009-02-23 | 2009-04-08 | Syntaxin Ltd | Modified non-cytotoxic proteases |
| JP5764550B2 (ja) * | 2009-04-14 | 2015-08-19 | エムシーダブリユー リサーチ フオンデーシヨン インコーポレーテツド | 遺伝子工学的ボツリヌス神経毒 |
| AU2010353292A1 (en) * | 2009-12-16 | 2012-07-12 | Allergan, Inc. | Modified Clostridial toxins comprising an integrated protease cleavage site-binding domain |
| WO2012112434A1 (en) | 2011-02-14 | 2012-08-23 | Allergan, Inc. | Inhibiting aberrant blood vessel formation using retargeted endopeptidases |
| GB201219602D0 (en) * | 2012-10-31 | 2012-12-12 | Syntaxin Ltd | Recombinant clostridium botulinum neurotoxins |
| GB201407525D0 (en) * | 2014-04-29 | 2014-06-11 | Syntaxin Ltd | Manufacture of recombinant clostridium botulinum neurotoxins |
| EP3504226A1 (en) * | 2016-08-24 | 2019-07-03 | President and Fellows of Harvard College | Engineered botulinum neurotoxin |
-
2012
- 2012-10-31 GB GB201219602A patent/GB201219602D0/en not_active Ceased
-
2013
- 2013-10-31 HU HUE17201198A patent/HUE048802T2/hu unknown
- 2013-10-31 DK DK13811605.8T patent/DK2914282T3/en active
- 2013-10-31 PL PL13811605T patent/PL2914282T3/pl unknown
- 2013-10-31 SG SG10201701140WA patent/SG10201701140WA/en unknown
- 2013-10-31 KR KR1020207026658A patent/KR102264478B1/ko active Active
- 2013-10-31 US US14/427,234 patent/US10030238B2/en active Active
- 2013-10-31 SG SG11201502372SA patent/SG11201502372SA/en unknown
- 2013-10-31 ES ES17201198T patent/ES2788199T3/es active Active
- 2013-10-31 PL PL17201198T patent/PL3326644T3/pl unknown
- 2013-10-31 EP EP17201198.3A patent/EP3326644B1/en active Active
- 2013-10-31 IN IN436MUN2015 patent/IN2015MN00436A/en unknown
- 2013-10-31 AU AU2013340610A patent/AU2013340610B2/en not_active Ceased
- 2013-10-31 DK DK17201198.3T patent/DK3326644T3/da active
- 2013-10-31 CA CA2885519A patent/CA2885519A1/en not_active Abandoned
- 2013-10-31 BR BR112015005384A patent/BR112015005384A2/pt not_active Application Discontinuation
- 2013-10-31 EP EP13811605.8A patent/EP2914282B1/en active Active
- 2013-10-31 PT PT172011983T patent/PT3326644T/pt unknown
- 2013-10-31 CN CN201910795176.3A patent/CN110499321A/zh active Pending
- 2013-10-31 ES ES13811605.8T patent/ES2662402T3/es active Active
- 2013-10-31 HU HUE13811605A patent/HUE036764T2/hu unknown
- 2013-10-31 TW TW102139558A patent/TWI626307B/zh not_active IP Right Cessation
- 2013-10-31 PT PT138116058T patent/PT2914282T/pt unknown
- 2013-10-31 MX MX2015005156A patent/MX367080B/es active IP Right Grant
- 2013-10-31 UA UAA201502159A patent/UA118837C2/uk unknown
- 2013-10-31 TW TW108125708A patent/TW202012622A/zh unknown
- 2013-10-31 NO NO13811605A patent/NO2914282T3/no unknown
- 2013-10-31 AR ARP130103981A patent/AR093309A1/es active IP Right Grant
- 2013-10-31 EA EA201590794A patent/EA201590794A8/ru unknown
- 2013-10-31 CN CN201380047542.8A patent/CN104755098A/zh active Pending
- 2013-10-31 EP EP20153122.5A patent/EP3673914B1/en active Active
- 2013-10-31 TW TW107110108A patent/TWI673361B/zh not_active IP Right Cessation
- 2013-10-31 NZ NZ705575A patent/NZ705575A/en not_active IP Right Cessation
- 2013-10-31 WO PCT/GB2013/052845 patent/WO2014068317A1/en not_active Ceased
- 2013-10-31 KR KR1020157010099A patent/KR102188539B1/ko active Active
-
2015
- 2015-03-03 ZA ZA2015/01449A patent/ZA201501449B/en unknown
- 2015-03-08 IL IL237623A patent/IL237623B/en active IP Right Grant
- 2015-04-23 MX MX2019009222A patent/MX2019009222A/es unknown
-
2018
- 2018-05-21 AU AU2018203556A patent/AU2018203556B2/en not_active Ceased
- 2018-12-10 JP JP2018230980A patent/JP2019068823A/ja not_active Ceased
-
2019
- 2019-12-26 AR ARP190103867A patent/AR117738A2/es unknown
-
2020
- 2020-02-05 JP JP2020017612A patent/JP2020078321A/ja active Pending
- 2020-09-30 AU AU2020244481A patent/AU2020244481A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006011966A1 (en) * | 2004-06-30 | 2006-02-02 | Allergan, Inc. | Optimizing expression of active botulinum toxin type e |
| WO2008008805A2 (en) * | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for non-clostridial toxin target cells |
Non-Patent Citations (4)
| Title |
|---|
| Fischer A et al," Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.", J Biol Chem. 2008 Feb 15;283(7):3997-4003. |
| GenBank: PDB: 3FFZ_A,Source: Clostridium botulinum, deposition: Dec 4, 2008. |
| UniProtKB_P30995 (BXE_CLOBU)，http://www.uniprot.org/uniprot/P30995. |
| UniProtKB_P30995 (BXE_CLOBU)，http://www.uniprot.org/uniprot/P30995. Fischer A et al," Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.", J Biol Chem. 2008 Feb 15;283(7):3997-4003. GenBank: PDB: 3FFZ_A,Source: Clostridium botulinum, deposition: Dec 4, 2008. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI626307B (zh) | 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 | |
| JP6994523B2 (ja) | 組換えボツリヌス菌神経毒の生産 | |
| JP2015534814A (ja) | 組換えクロストリジウムボツリヌス神経毒 | |
| HK1254485B (en) | Recombinant clostridium botulinum neurotoxins | |
| HK1254485A1 (en) | Recombinant clostridium botulinum neurotoxins | |
| HK40015514A (en) | Recombinant clostridium botulinum neurotoxins | |
| HK1208359B (en) | Recombinant clostridium botulinum neurotoxins | |
| HK40020226B (en) | Manufacture of recombinant clostridium botulinum neurotoxins | |
| HK1233682B (zh) | 重组肉毒梭菌神经毒素的制造 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |