JP2006512090A - ボツリヌス神経毒b受容体およびその使用 - Google Patents
ボツリヌス神経毒b受容体およびその使用 Download PDFInfo
- Publication number
- JP2006512090A JP2006512090A JP2005507928A JP2005507928A JP2006512090A JP 2006512090 A JP2006512090 A JP 2006512090A JP 2005507928 A JP2005507928 A JP 2005507928A JP 2005507928 A JP2005507928 A JP 2005507928A JP 2006512090 A JP2006512090 A JP 2006512090A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- amino acids
- bont
- acid sequence
- binding
- 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.)
- Pending
Links
- 108010074523 rimabotulinumtoxinB Proteins 0.000 title abstract 2
- 108030001720 Bontoxilysin Proteins 0.000 claims abstract description 324
- 230000027455 binding Effects 0.000 claims abstract description 215
- 150000002270 gangliosides Chemical class 0.000 claims abstract description 142
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 108
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 96
- 229920001184 polypeptide Polymers 0.000 claims abstract description 94
- 238000000034 method Methods 0.000 claims abstract description 66
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 57
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 41
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 41
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 41
- 231100000419 toxicity Toxicity 0.000 claims abstract description 19
- 230000001988 toxicity Effects 0.000 claims abstract description 19
- 102100036151 Synaptotagmin-2 Human genes 0.000 claims abstract description 18
- 108010055445 Synaptotagmin II Proteins 0.000 claims abstract description 14
- 102100036417 Synaptotagmin-1 Human genes 0.000 claims abstract description 12
- 241000193155 Clostridium botulinum Species 0.000 claims abstract description 10
- 230000000903 blocking effect Effects 0.000 claims abstract description 10
- 230000003834 intracellular effect Effects 0.000 claims abstract description 5
- 108010055170 Synaptotagmin I Proteins 0.000 claims abstract 10
- 150000001413 amino acids Chemical class 0.000 claims description 212
- 210000004027 cell Anatomy 0.000 claims description 125
- 108091033319 polynucleotide Proteins 0.000 claims description 35
- 102000040430 polynucleotide Human genes 0.000 claims description 35
- 239000002157 polynucleotide Substances 0.000 claims description 35
- 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 25
- 102000003137 synaptotagmin Human genes 0.000 claims description 16
- 108060008004 synaptotagmin Proteins 0.000 claims description 16
- 241001465754 Metazoa Species 0.000 claims description 14
- 238000012360 testing method Methods 0.000 claims description 14
- 239000013598 vector Substances 0.000 claims description 13
- 230000000295 complement effect Effects 0.000 claims description 10
- 238000009396 hybridization Methods 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 5
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 48
- 125000002421 ganglioside group Chemical group 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
- 230000001413 cellular effect Effects 0.000 abstract description 3
- 239000012634 fragment Substances 0.000 description 69
- 239000003053 toxin Substances 0.000 description 56
- 231100000765 toxin Toxicity 0.000 description 56
- 108700012359 toxins Proteins 0.000 description 56
- 108090000623 proteins and genes Proteins 0.000 description 33
- 241000699666 Mus <mouse, genus> Species 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 30
- 238000002474 experimental method Methods 0.000 description 29
- 235000018102 proteins Nutrition 0.000 description 29
- 102000005962 receptors Human genes 0.000 description 20
- 108020003175 receptors Proteins 0.000 description 20
- 230000003993 interaction Effects 0.000 description 19
- 238000003776 cleavage reaction Methods 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 230000007017 scission Effects 0.000 description 17
- 230000006870 function Effects 0.000 description 15
- 230000024033 toxin binding Effects 0.000 description 15
- 238000003556 assay Methods 0.000 description 14
- 230000001419 dependent effect Effects 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 230000028023 exocytosis Effects 0.000 description 13
- 239000002581 neurotoxin Substances 0.000 description 12
- 231100000618 neurotoxin Toxicity 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 239000011324 bead Substances 0.000 description 11
- 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 description 10
- 102000004183 Synaptosomal-Associated Protein 25 Human genes 0.000 description 10
- 231100000518 lethal Toxicity 0.000 description 10
- 230000001665 lethal effect Effects 0.000 description 10
- 229920004890 Triton X-100 Polymers 0.000 description 9
- 239000013504 Triton X-100 Substances 0.000 description 9
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 9
- 238000003119 immunoblot Methods 0.000 description 9
- 230000009545 invasion Effects 0.000 description 9
- 102200024062 rs1235912910 Human genes 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 230000009471 action Effects 0.000 description 8
- 230000000875 corresponding effect Effects 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 210000001640 nerve ending Anatomy 0.000 description 8
- 238000006386 neutralization reaction Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 108030001722 Tentoxilysin Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 210000000170 cell membrane Anatomy 0.000 description 7
- 230000001086 cytosolic effect Effects 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 241000283707 Capra Species 0.000 description 6
- 101710138657 Neurotoxin Proteins 0.000 description 6
- 206010043376 Tetanus Diseases 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 230000012202 endocytosis Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000000159 protein binding assay Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000010166 immunofluorescence Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 239000003656 tris buffered saline Substances 0.000 description 5
- 208000003508 Botulism Diseases 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 108010058683 Immobilized Proteins Proteins 0.000 description 4
- 102000006384 Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins Human genes 0.000 description 4
- 108010019040 Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins Proteins 0.000 description 4
- 101710124561 Synaptotagmin-2 Proteins 0.000 description 4
- 108010055044 Tetanus Toxin Proteins 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
- 238000012230 antisense oligonucleotides Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000003599 detergent Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 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 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 238000006384 oligomerization reaction Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- 210000002504 synaptic vesicle Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 101150062179 II gene Proteins 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 101150052863 THY1 gene Proteins 0.000 description 3
- 229940053031 botulinum toxin Drugs 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002041 carbon nanotube Substances 0.000 description 3
- 238000000749 co-immunoprecipitation Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000001378 electrochemiluminescence detection Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000028161 membrane depolarization Effects 0.000 description 3
- 102000006240 membrane receptors Human genes 0.000 description 3
- 230000003957 neurotransmitter release Effects 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 239000000816 peptidomimetic Substances 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 230000001960 triggered effect Effects 0.000 description 3
- 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 2
- 229920000936 Agarose Polymers 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
- 241000283690 Bos taurus Species 0.000 description 2
- 102000002110 C2 domains Human genes 0.000 description 2
- 108050009459 C2 domains Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 108010010469 Qa-SNARE Proteins Proteins 0.000 description 2
- 108010005730 R-SNARE Proteins Proteins 0.000 description 2
- 102000001435 Synapsin Human genes 0.000 description 2
- 108050009621 Synapsin Proteins 0.000 description 2
- 102000002215 Synaptobrevin Human genes 0.000 description 2
- 101710124574 Synaptotagmin-1 Proteins 0.000 description 2
- 102000050389 Syntaxin Human genes 0.000 description 2
- 102000013265 Syntaxin 1 Human genes 0.000 description 2
- 108010090618 Syntaxin 1 Proteins 0.000 description 2
- 102000011759 adducin Human genes 0.000 description 2
- 108010076723 adducin Proteins 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 210000004671 cell-free system Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 150000002339 glycosphingolipids Chemical class 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000034217 membrane fusion Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000004412 neuroendocrine cell Anatomy 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 238000010379 pull-down assay Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000004739 secretory vesicle Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 229940118376 tetanus toxin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 101500000960 Bacillus anthracis Protective antigen PA-63 Proteins 0.000 description 1
- 101710117524 Botulinum neurotoxin type B Proteins 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000064494 Diplobatis ommata Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 101000891891 Rattus norvegicus Synaptotagmin-2 Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
- 102000036859 Zinc-dependent proteases Human genes 0.000 description 1
- 108091006973 Zinc-dependent proteases Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 238000013459 approach Methods 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
- 238000012984 biological imaging Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- LEZNRPFLOGYEIO-QSEDPUOVSA-N ganglioside GT1b Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@@H](CO)O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@]4(O[C@H]([C@H](NC(C)=O)[C@@H](O)C4)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 LEZNRPFLOGYEIO-QSEDPUOVSA-N 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 210000005061 intracellular organelle Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000032537 response to toxin Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000009844 retrograde axon cargo transport Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70571—Receptors; Cell surface antigens; Cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cell Biology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Neurosurgery (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- External Artificial Organs (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42295102P | 2002-10-31 | 2002-10-31 | |
| US49812803P | 2003-08-27 | 2003-08-27 | |
| PCT/US2003/034348 WO2005016233A2 (en) | 2002-10-31 | 2003-10-28 | Botulinum neurotoxin b receptors and use thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009229744A Division JP2010006833A (ja) | 2002-10-31 | 2009-10-01 | ボツリヌス神経毒b受容体およびその使用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006512090A true JP2006512090A (ja) | 2006-04-13 |
| JP2006512090A5 JP2006512090A5 (enExample) | 2006-06-01 |
Family
ID=34197667
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2005507928A Pending JP2006512090A (ja) | 2002-10-31 | 2003-10-28 | ボツリヌス神経毒b受容体およびその使用 |
| JP2009229744A Pending JP2010006833A (ja) | 2002-10-31 | 2009-10-01 | ボツリヌス神経毒b受容体およびその使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009229744A Pending JP2010006833A (ja) | 2002-10-31 | 2009-10-01 | ボツリヌス神経毒b受容体およびその使用 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20040191887A1 (enExample) |
| EP (1) | EP1578382B1 (enExample) |
| JP (2) | JP2006512090A (enExample) |
| AT (1) | ATE442161T1 (enExample) |
| AU (1) | AU2003304419A1 (enExample) |
| CA (1) | CA2504532C (enExample) |
| DE (1) | DE60329225D1 (enExample) |
| ES (1) | ES2333319T3 (enExample) |
| IL (1) | IL167943A (enExample) |
| WO (1) | WO2005016233A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023210585A1 (ja) * | 2022-04-25 | 2023-11-02 | 株式会社Jiksak Bioengineering | 標的化剤 |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1578382B1 (en) * | 2002-10-31 | 2009-09-09 | Wisconsin Alumni Research Foundation | Botulinum neurotoxin b receptors and use thereof |
| US7341843B2 (en) * | 2003-04-11 | 2008-03-11 | Allergan, Inc. | Botulinum toxin A peptides and methods of predicting and reducing immunoresistance to botulinum toxin therapy |
| WO2006113648A2 (en) * | 2005-04-18 | 2006-10-26 | University Of Massachusetts | Hn-33 compositions and methods |
| DE102005019302A1 (de) | 2005-04-26 | 2006-11-16 | Toxogen Gmbh | Carrier zum Targeting von Nervenzellen |
| US7985554B2 (en) | 2005-10-14 | 2011-07-26 | Wisconsin Alumni Research Foundation | Botulinum neurotoxin A receptor and the use thereof |
| DE102005051789B4 (de) | 2005-10-28 | 2014-08-07 | Toxogen Gmbh | Der Botulinus Neurotoxin A Proteinrezeptor und seine Anwendungen |
| CN101932936B (zh) | 2007-09-14 | 2016-04-27 | 拜奥麦迪逊公司 | 利用切割序列和间隔子的共振能量转移测定 |
| US10908146B2 (en) | 2011-06-01 | 2021-02-02 | Biomadison, Inc. | Compositions and methods for improving sensitivity in cell based assays |
| US9303285B2 (en) | 2012-01-04 | 2016-04-05 | Biomadison, Inc. | Methods and compounds for increasing sensitivity of botulinum assays |
| US12422428B2 (en) | 2011-06-01 | 2025-09-23 | Biomadison, Inc. | Compositions and methods for cell-based assays |
| LT2715355T (lt) | 2011-06-01 | 2017-06-12 | Biomadison, Inc. | Ne fret (fluorescencijos rezonansinės energijos perdavimas) būdu atliekamas botulino tyrimas |
| US11325954B2 (en) | 2011-06-01 | 2022-05-10 | Biomadison, Inc. | Compositions and methods for stability testing of botulinum toxin |
| WO2015021433A1 (en) | 2013-08-09 | 2015-02-12 | Biomadison, Inc. | Botulinum toxin assay with improved sensitivity |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6994995B1 (en) * | 2001-03-16 | 2006-02-07 | Lexicon Genetics Incorporated | Human synaptotagmin and polynucleotides encoding the same |
| US8022172B2 (en) * | 2001-08-28 | 2011-09-20 | Allergan, Inc. | Luminescence resonance energy transfer (LRET) assays for clostridial toxin activity |
| US7176278B2 (en) * | 2001-08-30 | 2007-02-13 | Biorexis Technology, Inc. | Modified transferrin fusion proteins |
| EP1578382B1 (en) * | 2002-10-31 | 2009-09-09 | Wisconsin Alumni Research Foundation | Botulinum neurotoxin b receptors and use thereof |
| EP1751284A4 (en) * | 2003-12-19 | 2010-01-13 | Wisconsin Alumni Res Found | METHOD AND COMPOSITIONS FOR DETECTING BOTULINUM NEUROTOXINE |
| EP1920248B1 (en) * | 2005-04-05 | 2010-09-29 | Allergan, Inc. | Clostridial toxin activity assays |
| AU2006299933A1 (en) * | 2005-08-02 | 2007-04-19 | Planet Biotechnology, Inc. | Improved chimeric toxin receptor proteins and chimeric toxin receptor proteins for treatment and prevention of anthrax |
| US7985554B2 (en) * | 2005-10-14 | 2011-07-26 | Wisconsin Alumni Research Foundation | Botulinum neurotoxin A receptor and the use thereof |
| WO2013011055A1 (en) * | 2011-07-19 | 2013-01-24 | ETH Zürich | Means and methods for determining clostridial neurotoxins |
-
2003
- 2003-10-28 EP EP03816739A patent/EP1578382B1/en not_active Expired - Lifetime
- 2003-10-28 DE DE60329225T patent/DE60329225D1/de not_active Expired - Lifetime
- 2003-10-28 CA CA2504532A patent/CA2504532C/en not_active Expired - Fee Related
- 2003-10-28 ES ES03816739T patent/ES2333319T3/es not_active Expired - Lifetime
- 2003-10-28 WO PCT/US2003/034348 patent/WO2005016233A2/en not_active Ceased
- 2003-10-28 JP JP2005507928A patent/JP2006512090A/ja active Pending
- 2003-10-28 AU AU2003304419A patent/AU2003304419A1/en not_active Abandoned
- 2003-10-28 AT AT03816739T patent/ATE442161T1/de not_active IP Right Cessation
- 2003-10-28 US US10/695,577 patent/US20040191887A1/en not_active Abandoned
-
2005
- 2005-04-10 IL IL167943A patent/IL167943A/en unknown
-
2009
- 2009-10-01 JP JP2009229744A patent/JP2010006833A/ja active Pending
-
2011
- 2011-10-26 US US13/281,501 patent/US8617573B2/en not_active Expired - Lifetime
Non-Patent Citations (4)
| Title |
|---|
| JPN6008055677, FEBS Lett.,Vol.378(1996)p.253−257 * |
| JPN6008055678, Neurosci.Lett.,Vol.208(1996)p.105−108 * |
| JPN6008055748, J.Cell Biol.,Vol.162,No.7(Sept.2003)p.1293−1303 * |
| JPN6008055749, Microb.Pathog.,Vol.25(1998)p.91−99 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023210585A1 (ja) * | 2022-04-25 | 2023-11-02 | 株式会社Jiksak Bioengineering | 標的化剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1578382A4 (en) | 2007-08-29 |
| EP1578382B1 (en) | 2009-09-09 |
| US8617573B2 (en) | 2013-12-31 |
| WO2005016233A3 (en) | 2005-08-18 |
| EP1578382A2 (en) | 2005-09-28 |
| US20120082672A1 (en) | 2012-04-05 |
| ES2333319T3 (es) | 2010-02-19 |
| CA2504532A1 (en) | 2005-02-24 |
| ATE442161T1 (de) | 2009-09-15 |
| AU2003304419A1 (en) | 2005-03-07 |
| CA2504532C (en) | 2014-09-16 |
| AU2003304419A8 (en) | 2005-03-07 |
| WO2005016233A2 (en) | 2005-02-24 |
| US20040191887A1 (en) | 2004-09-30 |
| DE60329225D1 (de) | 2009-10-22 |
| IL167943A (en) | 2010-12-30 |
| JP2010006833A (ja) | 2010-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2010006833A (ja) | ボツリヌス神経毒b受容体およびその使用 | |
| Dong et al. | Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells | |
| US8450277B2 (en) | Methods for reducing botulinum neurotoxin A toxicity | |
| Rummel et al. | The HCC‐domain of botulinum neurotoxins A and B exhibits a singular ganglioside binding site displaying serotype specific carbohydrate interaction | |
| Rummel et al. | Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation‐dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor | |
| Wendler et al. | Homotypic fusion of immature secretory granules during maturation requires syntaxin 6 | |
| Pirazzini et al. | Double anchorage to the membrane and intact inter‐chain disulfide bond are required for the low pH induced entry of tetanus and botulinum neurotoxins into neurons | |
| US20080090270A1 (en) | Nogo receptor homologues and their use | |
| US8771707B2 (en) | Botulinum neurotoxin E receptors and uses thereof | |
| Rickman et al. | Comparative analysis of tandem C2 domains from the mammalian synaptotagmin family | |
| US8476024B2 (en) | Botulinum neurotoxin a protein receptor and uses thereof | |
| JP2004526421A (ja) | 真核細胞分裂遺伝子並びに増殖疾患の診断および処置におけるそれらの使用 | |
| US20080026363A1 (en) | Acetyl coa carboxylase 2 sequences and methods | |
| Wattenberg et al. | An artificial mitochondrial tail signal/anchor sequence confirms a requirement for moderate hydrophobicity for targeting | |
| Yelin et al. | Glycosylation of a vesicular monoamine transporter: a mutation in a conserved proline residue affects the activity, glycosylation, and localization of the transporter | |
| CA2292644A1 (en) | Receptor for a bacillus thuringiensis toxin | |
| AU1614400A (en) | Human glycine transporter type 2 | |
| EP1466975A1 (en) | Postsynaptic proteins | |
| Koticha | The cysteine-rich domain of SNAP-25 is necessary for plasma membrane targeting and regulated exocytosis | |
| Dürr | Functional Significance of Na, K-and H, K-ATPase-subunits studied by Voltage-Clamp Fluorometry | |
| JP2002238578A (ja) | ラットedg7受容体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060324 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060324 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081104 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090122 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090129 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090507 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090601 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091001 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091110 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091125 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20091125 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091218 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20091225 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100125 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100423 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100506 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100726 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20101029 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20111107 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111111 |