RU2582266C2 - Нейротоксины, проявляющие сокращенную биологическую активность - Google Patents
Нейротоксины, проявляющие сокращенную биологическую активность Download PDFInfo
- Publication number
- RU2582266C2 RU2582266C2 RU2012103376/10A RU2012103376A RU2582266C2 RU 2582266 C2 RU2582266 C2 RU 2582266C2 RU 2012103376/10 A RU2012103376/10 A RU 2012103376/10A RU 2012103376 A RU2012103376 A RU 2012103376A RU 2582266 C2 RU2582266 C2 RU 2582266C2
- Authority
- RU
- Russia
- Prior art keywords
- polypeptide
- biological effect
- neurotoxin
- present
- reduced duration
- Prior art date
Links
- 239000002581 neurotoxin Substances 0.000 title claims abstract description 72
- 231100000618 neurotoxin Toxicity 0.000 title claims abstract description 72
- 230000004071 biological effect Effects 0.000 title claims abstract description 39
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 115
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 114
- 229920001184 polypeptide Polymers 0.000 claims abstract description 111
- 101710138657 Neurotoxin Proteins 0.000 claims abstract description 66
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 54
- 239000002157 polynucleotide Substances 0.000 claims abstract description 54
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 54
- 230000015556 catabolic process Effects 0.000 claims abstract description 18
- 238000006731 degradation reaction Methods 0.000 claims abstract description 18
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- 108010055044 Tetanus Toxin Proteins 0.000 claims abstract description 9
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 claims abstract description 5
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 claims abstract description 5
- 241000607479 Yersinia pestis Species 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims description 44
- 229940079593 drug Drugs 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 239000013598 vector Substances 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 14
- 210000003205 muscle Anatomy 0.000 claims description 9
- 230000001580 bacterial effect Effects 0.000 claims description 8
- 241000894006 Bacteria Species 0.000 claims description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 7
- 238000001356 surgical procedure Methods 0.000 claims description 7
- 206010033799 Paralysis Diseases 0.000 claims description 5
- 230000029663 wound healing Effects 0.000 claims description 5
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 4
- 206010043248 Tendon rupture Diseases 0.000 claims description 4
- 206010000496 acne Diseases 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 claims description 4
- 239000004053 dental implant Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000014617 hemorrhoid Diseases 0.000 claims description 4
- 210000004394 hip joint Anatomy 0.000 claims description 4
- 210000000629 knee joint Anatomy 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 241000193403 Clostridium Species 0.000 claims description 3
- 241000588724 Escherichia coli Species 0.000 claims description 3
- 230000007794 irritation Effects 0.000 claims description 3
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 230000008602 contraction Effects 0.000 claims description 2
- 230000008450 motivation Effects 0.000 claims description 2
- 239000002773 nucleotide Substances 0.000 claims description 2
- 125000003729 nucleotide group Chemical group 0.000 claims description 2
- 230000000968 intestinal effect Effects 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 108020004707 nucleic acids Proteins 0.000 abstract 2
- 102000039446 nucleic acids Human genes 0.000 abstract 2
- 108091060210 Heavy strand Proteins 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 108030001720 Bontoxilysin Proteins 0.000 description 47
- 210000004027 cell Anatomy 0.000 description 38
- 108090000623 proteins and genes Proteins 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 15
- 239000000203 mixture Substances 0.000 description 12
- 239000002537 cosmetic Substances 0.000 description 9
- 108030001722 Tentoxilysin Proteins 0.000 description 8
- 241000700605 Viruses Species 0.000 description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 230000000536 complexating effect Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000006337 proteolytic cleavage Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 241000193155 Clostridium botulinum Species 0.000 description 4
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 4
- 229940053031 botulinum toxin Drugs 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 241001112695 Clostridiales Species 0.000 description 3
- 241000193449 Clostridium tetani Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000006652 catabolic pathway Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 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 description 2
- 101100272852 Clostridium botulinum (strain Langeland / NCTC 10281 / Type F) F gene Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 208000014094 Dystonic disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 208000004350 Strabismus Diseases 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000001153 anti-wrinkle effect Effects 0.000 description 2
- 210000004507 artificial chromosome Anatomy 0.000 description 2
- 206010005159 blepharospasm Diseases 0.000 description 2
- 230000000744 blepharospasm Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- -1 hsRNA Proteins 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004118 muscle contraction Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 229940124272 protein stabilizer Drugs 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001256 tonic effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 240000004507 Abelmoschus esculentus Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102100036826 Aldehyde oxidase 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
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 description 1
- 241000194107 Bacillus megaterium Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101710117542 Botulinum neurotoxin type A Proteins 0.000 description 1
- 208000003508 Botulism Diseases 0.000 description 1
- XMWRBQBLMFGWIX-UHFFFAOYSA-N C60 fullerene Chemical class C12=C3C(C4=C56)=C7C8=C5C5=C9C%10=C6C6=C4C1=C1C4=C6C6=C%10C%10=C9C9=C%11C5=C8C5=C8C7=C3C3=C7C2=C1C1=C2C4=C6C4=C%10C6=C9C9=C%11C5=C5C8=C3C3=C7C1=C1C2=C4C6=C2C9=C5C3=C12 XMWRBQBLMFGWIX-UHFFFAOYSA-N 0.000 description 1
- 241000219357 Cactaceae Species 0.000 description 1
- 101100457461 Caenorhabditis elegans mnm-2 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 101100382092 Clostridium botulinum D phage ntnha gene Proteins 0.000 description 1
- 101100004794 Clostridium botulinum ant gene Proteins 0.000 description 1
- 101710101803 DNA-binding protein J Proteins 0.000 description 1
- 241000283323 Delphinapterus leucas Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 102100035493 E3 ubiquitin-protein ligase NEDD4-like Human genes 0.000 description 1
- 101710155393 E3 ubiquitin-protein ligase NEDD4-like Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 102100028501 Galanin peptides Human genes 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101000582320 Homo sapiens Neurogenic differentiation factor 6 Proteins 0.000 description 1
- 101000761717 Hydrophis lapemoides Short neurotoxin 1 Proteins 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 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
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101100396982 Mus musculus Inmt gene Proteins 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 102100030589 Neurogenic differentiation factor 6 Human genes 0.000 description 1
- 101000800747 Ophiophagus hannah Long neurotoxin 1 Proteins 0.000 description 1
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 1
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 101710118538 Protease Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 102000000583 SNARE Proteins Human genes 0.000 description 1
- 108010041948 SNARE Proteins Proteins 0.000 description 1
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 description 1
- 101100484930 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) VPS41 gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000000692 Student's t-test Methods 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 108010079650 abobotulinumtoxinA Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940089093 botox Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940098753 dysport Drugs 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003241 endoproteolytic effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000010228 ex vivo assay Methods 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 201000002904 focal dystonia Diseases 0.000 description 1
- 229910003472 fullerene Inorganic materials 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000037315 hyperhidrosis Effects 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 108010024001 incobotulinumtoxinA Proteins 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 108010059642 isinglass Proteins 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000006655 lysosomal degradation pathway Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000007319 proteasomal degradation pathway Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229940102127 rubidium chloride Drugs 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 210000002182 synaptic membrane Anatomy 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 229940018272 xeomin Drugs 0.000 description 1
Images
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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- 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
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1282—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Clostridium (G)
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/95—Fusion polypeptide containing a motif/fusion for degradation (ubiquitin fusions, PEST sequence)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Mycology (AREA)
- Birds (AREA)
- Toxicology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Surgery (AREA)
- Ophthalmology & Optometry (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27019809P | 2009-07-02 | 2009-07-02 | |
| EP09164365 | 2009-07-02 | ||
| US61/270,198 | 2009-07-02 | ||
| EP09164365.0 | 2009-07-02 | ||
| PCT/EP2010/059398 WO2011000929A1 (en) | 2009-07-02 | 2010-07-01 | Neurotoxins exhibiting shortened biological activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2012103376A RU2012103376A (ru) | 2013-08-10 |
| RU2582266C2 true RU2582266C2 (ru) | 2016-04-20 |
Family
ID=40911088
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012103376/10A RU2582266C2 (ru) | 2009-07-02 | 2010-07-01 | Нейротоксины, проявляющие сокращенную биологическую активность |
Country Status (14)
| Country | Link |
|---|---|
| US (4) | US8586329B2 (enExample) |
| EP (1) | EP2449101B1 (enExample) |
| JP (2) | JP6059986B2 (enExample) |
| KR (2) | KR20120104140A (enExample) |
| CN (1) | CN102471765B9 (enExample) |
| AU (1) | AU2010267963B2 (enExample) |
| BR (1) | BRPI1014253A2 (enExample) |
| CA (1) | CA2763692A1 (enExample) |
| ES (1) | ES2693705T3 (enExample) |
| IL (1) | IL216414A (enExample) |
| IN (1) | IN2012DN00733A (enExample) |
| MX (2) | MX352265B (enExample) |
| RU (1) | RU2582266C2 (enExample) |
| WO (1) | WO2011000929A1 (enExample) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19925739A1 (de) * | 1999-06-07 | 2000-12-21 | Biotecon Ges Fuer Biotechnologische Entwicklung & Consulting Mbh | Therapeutikum mit einem Botulinum-Neurotoxin |
| AR061669A1 (es) * | 2006-06-29 | 2008-09-10 | Merz Pharma Gmbh & Co Kgaa | Aplicacion de alta frecuencia de terapia con toxina botulinica |
| US9746475B2 (en) | 2011-03-14 | 2017-08-29 | University Of Southern California | Antibody and antibody mimetic for visualization and ablation of endogenous proteins |
| CA2855173A1 (en) * | 2011-11-09 | 2013-05-16 | Merz Pharma Gmbh & Co. Kgaa | Neurotoxins exhibiting shortened biological activity |
| JP2015527067A (ja) * | 2012-08-20 | 2015-09-17 | メルツ ファーマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト アウフ アクティーン | N末端リシンを包有する組換タンパク質を製造する新規の方法 |
| AP2015008328A0 (en) | 2012-10-16 | 2015-03-31 | Almirall Sa | Pyrrolotriazinone derivatives as pi3k inhibitors |
| MX381995B (es) * | 2012-11-21 | 2025-03-13 | Ipsen Bioinnovation Ltd | Métodos para la producción de polipéptidos procesados proteolíticamente. |
| US10494645B2 (en) | 2013-04-18 | 2019-12-03 | Fondazione Telethon | Effective delivery of large genes by dual AAV vectors |
| PL2952205T3 (pl) | 2014-06-06 | 2018-01-31 | Kleiner Fisman Galit | Toksyna botulinowa do zastosowania do leczenia paratonii |
| EP3154562A1 (en) * | 2014-06-13 | 2017-04-19 | Merz Pharma GmbH & Co. KGaA | Novel uses of recombinant clostridial neurotoxins with decreased duration of effect |
| US20170189500A1 (en) | 2014-06-13 | 2017-07-06 | Merz Pharma Gmbh & Co. Kgaa | Use of recombinant clostridial neurotoxins for the treatment of patients having certain muscle-related disorders |
| EP3154635A1 (en) | 2014-06-13 | 2017-04-19 | Merz Pharma GmbH & Co. KGaA | Novel uses of recombinant clostridial neurotoxins with decreased duration of effect |
| EP3154572A1 (en) * | 2014-06-13 | 2017-04-19 | Merz Pharma GmbH & Co. KGaA | Novel uses of recombinant clostridial neurotoxins with decreased duration of effect |
| JP6798993B2 (ja) | 2014-12-23 | 2020-12-09 | メルツ ファーマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディト ゲゼルシャフト アウフ アクティーン | ボツリヌス毒素プレフィルド容器 |
| DK3242884T3 (da) | 2015-01-09 | 2021-04-19 | Ipsen Bioinnovation Ltd | Kationiske neurotoksiner |
| DK3265571T3 (da) * | 2015-03-03 | 2022-06-27 | Fond Telethon | Fler-vektorsystem og anvendelse heraf |
| WO2016168740A2 (en) * | 2015-04-16 | 2016-10-20 | Spencer Juliet V | Detection of human cytomegalovirus in breast cancer |
| TW201718627A (zh) * | 2015-06-11 | 2017-06-01 | 梅茲製藥有限兩合公司 | 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞 |
| KR101793328B1 (ko) * | 2015-07-03 | 2017-11-03 | 씨제이제일제당 (주) | L-라이신 생산능을 갖는 미생물 및 이를 이용한 l-라이신 생산 방법 |
| WO2017063743A1 (en) | 2015-10-14 | 2017-04-20 | Merz Pharma Gmbh & Co. Kgaa | Improvements to ultrasound-based therapy of photoaged tissue |
| ES2893838T3 (es) | 2016-03-02 | 2022-02-10 | Merz Pharma Gmbh & Co Kgaa | Composición que comprende toxina botulínica |
| EP3467499A4 (en) * | 2016-06-02 | 2020-02-19 | Hoyu Co., Ltd. | EIALLERGIEANTIGEN |
| TWI737742B (zh) | 2016-06-22 | 2021-09-01 | 德商梅茲製藥有限兩合公司 | 肉毒桿菌毒素的預填充式注射器系統、具有其之套組以及其之使用 |
| EP3290437A1 (en) | 2016-08-31 | 2018-03-07 | Merz Pharma GmbH & Co. KGaA | Novel recombinant clostridial neurotoxins with decreased duration of effect |
| EP3312193A1 (en) | 2016-10-19 | 2018-04-25 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum neurotoxins with accelerated onset of effect |
| PT3545084T (pt) * | 2016-11-28 | 2025-11-17 | New Matterhorn Llc | Trealose fosforilase |
| EP3642222A1 (en) | 2017-06-20 | 2020-04-29 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum toxin with increased duration of effect |
| EP3649143B1 (en) | 2017-07-06 | 2022-08-31 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum neurotoxins with increased duration of effect |
| US11707510B2 (en) * | 2018-02-16 | 2023-07-25 | Preclinics Discovery Gmbh | Nucleic acid-based botulinum neurotoxin for therapeutic use |
| CN111868252B (zh) * | 2018-03-12 | 2025-06-03 | 科纳根公司 | 甜菊糖苷莱苞迪苷j和莱苞迪苷n的生物合成生产 |
| AU2019233603B2 (en) * | 2018-03-13 | 2025-06-26 | Smivet B.V. | Single domain antibodies binding to tetanus neurotoxin |
| US10751399B2 (en) * | 2018-03-20 | 2020-08-25 | Cho Pharma Usa, Inc. | Chimeric antigen receptors that bind to SSEA4 and uses thereof |
| JP7311496B2 (ja) * | 2018-05-02 | 2023-07-19 | 天野エンザイム株式会社 | 改変型エステラーゼ及びその用途 |
| CN108588087B (zh) * | 2018-05-16 | 2022-06-03 | 南京农业大学 | 一种提高植物抗病性的基因GmLecRK-R及其应用 |
| CN111757931B (zh) * | 2018-12-21 | 2023-11-28 | 福尼亚生物处理股份有限公司 | 变体g6p g7p葡糖淀粉酶组合物及方法 |
| CN109998055B (zh) * | 2019-04-09 | 2022-03-25 | 黑龙江省科学院大庆分院 | 一种汉麻籽抗氧化多肽咀嚼片及其制备方法 |
| CN110100945B (zh) * | 2019-05-05 | 2022-05-03 | 黑龙江省科学院大庆分院 | 一种汉麻降血脂肽组合物及其应用 |
| WO2020253537A1 (zh) * | 2019-06-21 | 2020-12-24 | 苏州克睿基因生物科技有限公司 | 一种检测非洲猪瘟病毒的方法和试剂盒 |
| CN110295150A (zh) * | 2019-07-17 | 2019-10-01 | 天津润德生物科技有限公司 | 一类腺依赖病毒病毒重组质粒、重组病毒及构建方法 |
| CN110540996B (zh) * | 2019-08-29 | 2022-01-28 | 华中农业大学 | 一种克氏原螯虾i型溶菌酶gLysi2基因、其编码的gLysi2蛋白及其应用 |
| EP4458975A3 (en) * | 2019-09-30 | 2025-02-12 | Gilead Sciences, Inc. | Hbv vaccines and methods treating hbv |
| CN110643616A (zh) * | 2019-10-22 | 2020-01-03 | 云南省烟草农业科学研究院 | 一种烟草降烟碱合成调控基因NtERF91的克隆和应用 |
| EP4108676A4 (en) * | 2020-02-22 | 2024-06-05 | JCR Pharmaceuticals Co., Ltd. | HUMAN TRANSFERRIN RECEPTOR BINDING PEPTIDE |
| CN112540178B (zh) * | 2020-08-06 | 2023-12-19 | 武汉天德生物科技有限公司 | 一种检测早期老年痴呆症的免疫组化试剂盒及其使用方法 |
| CN112662644B (zh) * | 2021-01-19 | 2022-04-22 | 华南理工大学 | 一种甘油磷酸二酯磷酸二酯酶突变体及其应用 |
| CN113899907B (zh) * | 2021-09-07 | 2023-06-27 | 中国农业科学院油料作物研究所 | 一步式高效筛选黄曲霉毒素绿色防控材料的方法及其应用 |
| CN115109759B (zh) * | 2022-06-24 | 2024-05-03 | 浙江工业大学 | 羰基还原酶LsCR突变体、工程菌及在不对称还原羰基化合物制备手性醇中的应用 |
| CN115944721B (zh) * | 2022-12-14 | 2025-11-25 | 内蒙古华希生物科技有限公司 | 一种免疫组合物、其制备方法及应用 |
| CN117741160B (zh) * | 2023-12-21 | 2024-07-12 | 汉王科技股份有限公司 | 嗅觉受体在识别乙醇中的用途和检测乙醇的方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002008268A2 (en) * | 2000-07-21 | 2002-01-31 | Allergan, Inc. | Leucine-based motif and clostridial neurotoxins |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW574036B (en) | 1998-09-11 | 2004-02-01 | Elan Pharm Inc | Stable liquid compositions of botulinum toxin |
| US7491799B2 (en) * | 2000-07-21 | 2009-02-17 | Allergan, Inc. | Modified botulinum neurotoxins |
| US20020127247A1 (en) * | 2000-11-17 | 2002-09-12 | Allergen Sales, Inc. | Modified clostridial neurotoxins with altered biological persistence |
| DE10333317A1 (de) | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
| US7172764B2 (en) * | 2003-11-17 | 2007-02-06 | Allergan, Inc. | Rescue agents for treating botulinum toxin intoxications |
| US7825233B2 (en) * | 2004-06-30 | 2010-11-02 | Allergan, Inc. | Optimizing expression of active Botulinum Toxin type E |
| US20060004334A1 (en) | 2004-06-30 | 2006-01-05 | Kimberly-Clark Worldwide, Inc. | Stabilized absorbent structures |
| BRPI0513850A (pt) | 2004-07-26 | 2008-05-20 | Merz Pharma Gmbh & Co Kgaa | composição terapêutica com uma neurotoxina botulìnica |
-
2010
- 2010-07-01 AU AU2010267963A patent/AU2010267963B2/en not_active Ceased
- 2010-07-01 CN CN201080027593.0A patent/CN102471765B9/zh not_active Expired - Fee Related
- 2010-07-01 KR KR1020127001754A patent/KR20120104140A/ko not_active Ceased
- 2010-07-01 MX MX2014014585A patent/MX352265B/es unknown
- 2010-07-01 IN IN733DEN2012 patent/IN2012DN00733A/en unknown
- 2010-07-01 EP EP10726549.8A patent/EP2449101B1/en active Active
- 2010-07-01 ES ES10726549.8T patent/ES2693705T3/es active Active
- 2010-07-01 BR BRPI1014253A patent/BRPI1014253A2/pt not_active Application Discontinuation
- 2010-07-01 MX MX2011013014A patent/MX2011013014A/es active IP Right Grant
- 2010-07-01 JP JP2012516796A patent/JP6059986B2/ja not_active Expired - Fee Related
- 2010-07-01 US US13/381,533 patent/US8586329B2/en not_active Expired - Fee Related
- 2010-07-01 WO PCT/EP2010/059398 patent/WO2011000929A1/en not_active Ceased
- 2010-07-01 KR KR1020177003042A patent/KR101818895B1/ko not_active Expired - Fee Related
- 2010-07-01 RU RU2012103376/10A patent/RU2582266C2/ru not_active IP Right Cessation
- 2010-07-01 CA CA2763692A patent/CA2763692A1/en active Pending
-
2011
- 2011-11-17 IL IL216414A patent/IL216414A/en not_active IP Right Cessation
-
2013
- 2013-10-17 US US14/056,247 patent/US9193771B2/en active Active
-
2015
- 2015-07-16 JP JP2015141904A patent/JP2015231378A/ja active Pending
- 2015-10-19 US US14/886,485 patent/US9511114B2/en active Active
-
2016
- 2016-11-03 US US15/342,376 patent/US9827298B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002008268A2 (en) * | 2000-07-21 | 2002-01-31 | Allergan, Inc. | Leucine-based motif and clostridial neurotoxins |
Non-Patent Citations (1)
| Title |
|---|
| OYLER G.A. ET AL., Therapeutics which accelerate degradation BoNT/A LC within neurons, Toxicon, 2008, v. 51, p. 17. DASGUPTA B.R., Botulinum neurotoxins: perspective on their existence and as polyproteins harboring viral proteases, J Gen Appl Microbiol, 2006, v.52, no.1, pp. 1-8. FALNES P.O. ET AL., Modulation of the intracellular stability and toxicity of diphtheria toxin through degradation by the N-end rule pathway, EMBO JOURNAL, 1998, v. 17, no. 2, p. 615-625. GUPTA P.K. ET AL., Role of N-terminal amino acids in the potency of anthrax lethal factor, PLoS One, 2008, v.3, no.9, e3130. doi: 10.1371/journal.pone.0003130. SUZUKI T. ET AL., Degradation signal in the lysine-asparagine sequence space, EMBO JOURNAL, 1999, v. 18, no. 21, p. 6017-6026. * |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI1014253A2 (pt) | 2016-04-12 |
| JP2015231378A (ja) | 2015-12-24 |
| US20120107362A1 (en) | 2012-05-03 |
| US9193771B2 (en) | 2015-11-24 |
| RU2012103376A (ru) | 2013-08-10 |
| KR101818895B1 (ko) | 2018-01-15 |
| AU2010267963A1 (en) | 2011-12-22 |
| MX2011013014A (es) | 2012-01-27 |
| CA2763692A1 (en) | 2011-01-06 |
| US9511114B2 (en) | 2016-12-06 |
| WO2011000929A1 (en) | 2011-01-06 |
| CN102471765A (zh) | 2012-05-23 |
| US20140045760A1 (en) | 2014-02-13 |
| EP2449101A1 (en) | 2012-05-09 |
| US20160030511A1 (en) | 2016-02-04 |
| CN102471765B (zh) | 2016-05-11 |
| IN2012DN00733A (enExample) | 2015-06-19 |
| EP2449101B1 (en) | 2018-10-10 |
| JP6059986B2 (ja) | 2017-01-11 |
| US9827298B2 (en) | 2017-11-28 |
| US8586329B2 (en) | 2013-11-19 |
| IL216414A (en) | 2016-08-31 |
| CN102471765B9 (zh) | 2016-07-27 |
| IL216414A0 (en) | 2012-02-29 |
| AU2010267963B2 (en) | 2015-09-24 |
| MX352265B (es) | 2017-11-16 |
| KR20120104140A (ko) | 2012-09-20 |
| ES2693705T3 (es) | 2018-12-13 |
| JP2012531191A (ja) | 2012-12-10 |
| KR20170016529A (ko) | 2017-02-13 |
| HK1171246A1 (zh) | 2013-03-22 |
| US20170072030A1 (en) | 2017-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2582266C2 (ru) | Нейротоксины, проявляющие сокращенную биологическую активность | |
| AU2012334080B2 (en) | Neurotoxins exhibiting shortened biological activity | |
| US9314514B2 (en) | Modified neurotoxins with poly-glycine and uses thereof | |
| JP2013139454A (ja) | 神経細胞に化合物を導入するために用いられる輸送タンパク質 | |
| AU2005205597A1 (en) | Chimera botulinum toxin type E | |
| TW201718627A (zh) | 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞 | |
| US20140170133A1 (en) | Alteration of proteolytic cleavage of botulinum neurotoxins | |
| HK1171246B (en) | Neurotoxins exhibiting shortened biological activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20190702 |