JP2019533430A5 - - Google Patents
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- Publication number
- JP2019533430A5 JP2019533430A5 JP2019510791A JP2019510791A JP2019533430A5 JP 2019533430 A5 JP2019533430 A5 JP 2019533430A5 JP 2019510791 A JP2019510791 A JP 2019510791A JP 2019510791 A JP2019510791 A JP 2019510791A JP 2019533430 A5 JP2019533430 A5 JP 2019533430A5
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- bont
- chimeric molecule
- serotype
- substitution mutations
- 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.)
- Granted
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- 229920001184 polypeptide Polymers 0.000 claims description 86
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 86
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 86
- 230000035772 mutation Effects 0.000 claims description 65
- 238000006467 substitution reaction Methods 0.000 claims description 65
- 108030001720 Bontoxilysin Proteins 0.000 claims description 48
- 231100001103 botulinum neurotoxin Toxicity 0.000 claims description 48
- 108091005804 Peptidases Proteins 0.000 claims description 25
- 239000004365 Protease Substances 0.000 claims description 25
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 25
- 102000039446 nucleic acids Human genes 0.000 claims description 20
- 108020004707 nucleic acids Proteins 0.000 claims description 20
- 150000007523 nucleic acids Chemical class 0.000 claims description 20
- 238000003776 cleavage reaction Methods 0.000 claims description 15
- 230000007017 scission Effects 0.000 claims description 15
- 102000005962 receptors Human genes 0.000 claims description 14
- 108020003175 receptors Proteins 0.000 claims description 14
- 208000014094 Dystonic disease Diseases 0.000 claims description 12
- 238000012986 modification Methods 0.000 claims description 12
- 230000004048 modification Effects 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 208000010118 dystonia Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 230000005945 translocation Effects 0.000 claims description 9
- 241000193155 Clostridium botulinum Species 0.000 claims description 8
- 101000874762 Homo sapiens Synaptotagmin-2 Proteins 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 230000001755 vocal effect Effects 0.000 claims description 6
- 230000001537 neural effect Effects 0.000 claims description 5
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 4
- 206010005159 blepharospasm Diseases 0.000 claims description 4
- 230000000744 blepharospasm Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000001148 spastic effect Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 238000013508 migration Methods 0.000 claims description 3
- 230000005012 migration Effects 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 241000238876 Acari Species 0.000 claims description 2
- 208000019505 Deglutition disease Diseases 0.000 claims description 2
- 208000012661 Dyskinesia Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 208000004095 Hemifacial Spasm Diseases 0.000 claims description 2
- 208000008454 Hyperhidrosis Diseases 0.000 claims description 2
- 208000015592 Involuntary movements Diseases 0.000 claims description 2
- 208000007101 Muscle Cramp Diseases 0.000 claims description 2
- 208000026025 Muscle tone disease Diseases 0.000 claims description 2
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 claims description 2
- 206010029279 Neurogenic bladder Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 206010033799 Paralysis Diseases 0.000 claims description 2
- 208000036496 Pelvic floor dyssynergia Diseases 0.000 claims description 2
- 208000005392 Spasm Diseases 0.000 claims description 2
- 206010067672 Spasmodic dysphonia Diseases 0.000 claims description 2
- 208000004350 Strabismus Diseases 0.000 claims description 2
- 206010044074 Torticollis Diseases 0.000 claims description 2
- 206010044565 Tremor Diseases 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 201000002898 anismus Diseases 0.000 claims description 2
- 230000000975 bioactive effect Effects 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 201000002866 cervical dystonia Diseases 0.000 claims description 2
- 206010009887 colitis Diseases 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 210000003414 extremity Anatomy 0.000 claims description 2
- 201000002904 focal dystonia Diseases 0.000 claims description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 230000037315 hyperhidrosis Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 claims description 2
- 201000002851 oromandibular dystonia Diseases 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 150000003384 small molecules Chemical class 0.000 claims description 2
- 201000002849 spasmodic dystonia Diseases 0.000 claims description 2
- 208000018198 spasticity Diseases 0.000 claims description 2
- 210000001364 upper extremity Anatomy 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 101710138657 Neurotoxin Proteins 0.000 claims 1
- 239000002581 neurotoxin Substances 0.000 claims 1
- 231100000618 neurotoxin Toxicity 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 5
- 241001112695 Clostridiales Species 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662378967P | 2016-08-24 | 2016-08-24 | |
| US62/378,967 | 2016-08-24 | ||
| PCT/US2017/048508 WO2018039506A1 (en) | 2016-08-24 | 2017-08-24 | Engineered botulinum neurotoxin |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019533430A JP2019533430A (ja) | 2019-11-21 |
| JP2019533430A5 true JP2019533430A5 (enExample) | 2020-10-01 |
| JP7100020B2 JP7100020B2 (ja) | 2022-07-12 |
Family
ID=59799485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019510791A Active JP7100020B2 (ja) | 2016-08-24 | 2017-08-24 | 操作されたボツリヌス神経毒素 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US11117935B2 (enExample) |
| EP (1) | EP3504226A1 (enExample) |
| JP (1) | JP7100020B2 (enExample) |
| CN (1) | CN110072880B (enExample) |
| WO (1) | WO2018039506A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2690773C (en) * | 2007-07-10 | 2013-09-17 | Medy-Tox, Inc. | Pharmaceutical liquid composition of botulinum toxin with improved stability |
| ES2847241T3 (es) | 2012-05-30 | 2021-08-02 | Harvard College | Neurotoxina botulínica genéticamente modificada |
| GB201219602D0 (en) * | 2012-10-31 | 2012-12-12 | Syntaxin Ltd | Recombinant clostridium botulinum neurotoxins |
| CN115925835A (zh) * | 2015-03-26 | 2023-04-07 | 哈佛大学校长及研究员协会 | 工程改造的肉毒杆菌神经毒素 |
| 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 |
| GB201607901D0 (en) | 2016-05-05 | 2016-06-22 | Ipsen Biopharm Ltd | Chimeric neurotoxins |
| PL3481852T3 (pl) * | 2016-07-08 | 2023-07-24 | Children's Medical Center Corporation | Nowa neurotoksyna botulinowa i jej pochodne |
| US11117935B2 (en) | 2016-08-24 | 2021-09-14 | President And Fellows Of Harvard College | Engineered botulinum neurotoxin |
| US11707510B2 (en) * | 2018-02-16 | 2023-07-25 | Preclinics Discovery Gmbh | Nucleic acid-based botulinum neurotoxin for therapeutic use |
| CN114958887B (zh) * | 2021-02-26 | 2024-10-25 | 重庆誉颜制药有限公司 | 一种经修饰的毒素多肽的制备方法 |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4737462A (en) | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
| US4518584A (en) | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
| US5053005A (en) | 1989-04-21 | 1991-10-01 | Gary E. Borodic | Chemomodulation of curvature of the juvenile spine |
| US5766605A (en) | 1994-04-15 | 1998-06-16 | Mount Sinai School Of Medicine Of The City University Of New York | Treatment of autonomic nerve dysfunction with botulinum toxin |
| DE69526340T2 (de) | 1994-05-09 | 2002-11-14 | William J. Binder | Botulinumtoxin ZUR REDUKTION VON Migraine -KOPFSCHMERZEN |
| DE69511860T2 (de) | 1994-05-31 | 2000-02-10 | Allergan, Inc. | Modifizierung von clostridium-toxinen und ihre anwendung als transport proteine |
| GB9411138D0 (en) | 1994-06-03 | 1994-07-27 | Microbiological Res Authority | Toxin assay |
| US6967088B1 (en) | 1995-03-16 | 2005-11-22 | Allergan, Inc. | Soluble recombinant botulinum toxin proteins |
| GB9508204D0 (en) | 1995-04-21 | 1995-06-07 | Speywood Lab Ltd | A novel agent able to modify peripheral afferent function |
| US5721215A (en) | 1996-03-20 | 1998-02-24 | Allergan | Injectable therapy for control of muscle spasms and pain related to muscle spasms |
| GB9617671D0 (en) | 1996-08-23 | 1996-10-02 | Microbiological Res Authority | Recombinant toxin fragments |
| EP1105153A4 (en) | 1996-08-28 | 2005-01-19 | Ophidian Pharm Inc | POLYVALENT VACCINE AGAINST NEUROTOXIN (CLOSTRIDIUM BOTILINUM) |
| GB9721189D0 (en) | 1997-10-08 | 1997-12-03 | Speywood Lab The Limited | Analgesic conjugates |
| US20080032931A1 (en) | 1999-08-25 | 2008-02-07 | Steward Lance E | Activatable clostridial toxins |
| CA2380457A1 (en) * | 1999-08-25 | 2001-03-01 | Allergan Sales, Inc. | Activatable recombinant neurotoxins |
| US6113915A (en) | 1999-10-12 | 2000-09-05 | Allergan Sales, Inc. | Methods for treating pain |
| US20040033241A1 (en) | 2000-06-02 | 2004-02-19 | Allergan, Inc. | Controlled release botulinum toxin system |
| AU2003237346A1 (en) | 2002-05-31 | 2003-12-19 | Thomas Jefferson University | Compositions and methods for transepithelial molecular transport |
| US7148041B2 (en) | 2003-09-25 | 2006-12-12 | Allergan, Inc. | Animal product free media and processes for obtaining a botulinum toxin |
| ATE533853T1 (de) | 2004-02-24 | 2011-12-15 | Allergan Inc | Botulinumtoxin-screening-assays |
| KR100668570B1 (ko) | 2004-06-28 | 2007-01-16 | 입센 리미티드 | 복재신경 포착에 의한 무릎 관절 통증 치료를 위한,보툴리눔 독소를 포함하는 제약 조성물 |
| US7514088B2 (en) | 2005-03-15 | 2009-04-07 | Allergan, Inc. | Multivalent Clostridial toxin derivatives and methods of their use |
| WO2006026780A1 (en) | 2004-09-01 | 2006-03-09 | Allergan, Inc. | Degradable clostridial toxins |
| DE102004043009A1 (de) | 2004-09-06 | 2006-03-23 | Toxogen Gmbh | Transportprotein zum Einbringen chemischer Verbindungen in Nervenzellen |
| CA2601592A1 (en) | 2005-03-15 | 2006-09-28 | Allergan, Inc. | Modified clostridial toxins with enhanced targeting capabilities for endogenous clostridial toxin receptor systems |
| DE102005019302A1 (de) | 2005-04-26 | 2006-11-16 | Toxogen Gmbh | Carrier zum Targeting von Nervenzellen |
| DK1926744T4 (en) | 2005-09-19 | 2019-01-28 | Allergan Inc | CLOSTRIDIUM TOXIN-ACTIVABLE CLOSTRIDIAL TOXINES |
| 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 |
| FR2902341B1 (fr) | 2006-06-16 | 2011-02-25 | Scras | Utilisation therapeutique simultanee, separee ou etalee dans le temps d'au moins une neurotoxine botulique, et d'au moins un derive opiace |
| FR2907680B1 (fr) | 2006-10-27 | 2012-12-28 | Scras | Utilisation therapeutique d'au moins une neurotoxine botulique dans le traitement de la douleur induite par au moins un agent anti-cancereux |
| FR2910327B1 (fr) | 2006-12-22 | 2013-04-26 | Scras | Utilisation d'au moins une neurotoxine botulique pour traiter la douleur induite par les traitements therapeutiques du virus du sida. |
| EP2178905B1 (en) | 2007-07-26 | 2013-11-06 | Allergan, Inc. | Methods of activiting clostridial toxins |
| WO2009015840A2 (en) | 2007-07-27 | 2009-02-05 | Merz Pharma Gmbh & Co. Kgaa | Polypeptide for targeting of neural cells |
| US8586081B2 (en) | 2007-09-20 | 2013-11-19 | University Of Massachusetts | Detoxified recombinant botulinum neurotoxin |
| WO2009042165A2 (en) | 2007-09-25 | 2009-04-02 | Thomas Jefferson University | Mutant botulinum neurotoxin serotype a polypeptide and uses thereof |
| US20090104234A1 (en) * | 2007-10-23 | 2009-04-23 | Allergan, Inc. | Methods of treating chronic neurogenic inflammation using modified clostridial toxins |
| RU2010120016A (ru) * | 2007-10-23 | 2011-11-27 | Аллерган, Инк. (Us) | Способы лечения хронического нейрогенного воспаления с применением модифицированных клостридиальных токсинов |
| FR2930447B1 (fr) | 2008-04-25 | 2010-07-30 | Sod Conseils Rech Applic | Utilisation therapeutique d'au moins une neurotoxine botulique dans le traitement de la douleur dans le cas de la neuropathie diabetique |
| JP5746624B2 (ja) | 2008-08-29 | 2015-07-08 | メルツ・ファルマ・ゲーエムベーハー・ウント・コ・カーゲーアーアー | 変化した持続性を有するクロストリジウム性神経毒 |
| TW201023928A (en) | 2008-11-12 | 2010-07-01 | Kythera Biopharmaceuticals Inc | Systems and methods for delivery of biologically active agents |
| AU2010236613B2 (en) | 2009-04-14 | 2016-07-07 | Mcw Research Foundation, Inc. | Engineered botulinum neurotoxin |
| US8440204B2 (en) | 2009-04-30 | 2013-05-14 | Wisconsin Alumni Research Foundation | Subtype of Closteridium botulinum neurotoxin type A and uses thereof |
| JP6148979B2 (ja) | 2010-05-20 | 2017-06-14 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | 分解性クロストリジウム毒素 |
| ES2847241T3 (es) * | 2012-05-30 | 2021-08-02 | Harvard College | Neurotoxina botulínica genéticamente modificada |
| GB201219602D0 (en) | 2012-10-31 | 2012-12-12 | Syntaxin Ltd | Recombinant clostridium botulinum neurotoxins |
| US9216210B2 (en) | 2013-12-23 | 2015-12-22 | Dublin City University | Multiprotease therapeutics for chronic pain |
| CN115925835A (zh) * | 2015-03-26 | 2023-04-07 | 哈佛大学校长及研究员协会 | 工程改造的肉毒杆菌神经毒素 |
| GB201607901D0 (en) | 2016-05-05 | 2016-06-22 | Ipsen Biopharm Ltd | Chimeric neurotoxins |
| KR20190025906A (ko) | 2016-06-08 | 2019-03-12 | 칠드런'즈 메디컬 센터 코포레이션 | 조작된 보툴리눔 신경독소 |
| US11117935B2 (en) | 2016-08-24 | 2021-09-14 | President And Fellows Of Harvard College | Engineered botulinum neurotoxin |
-
2017
- 2017-08-24 US US16/326,905 patent/US11117935B2/en active Active
- 2017-08-24 JP JP2019510791A patent/JP7100020B2/ja active Active
- 2017-08-24 WO PCT/US2017/048508 patent/WO2018039506A1/en not_active Ceased
- 2017-08-24 CN CN201780061528.1A patent/CN110072880B/zh active Active
- 2017-08-24 EP EP17762292.5A patent/EP3504226A1/en active Pending
-
2021
- 2021-08-12 US US17/400,441 patent/US20220033447A1/en not_active Abandoned
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