SG11201810210UA - Engineered botulinum neurotoxins - Google Patents
Engineered botulinum neurotoxinsInfo
- Publication number
- SG11201810210UA SG11201810210UA SG11201810210UA SG11201810210UA SG11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA
- Authority
- SG
- Singapore
- Prior art keywords
- international
- boston
- pct
- disclosed
- substitution mutations
- Prior art date
Links
- 108030001720 Bontoxilysin Proteins 0.000 title abstract 4
- 231100001103 botulinum neurotoxin Toxicity 0.000 title abstract 4
- 230000035772 mutation Effects 0.000 abstract 3
- 238000006467 substitution reaction Methods 0.000 abstract 3
- 241001112695 Clostridiales Species 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- 102000005962 receptors Human genes 0.000 abstract 2
- 108020003175 receptors Proteins 0.000 abstract 2
- 102000007469 Actins Human genes 0.000 abstract 1
- 108010085238 Actins Proteins 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000008520 organization Effects 0.000 abstract 1
Classifications
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- 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
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- 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)
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- 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)
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- 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
- A61P1/04—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
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- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- 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
Abstract
INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization 111111111111111111111111111111111111111111111111111111111111111111111111111111111111 International Bureau (10) International Publication Number (43) International Publication Date .....0\"\" WO 2017/214447 Al 14 December 2017 (14.12.2017) WIP0 I PCT (51) International Patent Classification: (74) Agent: EL-HAYEK, Roque; Wo1f, Greenfield & Sacks, C07K 14/33 (2006.01) A61K 38/48 (2006.01) P.c., 600 Atlantic Avenue, Boston, MA 02210-2206 (US). A61K 38/00 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: PCT/US2017/036628 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (22) International Filing Date: 08 June 2017 (08.06.2017) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, (25) Filing Language: English KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 62/347,579 08 June 2016 (08.06.2016) US TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant. CHILDREN'S MEDICAL CENTER COR- (84) Designated States (unless otherwise indicated, for every PORATION [US/US]; 55 Shattuck Street, Boston, MA kind of regional protection available): ARIPO (BW, GH, 02115 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (72) Inventor; and UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (71) Applicant: STENMARK, Paul [SE/SE]; Svantearrhenius- EE, ES, FL FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, — vag 16c, 10691 Stockholm (SE). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Inventors: ZHANG, Sicai; En 1070, 300 Longwood Ave, (72) TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, = Boston, MA (US). DONG, Min; 12 Croft Lane, Weatogue, CT 06089 (US). KM, ML, MR, NE, SN, TD, TG). = Title: ENGINEERED BOTULINUM NEUROTOXINS (54) = (57) : Disclosed herein are modified Clostridial Botulinum neurotoxin (BoNT) polypep- 3 tides with a modified receptor binding domain of Clostridial Botulinum serotype B, compris- = — ing one or more substitution mutations at positions corresponding 1248 or 1249 in serotype B, Z strain 1. Specific substitution mutations include I1248F, I1248Y, I1248H, I1248W, V1249W, = g g. V1249F, V1249Y, V1249H, I1248WN1249F, I1248WN1249Y, I1248WN1249H, I1248F/ = = = 1 V1249Y, I1248FN1249H, I1248YN1249H, I1248F/V1249W, I1248YN1249W, I1248H/ bind i V 1249W, I1248Y/V1249F, I1248H/V1249F, or I1248HN1249Y. Other substitution mutations are = = also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical _ total compositions, and methods of using the same are also disclosed. = ..... actin = = FIG. 4A 4 = — = 2 1 — Il Ir ... ' Il ei 4. 1' ‘., IN 4B FIG. P S I ei C [Continued on next page] WO 2017/214447 Al MIDEDIMOMMIDIRMEM001101011101110HOHNEVOIMIE Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event amendments (Rule 48.2(h)) of receipt of
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662347579P | 2016-06-08 | 2016-06-08 | |
PCT/US2017/036628 WO2017214447A1 (en) | 2016-06-08 | 2017-06-08 | Engineered botulinum neurotoxins |
Publications (1)
Publication Number | Publication Date |
---|---|
SG11201810210UA true SG11201810210UA (en) | 2018-12-28 |
Family
ID=59227906
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG11201810210UA SG11201810210UA (en) | 2016-06-08 | 2017-06-08 | Engineered botulinum neurotoxins |
SG10201912099TA SG10201912099TA (en) | 2016-06-08 | 2017-06-08 | Engineered botulinum neurotoxins |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG10201912099TA SG10201912099TA (en) | 2016-06-08 | 2017-06-08 | Engineered botulinum neurotoxins |
Country Status (13)
Country | Link |
---|---|
US (1) | US11104891B2 (en) |
EP (1) | EP3468985A1 (en) |
JP (2) | JP7152392B2 (en) |
KR (1) | KR20190025906A (en) |
CN (1) | CN109476713A (en) |
AU (1) | AU2017277905B2 (en) |
BR (1) | BR112018075363A2 (en) |
CA (1) | CA3026492A1 (en) |
EA (1) | EA201892784A1 (en) |
IL (1) | IL263058B2 (en) |
MX (1) | MX2018015254A (en) |
SG (2) | SG11201810210UA (en) |
WO (1) | WO2017214447A1 (en) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG11201407784UA (en) | 2012-05-30 | 2014-12-30 | Harvard College | Engineered botulinum neurotoxin |
EP3274364B1 (en) * | 2015-03-26 | 2021-08-04 | President and Fellows of Harvard College | Engineered botulinum neurotoxin |
TW201718627A (en) * | 2015-06-11 | 2017-06-01 | 梅茲製藥有限兩合公司 | Recombinant clostridial neurotoxin, a use thereof, and a method for generating the same, a pharmaceutical composition comprising the same and a precursor corresponding to the same, a nucleic acid sequence encoding the precursor and a method for obtaining |
GB201607901D0 (en) * | 2016-05-05 | 2016-06-22 | Ipsen Biopharm Ltd | Chimeric neurotoxins |
UA127310C2 (en) * | 2016-05-16 | 2023-07-19 | Презідент Енд Феллоуз Оф Гарвард Колледж | Method for purification and activation of botulinum neurotoxin |
EA201990229A1 (en) * | 2016-07-08 | 2019-06-28 | Пол Стенмарк | NEW BOTULINIC NEUROTOXIN AND ITS DERIVATIVES |
US11117935B2 (en) | 2016-08-24 | 2021-09-14 | President And Fellows Of Harvard College | Engineered botulinum neurotoxin |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
TWI810228B (en) * | 2017-12-20 | 2023-08-01 | 英商艾普森生物製藥有限公司 | Treatment of autonomic disorders |
JP2021517825A (en) * | 2018-01-30 | 2021-07-29 | チルドレンズ メディカル センター コーポレーションChildren’S Medical Center Corporation | Production of botulinum toxin using the BACILLUS system |
US11707510B2 (en) * | 2018-02-16 | 2023-07-25 | Preclinics Discovery Gmbh | Nucleic acid-based botulinum neurotoxin for therapeutic use |
SE542539C2 (en) * | 2018-02-26 | 2020-06-02 | Toxotech Ab | Chimeric botulinum neurotoxin heavy chain binding domain |
CN114957482A (en) * | 2021-02-26 | 2022-08-30 | 重庆誉颜制药有限公司 | Modified single-chain polypeptide of neurotoxin and application thereof |
KR20230001254A (en) | 2021-06-28 | 2023-01-04 | (주)메디톡스 | Recombinant botulinum toxin type A light chain, recombinant botulinum toxin, and its compositions, uses and methods |
KR20230001260A (en) | 2021-06-28 | 2023-01-04 | (주)메디톡스 | Recombinant botulinum toxin type A light chain, recombinant botulinum toxin, and its compositions, uses and methods |
WO2023068485A1 (en) * | 2021-10-22 | 2023-04-27 | 비피메드(주) | Composition for ameliorating hair loss comprising botulinum-derived peptide |
CA3234608A1 (en) * | 2021-11-22 | 2023-05-25 | Ipsen Biopharm Limited | Treatment of pain |
CN114369623B (en) * | 2022-01-12 | 2023-07-07 | 中国人民解放军空军军医大学 | Syntagmin 2-RNAi based on Cre-lox recombination system and application thereof |
CN114410683B (en) * | 2022-01-12 | 2023-11-28 | 中国人民解放军空军军医大学 | RIM3-RNAi based on Cre-lox recombination system and application thereof |
GB202206348D0 (en) * | 2022-04-29 | 2022-06-15 | Ipsen Biopharm Ltd | Treatment of limb spasticity |
WO2024080682A1 (en) * | 2022-10-12 | 2024-04-18 | 주식회사 알케미어 | Light chain mutant of botulinum toxin |
Family Cites Families (19)
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US4880635B1 (en) | 1984-08-08 | 1996-07-02 | Liposome Company | Dehydrated liposomes |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US4921757A (en) | 1985-04-26 | 1990-05-01 | Massachusetts Institute Of Technology | System for delayed and pulsed release of biologically active substances |
US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
JPH0825869B2 (en) | 1987-02-09 | 1996-03-13 | 株式会社ビタミン研究所 | Antitumor agent-embedded liposome preparation |
US4917951A (en) | 1987-07-28 | 1990-04-17 | Micro-Pak, Inc. | Lipid vesicles formed of surfactants and steroids |
US4911928A (en) | 1987-03-13 | 1990-03-27 | Micro-Pak, Inc. | Paucilamellar lipid vesicles |
US5053005A (en) | 1989-04-21 | 1991-10-01 | Gary E. Borodic | Chemomodulation of curvature of the juvenile spine |
JP3066079B2 (en) | 1994-05-09 | 2000-07-17 | ビンダー,ウィリアム,ジェイ. | How to reduce headaches |
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 |
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 |
DE102005019302A1 (en) | 2005-04-26 | 2006-11-16 | Toxogen Gmbh | Carrier for targeting nerve cells |
CN102796743B (en) * | 2006-01-13 | 2015-11-18 | 美国政府健康及人类服务部国立卫生研究院 | For codon optimized IL-15 and the IL-15R α gene of expressing in mammalian cell |
US8273865B2 (en) | 2006-03-15 | 2012-09-25 | Allergan, Inc. | Multivalent clostridial toxins |
SG11201407784UA (en) * | 2012-05-30 | 2014-12-30 | Harvard College | Engineered botulinum neurotoxin |
CN107624115B (en) | 2015-03-16 | 2021-10-26 | 加州理工学院 | Botulinum neurotoxin specific capture agents, compositions, methods of use, and methods of manufacture |
GB201607901D0 (en) * | 2016-05-05 | 2016-06-22 | Ipsen Biopharm Ltd | Chimeric neurotoxins |
-
2017
- 2017-06-08 CN CN201780035648.4A patent/CN109476713A/en active Pending
- 2017-06-08 AU AU2017277905A patent/AU2017277905B2/en active Active
- 2017-06-08 CA CA3026492A patent/CA3026492A1/en active Pending
- 2017-06-08 US US16/308,146 patent/US11104891B2/en active Active
- 2017-06-08 SG SG11201810210UA patent/SG11201810210UA/en unknown
- 2017-06-08 WO PCT/US2017/036628 patent/WO2017214447A1/en unknown
- 2017-06-08 JP JP2019516917A patent/JP7152392B2/en active Active
- 2017-06-08 EA EA201892784A patent/EA201892784A1/en unknown
- 2017-06-08 IL IL263058A patent/IL263058B2/en unknown
- 2017-06-08 MX MX2018015254A patent/MX2018015254A/en unknown
- 2017-06-08 SG SG10201912099TA patent/SG10201912099TA/en unknown
- 2017-06-08 BR BR112018075363-7A patent/BR112018075363A2/en unknown
- 2017-06-08 KR KR1020197000585A patent/KR20190025906A/en not_active Application Discontinuation
- 2017-06-08 EP EP17733667.4A patent/EP3468985A1/en not_active Withdrawn
-
2022
- 2022-03-18 JP JP2022044568A patent/JP2022112031A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2017214447A1 (en) | 2017-12-14 |
AU2017277905B2 (en) | 2022-04-14 |
JP7152392B2 (en) | 2022-10-12 |
JP2019523015A (en) | 2019-08-22 |
CN109476713A (en) | 2019-03-15 |
CA3026492A1 (en) | 2017-12-14 |
US20190300869A1 (en) | 2019-10-03 |
AU2017277905A1 (en) | 2018-12-20 |
US11104891B2 (en) | 2021-08-31 |
IL263058A (en) | 2018-12-31 |
EA201892784A1 (en) | 2019-05-31 |
MX2018015254A (en) | 2019-08-16 |
IL263058B2 (en) | 2023-11-01 |
SG10201912099TA (en) | 2020-02-27 |
IL263058B1 (en) | 2023-07-01 |
BR112018075363A2 (en) | 2019-03-19 |
KR20190025906A (en) | 2019-03-12 |
EP3468985A1 (en) | 2019-04-17 |
JP2022112031A (en) | 2022-08-01 |
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