RU2017108448A - Конъюгаты и конъюгирующие реагенты - Google Patents
Конъюгаты и конъюгирующие реагенты Download PDFInfo
- Publication number
- RU2017108448A RU2017108448A RU2017108448A RU2017108448A RU2017108448A RU 2017108448 A RU2017108448 A RU 2017108448A RU 2017108448 A RU2017108448 A RU 2017108448A RU 2017108448 A RU2017108448 A RU 2017108448A RU 2017108448 A RU2017108448 A RU 2017108448A
- Authority
- RU
- Russia
- Prior art keywords
- group
- polyethylene glycol
- protein
- peptide
- conjugating reagent
- Prior art date
Links
- 239000003153 chemical reaction reagent Substances 0.000 title claims 14
- 230000001268 conjugating effect Effects 0.000 title claims 14
- 239000002202 Polyethylene glycol Substances 0.000 claims 16
- 229920001223 polyethylene glycol Polymers 0.000 claims 16
- 125000003827 glycol group Chemical group 0.000 claims 14
- 235000018102 proteins Nutrition 0.000 claims 13
- 102000004169 proteins and genes Human genes 0.000 claims 13
- 108090000623 proteins and genes Proteins 0.000 claims 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000006575 electron-withdrawing group Chemical group 0.000 claims 3
- 125000003107 substituted aryl group Chemical group 0.000 claims 3
- 125000004450 alkenylene group Chemical group 0.000 claims 2
- 125000002947 alkylene group Chemical group 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000000468 ketone group Chemical group 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 102000014914 Carrier Proteins Human genes 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
- 125000002877 alkyl aryl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- -1 atom hydrogen Chemical class 0.000 claims 1
- 108091008324 binding proteins Proteins 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 239000000032 diagnostic agent Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000012038 nucleophile Substances 0.000 claims 1
- 229920002704 polyhistidine Polymers 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1418989.8A GB201418989D0 (en) | 2014-10-24 | 2014-10-24 | Novel conjugation process and reagents |
| GB1418984.9A GB2531715A (en) | 2014-10-24 | 2014-10-24 | Novel drug conjugates |
| GB1418984.9 | 2014-10-24 | ||
| GB1418986.4 | 2014-10-24 | ||
| GBGB1418986.4A GB201418986D0 (en) | 2014-10-24 | 2014-10-24 | Novel conjugates and novel conjugating reagents |
| GB1418989.8 | 2014-10-24 | ||
| PCT/GB2015/052953 WO2016063006A1 (en) | 2014-10-24 | 2015-10-08 | Conjugates and conjugating reagents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2017108448A true RU2017108448A (ru) | 2018-11-27 |
Family
ID=54337308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017108448A RU2017108448A (ru) | 2014-10-24 | 2015-10-08 | Конъюгаты и конъюгирующие реагенты |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US20170290925A1 (enExample) |
| EP (1) | EP3220956B1 (enExample) |
| JP (1) | JP6612860B2 (enExample) |
| KR (1) | KR102513926B1 (enExample) |
| CN (1) | CN107073131B (enExample) |
| AU (1) | AU2015334717B2 (enExample) |
| BR (1) | BR112017005760A2 (enExample) |
| CA (1) | CA2963043A1 (enExample) |
| ES (1) | ES2960741T3 (enExample) |
| IL (1) | IL250644B (enExample) |
| MX (1) | MX2017005199A (enExample) |
| RU (1) | RU2017108448A (enExample) |
| SG (1) | SG11201701342XA (enExample) |
| WO (1) | WO2016063006A1 (enExample) |
| ZA (1) | ZA201701337B (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10098960B2 (en) | 2015-04-03 | 2018-10-16 | Ucl Business Plc | Polymer conjugate |
| CN108473590B (zh) | 2016-01-12 | 2023-04-14 | 克雷森多生物制剂有限公司 | 治疗分子 |
| WO2017161206A1 (en) | 2016-03-16 | 2017-09-21 | Halozyme, Inc. | Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use |
| US11273224B2 (en) | 2016-04-14 | 2022-03-15 | Polytherics Limited | Conjugates and conjugating reagents comprising a linker that includes at least two (-CH2—CH2—O-) units in a ring |
| GB201608936D0 (en) * | 2016-05-20 | 2016-07-06 | Polytherics Ltd | Novel conjugates and novel conjugating reagents |
| CN109311996B (zh) | 2016-06-06 | 2023-11-28 | 阿布泽纳(英国)有限公司 | 抗体、其用途及其缀合物 |
| GB201614162D0 (en) * | 2016-08-18 | 2016-10-05 | Polytherics Ltd | Antibodies, uses thereof and conjugates thereof |
| GB201615725D0 (en) | 2016-09-15 | 2016-11-02 | Polytherics Ltd | Novel cytotoxic agents and conjugates thereof |
| US11419946B2 (en) | 2017-03-30 | 2022-08-23 | Nof Corporation | Heterobifunctional monodispersed polyethylene glycol and conjugate using same |
| GB201711068D0 (en) | 2017-07-10 | 2017-08-23 | Crescendo Biologics Ltd | Therapeutic molecules binding PSMA |
| EP3766917B1 (en) | 2018-03-13 | 2023-04-19 | NOF Corporation | Heterobifunctional compound having monodispersed polyethylene glycol in main chain or side chain |
| EP3789401A1 (en) | 2019-09-03 | 2021-03-10 | Gamamabs Pharma | Amhrii-binding antibody drug conjugates and their use thereof in the treatment of cancers |
| AU2021262526A1 (en) * | 2020-04-29 | 2022-11-03 | Araclon Biotech, S.L. | Methods for quantification of amyloid beta peptides in plasma by mass spectrometry |
| GB2594753B (en) | 2020-05-27 | 2022-05-18 | Spirea Ltd | Antibody-drug conjugates |
| WO2023047090A1 (en) | 2021-09-21 | 2023-03-30 | Spirea Limited | Antibody-drug conjugates |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5446090A (en) * | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| ATE399809T1 (de) * | 1998-03-12 | 2008-07-15 | Nektar Therapeutics Al Corp | Verfahren zur herstellung von polymerkonjugaten |
| KR100511749B1 (ko) * | 2001-11-06 | 2005-09-02 | 선바이오(주) | 변형된 인터페론-베타, 및 이의 화학적으로 변형된 배합체 |
| NZ583292A (en) * | 2003-11-06 | 2012-03-30 | Seattle Genetics Inc | Monomethylvaline compounds capable of conjugation to ligands |
| AU2006277117B2 (en) * | 2005-08-05 | 2013-01-10 | Syntarga B.V. | Triazole-containing releasable linkers and conjugates comprising the same |
| US20070141134A1 (en) * | 2005-12-16 | 2007-06-21 | Kosak Matthew K | Shielded micelles for polynucleotide delivery |
| CN101541332A (zh) * | 2006-09-15 | 2009-09-23 | 安佐制药股份有限公司 | 含多官能连接基的靶向聚合物前药 |
| EP2118150B1 (en) * | 2007-02-14 | 2015-09-23 | Biocompatibles UK Limited | Derivatisation of biological molecules |
| GB0922354D0 (en) * | 2009-12-21 | 2010-02-03 | Polytherics Ltd | Novel polymer conjugates |
| EP2678037B1 (en) * | 2011-02-25 | 2014-12-03 | Lonza Ltd | Branched linker for protein drug conjugates |
| CN103384534B (zh) * | 2011-02-25 | 2015-09-30 | 隆萨有限公司 | 用于蛋白质药物偶联物的支链联接体 |
| GB201210770D0 (en) * | 2012-06-18 | 2012-08-01 | Polytherics Ltd | Novel conjugation reagents |
| US9650331B2 (en) * | 2012-06-18 | 2017-05-16 | Polytherics Limited | Conjugation reagents |
| EP2861261A2 (en) | 2012-06-19 | 2015-04-22 | Polytherics Limited | Process for preparation of antibody conjugates and antibody conjugates |
| NO2789793T3 (enExample) * | 2012-10-24 | 2018-01-27 | ||
| CN104870021B (zh) * | 2012-10-24 | 2018-03-13 | 宝力泰锐克斯有限公司 | 药物‑蛋白质缀合物 |
| BR112016007622A2 (pt) * | 2013-10-15 | 2018-01-23 | Seattle Genetics, Inc. | composto, composição farmacêutica, conjugado de ligante-droga, e, método para tratar câncer |
-
2015
- 2015-10-08 EP EP15782051.5A patent/EP3220956B1/en active Active
- 2015-10-08 RU RU2017108448A patent/RU2017108448A/ru unknown
- 2015-10-08 KR KR1020177010432A patent/KR102513926B1/ko active Active
- 2015-10-08 JP JP2017519672A patent/JP6612860B2/ja active Active
- 2015-10-08 CN CN201580057559.0A patent/CN107073131B/zh active Active
- 2015-10-08 US US15/517,969 patent/US20170290925A1/en not_active Abandoned
- 2015-10-08 CA CA2963043A patent/CA2963043A1/en not_active Abandoned
- 2015-10-08 WO PCT/GB2015/052953 patent/WO2016063006A1/en not_active Ceased
- 2015-10-08 AU AU2015334717A patent/AU2015334717B2/en active Active
- 2015-10-08 SG SG11201701342XA patent/SG11201701342XA/en unknown
- 2015-10-08 BR BR112017005760A patent/BR112017005760A2/pt not_active Application Discontinuation
- 2015-10-08 MX MX2017005199A patent/MX2017005199A/es unknown
- 2015-10-08 ES ES15782051T patent/ES2960741T3/es active Active
-
2017
- 2017-02-16 IL IL250644A patent/IL250644B/en active IP Right Grant
- 2017-02-22 ZA ZA2017/01337A patent/ZA201701337B/en unknown
-
2020
- 2020-03-03 US US16/807,298 patent/US20200268885A1/en active Pending
-
2024
- 2024-03-19 US US18/609,210 patent/US20240293549A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3220956A1 (en) | 2017-09-27 |
| AU2015334717A1 (en) | 2017-04-13 |
| KR20170075724A (ko) | 2017-07-03 |
| CN107073131B (zh) | 2021-05-25 |
| JP6612860B2 (ja) | 2019-11-27 |
| SG11201701342XA (en) | 2017-03-30 |
| ZA201701337B (en) | 2018-05-30 |
| US20240293549A1 (en) | 2024-09-05 |
| CN107073131A (zh) | 2017-08-18 |
| MX2017005199A (es) | 2017-07-26 |
| BR112017005760A2 (pt) | 2017-12-12 |
| AU2015334717B2 (en) | 2021-02-25 |
| ES2960741T3 (es) | 2024-03-06 |
| KR102513926B1 (ko) | 2023-03-23 |
| CA2963043A1 (en) | 2016-04-28 |
| EP3220956B1 (en) | 2023-08-09 |
| JP2017537062A (ja) | 2017-12-14 |
| IL250644B (en) | 2020-10-29 |
| US20200268885A1 (en) | 2020-08-27 |
| US20170290925A1 (en) | 2017-10-12 |
| WO2016063006A1 (en) | 2016-04-28 |
| IL250644A0 (en) | 2017-06-29 |
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