RU2018109902A - Виды комбинированной терапии для лечения рака - Google Patents
Виды комбинированной терапии для лечения рака Download PDFInfo
- Publication number
- RU2018109902A RU2018109902A RU2018109902A RU2018109902A RU2018109902A RU 2018109902 A RU2018109902 A RU 2018109902A RU 2018109902 A RU2018109902 A RU 2018109902A RU 2018109902 A RU2018109902 A RU 2018109902A RU 2018109902 A RU2018109902 A RU 2018109902A
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- Prior art keywords
- compound
- antibiotic
- cancer
- cancer cells
- administering
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims 12
- 201000011510 cancer Diseases 0.000 title claims 10
- 238000002648 combination therapy Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims 16
- 150000001875 compounds Chemical class 0.000 claims 10
- 230000003115 biocidal effect Effects 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 4
- CAOTVXGYTWCKQE-UHFFFAOYSA-N 3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)-1-adamantanecarboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCC=4C=CN=CC=4)CC2CC3C1 CAOTVXGYTWCKQE-UHFFFAOYSA-N 0.000 claims 3
- ZWBTYMGEBZUQTK-PVLSIAFMSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,23-dioxospiro[8,33-dioxa-24,27,29-triazapentacyclo[23.6.1.14,7.05,31.026,30]tritriaconta-1(32),2,4,9,19,21,24,26,30-nonaene-28,4'-piperidine]-13-yl] acetate Chemical compound CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c2c4NC5(CCN(CC(C)C)CC5)N=c4c(=NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(O)c2c(O)c3C ZWBTYMGEBZUQTK-PVLSIAFMSA-N 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims 2
- 229960002626 clarithromycin Drugs 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- 230000035755 proliferation Effects 0.000 claims 2
- -1 pyridin-4-ylmethyl Chemical group 0.000 claims 2
- 229960000885 rifabutin Drugs 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 229940034982 antineoplastic agent Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 238000001516 cell proliferation assay Methods 0.000 claims 1
- 230000001900 immune effect Effects 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 230000002584 immunomodulator Effects 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 claims 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims 1
- 230000002503 metabolic effect Effects 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 claims 1
- 230000002685 pulmonary effect Effects 0.000 claims 1
Classifications
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (32)
1. Комбинация, содержащая
(i) соединение структуры (I)
или его фармацевтически приемлемую соль; и
(ii) соединение структуры (II)
3-(4-хлорфенил)-адамантан-1-карбоновой кислоты (пиридин-4-илметил)-амид (II)
или его фармацевтически приемлемую соль.
2. Комбинация по п. 1, дополнительно содержащая соединение структуры (III)
или его фармацевтически приемлемую соль.
3. Комбинация по п. 1, дополнительно содержащая соединение структуры (IV)
или его фармацевтически приемлемую соль.
4. Способ лечения рака или предотвращения рецидива или прогрессирования рака у нуждающегося в этом человека, включающий одновременное или последовательное введение человеку терапевтически эффективного количества
(i) по меньшей мере одного антибиотика; и
(ii) соединения ариладамантана.
5. Способ по п. 4, в котором по меньшей мере один антибиотик и соединение ариладамантана вводят одновременно.
6. Способ по п. 4, в котором по меньшей мере один антибиотик и соединение ариладамантана вводят последовательно.
7. Способ по п. 4, в котором по меньшей мере один антибиотик выбирают из группы, состоящей из клофазамина, кларитромицина и рифабутина.
8. Способ по п. 4, в котором соединение ариладамантана представляет собой [3-(4-хлорфенил)-адамантан-1-карбоновой кислоты (пиридин-4-илметил)амид].
9. Способ по п. 4, в котором рак представляет собой солидную опухоль.
10. Способ по п. 9, в котором солидную опухоль выбирают из группы, состоящей из: легочной карциномы, легочной метастазы, карциномы толстой кишки и протоковой аденокарциномы поджелудочной железы.
11. Способ по п. 4, дополнительно включающий в себя введение человеку антинеопластического агента.
12. Способ по п. 4, дополнительно включающий в себя введение человеку иммуномодулятора.
13. Способ по п. 4, дополнительно включающий в себя введение человеку ингибитора иммунологических контрольных точек.
14. Способ по п. 4, дополнительно включающий в себя введение человеку ингибитора матриксных металлопротеиназ.
15. Способ ингибирования роста или пролиферации раковых клеток при раке, включающий приведение раковых клеток в контакт с эффективным количеством по меньшей мере одного антибиотика и эффективным количеством соединения ариладамантана, в результате чего ингибируется рост или пролиферация раковых клеток.
16. Способ по п. 15, в котором раковые клетки представляют собой клетки рака поджелудочной железы.
17. Способ по п. 15, в котором по меньшей мере один антибиотик выбирают из группы, состоящей из клофазамина, кларитромицина и рифабутина.
18. Способ по п. 15, в котором соединение ариладамантана представляет собой [3-(4-хлорфенил)-адамантан-1-карбоновой кислоты (пиридин-4-илметил)амид].
19. Способ по п. 15, в котором для измерения метаболической активности раковых клеток применяют анализ пролиферации клеток in vitro.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562237925P | 2015-10-06 | 2015-10-06 | |
| US62/237,925 | 2015-10-06 | ||
| PCT/IB2016/001526 WO2017060771A2 (en) | 2015-10-06 | 2016-10-06 | Combination therapies for treating cancer |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2018109902A true RU2018109902A (ru) | 2019-11-07 |
| RU2018109902A3 RU2018109902A3 (ru) | 2020-03-05 |
| RU2727474C2 RU2727474C2 (ru) | 2020-07-21 |
Family
ID=58446480
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018109902A RU2727474C2 (ru) | 2015-10-06 | 2016-10-06 | Виды комбинированной терапии для лечения рака |
Country Status (12)
| Country | Link |
|---|---|
| US (4) | US9844540B2 (ru) |
| EP (1) | EP3359255B1 (ru) |
| JP (1) | JP6963545B2 (ru) |
| KR (1) | KR20180058716A (ru) |
| CN (1) | CN108136207A (ru) |
| AU (1) | AU2016336133B2 (ru) |
| BR (1) | BR112018003232A2 (ru) |
| CA (1) | CA2997671A1 (ru) |
| HK (1) | HK1259342A1 (ru) |
| MX (1) | MX382754B (ru) |
| RU (1) | RU2727474C2 (ru) |
| WO (1) | WO2017060771A2 (ru) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015334590B2 (en) | 2014-10-24 | 2019-08-29 | Redhill Biopharma Ltd. | Therapy for inhibition of single-stranded RNA virus replication |
| US11229657B2 (en) | 2017-04-21 | 2022-01-25 | Lunella Biotech, Inc. | Targeting hypoxic cancer stem cells (CSCs) with doxycycline: implications for improving anti-angiogenic therapy |
| CA3060510A1 (en) | 2017-04-21 | 2018-10-25 | Lunella Biotech, Inc. | Vitamin c and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (cscs) |
| US12006553B2 (en) | 2017-05-19 | 2024-06-11 | Lunella Biotech, Inc. | Companion diagnostics for mitochondrial inhibitors |
| RU2019142102A (ru) | 2017-05-19 | 2021-06-21 | Лунелла Байотек, Инк. | Антимитосцины: направленные ингибиторы митохондриального биогенеза для эрадикации злокачественных стволовых клеток |
| MX2019014806A (es) | 2017-06-26 | 2020-02-10 | Lunella Biotech Inc | Mitocetoscinas: agentes terapeuticos basados en mitocondrias que fijan como objetivo el metabolismo de cetonas en celulas cancerosas. |
| JP2020534283A (ja) * | 2017-09-15 | 2020-11-26 | アンパサンド バイオファーマシューティカルズ インコーポレイテッドＡｍｐｅｒｓａｎｄ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． | システインプロテアーゼのタンパク質阻害剤を介した自然転移の阻害 |
| EP3681479B1 (en) | 2017-09-15 | 2024-01-31 | Dyve Biosciences, Inc. | Sodium bicarbonate for use in the treatment of gout and related disorders |
| JP7693206B2 (ja) * | 2019-01-16 | 2025-06-17 | アポジー・バイオテクノロジー・コーポレイション | 抗癌免疫応答を誘導する方法 |
| WO2020154716A1 (en) * | 2019-01-26 | 2020-07-30 | University Of Rochester | Compositions and methods for treating prostate cancer |
| IL295658A (en) * | 2020-03-10 | 2022-10-01 | Redhill Biopharma Ltd | Treatment of coronavirus infection |
| US11471448B2 (en) | 2020-12-15 | 2022-10-18 | Redhill Biopharma Ltd. | Sphingosine kinase 2 inhibitor for treating coronavirus infection in moderately severe patients with pneumonia |
| CN119700770A (zh) * | 2025-01-09 | 2025-03-28 | 首都医科大学附属北京佑安医院 | 氯法齐明在制备修复肠黏膜或改善肠道菌群药物中的应用 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0758549A4 (en) * | 1994-04-26 | 1997-07-02 | Nobuhiro Narita | MEDICAL COMPOSITION AS A MEDICINE FOR NON-SMALL CELL CANCER |
| AUPP437698A0 (en) | 1998-06-30 | 1998-07-23 | Baumgart, Karl | Methods for treatment of coronary, carotid and other vascular disease |
| DE59909210D1 (de) * | 1998-07-20 | 2004-05-19 | Wilex Ag | Urokinase-Inhibitoren |
| AUPR644301A0 (en) * | 2001-07-17 | 2001-08-09 | Unisearch Limited | Method and composition for treatment of cancer |
| US6864264B1 (en) * | 2002-08-20 | 2005-03-08 | Gloria L. Anderson | 1-adamantyl chalcones for the treatment of proliferative disorders |
| DE10323898A1 (de) * | 2003-05-26 | 2004-12-23 | Wilex Ag | Hydroxyamidin- und Hydroxyguanidin-Verbindungen als Urokinase-Hemmstoffe |
| DE102004057195A1 (de) * | 2004-11-26 | 2006-06-01 | Wilex Ag | Kristalline Modifikationen von N-Alpha-(2,4,6-Triisopropylphenylsulfonyl)-3-hydroxyamidino-(L)-phenylalanin-4-ethoxycarbonylpiperazid und/oder Salzen davon |
| US20060142304A1 (en) * | 2004-12-27 | 2006-06-29 | Michael Southall | Method for treating or preventing pruritic and neurogenic skin disorders |
| US20060270631A1 (en) * | 2005-05-26 | 2006-11-30 | Smith Charles D | Methods for the treatment and prevention of angiogenic diseases |
| CA2612338C (en) | 2005-06-17 | 2015-02-03 | Apogee Biotechnology Corporation | Sphingosine kinase inhibitors |
| TWI405756B (zh) * | 2005-12-21 | 2013-08-21 | Array Biopharma Inc | 新穎硫酸氫鹽 |
| US20080226624A1 (en) | 2007-03-07 | 2008-09-18 | Wolfgang Schmalix | Combined treatment of cancer by urokinase inhibition and a cytostatic anti-cancer agent for enhancing the anti-metastatic effect |
| DK2247291T3 (en) | 2008-02-08 | 2019-01-21 | Red Hill Biopharma Ltd | Methods and compositions for treating inflammatory bowel disease |
| TWI573590B (zh) * | 2011-09-20 | 2017-03-11 | 雷希爾生藥有限公司 | 治療自體免疫疾病之組成物及方法 |
| US20150017673A1 (en) * | 2012-08-30 | 2015-01-15 | James Sacchettini | Compositions and methods for drug-sensitization or inhibition of a cancer cell |
| AU2015334590B2 (en) * | 2014-10-24 | 2019-08-29 | Redhill Biopharma Ltd. | Therapy for inhibition of single-stranded RNA virus replication |
-
2016
- 2016-10-06 US US15/287,381 patent/US9844540B2/en active Active
- 2016-10-06 KR KR1020187007757A patent/KR20180058716A/ko not_active Ceased
- 2016-10-06 HK HK19101708.0A patent/HK1259342A1/zh unknown
- 2016-10-06 EP EP16853154.9A patent/EP3359255B1/en active Active
- 2016-10-06 WO PCT/IB2016/001526 patent/WO2017060771A2/en not_active Ceased
- 2016-10-06 BR BR112018003232A patent/BR112018003232A2/pt not_active IP Right Cessation
- 2016-10-06 MX MX2018004309A patent/MX382754B/es unknown
- 2016-10-06 CA CA2997671A patent/CA2997671A1/en not_active Abandoned
- 2016-10-06 RU RU2018109902A patent/RU2727474C2/ru active
- 2016-10-06 AU AU2016336133A patent/AU2016336133B2/en not_active Ceased
- 2016-10-06 JP JP2018517826A patent/JP6963545B2/ja active Active
- 2016-10-06 CN CN201680058309.3A patent/CN108136207A/zh active Pending
-
2017
- 2017-11-07 US US15/805,682 patent/US10463654B2/en active Active
-
2019
- 2019-09-17 US US16/573,325 patent/US10946000B2/en active Active
-
2021
- 2021-01-12 US US17/147,093 patent/US11633385B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20200113881A1 (en) | 2020-04-16 |
| US20210128538A1 (en) | 2021-05-06 |
| CA2997671A1 (en) | 2017-04-13 |
| BR112018003232A2 (pt) | 2018-09-25 |
| EP3359255B1 (en) | 2025-12-24 |
| WO2017060771A2 (en) | 2017-04-13 |
| JP6963545B2 (ja) | 2021-11-10 |
| EP3359255A2 (en) | 2018-08-15 |
| CN108136207A (zh) | 2018-06-08 |
| AU2016336133A1 (en) | 2018-03-15 |
| JP2018533560A (ja) | 2018-11-15 |
| MX2018004309A (es) | 2018-05-22 |
| MX382754B (es) | 2025-03-13 |
| US20170095460A1 (en) | 2017-04-06 |
| KR20180058716A (ko) | 2018-06-01 |
| US20180125831A1 (en) | 2018-05-10 |
| EP3359255A4 (en) | 2019-06-12 |
| HK1259342A1 (zh) | 2019-11-29 |
| US9844540B2 (en) | 2017-12-19 |
| AU2016336133B2 (en) | 2021-02-25 |
| WO2017060771A3 (en) | 2017-07-06 |
| RU2727474C2 (ru) | 2020-07-21 |
| US11633385B2 (en) | 2023-04-25 |
| RU2018109902A3 (ru) | 2020-03-05 |
| US10946000B2 (en) | 2021-03-16 |
| US10463654B2 (en) | 2019-11-05 |
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