AU2016306597A1 - Novel fusion polypeptide specific for LAG-3 and PD-1 - Google Patents
Novel fusion polypeptide specific for LAG-3 and PD-1 Download PDFInfo
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- AU2016306597A1 AU2016306597A1 AU2016306597A AU2016306597A AU2016306597A1 AU 2016306597 A1 AU2016306597 A1 AU 2016306597A1 AU 2016306597 A AU2016306597 A AU 2016306597A AU 2016306597 A AU2016306597 A AU 2016306597A AU 2016306597 A1 AU2016306597 A1 AU 2016306597A1
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- C—CHEMISTRY; METALLURGY
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| EP15180116.4 | 2015-08-07 | ||
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| EP16150707 | 2016-01-11 | ||
| EP16150707.4 | 2016-01-11 | ||
| PCT/EP2016/068860 WO2017025498A1 (en) | 2015-08-07 | 2016-08-08 | Novel fusion polypeptide specific for lag-3 and pd-1 |
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| AU2016306597A Abandoned AU2016306597A1 (en) | 2015-08-07 | 2016-08-08 | Novel fusion polypeptide specific for LAG-3 and PD-1 |
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| SG10201710472PA (en) | 2013-02-22 | 2018-02-27 | Curevac Ag | Combination of vaccination and inhibition of the pd-1 pathway |
| WO2017011580A2 (en) | 2015-07-13 | 2017-01-19 | Cytomx Therapeutics, Inc. | Anti-pd-1 antibodies, activatable anti-pd-1 antibodies, and methods of use thereof |
| RU2018142573A (ru) | 2016-06-20 | 2020-07-21 | Ф-Стар Бета Лимитед | Партнеры по связыванию lag-3 |
| SI3472207T1 (sl) | 2016-06-20 | 2021-04-30 | F-Star Delta Limited | Vezavne molekule, ki vežejo PD-L1 in LAG-3 |
| GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
| WO2018071500A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
| WO2018134279A1 (en) * | 2017-01-18 | 2018-07-26 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptides specific for lag-3 and pd-1 |
| CA3050614A1 (en) * | 2017-03-17 | 2018-09-20 | Curevac Ag | Rna vaccine and immune checkpoint inhibitors for combined anticancer therapy |
| IL322104A (en) | 2017-05-30 | 2025-09-01 | Bristol Myers Squibb Co | Treatment of lag-3 positive tumors |
| WO2018222722A2 (en) | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody |
| CN110691795A (zh) | 2017-05-30 | 2020-01-14 | 百时美施贵宝公司 | 包含抗-lag3抗体、pd-1途径抑制剂和免疫治疗剂组合的组合物 |
| CN111741976B (zh) | 2017-12-19 | 2024-09-17 | 英沃克斯制药有限公司 | 包括pd-l1抗原结合位点的fc结合片段 |
| JP2021511793A (ja) * | 2018-01-31 | 2021-05-13 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Ｌａｇ３に結合する抗原結合部位を含む二重特異性抗体 |
| FR3078536A1 (fr) * | 2018-03-05 | 2019-09-06 | Peptinov Sas | Composition vaccinale anti-pd-1 |
| WO2019179422A1 (en) * | 2018-03-20 | 2019-09-26 | Wuxi Biologics (Shanghai) Co., Ltd. | Novel bispecific pd-1/lag-3 antibody molecules |
| CN111886254B (zh) | 2018-03-30 | 2023-12-08 | 南京传奇生物科技有限公司 | 针对lag-3的单结构域抗体及其用途 |
| GB201811450D0 (en) | 2018-07-12 | 2018-08-29 | F Star Delta Ltd | Mesothelin and CD137 binding molecules |
| GB201811403D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Antibody molecules |
| GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
| GB201811415D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-Mesothelin Anti bodies |
| GB201811410D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | OX40 Binding molecules |
| MX2021000399A (es) | 2018-07-12 | 2021-05-27 | F Star Therapeutics Ltd | Moleculas de anticuerpo que se unen a cd137 y ox40. |
| US12344672B2 (en) | 2018-07-12 | 2025-07-01 | Invox Pharma Limited | Antibody molecules that bind PD-L1 and CD137 |
| WO2020021061A1 (en) * | 2018-07-26 | 2020-01-30 | Pieris Pharmaceuticals Gmbh | Humanized anti-pd-1 antibodies and uses thereof |
| JP2021532143A (ja) | 2018-07-26 | 2021-11-25 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 癌の処置のためのｌａｇ−３併用療法 |
| EP3866850B1 (en) | 2018-10-19 | 2024-07-24 | Bristol-Myers Squibb Company | Combination therapy for melanoma |
| MX2021005394A (es) * | 2018-11-07 | 2021-07-06 | Merck Sharp & Dohme Llc | Co-formulaciones de anticuerpos anti-gen de activacion de linfocitos 3 (anti-lag3) y anticuerpos anti-muerte programada-1 (anti-pd-1). |
| WO2020127369A1 (en) * | 2018-12-21 | 2020-06-25 | Ose Immunotherapeutics | Bifunctional molecule directed against human pd-1 |
| US20230071889A1 (en) * | 2018-12-21 | 2023-03-09 | Ose Immunotherapeutics | Bifunctional anti-pd-1/il-7 molecule |
| CN111423512B (zh) * | 2019-01-10 | 2024-01-05 | 北京比洋生物技术有限公司 | 阻断血管内皮细胞生长且活化t细胞的多靶向融合蛋白和包含其的药物组合物 |
| CN109912717B (zh) * | 2019-03-04 | 2020-05-26 | 北京天广实生物技术股份有限公司 | 结合cd40的抗体及其用途 |
| CN111763261B (zh) * | 2019-04-02 | 2022-08-09 | 杭州尚健生物技术有限公司 | 一种融合蛋白及其用途 |
| US20220233691A1 (en) | 2019-05-30 | 2022-07-28 | Bristol-Myers Squibb Company | Cell localization signature and combination therapy |
| CN114127315A (zh) | 2019-05-30 | 2022-03-01 | 百时美施贵宝公司 | 鉴定适合于免疫肿瘤学(i-o)疗法的受试者的方法 |
| JP2022534967A (ja) | 2019-05-30 | 2022-08-04 | ブリストル－マイヤーズ スクイブ カンパニー | 多腫瘍遺伝子シグネチャーおよびその使用 |
| CN112079925B (zh) * | 2019-06-13 | 2025-04-25 | 上海健信生物医药科技有限公司 | 靶向lag-3的抗体和双特异性抗体及其用途 |
| WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
| JP2022549273A (ja) | 2019-09-22 | 2022-11-24 | ブリストル－マイヤーズ スクイブ カンパニー | Ｌａｇ－３アンタゴニスト治療のための定量的空間プロファイリング |
| WO2021092220A1 (en) | 2019-11-06 | 2021-05-14 | Bristol-Myers Squibb Company | Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy |
| WO2021092221A1 (en) | 2019-11-06 | 2021-05-14 | Bristol-Myers Squibb Company | Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy |
| EP4056592A4 (en) * | 2019-11-08 | 2024-03-20 | Jiangsu Simcere Pharmaceutical Co., Ltd. | ANTIBODY AGAINST HUMAN PROGRAMMED CELL DEATH LIGAND 1 (PD-L1) AND USE THEREOF |
| CN115942973A (zh) | 2019-11-08 | 2023-04-07 | 百时美施贵宝公司 | 用于黑色素瘤的lag-3拮抗剂疗法 |
| JP2023514152A (ja) | 2020-02-06 | 2023-04-05 | ブリストル－マイヤーズ スクイブ カンパニー | Ｉｌ－１０およびその使用 |
| CN111533782A (zh) * | 2020-05-08 | 2020-08-14 | 中国药科大学 | 一种靶向免疫检查点lag-3的活性多肽及其应用 |
| CA3185657A1 (en) * | 2020-06-04 | 2021-12-09 | Leidos, Inc. | Immunomodulatory compounds |
| AU2021306613A1 (en) | 2020-07-07 | 2023-02-02 | BioNTech SE | Therapeutic RNA for HPV-positive cancer |
| KR20230058442A (ko) | 2020-08-28 | 2023-05-03 | 브리스톨-마이어스 스큅 컴퍼니 | 간세포성 암종에 대한 lag-3 길항제 요법 |
| BR112023003553A2 (pt) | 2020-08-31 | 2023-04-04 | Bristol Myers Squibb Co | Assinatura de localização celular e imunoterapia |
| JP2023548051A (ja) | 2020-10-23 | 2023-11-15 | ブリストル－マイヤーズ スクイブ カンパニー | 肺がんのためのｌａｇ－３アンタゴニスト療法 |
| WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
| WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
| TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性ｒｎａ |
| WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
| JP2024501029A (ja) | 2020-12-28 | 2024-01-10 | ブリストル－マイヤーズ スクイブ カンパニー | Ｐｄ１／ｐｄ－ｌ１抗体の皮下投与 |
| EP4566674A3 (en) | 2020-12-28 | 2025-08-06 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
| US20240384350A1 (en) | 2021-01-29 | 2024-11-21 | Board Of Regents, The University Of Texas System | Methods of treating cancer with kinase inhibitors |
| CN112500489B (zh) * | 2021-02-07 | 2021-05-04 | 天津一瑞生物科技股份有限公司 | 一种抗oxa-23型碳青霉烯酶杂交瘤细胞株，单克隆抗体及应用 |
| AU2022246593A1 (en) | 2021-03-29 | 2023-10-12 | Juno Therapeutics, Inc. | Methods for dosing and treatment with a combination of a checkpoint inhibitor therapy and a car t cell therapy |
| AU2022253474A1 (en) | 2021-04-08 | 2023-11-16 | Board Of Regents, The University Of Texas System | Compounds and methods for theranostic targeting of parp activity |
| WO2022240741A1 (en) | 2021-05-12 | 2022-11-17 | Dana-Farber Cancer Institute, Inc. | Lag3 and gal3 inhibitory agents, xbp1, cs1, and cd138 peptides, and methods of use thereof |
| JP2024525758A (ja) | 2021-07-13 | 2024-07-12 | ビオンテック・ソシエタス・エウロパエア | がんのための併用療法におけるｃｄ４０およびｃｄ１３７に対する多重特異性結合剤 |
| TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
| KR20240099362A (ko) | 2021-10-29 | 2024-06-28 | 브리스톨-마이어스 스큅 컴퍼니 | 혈액암에 대한 lag-3 길항제 요법 |
| JP2025503962A (ja) | 2022-01-26 | 2025-02-06 | ブリストル－マイヤーズ スクイブ カンパニー | 肝細胞がんのための併用療法 |
| US20250179174A1 (en) | 2022-02-25 | 2025-06-05 | Bristol-Myers Squibb Company | Combination therapy for colorectal carcinoma |
| WO2023168404A1 (en) | 2022-03-04 | 2023-09-07 | Bristol-Myers Squibb Company | Methods of treating a tumor |
| AU2023230110A1 (en) | 2022-03-08 | 2024-10-24 | Alentis Therapeutics Ag | Use of anti-claudin-1 antibodies to increase t cell availability |
| JP2025509749A (ja) | 2022-03-18 | 2025-04-11 | ブリストル－マイヤーズ スクイブ カンパニー | ポリペプチドの単離方法 |
| US20250332252A1 (en) | 2022-06-02 | 2025-10-30 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
| EP4624487A1 (en) * | 2022-11-24 | 2025-10-01 | Tokushima University | Production of antibodies against protein |
| US20250340648A1 (en) | 2022-12-01 | 2025-11-06 | Medimmune Limited | Combination therapy for treatment of cancer comprising anti-pd-l1 and anti-cd73 antibodies |
| KR20250120305A (ko) | 2022-12-14 | 2025-08-08 | 아스텔라스 파마 유럽 비.브이. | Cldn18.2 및 cd3에 결합하는 2중 특이성 결합제와 면역 체크포인트 저해제를 수반한 조합 요법 |
| KR20250123912A (ko) | 2022-12-21 | 2025-08-18 | 브리스톨-마이어스 스큅 컴퍼니 | 폐암에 대한 병용 요법 |
| CN115960269A (zh) * | 2023-01-30 | 2023-04-14 | 上海甲贝医药科技有限公司 | 一种重组长效人cxcr4&pd-1双靶点抗体融合蛋白及其制备方法 |
| WO2024196952A1 (en) | 2023-03-20 | 2024-09-26 | Bristol-Myers Squibb Company | Tumor subtype assessment for cancer therapy |
| WO2025038763A1 (en) | 2023-08-15 | 2025-02-20 | Bristol-Myers Squibb Company | Ceramic hydroxyapatite chromatography flow through method |
| WO2025120867A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and anti-vegfr2 antibodies |
| WO2025121445A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| WO2025120866A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| US20250215087A1 (en) | 2023-12-29 | 2025-07-03 | Bristol-Myers Squibb Company | Combination therapy of kras inhibitor and treg depleting agent |
| WO2025184208A1 (en) | 2024-02-27 | 2025-09-04 | Bristol-Myers Squibb Company | Anti-ceacam5 antibodies and uses thereof |
| EP4658320A1 (en) | 2024-02-27 | 2025-12-10 | Bristol-Myers Squibb Company | Anti-ceacam5 antibody drug conjugates |
| WO2025245489A1 (en) | 2024-05-24 | 2025-11-27 | Bristol-Myers Squibb Company | Treatment of tumors in subjects having fgl-1 positive samples |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US6080560A (en) | 1994-07-25 | 2000-06-27 | Monsanto Company | Method for producing antibodies in plant cells |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| AU2002258941A1 (en) | 2001-04-20 | 2002-11-05 | Mayo Foundation For Medical Education And Research | Methods of enhancing cell responsiveness |
| EP1456652A4 (en) | 2001-11-13 | 2005-11-02 | Dana Farber Cancer Inst Inc | IMMUNOCELL ACTIVATION MODULATING SUBSTANCES AND USE METHOD THEREFOR |
| IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
| ES2350687T3 (es) | 2002-07-03 | 2011-01-26 | Ono Pharmaceutical Co., Ltd. | Composiciones de inmunopotenciación. |
| ES2367430T3 (es) | 2002-12-23 | 2011-11-03 | Wyeth Llc | Anticuerpos contra pd-1 y sus usos. |
| AU2003275958A1 (en) | 2003-08-25 | 2005-03-10 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| EP1896582A4 (en) | 2005-05-09 | 2009-04-08 | Ono Pharmaceutical Co | HUMAN MONOCLONAL ANTIBODIES AGAINST PROGRAMMED CELL DEATH 1 (PD-1) AND METHOD FOR CREATING TREATMENT WITH ANTI-PD-1 ANTIBODIES ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPEUTICS |
| MX349137B (es) | 2005-06-08 | 2017-07-13 | Dana-Farber Cancer Inst | Metodos y composiciones para el tratamiento de infecciones persistentes y cancer por inhibicion de la ruta de muerte celular programada (pd-1). |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
| WO2008156712A1 (en) | 2007-06-18 | 2008-12-24 | N. V. Organon | Antibodies to human programmed death receptor pd-1 |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| EP2350129B1 (en) | 2008-08-25 | 2015-06-10 | Amplimmune, Inc. | Compositions of pd-1 antagonists and methods of use |
| WO2011110604A1 (en) | 2010-03-11 | 2011-09-15 | Ucb Pharma, S.A. | Pd-1 antibody |
| PT2699264T (pt) | 2011-04-20 | 2018-05-23 | Medimmune Llc | Anticorpos e outras moléculas que ligam b7-h1 e pd-1 |
| AU2012288413B2 (en) | 2011-07-24 | 2016-10-13 | Curetech Ltd. | Variants of humanized immunomodulatory monoclonal antibodies |
| JP6563906B2 (ja) | 2013-05-31 | 2019-08-21 | ソレント・セラピューティクス・インコーポレイテッドＳｏｒｒｅｎｔｏ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | Ｐｄ−１に結合する抗原結合蛋白質 |
| EA034666B1 (ru) | 2013-09-13 | 2020-03-04 | Бейджин Свитзерланд Гмбх | Антитело против pd-1 и его применение для лечения рака или вирусной инфекции и фрагмент антитела |
| US10081681B2 (en) * | 2013-09-20 | 2018-09-25 | Bristol-Myers Squibb Company | Combination of anti-LAG-3 antibodies and anti-PD-1 antibodies to treat tumors |
| AU2015205530B8 (en) * | 2014-01-13 | 2019-09-19 | Pieris Pharmaceuticals Gmbh | Multi-specific polypeptide useful for localized tumor immunomodulation |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| JOP20200094A1 (ar) * | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| US10239942B2 (en) | 2014-12-22 | 2019-03-26 | Pd-1 Acquisition Group, Llc | Anti-PD-1 antibodies |
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- 2016-08-08 BR BR112018000366A patent/BR112018000366A2/pt not_active Application Discontinuation
- 2016-08-08 US US15/750,651 patent/US20190010231A1/en not_active Abandoned
- 2016-08-08 AU AU2016306597A patent/AU2016306597A1/en not_active Abandoned
- 2016-08-08 MX MX2018001567A patent/MX2018001567A/es unknown
- 2016-08-08 CA CA2994631A patent/CA2994631A1/en not_active Abandoned
- 2016-08-08 KR KR1020187006631A patent/KR20180035906A/ko not_active Withdrawn
- 2016-08-08 JP JP2018506260A patent/JP2018526989A/ja not_active Withdrawn
- 2016-08-08 HK HK18113535.5A patent/HK1254450A1/zh unknown
- 2016-08-08 CN CN201680046086.9A patent/CN107922470A/zh active Pending
- 2016-08-08 EA EA201890456A patent/EA201890456A1/ru unknown
- 2016-08-08 EP EP16757830.1A patent/EP3331901A1/en not_active Withdrawn
- 2016-08-08 RU RU2018107991A patent/RU2018107991A/ru not_active Application Discontinuation
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| KR20180035906A (ko) | 2018-04-06 |
| RU2018107991A (ru) | 2019-09-09 |
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| CN107922470A (zh) | 2018-04-17 |
| EP3331901A1 (en) | 2018-06-13 |
| WO2017025498A1 (en) | 2017-02-16 |
| EA201890456A1 (ru) | 2018-07-31 |
| MX2018001567A (es) | 2018-11-09 |
| BR112018000366A2 (pt) | 2018-09-11 |
| US20190010231A1 (en) | 2019-01-10 |
| JP2018526989A (ja) | 2018-09-20 |
| CA2994631A1 (en) | 2017-02-16 |
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