MX2016010295A - Reduccion selectiva de proteinas. - Google Patents
Reduccion selectiva de proteinas.Info
- Publication number
- MX2016010295A MX2016010295A MX2016010295A MX2016010295A MX2016010295A MX 2016010295 A MX2016010295 A MX 2016010295A MX 2016010295 A MX2016010295 A MX 2016010295A MX 2016010295 A MX2016010295 A MX 2016010295A MX 2016010295 A MX2016010295 A MX 2016010295A
- Authority
- MX
- Mexico
- Prior art keywords
- antibody
- engineered cysteine
- uncapped
- antibody molecules
- preparations
- Prior art date
Links
- 102000004169 proteins and genes Human genes 0.000 title abstract 2
- 108090000623 proteins and genes Proteins 0.000 title abstract 2
- 238000000034 method Methods 0.000 abstract 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 abstract 3
- 235000018417 cysteine Nutrition 0.000 abstract 3
- 238000002360 preparation method Methods 0.000 abstract 3
- 238000006722 reduction reaction Methods 0.000 abstract 3
- 239000006227 byproduct Substances 0.000 abstract 2
- 239000003638 chemical reducing agent Substances 0.000 abstract 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 abstract 2
- 229940127121 immunoconjugate Drugs 0.000 abstract 2
- 235000018102 proteins Nutrition 0.000 abstract 1
- 230000000717 retained effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6817—Toxins
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/08—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents
- C07K1/086—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents containing sulfur
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1133—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by redox-reactions involving cystein/cystin side chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Water Supply & Treatment (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
La presente invención proporciona un método para hacer preparaciones de proteína de cisteína no coronada, que incluye las preparaciones del anticuerpo con cisteína diseñada no coronada. Los métodos incluyen, inter alia, poner en contacto un agente reductor con las moléculas del anticuerpo con cisteína diseñada, cada una de las moléculas del anticuerpo tiene al menos un residuo de cisteína diseñada coronada y al menos un enlace disulfuro intercadena y hacer reaccionar el agente reductor con las moléculas del anticuerpo bajo condiciones suficientes para eliminar la corona de los residuos de cisteína diseñada y formar subproducto coronados. El método también incluye eliminar el subproducto coronado durante la reacción de reducción. Sustancialmente todos los enlaces disulfuro intercadena presentes en las moléculas del anticuerpo antes de la reducción se retienen después de la reducción. Los conjugados de anticuerpo y los métodos para preparar los conjugados de anticuerpo utilizando las preparaciones del anticuerpo no coronado también se describen.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461938378P | 2014-02-11 | 2014-02-11 | |
| PCT/US2015/015369 WO2015123265A1 (en) | 2014-02-11 | 2015-02-11 | Selective reduction of proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2016010295A true MX2016010295A (es) | 2016-10-17 |
Family
ID=53800577
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2016010295A MX2016010295A (es) | 2014-02-11 | 2015-02-11 | Reduccion selectiva de proteinas. |
| MX2020002791A MX2020002791A (es) | 2014-02-11 | 2016-08-09 | Reduccion selectiva de proteinas. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2020002791A MX2020002791A (es) | 2014-02-11 | 2016-08-09 | Reduccion selectiva de proteinas. |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US10464997B2 (es) |
| EP (2) | EP4190809A1 (es) |
| JP (4) | JP6713931B2 (es) |
| KR (2) | KR102532137B1 (es) |
| CN (3) | CN112979786A (es) |
| CA (2) | CA3211226A1 (es) |
| HK (1) | HK1231400A1 (es) |
| MX (2) | MX2016010295A (es) |
| WO (1) | WO2015123265A1 (es) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX377339B (es) | 2013-08-28 | 2025-03-06 | Abbvie Stemcentrx Llc | Metodos de conjugacion de anticuerpos especificos de sitio y composiciones. |
| US10053511B2 (en) | 2013-11-06 | 2018-08-21 | Abbvie Stemcentrx Llc | Anti-claudin antibodies and methods of use |
| PE20160993A1 (es) | 2013-12-12 | 2016-10-14 | Abbvie Stemcentrx Llc | Nuevos anticuerpos anti-dpep3 y metodos de uso |
| KR102532137B1 (ko) | 2014-02-11 | 2023-05-12 | 씨젠 인크. | 단백질의 선택적 환원 |
| EP3107576A4 (en) | 2014-02-21 | 2017-09-06 | Abbvie Stemcentrx LLC | Anti-dll3 antibodies and drug conjugates for use in melanoma |
| TW201617368A (zh) | 2014-09-05 | 2016-05-16 | 史坦森特瑞斯公司 | 新穎抗mfi2抗體及使用方法 |
| SI3268047T1 (sl) * | 2015-03-09 | 2024-02-29 | Heidelberg Pharma Research Gmbh | Konjugati amatoksin-protitelo |
| PL3458100T3 (pl) | 2016-02-12 | 2020-11-30 | Byondis B.V. | Selektywna redukcja przeciwciał ze zmodyfikowaną cysteiną |
| US20190127476A1 (en) * | 2016-05-06 | 2019-05-02 | Abbvie Stemcentrx Llc | Novel anti-tnfrsf21 antibodies and methods of use |
| US10828375B2 (en) * | 2016-11-07 | 2020-11-10 | Seattle Genetics, Inc. | Distribution of engineered-cysteine caps |
| MX2019009372A (es) * | 2017-02-08 | 2019-12-11 | Pfizer | Produccion a gran escala para cisteinas de anticuerpo protegidas y no protegidas y su uso en la conjugacion de proteinas terapeuticas. |
| CN107247144B (zh) * | 2017-05-16 | 2019-12-24 | 上海科华生物工程股份有限公司 | 一种预处理丙肝抗原的方法和检测试剂盒 |
| US11696958B2 (en) | 2017-05-23 | 2023-07-11 | Byondis B.V. | Dual conjugation process for preparing antibody-drug conjugates |
| EP4464719A3 (en) * | 2017-08-04 | 2025-03-05 | Amgen Inc. | Method of conjugation of cys-mabs |
| CN107746424A (zh) * | 2017-10-30 | 2018-03-02 | 上海药明生物技术有限公司 | 一种IgG4抗体的生物偶联方法 |
| KR102788989B1 (ko) | 2019-02-15 | 2025-03-31 | 우시 엑스디씨 싱가포르 프라이빗 리미티드 | 동질성이 개선된 항체-약물 콘쥬게이트의 제조방법 |
| US12109273B2 (en) | 2019-02-15 | 2024-10-08 | Wuxi Xdc Singapore Private Limited | Process for preparing antibody-drug conjugates with improved homogeneity |
| CN113189184B (zh) * | 2021-04-28 | 2022-09-09 | 浙江大学 | 含有半胱氨酸的毛细管凝胶电泳样品缓冲液 |
| EP4488290A1 (en) * | 2022-03-04 | 2025-01-08 | ABTIS Co., Ltd. | Method for increasing production yield of antibody-drug conjugate by using thiol-reactive additive |
| CN114878728A (zh) * | 2022-05-06 | 2022-08-09 | 浙江大学 | 一种新型的抗体肽图检测还原方法 |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| GB8720833D0 (en) | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6111166A (en) | 1994-09-19 | 2000-08-29 | Medarex, Incorporated | Transgenic mice expressing human Fcα and β receptors |
| GB9422383D0 (en) * | 1994-11-05 | 1995-01-04 | Wellcome Found | Antibodies |
| US6130237A (en) | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| US20030083263A1 (en) | 2001-04-30 | 2003-05-01 | Svetlana Doronina | Pentapeptide compounds and uses related thereto |
| US20030105017A1 (en) * | 2001-07-10 | 2003-06-05 | Gregory Conn | Purification of human Troponin I |
| JP4741838B2 (ja) | 2002-07-31 | 2011-08-10 | シアトル ジェネティクス,インコーポレーテッド | 癌、自己免疫疾患または感染症を治療するための薬物結合体およびその使用 |
| US8088387B2 (en) | 2003-10-10 | 2012-01-03 | Immunogen Inc. | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates |
| CN104998273A (zh) | 2003-11-06 | 2015-10-28 | 西雅图基因公司 | 能够与配体偶联的单甲基缬氨酸化合物 |
| US7691962B2 (en) | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
| EP3088004B1 (en) | 2004-09-23 | 2018-03-28 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
| CA2605507C (en) | 2005-04-19 | 2016-06-28 | Seattle Genetics, Inc. | Humanized anti-cd70 binding agents and uses thereof |
| EP1893632B1 (en) | 2005-06-17 | 2015-08-12 | Novo Nordisk Health Care AG | Selective reduction and derivatization of engineered factor vii proteins comprising at least one non-native cysteine |
| GB0513852D0 (en) * | 2005-07-06 | 2005-08-10 | Celltech R&D Ltd | Biological products |
| CA2614436C (en) | 2005-07-07 | 2016-05-17 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus |
| WO2007008848A2 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus |
| PT1813614E (pt) | 2006-01-25 | 2012-01-09 | Sanofi Sa | Agentes citotóxicos compreendendo novos derivados de tomaimicina |
| WO2008025020A2 (en) | 2006-08-25 | 2008-02-28 | Seattle Genetics, Inc. | Cd30 binding agents and uses thereof |
| PT2211904T (pt) | 2007-10-19 | 2016-11-02 | Seattle Genetics Inc | Agentes de ligação a cd19 e seus usos |
| ES2613963T3 (es) * | 2008-01-18 | 2017-05-29 | Medimmune, Llc | Anticuerpos manipulados con cisteína para conjugación específica de sitio |
| EP2842575B1 (en) | 2008-03-18 | 2017-09-27 | Seattle Genetics, Inc. | Auristatin drug linker conjugates |
| CN102365021B (zh) | 2009-02-05 | 2015-07-15 | 伊缪诺金公司 | 新型苯并二氮杂*衍生物 |
| FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| GB0920127D0 (en) * | 2009-11-17 | 2009-12-30 | Ucb Pharma Sa | Antibodies |
| EP2638066A4 (en) * | 2010-11-09 | 2015-06-03 | Medimmune Llc | ANTIBODY EQUIPMENT FOR HOMOGENEOUS CONJUGATION |
| SMT201900181T1 (it) | 2011-02-15 | 2019-05-10 | Immunogen Inc | Metodi di preparazione di coniugati |
| US20130309223A1 (en) | 2012-05-18 | 2013-11-21 | Seattle Genetics, Inc. | CD33 Antibodies And Use Of Same To Treat Cancer |
| KR102532137B1 (ko) | 2014-02-11 | 2023-05-12 | 씨젠 인크. | 단백질의 선택적 환원 |
-
2015
- 2015-02-11 KR KR1020167022728A patent/KR102532137B1/ko active Active
- 2015-02-11 WO PCT/US2015/015369 patent/WO2015123265A1/en not_active Ceased
- 2015-02-11 EP EP22202155.2A patent/EP4190809A1/en active Pending
- 2015-02-11 CN CN202110215052.0A patent/CN112979786A/zh active Pending
- 2015-02-11 JP JP2016568485A patent/JP6713931B2/ja active Active
- 2015-02-11 HK HK17105164.0A patent/HK1231400A1/zh unknown
- 2015-02-11 CN CN202010117289.0A patent/CN111187348A/zh active Pending
- 2015-02-11 CA CA3211226A patent/CA3211226A1/en active Pending
- 2015-02-11 MX MX2016010295A patent/MX2016010295A/es active IP Right Grant
- 2015-02-11 KR KR1020237015699A patent/KR20230088389A/ko not_active Ceased
- 2015-02-11 US US15/117,254 patent/US10464997B2/en active Active
- 2015-02-11 EP EP15749202.6A patent/EP3104881A4/en not_active Withdrawn
- 2015-02-11 CA CA2938450A patent/CA2938450C/en active Active
- 2015-02-11 CN CN201580008306.4A patent/CN106456725B9/zh active Active
-
2016
- 2016-08-09 MX MX2020002791A patent/MX2020002791A/es unknown
-
2019
- 2019-09-24 US US16/580,290 patent/US11667696B2/en active Active
-
2020
- 2020-05-29 JP JP2020094209A patent/JP2020143145A/ja not_active Withdrawn
-
2022
- 2022-08-05 JP JP2022125651A patent/JP2022153663A/ja active Pending
-
2023
- 2023-04-26 US US18/139,592 patent/US20230391848A1/en not_active Abandoned
-
2024
- 2024-10-16 JP JP2024180684A patent/JP2025011264A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020143145A (ja) | 2020-09-10 |
| US20160347824A1 (en) | 2016-12-01 |
| CA3211226A1 (en) | 2015-08-20 |
| CN111187348A (zh) | 2020-05-22 |
| CN106456725B9 (zh) | 2022-08-09 |
| KR20230088389A (ko) | 2023-06-19 |
| CN106456725A (zh) | 2017-02-22 |
| KR20160136289A (ko) | 2016-11-29 |
| JP2017506262A (ja) | 2017-03-02 |
| HK1231400A1 (zh) | 2017-12-22 |
| US20230391848A1 (en) | 2023-12-07 |
| MX2020002791A (es) | 2020-07-22 |
| US11667696B2 (en) | 2023-06-06 |
| JP2022153663A (ja) | 2022-10-12 |
| US20200115438A1 (en) | 2020-04-16 |
| JP2025011264A (ja) | 2025-01-23 |
| EP3104881A1 (en) | 2016-12-21 |
| KR102532137B1 (ko) | 2023-05-12 |
| US10464997B2 (en) | 2019-11-05 |
| CN106456725B (zh) | 2021-03-12 |
| CA2938450A1 (en) | 2015-08-20 |
| CN112979786A (zh) | 2021-06-18 |
| JP6713931B2 (ja) | 2020-06-24 |
| CA2938450C (en) | 2023-10-17 |
| EP3104881A4 (en) | 2017-09-27 |
| WO2015123265A1 (en) | 2015-08-20 |
| EP4190809A1 (en) | 2023-06-07 |
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