CA2886036A1 - Purification of hetero-dimeric immunoglobulins - Google Patents
Purification of hetero-dimeric immunoglobulins Download PDFInfo
- Publication number
- CA2886036A1 CA2886036A1 CA2886036A CA2886036A CA2886036A1 CA 2886036 A1 CA2886036 A1 CA 2886036A1 CA 2886036 A CA2886036 A CA 2886036A CA 2886036 A CA2886036 A CA 2886036A CA 2886036 A1 CA2886036 A1 CA 2886036A1
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- immunoglobulin
- region
- fragment
- amino acid
- hetero
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- C07K16/46—Hybrid immunoglobulins
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- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 and B01D15/30 - B01D15/36, e.g. affinity, ligand exchange or chiral chromatography
- B01D15/3804—Affinity chromatography
- B01D15/3809—Affinity chromatography of the antigen-antibody type, e.g. protein A, G or L chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- 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
- C07K2317/522—CH1 domain
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- 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
- C07K2317/524—CH2 domain
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- 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
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
Landscapes
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
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- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Priority Applications (1)
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| CA3061557A Division CA3061557A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
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| CA2886036A1 true CA2886036A1 (en) | 2014-04-03 |
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| CA2886036A Abandoned CA2886036A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
| CA3061557A Pending CA3061557A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
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| CA3061557A Pending CA3061557A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
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| EP (2) | EP2900696A1 (enExample) |
| JP (5) | JP2015529236A (enExample) |
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| AU (2) | AU2013322710A1 (enExample) |
| CA (2) | CA2886036A1 (enExample) |
| HK (1) | HK1215950A1 (enExample) |
| IL (2) | IL237872B (enExample) |
| IN (1) | IN2015MN00139A (enExample) |
| WO (1) | WO2014049003A1 (enExample) |
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| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| WO2010115589A1 (en) | 2009-04-07 | 2010-10-14 | Roche Glycart Ag | Trivalent, bispecific antibodies |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| US20120302737A1 (en) | 2009-09-16 | 2012-11-29 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
| BR112013001847A2 (pt) | 2010-08-24 | 2016-05-31 | Hoffmann La Roche | anticorpo biespecífico, método de preparação do anticorpo biespecífico, do anticorpo biespecífico trivalente, métodos e composição farmacêutica |
| JP5764677B2 (ja) | 2011-02-28 | 2015-08-19 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 抗原結合タンパク質 |
| CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
| WO2014049003A1 (en) * | 2012-09-25 | 2014-04-03 | Glenmark Pharmaceuticals S.A. | Purification of hetero-dimeric immunoglobulins |
| CN105143262A (zh) | 2013-04-29 | 2015-12-09 | 豪夫迈·罗氏有限公司 | 结合人fcrn的修饰的抗体和使用方法 |
| WO2015033223A2 (en) * | 2013-09-03 | 2015-03-12 | Novimmune S.A. | Readily isolated bispecific binding molecules with native format having mutated constant regions |
| RU2016115866A (ru) | 2013-10-11 | 2017-11-16 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифические антитела с обменянными доменами и одинаковыми вариабельными доменами легкой цепи |
| PE20160724A1 (es) | 2013-11-04 | 2016-08-04 | Glenmark Pharmaceuticals Sa | Produccion de inmunoglobulinas heterodimericas de redireccionamiento de celulas t |
| WO2015107015A1 (en) | 2014-01-15 | 2015-07-23 | F. Hoffmann-La Roche Ag | Fc-region variants with improved protein a-binding |
| AU2015237184B2 (en) | 2014-03-28 | 2020-11-26 | Xencor, Inc. | Bispecific antibodies that bind to CD38 and CD3 |
| AR101262A1 (es) * | 2014-07-26 | 2016-12-07 | Regeneron Pharma | Plataforma de purificación para anticuerpos biespecíficos |
| EP3174897B1 (en) * | 2014-07-29 | 2020-02-12 | F.Hoffmann-La Roche Ag | Multispecific antibodies |
| MA40894A (fr) * | 2014-11-04 | 2017-09-12 | Glenmark Pharmaceuticals Sa | Immunoglobulines hétéro-dimères reciblant des lymphocytes t cd3/cd38 et leurs procédés de production |
| US11773166B2 (en) | 2014-11-04 | 2023-10-03 | Ichnos Sciences SA | CD3/CD38 T cell retargeting hetero-dimeric immunoglobulins and methods of their production |
| PE20171103A1 (es) | 2014-11-26 | 2017-08-07 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38 |
| JP6721590B2 (ja) | 2014-12-03 | 2020-07-15 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 多重特異性抗体 |
| EP3319996B1 (en) | 2015-07-09 | 2024-01-03 | Genmab A/S | Bispecific and multispecific antibodies and method for isolation of such |
| EP3365366B1 (en) | 2015-10-25 | 2021-07-14 | Sanofi | Trispecific and/or trivalent binding proteins for prevention or treatment of hiv infection |
| GB201602156D0 (en) * | 2016-02-05 | 2016-03-23 | Jones Philip C And Boku University Of Natural Resources And Life Sciences | Heterodimers and purification thereof |
| FI3443006T3 (fi) | 2016-04-13 | 2023-10-23 | Sanofi Sa | Trispesifisiä ja/tai kolmiarvoisia sitojaproteiineja |
| EP3452502B1 (en) * | 2016-05-02 | 2021-03-03 | H. Hoffnabb-La Roche Ag | The contorsbody - a single chain target binder |
| IL265605B2 (en) * | 2016-09-29 | 2024-06-01 | Beijing Hanmi Pharmaceutical Co Ltd | Heterodimeric immunoglobulin constructs, pharmaceutical composition comprising the same, use and preparation methods thereof |
| WO2018090950A1 (zh) | 2016-11-18 | 2018-05-24 | 北京韩美药品有限公司 | 抗pd‐1/抗her2天然抗体结构样异源二聚体形式双特异抗体及其制备 |
| MA44670B1 (fr) * | 2017-03-17 | 2023-11-30 | Sanofi Sa | Protéines de liaison trispécifiques et/ou trivalentes |
| KR102732040B1 (ko) | 2017-04-11 | 2024-11-21 | 인히브릭스 바이오사이언스, 인크. | 제한된 ｃｄ3 결합을 갖는 다중특이적 폴리펩티드 컨스트럭트 및 이를 이용한 방법 |
| WO2019153200A1 (zh) | 2018-02-08 | 2019-08-15 | 北京韩美药品有限公司 | 抗pd-1/抗her2天然抗体结构样异源二聚体形式双特异抗体及其制备 |
| CN111902720B (zh) | 2018-03-21 | 2025-02-07 | 沃特世科技公司 | 基于非抗体高亲和力的样品制备、吸附剂、装置和方法 |
| WO2019200022A1 (en) | 2018-04-11 | 2019-10-17 | Inhibrx, Inc. | Multispecific polypeptide constructs having constrained cd3 binding and related methods and uses |
| FR3080621B1 (fr) * | 2018-04-26 | 2022-12-09 | Univ Limoges | Nouvelle classe d'immunoglobuline recombinante de type g : igg5, codee par le pseudo-gene gamma humain de chaine lourde |
| EP3810649A1 (en) | 2018-06-22 | 2021-04-28 | Genmab A/S | Method for producing a controlled mixture of two or more different antibodies |
| US12195533B2 (en) | 2018-07-24 | 2025-01-14 | Inhibrx Biosciences, Inc. | Multispecific polypeptide constructs containing a constrained CD3 binding domain and a receptor binding region and methods of using the same |
| US20210340273A1 (en) | 2018-10-11 | 2021-11-04 | Inhlbrx, inc. | 5t4 single domain antibodies and therapeutic compositions thereof |
| US11208485B2 (en) | 2018-10-11 | 2021-12-28 | Inhibrx, Inc. | PD-1 single domain antibodies and therapeutic compositions thereof |
| US20230124851A1 (en) | 2018-10-11 | 2023-04-20 | Inhibrx, lnc. | B7h3 single domain antibodies and therapeutic compositions thereof |
| WO2020076977A2 (en) | 2018-10-11 | 2020-04-16 | Inhibrx, Inc. | Dll3 single domain antibodies and therapeutic compositions thereof |
| WO2020136564A1 (en) | 2018-12-24 | 2020-07-02 | Sanofi | Pseudofab-based multispecific binding proteins |
| US11613576B2 (en) | 2019-04-09 | 2023-03-28 | Sanofi | Trispecific binding proteins, methods, and uses thereof |
| IL293845A (en) * | 2019-12-26 | 2022-08-01 | Abl Bio Inc | Method for purifying biologically active peptide by using protein a affinity chromatography |
| IL294879A (en) | 2020-01-29 | 2022-09-01 | Inhibrx Inc | Cd28 single domain antibodies and multivalent and multispecific constructs thereof |
| WO2022077006A1 (en) | 2020-10-07 | 2022-04-14 | Dren Bio, Inc. | Anti-dectin-1 antibodies and methods of use thereof |
| JP2024527262A (ja) | 2021-06-16 | 2024-07-24 | アレクトル エルエルシー | 二重特異性抗ＭｅｒＴＫ及び抗ＰＤＬ１抗体ならびにその使用方法 |
| WO2022266221A1 (en) | 2021-06-16 | 2022-12-22 | Alector Llc | Monovalent anti-mertk antibodies and methods of use thereof |
| JP2023092810A (ja) * | 2021-12-22 | 2023-07-04 | 国立大学法人東京農工大学 | 変異抗体、変異抗体の製造方法 |
| CN119584978A (zh) | 2022-06-07 | 2025-03-07 | 再生元制药公司 | 用于调节t细胞活性的多特异性分子及其用途 |
| JP2025528752A (ja) | 2022-07-29 | 2025-09-02 | アレクトル エルエルシー | トランスフェリン受容体抗原結合ドメイン及びその使用法 |
| CA3261511A1 (en) | 2022-07-29 | 2024-02-01 | Alector Llc | CD98HC ANTIGEN BINDING DOMAINS AND THEIR USES |
| AU2023334360A1 (en) * | 2022-09-02 | 2025-03-06 | Zoetis Services Llc | Equine antibody mutants |
| WO2024102948A1 (en) | 2022-11-11 | 2024-05-16 | Celgene Corporation | Fc receptor-homolog 5 (fcrh5) specific binding molecules and bispecific t-cell engaging antibodies including same and related methods |
| US12195546B2 (en) | 2022-12-19 | 2025-01-14 | Sanofi | CD28/OX40 bispecific antibodies |
| WO2025038668A1 (en) | 2023-08-14 | 2025-02-20 | Voro Therapeutics, Inc. | Therapeutic binding agents that conditionally promote myeloid cell activity against target cells and uses thereof |
| WO2025087386A1 (zh) * | 2023-10-25 | 2025-05-01 | 正大天晴药业集团南京顺欣制药有限公司 | 抗her2抗体药物偶联物治疗乳腺癌的用途 |
| WO2025166042A1 (en) | 2024-01-31 | 2025-08-07 | Alector Llc | Cd98hc antigen-binding domains and uses therefor |
| WO2025166045A1 (en) | 2024-01-31 | 2025-08-07 | Alector Llc | β-GLUCOCEREBROSIDASE ENZYMES, FUSION PROTEINS AND COMPLEXES COMPRISING THE SAME, AND METHODS OF USE THEREOF |
| WO2025166077A1 (en) | 2024-01-31 | 2025-08-07 | Alector Llc | Compositions comprising progranulin and uses thereof |
| WO2025166040A1 (en) | 2024-01-31 | 2025-08-07 | Alector Llc | Multi-specific binding proteins that bind to gpnmb and a blood brain barrier target and methods of use thereof |
| WO2025240670A2 (en) | 2024-05-15 | 2025-11-20 | Abalytics Oncology, Inc. | Anti-pd-1 antibodies and related binding molecules and methods and uses thereof |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2413974A1 (fr) | 1978-01-06 | 1979-08-03 | David Bernard | Sechoir pour feuilles imprimees par serigraphie |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| DK0479909T3 (da) | 1989-06-29 | 1997-04-07 | Medarex Inc | Bispecifikke reagenser til AIDS-behandling |
| JPH06500011A (ja) | 1990-06-29 | 1994-01-06 | ラージ スケール バイオロジー コーポレイション | 形質転換された微生物によるメラニンの製造 |
| JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
| WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
| DE4419399C1 (de) | 1994-06-03 | 1995-03-09 | Gsf Forschungszentrum Umwelt | Verfahren zur Herstellung von heterologen bispezifischen Antikörpern |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| EP0826696B1 (de) | 1996-09-03 | 2002-05-29 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Verwendung bi-und trispezifischer Antikörper zur Induktion einer Tumorimmunität |
| US8142780B2 (en) * | 1998-08-20 | 2012-03-27 | Strox Biopharmaceuticals, Llc | Anti-bacterial antibodies |
| US6322788B1 (en) * | 1998-08-20 | 2001-11-27 | Stanley Arthur Kim | Anti-bacterial antibodies and methods of use |
| ES2402650T3 (es) * | 2005-06-17 | 2013-05-07 | Janssen Alzheimer Immunotherapy | Métodos de purificación de anticuerpos anti A beta |
| AR056857A1 (es) | 2005-12-30 | 2007-10-24 | U3 Pharma Ag | Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos |
| US8871912B2 (en) | 2006-03-24 | 2014-10-28 | Merck Patent Gmbh | Engineered heterodimeric protein domains |
| WO2007147901A1 (en) | 2006-06-22 | 2007-12-27 | Novo Nordisk A/S | Production of bispecific antibodies |
| SI2129396T1 (sl) | 2007-02-16 | 2013-12-31 | Merrimack Pharmaceuticals, Inc. | Protitelesa proti ErbB3 in njihove uporabe |
| SI2235064T1 (sl) | 2008-01-07 | 2016-04-29 | Amgen Inc. | Metoda za izdelavo heterodimernih molekul - protitelesa fc z uporabo elektrostatičnih usmerjevalnih učinkov |
| WO2010037836A2 (en) * | 2008-10-01 | 2010-04-08 | Micromet Ag | Cross-species-specific psmaxcd3 bispecific single chain antibody |
| US20120009182A1 (en) * | 2008-12-23 | 2012-01-12 | Genentech, Inc. | Immunoglobulin variants with altered binding to protein a |
| US8679492B2 (en) | 2009-02-23 | 2014-03-25 | Glenmark Pharmaceuticals S.A. | Humanized antibodies that bind to CD19 and their uses |
| AR075896A1 (es) | 2009-03-20 | 2011-05-04 | Genentech Inc | Anticuerpos anti-her (factor de crecimiento epidermico) |
| RU2522002C2 (ru) | 2009-06-26 | 2014-07-10 | Ридженерон Фармасьютикалз, Инк. | Легковыделяемые биспецифические антитела с природным иммуноглобулиновым форматом |
| WO2011078332A1 (ja) * | 2009-12-25 | 2011-06-30 | 中外製薬株式会社 | ポリペプチド多量体を精製するためのポリペプチドの改変方法 |
| EA201201435A1 (ru) * | 2010-04-20 | 2013-04-30 | Генмаб А/С | ГЕТЕРОДИМЕРНЫЕ АНТИТЕЛО-Fc-СОДЕРЖАЩИЕ БЕЛКИ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ |
| NZ608724A (en) | 2011-03-25 | 2015-12-24 | Glenmark Pharmaceuticals Sa | Hetero-dimeric immunoglobulins |
| US9114516B2 (en) | 2011-07-21 | 2015-08-25 | Illinois Tool Works Inc. | Portable combustion gas-powered tools with combustion chamber lockout system |
| LT2771364T (lt) * | 2011-10-27 | 2019-09-10 | Genmab A/S | Heterodimerinių baltymų gamyba |
| US20150088787A1 (en) | 2012-03-06 | 2015-03-26 | Foss Analytical Ab | Method, software and graphical user interface for forming a prediction model for chemometric analysis |
| EP3517548A1 (en) | 2012-03-13 | 2019-07-31 | NovImmune S.A. | Readily isolated bispecific antibodies with native immunoglobulin format |
| WO2014049003A1 (en) * | 2012-09-25 | 2014-04-03 | Glenmark Pharmaceuticals S.A. | Purification of hetero-dimeric immunoglobulins |
| PE20160724A1 (es) * | 2013-11-04 | 2016-08-04 | Glenmark Pharmaceuticals Sa | Produccion de inmunoglobulinas heterodimericas de redireccionamiento de celulas t |
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| JP2018104444A (ja) | 2018-07-05 |
| JP2015529236A (ja) | 2015-10-05 |
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| KR20150076172A (ko) | 2015-07-06 |
| CN104968685A (zh) | 2015-10-07 |
| US20150239991A1 (en) | 2015-08-27 |
| WO2014049003A1 (en) | 2014-04-03 |
| AU2013322710A1 (en) | 2015-04-16 |
| EP3401337A1 (en) | 2018-11-14 |
| AU2013322710A2 (en) | 2015-05-07 |
| AU2018204314A1 (en) | 2018-07-05 |
| JP2019073512A (ja) | 2019-05-16 |
| HK1215950A1 (zh) | 2016-09-30 |
| IL237872B (en) | 2019-09-26 |
| JP2020105203A (ja) | 2020-07-09 |
| JP2022116326A (ja) | 2022-08-09 |
| US20200010568A1 (en) | 2020-01-09 |
| IL269207A (en) | 2019-11-28 |
| AU2018204314B2 (en) | 2020-05-14 |
| IL237872A0 (en) | 2015-05-31 |
| IN2015MN00139A (enExample) | 2015-10-16 |
| IL269207B (en) | 2022-02-01 |
| CA3061557A1 (en) | 2014-04-03 |
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