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
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- 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
-
- 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
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Biophysics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- 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)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA3061557A CA3061557A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
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| US201261705278P | 2012-09-25 | 2012-09-25 | |
| US61/705,278 | 2012-09-25 | ||
| PCT/EP2013/069989 WO2014049003A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
Related Child Applications (1)
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| CA3061557A Division CA3061557A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
Publications (1)
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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 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3061557A Pending CA3061557A1 (en) | 2012-09-25 | 2013-09-25 | Purification of hetero-dimeric immunoglobulins |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20150239991A1 (OSRAM) |
| EP (2) | EP2900696A1 (OSRAM) |
| JP (5) | JP2015529236A (OSRAM) |
| KR (1) | KR20150076172A (OSRAM) |
| CN (1) | CN104968685A (OSRAM) |
| AU (2) | AU2013322710A1 (OSRAM) |
| CA (2) | CA2886036A1 (OSRAM) |
| HK (1) | HK1215950A1 (OSRAM) |
| IL (2) | IL237872B (OSRAM) |
| IN (1) | IN2015MN00139A (OSRAM) |
| WO (1) | WO2014049003A1 (OSRAM) |
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| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| ES2537100T3 (es) | 2009-04-07 | 2015-06-02 | Roche Glycart Ag | Anticuerpos biespecíficos trivalentes |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| AU2010296018B2 (en) | 2009-09-16 | 2016-05-05 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| AR080793A1 (es) | 2010-03-26 | 2012-05-09 | Roche Glycart Ag | Anticuerpos biespecificos |
| EP2609111B1 (en) | 2010-08-24 | 2017-11-01 | F. Hoffmann-La Roche AG | Bispecific antibodies comprising a disulfide stabilized-fv fragment |
| CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
| BR112013019975A2 (pt) | 2011-02-28 | 2017-08-01 | Hoffmann La Roche | proteínas de ligação de antígeno, composição farmacêutica, uso de uma proteína de ligação de antígeno, método para o tratamento de um paciente e método para a preparação de uma proteína de ligação de antígeno, ácido nucleico, vetor e célula hospedeira" |
| HK1215950A1 (zh) * | 2012-09-25 | 2016-09-30 | 艾科诺斯科技股份有限公司 | 异源二聚免疫球蛋白的纯化 |
| ES2746136T3 (es) | 2013-04-29 | 2020-03-04 | Hoffmann La Roche | Anticuerpos modificados de unión a FcRn humano y procedimientos de uso |
| EP3041865A2 (en) * | 2013-09-03 | 2016-07-13 | 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 |
| AP2016009222A0 (en) * | 2013-11-04 | 2016-05-31 | Glenmark Pharmaceuticals Sa | Production of t cell retargeting hetero-dimeric immunoglobulins |
| RU2698969C2 (ru) | 2014-01-15 | 2019-09-02 | Ф.Хоффманн-Ля Рош Аг | Варианты fc-области с улучшенной способностью связываться с белком а |
| BR112016022385A2 (pt) | 2014-03-28 | 2018-06-19 | Xencor, Inc | anticorpos específicos que se ligam a cd38 e 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 |
| CN107406512A (zh) | 2014-11-26 | 2017-11-28 | Xencor公司 | 结合cd3和cd38的异二聚体抗体 |
| 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 |
| WO2017005649A1 (en) | 2015-07-09 | 2017-01-12 | Genmab A/S | Bispecific and multispecific antibodies and method for isolation of such |
| NZ781602A (en) | 2015-10-25 | 2025-07-25 | Sanofi Sa | 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 |
| EP4257193B1 (en) | 2016-04-13 | 2025-12-31 | Sanofi | TRISPECIFIC AND/OR TRIVALENT LINKING PROTEINS |
| EP3443006B1 (en) * | 2016-04-13 | 2023-08-02 | Sanofi | Trispecific and/or trivalent binding proteins |
| BR112018069890A2 (pt) * | 2016-05-02 | 2019-02-05 | Hoffmann La Roche | polipeptídio de fusão que se liga de forma específica a um alvo, polipeptídio de fusão dimérico, ácido nucleico isolado, par de ácidos nucleicos isolados, célula hospedeira, método para produzir um polipeptídio de fusão, imunoconjugado, formulação farmacêutica, polipeptídio de fusão e uso do polipeptídio de fusão |
| WO2018059502A1 (en) | 2016-09-29 | 2018-04-05 | Beijing Hanmi Pharmaceutical Co., Ltd. | Heterodimeric immunoglobulin constructs and preparation methods thereof |
| CA3043652A1 (en) | 2016-11-18 | 2018-05-24 | Beijing Hanmi Pharmaceutical Co., Ltd. | Anti-pd-1/anti-her2 natural antibody structural heterodimeric bispecific antibody and method of preparing the same |
| IL269826B1 (en) | 2017-04-11 | 2025-09-01 | Inhibrx Inc | Multispecific polypeptide constructs having constrained cd3 binding and methods of using the same |
| 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 |
| CN119881293A (zh) | 2018-03-21 | 2025-04-25 | 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 |
| JP7724061B2 (ja) | 2018-04-11 | 2025-08-15 | インヒブルクス バイオサイエンシズ インコーポレイテッド | 制約されたｃｄ３結合を有する多重特異性ポリペプチド構築物ならびに関連する方法および使用 |
| 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 |
| MA52945A (fr) | 2018-06-22 | 2021-04-28 | Genmab As | Procédé de production d'un mélange contrôlé d'au moins deux anticorps différents |
| TW202035451A (zh) | 2018-07-24 | 2020-10-01 | 美商英伊布里克斯公司 | 含有受限cd3結合域及受體結合區之多重特異性多肽構築體及其使用方法 |
| US20230124851A1 (en) | 2018-10-11 | 2023-04-20 | Inhibrx, lnc. | B7h3 single domain antibodies and therapeutic compositions thereof |
| CN113166263A (zh) | 2018-10-11 | 2021-07-23 | 印希比股份有限公司 | Dll3单域抗体及其治疗性组合物 |
| US20210340273A1 (en) | 2018-10-11 | 2021-11-04 | Inhlbrx, inc. | 5t4 single domain antibodies and therapeutic compositions thereof |
| CN120623346A (zh) | 2018-10-11 | 2025-09-12 | 因荷布瑞克斯生物科学公司 | Pd-1单结构域抗体及其治疗组合物 |
| JP7734075B2 (ja) | 2018-12-24 | 2025-09-04 | サノフイ | 疑似ｆａｂベースの多重特異性結合タンパク質 |
| US11613576B2 (en) | 2019-04-09 | 2023-03-28 | Sanofi | Trispecific binding proteins, methods, and uses thereof |
| EP4141025A4 (en) * | 2019-12-26 | 2024-04-24 | 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 | Monodomain antibodies of cd28 and their multivalent and multispecific constructs |
| CA3198102A1 (en) | 2020-10-07 | 2022-04-14 | Dren Bio, Inc. | Anti-dectin-1 antibodies and methods of use thereof |
| EP4355786A1 (en) | 2021-06-16 | 2024-04-24 | Alector LLC | Bispecific anti-mertk and anti-pdl1 antibodies and methods of use thereof |
| EP4355783A1 (en) | 2021-06-16 | 2024-04-24 | 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 |
| CA3258639A1 (en) | 2022-06-07 | 2023-12-14 | Regeneron Pharmaceuticals, Inc. | Multispecific molecules to modulate T lymphocyte activity, and their uses |
| EP4562044A2 (en) | 2022-07-29 | 2025-06-04 | Alector LLC | Transferrin receptor antigen-binding domains and uses therefor |
| JP2025528751A (ja) | 2022-07-29 | 2025-09-02 | アレクトル エルエルシー | Ｃｄ９８ｈｃ抗原結合ドメイン及びその使用法 |
| CA3265515A1 (en) * | 2022-09-02 | 2024-03-07 | 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 |
| 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 |
| 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 |
| WO2025166042A1 (en) | 2024-01-31 | 2025-08-07 | Alector Llc | Cd98hc antigen-binding domains and uses therefor |
| WO2025166077A1 (en) | 2024-01-31 | 2025-08-07 | Alector Llc | Compositions comprising progranulin and uses 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 |
| AU641673B2 (en) | 1989-06-29 | 1993-09-30 | Medarex, Inc. | Bispecific reagents for aids therapy |
| AU8295491A (en) | 1990-06-29 | 1992-01-23 | Biosource Technologies Incorporated | Melanin production by transformed microorganisms |
| DE122004000008I1 (de) | 1991-06-14 | 2005-06-09 | Genentech Inc | Humanisierter Heregulin Antikörper. |
| WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
| DE122009000068I2 (de) | 1994-06-03 | 2011-06-16 | Ascenion Gmbh | Verfahren zur Herstellung von heterologen bispezifischen Antikörpern |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| ATE218143T1 (de) | 1996-09-03 | 2002-06-15 | Gsf Forschungszentrum Umwelt | 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 |
| EP1896504B1 (en) * | 2005-06-17 | 2012-11-21 | Wyeth LLC | Methods of purifying fc region containing antibodies |
| 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 |
| EP1999154B1 (en) | 2006-03-24 | 2012-10-24 | Merck Patent GmbH | Engineered heterodimeric protein domains |
| EP2035456A1 (en) | 2006-06-22 | 2009-03-18 | Novo Nordisk A/S | Production of bispecific antibodies |
| BRPI0808055A2 (pt) | 2007-02-16 | 2013-07-30 | Merrimack Pharmaceuticals Inc | anticorpo monoclonal isolado ou porÇço do mesmo que se liga ao antÍgeno, composiÇço, Ácido nucleico isolado, vetor de expressço, cÉlula hospedeira, hibridoma, kit, uso de um anticorpo monoclonal isolado ou porÇço do mesmo que se liga ao antÍgeno, mÉtodo para diagnosticar um cÂncer associado com erbb3 em um paciente, e, anticorpo |
| WO2009089004A1 (en) | 2008-01-07 | 2009-07-16 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| EP4180458A1 (en) * | 2008-10-01 | 2023-05-17 | Amgen Research (Munich) GmbH | Cross-species-specific psma x cd3 bispecific single chain antibody |
| WO2010075548A2 (en) * | 2008-12-23 | 2010-07-01 | Genentech, Inc. | Immunoglobulin variants with altered binding to protein a |
| CN102421800A (zh) | 2009-02-23 | 2012-04-18 | 格兰马克药品股份有限公司 | 结合cd19的人源化抗体及其用途 |
| NZ594665A (en) | 2009-03-20 | 2013-08-30 | Genentech Inc | Bispecific anti-her antibodies |
| SI2975051T1 (sl) | 2009-06-26 | 2021-08-31 | Regeneron Pharmaceuticals, Inc. | Zlahka izolirana bispecifična protitelesa z nativnim imunoglobulinskim formatom |
| PL2522724T3 (pl) * | 2009-12-25 | 2020-07-13 | Chugai Seiyaku Kabushiki Kaisha | Sposób modyfikowania polipetydów do oczyszczania multimerów polipeptydowych |
| PL2560993T3 (pl) * | 2010-04-20 | 2024-11-04 | Genmab A/S | Heterodimeryczne białka zawierające region FC przeciwciała i sposoby ich wytwarzania |
| SG10201602371VA (en) | 2011-03-25 | 2016-04-28 | 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 |
| SG10201805291TA (en) * | 2011-10-27 | 2018-08-30 | Genmab As | Production of heterodimeric proteins |
| 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 |
| DK2825559T3 (da) | 2012-03-13 | 2019-06-03 | Novimmune Sa | Letisolerbare bispecifikke antistoffer med nativt immunoglobulinformat |
| HK1215950A1 (zh) * | 2012-09-25 | 2016-09-30 | 艾科诺斯科技股份有限公司 | 异源二聚免疫球蛋白的纯化 |
| AP2016009222A0 (en) * | 2013-11-04 | 2016-05-31 | Glenmark Pharmaceuticals Sa | Production of t cell retargeting hetero-dimeric immunoglobulins |
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- 2013-09-25 US US14/431,207 patent/US20150239991A1/en not_active Abandoned
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| WO2014049003A1 (en) | 2014-04-03 |
| JP2015529236A (ja) | 2015-10-05 |
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| JP6856610B2 (ja) | 2021-04-07 |
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| US20200010568A1 (en) | 2020-01-09 |
| AU2018204314A1 (en) | 2018-07-05 |
| CN104968685A (zh) | 2015-10-07 |
| JP2020105203A (ja) | 2020-07-09 |
| IN2015MN00139A (OSRAM) | 2015-10-16 |
| KR20150076172A (ko) | 2015-07-06 |
| IL237872B (en) | 2019-09-26 |
| JP2022116326A (ja) | 2022-08-09 |
| EP2900696A1 (en) | 2015-08-05 |
| IL237872A0 (en) | 2015-05-31 |
| JP2018104444A (ja) | 2018-07-05 |
| CA3061557A1 (en) | 2014-04-03 |
| IL269207A (en) | 2019-11-28 |
| AU2013322710A1 (en) | 2015-04-16 |
| AU2013322710A2 (en) | 2015-05-07 |
| US20150239991A1 (en) | 2015-08-27 |
| EP3401337A1 (en) | 2018-11-14 |
| IL269207B (en) | 2022-02-01 |
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