BR112015011011A2 - cromatografia por troca de íon com gradiente de ph mediada por força iônica - Google Patents
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
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- Molecular Biology (AREA)
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- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261727051P | 2012-11-15 | 2012-11-15 | |
| US201361780707P | 2013-03-13 | 2013-03-13 | |
| PCT/US2013/070415 WO2014078729A1 (en) | 2012-11-15 | 2013-11-15 | IONIC STRENGTH-MEDIATED pH GRADIENT ION EXCHANGE CHROMATOGRAPHY |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112015011011A2 true BR112015011011A2 (pt) | 2019-12-17 |
Family
ID=50731733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112015011011A BR112015011011A2 (pt) | 2012-11-15 | 2013-11-15 | cromatografia por troca de íon com gradiente de ph mediada por força iônica |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US9810670B2 (enExample) |
| EP (1) | EP2920586A4 (enExample) |
| JP (1) | JP2015537212A (enExample) |
| KR (1) | KR20150084046A (enExample) |
| CN (1) | CN105051528A (enExample) |
| BR (1) | BR112015011011A2 (enExample) |
| CA (1) | CA2890979A1 (enExample) |
| HK (1) | HK1217232A1 (enExample) |
| MX (1) | MX2015006149A (enExample) |
| RU (1) | RU2015122726A (enExample) |
| WO (1) | WO2014078729A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2890979A1 (en) | 2012-11-15 | 2014-05-22 | Genentech, Inc. | Ionic strength-mediated ph gradient ion exchange chromatography |
| CN105377873B (zh) * | 2013-07-12 | 2021-03-30 | 豪夫迈·罗氏有限公司 | 阐明离子交换层析输入优化 |
| CN108472360B (zh) * | 2015-04-10 | 2023-01-17 | 阿迪马布有限责任公司 | 从亲代同源二聚抗体种类中纯化异源二聚多特异性抗体的方法 |
| GB2539420B (en) * | 2015-06-16 | 2021-01-13 | Cytiva Sweden Ab | Determination of chromatography conditions |
| AU2016355739A1 (en) * | 2015-11-18 | 2018-07-05 | Merck Patent Gmbh | Improved protein separation in ion exchange chromatography |
| RU2018121657A (ru) * | 2015-11-18 | 2019-12-19 | Мерк Патент Гмбх | ПРОТИВОПОЛОЖНЫЕ ГРАДИЕНТЫ pH-СОЛЬ ДЛЯ УЛУЧШЕННОГО РАЗДЕЛЕНИЯ БЕЛКОВ |
| CN108333264A (zh) * | 2017-01-20 | 2018-07-27 | 湖北生物医药产业技术研究院有限公司 | 检测蛋白电荷变异体的方法及确定生物制品生产工艺的方法 |
| US20190126241A1 (en) * | 2017-09-26 | 2019-05-02 | Waters Technologies Corporation | High purity chromatographic materials comprising an ionizable modifier for retention of acidic analytes |
| US11612885B2 (en) | 2018-05-08 | 2023-03-28 | Waters Technologies Corporation | Methods, compositions and kits useful for pH gradient cation exchange chromatography |
| KR20200080748A (ko) * | 2018-12-27 | 2020-07-07 | 주식회사 폴루스 | 음이온 교환 크로마토그래피를 이용한 인슐린 전구체의 정제방법 |
| TW202128264A (zh) * | 2019-09-25 | 2021-08-01 | 瑞士商赫孚孟拉羅股份公司 | 使用經預測之溶離緩衝鹽濃度的陽離子層析法 |
| CN111024883B (zh) * | 2019-12-31 | 2022-12-06 | 上海博威生物医药有限公司 | 一种奥马珠单抗的电荷异质体的分离方法 |
| CN111239278B (zh) * | 2020-02-05 | 2022-11-04 | 康立泰生物医药(青岛)有限公司 | 一种检测重组人白介素-12蛋白电荷变异体的方法及应用 |
| JP7686180B2 (ja) * | 2020-04-17 | 2025-06-02 | 小野薬品工業株式会社 | タンパク質製剤原薬の着色除去方法 |
| KR102283871B1 (ko) * | 2021-03-02 | 2021-08-02 | 한국원자력연구원 | 크로마토그래피를 이용한 무담체 홀뮴-166의 분리 방법, 분리 장치 및 이에 의하여 분리된 무담체 홀뮴-166 |
| AU2022309872A1 (en) * | 2021-07-13 | 2024-01-25 | Regeneron Pharmaceuticals, Inc. | Characterization of proteins by anion-exchange chromatography mass spectrometry (aex-ms) |
| WO2023107510A1 (en) * | 2021-12-06 | 2023-06-15 | Staveness Daryl | Exciplex-based methods for contaminant and disease detection and methods for use of extraction buffers |
| CN114544839B (zh) * | 2022-01-20 | 2024-08-20 | 未名生物医药有限公司 | 一种抗人神经生长因子抗体的电荷变异体检测方法 |
| EP4637838A1 (en) * | 2022-12-20 | 2025-10-29 | Seqirus Inc. | Lipid nanoparticle composition |
| WO2024261724A1 (en) * | 2023-06-23 | 2024-12-26 | Lupin Limited | Ion-exchange chromatography for separation and analysis of charge variants |
| WO2025038736A1 (en) * | 2023-08-15 | 2025-02-20 | Gigagen, Inc. | Methods of analyzing recombinant polyclonal proteins |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| 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 |
| US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| ES2058199T3 (es) | 1987-09-23 | 1994-11-01 | Bristol Myers Squibb Co | Heteroconjugados de anticuerpos para la eliminacion de celulas infectadas por el vih. |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| DE69029036T2 (de) | 1989-06-29 | 1997-05-22 | Medarex Inc | Bispezifische reagenzien für die aids-therapie |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5356788A (en) * | 1990-03-14 | 1994-10-18 | Her Majesty The Queen In Right Of Canada, As Represented By The National Research Council Of Canada | Isolation, quantitation and purification of insecticidal proteins from Bacillus thuringiensis |
| US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
| US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
| JPH06507398A (ja) | 1991-05-14 | 1994-08-25 | リプリジェン コーポレーション | Ｈｉｖ感染治療のための異種複合抗体 |
| CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
| MX9204374A (es) | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | Anticuerpo recombinante y metodo para su produccion. |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| FI941572L (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä |
| WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| EP1997894B1 (en) | 1992-02-06 | 2011-03-30 | Novartis Vaccines and Diagnostics, Inc. | Biosynthetic binding protein for cancer marker |
| JP3571337B2 (ja) | 1992-02-11 | 2004-09-29 | セル ジェネシス，インコーポレーテッド | 遺伝子標的現象による同型遺伝子接合 |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| CA2140280A1 (en) | 1992-08-17 | 1994-03-03 | Avi J. Ashkenazi | Bispecific immunoadhesins |
| PT752248E (pt) | 1992-11-13 | 2001-01-31 | Idec Pharma Corp | Aplicacao terapeutica de anticorpos quimericos e marcados radioactivamente contra antigenios de diferenciacao restrita de linfocitos b humanos para o tratamento do linfoma de celulas b |
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
| IL127127A0 (en) | 1998-11-18 | 1999-09-22 | Peptor Ltd | Small functional units of antibody heavy chain variable regions |
| JP4732590B2 (ja) * | 1999-03-15 | 2011-07-27 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ−１及び近縁ペプチドのイオン交換クロマトグラフィー分離 |
| AU2002226095A1 (en) * | 2000-12-13 | 2002-06-24 | Wackvom Limited | Compositions containing an active fraction isolated from tricholoma conglobatum and methods of use |
| WO2002051870A2 (en) | 2000-12-22 | 2002-07-04 | GRAD, Carole Legal Representative of KAPLAN, Howard | Phage display libraries of human vh fragments |
| US20030031627A1 (en) * | 2001-07-31 | 2003-02-13 | Mallinckrodt Inc. | Internal image antibodies for optical imaging and therapy |
| JP2005289809A (ja) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 突然変異重鎖抗体 |
| DK1601697T3 (da) * | 2003-02-28 | 2007-10-01 | Lonza Biologics Plc | Oprensning af antistof ved protein A- og ionbytningskromatografi |
| CA2529819A1 (en) | 2003-06-30 | 2004-09-23 | Domantis Limited | Pegylated single domain antibodies |
| SE0303532D0 (sv) * | 2003-12-23 | 2003-12-23 | Amersham Biosciences Ab | Purification of immunoglobulins |
| CN101023101A (zh) * | 2004-07-20 | 2007-08-22 | 西福根有限公司 | 抗－恒河猴d重组多克隆抗体和生产方法 |
| KR20070057839A (ko) | 2004-08-19 | 2007-06-07 | 제넨테크, 인크. | 변경된 이펙터 기능을 갖는 폴리펩티드 변이체 |
| EP1789446A2 (en) * | 2004-09-02 | 2007-05-30 | Genentech, Inc. | Heteromultimeric molecules |
| EP3088004B1 (en) | 2004-09-23 | 2018-03-28 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
| CN101198862A (zh) | 2005-04-20 | 2008-06-11 | 谢佳辉 | Ph梯度离子交换lc-ms和与质谱相容的缓冲液 |
| CA2632519A1 (en) | 2005-12-06 | 2007-07-05 | Amgen Inc. | Polishing steps used in multi-step protein purification processes |
| CN100506983C (zh) * | 2006-05-25 | 2009-07-01 | 齐鲁制药有限公司 | 一种从矛头蝮蛇毒中提取单一成份巴曲酶的方法 |
| JP2010510963A (ja) | 2006-06-14 | 2010-04-08 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | セラミックヒドロキシアパタイトを使用する抗体の精製方法 |
| US20100330600A1 (en) * | 2008-02-29 | 2010-12-30 | Sekisui Medical Co., Ltd. | High-molecular-weight adiponectin measurement method |
| US20120177640A1 (en) * | 2009-07-24 | 2012-07-12 | Josef Burg | Optimizing the production of antibodies |
| EP2480561B1 (en) * | 2009-09-23 | 2016-07-13 | E. R. Squibb & Sons, L.L.C. | Cation exchange chromatography |
| EP2655412B1 (en) | 2010-12-21 | 2018-01-17 | F. Hoffmann-La Roche AG | Isoform enriched antibody preparation and method for obtaining it |
| WO2012116926A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Antigen binding proteins |
| US9442050B2 (en) * | 2012-02-14 | 2016-09-13 | Bio-Rad Laboratories, Inc. | Reducing pH excursions in ion exchange chromatography using displacing counter ions |
| CA2890979A1 (en) | 2012-11-15 | 2014-05-22 | Genentech, Inc. | Ionic strength-mediated ph gradient ion exchange chromatography |
-
2013
- 2013-11-15 CA CA2890979A patent/CA2890979A1/en not_active Abandoned
- 2013-11-15 RU RU2015122726A patent/RU2015122726A/ru not_active Application Discontinuation
- 2013-11-15 MX MX2015006149A patent/MX2015006149A/es unknown
- 2013-11-15 EP EP13855528.9A patent/EP2920586A4/en not_active Withdrawn
- 2013-11-15 HK HK16105250.6A patent/HK1217232A1/zh unknown
- 2013-11-15 JP JP2015542849A patent/JP2015537212A/ja active Pending
- 2013-11-15 KR KR1020157015377A patent/KR20150084046A/ko not_active Withdrawn
- 2013-11-15 BR BR112015011011A patent/BR112015011011A2/pt not_active Application Discontinuation
- 2013-11-15 CN CN201380070366.XA patent/CN105051528A/zh active Pending
- 2013-11-15 US US14/443,329 patent/US9810670B2/en active Active
- 2013-11-15 WO PCT/US2013/070415 patent/WO2014078729A1/en not_active Ceased
-
2017
- 2017-09-29 US US15/721,389 patent/US10712322B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| HK1217232A1 (zh) | 2016-12-30 |
| KR20150084046A (ko) | 2015-07-21 |
| JP2015537212A (ja) | 2015-12-24 |
| RU2015122726A (ru) | 2017-01-10 |
| MX2015006149A (es) | 2015-08-05 |
| EP2920586A4 (en) | 2017-01-04 |
| EP2920586A1 (en) | 2015-09-23 |
| US20150285771A1 (en) | 2015-10-08 |
| US20180120273A1 (en) | 2018-05-03 |
| US9810670B2 (en) | 2017-11-07 |
| US10712322B2 (en) | 2020-07-14 |
| CA2890979A1 (en) | 2014-05-22 |
| WO2014078729A1 (en) | 2014-05-22 |
| CN105051528A (zh) | 2015-11-11 |
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| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B09B | Patent application refused [chapter 9.2 patent gazette] | ||
| B350 | Update of information on the portal [chapter 15.35 patent gazette] | ||
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