CA2696809A1 - Method of increasing protein titres - Google Patents
Method of increasing protein titres Download PDFInfo
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- CA2696809A1 CA2696809A1 CA2696809A CA2696809A CA2696809A1 CA 2696809 A1 CA2696809 A1 CA 2696809A1 CA 2696809 A CA2696809 A CA 2696809A CA 2696809 A CA2696809 A CA 2696809A CA 2696809 A1 CA2696809 A1 CA 2696809A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
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- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07115227A EP2031064A1 (de) | 2007-08-29 | 2007-08-29 | Verfahren zur Steigerung von Proteintitern |
| EP07115227.6 | 2007-08-29 | ||
| PCT/EP2008/061310 WO2009027471A1 (de) | 2007-08-29 | 2008-08-28 | Verfahren zur steigerung von proteintitern |
Publications (1)
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|---|---|
| CA2696809A1 true CA2696809A1 (en) | 2009-03-05 |
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| CA2696809A Abandoned CA2696809A1 (en) | 2007-08-29 | 2008-08-28 | Method of increasing protein titres |
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|---|---|
| US (1) | US20100297697A1 (OSRAM) |
| EP (2) | EP2031064A1 (OSRAM) |
| JP (1) | JP2010536396A (OSRAM) |
| KR (1) | KR20100046219A (OSRAM) |
| CA (1) | CA2696809A1 (OSRAM) |
| WO (1) | WO2009027471A1 (OSRAM) |
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| DK3050963T3 (da) | 2005-03-31 | 2019-12-09 | Chugai Pharmaceutical Co Ltd | Fremgangsmåde til fremstilling af polypeptid ved regulering af arrangement |
| EP2006381B1 (en) | 2006-03-31 | 2016-02-03 | Chugai Seiyaku Kabushiki Kaisha | Method for controlling blood pharmacokinetics of antibodies |
| DK2009101T3 (en) | 2006-03-31 | 2018-01-15 | Chugai Pharmaceutical Co Ltd | Antibody modification method for purification of a bispecific antibody |
| EP1878747A1 (en) * | 2006-07-11 | 2008-01-16 | greenovation Biotech GmbH | Glyco-engineered antibodies |
| CA2700701C (en) | 2007-09-26 | 2020-12-29 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in cdr |
| CL2008002886A1 (es) | 2007-09-26 | 2009-12-04 | Chugai Pharmaceutical Co Ltd | Region constante de un anticuerpo humano; anticuerpo anti-receptor de interleucina-6 (il-6) y composicion farmaceutica que la comprende. |
| WO2009072604A1 (ja) | 2007-12-05 | 2009-06-11 | Chugai Seiyaku Kabushiki Kaisha | 抗nr10抗体、およびその利用 |
| NZ717429A (en) | 2008-04-11 | 2018-07-27 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
| TWI440469B (zh) | 2008-09-26 | 2014-06-11 | Chugai Pharmaceutical Co Ltd | Improved antibody molecules |
| EP2826789A1 (en) | 2009-03-19 | 2015-01-21 | Chugai Seiyaku Kabushiki Kaisha | Antibody constant region variant |
| WO2010107110A1 (ja) | 2009-03-19 | 2010-09-23 | 中外製薬株式会社 | 抗体定常領域改変体 |
| EP2481752B1 (en) | 2009-09-24 | 2016-11-09 | Chugai Seiyaku Kabushiki Kaisha | Modified antibody constant regions |
| WO2011108714A1 (ja) | 2010-03-04 | 2011-09-09 | 中外製薬株式会社 | 抗体定常領域改変体 |
| EP2455403A1 (en) * | 2010-11-23 | 2012-05-23 | Pierre Fabre Medicament | Homogeneous humanized antibodies against JAM-A that inhibit proliferation |
| CN108715614A (zh) | 2010-11-30 | 2018-10-30 | 中外制药株式会社 | 与多分子的抗原重复结合的抗原结合分子 |
| US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
| EP2702164B8 (en) | 2011-04-29 | 2016-03-16 | Biocon Research Limited | A method for reducing heterogeneity of antibodies and a process of producing the antibodies thereof |
| JP6454547B2 (ja) * | 2011-07-06 | 2019-01-16 | ゲンマブ エー／エス | 抗体重鎖のｃ末端の修飾による補体依存性細胞傷害の調節 |
| JP2020141710A (ja) * | 2011-07-06 | 2020-09-10 | ゲンマブ エー／エス | 抗体重鎖のｃ末端の修飾による補体依存性細胞傷害の調節 |
| CN103717729B (zh) | 2011-07-08 | 2017-11-21 | 动量制药公司 | 细胞培养方法 |
| EP3378535B1 (en) | 2011-10-28 | 2023-01-04 | Prothena Biosciences Limited | Humanized antibodies that recognize alpha-synuclein |
| KR102086061B1 (ko) | 2012-01-27 | 2020-03-11 | 프로테나 바이오사이언시즈 리미티드 | 알파-시누클레인을 인식하는 인간화된 항체 |
| US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
| US9505833B2 (en) | 2012-04-20 | 2016-11-29 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
| US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
| US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
| CN104619853B (zh) * | 2012-04-23 | 2021-10-12 | 帝斯曼知识产权资产管理有限公司 | 多肽表达方法 |
| ES2938182T3 (es) * | 2012-04-30 | 2023-04-05 | Biocon Ltd | Proteínas de fusión dirigidas/inmunomoduladoras y métodos de preparación de las mismas |
| US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
| US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
| KR20150043523A (ko) | 2012-09-02 | 2015-04-22 | 애브비 인코포레이티드 | 단백질 불균일성의 제어 방법 |
| UA118441C2 (uk) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| EP2970512B1 (en) | 2013-03-12 | 2018-10-10 | Biocon Limited | Fusion immunomodulatory proteins and methods for making same |
| EP2970453B1 (en) | 2013-03-13 | 2019-12-04 | Prothena Biosciences Limited | Tau immunotherapy |
| US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
| US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
| US8921526B2 (en) | 2013-03-14 | 2014-12-30 | Abbvie, Inc. | Mutated anti-TNFα antibodies and methods of their use |
| US10513555B2 (en) | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
| US9951131B2 (en) | 2013-07-12 | 2018-04-24 | Prothena Biosciences Limited | Antibodies that recognize IAPP |
| WO2015004632A1 (en) | 2013-07-12 | 2015-01-15 | Neotope Biosciences Limited | Antibodies that recognize iapp |
| MX382731B (es) | 2013-09-27 | 2025-03-13 | Chugai Pharmaceutical Co Ltd | Metodo para producir heteromultimeros de polipeptidos. |
| EP3052640A2 (en) | 2013-10-04 | 2016-08-10 | AbbVie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
| US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
| US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
| US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
| US20150139988A1 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
| EP3071974A2 (en) | 2013-11-19 | 2016-09-28 | Prothena Biosciences Limited | Monitoring immunotherapy of lewy body disease from constipation symptoms |
| EP3116911B8 (en) | 2014-03-12 | 2019-10-23 | Prothena Biosciences Limited | Anti-mcam antibodies and associated methods of use |
| US10059761B2 (en) | 2014-03-12 | 2018-08-28 | Prothena Biosciences Limited | Anti-Laminin4 antibodies specific for LG4-5 |
| TW201623331A (zh) | 2014-03-12 | 2016-07-01 | 普羅帝納生物科學公司 | 抗黑色素瘤細胞黏著分子（ｍｃａｍ）抗體類及使用彼等之相關方法 |
| US20170158755A1 (en) | 2014-03-12 | 2017-06-08 | Prothena Biosciences Limited | Anti-laminin4 antibodies specific for lg1-3 |
| WO2015155694A1 (en) | 2014-04-08 | 2015-10-15 | Prothena Biosciences Limited | Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein |
| TWI781507B (zh) | 2015-01-28 | 2022-10-21 | 愛爾蘭商普羅佘納生物科技有限公司 | 抗甲狀腺素運送蛋白抗體 |
| TWI769570B (zh) | 2015-01-28 | 2022-07-01 | 愛爾蘭商普羅佘納生物科技有限公司 | 抗甲狀腺素運送蛋白抗體 |
| TWI718122B (zh) | 2015-01-28 | 2021-02-11 | 愛爾蘭商普羅佘納生物科技有限公司 | 抗甲狀腺素運送蛋白抗體 |
| EP4269440A3 (en) | 2015-02-27 | 2024-02-28 | Chugai Seiyaku Kabushiki Kaisha | Composition for treating il-6-related diseases |
| WO2016159213A1 (ja) | 2015-04-01 | 2016-10-06 | 中外製薬株式会社 | ポリペプチド異種多量体の製造方法 |
| JP6934860B2 (ja) * | 2015-09-01 | 2021-09-15 | オンコクール・エムエル・ゲーエムベーハー | コイルドコイルコネクタ |
| WO2017046774A2 (en) | 2015-09-16 | 2017-03-23 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of giant cell arteritis, polymyalgia rheumatica or takayasu's arteritis |
| EP3350226A2 (en) | 2015-09-16 | 2018-07-25 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of giant cell arteritis, polymyalgia rheumatica or takayasu's arteritis |
| MX2018007781A (es) | 2015-12-28 | 2018-09-05 | Chugai Pharmaceutical Co Ltd | Metodo para promover la eficiencia de purificacion del polipeptido que contiene la region de fragmento cristalizable (fc). |
| WO2017149513A1 (en) | 2016-03-03 | 2017-09-08 | Prothena Biosciences Limited | Anti-mcam antibodies and associated methods of use |
| WO2017153953A1 (en) | 2016-03-09 | 2017-09-14 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of granulomatous lung diseases |
| WO2017153955A1 (en) | 2016-03-09 | 2017-09-14 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of granulomatous lung diseases |
| PT3452507T (pt) | 2016-05-02 | 2022-12-20 | Prothena Biosciences Ltd | Imunoterapia anti-tau |
| SG11201808434WA (en) | 2016-05-02 | 2018-10-30 | Prothena Biosciences Ltd | Antibodies recognizing tau |
| US10906964B2 (en) | 2016-05-02 | 2021-02-02 | Prothena Biosciences Limited | Antibodies recognizing tau |
| WO2017208210A1 (en) | 2016-06-03 | 2017-12-07 | Prothena Biosciences Limited | Anti-mcam antibodies and associated methods of use |
| EP3478715A2 (en) | 2016-07-02 | 2019-05-08 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| WO2018007924A2 (en) | 2016-07-02 | 2018-01-11 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| WO2018007922A2 (en) | 2016-07-02 | 2018-01-11 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
| EP3620531A4 (en) | 2017-05-02 | 2021-03-17 | National Center of Neurology and Psychiatry | METHOD OF PREDICTION AND EVALUATION OF THERAPEUTIC EFFECT IN DISEASES RELATING TO IL-6 AND NEUTROPHILS |
| CN110881274B (zh) | 2017-05-02 | 2024-11-15 | 普罗塞纳生物科学有限公司 | 识别tau的抗体 |
| CA3076313A1 (en) | 2017-09-28 | 2019-04-04 | Prothena Biosciences Limited | Dosing regimes for treatment of synucleinopathies |
| CN111757730A (zh) | 2017-10-06 | 2020-10-09 | 普罗塞纳生物科学有限公司 | 检测甲状腺素运载蛋白的方法 |
| BR112020010483A2 (pt) | 2017-11-29 | 2020-10-20 | Prothena Biosciences Limited | formulação liofilizada de um anticorpo monoclonal contra transtirretina |
| KR20200132938A (ko) | 2018-03-15 | 2020-11-25 | 추가이 세이야쿠 가부시키가이샤 | 지카 바이러스에 대해 교차-반응성을 갖는 항-뎅기 바이러스 항체 및 사용 방법 |
| CN112166120B (zh) | 2018-03-30 | 2024-09-10 | 安姆根有限公司 | C末端抗体变体 |
| JP7623699B2 (ja) | 2018-11-08 | 2025-01-29 | プロセナ バイオサイエンシーズ リミテッド | タウ認識抗体 |
| PL3817773T3 (pl) | 2018-11-26 | 2024-10-28 | Forty Seven, Inc. | Humanizowane przeciwciała przeciwko c-kit |
| CA3131531A1 (en) | 2019-03-03 | 2020-09-10 | Prothena Biosciences Limited | Antibodies recognizing tau |
| CN117398459A (zh) | 2019-07-01 | 2024-01-16 | 卫材R&D管理有限公司 | 抗EphA4抗体 |
| US20230235048A1 (en) | 2020-06-24 | 2023-07-27 | Andriani IOANNOU | Antibodies recognizing sortilin |
| KR20230123923A (ko) | 2020-12-24 | 2023-08-24 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 항-EphA4 항체 |
| WO2022138707A1 (ja) | 2020-12-24 | 2022-06-30 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 筋萎縮性側索硬化症の治療用医薬組成物 |
| JPWO2023085320A1 (OSRAM) | 2021-11-11 | 2023-05-19 | ||
| AR133830A1 (es) | 2023-09-15 | 2025-11-05 | Prothena Platform Tech Limited | Métodos, composiciones y kits que incluyen agentes de penetración celular |
| TW202530246A (zh) | 2023-09-15 | 2025-08-01 | 愛爾蘭商歐賽爾普羅希那有限公司 | 細胞穿透劑及其用途 |
| WO2025059486A1 (en) | 2023-09-15 | 2025-03-20 | Prothena Biosciences Limited | Anti-tdp-43 antibodies and uses thereof |
| WO2025059515A2 (en) | 2023-09-15 | 2025-03-20 | Prothena Biosciences Limited | Cell penetrating agents and uses thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO105652B1 (ro) * | 1988-09-28 | 1992-11-30 | Lilly Co Eli | Procedeu de reducere a heterogenitatii anticorpilor monoclonali |
| EE200300509A (et) * | 2001-04-13 | 2004-08-16 | Biogen, Inc. | Antikehad VLA-1 vastu |
| AU2004251145C1 (en) * | 2003-06-12 | 2011-04-14 | Eli Lilly And Company | GLP-1 analog fusion proteins |
| US20060024272A1 (en) * | 2004-07-29 | 2006-02-02 | Large Scale Biology Corporation | C-terminally truncated interferon |
| DK1831252T3 (da) * | 2004-12-22 | 2009-10-05 | Lilly Co Eli | GLP-1 analog fusionsproteinformuleringer |
| CN104072614B (zh) * | 2005-07-08 | 2017-04-26 | 生物基因Ma公司 | 抗-αvβ6 抗体及其用途 |
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- 2008-08-28 KR KR1020107004046A patent/KR20100046219A/ko not_active Withdrawn
- 2008-08-28 WO PCT/EP2008/061310 patent/WO2009027471A1/de not_active Ceased
- 2008-08-28 US US12/675,218 patent/US20100297697A1/en not_active Abandoned
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| EP2031064A1 (de) | 2009-03-04 |
| US20100297697A1 (en) | 2010-11-25 |
| EP2195431A1 (de) | 2010-06-16 |
| KR20100046219A (ko) | 2010-05-06 |
| WO2009027471A1 (de) | 2009-03-05 |
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