ZA200208944B - Soluble CTLA4 mutant molecules and uses thereof. - Google Patents
Soluble CTLA4 mutant molecules and uses thereof. Download PDFInfo
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- ZA200208944B ZA200208944B ZA200208944A ZA200208944A ZA200208944B ZA 200208944 B ZA200208944 B ZA 200208944B ZA 200208944 A ZA200208944 A ZA 200208944A ZA 200208944 A ZA200208944 A ZA 200208944A ZA 200208944 B ZA200208944 B ZA 200208944B
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- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
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Landscapes
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| US57992700A | 2000-05-26 | 2000-05-26 | |
| US21406500P | 2000-06-26 | 2000-06-26 |
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| US6887471B1 (en) | 1991-06-27 | 2005-05-03 | Bristol-Myers Squibb Company | Method to inhibit T cell interactions with soluble B7 |
| US7094874B2 (en) | 2000-05-26 | 2006-08-22 | Bristol-Myers Squibb Co. | Soluble CTLA4 mutant molecules |
| DE60135029D1 (de) | 2000-07-03 | 2008-09-04 | Bristol Myers Squibb Co | Verwendung von löslichen ctla4-mutanten zur behandlung von rheumatoider arthritis |
| US20040022787A1 (en) | 2000-07-03 | 2004-02-05 | Robert Cohen | Methods for treating an autoimmune disease using a soluble CTLA4 molecule and a DMARD or NSAID |
| WO2002094202A2 (en) | 2001-05-23 | 2002-11-28 | Bristol-Myers Squibb Company | Methods for protecting allogeneic islet transplant using soluble ctla4 mutant molecules |
| EP1496931A4 (en) * | 2002-04-19 | 2009-07-01 | Bristol Myers Squibb Co | METHODS OF TREATING AUTOIMMUNE DISEASE USING SOLUBLE CTLA4 MOLECULE AND ARMM OR NSAID |
| DE10232697A1 (de) * | 2002-07-15 | 2004-02-05 | Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität zu Berlin | Verwendung von CD152 zur Behandlung von Autoimmunkrankheiten und Entzündungen |
| MXPA05006523A (es) | 2002-12-23 | 2005-08-26 | Squibb Bristol Myers Co | Procesos de cultivo de celulas de mamiferos para la produccion de proteinas. |
| KR101088223B1 (ko) | 2002-12-23 | 2011-11-30 | 브리스톨-마이어스 스큅 컴퍼니 | 단백질 생산을 위한 포유류 세포 배양 방법에서의 생산물품질 향상 |
| WO2004060911A2 (en) | 2002-12-30 | 2004-07-22 | Amgen Inc. | Combination therapy with co-stimulatory factors |
| AU2004287431B2 (en) | 2003-10-27 | 2010-03-11 | Amgen Inc. | Compositions and methods to modulate an immune response to an immunogenic therapeutic agent |
| AR058568A1 (es) | 2005-12-20 | 2008-02-13 | Bristol Myers Squibb Co | Metodos para producir una composicion con moleculas ctla4-ig a partir de un medio de cultivo |
| CA2836123C (en) | 2005-12-20 | 2017-09-12 | Bristol-Myers Squibb Company | Compositions and methods for producing a composition |
| US7510844B2 (en) | 2006-01-24 | 2009-03-31 | Bristol-Myers Squibb Company | CD86 and CD80 receptor competition assays |
| WO2008005290A2 (en) | 2006-06-29 | 2008-01-10 | The Trustees Of Columbia University In The City Of New York | Methods for testing anti-thrombotic agents |
| GB0620934D0 (en) * | 2006-10-20 | 2006-11-29 | Cambridge Antibody Tech | Protein variants |
| CA2832111A1 (en) | 2006-12-20 | 2008-07-03 | Mmrglobal, Inc. | Antibodies and methods for making and using them |
| CA2703263C (en) | 2007-11-01 | 2014-03-18 | Perseid Therapeutics Llc | Immunosuppressive polypeptides and nucleic acids |
| NO2344540T3 (en:Method) * | 2008-10-02 | 2018-04-28 | ||
| US9540426B2 (en) | 2009-10-06 | 2017-01-10 | Bristol-Myers Squibb Company | Mammalian cell culture processes for protein production |
| EP2545073B1 (en) * | 2010-03-12 | 2015-09-30 | AbbVie Biotherapeutics Inc. | Ctla4 proteins and their uses |
| EA201370187A1 (ru) | 2011-02-23 | 2013-12-30 | Амген Инк. | Клеточная культуральная среда для уфс воздействия и относящиеся к ней способы |
| WO2013010537A1 (en) | 2011-07-20 | 2013-01-24 | Aarhus Universitet | Method of treating morphea |
| WO2013148049A1 (en) * | 2012-03-29 | 2013-10-03 | The General Hospital Corporation | Recombinant cytotoxic t-lymphocyte-associated protein 4 (ctla4) |
| CN104302309B (zh) | 2012-05-11 | 2017-07-28 | 米迪缪尼有限公司 | Ctla‑4变体 |
| US8735359B2 (en) | 2012-05-24 | 2014-05-27 | Orban Biotech Llc | Combinations of modalities for the treatment of diabetes |
| MX377570B (es) * | 2012-06-27 | 2025-03-10 | Orban Biotech Llc | Proteínas de fusión ctla4 para el tratamiento de la diabetes. |
| US20140112958A1 (en) | 2012-10-24 | 2014-04-24 | Mwm Biomodels Gmbh | Pancreatic islets of transgenic LEA29Y animals for treating diabetes |
| CN104740608A (zh) * | 2013-12-30 | 2015-07-01 | 上海中信国健药业股份有限公司 | 可溶性ctla4分子用于制备治疗类风湿性关节炎药物的用途 |
| SG11201605640UA (en) | 2014-01-13 | 2016-08-30 | Amgen Inc | Regulating ornithine metabolism to manipulate the high mannose glycoform content of recombinant proteins |
| GB2523399B (en) | 2014-02-25 | 2019-03-13 | Orban Tihamer | A composition comprising ten overlapping peptide fragments of the entire preproinsulin sequence |
| TR201900776T4 (tr) | 2014-06-04 | 2019-02-21 | Amgen Inc | Memeli hücre kültürlerinin hasadına ilişkin yöntem. |
| MX385409B (es) | 2014-12-01 | 2025-03-04 | Amgen Inc | Proceso para manipular el nivel de contenido de glicano de una glicoproteína. |
| US10590457B2 (en) | 2015-02-11 | 2020-03-17 | Bristol Myers-Squibb Company | Compositions for cell culture and methods of using the same |
| PL3283508T3 (pl) | 2015-04-17 | 2021-10-11 | Alpine Immune Sciences, Inc. | Białka immunomodulacyjne o dostrajalnym powinowactwie |
| WO2017044807A2 (en) | 2015-09-09 | 2017-03-16 | The Trustees Of Columbia University In The City Of New York | Reduction of er-mam-localized app-c99 and methods of treating alzheimer's disease |
| CN108350416A (zh) | 2015-11-09 | 2018-07-31 | 百时美施贵宝公司 | 操纵在cho细胞中产生的多肽的品质属性的方法 |
| CN116942793A (zh) | 2016-09-19 | 2023-10-27 | 昂科医药 | Cd80和cd86结合蛋白组合物及其用途 |
| CN107987153A (zh) * | 2016-10-27 | 2018-05-04 | 广东香雪精准医疗技术有限公司 | 高亲和力的可溶性pd-1分子 |
| MX2019012567A (es) | 2017-04-20 | 2020-02-13 | Egenesis Inc | Metodos para generar animales geneticamente modificados. |
| JP7749319B2 (ja) | 2017-10-10 | 2025-10-06 | アルパイン イミューン サイエンシズ インコーポレイテッド | Ｃｔｌａ－４変異型免疫調節タンパク質およびそれらの使用 |
| BR112020013236A2 (pt) | 2018-01-03 | 2020-12-01 | Alpine Immune Sciences, Inc. | proteínas imunomoduladoras de múltiplos domínios e métodos de seu uso |
| CN115227824A (zh) * | 2018-11-12 | 2022-10-25 | 中南大学湘雅二医院 | 免疫检查点的抑制剂在制备治疗青光眼和其他眼部免疫损伤机制相关疾病药物中的应用 |
| US20220281939A1 (en) | 2019-08-27 | 2022-09-08 | Tonix Pharma Limited | Modified tff2 polypeptides |
| KR20240007293A (ko) | 2019-12-06 | 2024-01-16 | 리제너론 파아마슈티컬스, 인크. | 항-vegf 단백질 조성물 및 이를 생산하는 방법 |
| EP4146686A2 (en) | 2020-05-08 | 2023-03-15 | Regeneron Pharmaceuticals, Inc. | Vegf traps and mini-traps and methods for treating ocular disorders and cancer |
| BR112022024135A2 (pt) | 2020-06-18 | 2022-12-27 | Regeneron Pharma | Metodologia de peptídeo pesado para medir com precisão lisina c-terminal não processada |
| WO2022027013A1 (en) | 2020-07-28 | 2022-02-03 | Seagen Inc. | Methods and systems for producing polypeptides |
| KR20240125949A (ko) | 2021-12-16 | 2024-08-20 | 브리스톨-마이어스 스큅 컴퍼니 | 바이러스 불활성화를 위한 세제 |
| IL315321A (en) | 2022-03-02 | 2024-10-01 | Regeneron Pharma | Manufacturing process for high titer antibody |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| WO1993000431A1 (en) * | 1991-06-27 | 1993-01-07 | Bristol-Myers Squibb Company | Ctl4a receptor, fusion proteins containing it and uses thereof |
| US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
| US5637481A (en) | 1993-02-01 | 1997-06-10 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
| US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
| ZA98533B (en) * | 1997-01-31 | 1999-07-22 | Bristol Myers Squibb Co | Soluble CTLA4 mutant molecules and uses thereof. |
| JP3521382B2 (ja) * | 1997-02-27 | 2004-04-19 | 日本たばこ産業株式会社 | 細胞間接着及びシグナル伝達を媒介する細胞表面分子 |
| GB9809280D0 (en) * | 1998-04-30 | 1998-07-01 | Rpms Technology Ltd | Immunosupression |
| EP1119253A4 (en) * | 1998-10-07 | 2005-12-21 | Millennium Pharm Inc | NEW SPECIFIC MOLECULES OF Th2 AND USES THEREOF |
| DE60135029D1 (de) * | 2000-07-03 | 2008-09-04 | Bristol Myers Squibb Co | Verwendung von löslichen ctla4-mutanten zur behandlung von rheumatoider arthritis |
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