NO330797B1 - CTLA4-mutantmolekyler, anvendelse og fremstilling derav, samt nukleinsyremolekyl, vektor, vertsvektorsystem, vertscelle, opploslig CTLA-4 mutantprotein og farmasoytisk sammensetning - Google Patents
CTLA4-mutantmolekyler, anvendelse og fremstilling derav, samt nukleinsyremolekyl, vektor, vertsvektorsystem, vertscelle, opploslig CTLA-4 mutantprotein og farmasoytisk sammensetning Download PDFInfo
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—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
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
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- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—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
- 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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- G01N33/5044—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 involving specific cell types
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- 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
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- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
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- Genetics & Genomics (AREA)
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- Biophysics (AREA)
- Zoology (AREA)
- Transplantation (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| US57992700A | 2000-05-26 | 2000-05-26 | |
| US21406500P | 2000-06-26 | 2000-06-26 | |
| PCT/US2001/017139 WO2001092337A2 (en) | 2000-05-26 | 2001-05-23 | Soluble ctla4 mutant molecules and uses thereof |
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| NO20025656D0 NO20025656D0 (no) | 2002-11-25 |
| NO20025656L NO20025656L (no) | 2002-11-25 |
| NO330797B1 true NO330797B1 (no) | 2011-07-18 |
Family
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| NO20025656A NO330797B1 (no) | 2000-05-26 | 2002-11-25 | CTLA4-mutantmolekyler, anvendelse og fremstilling derav, samt nukleinsyremolekyl, vektor, vertsvektorsystem, vertscelle, opploslig CTLA-4 mutantprotein og farmasoytisk sammensetning |
| NO2011027C NO2011027I1 (no) | 2000-05-26 | 2011-12-15 | Belatacept |
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| NO2011027C NO2011027I1 (no) | 2000-05-26 | 2011-12-15 | Belatacept |
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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 |
| WO2002002638A2 (en) | 2000-07-03 | 2002-01-10 | Bristol-Myers Squibb Company | Methods for treating rheumatic diseases using a soluble ctla4 molecule |
| 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 |
| MXPA03010568A (es) | 2001-05-23 | 2005-03-07 | Squibb Bristol Myers Co | Metodos para proteger trasplantes alogenicos de celulas de isletas usando moleculas mutantes ctla4 solubles. |
| AU2003243152A1 (en) * | 2002-04-19 | 2003-11-03 | Bristol-Myers Squibb Company | Methods for treating an autoimmune disease using a soluble ctla4 molecule and a dmard 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 |
| ES2354610T5 (es) | 2002-12-23 | 2020-09-14 | Bristol Myers Squibb Co | Mejora de la calidad del producto en procedimientos de cultivo de células de mamífero para la producción de proteína |
| JP4541157B2 (ja) * | 2002-12-23 | 2010-09-08 | ブリストル−マイヤーズ スクイブ カンパニー | タンパク質を製造するための哺乳類細胞培養法 |
| CA2511823A1 (en) | 2002-12-30 | 2004-07-22 | Amgen Inc. | Combination therapy with co-stimulatory factors |
| WO2005044188A2 (en) | 2003-10-27 | 2005-05-19 | 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 |
| KR101398713B1 (ko) * | 2005-12-20 | 2014-06-12 | 브리스톨-마이어스 스큅 컴퍼니 | 조성물 및 조성물의 제조 방법 |
| 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 |
| CN101675074B (zh) | 2006-12-20 | 2016-02-24 | Mmr全球公司 | 抗体及其制备和使用方法 |
| CA2703263C (en) | 2007-11-01 | 2014-03-18 | Perseid Therapeutics Llc | Immunosuppressive polypeptides and nucleic acids |
| CA3038442A1 (en) * | 2008-10-02 | 2010-04-08 | Aptevo Research And Development Llc | Cd86 antagonist multi-target binding proteins |
| US9540426B2 (en) | 2009-10-06 | 2017-01-10 | Bristol-Myers Squibb Company | Mammalian cell culture processes for protein production |
| CN102822198B (zh) | 2010-03-12 | 2016-08-31 | 艾伯维生物医疗股份有限公司 | Ctla4蛋白和其用途 |
| KR20130129438A (ko) | 2011-02-23 | 2013-11-28 | 암젠 인크 | Uvc 노출을 위한 세포 배양 배지 및 이와 관련된 방법 |
| 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 |
| KR20150033703A (ko) | 2012-06-27 | 2015-04-01 | 오르반 바이오테크 엘엘씨 | 당뇨병 치료를 위한 ctla4 융합 단백질 |
| 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 |
| WO2015105609A1 (en) | 2014-01-13 | 2015-07-16 | 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 |
| MX2016015944A (es) | 2014-06-04 | 2017-08-15 | Amgen Inc | Metodos para cosechar cultivos de celulas de mamifero. |
| SG10202002458PA (en) | 2014-12-01 | 2020-04-29 | Amgen Inc | Process for manipulating the level of glycan content of a glycoprotein |
| US10590457B2 (en) | 2015-02-11 | 2020-03-17 | Bristol Myers-Squibb Company | Compositions for cell culture and methods of using the same |
| CA2982246A1 (en) | 2015-04-17 | 2016-10-20 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
| 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 |
| US11401509B2 (en) | 2015-11-09 | 2022-08-02 | Bristol-Myers Squibb Company | Methods of minimizing glycoprotein agregation in CHO cell production |
| 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 |
| JP2020536552A (ja) | 2017-10-10 | 2020-12-17 | 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 |
| CN109453383A (zh) * | 2018-11-12 | 2019-03-12 | 陈慧慧 | 免疫检查点的抑制剂在制备治疗青光眼及其他眼部免疫损伤机制相关疾病药物中的应用 |
| JP2022545917A (ja) | 2019-08-27 | 2022-11-01 | トニックス ファーマ リミテッド | 修飾ｔｆｆ２ポリペプチド |
| SG11202110955VA (en) | 2019-12-06 | 2021-10-28 | Regeneron Pharma | Anti-vegf protein compositions and methods for producing the same |
| US20220011318A1 (en) | 2020-06-18 | 2022-01-13 | Regeneron Pharmaceuticals, Inc. | Heavy peptide approach to accurately measure unprocessed c-terminal lysine in antibodies |
| US20230287322A1 (en) | 2020-07-28 | 2023-09-14 | Seagen Inc. | Methods and systems for producing polypeptides |
| WO2023115027A2 (en) | 2021-12-16 | 2023-06-22 | Bristol-Myers Squibb Company | Detergent for viral inactivation |
| WO2023167852A2 (en) | 2022-03-02 | 2023-09-07 | Regeneron Pharmaceuticals, Inc. | Cell culture methods for antibody production |
Family Cites Families (10)
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| 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 |
| US5851795A (en) * | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
| AU661854B2 (en) * | 1991-06-27 | 1995-08-10 | 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 |
| 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 |
| CA2346496A1 (en) * | 1998-10-07 | 2000-04-13 | Millennium Pharmaceuticals, Inc. | Novel th2-specific molecules and uses thereof |
| WO2002002638A2 (en) * | 2000-07-03 | 2002-01-10 | Bristol-Myers Squibb Company | Methods for treating rheumatic diseases using a soluble ctla4 molecule |
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