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
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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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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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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- G01N33/5005—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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- G01N33/5008—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
- G01N33/5044—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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- G01N33/68—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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- 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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- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
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- Transplantation (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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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 |
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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 |
| MY137552A (en) * | 2000-07-03 | 2009-02-27 | Bristol Myers Squibb Co | 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 |
| HU229680B1 (hu) | 2001-05-23 | 2014-04-28 | Bristol Myers Squibb Co | Eljárások allogén sziget átültetés védelmére oldható CTLA4 mutáns molekulák alkalmazásával |
| 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 |
| CN101044239B (zh) * | 2002-12-23 | 2010-12-08 | 布里斯托尔-迈尔斯斯奎布公司 | 用于蛋白质生产的哺乳动物细胞培养方法 |
| AU2003303394B2 (en) * | 2002-12-23 | 2009-02-19 | Bristol-Myers Squibb Company | Product quality enhancement in mammalian cell culture processes for protein production |
| JP2006517191A (ja) | 2002-12-30 | 2006-07-20 | アムジエン・インコーポレーテツド | 共刺激因子を用いた併用療法 |
| EP1684791A4 (en) | 2003-10-27 | 2009-07-01 | Amgen Inc | COMPOSITIONS AND METHODS FOR MODULATION OF IMMUNE REACTION TO AN IMMUNOGENIC THERAPEUTIC AGENT |
| TWI423986B (zh) | 2005-12-20 | 2014-01-21 | 必治妥美雅史谷比公司 | 組合物及製造組合物之方法 |
| 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 |
| 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 |
| CA2673725C (en) | 2006-12-20 | 2016-01-12 | Mmr Information Systems, Inc. | Antibodies and methods for making and using them |
| CN101998965B (zh) | 2007-11-01 | 2014-03-12 | 安斯泰来制药有限公司 | 免疫抑制性多肽与核酸 |
| DK2344540T3 (da) * | 2008-10-02 | 2018-01-29 | Aptevo Res & Development Llc | Cd86-antagonist multimål bindingsproteiner |
| 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 |
| CA2827492A1 (en) | 2011-02-23 | 2012-08-30 | Amgen Inc. | Cell culture media for uvc exposure and methods related thereto |
| 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) |
| US9884902B2 (en) * | 2012-05-11 | 2018-02-06 | Medimmune Limited | CTLA-4 variants |
| US8735359B2 (en) | 2012-05-24 | 2014-05-27 | Orban Biotech Llc | Combinations of modalities for the treatment of diabetes |
| CA2877986A1 (en) * | 2012-06-27 | 2014-01-03 | Orban Biotech Llc | Ctla4 fusion proteins for the treatment of 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 |
| 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 |
| SG10202113019XA (en) | 2014-06-04 | 2021-12-30 | Amgen Inc | Methods for harvesting mammalian cell cultures |
| WO2016089919A1 (en) | 2014-12-01 | 2016-06-09 | 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 |
| KR20180012260A (ko) | 2015-04-17 | 2018-02-05 | 알파인 이뮨 사이언시즈, 인코포레이티드 | 조율가능한 친화성을 갖는 면역조절 단백질 |
| EP3347486A4 (en) | 2015-09-09 | 2019-06-19 | The Trustees of Columbia University in the City of New York | REDUCTION OF ER-MAM-LOCALIZED APP-C99 AND METHOD FOR THE TREATMENT OF ALZHEIMER DISEASE |
| WO2017083224A1 (en) | 2015-11-09 | 2017-05-18 | Bristol-Myers Squibb Company | Methods to manipulate quality attributes of polypeptides produced in cho cells |
| CN109715210B (zh) * | 2016-09-19 | 2023-05-30 | 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 |
| AU2020338947A1 (en) | 2019-08-27 | 2022-03-31 | Tonix Pharma Limited | Modified TFF2 polypeptides |
| SG11202110968VA (en) | 2019-12-06 | 2021-10-28 | Regeneron Pharma | Anti-vegf protein compositions and methods for producing the same |
| EP4168807A1 (en) | 2020-06-18 | 2023-04-26 | Regeneron Pharmaceuticals, Inc. | Heavy peptide approach to accurately measure unprocessed c-terminal lysine |
| AU2021315939A1 (en) | 2020-07-28 | 2023-02-23 | Seagen Inc. | Methods and systems for producing polypeptides |
| WO2023115027A2 (en) | 2021-12-16 | 2023-06-22 | Bristol-Myers Squibb Company | Detergent for viral inactivation |
| WO2023167863A1 (en) | 2022-03-02 | 2023-09-07 | Regeneron Pharmaceuticals, Inc. | Manufacturing process for high titer antibody |
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 |
| ES2123001T5 (es) * | 1991-06-27 | 2009-04-16 | Bristol-Myers Squibb Company | Receptor ctl4a, proteinas de fusion que lo contienen y sus usos. |
| 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 |
| US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
| 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 |
| WO2000019988A1 (en) * | 1998-10-07 | 2000-04-13 | Millennium Pharmaceuticals, Inc. | NOVEL Th2-SPECIFIC MOLECULES AND USES THEREOF |
| MY137552A (en) * | 2000-07-03 | 2009-02-27 | Bristol Myers Squibb Co | Methods for treating rheumatic diseases using a soluble ctla4 molecule |
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