JP2012517818A - 改善された抗ｔｎｆｒ１ポリペプチド、抗体可変ドメインおよびアンタゴニスト - Google Patents
改善された抗ｔｎｆｒ１ポリペプチド、抗体可変ドメインおよびアンタゴニスト Download PDFInfo
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| AU2011254559B2 (en) * | 2010-05-20 | 2014-09-04 | Glaxo Group Limited | Improved anti-serum albumin binding variants |
| WO2012172070A1 (en) * | 2011-06-17 | 2012-12-20 | Glaxo Group Limited | Tumour necrosis factor receptor 1 antagonists |
| WO2015104322A1 (en) | 2014-01-09 | 2015-07-16 | Glaxosmithkline Intellectual Property Development Limited | Treatment of inflammatory diseases with non-competitive tnfr1 antagonists |
| US9107906B1 (en) | 2014-10-28 | 2015-08-18 | Adma Biologics, Inc. | Compositions and methods for the treatment of immunodeficiency |
| WO2016094309A1 (en) * | 2014-12-10 | 2016-06-16 | Myosotis | Inhibition of tnf signaling in cancer immunotherapy |
| NO2768984T3 (OSRAM) * | 2015-11-12 | 2018-06-09 | ||
| CN107043413A (zh) * | 2016-02-05 | 2017-08-15 | 华中农业大学 | 一种肺结核相关的尿液生物标志蛋白及其应用 |
| US10259865B2 (en) | 2017-03-15 | 2019-04-16 | Adma Biologics, Inc. | Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection |
| EP3919906B1 (en) * | 2019-01-31 | 2025-01-01 | Sekisui Medical Co., Ltd. | Method for immunologically analyzing free aim in biological specimen, and method for detecting nash in subject |
| EP3927828A4 (en) | 2019-02-21 | 2023-02-01 | Enosi Life Sciences Corp. | ANTIBODIES AND ENONOMERS |
| WO2022047243A1 (en) | 2020-08-27 | 2022-03-03 | Enosi Life Sciences Corp. | Methods and compositions to treat autoimmune diseases and cancer |
| WO2022117569A1 (en) | 2020-12-02 | 2022-06-09 | Oncurious Nv | A ccr8 antagonist antibody in combination with a lymphotoxin beta receptor agonist antibody in therapy against cancer |
| WO2025021184A1 (zh) * | 2023-07-27 | 2025-01-30 | 上海复宏汉霖生物医药有限公司 | 编码尿酸氧化酶的多核苷酸及其相关组合物和方法 |
| WO2025049818A1 (en) | 2023-08-29 | 2025-03-06 | Enosi Therapeutics Corporation | Tnfr1 antagonists lacking agonist activity and uses thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008515420A (ja) * | 2004-10-08 | 2008-05-15 | ドマンティス リミテッド | Ｔｎｆｒ１に対する単一ドメイン抗体およびその使用方法 |
| WO2008149144A2 (en) * | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| WO2008149148A2 (en) * | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| JP2012532619A (ja) * | 2009-07-16 | 2012-12-20 | グラクソ グループ リミテッド | Ｔｎｆｒ１を部分的に阻害するためのアンタゴニスト、用途および方法 |
| JP2012532620A (ja) * | 2009-07-16 | 2012-12-20 | グラクソ グループ リミテッド | 改良型抗血清アルブミン結合単一可変ドメイン |
| JP2013507978A (ja) * | 2009-10-27 | 2013-03-07 | グラクソ グループ リミテッド | 安定な抗ｔｎｆｒ１ポリペプチド、抗体可変ドメイン及びアンタゴニスト |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
| JP3095168B2 (ja) | 1988-02-05 | 2000-10-03 | エル． モリソン，シェリー | ドメイン‐変性不変部を有する抗体 |
| AU4308689A (en) | 1988-09-02 | 1990-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| ATE92107T1 (de) | 1989-04-29 | 1993-08-15 | Delta Biotechnology Ltd | N-terminale fragmente von menschliches serumalbumin enthaltenden fusionsproteinen. |
| US5977307A (en) | 1989-09-07 | 1999-11-02 | Alkermes, Inc. | Transferrin receptor specific ligand-neuropharmaceutical agent fusion proteins |
| US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
| WO1994026087A2 (en) | 1993-05-14 | 1994-11-24 | Connor Kim C O | Recombinant protein production and insect cell culture and process |
| EP0714409A1 (en) | 1993-06-16 | 1996-06-05 | Celltech Therapeutics Limited | Antibodies |
| DE69826697T2 (de) | 1997-07-07 | 2006-02-16 | Medical Research Council | In vitro selektionsmethode |
| IL127127A0 (en) | 1998-11-18 | 1999-09-22 | Peptor Ltd | Small functional units of antibody heavy chain variable regions |
| US7148061B2 (en) | 2000-02-11 | 2006-12-12 | The United States Of America As Represented By The Department Of Health And Human Services | Identification of a novel domain in the tumor necrosis factor receptor family that mediates pre-ligand receptor assembly and function |
| DE60237282D1 (de) | 2001-06-28 | 2010-09-23 | Domantis Ltd | Doppelspezifischer ligand und dessen verwendung |
| WO2005077042A2 (en) | 2004-02-09 | 2005-08-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP1572936A2 (en) | 2002-03-05 | 2005-09-14 | Eli Lilly And Company | Heterologous g-csf fusion proteins |
| US9321832B2 (en) * | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| EP2135879A3 (en) | 2002-06-28 | 2010-06-23 | Domantis Limited | Ligand |
| US7696320B2 (en) | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| NZ540196A (en) | 2002-11-08 | 2008-09-26 | Ablynx Nv | Camelidae antibodies against imminoglobulin E and use thereof for the treatment of allergic disorders |
| CA2511910A1 (en) | 2002-12-27 | 2004-07-15 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| GB0230203D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
| US20090005257A1 (en) | 2003-05-14 | 2009-01-01 | Jespers Laurent S | Process for Recovering Polypeptides that Unfold Reversibly from a Polypeptide Repertoire |
| DK1639011T3 (da) | 2003-06-30 | 2009-02-16 | Domantis Ltd | Pegylerede enkelt-domæne antistoffer (dAb) |
| SI1737962T1 (sl) | 2004-03-24 | 2011-01-31 | Domantis Ltd | Univerzalni signalni peptid GAS1 |
| GB0418651D0 (en) | 2004-08-20 | 2004-09-22 | Medical Res Council | Method |
| CN101084014A (zh) * | 2004-10-08 | 2007-12-05 | 杜门蒂斯有限公司 | 抗肿瘤坏死因子受体1的单域抗体及其使用方法 |
| GB0521621D0 (en) | 2005-10-24 | 2005-11-30 | Domantis Ltd | Tumor necrosis factor receptor 1 antagonists for treating respiratory diseases |
| JP2009519011A (ja) * | 2005-12-01 | 2009-05-14 | ドマンティス リミテッド | インターロイキン１受容体１型に結合する非競合ドメイン抗体フォーマット |
| CA2632417A1 (en) * | 2005-12-06 | 2007-06-14 | Domantis Limited | Ligands that have binding specificity for egfr and/or vegf and methods of use therefor |
| US7868885B2 (en) | 2007-06-22 | 2011-01-11 | Microsoft Corporation | Direct manipulation of subdivision surfaces using a graphics processing unit |
-
2010
- 2010-02-17 SG SG2011054459A patent/SG173173A1/en unknown
- 2010-02-17 CN CN2010800173301A patent/CN102405236A/zh active Pending
- 2010-02-17 AU AU2010215479A patent/AU2010215479B2/en not_active Ceased
- 2010-02-17 MX MX2011008799A patent/MX2011008799A/es not_active Application Discontinuation
- 2010-02-17 EA EA201190116A patent/EA022925B1/ru not_active IP Right Cessation
- 2010-02-17 JP JP2011550552A patent/JP2012517818A/ja active Pending
- 2010-02-17 WO PCT/EP2010/052005 patent/WO2010094720A2/en not_active Ceased
- 2010-02-17 CA CA2750477A patent/CA2750477A1/en not_active Abandoned
- 2010-02-17 BR BRPI1008014A patent/BRPI1008014A2/pt not_active IP Right Cessation
- 2010-02-17 US US13/202,349 patent/US20110301335A1/en not_active Abandoned
- 2010-02-17 KR KR1020117021824A patent/KR20110119806A/ko not_active Ceased
- 2010-02-17 EP EP10704151A patent/EP2398827A2/en not_active Withdrawn
-
2011
- 2011-07-29 ZA ZA2011/05627A patent/ZA201105627B/en unknown
- 2011-08-15 IL IL214648A patent/IL214648A0/en unknown
-
2015
- 2015-07-31 JP JP2015151376A patent/JP2016007218A/ja active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008515420A (ja) * | 2004-10-08 | 2008-05-15 | ドマンティス リミテッド | Ｔｎｆｒ１に対する単一ドメイン抗体およびその使用方法 |
| WO2008149144A2 (en) * | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| WO2008149148A2 (en) * | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| JP2012532619A (ja) * | 2009-07-16 | 2012-12-20 | グラクソ グループ リミテッド | Ｔｎｆｒ１を部分的に阻害するためのアンタゴニスト、用途および方法 |
| JP2012532620A (ja) * | 2009-07-16 | 2012-12-20 | グラクソ グループ リミテッド | 改良型抗血清アルブミン結合単一可変ドメイン |
| JP2013507978A (ja) * | 2009-10-27 | 2013-03-07 | グラクソ グループ リミテッド | 安定な抗ｔｎｆｒ１ポリペプチド、抗体可変ドメイン及びアンタゴニスト |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013541522A (ja) * | 2010-09-16 | 2013-11-14 | バリオファルム・アクチェンゲゼルシャフト | 抗ｈｕＴＮＦＲ１抗体 |
Also Published As
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| AU2010215479B2 (en) | 2015-01-22 |
| IL214648A0 (en) | 2011-09-27 |
| CN102405236A (zh) | 2012-04-04 |
| EA022925B1 (ru) | 2016-03-31 |
| KR20110119806A (ko) | 2011-11-02 |
| WO2010094720A2 (en) | 2010-08-26 |
| CA2750477A1 (en) | 2010-08-26 |
| BRPI1008014A2 (pt) | 2016-10-04 |
| SG173173A1 (en) | 2011-08-29 |
| AU2010215479A1 (en) | 2011-08-25 |
| ZA201105627B (en) | 2013-01-30 |
| WO2010094720A3 (en) | 2011-01-13 |
| EP2398827A2 (en) | 2011-12-28 |
| US20110301335A1 (en) | 2011-12-08 |
| MX2011008799A (es) | 2011-09-27 |
| JP2016007218A (ja) | 2016-01-18 |
| EA201190116A1 (ru) | 2012-06-29 |
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