TW201619200A - 人類化抗－ｏｘ４０抗體及其用途 - Google Patents
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Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10201708048XA (en) | 2013-03-18 | 2017-10-30 | Biocerox Prod Bv | Humanized anti-cd134 (ox40) antibodies and uses thereof |
| US20150190506A1 (en) * | 2013-12-17 | 2015-07-09 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
| AU2015241038A1 (en) | 2014-03-31 | 2016-10-13 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and OX40 binding agonists |
| WO2016110584A1 (en) * | 2015-01-08 | 2016-07-14 | Biontech Ag | Agonistic tnf receptor binding agents |
| GB201506411D0 (en) | 2015-04-15 | 2015-05-27 | Bergenbio As | Humanized anti-axl antibodies |
| SG11201708804WA (en) | 2015-05-07 | 2017-11-29 | Agenus Inc | Anti-ox40 antibodies and methods of use thereof |
| US20160347848A1 (en) * | 2015-05-28 | 2016-12-01 | Medimmune Limited | Therapeutic combinations and methods for treating neoplasia |
| SG10202008304TA (en) | 2015-05-29 | 2020-10-29 | Bristol Myers Squibb Co | Antibodies against ox40 and uses thereof |
| CN108602887B (zh) | 2015-10-02 | 2022-06-21 | 豪夫迈·罗氏有限公司 | 对共刺激性tnf受体特异性的双特异性抗体 |
| CN114380908B (zh) | 2015-10-15 | 2023-03-17 | 苏州丁孚靶点生物技术有限公司 | 抗ox40抗体及其应用 |
| AU2016364889B2 (en) | 2015-12-02 | 2024-01-04 | Agenus Inc. | Antibodies and methods of use thereof |
| AR108377A1 (es) | 2016-05-06 | 2018-08-15 | Medimmune Llc | Proteínas de unión biespecíficas y sus usos |
| US11214618B2 (en) | 2016-06-20 | 2022-01-04 | F-Star Therapeutics Limited | LAG-3 binding members |
| NZ789594A (en) | 2016-06-20 | 2025-07-25 | Kymab Ltd | Anti-PD-L1 antibodies |
| GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
| WO2018017888A1 (en) * | 2016-07-20 | 2018-01-25 | Igm Biosciences, Inc. | Multimeric ox40 binding molecules and uses thereof |
| US11046776B2 (en) | 2016-08-05 | 2021-06-29 | Genentech, Inc. | Multivalent and multiepitopic antibodies having agonistic activity and methods of use |
| EP3538152A4 (en) | 2016-11-09 | 2020-09-30 | Agenus Inc. | ANTI-OX40 ANTIBODIES, ANTI-GITR ANTIBODIES, AND PROCESSES FOR USE |
| HRP20201259T1 (hr) | 2016-12-15 | 2020-11-13 | Abbvie Biotherapeutics Inc. | Protutijela protiv ox40 i njihova upotreba |
| AU2017384528A1 (en) | 2016-12-19 | 2019-07-04 | Ichnos Sciences SA | Novel TNFR agonists and uses thereof |
| WO2018178055A1 (en) | 2017-03-29 | 2018-10-04 | F. Hoffmann-La Roche Ag | Bispecific antigen binding molecule for a costimulatory tnf receptor |
| WO2018193102A1 (en) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
| US11596696B2 (en) | 2017-04-20 | 2023-03-07 | Adc Therapeutics Sa | Combination therapy with an anti-CD25 antibody-drug conjugate |
| KR20200074214A (ko) * | 2017-11-01 | 2020-06-24 | 브리스톨-마이어스 스큅 컴퍼니 | 암을 치료하는데 사용하기 위한 면역자극 효능작용 항체 |
| EP3713958A4 (en) * | 2017-11-24 | 2021-11-03 | Eucure (Beijing) Biopharma Co., Ltd | ANTI-OX40 ANTIBODIES AND USES THEREOF |
| CN108218990B (zh) * | 2017-12-29 | 2021-03-02 | 南京优迈生物科技有限公司 | 分离的抗体或其抗原结合片段及其在肿瘤治疗中的应用 |
| CA3082036C (en) | 2017-12-29 | 2025-06-17 | Ap Biosciences Inc | MONOSPACTIC AND BISPACTIC PROTEINS WITH IMMUNE CHECKPOINT REGULATION ROLE FOR CANCER TREATMENT |
| CN111393529B (zh) * | 2018-01-29 | 2022-02-22 | 康源博创生物科技(北京)有限公司 | 与ox40l非竞争结合的抗ox40抗体 |
| EP3768715A1 (en) | 2018-03-23 | 2021-01-27 | Bristol-Myers Squibb Company | Antibodies against mica and/or micb and uses thereof |
| CN111936507B (zh) * | 2018-03-23 | 2022-11-01 | 苏州丁孚靶点生物技术有限公司 | Ox40抗原多肽及其用途 |
| US20210024873A1 (en) | 2018-03-27 | 2021-01-28 | Bristol-Myers Squibb Company | Real-time monitoring of protein concentration using ultraviolet signal |
| KR20210039986A (ko) * | 2018-05-11 | 2021-04-12 | 우시 바이올로직스 (상하이) 컴퍼니 리미티드 | Ox40에 대한 완전한 인간 항체, 이를 준비하는 방법 및 이의 용도 |
| CA3100766A1 (en) | 2018-05-23 | 2019-11-28 | Beigene, Ltd. | Anti-ox40 antibodies and methods of use |
| KR20210016562A (ko) | 2018-05-23 | 2021-02-16 | 에이디씨 테라퓨틱스 에스에이 | 분자 애쥬번트 |
| GB201811403D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Antibody molecules |
| GB201811415D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-Mesothelin Anti bodies |
| SG11202100170RA (en) | 2018-07-12 | 2021-02-25 | F Star Beta Ltd | Antibody molecules that bind pd-l1 and cd137 |
| EP3820898B1 (en) | 2018-07-12 | 2025-09-03 | invoX Pharma Limited | Antibody molecules that bind cd137 and ox40 |
| GB201811410D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | OX40 Binding molecules |
| GB201811450D0 (en) | 2018-07-12 | 2018-08-29 | F Star Delta Ltd | Mesothelin and CD137 binding molecules |
| GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
| WO2020014583A1 (en) | 2018-07-13 | 2020-01-16 | Bristol-Myers Squibb Company | Ox-40 agonist, pd-1 pathway inhibitor and ctla-4 inhibitor combination for use in a mehtod of treating a cancer or a solid tumor |
| CN111040034B (zh) * | 2018-10-12 | 2022-08-30 | 广东旋玉健康生物科技有限公司 | 一种抗人cd358的单克隆抗体及其用途 |
| TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| US12269890B2 (en) | 2018-11-26 | 2025-04-08 | Nanjing GenScript Biotech Co., Ltd. | Humanized anti-human OX40 monoclonal antibody, preparation method therefor and use thereof |
| WO2020119789A1 (en) * | 2018-12-14 | 2020-06-18 | Wuxi Biologics (Shanghai) Co., Ltd. | Fully human antibodies against ox40, method for preparing the same, and use thereof |
| US12195545B2 (en) | 2018-12-25 | 2025-01-14 | Hanx Biopharmaceutics, Inc | Anti-OX40 monoclonal antibody and application thereof |
| US10442866B1 (en) | 2019-01-23 | 2019-10-15 | Beijing Mabworks Biotech Co. Ltd | Antibodies binding OX40 and uses thereof |
| US20220135619A1 (en) | 2019-02-24 | 2022-05-05 | Bristol-Myers Squibb Company | Methods of isolating a protein |
| SG11202108450SA (en) | 2019-02-27 | 2021-09-29 | Ionis Pharmaceuticals Inc | Modulators of malat1 expression |
| JP7744829B2 (ja) * | 2019-03-25 | 2025-09-26 | オハイオ・ステイト・イノベーション・ファウンデーション | 組み合わせ免疫調節及びその使用 |
| CN114245869A (zh) | 2019-05-23 | 2022-03-25 | 百时美施贵宝公司 | 监测细胞培养基的方法 |
| CN114127315A (zh) | 2019-05-30 | 2022-03-01 | 百时美施贵宝公司 | 鉴定适合于免疫肿瘤学(i-o)疗法的受试者的方法 |
| WO2020243570A1 (en) | 2019-05-30 | 2020-12-03 | Bristol-Myers Squibb Company | Cell localization signature and combination therapy |
| KR20220016156A (ko) | 2019-05-30 | 2022-02-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역-종양학 요법에의 적합성을 위한 다종양 유전자 시그너쳐 |
| IL293117A (en) * | 2019-11-21 | 2022-07-01 | Beigene Ltd | Methods of cancer treatment using anti-ox40 antibodies in combination with anti-tim3 antibodies |
| BR112022009265A2 (pt) * | 2019-11-21 | 2022-08-02 | Beigene Ltd | Método de tratamento do câncer e método para aumentar, potencializar ou estimular uma resposta ou função imune |
| KR20220103708A (ko) * | 2019-11-21 | 2022-07-22 | 베이진 엘티디 | 항-pd1 또는 항-pdl1 항체와의 병용물 형태로 항-ox40 항체를 사용하는 암 치료의 방법 |
| WO2021098777A1 (en) * | 2019-11-21 | 2021-05-27 | Beigene, Ltd. | Methods of cancer treatment using anti-ox40 antibodies in combination with pi3 kinase delta inhibitors |
| US20230002499A1 (en) * | 2019-11-21 | 2023-01-05 | Beigene (Beijing) Co., Ltd. | Methods of cancer treatment with anti-ox40 antibody in combination with chemotherapeutic agents |
| GB201917254D0 (en) | 2019-11-27 | 2020-01-08 | Adc Therapeutics Sa | Combination therapy |
| CA3162705A1 (en) | 2019-12-17 | 2021-06-24 | Amgen Inc. | Dual interleukin-2 /tnf receptor agonist for use in therapy |
| CN113429483A (zh) | 2020-03-23 | 2021-09-24 | 百奥泰生物制药股份有限公司 | 一种免疫细胞激活剂的开发及应用 |
| AU2021256226A1 (en) * | 2020-04-17 | 2022-11-17 | Hutchison Medipharma Limited | Anti-OX40 antibody and uses thereof |
| WO2021228836A1 (en) | 2020-05-13 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Recombinant proteins with ox40 activating properties |
| KR20230061430A (ko) | 2020-08-31 | 2023-05-08 | 브리스톨-마이어스 스큅 컴퍼니 | 세포 국재화 시그너쳐 및 면역요법 |
| KR20230080460A (ko) | 2020-10-05 | 2023-06-07 | 브리스톨-마이어스 스큅 컴퍼니 | 단백질을 농축시키는 방법 |
| CN114457022A (zh) * | 2020-10-30 | 2022-05-10 | 未来智人再生医学研究院(广州)有限公司 | 一种表达ox40激活型抗体的多能干细胞及其衍生物与应用 |
| WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
| EP4263600A1 (en) | 2020-12-18 | 2023-10-25 | Century Therapeutics, Inc. | Chimeric antigen receptor systems with adaptable receptor specificity |
| CA3196999A1 (en) | 2020-12-28 | 2022-07-07 | Masano HUANG | Methods of treating tumors |
| SI4267105T1 (sl) | 2020-12-28 | 2025-07-31 | Bristol-Myers Squibb Company | Sestave protiteles in načini njihove uporabe |
| GB202102396D0 (en) | 2021-02-19 | 2021-04-07 | Adc Therapeutics Sa | Molecular adjuvant |
| JP2024514530A (ja) | 2021-04-02 | 2024-04-02 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 切断型ｃｄｃｐ１に対する抗体およびその使用 |
| KR20240038722A (ko) * | 2021-06-29 | 2024-03-25 | 하이파이바이오 (에이치케이) 리미티드 | 항-ox40 모노클로날 항체 및 그의 사용 방법 |
| KR20240122784A (ko) | 2021-12-17 | 2024-08-13 | 상하이 헨리우스 바이오테크, 인크. | 항-ox40 항체 및 사용 방법 |
| CN118488965A (zh) | 2021-12-17 | 2024-08-13 | 上海复宏汉霖生物技术股份有限公司 | 抗ox40抗体、多特异性抗体及其使用方法 |
| US20250057931A1 (en) | 2022-02-08 | 2025-02-20 | Hookipa Biotech Gmbh | Combination therapy with arenavirus particles and immune checkpoint modulators or cytokines |
| US20250188152A1 (en) | 2022-03-09 | 2025-06-12 | Bristol-Myers Squibb Company | Transient expression of therapeutic proteins |
| US20250206775A1 (en) | 2022-03-18 | 2025-06-26 | Bristol-Myers Squibb Company | Methods of isolating polypeptides |
| CN114591988B (zh) * | 2022-03-30 | 2023-01-13 | 北京贝来生物科技有限公司 | 一种激活肿瘤免疫的基因修饰干细胞制备方法 |
| CA3258064A1 (en) | 2022-06-02 | 2023-12-07 | Bristol Myers Squibb Co | ANTIBODY COMPOSITIONS AND THEIR METHODS OF USE |
| CN114966061B (zh) * | 2022-07-28 | 2022-10-21 | 中国食品药品检定研究院 | 一种抗ox40抗体的生物活性检测方法 |
| WO2024054992A1 (en) | 2022-09-09 | 2024-03-14 | Bristol-Myers Squibb Company | Methods of separating chelator |
| WO2024196952A1 (en) | 2023-03-20 | 2024-09-26 | Bristol-Myers Squibb Company | Tumor subtype assessment for cancer therapy |
| WO2025038763A1 (en) | 2023-08-15 | 2025-02-20 | Bristol-Myers Squibb Company | Ceramic hydroxyapatite chromatography flow through method |
| US20250215087A1 (en) | 2023-12-29 | 2025-07-03 | Bristol-Myers Squibb Company | Combination therapy of kras inhibitor and treg depleting agent |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681718A (en) | 1986-03-14 | 1997-10-28 | Celltech Limited | Methods for enhanced production of tissue plasminogen activator in cell culture using alkanoic acids or salts thereof |
| US5457035A (en) | 1993-07-23 | 1995-10-10 | Immunex Corporation | Cytokine which is a ligand for OX40 |
| US6242566B1 (en) | 1994-02-10 | 2001-06-05 | Board Of Trustees Of The Leland Stanford Junior University | Ligand (ACT-4-L) to a receptor on the surface of activated CD4+ T-cells |
| US6312700B1 (en) | 1998-02-24 | 2001-11-06 | Andrew D. Weinberg | Method for enhancing an antigen specific immune response with OX-40L |
| AU7603800A (en) | 1999-09-24 | 2001-04-24 | Human Genome Sciences, Inc. | 32 human secreted proteins |
| GB0216648D0 (en) | 2002-07-18 | 2002-08-28 | Lonza Biologics Plc | Method of expressing recombinant protein in CHO cells |
| US20080187954A1 (en) | 2004-03-10 | 2008-08-07 | Lonza Ltd. | Method For Producing Antibodies |
| CA2581208A1 (en) | 2004-08-30 | 2006-03-09 | Lonza Biologics Plc. | Affinity- plus ion exchange- chromatography for purifying antibodies |
| SI2650020T1 (sl) | 2005-05-06 | 2017-03-31 | Providence Health & Services - Oregon Technology Transfer | Trimerični OX40 imunoglobulinski fuzijski protein in postopek za njegovo uporabo |
| TWI461436B (zh) * | 2005-11-25 | 2014-11-21 | Kyowa Hakko Kirin Co Ltd | 人類ｃｄ１３４（ｏｘ４０）之人類單株抗體及其製造及使用方法 |
| CL2007002404A1 (es) * | 2006-08-21 | 2008-04-18 | Hoffmann La Roche | Uso de un anticuerpo anti-vegf (factor de crecimiento endotelial vascular) para el tratamiento de un paciente que padece una recaida de cancer her2 positivo durante o despues del tratamiento con un anticuerpo anti-her2. |
| US7691980B2 (en) | 2007-01-09 | 2010-04-06 | Bio-Rad Laboratories, Inc. | Enhanced capacity and purification of antibodies by mixed mode chromatography in the presence of aqueous-soluble nonionic organic polymers |
| AU2008219666A1 (en) * | 2007-02-27 | 2008-09-04 | Genentech, Inc. | Antagonist OX40 antibodies and their use in the treatment of inflammatory and autoimmune diseases |
| PT2851374T (pt) * | 2007-12-14 | 2017-06-20 | Pfizer | Moléculas de ligação ao recetor humano ox40 |
| US20090186396A1 (en) | 2008-01-18 | 2009-07-23 | Gagnon Peter S | Enhanced purification of phosphorylated and nonphosphorylated biomolecules by apatite chromatography |
| HRP20160855T1 (hr) | 2008-02-08 | 2016-09-23 | Medimmune, Llc | Anti-ifnar1 protutijela sa smanjenim afinitetom fc liganda |
| EA037792B1 (ru) * | 2009-02-17 | 2021-05-21 | Юсб Биофарма Спрл | Антитела к человеческому ox40 и их применение |
| DK2663579T3 (en) | 2011-01-14 | 2017-07-31 | Univ California | THERAPEUTIC ANTIBODIES AGAINST ROR-1 PROTEIN AND PROCEDURES FOR USE THEREOF |
| HUE037700T2 (hu) * | 2011-07-11 | 2018-09-28 | Glenmark Pharmaceuticals Sa | OX40-hez kötõdõ ellenanyagok és felhasználásuk |
| JP6038920B2 (ja) | 2011-08-23 | 2016-12-07 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | 抗ｏｘ４０抗体およびそれを使用する方法 |
| GB201116092D0 (en) * | 2011-09-16 | 2011-11-02 | Bioceros B V | Antibodies and uses thereof |
| CA2863818A1 (en) | 2012-02-06 | 2013-08-15 | Brendan CURTI | Cancer treatment and monitoring methods using ox40 agonists |
| CA2865899A1 (en) * | 2012-03-02 | 2013-09-06 | William Redmond | Dual ox40 agonist/il-2 cancer therapy methods |
| US9409977B2 (en) * | 2013-03-12 | 2016-08-09 | Decimmune Therapeutics, Inc. | Humanized, anti-N2 antibodies |
| SG10201708048XA (en) * | 2013-03-18 | 2017-10-30 | Biocerox Prod Bv | Humanized anti-cd134 (ox40) antibodies and uses thereof |
-
2015
- 2015-10-01 TW TW104132442A patent/TW201619200A/zh unknown
- 2015-10-07 RU RU2017115662A patent/RU2709742C2/ru active
- 2015-10-07 US US14/877,547 patent/US9738723B2/en active Active
- 2015-10-07 KR KR1020177012413A patent/KR20170064550A/ko not_active Withdrawn
- 2015-10-07 BR BR112017007170A patent/BR112017007170A2/pt not_active Application Discontinuation
- 2015-10-07 MX MX2017004715A patent/MX2017004715A/es unknown
- 2015-10-07 AU AU2015328090A patent/AU2015328090A1/en not_active Abandoned
- 2015-10-07 SG SG11201702826XA patent/SG11201702826XA/en unknown
- 2015-10-07 ES ES15848683T patent/ES2914177T3/es active Active
- 2015-10-07 WO PCT/US2015/054490 patent/WO2016057667A1/en not_active Ceased
- 2015-10-07 EP EP15848683.7A patent/EP3204422B1/en active Active
- 2015-10-07 JP JP2017518907A patent/JP6794348B2/ja active Active
- 2015-10-07 CN CN201580056175.7A patent/CN107074953A/zh active Pending
- 2015-10-07 CA CA2963798A patent/CA2963798A1/en not_active Abandoned
- 2015-10-08 GB GB1517855.1A patent/GB2536324A/en not_active Withdrawn
- 2015-10-09 AR ARP150103284A patent/AR102239A1/es unknown
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2017
- 2017-04-03 IL IL251537A patent/IL251537A0/en unknown
- 2017-04-10 CL CL2017000885A patent/CL2017000885A1/es unknown
- 2017-05-04 CO CONC2017/0004516A patent/CO2017004516A2/es unknown
- 2017-06-28 US US15/635,847 patent/US10150815B2/en active Active
-
2018
- 2018-12-10 US US16/215,263 patent/US20190169303A1/en not_active Abandoned
-
2020
- 2020-11-11 JP JP2020187650A patent/JP2021036887A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US9738723B2 (en) | 2017-08-22 |
| KR20170064550A (ko) | 2017-06-09 |
| SG11201702826XA (en) | 2017-05-30 |
| US20180072808A1 (en) | 2018-03-15 |
| CA2963798A1 (en) | 2016-04-14 |
| JP2017532037A (ja) | 2017-11-02 |
| EP3204422A1 (en) | 2017-08-16 |
| ES2914177T3 (es) | 2022-06-07 |
| EP3204422B1 (en) | 2022-03-30 |
| MX2017004715A (es) | 2017-06-19 |
| US20190169303A1 (en) | 2019-06-06 |
| CO2017004516A2 (es) | 2017-09-29 |
| CL2017000885A1 (es) | 2017-12-15 |
| AU2015328090A1 (en) | 2017-04-27 |
| CN107074953A (zh) | 2017-08-18 |
| RU2017115662A (ru) | 2018-11-13 |
| EP3204422A4 (en) | 2018-08-15 |
| US20160137740A1 (en) | 2016-05-19 |
| US10150815B2 (en) | 2018-12-11 |
| IL251537A0 (en) | 2017-05-29 |
| BR112017007170A2 (pt) | 2017-12-19 |
| JP6794348B2 (ja) | 2020-12-09 |
| GB2536324A (en) | 2016-09-14 |
| AR102239A1 (es) | 2017-02-15 |
| WO2016057667A1 (en) | 2016-04-14 |
| GB201517855D0 (en) | 2015-11-25 |
| RU2017115662A3 (enExample) | 2019-05-20 |
| JP2021036887A (ja) | 2021-03-11 |
| RU2709742C2 (ru) | 2019-12-19 |
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