JP6621741B2 - Ｃｔｌａ−４に対する親和性が改善したｃｄ８６バリアント - Google Patents
Ｃｔｌａ−４に対する親和性が改善したｃｄ８６バリアント Download PDFInfo
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1311475.6A GB201311475D0 (en) | 2013-06-27 | 2013-06-27 | Polypeptides |
| GB1311475.6 | 2013-06-27 | ||
| PCT/EP2014/063442 WO2014207063A1 (en) | 2013-06-27 | 2014-06-25 | Cd86 variants with improved affinity for ctla-4 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016526885A JP2016526885A (ja) | 2016-09-08 |
| JP2016526885A5 JP2016526885A5 (enExample) | 2017-08-03 |
| JP6621741B2 true JP6621741B2 (ja) | 2019-12-18 |
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| Country | Link |
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| US (1) | US9834589B2 (enExample) |
| EP (1) | EP3013854B1 (enExample) |
| JP (1) | JP6621741B2 (enExample) |
| GB (1) | GB201311475D0 (enExample) |
| WO (1) | WO2014207063A1 (enExample) |
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| CN105121715B (zh) | 2012-12-11 | 2018-10-26 | 艾伯特叶史瓦大学爱因斯坦医学院 | 高通量受体:配体鉴定方法 |
| EP3283508B1 (en) | 2015-04-17 | 2021-03-17 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
| RU2017142008A (ru) | 2015-05-21 | 2019-06-24 | Эллигейтор Биосайенс Аб | Новые полипептиды |
| EA201890729A1 (ru) * | 2015-09-14 | 2018-09-28 | Элпайн Имьюн Сайнс, Инк. | Настраиваемые варианты доменов суперсемейства иммуноглобулинов и терапия сконструированными клетками |
| HUE064857T2 (hu) | 2016-03-04 | 2024-04-28 | Io Biotech Aps | Kombinációs terápia a rák ellen |
| KR102824067B1 (ko) | 2016-04-15 | 2025-06-23 | 알파인 이뮨 사이언시즈, 인코포레이티드 | Icos 리간드 변이체 면역조절 단백질 및 그의 용도 |
| EP3443000B1 (en) | 2016-04-15 | 2025-11-12 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
| CA3022331A1 (en) | 2016-05-18 | 2017-11-23 | Albert Einstein College Of Medicine, Inc. | Variant pd-l1 polypeptides, t-cell modulatory multimeric polypeptides, and methods of use thereof |
| CN109475628A (zh) | 2016-05-18 | 2019-03-15 | 库尔生物制药有限公司 | T细胞调节性多聚体多肽及其使用方法 |
| US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
| US11834490B2 (en) | 2016-07-28 | 2023-12-05 | Alpine Immune Sciences, Inc. | CD112 variant immunomodulatory proteins and uses thereof |
| GB201619652D0 (en) | 2016-11-21 | 2017-01-04 | Alligator Bioscience Ab | Novel polypeptides |
| AU2017379900B2 (en) | 2016-12-22 | 2024-12-05 | Cue Biopharma, Inc. | T-cell modulatory multimeric polypeptides and methods of use thereof |
| WO2018129474A1 (en) | 2017-01-09 | 2018-07-12 | Cue Biopharma, Inc. | T-cell modulatory multimeric polypeptides and methods of use thereof |
| US20200009135A1 (en) | 2017-02-01 | 2020-01-09 | Medivir Ab | Therapeutic applications of malt1 inhibitors |
| EP3596118B1 (en) | 2017-03-15 | 2024-08-21 | Cue Biopharma, Inc. | Combination of multimeric fusion polypeptides and immune checkpoint inhibitor for treating hpv-associated cancer |
| CA3054068A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
| CN110809581A (zh) | 2017-03-16 | 2020-02-18 | 高山免疫科学股份有限公司 | Pd-l2变体免疫调节蛋白及其用途 |
| KR20200002889A (ko) | 2017-05-02 | 2020-01-08 | 엘리게이터 바이오사이언스 에이비 | Ox40 및 ctla-4에 대한 이중특이적 항체 |
| KR102813968B1 (ko) | 2017-10-10 | 2025-05-29 | 알파인 이뮨 사이언시즈, 인코포레이티드 | Ctla-4 변이체 면역조절 단백질 및 이의 용도 |
| MX2020004540A (es) | 2017-10-18 | 2020-08-03 | Alpine Immune Sciences Inc | Proteinas inmunomoduladoras de ligando icos variante y composiciones y metodos relacionados. |
| EP3735417A1 (en) | 2018-01-03 | 2020-11-11 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
| WO2019139896A1 (en) | 2018-01-09 | 2019-07-18 | Cue Biopharma, Inc. | Multimeric t-cell modulatory polypeptides and methods of use thereof |
| CN112105624B (zh) | 2018-03-09 | 2023-09-22 | 美迪维尔公司 | 使用(2,2-双羟甲基)亚甲基环丙烷核苷酸治疗癌症 |
| WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
| KR20220044495A (ko) | 2019-07-04 | 2022-04-08 | 치루 레고르 테라퓨틱스 인코포레이티드 | Hpk1 억제제 및 그의 용도 |
| JP7477182B2 (ja) * | 2019-10-08 | 2024-05-01 | ジーンフロンティア株式会社 | Ｃｔｌａ－４阻害活性を有する環状ペプチド、及びその用途 |
| EP4149534A4 (en) | 2020-05-12 | 2024-09-04 | Cue Biopharma, Inc. | MULTIMERIC POLYPEPTIDES MODULATING T CELLS AND METHODS OF USE THEREOF |
| WO2022056014A1 (en) | 2020-09-09 | 2022-03-17 | Cue Biopharma, Inc. | Mhc class ii t-cell modulatory multimeric polypeptides for treating type 1 diabetes mellitus (t1d) and methods of use thereof |
| GB202103122D0 (en) | 2021-03-05 | 2021-04-21 | Univ London Queen Mary | Treatment |
| GB202103673D0 (en) | 2021-03-17 | 2021-04-28 | Io Biotech Aps | Combination therapy for cancer |
| WO2023148501A1 (en) | 2022-02-03 | 2023-08-10 | C4X Discovery Limited | Heterocyclic derivatives as malt1 inhibitors |
| US20250327041A1 (en) | 2022-02-24 | 2025-10-23 | Io Biotech Aps | Nucleotide delivery of cancer therapy |
| GB202207050D0 (en) | 2022-05-13 | 2022-06-29 | C4X Discovery Ltd | Therapeutic compounds |
| WO2025104411A1 (en) | 2023-11-15 | 2025-05-22 | C4X Discovery Limited | Therapeutic compounds |
| WO2025104412A1 (en) | 2023-11-15 | 2025-05-22 | C4X Discovery Limited | Therapeutic compounds |
| WO2025137168A2 (en) | 2023-12-19 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Salt and solid forms of a hpk1 inhibitor |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US6130316A (en) | 1993-07-26 | 2000-10-10 | Dana Farber Cancer Institute | Fusion proteins of novel CTLA4/CD28 ligands and uses therefore |
| EP1186300A1 (en) | 1996-03-20 | 2002-03-13 | Bristol-Myers Squibb Company | Pharmaceutical compositions useful for inhibiting an immune response by blocking the GP39/CD40 and CTLA4/CD28/B7 pathways |
| EE05627B1 (et) | 1998-12-23 | 2013-02-15 | Pfizer Inc. | CTLA-4 vastased inimese monoklonaalsed antikehad |
| US7183376B2 (en) | 2000-06-23 | 2007-02-27 | Maxygen, Inc. | Variant B7 co-stimulatory molecules |
| JP4430303B2 (ja) | 2000-12-12 | 2010-03-10 | アリゲーター・バイオサイエンス・アーベー | タンパク質機能のインビトロ分子進化方法 |
| US7262012B2 (en) | 2002-05-17 | 2007-08-28 | Alligator Bioscience Ab | Method for in vitro molecular evolution of protein function using varied exonuclease digestion in two polynucleotide populations |
| EP2899277A1 (en) | 2004-11-26 | 2015-07-29 | Pieris AG | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| GB2432366B (en) | 2005-11-19 | 2007-11-21 | Alligator Bioscience Ab | A method for in vitro molecular evolution of protein function |
| GB0920258D0 (en) * | 2009-11-19 | 2010-01-06 | Alligator Bioscience Ab | New medical agents and use thereof |
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| US9834589B2 (en) | 2017-12-05 |
| WO2014207063A1 (en) | 2014-12-31 |
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