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)
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| 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)
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| JP2016526885A JP2016526885A (ja) | 2016-09-08 |
| JP2016526885A5 JP2016526885A5 (enExample) | 2017-08-03 |
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| EP (1) | EP3013854B1 (enExample) |
| JP (1) | JP6621741B2 (enExample) |
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| SG11201504558TA (en) | 2012-12-11 | 2015-07-30 | Einstein Coll Med | Methods for high throughput receptor:ligand identification |
| SMT202100467T1 (it) | 2015-04-17 | 2021-09-14 | Alpine Immune Sciences Inc | Proteine immunomodulatorie con affinità regolabili |
| BR112017024770A2 (pt) | 2015-05-21 | 2018-07-31 | Alligator Bioscience Ab | polipeptídeos inovadores |
| EP3350206A1 (en) * | 2015-09-14 | 2018-07-25 | Alpine Immune Sciences, Inc. | Tunable variant immunoglobulin superfamily domains and engineered cell therapy |
| HUE064857T2 (hu) | 2016-03-04 | 2024-04-28 | Io Biotech Aps | Kombinációs terápia a rák ellen |
| SG11201808457PA (en) | 2016-04-15 | 2018-10-30 | Alpine Immune Sciences Inc | Icos ligand variant immunomodulatory proteins and uses thereof |
| AU2017248830B2 (en) | 2016-04-15 | 2023-03-09 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
| IL262606B2 (en) | 2016-05-18 | 2023-04-01 | Albert Einstein College Medicine Inc | pd-l1 variant polypeptides, T-cell modulatory multimeric polypeptides, and methods of using them |
| SG11201808552XA (en) | 2016-05-18 | 2018-10-30 | Cue Biopharma Inc | T-cell modulatory multimeric polypeptides and methods of use thereof |
| US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
| EP3491013A1 (en) | 2016-07-28 | 2019-06-05 | Alpine Immune Sciences, Inc. | Cd155 variant immunomodulatory proteins and uses thereof |
| WO2018022945A1 (en) | 2016-07-28 | 2018-02-01 | Alpine Immune Sciences, Inc. | Cd112 variant immunomodulatory proteins and uses thereof |
| GB201619652D0 (en) | 2016-11-21 | 2017-01-04 | Alligator Bioscience Ab | Novel polypeptides |
| CN110325205B (zh) | 2016-12-22 | 2023-08-15 | 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 |
| US11851471B2 (en) | 2017-01-09 | 2023-12-26 | Cue Biopharma, Inc. | T-cell modulatory multimeric polypeptides and methods of use thereof |
| EP3576744A1 (en) | 2017-02-01 | 2019-12-11 | Medivir Aktiebolag | Therapeutic applications of malt1 inhibitors |
| KR20240005989A (ko) | 2017-03-15 | 2024-01-12 | 큐 바이오파마, 인크. | 면역 반응을 조절하는 방법 |
| MX2019010887A (es) | 2017-03-16 | 2019-10-15 | Alpine Immune Sciences Inc | Proteinas inmunomoduladoras de cb80 variante y usos de estas. |
| JP2020511144A (ja) | 2017-03-16 | 2020-04-16 | 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 | Ｐｄ−ｌ２バリアント免疫調節タンパク質及びその使用 |
| MX2019012953A (es) | 2017-05-02 | 2020-02-12 | Alligator Bioscience Ab | Anticuerpo biespecifico contra ox40 y ctla-4. |
| EP3694870A1 (en) | 2017-10-10 | 2020-08-19 | Alpine Immune Sciences, Inc. | Ctla-4 variant immunomodulatory proteins and uses thereof |
| JP7282760B2 (ja) | 2017-10-18 | 2023-05-29 | 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 | バリアントｉｃｏｓリガンド免疫調節タンパク質ならびに関連する組成物および方法 |
| SG11202006148UA (en) | 2018-01-03 | 2020-07-29 | 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 |
| AU2019232478B2 (en) | 2018-03-09 | 2024-06-06 | Medivir Aktiebolag | Cancer treatment with (2,2-bishydroxymethyl) methylenecyclopropane nucleotides |
| WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
| CN113727998A (zh) | 2018-11-30 | 2021-11-30 | 高山免疫科学股份有限公司 | Cd86变体免疫调节蛋白及其用途 |
| WO2021000935A1 (en) | 2019-07-04 | 2021-01-07 | Qilu Regor Therapeutics Inc. | Hpk1 inhibitors and uses thereof |
| 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 |
| US12686725B2 (en) | 2020-05-05 | 2026-07-21 | Mythic Therapeutics, Inc. | Anti-DLL3 antibodies and methods of use |
| US12202882B2 (en) | 2020-05-08 | 2025-01-21 | Alpine Immune Sciences, Inc. | APRIL and BAFF inhibitory immunomodulatory proteins and methods of use thereof |
| IL296209A (en) | 2020-05-12 | 2022-11-01 | Cue Biopharma Inc | Multimeric t-cell modulatory polypeptides and methods of using them |
| JP2023541366A (ja) | 2020-09-09 | 2023-10-02 | キュー バイオファーマ， インコーポレイテッド | １型真性糖尿病（ｔ１ｄ）を治療するためのｍｈｃクラスｉｉ ｔ細胞調節多量体ポリペプチド及びその使用方法 |
| 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 |
| CN119095837A (zh) | 2022-02-03 | 2024-12-06 | 希四克斯探索有限公司 | 作为malt1抑制剂的杂环衍生物 |
| 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 |
| US6682736B1 (en) | 1998-12-23 | 2004-01-27 | Abgenix, Inc. | Human monoclonal antibodies to CTLA-4 |
| US7183376B2 (en) | 2000-06-23 | 2007-02-27 | Maxygen, Inc. | Variant B7 co-stimulatory molecules |
| PT1341909E (pt) | 2000-12-12 | 2005-10-31 | Alligator Bioscience Ab | Metodo para a evolucao molecular in vitro da funcao de proteina |
| ATE356871T1 (de) | 2002-05-17 | 2007-04-15 | Alligator Bioscience Ab | Eine methode zur in vitro molekularen evolution der proteinfunktion |
| US7892827B2 (en) | 2004-11-26 | 2011-02-22 | 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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- 2014-06-25 JP JP2016522479A patent/JP6621741B2/ja not_active Expired - Fee Related
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| WO2014207063A1 (en) | 2014-12-31 |
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| EP3013854A1 (en) | 2016-05-04 |
| JP2016526885A (ja) | 2016-09-08 |
| US20160304580A1 (en) | 2016-10-20 |
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