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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| PCT/EP2014/063442 WO2014207063A1 (en) | 2013-06-27 | 2014-06-25 | Cd86 variants with improved affinity for ctla-4 |
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| SI3283508T1 (sl) | 2015-04-17 | 2021-09-30 | Alpine Immune Sciences, Inc. | Imunomodulirajoči proteini z nastavljivimi afinitetami |
| IL255767B2 (en) | 2015-05-21 | 2024-04-01 | Alligator Bioscience Ab | Novel polypeptides |
| JP2018534245A (ja) * | 2015-09-14 | 2018-11-22 | 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 | 調整可能なバリアント免疫グロブリンスーパーファミリードメインおよび改変細胞療法 |
| ES2965009T3 (es) | 2016-03-04 | 2024-04-10 | Io Biotech Aps | Terapia combinada contra el cancer |
| SG11201808457PA (en) | 2016-04-15 | 2018-10-30 | Alpine Immune Sciences Inc | Icos ligand variant immunomodulatory proteins and uses thereof |
| WO2017181152A2 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
| US11505591B2 (en) | 2016-05-18 | 2022-11-22 | Cue Biopharma, Inc. | T-cell modulatory multimeric polypeptides and methods of use thereof |
| KR20190044029A (ko) | 2016-05-18 | 2019-04-29 | 알버트 아인슈타인 컬리지 오브 메디슨, 인크. | 변이체 pd-l1 폴리펩타이드, t-세포 조절 다량체 폴리펩타이드 및 이들의 사용 방법 |
| WO2018022945A1 (en) | 2016-07-28 | 2018-02-01 | Alpine Immune Sciences, Inc. | Cd112 variant immunomodulatory proteins and uses thereof |
| US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
| GB201619652D0 (en) | 2016-11-21 | 2017-01-04 | Alligator Bioscience Ab | Novel polypeptides |
| DK3558339T5 (da) | 2016-12-22 | 2024-09-02 | Cue Biopharma Inc | T-celle-modulerende multimere polypeptider og fremgangsmåder til anvendelse deraf |
| EP3565829A4 (en) | 2017-01-09 | 2021-01-27 | Cue Biopharma, Inc. | T-CELL-MODULATING MULTIMERIC POLYPEPTIDES AND METHOD OF USING THEREOF |
| EP3576744A1 (en) | 2017-02-01 | 2019-12-11 | Medivir Aktiebolag | Therapeutic applications of malt1 inhibitors |
| US20200010528A1 (en) | 2017-03-15 | 2020-01-09 | Cue Biopharma, Inc. | Methods for modulating an immune response |
| WO2018170026A2 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
| CA3053812A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l2 variant immunomodulatory proteins and uses thereof |
| 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 |
| MY203416A (en) | 2017-10-18 | 2024-06-27 | Alpine Immune Sciences Inc | Variant icos ligand immunomodulatory proteins and related compositions and methods |
| BR112020013236A2 (pt) | 2018-01-03 | 2020-12-01 | Alpine Immune Sciences, Inc. | proteínas imunomoduladoras de múltiplos domínios e métodos de seu uso |
| CN111886241A (zh) | 2018-01-09 | 2020-11-03 | 库尔生物制药有限公司 | 多聚体t细胞调节多肽及其使用方法 |
| 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 |
| MA56462A (fr) | 2019-07-04 | 2022-05-11 | Qilu Regor Therapeutics Inc | Inhibiteurs de hpk1 et leurs utilisations |
| WO2021070696A1 (ja) * | 2019-10-08 | 2021-04-15 | 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 |
| IL296209A (en) | 2020-05-12 | 2022-11-01 | Cue Biopharma Inc | Multimeric t-cell modulatory polypeptides and methods of using them |
| EP4211149A4 (en) | 2020-09-09 | 2024-10-09 | Cue Biopharma, Inc. | MULTIMERIC POLYPEPTIDES MODULATING MHC CLASS II T CELLS FOR THE TREATMENT OF 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 |
| JP2025506410A (ja) | 2022-02-03 | 2025-03-11 | シーフォーエックス・ディスカバリー・リミテッド | Ｍａｌｔ１阻害剤としてのヘテロ環誘導体 |
| JP2025508467A (ja) | 2022-02-24 | 2025-03-26 | アイオー バイオテック エーピーエス | 癌治療のヌクレオチド送達 |
| 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 |
| PT1341909E (pt) | 2000-12-12 | 2005-10-31 | Alligator Bioscience Ab | Metodo para a evolucao molecular in vitro da funcao de proteina |
| ES2285118T5 (es) | 2002-05-17 | 2012-09-21 | Alligator Bioscience Ab | Un método para el desarrollo molecular in vitro de una función proteica. |
| WO2006056464A2 (en) | 2004-11-26 | 2006-06-01 | 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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| GB201311475D0 (en) | 2013-08-14 |
| EP3013854A1 (en) | 2016-05-04 |
| EP3013854B1 (en) | 2021-02-24 |
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