CA2955006C - Modified il-2 variants that selectively activate regulatory t cells for the treatment of autoimmune diseases - Google Patents
Modified il-2 variants that selectively activate regulatory t cells for the treatment of autoimmune diseases Download PDFInfo
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- CA2955006C CA2955006C CA2955006A CA2955006A CA2955006C CA 2955006 C CA2955006 C CA 2955006C CA 2955006 A CA2955006 A CA 2955006A CA 2955006 A CA2955006 A CA 2955006A CA 2955006 C CA2955006 C CA 2955006C
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462070016P | 2014-08-11 | 2014-08-11 | |
| US62/070,016 | 2014-08-11 | ||
| PCT/US2015/044462 WO2016025385A1 (en) | 2014-08-11 | 2015-08-10 | Modified il-2 variants that selectively activate regulatory t cells for the treatment of autoimmune diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2955006A1 CA2955006A1 (en) | 2016-02-18 |
| CA2955006C true CA2955006C (en) | 2023-07-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2955006A Active CA2955006C (en) | 2014-08-11 | 2015-08-10 | Modified il-2 variants that selectively activate regulatory t cells for the treatment of autoimmune diseases |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US10035836B1 (show.php) |
| EP (2) | EP3180020B1 (show.php) |
| JP (2) | JP6640834B2 (show.php) |
| KR (1) | KR20170035910A (show.php) |
| CN (2) | CN107106654B (show.php) |
| AU (1) | AU2015301936B2 (show.php) |
| CA (1) | CA2955006C (show.php) |
| EA (1) | EA034925B1 (show.php) |
| ES (2) | ES2807260T3 (show.php) |
| HK (1) | HK1243001A1 (show.php) |
| HU (2) | HUE051414T2 (show.php) |
| IL (1) | IL250059B (show.php) |
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Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3482766T3 (pl) | 2014-08-11 | 2020-11-16 | Delinia, Inc. | Modyfikowane warianty il-2, które selektywnie aktywują limfocyty t regulatorowe do leczenia chorób autoimmunologicznych |
| US10851144B2 (en) | 2015-04-10 | 2020-12-01 | Amgen Inc. | Interleukin-2 muteins for the expansion of T-regulatory cells |
| EP3347056A4 (en) | 2015-09-11 | 2019-02-27 | The Board of Trustees of the Leland Stanford Junior University | BIOLOGICALLY RELEVANT ORTHOGONAL CYTOKINE / RECEPTOR COUPLES |
| IL316210A (en) | 2015-10-01 | 2024-12-01 | Heat Biologics Inc | Compounds and methods for connecting type 1 and 2 extracellular complexes as heterologous chimeric proteins |
| US20170204154A1 (en) | 2016-01-20 | 2017-07-20 | Delinia, Inc. | Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases |
| KR20250133490A (ko) * | 2016-05-04 | 2025-09-05 | 암젠 인크 | T-조절 세포의 증식을 위한 인터류킨-2 뮤테인 |
| CN109478421B (zh) * | 2016-05-25 | 2024-07-09 | 豪夫迈·罗氏有限公司 | 剂量方案设计相关的材料与方法 |
| MX2019005400A (es) | 2016-11-08 | 2019-08-05 | Delinia Inc | Variantes de il-2 para el tratamiento de enfermedades autoinmunes. |
| US11384154B2 (en) | 2017-02-06 | 2022-07-12 | Orionis Biosciences BV | Targeted chimeric proteins and uses thereof |
| CN110381983B (zh) | 2017-02-27 | 2024-07-09 | 沙塔克实验室有限公司 | 基于tigit和light的嵌合蛋白 |
| AU2018224852B2 (en) | 2017-02-27 | 2025-03-06 | Shattuck Labs, Inc. | VSIG8-based chimeric proteins |
| SG11201906464UA (en) | 2017-02-27 | 2019-08-27 | Shattuck Labs Inc | Csf1r-based chimeric proteins |
| CN110520436A (zh) | 2017-03-15 | 2019-11-29 | 潘迪恩治疗公司 | 靶向免疫耐受性 |
| KR20200010354A (ko) | 2017-05-24 | 2020-01-30 | 팬디온 테라퓨틱스, 인코포레이티드 | 표적화된 면역관용 |
| CA3069321A1 (en) | 2017-07-11 | 2019-01-17 | The Scripps Research Institute | Incorporation of unnatural nucleotides and methods thereof |
| KR102708105B1 (ko) * | 2017-08-03 | 2024-09-24 | 신톡스, 인크. | 자가면역 질환의 치료를 위한 사이토카인 접합체 |
| KR20200057051A (ko) | 2017-09-27 | 2020-05-25 | 시질론 테라퓨틱스, 인크. | 활성 세포를 포함하는 방법, 조성물 및 이식 가능한 요소 |
| EP3713592A4 (en) | 2017-11-21 | 2022-01-12 | The Board of Trustees of the Leland Stanford Junior University | INTERLEUKIN-2 PARTIAL AGONISTS |
| US10946068B2 (en) | 2017-12-06 | 2021-03-16 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| US10174092B1 (en) | 2017-12-06 | 2019-01-08 | Pandion Therapeutics, Inc. | IL-2 muteins |
| USRE50550E1 (en) | 2017-12-06 | 2025-08-26 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| AU2018390418B2 (en) | 2017-12-19 | 2023-12-21 | Xencor, Inc. | Engineered IL-2 Fc fusion proteins |
| EP3733693A4 (en) | 2017-12-27 | 2021-12-22 | Kyowa Kirin Co., Ltd. | IL-2 VARIANT |
| US20200354424A1 (en) | 2018-01-26 | 2020-11-12 | Orionis Biosciences, Inc. | Xcr1 binding agents and uses thereof |
| KR102877915B1 (ko) | 2018-02-05 | 2025-10-29 | 오리오니스 바이오사이언시즈 인코포레이티드 | 섬유아세포 결합제 및 이의 용도 |
| US11534479B2 (en) | 2018-02-16 | 2022-12-27 | Iltoo Pharma | Use of interleukin 2 for treating Sjögren's syndrome |
| WO2019173832A2 (en) * | 2018-03-09 | 2019-09-12 | AskGene Pharma, Inc. | Novel cytokine prodrugs |
| EP3774861A1 (en) | 2018-03-28 | 2021-02-17 | Bristol-Myers Squibb Company | Interleukin-2/interleukin-2 receptor alpha fusion proteins and methods of use |
| SG11202007524QA (en) * | 2018-03-28 | 2020-09-29 | Ascendis Pharma Oncology Div A/S | Il-2 conjugates |
| WO2019195056A1 (en) | 2018-04-04 | 2019-10-10 | Sigilon Therapeutics, Inc. | Methods, compositions, and implantable elements comprising stem cells |
| KR20210005608A (ko) | 2018-04-04 | 2021-01-14 | 시질론 테라퓨틱스, 인크. | 이식 가능한 입자 및 관련 방법 |
| BR112020025287A2 (pt) | 2018-06-25 | 2021-03-09 | University Of Washington | Projeto de novo de miméticos de interleucina potentes e seletivos |
| WO2020007937A1 (en) | 2018-07-03 | 2020-01-09 | Iltoo Pharma | Use of interleukin-2 for treating systemic sclerosis |
| CN113382754A (zh) * | 2018-07-13 | 2021-09-10 | Il-2Rx公司 | 治疗癌症和免疫病症的化合物、组合物、方法和用途 |
| EP3827079A1 (en) | 2018-07-25 | 2021-06-02 | Askgene Pharma, Inc. | Novel il-21 prodrugs and methods of use thereof |
| JP7307500B2 (ja) * | 2018-08-06 | 2023-07-12 | メディカイン、インコーポレイテッド | Ｉｌ－２受容体結合化合物 |
| WO2020033312A1 (en) * | 2018-08-06 | 2020-02-13 | Medikine, Inc. | Il-2 receptor binding compounds |
| WO2020035482A1 (en) | 2018-08-13 | 2020-02-20 | Iltoo Pharma | Combination of interleukin-2 with an interleukin 1 inhibitor, conjugates and therapeutic uses thereof |
| US10780121B2 (en) | 2018-08-29 | 2020-09-22 | Shattuck Labs, Inc. | FLT3L-based chimeric proteins |
| MX2021002575A (es) * | 2018-09-11 | 2021-06-08 | Ambrx Inc | Conjugados de polipeptidos de interleucina-2 y sus usos. |
| UY38389A (es) | 2018-09-27 | 2020-04-30 | Sigilon Therapeutics Inc | Dispositivos implantables para terapia celular y métodos relacionados |
| US12410225B2 (en) | 2018-11-08 | 2025-09-09 | Orionis Biosciences, Inc | Modulation of dendritic cell lineages |
| EA202190593A1 (ru) * | 2018-11-20 | 2021-11-18 | Юниверсити Оф Вашингтон | Расщепленные миметики интерлейкина и их применение |
| CN111378026A (zh) * | 2018-12-27 | 2020-07-07 | 天津键凯科技有限公司 | 一种制备结合位点可控的peg化生物分子的方法 |
| WO2020163532A1 (en) | 2019-02-06 | 2020-08-13 | Synthorx, Inc. | Il-2 conjugates and methods of use thereof |
| CN113661175A (zh) | 2019-02-15 | 2021-11-16 | 整体分子公司 | 包含共同轻链的抗体及其用途 |
| CA3129834A1 (en) | 2019-02-15 | 2020-08-20 | Integral Molecular, Inc. | Claudin 6 antibodies and uses thereof |
| KR20220008811A (ko) * | 2019-03-29 | 2022-01-21 | 엥스띠뛰 퀴리 | 변형된 생물학적 활성을 갖는 인터류킨-2 변이체. |
| EP3958888A4 (en) * | 2019-04-26 | 2023-07-12 | Prolynx LLC | SLOW-RELEASE CYTOKINE CONJUGATES |
| WO2020236875A1 (en) | 2019-05-20 | 2020-11-26 | Pandion Therapeutics, Inc. | Madcam targeted immunotolerance |
| CN114651004B (zh) * | 2019-06-14 | 2025-06-27 | 科优基因公司 | 用于癌症治疗的新型白介素-2变体 |
| TWI889694B (zh) | 2019-07-26 | 2025-07-11 | 美商威特拉公司 | 介白素-2藥劑及其用途 |
| CN110642934B (zh) * | 2019-09-10 | 2022-08-23 | 中国医学科学院北京协和医院 | 靶向调节t细胞的长效白介素-2及其在治疗自身免疫病中的应用 |
| CN114746122A (zh) | 2019-09-10 | 2022-07-12 | 新索思股份有限公司 | Il-2缀合物和治疗自身免疫性疾病的使用方法 |
| MX2022005404A (es) * | 2019-11-05 | 2022-09-09 | Medikine Inc | Compuestos de fijación a il-2r e il-7r dual. |
| MX2022005411A (es) | 2019-11-05 | 2022-08-10 | Medikine Inc | COMPUESTOS DE UNIÓN A IL-2RßYC. |
| US11692020B2 (en) | 2019-11-20 | 2023-07-04 | Anwita Biosciences, Inc. | Cytokine fusion proteins, and their pharmaceutical compositions and therapeutic applications |
| JP2023506223A (ja) | 2019-12-13 | 2023-02-15 | シンセカイン インコーポレイテッド | Ｉｌ－２オルソログおよび使用法 |
| CN114437198A (zh) * | 2019-12-17 | 2022-05-06 | 北京志道生物科技有限公司 | 白介素-2衍生物 |
| CA3162406A1 (en) | 2020-01-10 | 2021-07-15 | Vijaya Raghavan PATTABIRAMAN | Modified il-2 polypeptides and uses thereof |
| KR20240046306A (ko) | 2020-01-14 | 2024-04-08 | 신테카인, 인크. | 편향된 il2 뮤테인 방법 및 조성물 |
| JP2023511274A (ja) | 2020-01-14 | 2023-03-17 | シンセカイン インコーポレイテッド | Ｉｌ２オルソログおよび使用法 |
| CN113121670B (zh) * | 2020-01-15 | 2022-11-22 | 天津键凯科技有限公司 | 二取代peg化白细胞介素2及其制备方法、应用 |
| US20230102464A1 (en) * | 2020-01-15 | 2023-03-30 | Jenkem Technology Co., Ltd. (Tianjin) | Method for preparing pegylated biomolecule with controllable binding sites |
| CN115315435A (zh) | 2020-02-03 | 2022-11-08 | 麦地金公司 | IL-7Rαγc结合化合物 |
| US11981715B2 (en) | 2020-02-21 | 2024-05-14 | Pandion Operations, Inc. | Tissue targeted immunotolerance with a CD39 effector |
| KR20220149554A (ko) * | 2020-03-05 | 2022-11-08 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | 설계된 il-2 변이체 |
| TWI894224B (zh) | 2020-03-06 | 2025-08-21 | 尼姆大學醫學中心 | 用於肌肉萎縮性脊髓側索硬化症之治療的低劑量人類介白素-2 |
| EP4139340A1 (en) * | 2020-04-22 | 2023-03-01 | Merck Sharp & Dohme LLC | Human interleukin-2 conjugates biased for the interleukin-2 receptor beta gammac dimer and conjugated to a nonpeptidic, water-soluble polymer |
| EP4143329A4 (en) | 2020-04-28 | 2024-10-16 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
| MX2022014082A (es) | 2020-06-03 | 2022-12-07 | Ascendis Pharma Oncology Div A/S | Secuencias de interleucina (il-2) y usos de las mismas. |
| WO2022009123A1 (en) * | 2020-07-09 | 2022-01-13 | Eutilex Co., Ltd. | Il-2 variants |
| MX2023005030A (es) | 2020-10-29 | 2023-05-16 | Bristol Myers Squibb Co | Proteinas de fusion para el tratamiento de enfermedades. |
| AU2021376351A1 (en) * | 2020-11-04 | 2023-06-08 | Medikine, Inc. | IL-2Rβγc BINDING COMPOUNDS AND USES THEREOF |
| JP2024502708A (ja) | 2020-12-04 | 2024-01-23 | ビステラ， インコーポレイテッド | インターロイキン－２作用物質を使用する方法 |
| CN117769564A (zh) * | 2021-03-31 | 2024-03-26 | 安维塔生物科学股份有限公司 | 融合蛋白、药物组合物和治疗应用 |
| US20240199714A1 (en) * | 2021-04-16 | 2024-06-20 | Orionis Biosciences, Inc. | Il-2 based constructs |
| US11999771B2 (en) | 2022-04-07 | 2024-06-04 | Medikine, Inc. | IL-7Rαγc ligand immunoglobulin fusion proteins |
| WO2024056154A1 (en) | 2022-09-12 | 2024-03-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Interleukin-2 for use in treating autism spectrum disorder |
| WO2024103860A1 (zh) * | 2022-11-18 | 2024-05-23 | 南京诺艾新生物技术有限公司 | 受体亲和力偏好性的定点偶联聚乙二醇化白介素-2突变体及其用途 |
| JP2026500995A (ja) | 2022-11-30 | 2026-01-13 | インテグラル・モレキュラー・インコーポレイテッド | 二重特異性形式を含むクローディン６を対象とする抗体 |
| EP4630035A1 (en) | 2022-12-05 | 2025-10-15 | Centre Hospitalier Universitaire de Nimes | Low dose human interleukin-2 for the treatment of amyotrophic lateral sclerosis in a subgroup of patients |
| AU2024207151A1 (en) | 2023-01-09 | 2025-06-19 | Odyssey Therapeutics, Inc. | Anti-tnfr2 antigen-binding proteins and uses thereof |
| CN119708194A (zh) * | 2023-09-28 | 2025-03-28 | 南京诺艾新生物技术有限公司 | Il-22突变体及其制备方法与应用 |
| WO2025129120A2 (en) | 2023-12-15 | 2025-06-19 | Port Therapeutics, Inc. | Use of thermal bioswitches for treating autoimmune diseases |
| WO2025217240A1 (en) | 2024-04-10 | 2025-10-16 | Odyssey Therapeutics, Inc. | Anti-tnfr2 antigen-binding proteins and uses thereof |
| WO2026006809A1 (en) | 2024-06-27 | 2026-01-02 | Odyssey Therapeutics, Inc. | Multispecific molecules binding tnfr2 and cd25 and uses thereof |
Family Cites Families (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4853332A (en) | 1982-10-19 | 1989-08-01 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of biologically active proteins |
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US5466447A (en) | 1988-06-29 | 1995-11-14 | Amgen Inc. | Method for treating psoriasis |
| EP0378666A4 (en) * | 1988-07-05 | 1992-01-22 | Amgen Inc. | Interleukin ii analogs |
| US5089261A (en) | 1989-01-23 | 1992-02-18 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US4902502A (en) | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US6541610B1 (en) | 1989-09-05 | 2003-04-01 | Immunex Corporation | Fusion proteins comprising tumor necrosis factor receptor |
| US5650150A (en) | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
| US5281698A (en) | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
| WO1995008340A1 (en) | 1993-09-21 | 1995-03-30 | Amgen Inc. | Method for treating psoriasis |
| CA2320403A1 (en) | 1998-02-25 | 1999-09-02 | Lexigen Pharmaceuticals Corporation | Enhancing the circulating half-life of antibody-based fusion proteins |
| DZ2788A1 (fr) * | 1998-05-15 | 2003-12-01 | Bayer Ag | Agonistes et antagonistes selectifs à IL-2. |
| US6955807B1 (en) | 1998-05-15 | 2005-10-18 | Bayer Pharmaceuticals Corporation | IL-2 selective agonists and antagonists |
| US6348192B1 (en) | 1999-05-11 | 2002-02-19 | Bayer Corporation | Interleukin-2 mutein expressed from mammalian cells |
| SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| WO2001062827A2 (en) | 2000-02-22 | 2001-08-30 | Shearwater Corporation | N-maleimidyl polymer derivatives |
| AU2001259253A1 (en) * | 2000-04-26 | 2001-11-07 | National Jewish Medical And Research Center | Product and process for regulation of t cell responses |
| US6689353B1 (en) | 2000-06-28 | 2004-02-10 | Bayer Pharmaceuticals Corporation | Stabilized interleukin 2 |
| RU2280255C2 (ru) * | 2000-09-14 | 2006-07-20 | Бет Изрейэл Диконисс Медикал Сентер, Инк. | Модуляция il-2- и il-15-опосредованных т-клеточных ответов |
| PT1366067E (pt) | 2001-03-07 | 2012-11-29 | Merck Patent Gmbh | Tecnologia de expressão para proteínas contendo uma unidade de anticorpo de isotipo híbrido |
| CA2452582C (en) * | 2001-07-11 | 2013-01-22 | Maxygen, Inc. | G-csf conjugates |
| ATE375388T1 (de) | 2001-07-27 | 2007-10-15 | Us Gov Health & Human Serv | Systeme zur stellengerichteten in-vivo-mutagenese mit oligonukleotiden |
| WO2003015697A2 (en) | 2001-08-13 | 2003-02-27 | University Of Southern California | Interleukin-2 mutants with reduced toxicity |
| PT1454138E (pt) * | 2001-12-04 | 2012-03-28 | Merck Patent Gmbh | Imunocitoquinas com seletividade modulada |
| MXPA05013565A (es) | 2003-06-12 | 2006-03-09 | Lilly Co Eli | Proteinas de fusion analogas al glp-1. |
| US7569215B2 (en) | 2003-07-18 | 2009-08-04 | Massachusetts Institute Of Technology | Mutant interleukin-2 (IL-2) polypeptides |
| CA2678736A1 (en) * | 2003-07-21 | 2005-02-17 | Transgene S.A. | Novel multifunctional il-2 - il-18 fusion proteins |
| CA2557677A1 (en) | 2004-03-05 | 2005-10-06 | Chiron Corporation | In vitro test system for predicting patient tolerability of therapeutic agents |
| CN1930300A (zh) * | 2004-03-05 | 2007-03-14 | 希龙公司 | 预测患者治疗药物耐受性的体外试验系统 |
| BRPI0606774A2 (pt) | 2005-01-27 | 2009-07-14 | Novartis Vaccines & Diagnostic | método para o tratamento de um paciente humano que tem carcinoma de célula renal e uso de il-2 |
| DE602005001688T2 (de) | 2005-02-07 | 2008-04-10 | Novartis Vaccines and Diagnostics, Inc., Emeryville | Aufbereitung von Aldesleukin zur pharmazeutischen Verwendung |
| FR2918770B1 (fr) | 2007-07-10 | 2009-09-11 | Essilor Int | Afficheur destine a etre integre a une paire de lunettes. |
| US8906356B2 (en) | 2007-11-05 | 2014-12-09 | Massachusetts Institute Of Technology | Mutant interleukin-2 (IL-2) polypeptides |
| KR20090103209A (ko) * | 2008-03-27 | 2009-10-01 | (주)한국비엠아이 | 사람 인터루킨-2 동종체 |
| DE102008023820A1 (de) * | 2008-05-08 | 2009-11-12 | Aicuris Gmbh & Co. Kg | Mittel zur Behandlung und/oder Prophylaxe einer Autoimmunerkrankung und zur Bildung von Regulatorischen T-Zellen |
| MX2011007647A (es) * | 2009-01-21 | 2011-09-01 | Amgen Inc | Composiciones y metodos para el tratamiento de enfermedades inflamatorias y autoinmunes. |
| PL2542590T5 (pl) | 2010-03-05 | 2020-08-10 | The Johns Hopkins University | Kompozycje i sposoby dla ukierunkowanych immunomodulatorowych przeciwciał i białek fuzyjnych |
| CU23923B1 (es) | 2010-11-12 | 2013-07-31 | Ct De Inmunología Molecular | Polipéptidos derivados de la il-2 con actividad agonista |
| MX388465B (es) | 2010-11-12 | 2025-03-20 | Nektar Therapeutics | Conjugados de un resto de interleucina-2 y un polímero. |
| CN102462837B (zh) | 2010-11-19 | 2016-08-03 | 生物林格斯Ip有限公司 | 抗炎组合物 |
| EP2655409A4 (en) | 2010-12-22 | 2015-07-01 | Univ Leland Stanford Junior | SUPERAGONISTS AND ANTAGONISTS OF INTERLEUKIN-2 |
| CN102174111B (zh) | 2011-01-25 | 2013-01-09 | 江苏省弗泰生物科技有限公司 | 人白介素2-Fc融合蛋白及其用途 |
| PH12013501657A1 (en) | 2011-02-10 | 2013-10-07 | Roche Glycart Ag | Mutant interleukin-2 polypeptides |
| BR112013023151A2 (pt) | 2011-03-11 | 2020-09-15 | Assistance Publique - Hôpitaux De Paris | interleucina-2 para uso no tratamento de desordem auto-imune, !muno-relacionada ou inflamatória e método para determinar se um regime ou dose de il-2 tem de ser modificado |
| EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
| WO2013107413A1 (zh) * | 2012-01-19 | 2013-07-25 | 中国科学院上海巴斯德研究所 | 磷酸化途径相关因子在调控调节性t细胞功能中的应用 |
| WO2013177187A2 (en) | 2012-05-22 | 2013-11-28 | Massachusetts Institute Of Technology | Synergistic tumor treatment with extended-pk il-2 and therapeutic agents |
| US20140044675A1 (en) * | 2012-08-10 | 2014-02-13 | Roche Glycart Ag | Interleukin-2 fusion proteins and uses thereof |
| CN103193879A (zh) * | 2013-02-07 | 2013-07-10 | 深圳市亚太兴实业有限公司 | 一种聚乙二醇修饰的重组人白介素2的制备方法 |
| US9546203B2 (en) | 2013-03-14 | 2017-01-17 | Amgen Inc. | Aglycosylated Fc-containing polypeptides with cysteine substitutions |
| DK2970486T3 (en) | 2013-03-15 | 2018-08-06 | Xencor Inc | MODULATION OF T-CELLS WITH BISPECIFIC ANTIBODIES AND FC-FUSIONS |
| CN103193887B (zh) | 2013-04-03 | 2015-02-04 | 江苏众红生物工程创药研究院有限公司 | 一种重组猪白细胞介素2-Fc融合蛋白及其编码基因和表达方法 |
| WO2014201378A1 (en) | 2013-06-13 | 2014-12-18 | Massachusetts Institute Of Technology | Synergistic tumor treatment with extended-pk il -2 and adoptive cell therapy |
| CN111423513A (zh) | 2014-02-06 | 2020-07-17 | 豪夫迈·罗氏有限公司 | 白介素-2融合蛋白和其用途 |
| EP3134102B1 (en) | 2014-04-24 | 2019-07-03 | The Board of Trustees of The Leland Stanford Junior University | Superagonists, partial agonists and antagonists of interleukin-2 |
| KR20150133576A (ko) | 2014-05-20 | 2015-11-30 | 삼성전자주식회사 | 화학적 개질된 표적화 단백질 및 그의 이용 |
| DK3172227T3 (da) | 2014-07-21 | 2019-12-02 | Delinia Inc | Molekyler der selektivt aktiverer regulatoriske t-celler til behandlingen af autoimmune sygdomme |
| PL3482766T3 (pl) | 2014-08-11 | 2020-11-16 | Delinia, Inc. | Modyfikowane warianty il-2, które selektywnie aktywują limfocyty t regulatorowe do leczenia chorób autoimmunologicznych |
| US20170224777A1 (en) | 2014-08-12 | 2017-08-10 | Massachusetts Institute Of Technology | Synergistic tumor treatment with il-2, a therapeutic antibody, and a cancer vaccine |
| EP3204119B1 (en) | 2014-10-09 | 2021-06-09 | Dana-Farber Cancer Institute, Inc. | Multiple-variable il-2 dose regimen for treating immune disorders |
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