CN110615835A - 选择性地操纵靶细胞中对两个或更多个共有受体多肽识别的配体的细胞反应的方法 - Google Patents
选择性地操纵靶细胞中对两个或更多个共有受体多肽识别的配体的细胞反应的方法 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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| JP2018157812A (ja) * | 2017-03-23 | 2018-10-11 | 東ソー株式会社 | 試料中に含まれる細胞の検出方法 |
| JP7728635B2 (ja) * | 2017-03-31 | 2025-08-25 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | シンセカイン組成物及び使用方法 |
| JP7497340B2 (ja) | 2018-05-14 | 2024-06-10 | ウェアウルフ セラピューティクス， インコーポレイテッド | 活性化可能なインターロイキン１２ポリペプチド及びその使用方法 |
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| US20210214410A1 (en) | 2018-06-01 | 2021-07-15 | The Board Of Trustees Of The Leland Stanford Junior University | Il-13/il-4 superkines: immune cell targeting constructs and methods of use thereof |
| WO2020212602A1 (en) | 2019-04-19 | 2020-10-22 | Synerkine Pharma B.V. | Therapeutic crosslinking of cytokine receptors |
| EP3969035A4 (en) | 2019-05-14 | 2023-06-21 | Werewolf Therapeutics, Inc. | SEPARATION UNITS AND METHODS AND THEIR USE |
| MX2022005666A (es) | 2019-11-14 | 2022-10-07 | Werewolf Therapeutics Inc | Polipeptidos de citocina activables y metodos de uso de los mismos. |
| EP4532018A1 (en) * | 2022-05-24 | 2025-04-09 | University of Pittsburgh - of the Commonwealth System of Higher Education | Interleukin 4 and/or interleukin 13-based eye compositions |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6335426B1 (en) * | 1996-06-14 | 2002-01-01 | Bayer Corporation | T-cell selective interleukin-4 agonists |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0656947A1 (en) | 1992-08-21 | 1995-06-14 | Schering Corporation | Human interleukin-13 |
| US5635599A (en) | 1994-04-08 | 1997-06-03 | The United States Of America As Represented By The Department Of Health And Human Services | Fusion proteins comprising circularly permuted ligands |
| DE4423131A1 (de) * | 1994-07-01 | 1996-01-04 | Bayer Ag | Neue hIL-4-Mutantenproteine als Antagonisten oder partielle Agonisten des humanen Interleukin 4 |
| FR2742156A1 (fr) | 1995-12-06 | 1997-06-13 | Sanofi Sa | Polypeptide recepteur de l'il-13 |
| US6028176A (en) * | 1996-07-19 | 2000-02-22 | Bayer Corporation | High-affinity interleukin-4 muteins |
| US6673602B1 (en) | 1999-06-11 | 2004-01-06 | The General Hospital Corporation | Herpes simplex virus amplicon vector targeting system and method of using same |
| US6737511B1 (en) | 1999-08-16 | 2004-05-18 | The United States Of America As Represented By The Department Of Health And Human Services | Receptor-mediated uptake of an extracellular BCL-xL fusion protein inhibits apoptosis |
| JP4505166B2 (ja) | 1999-09-09 | 2010-07-21 | シェーリング コーポレイション | 哺乳動物インターロイキン−１２ｐ４０およびインターロイキンｂ３０、その組成物、抗体、薬学的組成物における使用 |
| JP2003511019A (ja) | 1999-10-06 | 2003-03-25 | ザ ペン ステート リサーチ ファウンデーション | Ｉｌ１３変異体 |
| WO2001034645A2 (en) | 1999-11-11 | 2001-05-17 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Mutated il-13 molecules and their uses |
| GB0004016D0 (en) | 2000-02-22 | 2000-04-12 | Royal Brompton Hospital | Biological material and uses thereof |
| US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
| JP4863150B2 (ja) | 2000-08-30 | 2012-01-25 | ザ・ペン・ステート・リサーチ・ファンデーション | インターロイキン１３のアミノ酸置換変異体 |
| AU2440802A (en) | 2000-10-18 | 2002-04-29 | Massachusetts Inst Technology | Methods and products related to pulmonary delivery of polysaccharides |
| US7087224B2 (en) | 2000-10-31 | 2006-08-08 | Amgen Inc. | Method of treating anemia by administering IL-1ra |
| US20030013851A1 (en) | 2001-06-07 | 2003-01-16 | Robert Powers | Solution structure of IL-13 and uses thereof |
| US20040248260A1 (en) | 2001-10-26 | 2004-12-09 | Heavner George A. | IL-13 mutein proteins, antibodies, compositions, methods and uses |
| JP2008526889A (ja) | 2005-01-10 | 2008-07-24 | リサーチ ディベロップメント ファウンデーション | 癌治療のための標的化キメラ分子 |
| AU2006347606B2 (en) | 2005-09-09 | 2012-10-11 | Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods and compositions for inhibiting cell death or enhancing cell proliferation |
| US20070160658A1 (en) | 2005-10-20 | 2007-07-12 | The Penn State Research Foundation | Delivery system for diagnostic and therapeutic agents |
| CA2654292C (en) | 2006-06-07 | 2022-01-11 | Genzyme Corporation | Gene therapy for motor neuron disorders |
| WO2008101671A2 (en) | 2007-02-19 | 2008-08-28 | Apogenix Gmbh | Il-4 fc fusion proteins |
| CA2697529A1 (en) | 2007-08-24 | 2009-03-05 | Regents Of The University Of Minnesota | Receptor-targeting reagents |
| JP5997443B2 (ja) | 2008-05-16 | 2016-09-28 | バイエル・ヘルスケア・エルエルシーＢａｙｅｒ ＨｅａｌｔｈＣａｒｅ ＬＬＣ | 標的化凝固因子およびそれを使用する方法 |
| EP2352526A1 (en) | 2008-09-19 | 2011-08-10 | Protox Therapeutics Inc. | Treating cancer stem cells using targeted cargo proteins |
| US20100183545A1 (en) | 2008-10-14 | 2010-07-22 | The United States Of America, As Represented By The Secretary, | Targeted cargo protein combination therapy |
| JP2010154842A (ja) | 2008-12-03 | 2010-07-15 | Koji Kawakami | Ｅｇｆｒを標的にした新規抗がんキメラペプチド |
| US20110023680A1 (en) | 2009-07-30 | 2011-02-03 | Kuo-Chung Wang | Pcb cutter module with detachable cutters |
| TWI397428B (zh) | 2009-12-29 | 2013-06-01 | Ind Tech Res Inst | 標的第四介白素受體之傳輸系統 |
| WO2011106779A1 (en) * | 2010-02-26 | 2011-09-01 | Aerovance Inc. | Use of modified il-4 mutien receptor antagonists to treat dermatitis |
| JP5734951B2 (ja) | 2010-03-03 | 2015-06-17 | シャープ株式会社 | 表示装置およびその駆動方法、ならびに液晶表示装置 |
| EP2629788A4 (en) | 2010-10-22 | 2014-03-19 | Protox Therapeutics Corp | USE OF HUMAN SERUM ALBUMIN TO REDUCE THE ANTIGENICITY OF THERAPEUTIC PROTEINS |
| WO2012088446A1 (en) | 2010-12-22 | 2012-06-28 | Board Of Trustees Of The Leland Stanford Junior University | Superagonists and antagonists of interleukin-2 |
| WO2012139112A1 (en) | 2011-04-08 | 2012-10-11 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Ubiquitin fusions for improving the efficacy of cytosolic acting targeted toxins |
| US10548921B2 (en) | 2011-04-08 | 2020-02-04 | Baylor College Of Medicine | Reversing the effects of the tumor microenvironment using chimeric cytokine receptors |
| EP2850093B1 (en) | 2012-01-27 | 2019-01-09 | The Board of Trustees of the Leland Stanford Junior University | Therapeutic il-13 polypeptides |
| US10781242B2 (en) | 2013-09-24 | 2020-09-22 | Medicenna Therapeutics Inc. | Interleukin-2 fusion proteins and uses thereof |
| EP3049526B1 (en) | 2013-09-24 | 2021-02-24 | Medicenna Therapeutics, Inc. | Interleukin-4 receptor-binding fusion proteins and uses thereof |
| US9975942B2 (en) | 2013-11-11 | 2018-05-22 | Wake Forest University Health Services | EPHA3 And multi-valent targeting of tumors |
| KR102480433B1 (ko) | 2014-02-07 | 2022-12-21 | 맥마스터 유니버시티 | 3기능성 t 세포-항원 커플러 및 이의 제조 방법 및 용도 |
| JP2017527310A (ja) | 2014-09-09 | 2017-09-21 | ユーナム・セラピューティクスＵｎｕｍ Ｔｈｅｒａｐｅｕｔｉｃｓ | キメラ受容体および免疫療法におけるその使用 |
| AU2015317351B2 (en) | 2014-09-19 | 2020-07-02 | City Of Hope | Costimulatory chimeric antigen receptor T cells targeting IL3Ra2 |
| SG11201704519YA (en) | 2014-12-02 | 2017-07-28 | Roger Williams Hospital | Methods and compositons for treating cancer |
| MA43859A (fr) | 2016-01-11 | 2018-11-21 | Novartis Ag | Anticorps monoclonaux humainisés immunostimulants dirigés contre l'interleukine -2 humaine, et leurs protéines de fusion |
| WO2018112266A1 (en) | 2016-12-14 | 2018-06-21 | The Board Of Trustees Of The Leland Stanford Junior University | Il-13 superkine: immune cell targeting constructs and methods of use thereof |
| WO2019051204A1 (en) | 2017-09-08 | 2019-03-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | SYNERGISTIC COMBINATION OF IL4, INTERFERON GAMMA AND INTERFERON ALPHA RECEPTOR AGENTS FOR USE IN THE TREATMENT OF OVARIAN CANCER |
| EP3694558B1 (en) | 2017-10-10 | 2024-04-10 | Medicenna Therapeutics Inc. | Il-4-fusion formulations for treatment of central nervous system (cns) tumors |
| CA3129200A1 (en) | 2019-02-07 | 2020-08-13 | Medicenna Therapeutics, Inc. | Il-4r as a biomarker in cancer |
| CN116390744A (zh) | 2020-06-24 | 2023-07-04 | 梅迪塞纳医疗股份有限公司 | 双功能性超级因子及其用途 |
-
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- 2013-08-08 CN CN201910717548.0A patent/CN110615835A/zh active Pending
- 2013-08-08 EP EP13852778.3A patent/EP2882449B1/en active Active
- 2013-08-08 US US14/419,873 patent/US9738696B2/en active Active
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- 2013-08-08 IN IN329KON2015 patent/IN2015KN00329A/en unknown
- 2013-08-08 CN CN201380047839.4A patent/CN104619334A/zh active Pending
- 2013-08-08 WO PCT/US2013/054164 patent/WO2014074186A2/en not_active Ceased
-
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- 2017-07-27 US US15/662,180 patent/US10738096B2/en active Active
-
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- 2018-06-22 JP JP2018118931A patent/JP2018161143A/ja active Pending
-
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- 2020-08-07 US US16/988,460 patent/US12187771B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6335426B1 (en) * | 1996-06-14 | 2002-01-01 | Bayer Corporation | T-cell selective interleukin-4 agonists |
Non-Patent Citations (2)
| Title |
|---|
| BATES D.L.等: "3QB7：Interleukin-4 mutant RGA bound to cytokine receptor common gamma", 《PCSB PDB》 * |
| REMI CREUSOT等: "Engineering cell-type selective immune responses using mechanism-based designer IL-4 cytokines", 《THE JOURNAL OF IMMUNOLOGY》 * |
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| JP2015525574A (ja) | 2015-09-07 |
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| WO2014074186A2 (en) | 2014-05-15 |
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| US12187771B2 (en) | 2025-01-07 |
| EP2882449A2 (en) | 2015-06-17 |
| CN104619334A (zh) | 2015-05-13 |
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