ES2863278T3 - Proteínas terapéuticas biespecíficas para la reparación de tejidos - Google Patents
Proteínas terapéuticas biespecíficas para la reparación de tejidos Download PDFInfo
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- ES2863278T3 ES2863278T3 ES16852701T ES16852701T ES2863278T3 ES 2863278 T3 ES2863278 T3 ES 2863278T3 ES 16852701 T ES16852701 T ES 16852701T ES 16852701 T ES16852701 T ES 16852701T ES 2863278 T3 ES2863278 T3 ES 2863278T3
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Landscapes
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562236169P | 2015-10-02 | 2015-10-02 | |
| US201562237889P | 2015-10-06 | 2015-10-06 | |
| US201662322910P | 2016-04-15 | 2016-04-15 | |
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|---|---|---|---|---|
| ES2674567T3 (es) * | 2010-05-21 | 2018-07-02 | Merrimack Pharmaceuticals, Inc. | Proteínas de fusión biespecíficas |
| EP3355907B1 (en) | 2015-10-02 | 2021-01-20 | Silver Creek Pharmaceuticals, Inc. | Bi-specific therapeutic proteins for tissue repair |
| CN111763680A (zh) * | 2019-05-22 | 2020-10-13 | 杭州杰迪生物科技有限公司 | 一种人胰岛素样生长因子-i或其类似物的制备方法、编码基因、表达载体及宿主细胞 |
| JP7355326B2 (ja) * | 2019-08-05 | 2023-10-03 | デンカ株式会社 | 経粘膜投与薬剤 |
| CN118772293A (zh) * | 2019-09-06 | 2024-10-15 | 诺华股份有限公司 | 治疗性融合蛋白 |
| CN112584507B (zh) | 2019-09-30 | 2022-05-17 | 华为技术有限公司 | 一种数据处理方法、装置及存储介质 |
| CN115379850A (zh) | 2019-12-24 | 2022-11-22 | 裘美娜治疗公司 | 再生性多肽及其用途 |
| CN111195350A (zh) * | 2020-01-15 | 2020-05-26 | 重庆大学 | IGF1和IGF1Ec24联合在制备促进组织修复与再生的药物中的应用 |
| JP2023537318A (ja) * | 2020-07-30 | 2023-08-31 | シルバー・クリーク・ファーマシューティカルズ・インコーポレイテッド | 中枢神経系障害の処置のためのキメラタンパク質および使用方法 |
| EP4355765A2 (en) * | 2021-06-14 | 2024-04-24 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Mutated annexin a5 polypeptides and uses thereof for therapeutic purposes |
| WO2022271466A1 (en) | 2021-06-21 | 2022-12-29 | Juvena Therapeutics, Inc. | Regenerative polypeptides and uses thereof |
| WO2023278786A1 (en) * | 2021-06-30 | 2023-01-05 | Silver Creek Pharmaceuticals, Inc. | Chimeric proteins for targeted delivery of growth factors to the glomerulus |
| US20250144175A1 (en) * | 2022-02-15 | 2025-05-08 | Silver Creek Pharmaceuticals, Inc. | Chimeric proteins for treatment of acute radiation syndrome |
| EP4652192A1 (en) * | 2024-03-25 | 2025-11-26 | Cavalry Biosciences, Inc. | Igf-1-related compositions and uses of the same |
Family Cites Families (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL269416A (cg-RX-API-DMAC7.html) | 1960-09-21 | |||
| GB8819826D0 (en) | 1988-08-20 | 1988-09-21 | Kabivitrum Ab | Glycosylated igf-1 |
| US5679771A (en) | 1990-02-13 | 1997-10-21 | Gropep Pty. Ltd. | Method for treating intestinal diseases |
| DE69133036T2 (de) | 1990-11-09 | 2003-02-06 | Stephen D. Gillies | Cytokine immunokonjugate |
| US5632986A (en) | 1991-05-09 | 1997-05-27 | The University Of Washington | Phospholipid-targeted thrombolytic agents |
| US5444045A (en) * | 1992-09-17 | 1995-08-22 | Gropep, Pty. Ltd. | Method of administering IGF-1, IGF-2, and analogs thereof to birds |
| WO1995019791A1 (en) * | 1994-01-24 | 1995-07-27 | Neorx Corporation | Radiolabeled annexins |
| AU2601895A (en) | 1994-05-24 | 1995-12-18 | Amgen Boulder Inc. | Modified insulin-like growth factors |
| US5780052A (en) | 1995-04-24 | 1998-07-14 | Northeastern University | Compositions and methods useful for inhibiting cell death and for delivering an agent into a cell |
| AU2676297A (en) | 1996-04-17 | 1997-11-07 | Neurocrine Biosciences, Inc. | Ligand inhibitors of insulin-like growth factor binding proteins and methods of use therefor |
| US6121416A (en) | 1997-04-04 | 2000-09-19 | Genentech, Inc. | Insulin-like growth factor agonist molecules |
| ES2188202T3 (es) | 1998-07-13 | 2003-06-16 | Univ Texas | Metodos de tratamiento para el cancer usando conjugados terapeuticos que se enlazan con aminofosfolipidos. |
| US6387663B1 (en) | 1998-07-31 | 2002-05-14 | University Of Southern California | Targeting pharmaceutical agents to injured tissues |
| AUPP785098A0 (en) | 1998-12-21 | 1999-01-21 | Victor Chang Cardiac Research Institute, The | Treatment of heart disease |
| PT1141015E (pt) | 1999-01-06 | 2009-10-13 | Genentech Inc | Variantes mutantes do factor de crescimento do tipo insulina (igf)i |
| US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| DE60025830T2 (de) | 1999-07-21 | 2006-11-02 | University Of Southern California, Los Angeles | Fusions-polypeptide zur gewebegeneration und wundheilung zur gezielten matrixanwendung |
| JP2001251104A (ja) | 2000-03-03 | 2001-09-14 | Murata Mfg Co Ltd | 非可逆回路素子及び通信機装置 |
| EP1313499B1 (en) | 2000-08-29 | 2010-04-07 | Aurogen Incorporated | Method for treating the central nervous system by administration of igf structural analogs |
| ES2344592T3 (es) | 2001-01-05 | 2010-09-01 | Pfizer Inc. | Anticuerpos frente al receptor del factor de crecimiento similar a la insulina i. |
| US7635680B2 (en) | 2001-02-21 | 2009-12-22 | Alavita Pharmaceuticals, Inc. | Attenuation of reperfusion injury |
| DE60224816T2 (de) | 2001-04-30 | 2009-01-22 | ZyStor Therapeutics, Inc., Milwaukee | Subzelluläres targeting von therapeutischen proteinen |
| US7049286B2 (en) | 2001-08-30 | 2006-05-23 | Diatos, S.A. | Insulin conjugates and methods of use thereof |
| AU2008200706B2 (en) | 2001-10-16 | 2010-05-27 | Biomarin Pharmaceutical Inc. | Methods and compositions for targeting underglycosylated proteins across the blood brain barrier |
| US20030072761A1 (en) | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| AU2003241313A1 (en) | 2002-04-23 | 2003-11-10 | Roger Williams Hospital | Compositions and methods for stem cell delivery |
| WO2003103577A2 (en) * | 2002-06-06 | 2003-12-18 | Tze Chein Wun | Novel recombinant anticoagulant proteins |
| US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| US20040213738A1 (en) | 2003-03-31 | 2004-10-28 | Susan Croll-Kalish | CIRL3-Like proteins, nucleic acids, and methods of modulating CIRL3-L-mediated activity |
| US7355018B2 (en) | 2003-09-30 | 2008-04-08 | Regeneron Pharmaceuticals, Inc. | Modified IGF1 polypeptides with increased stability and potency |
| RU2356909C2 (ru) * | 2003-11-13 | 2009-05-27 | Ханми Фарм. Инд. Ко., Лтд. | Белковый комплекс, полученный с использованием фрагмента иммуноглобулина, и способ получения такого комплекса |
| CN1997382A (zh) | 2004-05-05 | 2007-07-11 | 梅里麦克制药股份有限公司 | 调节生物活性的双特异性结合剂 |
| US20060018897A1 (en) | 2004-06-28 | 2006-01-26 | Transtarget Inc. | Bispecific antibodies |
| US7511016B2 (en) | 2004-07-07 | 2009-03-31 | Mosamedix B.V. | Annexins, derivatives thereof, and annexin-cys variants, as well as therapeutic and diagnostic uses thereof |
| US7531318B2 (en) | 2004-08-20 | 2009-05-12 | Board Of Regents, The University Of Texas System | Screening of agents for activity against ischemic myocardial insults |
| EP1784204A4 (en) | 2004-08-20 | 2008-11-05 | Univ Texas | PROCESS FOR PREPARING, PREVENTING, INHIBITING OR REDUCING DAMAGE TO HEART TISSUE |
| CA2582552A1 (en) | 2004-10-21 | 2006-05-04 | Igf Oncology, Llc | Toxins and radionuclides coupled to igf-1 receptor ligands for treatment of cancer |
| ATE517120T1 (de) | 2005-01-07 | 2011-08-15 | Regeneron Pharma | Igf-1 fusion polypeptide und deren therapeutische verwendung |
| EP1841467A4 (en) | 2005-01-14 | 2009-01-28 | Cytogen Corp | COMBINATION CANCER THERAPY WITH ANTI-PSMA ANTIBODIES |
| NZ556065A (en) | 2005-01-24 | 2009-04-30 | Univ Texas | FC-fusion constructs binding to phosphatidylserine and their therapeutic use |
| WO2006091209A2 (en) | 2005-02-23 | 2006-08-31 | Merrimack Pharmaceuticals, Inc. | Bispecific binding agents for modulating biological activity |
| US7521211B2 (en) | 2005-04-05 | 2009-04-21 | Regeneron Pharmaceuticals, Inc | IGF-1 and IGF-2 chimeric polypeptides and therapeutic uses thereof |
| JP2008545715A (ja) | 2005-05-27 | 2008-12-18 | ファイブ プライム セラピューティクス， インコーポレイテッド | 筋細胞へのグルコース取り込みを刺激する方法および組成物ならびに疾患を治療する方法および組成物 |
| BRPI0614761A2 (pt) | 2005-08-12 | 2009-05-19 | Human Genome Sciences Inc | proteìnas de fusão de albumina |
| US7855279B2 (en) | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| WO2007044887A2 (en) | 2005-10-11 | 2007-04-19 | Transtarget, Inc. | Method for producing a population of homogenous tetravalent bispecific antibodies |
| ES2617002T3 (es) | 2005-12-12 | 2017-06-15 | Mosamedix B.V. | Derivados de anexina adecuados para la prefocalización en terapia y diagnóstico |
| US7776816B2 (en) | 2006-01-20 | 2010-08-17 | Board Of Regents, The University Of Texas System | Preserving hypoxic tissue |
| US20080071063A1 (en) | 2006-02-03 | 2008-03-20 | Medimmune, Inc. | Protein Formulations |
| CA2646508A1 (en) | 2006-03-17 | 2007-09-27 | Biogen Idec Ma Inc. | Stabilized polypeptide compositions |
| PT2032155E (pt) | 2006-06-09 | 2015-04-07 | Novartis Ag | Polipéptidos estabilizados do factor de crescimento tipo insulina |
| US9187517B2 (en) | 2006-11-13 | 2015-11-17 | The Brigham And Women's Hospital, Inc. | Methods of promoting cardiac repair using growth factors fused to heparin binding sequences |
| US8003761B2 (en) | 2007-01-23 | 2011-08-23 | Hoffmann-La Roche Inc. | Cancerous disease modifying antibodies |
| SE530073C2 (sv) | 2007-01-23 | 2008-02-26 | Teknikbolaget K Samuelsson Ab | Sprutmunstycksanordning för brandsläckningssystem |
| WO2008124086A2 (en) | 2007-04-05 | 2008-10-16 | President And Fellows Of Harvard College | Chimeric activators: quantitatively designed protein therapeutics and uses thereof |
| WO2008151005A2 (en) | 2007-05-31 | 2008-12-11 | Transtarget, Inc. | Compositions and methods for tissue repair |
| US20110045007A1 (en) | 2007-05-31 | 2011-02-24 | Genmab A/S | Fusion or linked proteins with extended half life |
| EA021222B8 (ru) | 2007-06-21 | 2015-11-30 | ИксЭль-ПРОТЕИН ГМБХ | Биологически активные белки, имеющие повышенную стабильность in vivo и/или in vitro |
| WO2009030720A2 (en) | 2007-09-06 | 2009-03-12 | Novozymes Biopharma Dk A/S | Process for producing a recombinant protein |
| EP2860260A1 (en) | 2008-04-11 | 2015-04-15 | Merrimack Pharmaceuticals, Inc. | Human serum albumin linkers and conjugates thereof |
| KR20110112301A (ko) | 2008-11-18 | 2011-10-12 | 메리맥 파마슈티컬즈, 인크. | 인간 혈청 알부민 링커 및 그 콘쥬게이트 |
| JP2012516330A (ja) * | 2009-01-31 | 2012-07-19 | アイジーエフ オンコロジー エルエルシー | 抗癌タンパク質−白金コンジュゲート |
| US8759299B2 (en) | 2009-07-22 | 2014-06-24 | Ipsen Pharma S.A.S. | Analogues of insulin-like growth factor-1 (IGF-1) having amino acid substitution at position 59 |
| WO2011011071A2 (en) | 2009-07-22 | 2011-01-27 | Ipsen Pharma S.A.S. | Analogues of insulin-like growth factor-1 (igf-1) |
| WO2011047180A1 (en) | 2009-10-14 | 2011-04-21 | Merrimack Pharmaceuticals, Inc. | Bispecific binding agents targeting igf-1r and erbb3 signalling and uses thereof |
| CN102741280B (zh) | 2009-10-30 | 2015-12-02 | 诺维信生物制药丹麦公司 | 白蛋白变体 |
| ES2674567T3 (es) | 2010-05-21 | 2018-07-02 | Merrimack Pharmaceuticals, Inc. | Proteínas de fusión biespecíficas |
| CN103354835B (zh) | 2010-12-08 | 2016-03-02 | 韦尔赛特公司 | 抑制人多能干细胞生长的试剂和方法 |
| US20140315817A1 (en) | 2011-11-18 | 2014-10-23 | Eleven Biotherapeutics, Inc. | Variant serum albumin with improved half-life and other properties |
| WO2013086785A1 (zh) | 2011-12-15 | 2013-06-20 | Qin Shulin | 具有降血糖作用的化合物、组合物及其用途 |
| CA2886228A1 (en) | 2012-09-26 | 2014-04-03 | Indiana University Research And Technology Corporation | Insulin analog dimers |
| MX2015013803A (es) | 2013-03-29 | 2016-02-16 | Merrimack Pharmaceuticals Inc | Proteina de fusion de enlace al cartilago. |
| CA2936675C (en) | 2014-01-12 | 2023-06-27 | Igf Oncology, Llc | Fusion proteins containing insulin-like growth factor-1 and epidermal growth factor and variants thereof and uses thereof |
| EP3355907B1 (en) | 2015-10-02 | 2021-01-20 | Silver Creek Pharmaceuticals, Inc. | Bi-specific therapeutic proteins for tissue repair |
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