CA2800173C - Bi-specific fusion proteins - Google Patents
Bi-specific fusion proteins Download PDFInfo
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- CA2800173C CA2800173C CA2800173A CA2800173A CA2800173C CA 2800173 C CA2800173 C CA 2800173C CA 2800173 A CA2800173 A CA 2800173A CA 2800173 A CA2800173 A CA 2800173A CA 2800173 C CA2800173 C CA 2800173C
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
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| US61/347,040 | 2010-05-21 | ||
| PCT/US2011/037459 WO2011146902A1 (en) | 2010-05-21 | 2011-05-20 | Bi-specific fusion proteins |
| US13/112,907 | 2011-05-20 | ||
| US13/068,808 US9238080B2 (en) | 2010-05-21 | 2011-05-20 | Bi-specific fusion proteins |
| US13/112,907 US8691771B2 (en) | 2010-05-21 | 2011-05-20 | Bi-specific fusion proteins for tissue repair |
| US13/068,808 | 2011-05-20 |
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| CA2800173A1 CA2800173A1 (en) | 2011-11-24 |
| CA2800173C true CA2800173C (en) | 2019-05-14 |
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| CA2800173A Active CA2800173C (en) | 2010-05-21 | 2011-05-20 | Bi-specific fusion proteins |
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| CA (1) | CA2800173C (enExample) |
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Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102282168A (zh) * | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| KR101722961B1 (ko) | 2009-02-11 | 2017-04-04 | 알부메딕스 에이/에스 | 알부민 변이체 및 접합체 |
| MX2012004793A (es) | 2009-10-30 | 2012-07-20 | Novozymes Biopharma Dk As | Variantes de albumina. |
| AU2011218294A1 (en) | 2010-02-16 | 2012-08-30 | Medimmune, Llc | HSA-related compositions and methods of use |
| JP5969458B2 (ja) | 2010-04-09 | 2016-08-17 | アルブミディクス アクティーゼルスカブ | アルブミン誘導体及び変異体 |
| JP6200806B2 (ja) * | 2010-05-21 | 2017-09-20 | メリマック ファーマシューティカルズ インコーポレーティッド | 二重特異的融合タンパク質 |
| US9045564B2 (en) | 2011-02-15 | 2015-06-02 | Medimmune, Llc | HSA-related compositions and methods of use |
| AU2012249539A1 (en) * | 2011-04-28 | 2013-11-14 | The Feinstein Institute For Medical Research | MFG-E8 and uses thereof |
| CA2830660A1 (en) | 2011-05-05 | 2012-11-08 | Novozymes Biopharma Dk A/S | Albumin variants |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對bcma之e3以及cd3的結合分子 |
| US20140315817A1 (en) | 2011-11-18 | 2014-10-23 | Eleven Biotherapeutics, Inc. | Variant serum albumin with improved half-life and other properties |
| DK2825556T3 (en) | 2012-03-16 | 2018-04-16 | Albumedix As | albumin Variants |
| CN108524919A (zh) | 2012-05-17 | 2018-09-14 | 延伸生物科学股份有限公司 | 用于改进的药物递送的载体 |
| WO2014004465A1 (en) * | 2012-06-25 | 2014-01-03 | The Brigham And Women's Hospital, Inc. | Targeted therapeutics |
| US9790264B2 (en) | 2012-06-25 | 2017-10-17 | The Brigham And Women's Hospital, Inc. | Compounds and methods for modulating pharmacokinetics |
| US20150202287A1 (en) | 2012-08-30 | 2015-07-23 | Merrimack Pharmaceuticals, Inc. | Combination therapies comprising anti-erbb3 agents |
| KR20150082422A (ko) | 2012-11-08 | 2015-07-15 | 노보자임스 바이오파마 디케이 에이/에스 | 알부민 변이체 |
| WO2014139468A1 (en) * | 2013-03-15 | 2014-09-18 | Admark Healthcare, Llc | Fusion protein molecules and method of use |
| CN106661125B (zh) | 2014-05-02 | 2021-10-01 | 动量制药公司 | 涉及工程化Fc构建体的组合物和方法 |
| WO2015198199A1 (en) * | 2014-06-23 | 2015-12-30 | Novartis Ag | Hsa-gdf-15 fusion polypeptide and use thereof. |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| CN105273087A (zh) * | 2014-07-14 | 2016-01-27 | 复旦大学 | NGF-Fc融合蛋白及其制备方法 |
| US9789197B2 (en) | 2014-10-22 | 2017-10-17 | Extend Biosciences, Inc. | RNAi vitamin D conjugates |
| WO2016065042A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Therapeutic vitamin d conjugates |
| WO2016065052A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Insulin vitamin d conjugates |
| HK1248539A1 (zh) | 2015-04-17 | 2018-10-19 | 梅里麦克制药股份有限公司 | 借助塞里班土单抗的组合治疗 |
| CN104946656B (zh) * | 2015-06-08 | 2018-08-17 | 吉林省农业科学院 | 一种人源碱性成纤维细胞生长因子、烟草叶绿体表达载体及生产方法 |
| EA039859B1 (ru) | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究(慕尼黑)公司 | Flt3及cd3抗體構築體 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究(慕尼黑)公司 | Egfrviii及cd3抗體構築體 |
| TWI796283B (zh) | 2015-07-31 | 2023-03-21 | 德商安美基研究(慕尼黑)公司 | Msln及cd3抗體構築體 |
| EP3337816B1 (en) | 2015-08-20 | 2024-02-14 | Albumedix Ltd | Albumin variants and conjugates |
| GB2542391A (en) * | 2015-09-17 | 2017-03-22 | Annexin Pharmaceuticals Ab | Process of manufacture |
| US10040840B2 (en) * | 2015-10-02 | 2018-08-07 | Silver Creek Pharmaceuticals, Inc. | Bi-specific annexin A5/IGF-1 proteins and methods of use thereof to promote regeneration and survival of tissue |
| EP3395366B1 (en) * | 2015-12-21 | 2023-11-22 | Hefei Lifeon Pharmaceutical Co., Ltd. | Drug design method, obtained drug and application thereof |
| US20190365656A1 (en) * | 2016-01-04 | 2019-12-05 | Cour Pharmaceuticals Development Company, Inc. | Particles encapsulating fusion proteins containing linked epitopes |
| LT3411404T (lt) | 2016-02-03 | 2022-12-27 | Amgen Research (Munich) Gmbh | Psma ir cd3 bispecifiniai, t ląsteles aktyvuojantys antikūno konstruktai |
| PT3411402T (pt) | 2016-02-03 | 2022-02-01 | Amgen Inc | Construtos de anticorpos biespecíficos engajadores de células t contra bcma e cd3 |
| US12391759B2 (en) | 2016-03-02 | 2025-08-19 | Momenta Pharmaceuticals, Inc. | Methods related to engineered Fc constructs |
| AU2017235450A1 (en) | 2016-03-15 | 2018-08-16 | Merrimack Pharmaceuticals, Inc. | Methods for treating ER+, HER2-, HRG+ breast cancer using combination therapies comprising an anti-ErbB3 antibody |
| KR102635635B1 (ko) * | 2016-05-23 | 2024-02-14 | 모멘타 파머슈티컬스 인코포레이티드 | 유전자 조작 Fc 작제물에 관한 조성물 및 방법 |
| CN110650748B (zh) | 2017-01-06 | 2024-01-02 | 动量制药公司 | 与经工程改造的Fc构建体相关的组合物和方法 |
| CA3069105A1 (en) * | 2017-07-03 | 2019-01-10 | Torque Therapeutics, Inc. | Polynucleotides encoding immunostimulatory fusion molecules and uses thereof |
| CA3070230A1 (en) * | 2017-07-24 | 2019-01-31 | Rutgers, The State University Of New Jersey | Phosphatidylserine targeting fusion molecules and methods for their use |
| CN107880133A (zh) * | 2017-11-04 | 2018-04-06 | 海南大学 | 促皮质素与胰岛素样生长因子1融合蛋白及其制备方法 |
| US11464803B2 (en) * | 2017-11-14 | 2022-10-11 | Arcellx, Inc. | D-domain containing polypeptides and uses thereof |
| GB201919019D0 (en) * | 2019-12-20 | 2020-02-05 | Autolus Ltd | Antigen-binding domain |
| EP4103609A1 (en) * | 2020-02-13 | 2022-12-21 | UCB Biopharma SRL | Bispecific antibodies against cd9 and cd7 |
| EP4188410B1 (en) * | 2020-07-30 | 2025-11-05 | Silver Creek Pharmaceuticals, Inc. | Chimeric proteins for use in the treatment of central nervous system disorders |
| CN115286714B (zh) * | 2020-10-27 | 2024-07-23 | 温州医科大学 | 一种以结缔组织生长因子为靶点的全人源拮抗抗体及其应用 |
| WO2022092974A1 (ko) * | 2020-10-30 | 2022-05-05 | (주)셀레메디 | 항체 유사 단백질 및 그 용도 |
| US11946055B2 (en) * | 2020-12-10 | 2024-04-02 | The Regents Of The University Of California | Protein engineering via error-prone orthogonal replication and yeast surface display |
| US20240218030A1 (en) * | 2021-05-03 | 2024-07-04 | Cellemedy Co., Ltd | Mutated ferritin protein |
| CN117659178B (zh) * | 2022-08-23 | 2024-09-24 | 东莞市朋志生物科技有限公司 | 抗甲型流感病毒抗体或其功能性片段、检测甲型流感病毒的试剂和试剂盒 |
| JP2025534350A (ja) | 2022-09-30 | 2025-10-15 | エクステンド バイオサイエンシズ インコーポレーテッド | 長時間作用型副甲状腺ホルモン |
| CN118420712A (zh) * | 2023-02-01 | 2024-08-02 | 上海健信生物医药科技有限公司 | 一种三特异性抗体技术平台及其应用 |
| CN116983407B (zh) * | 2023-08-03 | 2025-10-28 | 艾可泰科(浙江)控股有限公司 | 一种治疗膝关节炎的新一代干细胞治疗剂及其制备工艺 |
| CN117736344B (zh) * | 2024-01-30 | 2024-06-21 | 南通大学 | 具有自组装性能的重复结构单元重组蛋白ⅡAⅡB-ⅡAⅡBrQTY及应用 |
Family Cites Families (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8819826D0 (en) | 1988-08-20 | 1988-09-21 | Kabivitrum Ab | Glycosylated igf-1 |
| US6541610B1 (en) * | 1989-09-05 | 2003-04-01 | Immunex Corporation | Fusion proteins comprising tumor necrosis factor receptor |
| US5679771A (en) | 1990-02-13 | 1997-10-21 | Gropep Pty. Ltd. | Method for treating intestinal diseases |
| US6566098B1 (en) | 1990-09-14 | 2003-05-20 | The United States Of America As Represented By The Department Of Health And Human Services | DNA encoding truncated hepatocyte growth factor variants |
| ATE218889T1 (de) | 1990-11-09 | 2002-06-15 | Stephen D Gillies | Cytokine immunokonjugate |
| US5632986A (en) | 1991-05-09 | 1997-05-27 | The University Of Washington | Phospholipid-targeted thrombolytic agents |
| WO1994028133A1 (en) * | 1993-05-21 | 1994-12-08 | Amgen Inc. | Recombinant neu differentiation factors |
| EP0756494A1 (en) | 1994-05-24 | 1997-02-05 | 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 |
| CA2224859A1 (en) | 1996-04-17 | 1997-10-23 | Amitabh Gaur | 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 |
| CA2331789C (en) * | 1998-07-13 | 2013-09-10 | Board Of Regents, The University Of Texas System | Cancer treatment methods using therapeutic conjugates that bind to aminophospholipids |
| 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 |
| WO2001007059A1 (en) | 1999-07-21 | 2001-02-01 | University Of Southern California | Matrix-targeted fusion polypeptides for tissue regeneration and wound healing |
| GB2360771A (en) * | 2000-03-28 | 2001-10-03 | Antisoma Res Ltd | Compounds for targeting |
| ATE463252T1 (de) | 2000-08-29 | 2010-04-15 | Aurogen Inc | Methode zur behandlung des zentralnervensystems durch applikation von strukturanaloga von igf |
| AR032028A1 (es) | 2001-01-05 | 2003-10-22 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
| US7635680B2 (en) * | 2001-02-21 | 2009-12-22 | Alavita Pharmaceuticals, Inc. | Attenuation of reperfusion injury |
| ATE384736T1 (de) | 2001-04-30 | 2008-02-15 | Zystor Therapeutics Inc | 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 |
| US7576186B2 (en) | 2002-04-23 | 2009-08-18 | 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 |
| US7396818B2 (en) | 2003-05-19 | 2008-07-08 | Seikagaku Corporation | Sulfotransferase inhibitor |
| WO2005033134A2 (en) | 2003-09-30 | 2005-04-14 | Regeneron Pharmaceuticals, Inc. | Secreted protein therapeutics and uses thereof |
| BRPI0406606A (pt) | 2003-11-13 | 2005-12-06 | Hanmi Pharm Ind Co Ltd | Composição farmacêutica compreendendo uma região fc de imunoglobulina como um veìculo |
| US8420087B2 (en) * | 2004-01-05 | 2013-04-16 | Antisoma Research Limited | Interleukin-12 targeted to oncofoetal fibronectin |
| SI1729795T1 (sl) * | 2004-02-09 | 2016-04-29 | Human Genome Sciences, Inc. | Albuminski fuzijski proteini |
| WO2005117973A2 (en) * | 2004-05-05 | 2005-12-15 | Merrimack Pharmaceuticals, Inc. | Bispecific binding agents for modulating biological activity |
| WO2006004910A2 (en) | 2004-06-28 | 2006-01-12 | Transtarget Inc. | Improved 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 |
| JP2008510732A (ja) | 2004-08-20 | 2008-04-10 | ザ・ボード・オブ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・テキサス・システム | 心臓組織の損傷を処置、予防、阻害、または緩和する方法 |
| EP1812082B1 (en) | 2004-10-21 | 2013-08-14 | IGF Oncology, LLC | Toxins and radionuclides coupled to IGF-1 receptor ligands for the treatment of cancer |
| EP2289535B8 (en) * | 2004-12-21 | 2018-08-08 | MUSC Foundation for Research Development | Compositions and methods for promoting wound healing and tissue regeneration |
| WO2006074390A2 (en) | 2005-01-07 | 2006-07-13 | Regeneron Pharmaceuticals, Inc. | Methods of treating obesity with combination therapeautics of igf-i fusion polypeptides |
| JP2008526979A (ja) * | 2005-01-14 | 2008-07-24 | サイトジェン コーポレーション | 抗psma抗体による併用癌治療法 |
| DK1853631T3 (en) * | 2005-01-24 | 2016-03-29 | Univ Texas | Fc-FUSION CONSTRUCTIONS BINDING TO PHOSPHATIDYLSERINE AND THERAPEUTIC APPLICATION THEREOF |
| 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 |
| EP1890722A2 (en) * | 2005-05-27 | 2008-02-27 | Five Prime Therapeutics, Inc. | Methods of and compositions for stimulation of glucose uptake into muscle cells and treatment of diseases |
| KR20080071119A (ko) | 2005-08-12 | 2008-08-01 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 알부민 융합 단백질 |
| 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 |
| US8067357B2 (en) | 2005-12-12 | 2011-11-29 | Mosamedix B.V. | Annexin derivatives suitable for pretargeting in therapy and diagnosis |
| US7776816B2 (en) | 2006-01-20 | 2010-08-17 | Board Of Regents, The University Of Texas System | Preserving hypoxic tissue |
| AU2007212147A1 (en) * | 2006-02-03 | 2007-08-16 | Medimmune, Llc | Protein formulations |
| JP2009526857A (ja) | 2006-02-15 | 2009-07-23 | イムクローン・リミテッド・ライアビリティ・カンパニー | 機能性抗体 |
| US7951918B2 (en) * | 2006-03-17 | 2011-05-31 | Biogen Idec Ma Inc. | Stabilized polypeptide compositions |
| 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 |
| SE0700218L (sv) | 2007-01-23 | 2008-02-26 | Teknikbolaget K Samuelsson Ab | Sprutmunstycksanordning för brandsläckningssystem |
| US8003761B2 (en) | 2007-01-23 | 2011-08-23 | Hoffmann-La Roche Inc. | Cancerous disease modifying antibodies |
| US11535673B2 (en) | 2007-04-05 | 2022-12-27 | President and Fellows of Harvard CoHege | Chimeric activators: quantitatively designed protein therapeutics and uses thereof |
| US20110045007A1 (en) | 2007-05-31 | 2011-02-24 | Genmab A/S | Fusion or linked proteins with extended half life |
| US8889140B2 (en) | 2007-05-31 | 2014-11-18 | Transtarget, Inc. | Compositions and methods for tissue repair |
| DE602008005596D1 (de) | 2007-06-21 | 2011-04-28 | Univ Muenchen Tech | Biologisch aktive proteine mit erhöhter in-vivo- und/oder in-vitro-stabilität |
| WO2009030720A2 (en) | 2007-09-06 | 2009-03-12 | Novozymes Biopharma Dk A/S | Process for producing a recombinant protein |
| MX2010011145A (es) | 2008-04-11 | 2011-04-11 | Merrimack Pharmaceuticals Inc | Enlazadores de la albumina de suero humana y conjugados de la misma. |
| CN102282168A (zh) | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| EP2391630A2 (en) | 2009-01-31 | 2011-12-07 | IGF Oncology, LLC | Anti-cancer protein-platinum conjugates |
| WO2011011071A2 (en) | 2009-07-22 | 2011-01-27 | Ipsen Pharma S.A.S. | Analogues of insulin-like growth factor-1 (igf-1) |
| JP5571186B2 (ja) | 2009-07-22 | 2014-08-13 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | 59位にアミノ酸置換を有するインスリン様増殖因子−1(igf−1)の類似体 |
| CA2777242A1 (en) | 2009-10-14 | 2011-04-21 | Merrimack Pharmaceuticals, Inc. | Bispecific binding agents targeting igf-1r and erbb3 signalling and uses thereof |
| MX2012004793A (es) | 2009-10-30 | 2012-07-20 | Novozymes Biopharma Dk As | Variantes de albumina. |
| JP6200806B2 (ja) | 2010-05-21 | 2017-09-20 | メリマック ファーマシューティカルズ インコーポレーティッド | 二重特異的融合タンパク質 |
| 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 |
| CN104011070A (zh) | 2011-12-15 | 2014-08-27 | 爱德迪安(北京)生物技术有限公司 | 具有降血糖作用的化合物、组合物及其用途 |
| CN108383902A (zh) | 2012-09-26 | 2018-08-10 | 印第安纳大学研究及科技有限公司 | 胰岛素类似物二聚体 |
| BR112015024758A2 (pt) | 2013-03-29 | 2017-10-24 | Merrimack Pharmaceuticals Inc | proteínas de fusão de ligação à cartilagem |
| 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 |
| US10040840B2 (en) * | 2015-10-02 | 2018-08-07 | Silver Creek Pharmaceuticals, Inc. | Bi-specific annexin A5/IGF-1 proteins and methods of use thereof to promote regeneration and survival of tissue |
| US11290711B2 (en) | 2018-10-06 | 2022-03-29 | Mediatek Inc. | Method and apparatus of shared merge candidate list region for video coding |
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