JP2016512255A5 - - Google Patents
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- JP2016512255A5 JP2016512255A5 JP2016500671A JP2016500671A JP2016512255A5 JP 2016512255 A5 JP2016512255 A5 JP 2016512255A5 JP 2016500671 A JP2016500671 A JP 2016500671A JP 2016500671 A JP2016500671 A JP 2016500671A JP 2016512255 A5 JP2016512255 A5 JP 2016512255A5
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- seq
- glucagon
- group
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| JP6657230B2 (ja) | 2014-09-24 | 2020-03-04 | インディアナ ユニヴァーシティ リサーチ アンド テクノロジー コーポレイション | インクレチン−インスリンコンジュゲート |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
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| EP3341403B1 (en) | 2015-08-25 | 2022-01-05 | Novo Nordisk A/S | Novel insulin derivatives and the medical uses hereof |
| EP3377521A4 (en) * | 2015-10-27 | 2019-05-01 | Merck Sharp & Dohme Corp. | LONG-ACTING CO AGONISTS OF GLUCAGON AND GLP-1 RECEPTORS |
| WO2017160669A1 (en) * | 2016-03-18 | 2017-09-21 | Merck Sharp & Dohme Corp. | Insulin-incretin conjugates |
| WO2017189342A1 (en) * | 2016-04-26 | 2017-11-02 | Merck Sharp & Dohme Corp. | Insulin dimer-incretin conjugates |
| IL264330B2 (en) | 2016-07-22 | 2024-05-01 | Univ Utah Res Found | An insulin analog, pharmaceutical composition comprising it and its uses |
| CN110446496A (zh) * | 2017-02-03 | 2019-11-12 | 范德比尔特大学 | 用于治疗糖尿病的系统、组合物和方法 |
| EP3624828B1 (en) * | 2017-05-18 | 2024-08-07 | Merck Sharp & Dohme LLC | Pharmaceutical formulation comprising incretin-insulin conjugates |
| CA3071419A1 (en) | 2017-07-28 | 2019-01-31 | The Trustees Of Princeton University | Fusion tags for recombinant protein expression |
| BR112020002364A2 (pt) | 2017-08-17 | 2020-09-01 | Novo Nordisk A/S | derivado de insulina, produto intermediário, uso de um derivado de insulina, e, métodos para o tratamento ou prevenção de diabetes, diabetes do tipo 1, diabetes do tipo 2, tolerância à glicose comprometida, hiperglicemia, dislipidemia, obesidade, síndrome metabólica, hipertensão, distúrbios cognitivos, aterosclerose, infarto do miocárdio, acidente vascular cerebral, distúrbios cardiovasculares, doença cardíaca coronariana, síndrome intestinal inflamatória, dispepsia, hipotensão ou úlceras gástricas, e para determinar a seletividade de um composto de insulina |
| CN112074531B (zh) | 2018-05-04 | 2025-04-15 | 诺和诺德股份有限公司 | Gip衍生物及其用途 |
| ES2929416T3 (es) * | 2018-06-21 | 2022-11-29 | Novo Nordisk As | Nuevos compuestos para el tratamiento de la obesidad |
| CA3122636A1 (en) | 2018-12-11 | 2020-06-18 | Sanofi | Insulin analogs having reduced insulin receptor binding affinity |
| US12435116B2 (en) | 2019-10-16 | 2025-10-07 | Clarence Hurt | Compounds, compositions, methods, and uses for treating insulin resistance, type 2 diabetes and metabolic syndrome |
| MY208364A (en) | 2019-12-11 | 2025-05-01 | Novo Nordisk As | Novel insulin analogues and uses thereof |
| WO2022017309A1 (zh) * | 2020-07-24 | 2022-01-27 | 江苏晟斯生物制药有限公司 | 胰岛素-Fc融合蛋白及其应用 |
| WO2022094146A1 (en) | 2020-10-28 | 2022-05-05 | The Trustees Of Princeton University | Methods of converting precursor proteins to mature proteins using kex2 proteases |
| CN117242098A (zh) * | 2021-02-09 | 2023-12-15 | 印地安纳大学理事会 | 构象受限的胰高血糖素类似物及其在胰高血糖素-单链胰岛素融合蛋白中的用途 |
Family Cites Families (132)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3740385A (en) | 1970-05-07 | 1973-06-19 | M Ondetti | N-terminal derivatives of secretin |
| US4450150A (en) | 1973-05-17 | 1984-05-22 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery depots, and method for preparing and using the same |
| US4275152A (en) | 1977-02-03 | 1981-06-23 | Eastman Kodak Company | Hydrolysis of protein-bound cholesterol esters |
| DK119785D0 (da) | 1985-03-15 | 1985-03-15 | Nordisk Gentofte | Insulinpraeparat |
| PH25772A (en) | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| PT83613B (en) | 1985-10-28 | 1988-11-21 | Lilly Co Eli | Process for the selective chemical removal of a protein amino-terminal residue |
| US4741897A (en) | 1986-07-08 | 1988-05-03 | Baxter Travenol | Thyroxine analogs and reagents for thyroid hormone assays |
| US4876242A (en) | 1987-09-21 | 1989-10-24 | Merck & Co., Inc. | Human insulin-like growth factor analoges with reduced binding to serum carrier proteins and their production in yeast |
| GB8728561D0 (en) | 1987-12-07 | 1988-01-13 | Glaxo Group Ltd | Chemical compounds |
| US5514646A (en) | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
| JPH04504416A (ja) | 1989-02-17 | 1992-08-06 | コセルコ・ミモトープス・ピィ・ティ・ワイ.エル・ティ・ディ. | ペプチドの使用方法と合成方法 |
| US6225449B1 (en) | 1991-10-04 | 2001-05-01 | Washington University | Hormone analogs with multiple CTP extensions |
| ATE120762T1 (de) | 1989-04-20 | 1995-04-15 | Sinai School Medicine | Hepatospezifische insulin-analoga. |
| US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| US5510459A (en) | 1991-01-17 | 1996-04-23 | Zymogenetics, Inc. | Glucagon antagonists |
| US5268453A (en) | 1991-08-08 | 1993-12-07 | Scios Inc. | Tissue-selective insulin analogs |
| CA2157767A1 (en) | 1993-03-09 | 1994-09-15 | Elaine M. Brate | Genetically engineered enzymes and their conjugates for diagnostic assays |
| US5359030A (en) | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
| US5480867A (en) | 1993-12-29 | 1996-01-02 | The Rockefeller University | Glucagon analogs with serine replacements |
| US5512549A (en) | 1994-10-18 | 1996-04-30 | Eli Lilly And Company | Glucagon-like insulinotropic peptide analogs, compositions, and methods of use |
| US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
| US6476290B1 (en) | 1995-04-19 | 2002-11-05 | Dalhousie University | Transgenic tilapia comprising a humanized insulin gene |
| AU5724996A (en) | 1995-05-05 | 1996-11-21 | Eli Lilly And Company | Single chain insulin with high bioactivity |
| US6180767B1 (en) | 1996-01-11 | 2001-01-30 | Thomas Jefferson University | Peptide nucleic acid conjugates |
| CA2265454A1 (en) | 1996-09-09 | 1998-03-19 | Zealand Pharmaceuticals A/S | Peptide prodrugs containing an alpha-hydroxyacid linker |
| UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| CN1296417A (zh) | 1998-02-10 | 2001-05-23 | 卫福有限公司 | 控释制剂 |
| EP1056776A1 (en) | 1998-02-23 | 2000-12-06 | Neurocrine Biosciences, Inc. | Methods for treatment of diabetes using peptide analogues of insulin |
| EP1950224A3 (en) | 1998-03-09 | 2008-12-17 | Zealand Pharma A/S | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
| US6875741B2 (en) | 1998-09-02 | 2005-04-05 | Renuka Pillutla | Insulin and IGF-1 receptor agonists and antagonists |
| US20030236190A1 (en) | 1998-09-02 | 2003-12-25 | Renuka Pillutla | Isulin and IGF-1 receptor agonists and antagonists |
| GB2344287A (en) | 1998-12-03 | 2000-06-07 | Ferring Bv | Controlled release pharmaceutical formulation |
| DE19908041A1 (de) | 1999-02-24 | 2000-08-31 | Hoecker Hartwig | Kovalent verbrückte Insulindimere |
| PT1171465E (pt) | 1999-03-29 | 2004-12-31 | Uutech Ltd | Analogos de petido inibidor gastrico e sua utilizacao para o tratamento de diabetes |
| US6329336B1 (en) | 1999-05-17 | 2001-12-11 | Conjuchem, Inc. | Long lasting insulinotropic peptides |
| US6746853B1 (en) | 1999-05-19 | 2004-06-08 | Xencor, Inc. | Proteins with insulin-like activity useful in the treatment of diabetes |
| AUPQ661800A0 (en) | 2000-03-31 | 2000-05-04 | Metabolic Pharmaceuticals Limited | Insulin-potentiating compounds |
| US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
| JP2004503565A (ja) | 2000-06-14 | 2004-02-05 | サイトヴァックス・バイオテクノロジーズ・インコーポレーテッド | 構造特異的ペプチドを生産するためのコイルドコイル構造的骨格の使用 |
| US7449308B2 (en) | 2000-06-28 | 2008-11-11 | Glycofi, Inc. | Combinatorial DNA library for producing modified N-glycans in lower eukaryotes |
| KR100787073B1 (ko) | 2000-06-28 | 2007-12-21 | 글리코파이, 인크. | 변형된 당단백질의 제조방법 |
| BR0113178A (pt) | 2000-08-02 | 2004-04-06 | Theratechnologies Inc | Peptìdeos biológicos modificados com potência aumentada |
| AU2001284697A1 (en) | 2000-08-04 | 2002-02-18 | Dmi Biosciences, Inc. | Method of synthesizing diketopiperazines |
| ATE516820T1 (de) | 2000-09-29 | 2011-08-15 | Schering Corp | Pegyliertes interleukin 10 |
| KR100449454B1 (ko) | 2000-10-02 | 2004-09-21 | 이현철 | 단일사슬 인슐린 유도체의 유전자를 포함하는 당뇨병치료용 벡터 |
| ATE270306T1 (de) | 2000-10-02 | 2004-07-15 | Univ Yonsei Seoul | Einkettige insulinanaloge |
| KR101229995B1 (ko) | 2000-12-11 | 2013-02-06 | 씨제이 주식회사 | 생체내 에리스로포이에틴 활성이 증진된 융합단백질 |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| EP1490483B1 (en) | 2001-04-19 | 2015-06-03 | The Scripps Research Institute | In vivo incorporation of unnatural amino acids |
| AU2002327430A1 (en) | 2001-08-08 | 2003-02-24 | Genzyme Corporation | Methods for treating diabetes and other blood sugar disorders |
| CN1635900A (zh) | 2001-08-28 | 2005-07-06 | 伊莱利利公司 | Glp-1和基础胰岛素的预混合物 |
| GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| US7041646B2 (en) | 2001-10-05 | 2006-05-09 | Bayer Pharmaceuticals Corporation | Methods of treating type 2 diabetes with peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists |
| AR036711A1 (es) | 2001-10-05 | 2004-09-29 | Bayer Corp | Peptidos que actuan como agonistas del receptor del glp-1 y como antagonistas del receptor del glucagon y sus metodos de uso farmacologico |
| US7238670B2 (en) | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| EP1545460A4 (en) | 2001-12-20 | 2005-11-16 | Lilly Co Eli | INSULIN MOLECULE WITH TEMPORARY EFFECT |
| WO2003059378A2 (en) | 2001-12-29 | 2003-07-24 | Novo Nordisk A/S | Combined use of a glp-1 compound and another drug for treating dyslipidemia |
| EP1575490A4 (en) | 2002-06-04 | 2007-08-08 | Lilly Co Eli | MODIFIED ANALOGUES OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) |
| FR2842209B1 (fr) | 2002-07-09 | 2007-11-23 | Nouvelle protease aspartique dite saspase et son utilisation dans le domaine cosmetique et therapeutique | |
| DE60331455D1 (de) | 2002-10-04 | 2010-04-08 | Microchips Inc | Medizinische vorrichtung zur gesteuerten arzneimittelverabreichung sowie herzüberwachung und/oder herzstimulation |
| US7192922B2 (en) | 2002-11-19 | 2007-03-20 | Allegheny-Singer Research Institute | Method of treating left ventricular dysfunction |
| US20050059605A1 (en) | 2003-01-31 | 2005-03-17 | Krishna Peri | Chemically modified metabolites of regulatory peptides and methods of producing and using same |
| EP1626981A4 (en) | 2003-03-04 | 2006-11-22 | Biorexis Pharmaceutical Corp | PROTEINS PROTECTED AGAINST DIPEPTIDYLPEPTIDASE |
| BRPI0407936A (pt) | 2003-03-19 | 2006-02-21 | Lilly Co Eli | composto de glp-1 peguilado, método de estimular o receptor de glp-1 em um indivìduo, e, uso de composto glp-1 peguilado |
| CA2521784C (en) | 2003-04-08 | 2012-03-27 | Yeda Research And Development Co. Ltd. | Reversible pegylated drugs |
| CA2528591C (en) | 2003-06-12 | 2013-01-08 | Eli Lilly And Company | Glp-1 analog fusion proteins |
| US20050124550A1 (en) | 2003-06-18 | 2005-06-09 | Peri Krishna G. | Compounds that modulate the glucagon response and uses thereof |
| TW200526254A (en) | 2003-09-19 | 2005-08-16 | Novo Nordisk As | Novel GLP-1 derivatives |
| US20050187147A1 (en) | 2003-09-22 | 2005-08-25 | Newman Michael J. | Compositions and methods for increasing drug efficiency |
| US7364875B2 (en) | 2003-10-30 | 2008-04-29 | Cresent Innovations, Inc. | Method for producing medical and commercial grade poly-gamma-glutamic acid of high molecular weight |
| PT2332968T (pt) | 2003-11-05 | 2016-08-17 | Harvard College | Péptidos alfa-helicoidais adequados para a activação ou inibição da morte celular |
| ES2369895T3 (es) | 2003-12-03 | 2011-12-07 | Novo Nordisk A/S | Insulina monocatenaria. |
| ATE461217T1 (de) | 2003-12-18 | 2010-04-15 | Novo Nordisk As | Glp-1-verbindungen |
| US20060286129A1 (en) | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
| US20080318837A1 (en) | 2003-12-26 | 2008-12-25 | Nastech Pharmaceutical Company Inc. | Pharmaceutical Formation For Increased Epithelial Permeability of Glucose-Regulating Peptide |
| EP2417980A1 (en) * | 2004-02-11 | 2012-02-15 | Amylin Pharmaceuticals Inc. | Hybrid polypeptides with selectable properties |
| US7442682B2 (en) | 2004-10-19 | 2008-10-28 | Nitto Denko Corporation | Transepithelial delivery of peptides with incretin hormone activities |
| 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 |
| CA2589800A1 (en) * | 2004-12-02 | 2006-06-08 | Domantis Limited | Bispecific domain antibodies targeting serum albumin and glp-1 or pyy |
| US8263545B2 (en) | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| WO2006086769A2 (en) | 2005-02-11 | 2006-08-17 | Amylin Pharmaceuticals, Inc. | Gip analog and hybrid polypeptides with selectable properties |
| WO2006097521A1 (en) | 2005-03-18 | 2006-09-21 | Novo Nordisk A/S | Pegylated single-chain insulin |
| EP1863537A2 (en) | 2005-03-18 | 2007-12-12 | Novo Nordisk A/S | Dimeric peptide agonists of the glp-1 receptor |
| US7521211B2 (en) | 2005-04-05 | 2009-04-21 | Regeneron Pharmaceuticals, Inc | IGF-1 and IGF-2 chimeric polypeptides and therapeutic uses thereof |
| US20090209453A1 (en) | 2005-04-13 | 2009-08-20 | University Of Medicine And Dentistry Of New Jersey | Glycoprotein Hormone Analogs |
| WO2007056362A2 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| US8304386B2 (en) | 2006-02-03 | 2012-11-06 | Prolor Biotech, Inc. | Long-acting growth hormone and methods of producing same |
| US20090069216A1 (en) | 2006-02-21 | 2009-03-12 | Novo Nordisk A/S | Single-Chain Insulin Analogues and Pharmaceutical Formulations Thereof |
| WO2007104786A1 (en) | 2006-03-15 | 2007-09-20 | Novo Nordisk A/S | Mixtures of amylin and insulin |
| EP2004238A2 (en) | 2006-03-21 | 2008-12-24 | Amylin Pharmaceuticals, Inc. | Peptide-peptidase inhibitor conjugates and methods of using same |
| JP5256199B2 (ja) | 2006-08-07 | 2013-08-07 | テヴァ バイオファーマシューティカルズ ユーエスエー,インコーポレーティッド | アルブミン−インスリン融合タンパク質 |
| CA2660835A1 (en) | 2006-08-17 | 2008-02-21 | Amylin Pharmaceuticals, Inc. | Dpp-iv resistant gip hybrid polypeptides with selectable propperties |
| CL2007002502A1 (es) | 2006-08-31 | 2008-05-30 | Hoffmann La Roche | Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer. |
| WO2008030558A2 (en) | 2006-09-08 | 2008-03-13 | Ambrx, Inc. | Modified human plasma polypeptide or fc scaffolds and their uses |
| US20090098130A1 (en) | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
| CA2674354A1 (en) | 2007-01-05 | 2008-07-17 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility in physiological ph buffers |
| EA017849B1 (ru) | 2007-02-15 | 2013-03-29 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Соагонисты глюкагоновых/glp-1-рецепторов |
| KR20080092839A (ko) | 2007-04-12 | 2008-10-16 | 칫소가부시키가이샤 | 잉크젯용 잉크 |
| NZ580700A (en) | 2007-04-19 | 2012-01-12 | Dong A Pharm Co Ltd | A biodegradable microsphere composition suitable for the controlled release of glucose controlling peptide and formulation thereof |
| US7829664B2 (en) | 2007-06-01 | 2010-11-09 | Boehringer Ingelheim International Gmbh | Modified nucleotide sequence encoding glucagon-like peptide-1 (GLP-1), nucleic acid construct comprising same for production of glucagon-like peptide-1 (GLP-1), human cells comprising said construct and insulin-producing constructs, and methods of use thereof |
| WO2008152403A1 (en) | 2007-06-15 | 2008-12-18 | Zealand Pharma A/S | Glucagon analogues |
| EP2036539A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Stable formulations of amylin and its analogues |
| EP2036923A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Improved derivates of amylin |
| WO2009058734A1 (en) | 2007-10-30 | 2009-05-07 | Indiana University Research And Technology Corporation | Compounds exhibiting glucagon antagonist and glp-1 agonist activity |
| KR101656107B1 (ko) | 2007-11-20 | 2016-09-08 | 암브룩스, 인코포레이티드 | 변형된 인슐린 폴리펩티드 및 이의 용도 |
| JP2011511778A (ja) * | 2008-01-30 | 2011-04-14 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーション | エステルに基づいたペプチドプロドラッグ |
| AU2009209565B2 (en) | 2008-02-01 | 2013-09-19 | Ascendis Pharma As | Prodrug comprising a self-cleavable linker |
| WO2009148089A1 (ja) | 2008-06-05 | 2009-12-10 | 東芝機械株式会社 | ハンドリング装置、制御装置、制御方法およびプログラム |
| PA8830501A1 (es) | 2008-06-17 | 2010-07-27 | Univ Indiana Res & Tech Corp | Co-agonistas del receptor de glucagon/glp-1 |
| EA020326B9 (ru) | 2008-06-17 | 2015-03-31 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Агонисты смешанного действия на основе глюкозозависимого инсулинотропного пептида для лечения нарушений обмена веществ и ожирения |
| US8450270B2 (en) | 2008-06-17 | 2013-05-28 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability in physiological pH buffers |
| WO2010011313A2 (en) | 2008-07-23 | 2010-01-28 | President And Fellows Of Harvard College | Ligation of stapled polypeptides |
| US8481485B2 (en) | 2008-12-19 | 2013-07-09 | Indiana University Research And Technology Corporation | Insulin analogs |
| CN102325539A (zh) | 2008-12-19 | 2012-01-18 | 印第安纳大学研究及科技有限公司 | 基于酰胺的胰高血糖素超家族肽前药 |
| CA2747195A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Dipeptide linked medicinal agents |
| EP2376099A4 (en) | 2008-12-19 | 2012-04-25 | Univ Indiana Res & Tech Corp | INSULIN AGAIN YL-BASED GROWTH FACTORS WITH HIGH ACTIVITY AT THE INSULIN RECEPTOR |
| AU2009335715B2 (en) * | 2008-12-19 | 2016-09-15 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| US8569231B2 (en) * | 2009-03-20 | 2013-10-29 | Smartcells, Inc. | Soluble non-depot insulin conjugates and uses thereof |
| AU2010277559B2 (en) * | 2009-07-31 | 2016-08-11 | Sanofi-Aventis Deutschland Gmbh | Prodrugs comprising an insulin linker conjugate |
| EP2528618A4 (en) | 2010-01-27 | 2015-05-27 | Univ Indiana Res & Tech Corp | GLUCAGON ANTAGONISTE AND GIP AGONISTS CONJUGATES AND COMPOSITIONS FOR THE TREATMENT OF METABOLISM DISEASES AND ADIPOSITAS |
| AU2011268327B2 (en) | 2010-06-16 | 2016-02-25 | Indiana University Research And Technology Corporation | Single chain insulin agonists exhibiting high activity at the insulin receptor |
| WO2011159882A2 (en) | 2010-06-16 | 2011-12-22 | Indiana University Research And Technology Corporation | Novel stabilized insulin agonists |
| WO2011163460A1 (en) | 2010-06-24 | 2011-12-29 | Indiana University Research And Technology Corporation | Yl-based insulin-like growth factors exhibiting high activity at the insulin receptor |
| RU2580317C2 (ru) | 2010-06-24 | 2016-04-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов |
| US8946147B2 (en) | 2010-06-24 | 2015-02-03 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| WO2011163473A1 (en) | 2010-06-25 | 2011-12-29 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability in physiological ph buffers |
| MX2013008005A (es) * | 2011-01-20 | 2013-08-21 | Zealand Pharma As | Combinacion de analogos de glucagon acilados con analogos de insulina. |
| UA113626C2 (xx) * | 2011-06-02 | 2017-02-27 | Композиція для лікування діабету, що містить кон'югат інсуліну тривалої дії та кон'югат інсулінотропного пептиду тривалої дії | |
| EP2718317B1 (en) * | 2011-06-10 | 2018-11-14 | Beijing Hanmi Pharmaceutical Co., Ltd. | Glucose dependent insulinotropic polypeptide analogs, pharmaceutical compositions and use thereof |
| BR112014015156A2 (pt) | 2011-12-20 | 2020-10-27 | Indiana University Research And Technology Corporation | análogos de insulina à base de ctp, seus métodos de produção e uso no tratamento de hiperglicemia, bem como sequência de ácido nucleico e célula hospedeira |
| WO2014158900A1 (en) | 2013-03-14 | 2014-10-02 | Indiana University Research And Technology Corporation | Insulin-incretin conjugates |
-
2014
- 2014-03-05 WO PCT/US2014/020801 patent/WO2014158900A1/en not_active Ceased
- 2014-03-05 BR BR112015023071A patent/BR112015023071A2/pt not_active IP Right Cessation
- 2014-03-05 RU RU2015143472A patent/RU2678134C2/ru not_active IP Right Cessation
- 2014-03-05 KR KR1020157028780A patent/KR20150131213A/ko not_active Abandoned
- 2014-03-05 US US14/774,357 patent/US20160024169A1/en not_active Abandoned
- 2014-03-05 CA CA2904332A patent/CA2904332A1/en not_active Abandoned
- 2014-03-05 CN CN201480027381.0A patent/CN105324397B/zh not_active Expired - Fee Related
- 2014-03-05 JP JP2016500671A patent/JP6538645B2/ja not_active Expired - Fee Related
- 2014-03-05 EP EP14773636.7A patent/EP2970511B1/en not_active Not-in-force
- 2014-03-05 AU AU2014241743A patent/AU2014241743B2/en not_active Ceased
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2017
- 2017-12-19 US US15/846,485 patent/US10696726B2/en not_active Expired - Fee Related
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