UA81897C2 - Гетерологический пептидилированный глюкагон-1-подобный белок и его применение для изготовления лекарственного средства для лечения пациентов, страдающих ожирением и/или инсулиннезависимым диабетом - Google Patents
Гетерологический пептидилированный глюкагон-1-подобный белок и его применение для изготовления лекарственного средства для лечения пациентов, страдающих ожирением и/или инсулиннезависимым диабетом Download PDFInfo
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- UA81897C2 UA81897C2 UA2003065280A UA2003065280A UA81897C2 UA 81897 C2 UA81897 C2 UA 81897C2 UA 2003065280 A UA2003065280 A UA 2003065280A UA 2003065280 A UA2003065280 A UA 2003065280A UA 81897 C2 UA81897 C2 UA 81897C2
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
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Abstract
Изобретение относится к гетерологическому пептидилированному белку, в состав которого входит первый полипептид, сшитый со вторым полипептидом, где первым полипептидом является соединение GLP-1 (глюкагон-1-подобный пептид), а второй полипептид выбран среди: Fc-фрагмента иммуноглобулина, аналога Fc-фрагмента иммуноглобулина или фрагментов Fc-фрагмента иммуноглобулина. Данные белки имеют продленный период полувыведения из организма. Изобретение также относится к фармацевтической композиции, содержащей данные белки, и применение заявленного гетерологического пептидилированного белка для изготовления лекарственного средства для лечения пациентов, страдающих ожирением и/или инсулиннезависимым сахарным диабетом.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25195400P | 2000-12-07 | 2000-12-07 | |
PCT/US2001/043165 WO2002046227A2 (en) | 2000-12-07 | 2001-11-29 | Glp-1 fusion proteins |
Publications (1)
Publication Number | Publication Date |
---|---|
UA81897C2 true UA81897C2 (ru) | 2008-02-25 |
Family
ID=22954069
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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UA2003065280A UA81897C2 (ru) | 2000-12-07 | 2001-11-29 | Гетерологический пептидилированный глюкагон-1-подобный белок и его применение для изготовления лекарственного средства для лечения пациентов, страдающих ожирением и/или инсулиннезависимым диабетом |
UAA200706704A UA93662C2 (ru) | 2000-12-07 | 2001-11-29 | Гетерологический пептидилированный глюкагон-подобный белок и его применение для изготовления лекарственного средства для лечения пациентов, страдающих ожирением или инсулинонезависимым сахарным диабетом |
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Application Number | Title | Priority Date | Filing Date |
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UAA200706704A UA93662C2 (ru) | 2000-12-07 | 2001-11-29 | Гетерологический пептидилированный глюкагон-подобный белок и его применение для изготовления лекарственного средства для лечения пациентов, страдающих ожирением или инсулинонезависимым сахарным диабетом |
Country Status (30)
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US (1) | US7271149B2 (ru) |
EP (2) | EP1355942B1 (ru) |
JP (2) | JP2004528014A (ru) |
KR (2) | KR100942864B1 (ru) |
CN (2) | CN1483041A (ru) |
AT (2) | ATE437891T1 (ru) |
AU (2) | AU2002226897B2 (ru) |
BR (1) | BR0116024A (ru) |
CA (2) | CA2434237C (ru) |
CY (2) | CY1108485T1 (ru) |
CZ (2) | CZ306180B6 (ru) |
DE (2) | DE60135581D1 (ru) |
DK (2) | DK1355942T3 (ru) |
EA (1) | EA005584B1 (ru) |
EC (1) | ECSP064643A (ru) |
ES (2) | ES2328510T3 (ru) |
HK (1) | HK1061411A1 (ru) |
HR (1) | HRP20030455A2 (ru) |
HU (2) | HU229218B1 (ru) |
IL (3) | IL155812A0 (ru) |
MX (1) | MXPA03005036A (ru) |
NO (3) | NO331273B1 (ru) |
NZ (1) | NZ525577A (ru) |
PL (2) | PL393178A1 (ru) |
PT (2) | PT1724284E (ru) |
SI (2) | SI1724284T1 (ru) |
SK (2) | SK288088B6 (ru) |
UA (2) | UA81897C2 (ru) |
WO (1) | WO2002046227A2 (ru) |
ZA (1) | ZA200303642B (ru) |
Families Citing this family (321)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6444788B1 (en) | 1999-03-15 | 2002-09-03 | Novo Nordisk A/S | Ion exchange chromatography of GLP-1, analogs and derivatives thereof |
US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
CA2405701A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US20050100991A1 (en) * | 2001-04-12 | 2005-05-12 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US7084243B2 (en) * | 2000-06-16 | 2006-08-01 | Eli Lilly And Company | Glucagon-like peptide-1 analogs |
US7408041B2 (en) | 2000-12-08 | 2008-08-05 | Alexion Pharmaceuticals, Inc. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
US20060057651A1 (en) | 2000-12-08 | 2006-03-16 | Bowdish Katherine S | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
EP1341902A2 (en) | 2000-12-08 | 2003-09-10 | Alexion Pharmaceuticals, Inc. | Chronic lymphocytic leukemia cell line and its use for producing an antibody |
US7199217B2 (en) * | 2000-12-13 | 2007-04-03 | Eli Lilly And Company | Amidated glucagon-like peptide-1 |
DE60228972D1 (de) | 2001-07-31 | 2008-10-30 | Us Gov Health & Human Serv | Glp 1 exendin 4 peptidanaloga und deren verwendungen |
BR0212080A (pt) * | 2001-08-23 | 2006-04-04 | Lilly Co Eli | composto de glp-1, método de estimulação de receptor de glp-1 em um indivìduo necessitando de tal estimulação, e, uso de um composto de glp-1 |
US8129504B2 (en) | 2001-08-30 | 2012-03-06 | Biorexis Technology, Inc. | Oral delivery of modified transferrin fusion proteins |
US7176278B2 (en) | 2001-08-30 | 2007-02-13 | Biorexis Technology, Inc. | Modified transferrin fusion proteins |
RU2353625C2 (ru) * | 2001-10-18 | 2009-04-27 | Бристол-Маерс Сквибб Компани | Миметики человеческого глюканоподобного пептида-1 и их применение в лечении диабета и родственных состояний |
CA2471363C (en) | 2001-12-21 | 2014-02-11 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US20080194481A1 (en) * | 2001-12-21 | 2008-08-14 | Human Genome Sciences, Inc. | Albumin Fusion Proteins |
AU2002364587A1 (en) | 2001-12-21 | 2003-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US7482321B2 (en) * | 2002-01-08 | 2009-01-27 | Eli Lilly And Company | Extended glucagon-like peptide-1 analogs |
US20030191056A1 (en) * | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
DE60331226D1 (de) * | 2002-05-24 | 2010-03-25 | Medtronic Inc | Verfahren und dna-konstrukte zur produktion von polypeptiden mit hoher ausbeute |
JP2006504406A (ja) * | 2002-06-28 | 2006-02-09 | セントカー・インコーポレーテツド | 哺乳動物のch1欠失ミメティボディ、組成物、方法および使用 |
US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
DE60333306D1 (de) * | 2002-08-30 | 2010-08-19 | Biorexis Pharmaceutical Corp | Modifizierte transferrin-fusionsproteine mit doppelten transferrin-amino- oder carboxy-terminalen domänen |
WO2004050115A2 (en) * | 2002-12-03 | 2004-06-17 | Novo Nordisk A/S | Combination treatment using exendin-4 and thiazolidinediones |
EP1688148A1 (en) * | 2002-12-03 | 2006-08-09 | Novo Nordisk A/S | Combination treatment using exendin-4 and thiazolidinediones |
WO2004060387A1 (en) | 2002-12-27 | 2004-07-22 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
US7655618B2 (en) | 2002-12-27 | 2010-02-02 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
JP3974619B2 (ja) * | 2003-01-10 | 2007-09-12 | 株式会社新潟ティーエルオー | 遺伝子治療用ベクター及び該遺伝子治療用ベクターを投与された哺乳動物中又は培養細胞中の目的タンパク質の定量方法 |
WO2004069862A1 (ja) * | 2003-02-06 | 2004-08-19 | Keio University | ペプチド結合体 |
CN1832959A (zh) * | 2003-03-19 | 2006-09-13 | 伊莱利利公司 | 聚乙二醇连接的glp-1化合物 |
CN1771080B (zh) | 2003-04-08 | 2010-12-15 | 诺沃挪第克公司 | 包括至少一个色谱处理步骤的生产治疗用多肽或其前体的方法 |
WO2004089985A1 (en) | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | Stable pharmaceutical compositions |
WO2004103390A2 (en) | 2003-05-15 | 2004-12-02 | Trustees Of Tufts College | Stable analogs of peptide and polypeptide therapeutics |
SI1641483T1 (sl) * | 2003-06-12 | 2008-08-31 | Lilly Co Eli | Fuzijski proteini |
US7452966B2 (en) * | 2003-06-12 | 2008-11-18 | Eli Lilly And Company | GLP-1 analog fusion proteins |
WO2005028516A2 (en) * | 2003-09-19 | 2005-03-31 | Novo Nordisk A/S | Albumin-binding derivatives of therapeutic peptides |
CA2539253A1 (en) * | 2003-09-19 | 2005-03-31 | Novo Nordisk A/S | Albumin-binding derivatives of therapeutic peptides |
DK2256134T3 (en) | 2003-11-13 | 2014-02-24 | Hanmi Science Co Ltd | IgG Fc fragment to a drug carrier and process for preparation thereof |
KR101135244B1 (ko) * | 2007-11-29 | 2012-04-24 | 한미사이언스 주식회사 | 인슐린 분비 펩타이드 결합체를 포함하는 비만 관련질환 치료용 조성물 |
US8110665B2 (en) | 2003-11-13 | 2012-02-07 | Hanmi Holdings Co., Ltd. | Pharmaceutical composition comprising an immunoglobulin FC region as a carrier |
US8263084B2 (en) * | 2003-11-13 | 2012-09-11 | Hanmi Science Co., Ltd | Pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
US20090238838A1 (en) * | 2003-11-13 | 2009-09-24 | Hanmi Pharm. Ind. Co. Ltd. | Insulinotropic peptide conjugate using an immunoglobulin fc |
KR101243648B1 (ko) | 2003-11-20 | 2013-03-14 | 노보 노르디스크 에이/에스 | 제조 및 주사 장치용에 최적인 프로필렌 글리콜 함유펩티드 제제 |
EP2298337B1 (en) | 2003-12-09 | 2017-02-22 | Novo Nordisk A/S | Regulation of food preference using GLP-1 agonists |
EP1696962A2 (en) * | 2003-12-18 | 2006-09-06 | Novo Nordisk A/S | Novel glp-1 analogues linked to albumin-like agents |
US20060252693A1 (en) * | 2004-01-29 | 2006-11-09 | Wolfgang Glaesner | Glucagon-like peptide-1 analogs |
CN1980687B (zh) * | 2004-02-09 | 2015-05-13 | 人类基因科学公司 | 清蛋白融合蛋白 |
BRPI0507026A (pt) | 2004-02-09 | 2007-04-17 | Human Genome Sciences Inc | proteìnas de fusão de albumina |
EP2335715A3 (en) | 2004-02-11 | 2013-12-18 | Amylin Pharmaceuticals, LLC | Pancreatic polypeptide family motifs and polypeptides comprising the same |
US8076288B2 (en) | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
WO2005077072A2 (en) * | 2004-02-11 | 2005-08-25 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
JP2008537873A (ja) * | 2004-03-31 | 2008-10-02 | セントカー・インコーポレーテツド | ヒトglp−1ミメティボディ、組成物、方法および用途 |
WO2007081302A2 (en) * | 2005-03-28 | 2007-07-19 | Centocor, Inc. | Human glp-1 mimetibodies, compositions, methods and uses |
PT1759001E (pt) | 2004-04-21 | 2011-07-12 | Enobia Pharma Inc | Conjugados de libertação óssea e método de utilização dos mesmos para direccionar proteínas ao osso |
PL1751184T3 (pl) | 2004-05-13 | 2010-02-26 | Lilly Co Eli | Białka fuzyjne FGF-21 |
US8410047B2 (en) | 2004-06-11 | 2013-04-02 | Novo Nordisk A/S | Counteracting drug-induced obesity using GLP-1 agonists |
JP5107713B2 (ja) | 2004-10-07 | 2012-12-26 | ノヴォ ノルディスク アー/エス | 遅延性のエキセンディン−4化合物 |
JP2008515856A (ja) | 2004-10-07 | 2008-05-15 | ノボ ノルディスク アクティーゼルスカブ | 遅延性glp−1化合物 |
EP2769990A3 (en) * | 2004-12-02 | 2015-02-25 | Domantis Limited | Bispecific domain antibodies targeting serum albumin and GLP-1 or PYY |
WO2006068910A1 (en) * | 2004-12-22 | 2006-06-29 | Eli Lilly And Company | Glp-1 analog fusion protein formulations |
SG158158A1 (en) * | 2004-12-22 | 2010-01-29 | Centocor Inc | Glp-1 agonists, compositions, methods and uses |
US20090016959A1 (en) * | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
ES2484796T3 (es) | 2005-03-18 | 2014-08-12 | Novo Nordisk A/S | Compuestos de GLP-1 extendidos |
EP1877090B1 (en) * | 2005-05-06 | 2014-01-15 | Providence Health System | Trimeric ox40-immunoglobulin fusion protein and methods of use |
CN101166545B (zh) * | 2005-05-13 | 2011-06-15 | 伊莱利利公司 | Glp-1聚乙二醇化的化合物 |
WO2007012188A1 (en) * | 2005-07-27 | 2007-02-01 | Qinghua Wang | GLP/1/EXENDM 4 IgG Fc FUSION CONSTRUCTS FOR TREATMENT OF DIABETES |
CA2616551A1 (en) * | 2005-07-29 | 2007-02-15 | Amprotein Corporation | Chimeric therapeutic agents |
CN101277722A (zh) * | 2005-08-06 | 2008-10-01 | 王庆华 | 用于预防和治疗ⅰ型糖尿病的组合物及方法 |
AU2006279680B2 (en) * | 2005-08-11 | 2012-12-06 | Amylin Pharmaceuticals, Llc | Hybrid polypeptides with selectable properties |
JP2009504681A (ja) * | 2005-08-11 | 2009-02-05 | アミリン・ファーマシューティカルズ,インコーポレイテッド | 選択可能な特性を有するハイブリッドポリペプチド |
EP1767545B1 (en) | 2005-09-22 | 2009-11-11 | Biocompatibles UK Limited | GLP-1 (Glucagon-like peptide-1) fusion polypeptides with increased peptidase resistance |
US20090286724A1 (en) * | 2005-10-26 | 2009-11-19 | Chugai Seiyaku Kabushiki Kaisha | Aggregable glp-1 analogue and sustained-release pharmaceutical composition |
EP1965823B1 (en) * | 2005-11-04 | 2016-05-18 | Glaxosmithkline LLC | Methods for administering hypoglycemic agents |
CN1962695B (zh) * | 2005-11-09 | 2011-08-31 | 浙江德清安平生物制药有限公司 | 类胰高血素肽-1融合蛋白及其制备和用途 |
US8039432B2 (en) | 2005-11-09 | 2011-10-18 | Conjuchem, Llc | Method of treatment of diabetes and/or obesity with reduced nausea side effect |
US20080280328A1 (en) * | 2005-11-18 | 2008-11-13 | Novozymes A/S | Glucoamylase Variants |
EP1961764B1 (en) * | 2005-11-30 | 2011-05-11 | Shionogi Co., Ltd. | Sugar chain adduct of peptide and pharmaceutical comprising the same as active ingredient |
EP2364735A3 (en) | 2005-12-16 | 2012-04-11 | Nektar Therapeutics | Branched PEG conjugates of GLP-1 |
US8841255B2 (en) | 2005-12-20 | 2014-09-23 | Duke University | Therapeutic agents comprising fusions of vasoactive intestinal peptide and elastic peptides |
US20130172274A1 (en) | 2005-12-20 | 2013-07-04 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
US8334257B2 (en) | 2005-12-20 | 2012-12-18 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
EP2463305B1 (en) | 2006-01-12 | 2016-05-11 | Alexion Pharmaceuticals, Inc. | Antibodies to OX-2/CD200 and uses thereof |
US8946155B2 (en) | 2006-02-03 | 2015-02-03 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
US10351615B2 (en) | 2006-02-03 | 2019-07-16 | Opko Biologics Ltd. | Methods of treatment with long-acting growth hormone |
US20150038413A1 (en) | 2006-02-03 | 2015-02-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
US8450269B2 (en) | 2006-02-03 | 2013-05-28 | Prolor Biotech Ltd. | Long-acting growth hormone and methods of producing same |
US9458444B2 (en) | 2006-02-03 | 2016-10-04 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
US8048849B2 (en) | 2006-02-03 | 2011-11-01 | Modigene, Inc. | Long-acting polypeptides and methods of producing same |
US8759292B2 (en) | 2006-02-03 | 2014-06-24 | Prolor Biotech, Llc | Long-acting coagulation factors and methods of producing same |
US20140113860A1 (en) | 2006-02-03 | 2014-04-24 | Prolor Biotech Ltd. | Long-acting polypeptides and methods of producing and administering same |
US8476234B2 (en) * | 2006-02-03 | 2013-07-02 | Prolor Biotech Inc. | Long-acting coagulation factors and methods of producing same |
WO2007092252A2 (en) * | 2006-02-03 | 2007-08-16 | Modigene Inc | Long-acting polypeptides and methods of producing same |
US9249407B2 (en) | 2006-02-03 | 2016-02-02 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
US10221228B2 (en) | 2006-02-03 | 2019-03-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
CN101003574B (zh) * | 2006-02-21 | 2010-12-15 | 大连帝恩生物工程有限公司 | 长效降血糖肽的重组表达及其在糖尿病治疗药物中的应用 |
EP2573111A1 (en) | 2006-04-20 | 2013-03-27 | Amgen Inc. | GLP-1 compounds |
EP1854455B1 (en) | 2006-05-10 | 2009-10-07 | Biocompatibles UK Limited | Spherical microcapsules comprising GLP-1 peptides, their production and use |
MX2008015107A (es) | 2006-05-26 | 2008-12-09 | Amylin Pharmaceuticals Inc | Composicion y metodos para el tratamiento de insuficiecia cardiaca congestiva. |
WO2007146038A2 (en) * | 2006-06-07 | 2007-12-21 | Human Genome Sciences, Inc. | Albumin fusion proteins |
AR061930A1 (es) * | 2006-07-18 | 2008-10-01 | Centocor Inc | Mimeticuerpos de glp-1 humanos, composiciones, metodos y usos |
DK2046826T3 (da) | 2006-07-24 | 2011-10-24 | Biorexis Pharmaceutical Corp | Exendin-fusionsproteiner |
BRPI0715754A2 (pt) | 2006-08-31 | 2013-07-09 | Hoffmann La Roche | mÉtodo para a produÇço de fator do crescimento similar Á insulina i |
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. |
CA2663047A1 (en) * | 2006-09-06 | 2008-03-13 | Phase Bioscience, Inc. | Therapeutic elastin-like polypeptide (elp) fusion proteins |
TWI430806B (zh) * | 2006-09-13 | 2014-03-21 | Smithkline Beecham Corp | 用於投與長效降血糖藥劑之方法 |
TWI428346B (zh) * | 2006-12-13 | 2014-03-01 | Imp Innovations Ltd | 新穎化合物及其等對進食行為影響 |
JP2008169195A (ja) * | 2007-01-05 | 2008-07-24 | Hanmi Pharmaceutical Co Ltd | キャリア物質を用いたインスリン分泌ペプチド薬物結合体 |
AU2011254001B2 (en) * | 2007-01-05 | 2012-08-02 | Covx Technologies Ireland Limited | Glucagon-like protein-1 receptor (GLP-1R) agonist compounds |
US20090098130A1 (en) * | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
EP1972349A1 (en) * | 2007-03-21 | 2008-09-24 | Biocompatibles UK Limited | GLP-1 fusion peptides conjugated to polymer(s), their production and use |
EP1975176A1 (en) * | 2007-03-27 | 2008-10-01 | Biocompatibles UK Limited | Novel glp-1 fusion peptides, their production and use |
EP2144930A1 (en) | 2007-04-18 | 2010-01-20 | ZymoGenetics, Inc. | Single chain fc, methods of making and methods of treatment |
AU2008244523B2 (en) | 2007-04-23 | 2012-02-16 | Intarcia Therapeutics, Inc. | Suspension formulations of insulinotropic peptides and uses thereof |
JP2009019027A (ja) | 2007-07-16 | 2009-01-29 | Hanmi Pharmaceutical Co Ltd | アミノ末端のアミノ酸が変異したインスリン分泌ペプチド誘導体 |
CA2694121C (en) | 2007-07-25 | 2016-06-07 | Alexion Pharmaceuticals, Inc. | Methods and compositions for treating autoimmune disease |
ES2646614T3 (es) * | 2007-08-03 | 2017-12-14 | Eli Lilly And Company | Uso de un compuesto de FGF 21 y un compuesto de GLP 1 para el tratamiento de la obesidad |
ES2532116T3 (es) | 2007-09-05 | 2015-03-24 | Novo Nordisk A/S | Péptidos derivados con A-B-C-D y sus usos terapéuticos |
WO2009030738A1 (en) * | 2007-09-05 | 2009-03-12 | Novo Nordisk A/S | Glucagon-like peptide-1 derivatives and their pharmaceutical use |
ES2550363T3 (es) | 2007-09-05 | 2015-11-06 | Novo Nordisk A/S | Derivados truncados de GLP-1 y su uso terapéutico |
EP2200634B1 (en) * | 2007-09-21 | 2015-02-11 | The Regents of The University of California | Targeted interferon demonstrates potent apoptotic and anti-tumor activities |
WO2009059278A1 (en) * | 2007-11-02 | 2009-05-07 | Centocor, Inc. | Semi-synthetic glp-1 peptide-fc fusion constructs, methods and uses |
JP2011517561A (ja) * | 2008-03-31 | 2011-06-16 | グラクソ グループ リミテッド | 薬物融合体および複合体 |
CN101965516A (zh) * | 2008-04-03 | 2011-02-02 | 弗·哈夫曼-拉罗切有限公司 | 聚乙二醇化胰岛素样生长因子测定 |
CN101328221B (zh) * | 2008-04-14 | 2011-03-23 | 中国药科大学 | 一种降糖多肽融合蛋白及其衍生物的结构及用途 |
CN105727261A (zh) * | 2008-06-27 | 2016-07-06 | 杜克大学 | 包含弹性蛋白样肽的治疗剂 |
RU2483081C2 (ru) | 2008-07-23 | 2013-05-27 | Ханми Сайенс Ко.,Лтд.,Kr | Полипептидный комплекс, содержащий непептидильный полимер, обладающий тремя функциональными концами |
CN102112157B (zh) * | 2008-08-06 | 2013-05-29 | 诺沃-诺迪斯克保健股份有限公司 | 具有延长的体内效能的缀合蛋白 |
US20100075897A1 (en) * | 2008-09-23 | 2010-03-25 | Jinan University | Method for sustainedly releasing bioactive peptides and application thereof |
WO2010043047A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Conjugates of glp-1 agonists and uses thereof |
US8685895B2 (en) | 2008-12-05 | 2014-04-01 | Carolyn Enever | Methods for selecting protease resistant polypeptides |
MX2011005963A (es) | 2008-12-05 | 2011-09-01 | Angiochem Inc | Conjugados de neurotensina o analogos de neurotensina y sus usos. |
DK2373681T3 (en) | 2008-12-10 | 2017-04-24 | Glaxosmithkline Llc | PHARMACEUTICAL COMPOSITIONS OF ALBIGLUTID |
TWI504405B (zh) | 2009-01-22 | 2015-10-21 | Novo Nordisk Healthcare Ag | 穩定的生長激素化合物 |
JP5936112B2 (ja) | 2009-02-11 | 2016-06-15 | アルブミディクス アクティーゼルスカブ | アルブミン変異体及び複合体 |
WO2010096394A2 (en) | 2009-02-17 | 2010-08-26 | Redwood Biosciences, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
NZ595344A (en) | 2009-03-27 | 2013-09-27 | Glaxo Group Ltd | Drug fusions and conjugates |
EP2421562B1 (en) | 2009-04-20 | 2019-03-13 | Angiochem Inc. | Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog |
CN102596993A (zh) | 2009-07-02 | 2012-07-18 | 安吉奥开米公司 | 多聚体肽结合物以及其应用 |
US9663778B2 (en) | 2009-07-09 | 2017-05-30 | OPKO Biologies Ltd. | Long-acting coagulation factors and methods of producing same |
US8841249B2 (en) | 2009-08-06 | 2014-09-23 | Novo Nordisk A/S | Growth hormones with prolonged in-vivo efficacy |
PT3311828T (pt) | 2009-08-14 | 2021-05-05 | Phasebio Pharmaceuticals Inc | Péptidos intestinais vasoativos modificados |
CN101993485B (zh) * | 2009-08-20 | 2013-04-17 | 重庆富进生物医药有限公司 | 促胰岛素分泌肽类似物同源二聚体及其用途 |
CN101993496B (zh) * | 2009-08-20 | 2013-06-05 | 重庆富进生物医药有限公司 | 双重调节血糖血脂融合蛋白及其制法和用途 |
MX2012003939A (es) | 2009-09-30 | 2012-07-30 | Glaxo Group Ltd | Fusiones y conjugados de farmaco. |
WO2011043530A1 (ko) * | 2009-10-09 | 2011-04-14 | (주)알테오젠 | Glp-1 유사체의 융합체, 및 이를 유효성분으로 함유하는 당뇨병의 예방 또는 치료용 조성물 |
US8697648B2 (en) | 2009-10-20 | 2014-04-15 | Georgia State University Research Foundation, Inc. | Protein agent for diabetes treatment and β cell imaging |
BR112012009450A2 (pt) | 2009-10-30 | 2017-05-23 | Novozymes Biopharma Dk As | variantes de albumina |
CN102070717B (zh) * | 2009-11-19 | 2013-04-10 | 东莞太力生物工程有限公司 | 融合蛋白及其制备方法、编码该蛋白的dna序列、表达载体、宿主细胞、含有该蛋白的药物组合物 |
EP2826489A1 (en) | 2009-12-08 | 2015-01-21 | Teva Pharmaceutical Industries, Ltd. | BChE albumin fusions for the treatment of cocaine abuse |
RU2012134974A (ru) | 2010-01-22 | 2014-02-27 | Ново Нордиск Хелс Кеа Аг | Стабилизированное соединение гормона роста |
CN102834109B (zh) | 2010-01-22 | 2016-01-20 | 诺沃—诺迪斯克保健股份有限公司 | 稳定的生长激素化合物 |
US9981017B2 (en) | 2010-04-02 | 2018-05-29 | Hanmi Science Co., Ltd. | Insulin conjugate using an immunoglobulin fragment |
AR081066A1 (es) | 2010-04-02 | 2012-06-06 | Hanmi Holdings Co Ltd | Conjugado de insulina donde se usa un fragmento de inmunoglobulina |
CN101875700B (zh) * | 2010-04-09 | 2012-09-26 | 无锡和邦生物科技有限公司 | 一种增加促胰岛素分泌肽融合蛋白生物活性的方法 |
US9168288B2 (en) | 2010-04-09 | 2015-10-27 | Mount Sinai Hospital | Methods for treating disorders of the gastrointestinal tract using a GLP-1 agonist |
CN106977608A (zh) | 2010-04-09 | 2017-07-25 | 阿尔布麦狄克斯公司 | 白蛋白衍生物和变体 |
MX2012012383A (es) | 2010-04-30 | 2012-11-30 | Sanwa Kagaku Kenkyusho Co | Peptido para mejorar la bioestabilidad de una sustancia bioactica y sustancia bioactiva que tiene bioestabilidad mejorada. |
EP2566502A4 (en) | 2010-05-04 | 2013-10-09 | Glaxosmithkline Llc | METHODS OF TREATING OR PREVENTING CARDIOVASCULAR DISORDERS AND PROVIDING CARDIOVASCULAR PROTECTION |
WO2011153642A1 (en) * | 2010-06-10 | 2011-12-15 | Angiochem Inc. | Leptin and leptin analog conjugates and fusion proteins and uses thereof |
CN101891823B (zh) | 2010-06-11 | 2012-10-03 | 北京东方百泰生物科技有限公司 | 一种Exendin-4及其类似物融合蛋白 |
WO2011162830A2 (en) * | 2010-06-24 | 2011-12-29 | Biousian Biosystems, Inc. | Glucagon-like peptide-1 glycopeptides |
CN103080125A (zh) | 2010-07-02 | 2013-05-01 | 安吉奥开米公司 | 用于治疗性结合物的短且含d氨基酸的多肽及其使用 |
CN102311501A (zh) * | 2010-07-08 | 2012-01-11 | 天津药物研究院 | 含有glp-1或其类似物的融合蛋白、制备方法及其应用 |
CN101906158B (zh) * | 2010-07-14 | 2013-10-23 | 中国药科大学 | 一种聚乙二醇化降糖多肽及其制法和用途 |
KR101382593B1 (ko) | 2010-07-21 | 2014-04-10 | 한미사이언스 주식회사 | 신규한 지속형 글루카곤 결합체 및 이를 포함하는 비만 예방 및 치료용 약학적 조성물 |
CN102532323B (zh) * | 2010-12-09 | 2014-07-23 | 天津药物研究院 | 一种多肽复合物、药物组合物、其制备方法和应用 |
DK3326620T3 (da) | 2010-12-16 | 2020-05-25 | Novo Nordisk As | Faste sammensætninger omfattende en glp-1-agonist og et salt af n-(8-(2- hydroxybenzoyl)amino)caprylsyre |
CN102533655A (zh) * | 2010-12-21 | 2012-07-04 | 青岛黄海制药有限责任公司 | 高效表达人源重组蛋白GLP1/Fc的CHO-S细胞株及其建立方法 |
JP6055779B2 (ja) * | 2010-12-27 | 2016-12-27 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | ナトリウム利尿ペプチドを含む組成物およびその使用方法 |
CN103415621A (zh) | 2011-01-14 | 2013-11-27 | 雷德伍德生物科技股份有限公司 | 醛标记免疫球蛋白多肽及其使用方法 |
JP5948683B2 (ja) | 2011-02-28 | 2016-07-06 | 国立研究開発法人国立循環器病研究センター | 悪性腫瘍転移抑制用医薬 |
WO2012116453A1 (en) | 2011-03-03 | 2012-09-07 | Zymeworks Inc. | Multivalent heteromultimer scaffold design and constructs |
WO2012136790A1 (en) | 2011-04-07 | 2012-10-11 | Glaxo Group Limited | Compositions comprising fusion proteins or conjugates with an improved half -life |
WO2012136792A2 (en) | 2011-04-07 | 2012-10-11 | Glaxo Group Limited | Cck compositions |
KR101972836B1 (ko) | 2011-04-12 | 2019-04-29 | 노보 노르디스크 에이/에스 | 이중 아실화된 glp-1 유도체 |
WO2012170524A1 (en) | 2011-06-06 | 2012-12-13 | Phasebio Pharmaceuticals, Inc. | Use of modified vasoactive intestinal peptides in the treatment of hypertension |
ES2746052T3 (es) | 2011-06-28 | 2020-03-04 | Inhibrx Lp | Polipéptidos de fusión de serpina y métodos de uso de los mismos |
US10400029B2 (en) | 2011-06-28 | 2019-09-03 | Inhibrx, Lp | Serpin fusion polypeptides and methods of use thereof |
CA2839622A1 (en) * | 2011-06-28 | 2013-01-03 | Inhibrx Llc | Wap domain fusion polypeptides and methods of use thereof |
KR20140054009A (ko) | 2011-07-01 | 2014-05-08 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 릴랙신 융합 폴리펩타이드 및 그의 용도 |
CN103649116A (zh) | 2011-07-08 | 2014-03-19 | 拜耳知识产权有限责任公司 | 释放松弛素的融合蛋白及其用途 |
WO2013027680A1 (ja) | 2011-08-19 | 2013-02-28 | 独立行政法人国立循環器病研究センター | ナトリウム利尿ペプチド受容体gc-aアゴニスト及びgc-bアゴニストを組み合わせてなる悪性腫瘍の増悪防止用医薬 |
WO2013027823A1 (ja) * | 2011-08-25 | 2013-02-28 | 三菱化学メディエンス株式会社 | グルカゴン様ペプチド-1の測定方法及びそれに使用するキット |
CN107266558A (zh) | 2011-09-06 | 2017-10-20 | 诺沃—诺迪斯克有限公司 | Glp‑1衍生物 |
KR20130049671A (ko) | 2011-11-04 | 2013-05-14 | 한미사이언스 주식회사 | 생리활성 폴리펩타이드 결합체 제조 방법 |
EP2780364A2 (en) | 2011-11-18 | 2014-09-24 | Eleven Biotherapeutics, Inc. | Proteins with improved half-life and other properties |
JP2015500823A (ja) | 2011-12-09 | 2015-01-08 | ノヴォ ノルディスク アー/エス | Glp−1アゴニスト |
KR101895047B1 (ko) * | 2011-12-30 | 2018-09-06 | 한미사이언스 주식회사 | 면역글로불린 단편을 이용한 위치 특이적 글루카곤 유사 펩타이드-2 약물 결합체 |
EP2807266B1 (en) | 2012-01-26 | 2020-01-15 | Amgen Inc. | Growth differentiation factor 15 (gdf-15) polypeptides |
AR090281A1 (es) | 2012-03-08 | 2014-10-29 | Hanmi Science Co Ltd | Proceso mejorado para la preparacion de un complejo polipeptidico fisiologicamente activo |
US9944691B2 (en) | 2012-03-16 | 2018-04-17 | Albumedix A/S | Albumin variants |
DK2827845T3 (en) | 2012-03-22 | 2019-04-01 | Novo Nordisk As | COMPOSITIONS INCLUDING A PROCEDURE AND PREPARING THEREOF |
HUE062740T2 (hu) | 2012-03-22 | 2023-12-28 | Novo Nordisk As | GLP-1 peptidek készítményei és elõállításuk |
EP2838552A4 (en) | 2012-04-19 | 2016-05-18 | Opko Biolog Ltd | OXYNTOMODULIN VARIANTS WITH EXTENDED ACTION AND PROCESSES FOR PRODUCING SAME |
AU2013261214A1 (en) | 2012-05-16 | 2014-11-20 | Glaxo Group Limited | Polypeptide loaded POCA nanoparticles for oral administration |
NZ701573A (en) | 2012-05-17 | 2017-04-28 | Extend Biosciences Inc | Carriers for improved drug delivery |
CN112142855A (zh) * | 2012-05-18 | 2020-12-29 | 爱德迪安(北京)生物技术有限公司 | 用于糖尿病治疗的蛋白、蛋白缀合物及其应用 |
US10052366B2 (en) | 2012-05-21 | 2018-08-21 | Alexion Pharmaceuticsl, Inc. | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
ME03079B (me) | 2012-06-08 | 2019-01-20 | Alkermes Pharma Ireland Ltd | Ligandi modifikovani cirkularnom permutacijom као agonisтi i antagonisti |
ES2871328T3 (es) | 2012-06-20 | 2021-10-28 | Novo Nordisk As | Formulación de comprimido que comprende un péptido y un agente de suministro |
JP6498601B2 (ja) | 2012-07-13 | 2019-04-10 | ザイムワークス,インコーポレイテッド | 多価ヘテロ多量体足場設計および構築物 |
AR091902A1 (es) * | 2012-07-25 | 2015-03-11 | Hanmi Pharm Ind Co Ltd | Formulacion liquida de un conjugado de insulina de accion prolongada |
AR094821A1 (es) * | 2012-07-25 | 2015-09-02 | Hanmi Pharm Ind Co Ltd | Formulación líquida de un conjugado de péptido insulinotrópico de acción prolongada |
AR092862A1 (es) * | 2012-07-25 | 2015-05-06 | Hanmi Pharm Ind Co Ltd | Formulacion liquida de insulina de accion prolongada y un peptido insulinotropico y metodo de preparacion |
UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
GB2512156A (en) | 2012-11-08 | 2014-09-24 | Novozymes Biopharma Dk As | Albumin variants |
SG10202010383YA (en) | 2012-11-20 | 2020-11-27 | Opko Biologics Ltd | Method of increasing the hydrodynamic volume of polypeptides by attaching to gonadotrophin carboxy terminal peptides |
US9803021B2 (en) | 2012-12-07 | 2017-10-31 | The Regents Of The University Of California | CD138-targeted interferon demonstrates potent apoptotic and anti-tumor activities |
ES2653765T3 (es) | 2012-12-21 | 2018-02-08 | Sanofi | Agonistas duales de GLP1/GIP o trigonales de GLP1/GIP/glucagón |
CA2896793A1 (en) | 2013-01-15 | 2014-07-24 | Teva Pharmaceutical Industries Ltd. | Formulations of albu-bche, preparation and uses thereof |
US9546203B2 (en) * | 2013-03-14 | 2017-01-17 | Amgen Inc. | Aglycosylated Fc-containing polypeptides with cysteine substitutions |
JP6464145B2 (ja) | 2013-04-05 | 2019-02-06 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | 成長ホルモン化合物製剤 |
US10093745B2 (en) | 2013-05-29 | 2018-10-09 | The Regents Of The University Of California | Anti-CSPG4 fusions with interferon for the treatment of malignancy |
CN104277112B (zh) * | 2013-07-04 | 2018-01-26 | 嘉和生物药业有限公司 | 长效降血糖融合蛋白 |
BR112016002213A2 (pt) | 2013-07-31 | 2017-08-29 | Amgen Inc | Construtos do fator 15 de diferenciação de crescimento (gdf-15) |
CN103408669B (zh) * | 2013-08-01 | 2016-01-20 | 江苏泰康生物医药有限公司 | Glp-1类似物融合蛋白,及其制备方法和用途 |
CN104371019B (zh) | 2013-08-13 | 2019-09-10 | 鸿运华宁(杭州)生物医药有限公司 | 一种能与glp-1r特异性结合的抗体及其与glp-1的融合蛋白质 |
EP3033355A1 (en) * | 2013-08-16 | 2016-06-22 | Medimmune Limited | Gip and glp-1 receptor dual-agonists for the treatment of diabetes |
WO2015054427A1 (en) | 2013-10-10 | 2015-04-16 | Beth Israel Deaconess Medical Center, Inc. | Tm4sf1 binding proteins and methods of using same |
US20150158926A1 (en) | 2013-10-21 | 2015-06-11 | Opko Biologics, Ltd. | Long-acting polypeptides and methods of producing and administering same |
MX2016006741A (es) * | 2013-12-10 | 2016-08-12 | Hoffmann La Roche | Uso del dominio de union de una subunidad de una estructura de multiples subunidades para la liberacion dirigida de entidades farmaceuticamente activas a la estructura de multiples subunidades. |
EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
WO2015086730A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Non-acylated exendin-4 peptide analogues |
WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
TW201609799A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重glp-1/gip受體促效劑 |
AU2015242657B2 (en) * | 2014-03-31 | 2020-05-21 | Hanmi Pharm. Co., Ltd. | Method for improving solubility of protein and peptide by using immunoglobulin Fc fragment linkage |
TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重glp-1/昇糖素受體激動劑之艾塞那肽-4衍生物 |
TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑 |
TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自exendin-4之雙重glp-1/升糖素受體促效劑 |
WO2015165480A1 (en) | 2014-04-30 | 2015-11-05 | Institute For Research In Biomedicine | Human cytomegalovirus vaccine compositions and method of producing the same |
NO2776305T3 (ru) | 2014-04-23 | 2018-01-27 | ||
CA2947982C (en) | 2014-05-08 | 2022-11-29 | Phasebio Pharmaceuticals, Inc. | Methods and compositions for treating cystic fibrosis |
US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
WO2016007873A1 (en) | 2014-07-11 | 2016-01-14 | The Regents Of The University Of Michigan | Compositions and methods for treating craniosynostosis |
CN104558198A (zh) * | 2014-07-25 | 2015-04-29 | 成都贝爱特生物科技有限公司 | GLP-1类似物和amylin类似物的融合蛋白制备及其用途 |
CN104257696B (zh) * | 2014-09-04 | 2017-08-25 | 西安国誉生物科技有限公司 | 一种降糖稳糖酵母菌粉及其制备方法和应用 |
EP3530671A3 (en) | 2014-09-05 | 2019-11-13 | University of Copenhagen | Gip peptide analogues |
US9988430B2 (en) | 2014-10-10 | 2018-06-05 | Novo Nordisk A/S | Stable GLP-1 based GLP-1/glucagon receptor co-agonists |
CN104327187B (zh) * | 2014-10-11 | 2018-06-08 | 上海兴迪金生物技术有限公司 | 一种重组人GLP-1-Fc融合蛋白 |
US9789197B2 (en) | 2014-10-22 | 2017-10-17 | Extend Biosciences, Inc. | RNAi vitamin D conjugates |
US9585934B2 (en) | 2014-10-22 | 2017-03-07 | Extend Biosciences, Inc. | Therapeutic vitamin D conjugates |
WO2016065052A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Insulin vitamin d conjugates |
KR20180004094A (ko) * | 2014-11-06 | 2018-01-10 | 칠드런스 내셔널 메디컬 센터 | 암 및 자가면역 질환을 위한 면역 요법 |
EP3226891A1 (en) | 2014-12-05 | 2017-10-11 | Alexion Pharmaceuticals, Inc. | Treating seizure with recombinant alkaline phosphatase |
CN107108718B (zh) * | 2014-12-08 | 2022-07-22 | 北京强新生物科技有限公司 | 可溶性通用的增强adcc的合成融合基因和融合肽的技术及其应用 |
WO2016118577A1 (en) * | 2015-01-22 | 2016-07-28 | Medimmune, Llc | Thymosin-beta-four fusion proteins |
JP6868561B2 (ja) | 2015-01-28 | 2021-05-12 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | アルカリホスファターゼ欠損を有する被験者を治療する方法 |
CN114652817A (zh) | 2015-02-09 | 2022-06-24 | 费斯生物制药公司 | 用于治疗肌肉疾病和病症的方法和组合物 |
PL3257524T3 (pl) | 2015-02-11 | 2021-03-08 | Gmax Biopharm Llc | Stabilny preparat farmaceutyczny w postaci roztworu białka fuzyjnego przeciwciała przeciwko glp-1r |
US10745456B2 (en) * | 2015-04-01 | 2020-08-18 | The Scripps Research Institute | Methods and compositions related to GPCR agonist polypeptides |
IL304950A (en) | 2015-04-10 | 2023-10-01 | Amgen Inc | Interleukin for the expansion of myotonic control T-2 cells |
AR105616A1 (es) | 2015-05-07 | 2017-10-25 | Lilly Co Eli | Proteínas de fusión |
AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
US10980892B2 (en) | 2015-06-15 | 2021-04-20 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
WO2016203482A2 (en) | 2015-06-19 | 2016-12-22 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重glp-1/升糖素受體促效劑之新毒蜥外泌肽(exendin-4)衍生物 |
KR102644116B1 (ko) | 2015-08-17 | 2024-03-05 | 알렉시온 파마슈티칼스, 인코포레이티드 | 알칼린 포스파타제의 제조 |
CN108137674B (zh) | 2015-08-20 | 2022-12-06 | 阿尔布梅迪克斯医疗有限公司 | 白蛋白变体和缀合物 |
KR20180039726A (ko) | 2015-09-04 | 2018-04-18 | 더 캘리포니아 인스티튜트 포 바이오메디칼 리써치 | 인슐린 면역글로불린 융합 단백질 |
JP6868617B2 (ja) | 2015-09-28 | 2021-05-12 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | 低ホスファターゼ血症の組織非特異的アルカリホスファターゼ(tnsalp)酵素補充療法に有効な投薬計画の特定 |
WO2017074466A1 (en) | 2015-10-30 | 2017-05-04 | Alexion Pharmaceuticals, Inc. | Methods for treating craniosynostosis in a patient |
CN105367664B (zh) * | 2015-11-04 | 2019-09-20 | 成都贝爱特生物科技有限公司 | 激活GLP-1受体和Amylin受体双功能作用的融合蛋白制备及其用途 |
EP3960760A1 (en) * | 2015-11-16 | 2022-03-02 | Ubiprotein, Corp. | A method for extending half-life of a protein |
JP6810146B2 (ja) | 2015-11-24 | 2021-01-06 | トランスフェール プリュ エス.ウ.セ. | 受容体媒介化学療法による癌の治療のためのペプチド化合物およびペプチドコンジュゲート |
US11065306B2 (en) | 2016-03-08 | 2021-07-20 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in children |
JP2019513711A (ja) | 2016-04-01 | 2019-05-30 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | アルカリホスファターゼによって筋力低下を治療すること |
WO2017173395A1 (en) | 2016-04-01 | 2017-10-05 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
CN109071634A (zh) | 2016-04-26 | 2018-12-21 | R.P.谢勒技术有限责任公司 | 抗体偶联物及其制备和使用方法 |
US10988744B2 (en) | 2016-06-06 | 2021-04-27 | Alexion Pharmaceuticals, Inc. | Method of producing alkaline phosphatase |
CA3030533A1 (en) | 2016-07-11 | 2018-01-18 | Oren HERSHKOVITZ | Long-acting coagulation factor vii and methods of producing same |
CN106046176B (zh) * | 2016-08-16 | 2019-09-10 | 中国药科大学 | 一种高活性长效降糖融合蛋白及其制备方法与医药用途 |
EP3500289A4 (en) | 2016-08-18 | 2020-05-06 | Alexion Pharmaceuticals, Inc. | METHODS OF TREATING TRACHEOBRONCHOMALACIA |
WO2018045872A1 (zh) * | 2016-09-06 | 2018-03-15 | 中国药科大学 | 一种多肽及其用途 |
CN109200273B (zh) * | 2017-07-04 | 2021-02-19 | 中国药科大学 | 一种多肽用于制备预防或治疗脂肪肝病药物的用途 |
CN106279400A (zh) * | 2016-09-06 | 2017-01-04 | 中国药科大学 | P8降糖肽的设计及其用途 |
WO2018112282A1 (en) * | 2016-12-14 | 2018-06-21 | Ligandal, Inc. | Compositions and methods for nucleic acid and/or protein payload delivery |
CN106519016A (zh) * | 2016-12-20 | 2017-03-22 | 中国药科大学 | 降糖调脂肽——Progly肽的设计及其用途 |
CN107033234B (zh) * | 2017-01-03 | 2018-06-26 | 北京凯因科技股份有限公司 | 酰化的glp-1衍生物 |
US11192931B2 (en) * | 2017-01-25 | 2021-12-07 | Medlmmune, Llc | Relaxin fusion polypeptides and uses thereof |
CN110719786A (zh) | 2017-03-31 | 2020-01-21 | 阿雷克森制药公司 | 用于治疗成人和青少年的低磷酸酯酶症(hpp)的方法 |
CN108727486A (zh) * | 2017-04-24 | 2018-11-02 | 舒泰神(北京)生物制药股份有限公司 | 长效神经生长因子、制备方法及其组合物 |
WO2018213928A1 (en) | 2017-05-24 | 2018-11-29 | Transfert Plus, S.E.C. | Peptide compounds, conjugate compounds and uses thereof for treating inflammatory diseases |
EP4361173A3 (en) | 2017-05-31 | 2024-07-03 | University of Copenhagen | Long-acting gip peptide analogues |
AR112480A1 (es) | 2017-08-24 | 2019-10-30 | Novo Nordisk As | Composiciones de glp-1 y sus usos |
WO2019067499A1 (en) | 2017-09-27 | 2019-04-04 | Alexion Pharmaceuticals, Inc. | BIOMARKER SIGNATURE FOR PREDICTING A TUMOR RESPONSE TO ANTI-CD200 THERAPY |
MX2020005231A (es) | 2017-11-21 | 2020-08-24 | Lilly Co Eli | Metodos de uso y composiciones que contienen dulaglutida. |
CN116143939A (zh) * | 2017-11-24 | 2023-05-23 | 浙江道尔生物科技有限公司 | 一种治疗代谢疾病的多重活性蛋白 |
CN115109166A (zh) * | 2017-11-24 | 2022-09-27 | 浙江道尔生物科技有限公司 | 一种治疗代谢疾病的多结构域活性蛋白 |
CN109929806B (zh) | 2017-12-19 | 2020-05-08 | 北京吉源生物科技有限公司 | 一种表达glp1和fgf21的干细胞及其用途 |
CN113603794B (zh) * | 2018-01-11 | 2024-01-16 | 安源医药科技(上海)有限公司 | 用于调节血糖和脂质的增效型双功能蛋白 |
WO2019140021A1 (en) | 2018-01-12 | 2019-07-18 | Eli Lilly And Company | Combination therapy |
CN110092835A (zh) * | 2018-01-30 | 2019-08-06 | 上海惠盾生物技术有限公司 | 一种glp-1类似物-col3a1融合蛋白 |
CN111683676B (zh) | 2018-02-02 | 2024-06-18 | 诺和诺德股份有限公司 | 包含glp-1激动剂、n-(8-(2-羟基苯甲酰基)氨基)辛酸的盐和润滑剂的固体组合物 |
WO2019190752A1 (en) | 2018-03-30 | 2019-10-03 | Alexion Pharmaceuticals, Inc. | Manufacturing of glycoproteins |
AU2019247936C1 (en) | 2018-04-05 | 2023-06-15 | Sun Pharmaceutical Industries Limited | Novel GLP-1 analogues |
MX2020010659A (es) | 2018-04-09 | 2020-10-28 | Amgen Inc | Proteinas de fusion del factor de diferenciacion de crecimiento 15. |
WO2019200594A1 (zh) | 2018-04-19 | 2019-10-24 | 杭州先为达生物科技有限公司 | 酰化的glp-1衍生物 |
CN110964116A (zh) * | 2018-09-26 | 2020-04-07 | 北京辅仁瑞辉生物医药研究院有限公司 | GLP1-Fc融合蛋白及其缀合物 |
EA202191105A1 (ru) * | 2018-10-22 | 2021-08-03 | Янссен Фармацевтика Нв | Слитые белки, полученные из глюкагоноподобного пептида 1 (glp1) и ростового фактора дифференцировки 15 (gdf15), и их применение |
EP3891174A1 (en) | 2018-12-03 | 2021-10-13 | Antag Therapeutics ApS | Modified gip peptide analogues |
WO2020118843A1 (zh) * | 2018-12-12 | 2020-06-18 | 四川利通科创生物医药科技有限公司 | 一种glp-1突变体及其制备方法和用途 |
TW202024134A (zh) | 2018-12-21 | 2020-07-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 雙特異性蛋白 |
CA3056663C (en) | 2019-04-05 | 2022-10-18 | Jeffrey S. RIESMEYER | Use of dulaglutide in reducing risk of cardiovascular events in patients with type 2 diabetes mellitus |
CN110151980B (zh) * | 2019-06-30 | 2022-12-09 | 中国药科大学 | Glp-1受体激动剂融合蛋白在制备预防或治疗高血脂药物中的应用 |
US20230093542A1 (en) | 2020-02-18 | 2023-03-23 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
AU2021224412A1 (en) | 2020-02-22 | 2022-09-15 | Jcr Pharmaceuticals Co., Ltd. | Human transferrin receptor binding peptide |
CN115925995A (zh) * | 2020-09-30 | 2023-04-07 | 北京质肽生物医药科技有限公司 | 多肽缀合物和使用方法 |
US20240209027A1 (en) | 2021-03-22 | 2024-06-27 | PeptiAID Inc., | Peptide and peptide-containing composition |
TW202305012A (zh) | 2021-03-22 | 2023-02-01 | 日商肽夢想股份有限公司 | c-Met 蛋白質結合肽複合物 |
CN113150172B (zh) * | 2021-04-28 | 2023-09-22 | 中国药科大学 | Glp-1r/gipr双靶点激动剂融合蛋白及其制备方法与应用 |
AU2022294601A1 (en) | 2021-06-18 | 2023-12-14 | Peptidream Inc. | Ghr-binding pending peptide and composition comprising same |
JPWO2023022234A1 (ru) | 2021-08-19 | 2023-02-23 | ||
EP4389893A1 (en) | 2021-08-21 | 2024-06-26 | Takeda Pharmaceutical Company Limited | Human transferrin receptor binding peptide-drug conjugate |
WO2023027125A1 (ja) | 2021-08-24 | 2023-03-02 | ペプチドリーム株式会社 | ヒトトランスフェリンレセプター結合抗体-ペプチドコンジュゲート |
CA3234324A1 (en) | 2021-09-30 | 2023-04-06 | Peptidream Inc. | Peptide |
CN113801853B (zh) * | 2021-11-19 | 2022-03-15 | 山东兴瑞生物科技有限公司 | Exendin-4融合基因修饰的MSC及其应用 |
WO2023179796A1 (en) * | 2022-03-25 | 2023-09-28 | Beijing Ql Biopharmaceutical Co., Ltd. | Pharmaceutical compositions of polypeptide conjugates and methods of uses thereof |
CN116848243B (zh) * | 2022-03-30 | 2024-03-19 | 北京质肽生物医药科技有限公司 | 多肽缀合物的液体药物组合物和其使用方法 |
CN114774496B (zh) * | 2022-06-21 | 2022-10-04 | 北京惠之衡生物科技有限公司 | 一种高密度发酵制备glp-1类似物的方法 |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
US5766883A (en) | 1989-04-29 | 1998-06-16 | Delta Biotechnology Limited | Polypeptides |
ATE92107T1 (de) | 1989-04-29 | 1993-08-15 | Delta Biotechnology Ltd | N-terminale fragmente von menschliches serumalbumin enthaltenden fusionsproteinen. |
FR2650598B1 (fr) * | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
FR2686900B1 (fr) | 1992-01-31 | 1995-07-21 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activite de stimulation des colonies de granulocytes, leur preparation et compositions pharmaceutiques les contenant. |
DE69522965T2 (de) * | 1994-04-22 | 2002-04-04 | Corixa Corp | Verbindungen und methoden für die stimulierungen und die erhöhung von schutzimmunantworten und il-12 herstellung |
US5990077A (en) * | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
US5925351A (en) * | 1995-07-21 | 1999-07-20 | Biogen, Inc. | Soluble lymphotoxin-β receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological disease |
GB9526733D0 (en) | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
US6750334B1 (en) * | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
MY120425A (en) | 1996-07-26 | 2005-10-31 | Novartis Ag | Fusion polypeptides |
ATE417622T1 (de) | 1996-08-08 | 2009-01-15 | Amylin Pharmaceuticals Inc | Regulation gastrointestinaler beweglichkeit |
BRPI9711437B8 (pt) * | 1996-08-30 | 2021-05-25 | Novo Nordisk As | derivados de glp-1 |
UA65549C2 (ru) * | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Применение аналогов и производных glp-1 для периферического введения для борьбы с ожирением |
US6190909B1 (en) * | 1997-04-17 | 2001-02-20 | Millennium Pharmaceuticals, Inc. | TH2-specific gene |
EP0887061A1 (en) * | 1997-06-28 | 1998-12-30 | The Procter & Gamble Company | Faecal collector |
PT1019077E (pt) | 1997-08-08 | 2008-02-21 | Amylin Pharmaceuticals Inc | Novos compostos agonistas de exendina |
MXPA00004670A (es) | 1997-11-14 | 2003-07-14 | Amylin Pharmaceuticals Inc | Compuestos agonistas de exendina novedosos. |
BR9814189A (pt) | 1997-11-14 | 2000-10-03 | Amylin Pharmaceuticals Inc | "compostos agonistas da exendina" |
JP4677095B2 (ja) | 1998-02-13 | 2011-04-27 | アミリン・ファーマシューティカルズ,インコーポレイテッド | エキセンジンおよびglp−1の変力および利尿効果 |
AU2610899A (en) * | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | N-terminally modified glp-1 derivatives |
WO1999043708A1 (en) | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | Glp-1 derivatives of glp-1 and exendin with protracted profile of action |
AU2610799A (en) * | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | Glp-1 derivatives with helix-content exceeding 25 per cent, forming partially structured micellar-like aggregates |
JP2002512175A (ja) | 1998-02-27 | 2002-04-23 | ノボ ノルディスク アクティーゼルスカブ | Glp−1類似体の誘導体類 |
DE69933216T2 (de) * | 1998-06-15 | 2007-09-20 | GTC Biotherapeutics, Inc., Framingham | Erythropoietin-analog-menschliches serum-albumin fusionsprotein |
DK1137941T4 (da) * | 1998-12-10 | 2014-01-06 | Brystol Myers Squibb Company | Protein-scaffolds til antistof-mimetika og andre bindingsproteiner |
ATE252601T1 (de) * | 1999-05-17 | 2003-11-15 | Conjuchem Inc | Lang wirkende insulinotrope peptide |
US6514500B1 (en) * | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
CA2405701A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
AU2002364587A1 (en) | 2001-12-21 | 2003-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
CA2471363C (en) | 2001-12-21 | 2014-02-11 | Human Genome Sciences, Inc. | Albumin fusion proteins |
-
2001
- 2001-11-29 PL PL393178A patent/PL393178A1/pl unknown
- 2001-11-29 PL PL366208A patent/PL209550B1/pl unknown
- 2001-11-29 SK SK50057-2011A patent/SK288088B6/sk not_active IP Right Cessation
- 2001-11-29 SK SK670-2003A patent/SK288342B6/sk not_active IP Right Cessation
- 2001-11-29 CA CA2434237A patent/CA2434237C/en not_active Expired - Lifetime
- 2001-11-29 DE DE60135581T patent/DE60135581D1/de not_active Expired - Lifetime
- 2001-11-29 EA EA200300644A patent/EA005584B1/ru not_active IP Right Cessation
- 2001-11-29 US US10/433,108 patent/US7271149B2/en not_active Expired - Lifetime
- 2001-11-29 EP EP01995845A patent/EP1355942B1/en not_active Expired - Lifetime
- 2001-11-29 CN CNA018202322A patent/CN1483041A/zh active Pending
- 2001-11-29 AU AU2002226897A patent/AU2002226897B2/en not_active Expired
- 2001-11-29 PT PT06118975T patent/PT1724284E/pt unknown
- 2001-11-29 KR KR1020037007541A patent/KR100942864B1/ko active IP Right Grant
- 2001-11-29 ES ES06118975T patent/ES2328510T3/es not_active Expired - Lifetime
- 2001-11-29 NZ NZ525577A patent/NZ525577A/en not_active IP Right Cessation
- 2001-11-29 JP JP2002547963A patent/JP2004528014A/ja active Pending
- 2001-11-29 HU HU0302529A patent/HU229218B1/hu unknown
- 2001-11-29 WO PCT/US2001/043165 patent/WO2002046227A2/en active Application Filing
- 2001-11-29 KR KR1020087019148A patent/KR20080085082A/ko not_active Application Discontinuation
- 2001-11-29 BR BR0116024-9A patent/BR0116024A/pt not_active Application Discontinuation
- 2001-11-29 DK DK01995845T patent/DK1355942T3/da active
- 2001-11-29 DE DE60139430T patent/DE60139430D1/de not_active Expired - Lifetime
- 2001-11-29 EP EP06118975A patent/EP1724284B1/en not_active Expired - Lifetime
- 2001-11-29 AT AT06118975T patent/ATE437891T1/de active
- 2001-11-29 CZ CZ2003-1602A patent/CZ306180B6/cs not_active IP Right Cessation
- 2001-11-29 AT AT01995845T patent/ATE406384T1/de active
- 2001-11-29 MX MXPA03005036A patent/MXPA03005036A/es active IP Right Grant
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