JP4394279B2 - 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 - Google Patents
酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 Download PDFInfo
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- JP4394279B2 JP4394279B2 JP2000535659A JP2000535659A JP4394279B2 JP 4394279 B2 JP4394279 B2 JP 4394279B2 JP 2000535659 A JP2000535659 A JP 2000535659A JP 2000535659 A JP2000535659 A JP 2000535659A JP 4394279 B2 JP4394279 B2 JP 4394279B2
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK31798 | 1998-03-09 | ||
| DK0317/98 | 1998-03-09 | ||
| PCT/DK1999/000118 WO1999046283A1 (en) | 1998-03-09 | 1999-03-09 | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| JP2007142336A Division JP4394704B2 (ja) | 1998-03-09 | 2007-05-29 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
| JP2007188066A Division JP2007320961A (ja) | 1998-03-09 | 2007-07-19 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
Publications (3)
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| JP2002509082A JP2002509082A (ja) | 2002-03-26 |
| JP2002509082A5 JP2002509082A5 (https=) | 2007-09-27 |
| JP4394279B2 true JP4394279B2 (ja) | 2010-01-06 |
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| JP2000535659A Expired - Fee Related JP4394279B2 (ja) | 1998-03-09 | 1999-03-09 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
| JP2007142336A Expired - Fee Related JP4394704B2 (ja) | 1998-03-09 | 2007-05-29 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
| JP2007188066A Pending JP2007320961A (ja) | 1998-03-09 | 2007-07-19 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2007142336A Expired - Fee Related JP4394704B2 (ja) | 1998-03-09 | 2007-05-29 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
| JP2007188066A Pending JP2007320961A (ja) | 1998-03-09 | 2007-07-19 | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
Country Status (8)
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| US (7) | US7414107B2 (https=) |
| EP (3) | EP1950224A3 (https=) |
| JP (3) | JP4394279B2 (https=) |
| AU (1) | AU757658B2 (https=) |
| CA (1) | CA2321026A1 (https=) |
| IL (3) | IL138214A0 (https=) |
| NZ (1) | NZ506839A (https=) |
| WO (1) | WO1999046283A1 (https=) |
Families Citing this family (226)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CZ295838B6 (cs) * | 1996-09-09 | 2005-11-16 | Zealand Pharma A/S | Způsob výroby peptidů |
| JP4394279B2 (ja) | 1998-03-09 | 2010-01-06 | ジーランド ファーマ アクティーゼルスカブ | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
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| US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| CA2363712C (en) | 1999-05-17 | 2011-05-10 | Conjuchem Inc. | Long lasting insulinotropic peptides |
| PT1105409E (pt) * | 1999-05-17 | 2006-07-31 | Conjuchem Inc | Proteccao de peptidos terapeuticos endogenos da actividade de peptidases por conjugacao a componentes do sangue |
| EP1076066A1 (en) | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
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| US6890896B1 (en) * | 1999-11-18 | 2005-05-10 | Ceremedix, Inc. | Compositions and methods for counteracting effects of reactive oxygen species and free radicals |
| US6756480B2 (en) * | 2000-04-27 | 2004-06-29 | Amgen Inc. | Modulators of receptors for parathyroid hormone and parathyroid hormone-related protein |
| US7244701B2 (en) | 2000-06-16 | 2007-07-17 | Zealand Phama A/S | Diuretic peptide conjugate |
| JP4624639B2 (ja) * | 2000-06-16 | 2011-02-02 | ジーランド ファーマ アクティーゼルスカブ | 短い荷電ペプチド鎖によってn及び/又はc末端が修飾されたペプチド |
| US7550425B2 (en) | 2000-06-16 | 2009-06-23 | Zealand Pharma A/S | Diuretic peptide conjugates |
| US7371721B2 (en) | 2000-09-18 | 2008-05-13 | Sanos Bioscience A/S | Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes |
| ES2310192T3 (es) | 2000-09-18 | 2009-01-01 | Sanos Bioscience A/S | Uso de peptidos glp-2. |
| EP2343317A1 (en) | 2000-11-10 | 2011-07-13 | F. Hoffmann-La Roche Ltd. | Apolipoprotein analogues |
| JP2006516947A (ja) * | 2000-11-16 | 2006-07-13 | ニュー リバー ファーマシューティカルズ インコーポレイテッド | 新規な医薬化合物およびその製造方法と使用方法 |
| ATE396202T1 (de) | 2001-02-16 | 2008-06-15 | Conjuchem Biotechnologies Inc | Lang wirkendes glucagon-ähnliches peptid-2 für die behandlung von gastrointestinalen krankheiten und störungen |
| EP1411968B1 (en) | 2001-07-31 | 2008-09-17 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Glp-1 exendin-4 peptide analogs and uses thereof |
| 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 |
| JP2010229140A (ja) * | 2002-02-22 | 2010-10-14 | Shire Llc | 活性物質送達系及び活性物質を保護し投与する方法 |
| US7666979B2 (en) * | 2002-03-01 | 2010-02-23 | Bracco International B.V. | Methods for preparing multivalent constructs for therapeutic and diagnostic applications and methods of preparing the same |
| US7211240B2 (en) * | 2002-03-01 | 2007-05-01 | Bracco International B.V. | Multivalent constructs for therapeutic and diagnostic applications |
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| US7794693B2 (en) * | 2002-03-01 | 2010-09-14 | Bracco International B.V. | Targeting vector-phospholipid conjugates |
| US7261876B2 (en) | 2002-03-01 | 2007-08-28 | Bracco International Bv | Multivalent constructs for therapeutic and diagnostic applications |
| US8623822B2 (en) | 2002-03-01 | 2014-01-07 | Bracco Suisse Sa | KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy |
| WO2003090604A2 (en) * | 2002-04-24 | 2003-11-06 | University Of Florida | Method of endovascular brain mapping |
| US6881829B2 (en) * | 2002-04-26 | 2005-04-19 | Chimeracom, L.L.C. | Chimeric hybrid analgesics |
| EP1525219B1 (en) | 2002-07-04 | 2009-05-27 | Zealand Pharma A/S | Glp-1 and methods for treating diabetes |
| AU2003268621B2 (en) | 2002-10-02 | 2009-01-15 | Zealand Pharma A/S | Stabilized exendin-4 compounds |
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| US7648962B2 (en) * | 2002-11-26 | 2010-01-19 | Biocon Limited | Natriuretic compounds, conjugates, and uses thereof |
| AU2003297583B2 (en) * | 2002-11-26 | 2010-01-14 | Biocon, Ltd | Modified naturetic compounds, conjugates, and uses thereof |
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| GB0307777D0 (en) | 2003-04-04 | 2003-05-07 | Medical Res Council | Conjugate compounds |
| ES2295961T3 (es) | 2003-12-31 | 2008-04-16 | F. Hoffmann-La Roche Ag | Proceso para la sintesis peptidica utilizacndo una cantidad reducida de agente de desproteccion. |
| CA2560174A1 (en) | 2004-03-17 | 2005-09-29 | 7Tm Pharma A/S | Y4 selective receptor agonists for therapeutic interventions |
| EA011860B1 (ru) | 2004-03-17 | 2009-06-30 | 7ТиЭм ФАРМА А/С | Селективные агонисты рецептора y2 для терапевтического воздействия |
| DE602005027461D1 (de) | 2004-04-21 | 2011-05-26 | Enobia Pharma Inc | Konjugate zur zuführung an knochen und verfahren zu deren verwendung beim hinführen von proteinen zum knochen |
| DK2100904T3 (da) | 2004-04-23 | 2010-11-08 | Conjuchem Biotechnologies Inc | Fast fase til anvendelse i en fremgangsmåde til rensning af albuminkonjugater |
| US9006181B2 (en) | 2004-07-21 | 2015-04-14 | The Administrators Of The Tulane Educational Fund | Treatment of renal dysfunction and multiple myeloma using PACAP compounds |
| JO2937B1 (en) | 2004-08-11 | 2016-03-15 | فيرينغ.بي.في | Tight muscles of the peptide vascular tensioner receptor |
| EA011879B1 (ru) | 2004-09-24 | 2009-06-30 | Эмджин Инк. | МОЛЕКУЛЫ С МОДИФИЦИРОВАННЫМ Fc ФРАГМЕНТОМ |
| DK1737889T3 (da) | 2004-10-19 | 2011-01-03 | Lonza Ag | Fremgangsmåde til fastfase-peptidsyntese |
| WO2006076471A2 (en) * | 2005-01-12 | 2006-07-20 | Nobex Corporation | Bnp conjugates and methods of use |
| TWI376234B (en) * | 2005-02-01 | 2012-11-11 | Msd Oss Bv | Conjugates of a polypeptide and an oligosaccharide |
| GB0505420D0 (en) * | 2005-03-16 | 2005-04-20 | Isogenica Ltd | Stable ligand selection method |
| JP2008533114A (ja) * | 2005-03-18 | 2008-08-21 | ユーシーエル ビジネス パブリック リミテッド カンパニー | メカノ成長因子ペプチドおよびその使用 |
| DE602006020123D1 (de) | 2005-05-04 | 2011-03-31 | Zealand Pharma As | Glucagon-like-peptide-2- (glp-2-) analoga |
| US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
| CN103497237B (zh) * | 2005-08-26 | 2015-10-28 | 艾伯维有限公司 | 治疗活性的α-MSH类似物 |
| EP1919947B1 (en) | 2005-08-26 | 2013-02-27 | AbbVie Inc. | Therapeutically active alpha-msh analogues |
| JP2009508847A (ja) | 2005-09-16 | 2009-03-05 | イッサム リサーチ ディヴェロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム | 栄養状態、認知および生存を改善するための化合物 |
| ATE516301T1 (de) * | 2005-09-21 | 2011-07-15 | 7Tm Pharma As | Y2-selektive rezeptoragonisten für therapeutische eingriffe |
| AU2005337116A1 (en) | 2005-09-21 | 2007-04-12 | 7Tm Pharma A/S | Y4 selective receptor agonists for therapeutic interventions |
| PL1767545T3 (pl) | 2005-09-22 | 2010-04-30 | Biocompatibles Uk Ltd | Polipeptydy fuzyjne GLP-1 (glukagonopodobny peptyd-1) o zwiększonej odporności na peptydazy |
| EP2570133B1 (en) | 2005-11-07 | 2016-03-23 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| US8039432B2 (en) * | 2005-11-09 | 2011-10-18 | Conjuchem, Llc | Method of treatment of diabetes and/or obesity with reduced nausea side effect |
| EP1976876A4 (en) * | 2005-12-22 | 2010-01-13 | Conjuchem Biotechnologies Inc | PROCESS FOR PRODUCING PREFORMED ALBUMIN CONJUGATES AND THERAPEUTIC AGENT |
| RU2415149C2 (ru) | 2006-02-10 | 2011-03-27 | Ферринг Б.В. | Пептидные соединения |
| HUE027174T2 (en) | 2006-02-13 | 2016-10-28 | Ferring Bv | Use of peptide agonists of the vasopressin receptor |
| ATE444741T1 (de) | 2006-05-10 | 2009-10-15 | Biocompatibles Uk Ltd | Glp-1 peptide enthaltende kugelförmige mikrokapseln, deren produktion und deren verwendung |
| WO2007142926A1 (en) * | 2006-05-31 | 2007-12-13 | Immuneregen Biosciences, Inc. | Method to treat blood cell depletion |
| WO2008012629A2 (en) | 2006-07-24 | 2008-01-31 | Biorexis Pharmaceutical Corporation | Exendin fusion proteins |
| AU2007313001B2 (en) | 2006-10-13 | 2012-03-22 | Eli Lilly And Company | Pegylated PTH as PTH receptor modulators and uses thereof |
| AU2007319066B2 (en) | 2006-11-08 | 2013-09-19 | Zealand Pharma A/S | Selective glucagon-like-peptide-2 (GLP-2) analogues |
| EP1961765A1 (en) * | 2006-12-08 | 2008-08-27 | Zealand Pharma A/S | Truncated PTH peptides with a cyclic conformation |
| RU2477286C2 (ru) | 2007-01-05 | 2013-03-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | АНАЛОГИ ГЛЮКАГОНА, ОБЛАДАЮЩИЕ ПОВЫШЕННОЙ РАСТВОРИМОСТЬЮ В БУФЕРАХ С ФИЗИОЛОГИЧЕСКИМ ЗНАЧЕНИЕМ pH |
| EP2952522B1 (en) | 2007-01-31 | 2019-10-30 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| AU2008216265B2 (en) | 2007-02-15 | 2014-04-03 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| AU2008232709C1 (en) | 2007-03-28 | 2015-01-15 | President And Fellows Of Harvard College | Stitched polypeptides |
| JP5385266B2 (ja) | 2007-06-15 | 2014-01-08 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| WO2009037586A2 (en) | 2007-08-14 | 2009-03-26 | Ferring B.V. | Use of peptidic vasopressin receptor agonists |
| EP2187907A2 (en) * | 2007-09-11 | 2010-05-26 | Mondobiotech Laboratories AG | Use of tyr-w-mif-1 and urocortin 2 as therapeutic agents |
| WO2009043440A2 (en) * | 2007-09-11 | 2009-04-09 | Mondobiotech Laboratories Ag | Use of il-1 receptor peptide, alone or in combination with d-ala-gln-octadecyl ester, as a therapeutic agent |
| CA2699073A1 (en) * | 2007-09-11 | 2009-04-02 | Mondobiotech Laboratories Ag | Use of a peptide as a therapeutic agent |
| WO2009046848A1 (en) * | 2007-09-11 | 2009-04-16 | Mondobiotech Laboratories Ag | Use of the peptide thymosin beta 4 alone or in combination with cecropin a as a therapeutic agent |
| WO2009058662A2 (en) | 2007-10-30 | 2009-05-07 | Indiana University Research And Technology Corporation | Glucagon antagonists |
| US8980830B2 (en) | 2007-10-30 | 2015-03-17 | Indiana University Research And Technology Corporation | Peptide compounds exhibiting glucagon antagonist and GLP-1 agonist activity |
| CN101951937A (zh) * | 2007-12-21 | 2011-01-19 | 赫尔辛医疗股份公司 | 使用伊帕瑞林刺激胃肠系统动力的方法 |
| AU2009210570B2 (en) | 2008-01-30 | 2014-11-20 | Indiana University Research And Technology Corporation | Ester-based insulin prodrugs |
| EP2300037B1 (en) | 2008-06-17 | 2016-03-30 | Indiana University Research and Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| WO2009155257A1 (en) | 2008-06-17 | 2009-12-23 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability physiological ph buffers |
| DK2300035T3 (en) | 2008-06-17 | 2015-11-16 | Univ Indiana Res & Tech Corp | Mixed GIP-based agonists for the treatment of metabolic diseases and obesity |
| CN102256618A (zh) | 2008-10-17 | 2011-11-23 | 赛诺菲-安万特德国有限公司 | 胰岛素和glp-1激动剂的组合 |
| KR20110126592A (ko) | 2008-12-15 | 2011-11-23 | 질랜드 파마 에이/에스 | 글루카곤 유사체 |
| US8685919B2 (en) | 2008-12-15 | 2014-04-01 | Zealand Pharma A/S | Glucagon analogues |
| WO2010070255A1 (en) | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| JP5635531B2 (ja) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| 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 |
| WO2010080606A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Insulin analogs |
| WO2010080609A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| WO2010148089A1 (en) | 2009-06-16 | 2010-12-23 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| PL2451437T3 (pl) | 2009-07-06 | 2017-05-31 | Sanofi-Aventis Deutschland Gmbh | Wodne preparaty insuliny zawierające metioninę |
| AP3329A (en) | 2009-07-13 | 2015-06-30 | Zealand Pharma As | Acylated glucagon analogues |
| SG10201406930UA (en) | 2009-07-27 | 2014-11-27 | Nocicepta Llc | Methods For Treatment Of Pain |
| FR2948809B1 (fr) * | 2009-07-31 | 2012-08-17 | St Microelectronics Rousset | Amplificateur de lecture faible puissance auto-minute |
| US8916517B2 (en) | 2009-11-02 | 2014-12-23 | The Administrators Of The Tulane Educational Fund | Analogs of pituitary adenylate cyclase-activating polypeptide (PACAP) and methods for their use |
| NZ599847A (en) | 2009-11-13 | 2013-09-27 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a glp-1 agonist and methionine |
| TR201809460T4 (tr) | 2009-11-13 | 2018-07-23 | Sanofi Aventis Deutschland | Bir GLP- 1-agonisti, bir insülin ve metiyonin içeren farmasötik bileşim. |
| US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| US9249189B2 (en) * | 2010-01-18 | 2016-02-02 | Albany Medical College | Alpha-fetoprotein “ring and tail” peptides |
| US8883739B2 (en) | 2010-01-19 | 2014-11-11 | The Trustees Of Columbia University In The City Of New York | Osteocalcin as a treatment for male reproductive disorders |
| BR112012018104A2 (pt) | 2010-01-20 | 2017-10-17 | Zeland Pharma As | tratamento de doenças cardíacas |
| 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 |
| EA023925B1 (ru) | 2010-04-27 | 2016-07-29 | Зилэнд Фарма А/С | Пептидные конъюгаты агонистов рецептора glp-1 и их применение |
| WO2011143208A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting g protein-coupled receptor activity |
| CA2797095A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
| EP2582719B1 (en) | 2010-06-16 | 2016-08-10 | Indiana University Research and Technology Corporation | Single chain insulin agonists exhibiting high activity at the insulin receptor |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| RU2580317C2 (ru) | 2010-06-24 | 2016-04-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов |
| JP5912112B2 (ja) | 2010-06-24 | 2016-04-27 | 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Indiana University Research And Technology Corporation | アミド系インスリンプロドラッグ |
| PH12012502472A1 (en) | 2010-06-24 | 2013-03-25 | Zealand Pharma As | Glucagon analogues |
| KR20170058446A (ko) | 2010-08-13 | 2017-05-26 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| WO2012028172A1 (en) | 2010-08-30 | 2012-03-08 | Sanofi-Aventis Deutschland Gmbh | Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2 |
| US8796416B1 (en) | 2010-10-25 | 2014-08-05 | Questcor Pharmaceuticals, Inc | ACTH prophylactic treatment of renal disorders |
| US8507428B2 (en) | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| 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 |
| EP2678002A2 (en) | 2011-02-25 | 2014-01-01 | Medtronic, Inc. | Therapy for kidney disease and/or heart failure |
| EP3189835B1 (en) * | 2011-02-28 | 2018-07-25 | National Cerebral and Cardiovascular Center | Medical agent for suppressing malignant tumor metastasis |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| RS56173B1 (sr) | 2011-06-22 | 2017-11-30 | Univ Indiana Res & Tech Corp | Koagonisti receptora za glukagon/glp-1 receptora |
| BR112013032717A2 (pt) | 2011-06-22 | 2017-01-24 | Univ Indiana Res & Tech Corp | coagonistas do receptor de glucagon/glp-1 |
| AR087693A1 (es) | 2011-08-29 | 2014-04-09 | Sanofi Aventis Deutschland | Combinacion farmaceutica para uso en el control glucemico en pacientes con diabetes de tipo 2 |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| EP2750697A4 (en) | 2011-09-02 | 2015-03-25 | Medtronic Inc | CHIMERIC NATRIURETIC PEPTIDE COMPOSITIONS AND METHOD FOR THE PRODUCTION THEREOF |
| EP2753642B8 (en) | 2011-09-06 | 2017-12-13 | Novo Nordisk A/S | Glp-1 derivatives |
| AR088392A1 (es) | 2011-10-18 | 2014-05-28 | Aileron Therapeutics Inc | Macrociclos peptidomimeticos |
| MX2014005351A (es) | 2011-11-03 | 2014-05-28 | Zealand Pharma As | Conjugados de gastrina peptidicos de agonistas de receptor glp-1. |
| RU2014117678A (ru) | 2011-11-17 | 2015-12-27 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептиды глюкагонового суперсемейства, обладающие глюкокортикоидной рецепторной активностью |
| CN102504019B (zh) * | 2011-12-01 | 2014-04-23 | 北京龙科方舟生物工程技术有限公司 | 一种分离天蚕素抗菌肽的方法 |
| US9573987B2 (en) | 2011-12-20 | 2017-02-21 | Indiana University Research And Technology Corporation | CTP-based insulin analogs for treatment of diabetes |
| WO2013092703A2 (en) | 2011-12-23 | 2013-06-27 | Zealand Pharma A/S | Glucagon analogues |
| US10272068B2 (en) | 2012-01-17 | 2019-04-30 | Tyme, Inc. | Pharmaceutical compositions and methods |
| US20130183263A1 (en) | 2012-01-17 | 2013-07-18 | Steven Hoffman | Pharmaceutical compositions and methods |
| US10646552B2 (en) | 2012-01-17 | 2020-05-12 | Tyme, Inc. | Pharmaceutical compositions and methods |
| PL2804599T3 (pl) * | 2012-01-17 | 2019-06-28 | Tyme, Inc. | Terapia skojarzona do leczenia nowotworu złośliwego |
| US8481498B1 (en) | 2012-01-17 | 2013-07-09 | Steven Hoffman | Pharmaceutical compositions and methods |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| CA2862038C (en) | 2012-02-15 | 2021-05-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CN103308670B (zh) * | 2012-03-08 | 2017-06-09 | 思芬构技术有限公司 | 用于预测对象患糖尿病和/或代谢综合征的风险的方法 |
| AU2013255752B2 (en) | 2012-05-03 | 2017-11-09 | Zealand Pharma A/S | Glucagon-like-peptide-2 (GLP-2) analogues |
| JP6228187B2 (ja) | 2012-05-03 | 2017-11-08 | ジーランド ファーマ アクティーゼルスカブ | Gip−glp−1デュアルアゴニスト化合物及び方法 |
| US10052366B2 (en) | 2012-05-21 | 2018-08-21 | Alexion Pharmaceuticsl, Inc. | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
| CA2877358A1 (en) | 2012-06-21 | 2013-12-27 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| AU2013295035B2 (en) | 2012-07-23 | 2017-08-03 | Zealand Pharma A/S | Glucagon analogues |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| AU2013323669B2 (en) | 2012-09-26 | 2018-03-01 | Indiana University Research And Technology Corporation | Insulin analog dimers |
| JP5715104B2 (ja) * | 2012-09-27 | 2015-05-07 | アブビー インコーポレイティド | 治療的に活性なα−MSHアナログ |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| US9217023B2 (en) | 2012-10-19 | 2015-12-22 | Txp Pharma Gmbh | Alpha- and gamma-MSH analogues |
| BR112015009470A2 (pt) | 2012-11-01 | 2019-12-17 | Aileron Therapeutics Inc | aminoácidos dissubstituídos e seus métodos de preparação e uso |
| HK1211232A1 (en) | 2012-12-21 | 2016-05-20 | Sanofi | Exendin-4 derivatives as dual glp1/gip or trigonal glp1/gip/glucagon agonists |
| TWI780236B (zh) | 2013-02-04 | 2022-10-11 | 法商賽諾菲公司 | 胰島素類似物及/或胰島素衍生物之穩定化醫藥調配物 |
| WO2014158900A1 (en) | 2013-03-14 | 2014-10-02 | Indiana University Research And Technology Corporation | Insulin-incretin conjugates |
| WO2014152497A2 (en) | 2013-03-15 | 2014-09-25 | The Trustees Of Columbia University In The City Of New York | Osteocalcin as a treatment for cognitive disorders |
| WO2014147129A1 (en) | 2013-03-21 | 2014-09-25 | Sanofi-Aventis Deutschland Gmbh | Synthesis of cyclic imide containing peptide products |
| CN105189465B (zh) | 2013-03-21 | 2019-02-26 | 赛诺菲-安万特德国有限公司 | 合成含有乙内酰脲的肽产物 |
| WO2014180534A1 (de) * | 2013-05-07 | 2014-11-13 | Merck Patent Gmbh | Peptide und peptid-wirkstoff-konjugate für renales targeting |
| WO2015055801A1 (en) | 2013-10-17 | 2015-04-23 | Zealand Pharma A/S | Acylated glucagon analogues |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| US9585841B2 (en) | 2013-10-22 | 2017-03-07 | Tyme, Inc. | Tyrosine derivatives and compositions comprising them |
| US9763903B2 (en) | 2013-10-22 | 2017-09-19 | Steven Hoffman | Compositions and methods for treating intestinal hyperpermeability |
| US10751313B2 (en) | 2013-10-22 | 2020-08-25 | Yamo Pharmaceuticals Llc | Compositions and methods for treating autism |
| US9326962B2 (en) | 2013-10-22 | 2016-05-03 | Steven Hoffman | Compositions and methods for treating intestinal hyperpermeability |
| US10813901B2 (en) | 2013-10-22 | 2020-10-27 | Yamo Pharmaceuticals Llc | Compositions and methods for treating autism |
| AU2014345570B2 (en) | 2013-11-06 | 2019-01-24 | Zealand Pharma A/S | Glucagon-GLP-1-GIP triple agonist compounds |
| MX2016005556A (es) | 2013-11-06 | 2016-07-15 | Zealand Pharma As | Compuestos agonistas duales de gip-glp-1 y procedimientos. |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
| TW201609799A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重glp-1/gip受體促效劑 |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| JP6723921B2 (ja) | 2014-01-09 | 2020-07-15 | サノフイSanofi | インスリンアナログおよび/またはインスリン誘導体の、グリセリンを含まない安定化された医薬製剤 |
| CN105960249B (zh) | 2014-01-09 | 2021-03-16 | 赛诺菲 | 胰岛素类似物和/或胰岛素衍生物的稳定化药物制剂 |
| US9895423B2 (en) | 2014-01-09 | 2018-02-20 | Sanofi | Stabilized pharmaceutical formulations of insulin aspart |
| 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 |
| 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 |
| 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 |
| EP3838285A1 (en) * | 2014-04-22 | 2021-06-23 | TXP Pharma GmbH | Peptide analogues with branched amino acid probe(s) |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| US10822596B2 (en) | 2014-07-11 | 2020-11-03 | Alexion Pharmaceuticals, Inc. | Compositions and methods for treating craniosynostosis |
| ES2822994T3 (es) | 2014-09-24 | 2021-05-05 | Univ Indiana Res & Tech Corp | Conjugados de incretina-insulina |
| WO2016049359A1 (en) | 2014-09-24 | 2016-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2016049174A1 (en) | 2014-09-24 | 2016-03-31 | Indiana University Research And Technology Corporation | Lipidated amide-based insulin prodrugs |
| US10253078B2 (en) | 2014-10-29 | 2019-04-09 | Zealand Pharma A/S | GIP agonist compounds and methods |
| EP3226889A4 (en) | 2014-11-19 | 2018-11-21 | The Trustees of Columbia University in the City of New York | Osteocalcin as a treatment for frailty associated with aging |
| JP6787894B2 (ja) | 2014-12-05 | 2020-11-18 | 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 | 組換えアルカリホスファターゼを用いた発作の処置 |
| PE20171622A1 (es) | 2014-12-12 | 2017-11-02 | Sanofi Aventis Deutschland | Formulacion de relacion fija de insulina glargina/lixisenatida |
| SG11201705591PA (en) | 2015-01-07 | 2017-08-30 | Trigemina Inc | Magnesium-containing oxytocin formulations and methods of use |
| 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 |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患之治療 |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US10336802B2 (en) | 2015-04-16 | 2019-07-02 | Zealand Pharma A/S | Acylated glucagon analogue |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
| JP6993961B2 (ja) | 2015-08-17 | 2022-01-14 | 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の製造 |
| EP3355904A4 (en) | 2015-09-28 | 2019-06-12 | Alexion Pharmaceuticals, Inc. | IDENTIFICATION OF EFFECTIVE DOSE SHEETS FOR TISSUE-SPECIFIC ALKALINE PHOSPHATASE ENZYMERSAT THERAPY OF HYPOPHOSPHATASIA |
| WO2017068020A1 (en) | 2015-10-20 | 2017-04-27 | Txp Pharma Gmbh | W-peptide analog |
| WO2017074466A1 (en) | 2015-10-30 | 2017-05-04 | Alexion Pharmaceuticals, Inc. | Methods for treating craniosynostosis in a patient |
| WO2017155569A1 (en) | 2016-03-08 | 2017-09-14 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in children |
| US10898549B2 (en) | 2016-04-01 | 2021-01-26 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
| KR20240160671A (ko) | 2016-04-01 | 2024-11-11 | 알렉시온 파마슈티칼스, 인코포레이티드 | 알칼리성 포스파타아제로 근육 약화의 치료 |
| HUE070412T2 (hu) | 2016-04-12 | 2025-06-28 | Tonix Pharma Ltd | Magnézium tartalmú oxitocin készítmények és alkamazási eljárásaik |
| EP3464573B1 (en) | 2016-06-06 | 2026-03-04 | Alexion Pharmaceuticals, Inc. | Metal impact on manufacturing of alkaline phosphatases |
| EP3500289B1 (en) | 2016-08-18 | 2024-10-09 | Alexion Pharmaceuticals, Inc. | Asfotase alfa for use in treating tracheobronchomalacia |
| WO2018102616A1 (en) * | 2016-11-30 | 2018-06-07 | Purdue Research Foundation | Fracture targeted bone regeneration through parathyroid hormone receptor stimulation |
| AU2017371516C1 (en) | 2016-12-09 | 2021-09-02 | Zealand Pharma A/S | Acylated GLP-1/GLP-2 dual agonists |
| KR20190129058A (ko) | 2017-03-31 | 2019-11-19 | 알렉시온 파마슈티칼스, 인코포레이티드 | 성인 및 청소년에서 저포스파타제증 (hpp)을 치료하는 방법 |
| BR112019026711A2 (pt) | 2017-06-16 | 2020-06-30 | Zealand Pharma A/S | regimes de dosagem para a administração de análogos de peptídeo semelhante a glucagon- 2 (glp-2) |
| CA3067674A1 (en) * | 2017-06-29 | 2019-01-03 | Ureka Sarl | Pro-drug peptide with improved pharmaceutical properties |
| CN107964047B (zh) * | 2017-12-18 | 2018-11-02 | 哈尔滨工业大学 | 基于内吗啡肽-1和神经降压素(8-13)的嵌合肽及其合成方法和应用 |
| US11913039B2 (en) | 2018-03-30 | 2024-02-27 | Alexion Pharmaceuticals, Inc. | Method for producing recombinant alkaline phosphatase |
| WO2020018291A1 (en) | 2018-07-19 | 2020-01-23 | Yamo Pharmaceuticals Llc | Compositions and methods for treating autism |
| ES2972119T3 (es) | 2018-08-10 | 2024-06-11 | Alexion Pharma Inc | Cicatrización ósea en implantes utilizando fosfatasa alcalina |
| CN109879935B (zh) * | 2019-03-04 | 2020-11-20 | 南京工业大学 | 一种多肽的液相合成方法 |
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| WO2022034062A1 (en) | 2020-08-12 | 2022-02-17 | Txp Pharma Ag | Exendin-4 peptide analogues |
| US12083169B2 (en) | 2021-02-12 | 2024-09-10 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| CN116284329B (zh) * | 2023-04-28 | 2023-12-08 | 成都奥达生物科技有限公司 | 一种长效利钠肽化合物 |
| CN116284221A (zh) * | 2023-05-10 | 2023-06-23 | 安徽省华信生物药业股份有限公司 | 一种促肿瘤相关巨噬细胞向m1型极化的硒酵母活性肽及制备方法 |
| WO2025196125A1 (en) | 2024-03-19 | 2025-09-25 | Epoqe Pharma Aps | N-terminally modified calcitonin gene-related peptide analogues |
| CN120424236A (zh) * | 2025-07-04 | 2025-08-05 | 南开大学 | 一种具有igf-1功能的自组装多肽及其生发应用 |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5116666A (https=) * | 1974-07-30 | 1976-02-10 | Shionogi Seiyaku Kk | |
| US4018434A (en) * | 1976-04-12 | 1977-04-19 | Pitney-Bowes, Inc. | Pneumatic feed device |
| US4081434A (en) * | 1977-03-11 | 1978-03-28 | Hoffmann-La Roche Inc. | Novel analogs of β-endorphin |
| US4096237A (en) * | 1977-03-14 | 1978-06-20 | Hoffmann-La Roche Inc. | Immunoassay for β-endorphin |
| US4847240A (en) * | 1978-01-16 | 1989-07-11 | The Trustees Of Boston University | Method of effecting cellular uptake of molecules |
| US4288627A (en) | 1980-02-12 | 1981-09-08 | Phillips Petroleum Company | Oxidation of thiols employing cobalt molybdate/triethylamine catalyst |
| US4457864A (en) | 1981-10-23 | 1984-07-03 | University Patents, Inc. | Synthetic analogues of α-melanotropin |
| US4485039A (en) | 1982-06-11 | 1984-11-27 | University Patents, Inc. | Synthetic analogues of α-melanotropin |
| US4469679A (en) * | 1983-02-16 | 1984-09-04 | Smithkline Beckman Corporation | Octapeptide vasopressin antagonists |
| JPH0680079B2 (ja) * | 1984-11-09 | 1994-10-12 | エーザイ株式会社 | ポリペプチド |
| DE3546150A1 (de) * | 1985-06-24 | 1987-01-22 | Hoechst Ag | Membrananker-wirkstoffkonjugat, seine herstellung sowie seine verwendung |
| US4724229A (en) * | 1986-09-30 | 1988-02-09 | Smithkline Beckman Corporation | Arg-arg-arg-vasopressin antagonists |
| US5021550A (en) | 1986-10-07 | 1991-06-04 | Thomas Jefferson University | Method for preventing deletion sequences in solid phase synthesis |
| US4833125A (en) * | 1986-12-05 | 1989-05-23 | The General Hospital Corporation | Method of increasing bone mass |
| US5317090A (en) * | 1987-12-16 | 1994-05-31 | Institut Pasteur | Steroid/thyroid hormone receptor-related gene, which is inappropriately expressed in human hepatocellular carcinoma, and which is a retinoic acid receptor |
| DE69021335T2 (de) * | 1989-06-09 | 1996-04-11 | Gropep Pty. Ltd., Adelaide | Wachstumshormonfusionsproteine. |
| JP2807287B2 (ja) * | 1989-10-13 | 1998-10-08 | 株式会社医学生物学研究所 | ペプチドおよびその用途 |
| US5670617A (en) * | 1989-12-21 | 1997-09-23 | Biogen Inc | Nucleic acid conjugates of tat-derived transport polypeptides |
| US5545719A (en) * | 1990-05-01 | 1996-08-13 | Neuromedica, Inc. | Nerve growth peptides |
| CA2082279C (en) | 1990-05-09 | 2007-09-04 | Grethe Rasmussen | Cellulase preparation comprising an endoglucanase enzyme |
| IE66205B1 (en) * | 1990-06-14 | 1995-12-13 | Paul A Bartlett | Polypeptide analogs |
| US5831001A (en) * | 1990-10-24 | 1998-11-03 | Allelix Biopharmaceuticals Inc. | Treatment of herpesvirus infection |
| US5646120A (en) * | 1990-10-24 | 1997-07-08 | Allelix Biopharmaceuticals, Inc. | Peptide-based inhibitors of HIV replication |
| CA2096933C (en) * | 1990-12-13 | 2003-05-13 | Bruce E. Kemp | Compounds and compositions which inhibit bone resorption |
| US5723129A (en) * | 1991-10-16 | 1998-03-03 | University Of Saskatchewan | GnRH-leukotoxin chimeras |
| ES2139012T3 (es) | 1992-05-26 | 2000-02-01 | Univ Leiden | Peptidos de la proteina p53 humana destinados para ser utilizados en composiciones que inducen una reaccion en los linfocitos t humanos, y linfocitos t citotoxicos especificos de la proteina p53 humana. |
| US5814603A (en) | 1992-06-12 | 1998-09-29 | Affymax Technologies N.V. | Compounds with PTH activity |
| US5512473A (en) | 1993-01-29 | 1996-04-30 | Brent; Roger | Max-interacting proteins and related molecules and methods |
| SK121895A3 (en) * | 1993-03-29 | 1996-10-02 | Univ Cincinnati | Analogues of peptide yy and uses thereof |
| FR2708938B1 (fr) * | 1993-08-09 | 1995-11-03 | Bioeurope | Procédé enzymatique perfectionné de préparation d'oligomères de L-lysine. |
| CA2170030A1 (en) | 1993-09-14 | 1995-03-23 | Robert A. Lazarus | Pharmaceutical compositions containing ecotin and homologs thereof |
| AU1086595A (en) * | 1993-11-08 | 1995-05-29 | Demeter Biotechnologies, Ltd. | Methylated lysine-rich lytic peptides and method of making same by reductive alkylation |
| US5716614A (en) | 1994-08-05 | 1998-02-10 | Molecular/Structural Biotechnologies, Inc. | Method for delivering active agents to mammalian brains in a complex with eicosapentaenoic acid or docosahexaenoic acid-conjugated polycationic carrier |
| US6037145A (en) * | 1994-09-07 | 2000-03-14 | Suntory Limited | Process for production of protein |
| US5625048A (en) | 1994-11-10 | 1997-04-29 | The Regents Of The University Of California | Modified green fluorescent proteins |
| US5985829A (en) | 1994-12-19 | 1999-11-16 | The United States Of America As Represented By The Department Of Health And Human Services | Screening assays for compounds that cause apoptosis and related compounds |
| WO1996022067A2 (en) * | 1994-12-27 | 1996-07-25 | United Biomedical, Inc. | Peptide ratchet libraries for ctl-inducing vaccines and therapeutics |
| US5731408A (en) | 1995-04-10 | 1998-03-24 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Peptides having potent antagonist and agonist bioactivities at melanocortin receptors |
| AU5512096A (en) * | 1995-05-17 | 1996-11-29 | University Of Alberta | Method of inhibiting restenosis using calreticulin |
| GB9526733D0 (en) | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
| US5968513A (en) * | 1996-06-24 | 1999-10-19 | University Of Maryland Biotechnology Institute | Method of promoting hematopoiesis using derivatives of human chorionic gonadotropin |
| US5916872A (en) * | 1996-07-24 | 1999-06-29 | Intrabiotics Pharmaceuticals, Inc. | Cyclic peptides having broad spectrum antimicrobial activity |
| IL128332A0 (en) | 1996-08-30 | 2000-01-31 | Novo Nordisk As | GLP-1 derivatives |
| US6126939A (en) * | 1996-09-03 | 2000-10-03 | Yeda Research And Development Co. Ltd. | Anti-inflammatory dipeptide and pharmaceutical composition thereof |
| CZ295838B6 (cs) * | 1996-09-09 | 2005-11-16 | Zealand Pharma A/S | Způsob výroby peptidů |
| US7176282B1 (en) * | 1996-09-09 | 2007-02-13 | Zealand Pharma A/S | Solid-phase peptide synthesis and agent for use in such synthesis |
| WO1998011126A1 (en) * | 1996-09-09 | 1998-03-19 | Zealand Pharmaceuticals A/S | Peptide prodrugs containing an alpha-hydroxyacid linker |
| WO1998022577A1 (en) * | 1996-11-15 | 1998-05-28 | Maria Grazia Masucci | Fusion proteins having increased half-lives |
| WO1998028427A1 (en) | 1996-12-20 | 1998-07-02 | Amgen Inc. | Ob fusion protein compositions and methods |
| US5831513A (en) * | 1997-02-04 | 1998-11-03 | United Microelectronics Corp. | Magnetic field sensing device |
| IL132941A0 (en) | 1997-05-21 | 2001-03-19 | Univ Leland Stanford Junior | Composition and method for enhancing transport across biological membranes |
| US6737408B1 (en) * | 1997-08-07 | 2004-05-18 | University Of Cincinnati | Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm |
| JP4394279B2 (ja) | 1998-03-09 | 2010-01-06 | ジーランド ファーマ アクティーゼルスカブ | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
| SE9801571D0 (sv) | 1998-05-05 | 1998-05-05 | Wapharm Ab | Melanokortin-1-receptorselektiva föreningar |
| EP1076066A1 (en) | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
| GB9927346D0 (en) | 1999-11-18 | 2000-01-12 | Melacure Therapeutics Ab | Method for analysis and design of entities of a chemical or biochemical nature |
| GB0012370D0 (en) | 2000-05-22 | 2000-07-12 | Quadrant Holdings Cambridge | Peptoids |
| EP1919947B1 (en) | 2005-08-26 | 2013-02-27 | AbbVie Inc. | Therapeutically active alpha-msh analogues |
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- 1999-03-09 JP JP2000535659A patent/JP4394279B2/ja not_active Expired - Fee Related
- 1999-03-09 EP EP07010570A patent/EP1950224A3/en not_active Withdrawn
- 1999-03-09 EP EP99907329A patent/EP1062229A1/en not_active Withdrawn
- 1999-03-09 CA CA002321026A patent/CA2321026A1/en not_active Abandoned
- 1999-03-09 EP EP07021432A patent/EP1950223A3/en not_active Withdrawn
- 1999-03-09 IL IL13821499A patent/IL138214A0/xx unknown
- 1999-03-09 AU AU27132/99A patent/AU757658B2/en not_active Ceased
- 1999-03-09 WO PCT/DK1999/000118 patent/WO1999046283A1/en not_active Ceased
- 1999-03-09 NZ NZ506839A patent/NZ506839A/en unknown
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- 2007-07-16 US US11/879,104 patent/US20080015152A1/en not_active Abandoned
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- 2007-10-25 IL IL186955A patent/IL186955A/en not_active IP Right Cessation
- 2007-10-31 US US11/981,669 patent/US20080227954A1/en not_active Abandoned
- 2007-10-31 US US11/981,814 patent/US20080234467A1/en not_active Abandoned
- 2007-10-31 US US11/981,811 patent/US20080139785A1/en not_active Abandoned
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2011
- 2011-02-15 US US13/027,475 patent/US20110312878A1/en not_active Abandoned
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|---|---|
| AU2713299A (en) | 1999-09-27 |
| IL138214A0 (en) | 2001-10-31 |
| JP2007302675A (ja) | 2007-11-22 |
| EP1062229A1 (en) | 2000-12-27 |
| US20110312878A1 (en) | 2011-12-22 |
| US20080015152A1 (en) | 2008-01-17 |
| JP2002509082A (ja) | 2002-03-26 |
| WO1999046283A1 (en) | 1999-09-16 |
| EP1950224A2 (en) | 2008-07-30 |
| EP1950223A3 (en) | 2009-05-13 |
| IL184482A0 (en) | 2007-10-31 |
| CA2321026A1 (en) | 1999-09-16 |
| IL186955A (en) | 2012-12-31 |
| US20070293418A1 (en) | 2007-12-20 |
| NZ506839A (en) | 2003-05-30 |
| WO1999046283A9 (en) | 1999-11-18 |
| JP2007320961A (ja) | 2007-12-13 |
| US20080234467A1 (en) | 2008-09-25 |
| JP4394704B2 (ja) | 2010-01-06 |
| IL186955A0 (en) | 2008-02-09 |
| US20060063699A1 (en) | 2006-03-23 |
| EP1950223A2 (en) | 2008-07-30 |
| EP1950224A3 (en) | 2008-12-17 |
| US7414107B2 (en) | 2008-08-19 |
| AU757658B2 (en) | 2003-02-27 |
| US20080227954A1 (en) | 2008-09-18 |
| US7935786B2 (en) | 2011-05-03 |
| US20080139785A1 (en) | 2008-06-12 |
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