PT2621515T - Polipéptido quimérico de leptina de foca-ser humano com solubilidade aumentada - Google Patents
Polipéptido quimérico de leptina de foca-ser humano com solubilidade aumentada Download PDFInfo
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- PT2621515T PT2621515T PT118330752T PT11833075T PT2621515T PT 2621515 T PT2621515 T PT 2621515T PT 118330752 T PT118330752 T PT 118330752T PT 11833075 T PT11833075 T PT 11833075T PT 2621515 T PT2621515 T PT 2621515T
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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Landscapes
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| DK2729160T3 (da) | 2011-07-08 | 2019-07-01 | Aegerion Pharmaceuticals Inc | Manipulerede polypeptider, der har forbedret virkningstid og reduceret immunogenicitet |
| US20150133373A1 (en) * | 2012-03-28 | 2015-05-14 | Amylin Pharmaceuticals, Llc | Transmucosal delivery of engineered polypeptides |
| JP6590695B2 (ja) * | 2012-09-25 | 2019-10-16 | アフィボディ・アーベー | アルブミン結合ポリペプチド |
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| WO2014204816A2 (en) | 2013-06-17 | 2014-12-24 | Armo Biosciences, Inc. | Method for assessing protein identity and stability |
| CA2920679A1 (en) | 2013-08-30 | 2015-03-05 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| CN105848674A (zh) | 2013-11-11 | 2016-08-10 | 阿尔莫生物科技股份有限公司 | 将白细胞介素-10用于治疗疾病和病症的方法 |
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| US10293043B2 (en) | 2014-06-02 | 2019-05-21 | Armo Biosciences, Inc. | Methods of lowering serum cholesterol |
| CN106687474A (zh) | 2014-09-04 | 2017-05-17 | 诺和诺德股份有限公司 | 新型胰淀素和降钙素受体激动剂 |
| CA2963989A1 (en) | 2014-10-14 | 2016-04-21 | Armo Biosciences, Inc. | Interleukin-15 compositions and uses thereof |
| CN107106655A (zh) | 2014-10-22 | 2017-08-29 | 阿尔莫生物科技股份有限公司 | 使用白细胞介素‑10治疗疾病和病症的方法 |
| WO2016126615A1 (en) | 2015-02-03 | 2016-08-11 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| CN107847583A (zh) | 2015-05-28 | 2018-03-27 | 阿尔莫生物科技股份有限公司 | 用于治疗癌症的聚乙二醇化白细胞介素‑10 |
| CN108137653B (zh) * | 2015-08-05 | 2021-07-13 | 陕西麦科奥特科技有限公司 | 有抗凝血和抗血小板活性的多靶点化合物及制法和用途 |
| US10286079B2 (en) | 2015-09-22 | 2019-05-14 | The Regents Of The University Of California | Modified cytotoxins and their therapeutic use |
| AU2016326392B2 (en) | 2015-09-22 | 2021-02-11 | The Regents Of The University Of California | Modified cytotoxins and their therapeutic use |
| BR112018006263A2 (pt) | 2015-10-02 | 2018-10-16 | Memorial Sloan Kettering Cancer Center | inibidor de tonsl, molécula pequena, uso de uma molécula pequena ou de um inibidor, cristal tridimensional, métodos para selecionar ou desenhar uma molécula pequena, para identificar um inibidor de ligação de ard de tonsl à histona h4, para predizer o efeito de inibição de tonsl e para identificar um inibidor de tonsl e/ou determinar o efeito inibitório de um inibidor putativo de tonsl, sequência de polinucleotídeo ou sequência de aminoácidos isolada, e, polipeptídeo mutante de tonsl. |
| EP3509624B1 (en) | 2016-09-12 | 2023-08-09 | Amryt Pharmaceuticals Inc. | Methods of detecting anti-leptin neutralizing antibodies |
| KR20230173731A (ko) * | 2017-01-30 | 2023-12-27 | 알렉시온 파마슈티칼스, 인코포레이티드 | 1가 항-프로페르딘 항체 및 항체 단편 |
| JP2021520822A (ja) * | 2018-04-13 | 2021-08-26 | マサチューセッツ インスティテュート オブ テクノロジー | 毛髪の修復および長期にわたる色の保持のための改変された処置 |
| EP3711772A1 (en) * | 2019-03-20 | 2020-09-23 | Oslo Universitetssykehus HF | Recombinant proteins and fusion proteins |
| WO2023049357A2 (en) * | 2021-09-24 | 2023-03-30 | The Uab Research Foundation | Control of subunit stoichiometry in single-chain msp nanopores |
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| US4002531A (en) | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| US4572208A (en) | 1983-06-29 | 1986-02-25 | Utah Medical Products, Inc. | Metabolic gas monitoring apparatus and method |
| KR850004274A (ko) | 1983-12-13 | 1985-07-11 | 원본미기재 | 에리트로포이에틴의 제조방법 |
| US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
| NZ210501A (en) | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
| US6319685B1 (en) | 1984-09-27 | 2001-11-20 | Unigene Laboratories, Inc. | Alpha-amidating enzyme compositions and processes for their production and use |
| FI78231C (fi) | 1984-11-21 | 1989-07-10 | Instrumentarium Oy | Maetanordning foer metaboliska storheter anslutbar till en respirator. |
| US4695463A (en) | 1985-05-24 | 1987-09-22 | Warner-Lambert Company | Delivery system for active ingredients and preparation thereof |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4810643A (en) | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| JPS63500636A (ja) | 1985-08-23 | 1988-03-10 | 麒麟麦酒株式会社 | 多分化能性顆粒球コロニー刺激因子をコードするｄｎａ |
| US4904584A (en) | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US5075222A (en) | 1988-05-27 | 1991-12-24 | Synergen, Inc. | Interleukin-1 inhibitors |
| EP0401384B1 (en) | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| AU6541090A (en) | 1989-10-16 | 1991-05-16 | Amgen, Inc. | Stem cell factor |
| US5372808A (en) | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
| HU222249B1 (hu) | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására |
| ATE169031T1 (de) | 1991-04-05 | 1998-08-15 | Univ Washington | Zellrezeptor spezifische monoklonale antikörper gegen stammzell-faktor-rezeptor |
| NZ244778A (en) | 1991-10-21 | 1994-03-25 | Ortho Pharma Corp | Peg imidates and protein derivatives thereof |
| US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| US5581476A (en) | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| US5766627A (en) | 1993-11-16 | 1998-06-16 | Depotech | Multivescular liposomes with controlled release of encapsulated biologically active substances |
| US6288030B1 (en) | 1993-12-22 | 2001-09-11 | Amgen Inc. | Stem cell factor formulations and methods |
| US6048837A (en) | 1994-08-17 | 2000-04-11 | The Rockefeller University | OB polypeptides as modulators of body weight |
| US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
| US6001968A (en) | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| US5827734A (en) | 1995-01-20 | 1998-10-27 | University Of Washington | Materials and methods for determining ob protein in a biological sample |
| US5552523A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5569744A (en) | 1995-01-31 | 1996-10-29 | Eli Lilly And Company | Anti-obesity proteins |
| US5525705A (en) | 1995-01-31 | 1996-06-11 | Eli Lilly And Company | Anti-obesity proteins |
| US5559208A (en) | 1995-01-31 | 1996-09-24 | Eli Lilly And Company | Anti-obesity proteins |
| US5567803A (en) | 1995-01-31 | 1996-10-22 | Eli Lilly And Company | Anti-obesity proteins |
| US5569743A (en) | 1995-01-31 | 1996-10-29 | Eli Lilly And Company | Anti-obesity proteins |
| US5563243A (en) | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5580954A (en) | 1995-01-31 | 1996-12-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5552524A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5563244A (en) | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5554727A (en) | 1995-01-31 | 1996-09-10 | Eli Lilly And Company | Anti-obesity proteins |
| US5605886A (en) | 1995-01-31 | 1997-02-25 | Eli Lilly And Company | Anti-obesity proteins |
| US5563245A (en) | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| CA2211664A1 (en) * | 1995-01-31 | 1996-08-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5552522A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
| CA2211656A1 (en) | 1995-01-31 | 1996-08-08 | Margret B. Basinski | Anti-obesity proteins |
| AU4766596A (en) | 1995-01-31 | 1996-08-21 | Eli Lilly And Company | Ob gene product antibodies |
| US5594104A (en) | 1995-01-31 | 1997-01-14 | Eli Lilly And Company | Anti-obesity proteins |
| US5532336A (en) | 1995-01-31 | 1996-07-02 | Eli Lilly And Company | Anti-obesity proteins |
| US5574133A (en) | 1995-01-31 | 1996-11-12 | Eli Lilly And Company | Anti-obesity proteins |
| US5691309A (en) | 1995-01-31 | 1997-11-25 | Eli Lilly And Company | Anti-obesity proteins |
| US5567678A (en) | 1995-01-31 | 1996-10-22 | Eli Lilly And Company | Anti-obesity proteins |
| US5521283A (en) | 1995-01-31 | 1996-05-28 | Eli Lilly And Company | Anti-obesity proteins |
| US5594101A (en) | 1995-03-03 | 1997-01-14 | Eli Lilly And Company | Anti-obesity proteins |
| US5719266A (en) | 1995-03-17 | 1998-02-17 | Eli Lilly And Company | Anti-obesity proteins |
| EP0736599A3 (en) | 1995-04-03 | 1996-12-11 | Takeda Chemical Industries Ltd | The rat obesity gene, its gene product and its production |
| AU5539596A (en) | 1995-04-06 | 1996-10-23 | Amylin Pharmaceuticals, Inc. | Anti-obesity agents |
| US5840517A (en) * | 1995-04-26 | 1998-11-24 | Eli Lilly And Company | Process for preparing obesity protein analogs |
| US5614379A (en) | 1995-04-26 | 1997-03-25 | Eli Lilly And Company | Process for preparing anti-obesity protein |
| GB9509164D0 (en) | 1995-05-05 | 1995-06-28 | Smithkline Beecham Plc | Novel compounds |
| ES2093593T1 (es) | 1995-05-05 | 1997-01-01 | Hoffmann La Roche | Proteinas obesas (ob) recombinantes. |
| WO1996035787A1 (en) | 1995-05-08 | 1996-11-14 | Chiron Corporation | Nucleic acids for treating obesity |
| JP2001501906A (ja) | 1995-05-26 | 2001-02-13 | イーライ・リリー・アンド・カンパニー | Ｒｈｅｓｕｓ ｏｂタンパク質およびｄｎａ |
| WO1996040912A1 (en) | 1995-06-07 | 1996-12-19 | Amgen Inc. | Ob protein compositions and method |
| US5581005A (en) | 1995-06-16 | 1996-12-03 | The Procter & Gamble Company | Method for manufacturing cobalt catalysts |
| AU6284896A (en) | 1995-06-22 | 1997-01-22 | Eli Lilly And Company | Obesity protein intermediates and their preparation and use |
| GB2302559B (en) | 1995-06-23 | 1998-06-03 | Draftex Ind Ltd | Opening arrangements and methods for closure members |
| DE69632684T2 (de) | 1995-06-27 | 2005-06-09 | Takeda Pharmaceutical Co. Ltd. | Verfahren zur herstellung von zubereitungen mit verzögerter freisetzung |
| IL122718A0 (en) | 1995-06-30 | 1998-08-16 | Lilly Co Eli | Methods for treating diabetes |
| EP0865294B1 (en) | 1995-08-17 | 2004-02-18 | Amgen Inc. | Methods of reducing or maintaining reduced levels of blood lipids using ob protein compositions |
| WO1997016550A1 (en) | 1995-11-02 | 1997-05-09 | Bristol-Myers Squibb Company | Polypeptide fragments derived from the obese gene product |
| ES2217327T3 (es) | 1995-11-22 | 2004-11-01 | Amgen Inc., | Proteina ob para aumentar la masa de tejido magro. |
| US6936439B2 (en) | 1995-11-22 | 2005-08-30 | Amgen Inc. | OB fusion protein compositions and methods |
| AU1406497A (en) | 1995-12-06 | 1997-06-27 | Schering Corporation | Mutational variants of mammalian ob gene proteins |
| US6369027B1 (en) | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
| GB9526733D0 (en) * | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
| EP0877627A1 (en) | 1996-01-25 | 1998-11-18 | Eli Lilly And Company | Obesity protein analog compounds and formulations thereof |
| US6013009A (en) | 1996-03-12 | 2000-01-11 | Karkanen; Kip Michael | Walking/running heart rate monitoring system |
| WO1997038014A1 (en) | 1996-04-04 | 1997-10-16 | Amgen Inc. | Fibulin pharmaceutical compositions and related methods |
| US6025324A (en) | 1996-05-15 | 2000-02-15 | Hoffmann-La Roche Inc. | Pegylated obese (ob) protein compositions |
| AR008765A1 (es) | 1996-06-06 | 2000-02-23 | Smithkline Beecham Plc | Un peptido o un derivado, analogo o variante, funcional del mismo, un peptido recombinante o sintetico del mismo, una secuencia nucleotidica y vectorque la contiene, una celula huesped transformada, un procedimiento para su preparacion, una composicion farmaceutica que lo comprende, un compuesto del |
| US5922678A (en) | 1996-06-28 | 1999-07-13 | Eli Lilly And Company | Methods for treating diabetes |
| JP2001501177A (ja) | 1996-08-30 | 2001-01-30 | アムジエン・インコーポレーテツド | Ｏｂタンパク質受容体をアップレギュレートすることによりｏｂタンパク質に対する個体の感受性を増加させる方法 |
| BR9711513A (pt) | 1996-09-20 | 1999-08-24 | Hoechst Ag | Uso de antagonistas de leptina para o tratamento de resistencia a insulina em diabete do tipo ii |
| WO1998016545A1 (en) | 1996-10-11 | 1998-04-23 | Eli Lilly And Company | Therapeutic proteins |
| WO1998024896A2 (en) | 1996-12-06 | 1998-06-11 | F. Hoffmann-La Roche Ag | Muteins of obese protein |
| EA004790B1 (ru) | 1996-12-20 | 2004-08-26 | Амген Инк. | Композиции на основе слитого белка ов и способы их применения |
| US6309360B1 (en) | 1997-03-17 | 2001-10-30 | James R. Mault | Respiratory calorimeter |
| AU6569998A (en) * | 1997-03-20 | 1998-10-12 | Eli Lilly And Company | Obesity protein formulations |
| TR199902980T2 (xx) | 1997-06-06 | 2000-05-22 | Smithkline Beecham P.L.C. | Diabetin tedavisi i�in leptin antagonistlerinin kullan�m�. |
| ES2235336T3 (es) | 1997-06-13 | 2005-07-01 | Gryphon Therapeutics, Inc. | Ligacion quimica nativa en fase solida de peptidos desprotegidos o protegidos en la cisteina n-terminal en solucion acuosa. |
| EP1091440B1 (en) | 1998-05-29 | 2010-06-02 | JGC Catalysts and Chemicals Ltd. | Method of manufacturing photoelectric cell |
| PT1107793E (pt) | 1998-08-10 | 2005-02-28 | Amgen Inc | Conjugados de dextrano-leptina, composicoes farmaceuticas e processos relacionados |
| AU6396999A (en) | 1998-10-02 | 2000-04-26 | Amgen, Inc. | Method to determine a predisposition to leptin treatment |
| US6420339B1 (en) | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| US6194006B1 (en) | 1998-12-30 | 2001-02-27 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of microparticles having a selected release profile |
| DK1143989T3 (da) | 1999-01-14 | 2007-04-16 | Amylin Pharmaceuticals Inc | Exendiner til glucagonundertrykkelse |
| CA2359840C (en) | 1999-02-12 | 2012-10-23 | Amgen Inc. | Glycosylated leptin compositions and related methods |
| US6475984B2 (en) * | 1999-04-29 | 2002-11-05 | The Nemours Foundation | Administration of leptin |
| TW514510B (en) | 1999-06-11 | 2002-12-21 | Tanita Seisakusho Kk | Method and apparatus for measuring distribution of body fat |
| US6468222B1 (en) | 1999-08-02 | 2002-10-22 | Healthetech, Inc. | Metabolic calorimeter employing respiratory gas analysis |
| US6258932B1 (en) | 1999-08-09 | 2001-07-10 | Tripep Ab | Peptides that block viral infectivity and methods of use thereof |
| EP1214351A2 (en) * | 1999-09-22 | 2002-06-19 | Genset | Methods of screening for compounds that modulate the lsr-leptin interaction and their use in the prevention and treatment of obesity-related diseases |
| US6530886B1 (en) | 1999-10-08 | 2003-03-11 | Tanita Corporation | Method and apparatus for measuring subcutaneous fat using ultrasonic wave |
| US7057015B1 (en) * | 1999-10-20 | 2006-06-06 | The Salk Institute For Biological Studies | Hormone receptor functional dimers and methods of their use |
| JP2001199887A (ja) | 1999-11-10 | 2001-07-24 | Takeda Chem Ind Ltd | 体重増加抑制剤 |
| CN1423566A (zh) | 1999-11-10 | 2003-06-11 | 武田药品工业株式会社 | 体重增加抑制剂 |
| US20050287153A1 (en) * | 2002-06-28 | 2005-12-29 | Genentech, Inc. | Serum albumin binding peptides for tumor targeting |
| US7157564B1 (en) | 2000-04-06 | 2007-01-02 | Affymetrix, Inc. | Tag nucleic acids and probe arrays |
| CA2405550A1 (en) * | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US6264987B1 (en) | 2000-05-19 | 2001-07-24 | Alkermes Controlled Therapeutics Inc. Ii | Method for preparing microparticles having a selected polymer molecular weight |
| TW515705B (en) | 2000-05-31 | 2003-01-01 | Yamato Scale Co Ltd | Visceral fat meter |
| US6492117B1 (en) | 2000-07-12 | 2002-12-10 | Gendaq Limited | Zinc finger polypeptides capable of binding DNA quadruplexes |
| US6296842B1 (en) | 2000-08-10 | 2001-10-02 | Alkermes Controlled Therapeutics, Inc. | Process for the preparation of polymer-based sustained release compositions |
| US6475158B1 (en) | 2000-10-24 | 2002-11-05 | Korr Medical Technologies, Inc. | Calorimetry systems and methods |
| PL214862B1 (pl) | 2001-10-22 | 2013-09-30 | Amgen | Sposób in vitro do okreslania predyspozycji pacjenta ludzkiego z lipoatrofia do reagowania na leczenie bialkiem leptyny, kompozycje farmaceutyczne do zastosowania do leczenia lipoatrofii i kompozycje farmaceutyczne zawierajace bialko leptyny |
| US6899892B2 (en) | 2001-12-19 | 2005-05-31 | Regents Of The University Of Minnesota | Methods to reduce body fat |
| AU2002364586A1 (en) | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| WO2004039832A2 (en) | 2002-10-31 | 2004-05-13 | Albany Medical College | Leptin-related peptides |
| JPWO2004039853A1 (ja) | 2002-11-01 | 2006-03-02 | 株式会社トクヤマ | 重合性組成物、その硬化体の製造法および光学物品 |
| EP1667724A2 (en) * | 2003-09-19 | 2006-06-14 | Novo Nordisk A/S | Albumin-binding derivatives of therapeutic peptides |
| TW200526254A (en) * | 2003-09-19 | 2005-08-16 | Novo Nordisk As | Novel GLP-1 derivatives |
| US8263084B2 (en) | 2003-11-13 | 2012-09-11 | Hanmi Science Co., Ltd | Pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
| JP2008500281A (ja) | 2004-02-11 | 2008-01-10 | 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 | アミリンファミリーペプチドおよびそれらを作成し使用するための方法 |
| US7399744B2 (en) | 2004-03-04 | 2008-07-15 | Amylin Pharmaceuticals, Inc. | Methods for affecting body composition |
| US8394765B2 (en) | 2004-11-01 | 2013-03-12 | Amylin Pharmaceuticals Llc | Methods of treating obesity with two different anti-obesity agents |
| CA2589800A1 (en) | 2004-12-02 | 2006-06-08 | Domantis Limited | Bispecific domain antibodies targeting serum albumin and glp-1 or pyy |
| US7898623B2 (en) | 2005-07-04 | 2011-03-01 | Semiconductor Energy Laboratory Co., Ltd. | Display device, electronic device and method of driving display device |
| GB0524788D0 (en) * | 2005-12-05 | 2006-01-11 | Affibody Ab | Polypeptides |
| JP2009523177A (ja) | 2006-01-11 | 2009-06-18 | ブリストル−マイヤーズ スクイブ カンパニー | ヒトグルカゴン様ペプチド−１調節因子、並びに糖尿病および関連症状の治療におけるその使用 |
| JP5252435B2 (ja) | 2006-03-15 | 2013-07-31 | ノボ・ノルデイスク・エー／エス | アミリン誘導体 |
| AU2006341375B2 (en) | 2006-03-31 | 2013-03-21 | Amylin Pharmaceuticals, Llc | Amylin and amylin agonists for treating psychiatric diseases and disorders |
| EP2021014A1 (en) | 2006-05-26 | 2009-02-11 | Brystol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
| AU2007267833B2 (en) | 2006-05-26 | 2012-07-26 | Amylin Pharmaceuticals, Llc | Composition and methods for treatment of congestive heart failure |
| 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 |
| CN101113175A (zh) * | 2007-04-28 | 2008-01-30 | 中国科学院西北高原生物研究所 | 鼠兔家族瘦素蛋白及其cDNA序列 |
| 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 |
| DE08786222T1 (de) | 2007-07-31 | 2010-11-25 | Affibody Ab | Neue albuminbindende zusammensetzungen, verfahren und anwendungen |
| GB0715216D0 (en) | 2007-08-03 | 2007-09-12 | Asterion Ltd | Leptin |
| EP2036923A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Improved derivates of amylin |
| EP2195034A2 (en) * | 2007-09-27 | 2010-06-16 | Amylin Pharmaceuticals, Inc. | Peptide-peptidase inhibitor conjugates and methods of making and using same |
| BRPI0722276A2 (pt) | 2007-11-14 | 2014-04-22 | Amylin Pharmaceuticals Inc | Métodos para tratar obesidade e doenças e distúrbios relacionados à obesidade |
| CA2712606A1 (en) * | 2008-02-08 | 2009-08-13 | Ambrx, Inc. | Modified leptin polypeptides and their uses |
| US8501686B2 (en) | 2008-06-05 | 2013-08-06 | University Of Michigan | Method of treating fatty liver diseases and conditions in non-lipodystrophic subjects |
| WO2010046357A1 (en) | 2008-10-21 | 2010-04-29 | Novo Nordisk A/S | Amylin derivatives |
| WO2010054699A1 (en) * | 2008-11-17 | 2010-05-20 | Affibody Ab | Conjugates of albumin binding domain |
| BRPI1006943A2 (pt) | 2009-01-22 | 2021-06-15 | Unigene Laboratories Inc. | peptídeo, composição farmacêutica que compreende o peptídeo e método para supressão do apetite, prevenção ou tratamento de uma condição de sobrepeso ou obesidade, ou para tratar diabetes |
| WO2010091122A1 (en) | 2009-02-03 | 2010-08-12 | Amunix, Inc. | Extended recombinant polypeptides and compositions comprising same |
| WO2011152694A2 (en) * | 2010-06-04 | 2011-12-08 | Sk Chemicals Co., Ltd. | Fusion protein having factor vii activity |
| CN110437321A (zh) | 2010-07-09 | 2019-11-12 | 阿菲博迪公司 | 多肽 |
| EP3028720A1 (en) | 2010-09-28 | 2016-06-08 | Amylin Pharmaceuticals, LLC | Engineered polypeptides having enhanced duration of action |
| EA024507B1 (ru) * | 2010-09-28 | 2016-09-30 | Амилин Фармасьютикалс, Ллк | Хорошо растворимые лептины |
| CN104271588B (zh) | 2011-07-08 | 2017-10-10 | 安米林药品有限责任公司 | 具有增强的作用持续时间和降低的免疫原性的工程改造的多肽 |
| DK2729160T3 (da) | 2011-07-08 | 2019-07-01 | Aegerion Pharmaceuticals Inc | Manipulerede polypeptider, der har forbedret virkningstid og reduceret immunogenicitet |
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