CA3138758A1 - Highly soluble leptins - Google Patents
Highly soluble leptins Download PDFInfo
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- CA3138758A1 CA3138758A1 CA3138758A CA3138758A CA3138758A1 CA 3138758 A1 CA3138758 A1 CA 3138758A1 CA 3138758 A CA3138758 A CA 3138758A CA 3138758 A CA3138758 A CA 3138758A CA 3138758 A1 CA3138758 A1 CA 3138758A1
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- leptin
- amino acids
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2264—Obesity-gene products, e.g. leptin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
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- Chemical Kinetics & Catalysis (AREA)
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- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38740210P | 2010-09-28 | 2010-09-28 | |
| US61/387,402 | 2010-09-28 | ||
| US42209110P | 2010-12-10 | 2010-12-10 | |
| US61/422,091 | 2010-12-10 | ||
| CA2813038A CA2813038C (en) | 2010-09-28 | 2011-09-28 | Highly soluble leptins |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2813038A Division CA2813038C (en) | 2010-09-28 | 2011-09-28 | Highly soluble leptins |
Publications (1)
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|---|---|
| CA3138758A1 true CA3138758A1 (en) | 2012-04-19 |
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| CA2813087A Active CA2813087C (en) | 2010-09-28 | 2011-09-28 | Engineered polypeptides having enhanced duration of action |
| CA2813038A Active CA2813038C (en) | 2010-09-28 | 2011-09-28 | Highly soluble leptins |
| CA3138758A Pending CA3138758A1 (en) | 2010-09-28 | 2011-09-28 | Highly soluble leptins |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
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| CA2813087A Active CA2813087C (en) | 2010-09-28 | 2011-09-28 | Engineered polypeptides having enhanced duration of action |
| CA2813038A Active CA2813038C (en) | 2010-09-28 | 2011-09-28 | Highly soluble leptins |
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| EP (4) | EP3305315A1 (OSRAM) |
| JP (5) | JP2014502252A (OSRAM) |
| CN (2) | CN103403019B (OSRAM) |
| BR (3) | BR112013007385B1 (OSRAM) |
| CA (3) | CA2813087C (OSRAM) |
| CY (2) | CY1119023T1 (OSRAM) |
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| ES (3) | ES2873253T3 (OSRAM) |
| MX (2) | MX351128B (OSRAM) |
| PL (1) | PL3241558T3 (OSRAM) |
| PT (2) | PT2621515T (OSRAM) |
| WO (2) | WO2012050930A2 (OSRAM) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5827994B2 (ja) | 2010-07-09 | 2015-12-02 | アフィボディ・アーベー | ポリペプチド |
| MX351128B (es) | 2010-09-28 | 2017-10-03 | Aegerion Pharmaceuticals Inc | Polipeptidos manipulados que tienen duracion de accion incrementada. |
| US20140256621A1 (en) | 2011-07-08 | 2014-09-11 | Astrazeneca Pharmaceuticals Lp | Engineered poypeptides having enhanced duration of action and reduced immunogenicity |
| HK1208155A1 (en) * | 2012-03-28 | 2016-02-26 | Amylin Pharmaceuticals, Llc | Transmucosal delivery of engineered polypeptides |
| CN104662035A (zh) * | 2012-09-25 | 2015-05-27 | 阿菲博迪公司 | 白蛋白结合多肽 |
| HK1215681A1 (zh) | 2013-04-18 | 2016-09-09 | Armo Biosciences, Inc. | 使用白细胞介素-10治疗疾病和病症的方法 |
| US9823255B2 (en) | 2013-06-17 | 2017-11-21 | Armo Biosciences, Inc. | Method for assessing protein identity and stability |
| AU2014311432A1 (en) | 2013-08-30 | 2016-03-03 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| CA2928710A1 (en) | 2013-11-11 | 2015-05-14 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| EP3083675B1 (en) | 2013-12-20 | 2018-03-07 | Affibody AB | Engineered albumin binding polypeptide |
| WO2015187295A2 (en) | 2014-06-02 | 2015-12-10 | Armo Biosciences, Inc. | Methods of lowering serum cholesterol |
| TW201625671A (zh) | 2014-09-04 | 2016-07-16 | 諾佛 儂迪克股份有限公司 | 新穎澱粉素及降鈣素受體促效劑 |
| WO2016060996A2 (en) | 2014-10-14 | 2016-04-21 | Armo Biosciences, Inc. | Interleukin-15 compositions and uses thereof |
| CA2963995A1 (en) | 2014-10-22 | 2016-04-28 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| WO2016126615A1 (en) | 2015-02-03 | 2016-08-11 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| HK1246201A1 (zh) | 2015-05-28 | 2018-09-07 | Armo Biosciences, Inc. | 用於治疗癌症的聚乙二醇化白细胞介素-10 |
| WO2017020282A1 (zh) * | 2015-08-05 | 2017-02-09 | 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 |
| KR20180045001A (ko) | 2015-09-22 | 2018-05-03 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 개질된 세포독소 및 이의 치료 용도 |
| US10286079B2 (en) | 2015-09-22 | 2019-05-14 | The Regents Of The University Of California | Modified cytotoxins and their therapeutic use |
| WO2017054832A1 (en) | 2015-10-02 | 2017-04-06 | University Of Copenhagen | Small molecules blocking histone reader domains |
| DK3509624T3 (da) | 2016-09-12 | 2023-11-13 | Amryt Pharmaceuticals Inc | Fremgangsmåder til detektering af anti-leptin-neutraliserende antistoffer |
| KR102613874B1 (ko) * | 2017-01-30 | 2023-12-15 | 알렉시온 파마슈티칼스, 인코포레이티드 | 1가 항-프로페르딘 항체 및 항체 단편 |
| WO2019200233A1 (en) * | 2018-04-13 | 2019-10-17 | Massachusetts Institute Of Technology | Engineered treatments for hair repair and long-lasting color retention |
| EP3711772A1 (en) * | 2019-03-20 | 2020-09-23 | Oslo Universitetssykehus HF | Recombinant proteins and fusion proteins |
| US20240391963A1 (en) * | 2021-09-24 | 2024-11-28 | The Uab Research Foundation | Control of subunit stoichiometry in single-chain msp nanopores |
| US12466883B1 (en) * | 2024-05-13 | 2025-11-11 | Lumen Bioscience, Inc. | Leptin compositions and methods of making and using the same to support weight loss and/or maintenance |
Family Cites Families (156)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| 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 |
| US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
| KR850004274A (ko) | 1983-12-13 | 1985-07-11 | 원본미기재 | 에리트로포이에틴의 제조방법 |
| 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 |
| CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| WO1991005795A1 (en) | 1989-10-16 | 1991-05-02 | 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 |
| DE69226431T2 (de) | 1991-04-05 | 1999-04-22 | The Board Of Regents Of The University Of Washington, Seattle, Wash. | 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 |
| US6001968A (en) | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
| 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 |
| US6048837A (en) | 1994-08-17 | 2000-04-11 | The Rockefeller University | OB polypeptides as modulators of body weight |
| 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 |
| US5594104A (en) | 1995-01-31 | 1997-01-14 | Eli Lilly And Company | Anti-obesity proteins |
| US5559208A (en) | 1995-01-31 | 1996-09-24 | Eli Lilly And Company | Anti-obesity proteins |
| US5605886A (en) | 1995-01-31 | 1997-02-25 | Eli Lilly And Company | Anti-obesity proteins |
| US5563243A (en) | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5569743A (en) | 1995-01-31 | 1996-10-29 | Eli Lilly And Company | Anti-obesity proteins |
| US5563244A (en) | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5532336A (en) | 1995-01-31 | 1996-07-02 | Eli Lilly And Company | Anti-obesity proteins |
| WO1996023514A1 (en) | 1995-01-31 | 1996-08-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5552523A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5552522A (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 |
| US5567803A (en) | 1995-01-31 | 1996-10-22 | Eli Lilly And Company | Anti-obesity proteins |
| US5574133A (en) | 1995-01-31 | 1996-11-12 | Eli Lilly And Company | Anti-obesity proteins |
| US5554727A (en) | 1995-01-31 | 1996-09-10 | Eli Lilly And Company | Anti-obesity proteins |
| WO1996023815A1 (en) | 1995-01-31 | 1996-08-08 | Eli Lilly And Company | Ob gene product antibodies |
| US5552524A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5567678A (en) | 1995-01-31 | 1996-10-22 | Eli Lilly And Company | Anti-obesity proteins |
| US5525705A (en) | 1995-01-31 | 1996-06-11 | Eli Lilly And Company | Anti-obesity proteins |
| US5521283A (en) | 1995-01-31 | 1996-05-28 | Eli Lilly And Company | Anti-obesity proteins |
| EP0725078A1 (en) * | 1995-01-31 | 1996-08-07 | Eli Lilly And Company | Anti-obesity proteins |
| US5691309A (en) | 1995-01-31 | 1997-11-25 | Eli Lilly And Company | Anti-obesity proteins |
| US5580954A (en) | 1995-01-31 | 1996-12-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5563245A (en) | 1995-01-31 | 1996-10-08 | 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 |
| DE741187T1 (de) | 1995-05-05 | 1997-04-30 | Hoffmann La Roche | Rekombinante Obesitäts-(OB)-Proteine |
| EP0826045A1 (en) | 1995-05-08 | 1998-03-04 | 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 |
| EP0832220A1 (en) | 1995-06-07 | 1998-04-01 | 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 |
| WO1997001331A2 (en) | 1995-06-27 | 1997-01-16 | Takeda Chemical Industries, Ltd. | Method of producing sustained-release preparation |
| PL324284A1 (en) | 1995-06-30 | 1998-05-11 | Lilly Co Eli | Methods of 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 |
| NZ527007A (en) | 1995-11-22 | 2005-01-28 | Amgen Inc | Methods of increasing lean tissue mass using OB protein compositions |
| US6936439B2 (en) | 1995-11-22 | 2005-08-30 | Amgen Inc. | OB fusion protein compositions and methods |
| WO1997020933A2 (en) | 1995-12-06 | 1997-06-12 | 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 |
| TR199802534T2 (xx) | 1996-06-06 | 1999-03-22 | Smithkline Beecham P.L.C. | Leptin (OB Protein) fragmanlar� |
| US5922678A (en) | 1996-06-28 | 1999-07-13 | Eli Lilly And Company | Methods for treating diabetes |
| WO1998008512A1 (en) | 1996-08-30 | 1998-03-05 | Amgen Inc. | Methods of increasing sensitivity of an individual to ob protein by upregulating ob protein receptor |
| PL332458A1 (en) | 1996-09-20 | 1999-09-13 | Hoechst Ag | Application of leptin antagonists in treating insulin resistance in cases of diabeted of type ii |
| AU4582597A (en) | 1996-10-11 | 1998-05-11 | Eli Lilly And Company | Therapeutic proteins |
| WO1998024896A2 (en) | 1996-12-06 | 1998-06-11 | F. Hoffmann-La Roche Ag | Muteins of obese protein |
| ATE351910T1 (de) | 1996-12-20 | 2007-02-15 | Amgen Inc | Ob-fusionsprotein enthaltende zusammensetzungen und verfahren |
| 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 |
| IL133136A0 (en) | 1997-06-06 | 2001-03-19 | Smithkline Beecham Plc | Use of leptin antagonists for the treatment of diabetes |
| CA2292724A1 (en) | 1997-06-13 | 1998-12-17 | Gryphon Sciences | Solid phase native chemical ligation of unprotected or n-terminal cysteine protected peptides in aqueous solution |
| EP1091440B1 (en) | 1998-05-29 | 2010-06-02 | JGC Catalysts and Chemicals Ltd. | Method of manufacturing photoelectric cell |
| WO2000009165A1 (en) | 1998-08-10 | 2000-02-24 | Amgen Inc. | Dextran-leptin conjugates, pharmaceutical compositions and related methods |
| CA2344623A1 (en) | 1998-10-02 | 2000-04-13 | 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 |
| ATE460942T1 (de) | 1999-01-14 | 2010-04-15 | Amylin Pharmaceuticals Inc | Exendine zur glucagon suppression |
| 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 |
| CA2390932A1 (en) | 1999-11-10 | 2001-05-17 | Takeda Chemical Industries, Ltd. | Body weight gain inhibitors |
| 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 |
| AU2001266557A1 (en) * | 2000-04-12 | 2001-10-23 | 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 |
| EP1444516B1 (en) | 2001-10-22 | 2010-07-21 | Amgen, Inc. | Use of leptin for treating human lipoatrophy and method of determining predisposition to said treatment |
| US6899892B2 (en) | 2001-12-19 | 2005-05-31 | Regents Of The University Of Minnesota | Methods to reduce body fat |
| JP5424521B2 (ja) | 2001-12-21 | 2014-02-26 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | アルブミン融合タンパク質 |
| AU2003290563A1 (en) | 2002-10-31 | 2004-05-25 | Clf Medical Technology Acceleration Program, Inc. | 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 |
| KR101241862B1 (ko) * | 2003-09-19 | 2013-03-13 | 노보 노르디스크 에이/에스 | 신규 ｇｌｐ-1 유도체 |
| 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 |
| KR20070094909A (ko) | 2004-12-02 | 2007-09-27 | 도만티스 리미티드 | 혈청 알부민 및 ｇｌｐ-1 또는 ｐｙｙ를 표적으로 삼는이중특이성 도메인을 갖는 항체 |
| 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 |
| EP1976873A2 (en) | 2006-01-11 | 2008-10-08 | Brystol-Myers Squibb Company | Human glucagon-like-peptide-1 modulators and their use in the treatment of diabetes and related conditions |
| CN101400698A (zh) | 2006-03-15 | 2009-04-01 | 诺沃-诺迪斯克有限公司 | 胰岛淀粉样多肽衍生物 |
| MX2008012666A (es) | 2006-03-31 | 2008-10-13 | Amylin Pharmaceuticals Inc | Amilina y agonistas de amilina para tratar enfermedades y trastornos psiquiatricos. |
| EP2021014A1 (en) | 2006-05-26 | 2009-02-11 | Brystol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
| EA200870575A1 (ru) | 2006-05-26 | 2009-08-28 | Амилин Фармасьютикалз, Инк. | Композиции и способы лечения застойной сердечной недостаточности |
| 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 |
| EP2190863B1 (en) | 2007-07-31 | 2015-09-02 | Affibody AB | New albumin binding compositions, methods and uses |
| 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 |
| JP2011503180A (ja) | 2007-11-14 | 2011-01-27 | 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 | 肥満ならびに肥満関連の疾患および障害の処置方法 |
| EP3103880A1 (en) * | 2008-02-08 | 2016-12-14 | Ambrx, Inc. | Modified leptin polypeptides and their uses |
| WO2009149379A2 (en) | 2008-06-05 | 2009-12-10 | Regents Of The University Of Michigan | Use of leptin for the treatment of fatty liver diseases and conditions |
| JP5703226B2 (ja) | 2008-10-21 | 2015-04-15 | ノヴォ ノルディスク アー／エス | アミリン誘導体 |
| WO2010054699A1 (en) * | 2008-11-17 | 2010-05-20 | Affibody Ab | Conjugates of albumin binding domain |
| CA2750035C (en) | 2009-01-22 | 2018-02-27 | Unigene Laboratories Inc. | Treatment for obesity |
| EP3178835B1 (en) | 2009-02-03 | 2019-04-10 | Amunix Pharmaceuticals, Inc. | Extended recombinant polypeptides and compositions comprising same |
| JP6143297B2 (ja) * | 2010-06-04 | 2017-06-07 | チウムバイオ・カンパニー・リミテッドＴｉｕｍＢｉｏ Ｃｏ．， Ｌｔｄ． | 第ｖｉｉ因子活性を有する融合タンパク質 |
| JP5827994B2 (ja) | 2010-07-09 | 2015-12-02 | アフィボディ・アーベー | ポリペプチド |
| MX351128B (es) | 2010-09-28 | 2017-10-03 | Aegerion Pharmaceuticals Inc | Polipeptidos manipulados que tienen duracion de accion incrementada. |
| JP6121330B2 (ja) | 2010-09-28 | 2017-04-26 | アミリン・ファーマシューティカルズ, リミテッド・ライアビリティ・カンパニーAmylin Pharmaceuticals, Llc | 作用持続時間が増した改変ポリペプチド |
| US20140256621A1 (en) | 2011-07-08 | 2014-09-11 | Astrazeneca Pharmaceuticals Lp | Engineered poypeptides having enhanced duration of action and reduced immunogenicity |
| 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 |
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