CA2551916C - Fc-erythropoietin fusion protein with improved pharmacokinetics - Google Patents
Fc-erythropoietin fusion protein with improved pharmacokinetics Download PDFInfo
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- CA2551916C CA2551916C CA2551916A CA2551916A CA2551916C CA 2551916 C CA2551916 C CA 2551916C CA 2551916 A CA2551916 A CA 2551916A CA 2551916 A CA2551916 A CA 2551916A CA 2551916 C CA2551916 C CA 2551916C
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- erythropoietin
- fusion protein
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Classifications
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- 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
-
- 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
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- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
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- Diabetes (AREA)
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- Public Health (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53385803P | 2003-12-31 | 2003-12-31 | |
| US60/533,858 | 2003-12-31 | ||
| PCT/EP2004/014608 WO2005063808A1 (en) | 2003-12-31 | 2004-12-22 | Fc-ERYTHROPOIETIN FUSION PROTEIN WITH IMPROVED PHARMACOKINETICS |
Publications (2)
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|---|---|
| CA2551916A1 CA2551916A1 (en) | 2005-07-14 |
| CA2551916C true CA2551916C (en) | 2014-04-29 |
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|---|---|---|---|
| CA2551916A Expired - Fee Related CA2551916C (en) | 2003-12-31 | 2004-12-22 | Fc-erythropoietin fusion protein with improved pharmacokinetics |
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|---|---|
| US (2) | US7465447B2 (enExample) |
| EP (1) | EP1699821B1 (enExample) |
| JP (2) | JP2008504008A (enExample) |
| KR (1) | KR20060124656A (enExample) |
| CN (1) | CN1902222A (enExample) |
| AU (1) | AU2004309063B2 (enExample) |
| BR (1) | BRPI0417916A (enExample) |
| CA (1) | CA2551916C (enExample) |
| DK (1) | DK1699821T3 (enExample) |
| ES (1) | ES2387028T3 (enExample) |
| PT (1) | PT1699821E (enExample) |
| RU (1) | RU2370276C2 (enExample) |
| WO (1) | WO2005063808A1 (enExample) |
Families Citing this family (190)
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| US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
| HUP0204475A2 (en) | 2000-02-11 | 2003-04-28 | Merck Patent Gmbh | Enhancing the circulating half-life of antibody-based fusion proteins |
| RU2003129528A (ru) | 2001-03-07 | 2005-04-10 | Мерк Патент ГмбХ (DE) | Способ экспрессии белков, содержащих в качестве компонента гибридный изотип антитела |
| WO2002079415A2 (en) | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| DE60239454D1 (de) | 2001-05-03 | 2011-04-28 | Merck Patent Gmbh | Rekombinanter, tumorspezifischer antikörper und dessen verwendung |
| EP1454138B1 (en) | 2001-12-04 | 2012-01-18 | Merck Patent GmbH | Immunocytokines with modulated selectivity |
| US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
| CN100467488C (zh) * | 2003-12-30 | 2009-03-11 | 默克专利有限公司 | Il-7融合蛋白 |
| RU2370276C2 (ru) | 2003-12-31 | 2009-10-20 | Мерк Патент Гмбх | Fc-ЭРИТРОПОЭТИН СЛИТЫЙ БЕЛОК С УЛУЧШЕННОЙ ФАРМАКОКИНЕТИКОЙ |
| US7670595B2 (en) * | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| US7589179B2 (en) * | 2004-12-09 | 2009-09-15 | Merck Patent Gmbh | IL-7 variants with reduced immunogenicity |
| US7566456B2 (en) * | 2005-06-23 | 2009-07-28 | Haiming Chen | Allergen vaccine proteins for the treatment and prevention of allergic diseases |
| US8470318B2 (en) | 2005-11-07 | 2013-06-25 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| ES2439641T3 (es) | 2005-12-20 | 2014-01-24 | Bristol-Myers Squibb Company | Composiciones y procedimientos de producción de una composición |
| AR058568A1 (es) | 2005-12-20 | 2008-02-13 | Bristol Myers Squibb Co | Metodos para producir una composicion con moleculas ctla4-ig a partir de un medio de cultivo |
| ES2384055T3 (es) | 2005-12-30 | 2012-06-28 | Merck Patent Gmbh | Variantes de la interleucina-12p40 con estabilidad mejorada |
| ATE509954T1 (de) | 2005-12-30 | 2011-06-15 | Merck Patent Gmbh | Anti-cd19-antikörper mit reduzierter immunogenität |
| CN101002945B (zh) | 2006-01-20 | 2012-09-05 | 清华大学 | 一种用于肿瘤治疗的新型复合物 |
| CN100475270C (zh) | 2006-01-20 | 2009-04-08 | 清华大学 | 一种治疗肿瘤的药物及其应用 |
| US7625564B2 (en) | 2006-01-27 | 2009-12-01 | Novagen Holding Corporation | Recombinant human EPO-Fc fusion proteins with prolonged half-life and enhanced erythropoietic activity in vivo |
| EP1816201A1 (en) * | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| MX2008012843A (es) * | 2006-04-05 | 2009-01-19 | Univ Rockefeller | Polipeptidos con propiedades antiinflamatorias aumentadas y citotoxicas reducidas y metodos relacionados. |
| US8377448B2 (en) * | 2006-05-15 | 2013-02-19 | The Board Of Trustees Of The Leland Standford Junior University | CD47 related compositions and methods for treating immunological diseases and disorders |
| CA2652570A1 (en) * | 2006-05-15 | 2007-11-22 | Viral Logic Systems Technology Corp. | Cd47 related compositions and methods for treating immunological diseases and disorders |
| EP1873166B1 (en) * | 2006-06-30 | 2010-09-08 | CONARIS research institute AG | Improved sgp 130Fc dimers |
| AU2007317755A1 (en) * | 2006-10-27 | 2008-05-15 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| JP2010510794A (ja) | 2006-11-28 | 2010-04-08 | ハナル ファーマシューティカル カンパニー リミテッド | 修飾型エリスロポエチンポリペプチド及びこの治療用用途 |
| KR100888022B1 (ko) * | 2006-12-21 | 2009-03-09 | 재단법인 목암생명공학연구소 | 면역글로불린 Fc와 인간 아포리포단백질(a)크링글절편의 융합단백질 LK8Fc |
| KR101542752B1 (ko) | 2006-12-22 | 2015-08-10 | 체에스엘 베링 게엠베하 | 연장된 생체내 반감기를 갖는 변형된 응고 인자 |
| CN101219219B (zh) | 2007-01-10 | 2013-02-13 | 北京普罗吉生物科技发展有限公司 | 包含血管抑素或其片段的复合物、其制备方法及应用 |
| JP2010517529A (ja) | 2007-02-02 | 2010-05-27 | アムジエン・インコーポレーテツド | ヘプシジン及びヘプシジン抗体 |
| CA2678001C (en) | 2007-02-12 | 2017-07-11 | Stefan Schulte | Therapeutic application of kazal-type serine protease inhibitors |
| EP1961821B1 (en) | 2007-02-22 | 2009-06-10 | Polymun Scientific Immunbiologische Forschung GmbH | Erythropoietin fusion protein |
| WO2009006520A1 (en) * | 2007-07-03 | 2009-01-08 | Medimmune, Llc | Hinge domain engineering |
| US8067548B2 (en) | 2007-07-26 | 2011-11-29 | Novagen Holding Corporation | Fusion proteins having mutated immunoglobulin hinge region |
| ES2750254T3 (es) | 2007-09-27 | 2020-03-25 | Amgen Inc | Formulaciones farmacéuticas |
| EP2219602A1 (en) | 2007-11-15 | 2010-08-25 | Amgen, Inc | Aqueous formulation of erythropoiesis stimulating protein stablised by antioxidants for parenteral administration |
| EP2574628B1 (en) | 2008-01-25 | 2015-05-20 | Amgen Inc. | Ferroportin antibodies and methods of use |
| EP2279410B1 (en) | 2008-04-22 | 2015-11-11 | The Rockefeller University | Methods of identifying anti-inflammatory compounds |
| CA2722600C (en) | 2008-05-01 | 2014-01-21 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
| RU2528855C2 (ru) | 2008-06-24 | 2014-09-20 | Цсл Беринг Гмбх | Модифицированный фактор виллебранда с удлиненным полупериодом существования in vivo, его применения и способы получения |
| EP2184070A1 (en) * | 2008-11-07 | 2010-05-12 | Hla-G Technologies | HLA-G proteins and pharmaceutical uses thereof |
| US8318167B2 (en) | 2008-11-13 | 2012-11-27 | The General Hospital Corporation | Methods and compositions for regulating iron homeostasis by modulation of BMP-6 |
| JP5781501B2 (ja) * | 2009-04-22 | 2015-09-24 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | 改変されたFcRn結合部位を有する抗体融合タンパク質 |
| WO2011035914A1 (en) * | 2009-09-23 | 2011-03-31 | Biogenerix Ag | Process for the purification of recombinant human erythropoietin (epo), epo thus purified and pharmaceutical compositions comprising same |
| MX344382B (es) | 2009-10-23 | 2016-12-14 | Amgen Inc * | Adaptador de vial y sistema. |
| EP3460056B1 (en) | 2009-11-02 | 2020-08-19 | University Of Washington | Therapeutic nuclease compositions and methods |
| IN2012DN06589A (enExample) | 2010-01-19 | 2015-10-23 | Harvard College | |
| EP2371857A1 (en) | 2010-04-01 | 2011-10-05 | CSL Behring GmbH | Factor XII inhibitors for treating interstitial lung disease |
| MX2012014180A (es) | 2010-06-07 | 2013-05-06 | Amgen Inc | Dispositivo de administracion de farmacos. |
| WO2012068134A1 (en) * | 2010-11-15 | 2012-05-24 | Biogen Idec Inc. | Enrichment and concentration of select product isoforms by overloaded bind and elute chromatography |
| US10774304B2 (en) | 2011-03-08 | 2020-09-15 | University Of Maryland, Baltimore County | System and method for production of on-demand proteins in a portable unit for point of care delivery |
| US9982227B2 (en) * | 2011-03-08 | 2018-05-29 | University Of Maryland, Baltimore County | System and method for production of on-demand proteins in a portable unit for point of care delivery |
| US12227734B2 (en) | 2011-03-08 | 2025-02-18 | University Of Maryland, Baltimore County | Microscale bioprocessing system and method for protein manufacturing from human blood |
| PL2683397T3 (pl) | 2011-03-09 | 2018-01-31 | Csl Behring Gmbh | Inhibitory czynnika XII do podawania w zabiegach medycznych obejmujących kontakt z powierzchniami sztucznymi |
| EP2497489A1 (en) | 2011-03-09 | 2012-09-12 | CSL Behring GmbH | Factor XII inhibitors for the treatment of silent brain ischemia and ischemia of other organs |
| EP2691065B1 (en) | 2011-03-31 | 2017-03-01 | Amgen Inc. | Vial adapter and system |
| PL2699293T3 (pl) | 2011-04-20 | 2019-08-30 | Amgen Inc. | Urządzenie do wstrzykiwania automatycznego |
| KR20250037576A (ko) | 2011-04-29 | 2025-03-17 | 유니버시티 오브 워싱톤 스루 이츠 센터 포 커머셜리제이션 | 치료적 뉴클레아제 조성물 및 방법 |
| ES2758884T3 (es) | 2011-06-24 | 2020-05-06 | Stephen D Gillies | Proteínas de fusión de inmunoglobulina a través de cadena ligera y métodos de uso de ellas |
| IL230564B2 (en) | 2011-07-22 | 2023-09-01 | Csl Ltd | Anticoagulant monoclonal antibodies anti–factor xii/fxiia, a method for their preparation, a pharmaceutical compound containing them and medical uses. |
| IL308846B2 (en) | 2011-10-14 | 2025-03-01 | Amgen Inc | Injector and assembly method |
| EP2623110A1 (en) | 2012-01-31 | 2013-08-07 | CSL Behring GmbH | Factor XII inhibitors for the treatment of neurological inflammatory disorders |
| EP2814502B1 (en) | 2012-02-15 | 2017-09-13 | CSL Behring GmbH | Von willebrand factor variants having improved factor viii binding affinity |
| EP3799880A3 (en) * | 2012-03-03 | 2021-06-23 | ImmunGene, Inc. | Engineered antibody-interferon mutant fusion molecules |
| CN102690354B (zh) * | 2012-05-14 | 2015-03-25 | 安源生物科技(上海)有限公司 | 重组二聚化抗凝血酶III-Fc融合蛋白及其哺乳动物细胞高效表达系统 |
| DK3081249T3 (da) | 2012-11-21 | 2021-03-15 | Amgen Inc | Lægemiddeladministrationsanordning |
| US10286047B2 (en) | 2013-03-08 | 2019-05-14 | Csl Behring Gmbh | Treatment and prevention of remote ischemia-reperfusion injury |
| SG11201507417RA (en) | 2013-03-15 | 2015-10-29 | Amgen Inc | Body contour adaptable autoinjector device |
| EP3593839A1 (en) | 2013-03-15 | 2020-01-15 | Amgen Inc. | Drug cassette |
| BR112015022123B1 (pt) | 2013-03-15 | 2022-08-09 | Intrinsic Lifesciences, Llc | Anticorpos, fragmentos de ligação ao antígeno dos mesmos que se ligam especificamente à hepcidina ou um peptídeo de hepcidina, uso, meio contentor e kit |
| JP6336564B2 (ja) | 2013-03-15 | 2018-06-06 | アムゲン・インコーポレーテッド | 薬物カセット、自動注入器、および自動注入器システム |
| CN113559363B (zh) | 2013-03-22 | 2023-10-31 | 美国安进公司 | 注射器及装配方法 |
| DK2796145T3 (da) | 2013-04-22 | 2018-01-29 | Csl Ltd | Et kovalent kompleks af von Willebrand-faktor og faktor VIII linket af en disulfidbro |
| EP3848045A1 (en) | 2013-05-21 | 2021-07-14 | President and Fellows of Harvard College | Engineered heme-binding compositions and uses thereof |
| KR20160026905A (ko) | 2013-06-28 | 2016-03-09 | 체에스엘 베링 게엠베하 | 인자 xii 억제제 및 c1-억제제를 이용한 병용 치료요법 |
| BR112016008946B1 (pt) | 2013-10-24 | 2022-12-27 | Amgen Inc | Injetores e método para montar os injetor |
| CA3168888A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Drug delivery system with temperature-sensitive control |
| HRP20192080T1 (hr) | 2013-10-31 | 2020-02-07 | Resolve Therapeutics, Llc | Terapeutske fuzije nukleaza-albumine i postupci |
| WO2015095604A2 (en) | 2013-12-18 | 2015-06-25 | President And Fellows Of Harvard College | Methods and assays relating to circulating tumor cells |
| WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| AU2015227137B2 (en) * | 2014-03-05 | 2019-06-06 | Ultragenyx Pharmaceutical Inc. | Sialylated glycoprotein compositions and uses thereof |
| BR112016025852B1 (pt) | 2014-05-07 | 2022-11-01 | Amgen Inc | Dispositivo de injeção para aplicação de fármaco |
| SG11201609966SA (en) | 2014-06-03 | 2016-12-29 | Amgen Inc | Drug delivery system and method of use |
| DK3157548T3 (da) | 2014-06-18 | 2021-09-06 | Csl Behring Gmbh | Terapi anvendelse af en faktor xii-inhibitor i en neurotraumatisk sygdom |
| US10253088B2 (en) | 2014-07-02 | 2019-04-09 | CSL Behring Lengnau AG | Modified von Willebrand Factor |
| FR3024453B1 (fr) * | 2014-08-01 | 2018-06-29 | Lab Francais Du Fractionnement | Procede de production de variants ayant un fc presentant une sialylation amelioree |
| AU2015321462B2 (en) | 2014-09-22 | 2020-04-30 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
| US10695506B2 (en) | 2014-10-14 | 2020-06-30 | Amgen Inc. | Drug injection device with visual and audio indicators |
| EP3233159B1 (en) | 2014-12-19 | 2020-03-04 | Amgen Inc. | Drug delivery device with live button or user interface field |
| EP3848072A1 (en) | 2014-12-19 | 2021-07-14 | Amgen Inc. | Drug delivery device with proximity sensor |
| RU2673548C1 (ru) * | 2015-01-09 | 2018-11-28 | Генексин, Инк. | Способ лечения анемии с применением композиции ЕРО длительного действия |
| ES2748750T3 (es) | 2015-02-17 | 2020-03-17 | Amgen Inc | Dispositivo de administración de fármacos con sujeción asistida por vacío y/o realimentación |
| EP3261690B1 (en) | 2015-02-27 | 2021-12-15 | Amgen Inc. | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| KR20180012303A (ko) | 2015-05-22 | 2018-02-05 | 체에스엘 베링 리컴비넌트 퍼실리티 아게 | 변형된 폰 빌레브란트 인자의 제조 방법 |
| EP3297656B1 (en) | 2015-05-22 | 2020-01-08 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for treating hemophilia |
| US11820807B2 (en) * | 2015-06-12 | 2023-11-21 | Ubi Pharma Inc | Immunoglobulin fusion proteins and uses thereof |
| CN108289928B (zh) | 2015-08-06 | 2024-09-17 | 哈佛大学校长及研究员协会 | 改进的微生物-结合分子和其用途 |
| WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
| KR101847169B1 (ko) * | 2015-10-07 | 2018-04-09 | 주식회사 녹십자 | 지속형 에리트로포이에틴 함유 조성물 |
| EP3386573B1 (en) | 2015-12-09 | 2019-10-02 | Amgen Inc. | Auto-injector with signaling cap |
| EP3184149A1 (en) | 2015-12-23 | 2017-06-28 | Julius-Maximilians-Universität Würzburg | Soluble glycoprotein v for treating thrombotic diseases |
| WO2017120178A1 (en) | 2016-01-06 | 2017-07-13 | Amgen Inc. | Auto-injector with signaling electronics |
| DK3400238T3 (da) | 2016-01-07 | 2021-07-26 | CSL Behring Lengnau AG | Muteret von willebrand faktor |
| CA3010720A1 (en) | 2016-01-07 | 2017-07-13 | Csl Behring Recombinant Facility Ag | Mutated truncated von willebrand factor |
| EP4035711B1 (en) | 2016-03-15 | 2025-06-04 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
| AU2017247004B2 (en) | 2016-04-06 | 2022-07-07 | Csl Limited | Method of treating atherosclerosis |
| WO2017189089A1 (en) | 2016-04-29 | 2017-11-02 | Amgen Inc. | Drug delivery device with messaging label |
| WO2017192287A1 (en) | 2016-05-02 | 2017-11-09 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
| ES2959783T3 (es) | 2016-05-13 | 2024-02-28 | Amgen Inc | Conjunto de cubierta protectora de vial |
| US11238150B2 (en) | 2016-05-16 | 2022-02-01 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
| CN105884906B (zh) * | 2016-05-27 | 2021-11-19 | 广州太力生物医药科技有限公司 | 一种长效人促红细胞生成素融合蛋白的纯化方法 |
| WO2017209899A1 (en) | 2016-06-03 | 2017-12-07 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
| CA3026474A1 (en) | 2016-06-20 | 2017-12-28 | Kymab Limited | Anti-pd-l1 and il-2 cytokines |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| EP3478342B1 (en) | 2016-07-01 | 2025-03-12 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
| CA3029627A1 (en) | 2016-07-01 | 2018-01-04 | Resolve Therapeutics, Llc | Optimized binuclease fusions and methods |
| WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
| EP3532127A1 (en) | 2016-10-25 | 2019-09-04 | Amgen Inc. | On-body injector |
| US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
| SG10201912360SA (en) | 2016-11-11 | 2020-02-27 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for treating hemophilia |
| US11890327B2 (en) | 2016-11-11 | 2024-02-06 | CSL Behring Lengnau AG | Truncated von Willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| MX2019008432A (es) | 2017-01-17 | 2019-11-18 | Amgen Inc | Dispositivos de inyeccion y metodos relacionados de uso y ensamblaje. |
| MX2019009755A (es) | 2017-02-17 | 2019-10-07 | Amgen Inc | Mecanismo de insercion para dispositivo de suministro de farmacos. |
| MX2019009625A (es) | 2017-02-17 | 2019-10-09 | Amgen Inc | Dispositivo de administracion de farmacos con trayectoria de flujo de fluido esteril y metodo relacionado de ensamblaje. |
| JP2020508803A (ja) | 2017-03-06 | 2020-03-26 | アムジエン・インコーポレーテツド | 作動防止特徴部を備える薬物送達デバイス |
| CA3052482A1 (en) | 2017-03-07 | 2018-09-13 | Amgen Inc. | Needle insertion by overpressure |
| EP3592404A1 (en) | 2017-03-09 | 2020-01-15 | Amgen Inc. | Insertion mechanism for drug delivery device |
| CN110446499A (zh) | 2017-03-20 | 2019-11-12 | 豪夫迈·罗氏有限公司 | 一种体外糖基工程化红细胞生成刺激蛋白的方法 |
| PL3600491T3 (pl) | 2017-03-28 | 2024-03-04 | Amgen Inc. | Układ i sposób montażu trzonu tłoka i strzykawki |
| AU2018282077B2 (en) | 2017-06-08 | 2023-11-23 | Amgen Inc. | Torque driven drug delivery device |
| EP3634539A1 (en) | 2017-06-08 | 2020-04-15 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
| WO2018236619A1 (en) | 2017-06-22 | 2018-12-27 | Amgen Inc. | Device activation impact/shock reduction |
| CA3068098A1 (en) | 2017-06-22 | 2018-12-27 | CSL Behring Lengnau AG | Modulation of fviii immunogenicity by truncated vwf |
| MX2019015479A (es) | 2017-06-23 | 2020-02-20 | Amgen Inc | Dispositivo electronico de administracion de farmacos con tapa accionada por un conjunto de conmutador. |
| IL270784B2 (en) | 2017-07-14 | 2023-11-01 | Amgen Inc | Needle insertion-extraction system with a double torsion spring system |
| EP3655063A1 (en) | 2017-07-21 | 2020-05-27 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
| EP4085942A1 (en) | 2017-07-25 | 2022-11-09 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
| JP7242562B2 (ja) | 2017-07-25 | 2023-03-20 | アムジエン・インコーポレーテツド | 容器アクセスシステムを有する薬物送達デバイス及び関連する組立方法 |
| EP3664863A2 (en) | 2017-08-09 | 2020-06-17 | Amgen Inc. | Hydraulic-pneumatic pressurized chamber drug delivery system |
| WO2019036181A1 (en) | 2017-08-18 | 2019-02-21 | Amgen Inc. | BODY INJECTOR WITH STERILE ADHESIVE PATCH |
| US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
| JP7374091B2 (ja) | 2017-08-22 | 2023-11-06 | サナバイオ, エルエルシー | 可溶性インターフェロン受容体およびその使用 |
| US11759565B2 (en) | 2017-10-04 | 2023-09-19 | Amgen Inc. | Flow adapter for drug delivery device |
| IL272636B2 (en) | 2017-10-06 | 2024-10-01 | Amgen Inc | Drug delivery device with interlock assembly and related method of assembly |
| IL273323B2 (en) | 2017-10-09 | 2024-10-01 | Amgen Inc | Drug delivery device with drive assembly and related assembly method |
| IL273582B2 (en) | 2017-11-03 | 2024-12-01 | Amgen Inc | Systems and approaches for sterilizing a drug delivery device |
| MA50553A (fr) | 2017-11-06 | 2020-09-16 | Amgen Inc | Dispositif d'administration de médicament avec détection de positionnement et de débit |
| WO2019090303A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Fill-finish assemblies and related methods |
| SG11202002966QA (en) | 2017-11-10 | 2020-05-28 | Amgen Inc | Plungers for drug delivery devices |
| MX2020004996A (es) | 2017-11-16 | 2020-08-27 | Amgen Inc | Un mecanismo de pestillo de puerta para un dispositivo de administracion de farmacos. |
| EP3710089A1 (en) | 2017-11-16 | 2020-09-23 | Amgen Inc. | Autoinjector with stall and end point detection |
| CN107937425A (zh) * | 2017-12-27 | 2018-04-20 | 北京四环生物制药有限公司 | 长效重组人促红素的生产方法 |
| EP3792276A4 (en) | 2018-04-26 | 2022-02-16 | Good T Cells, Inc. | NOVEL FUSION PROTEIN AND PHARMACEUTICAL COMPOSITION TO PREVENT OR TREAT CANCER THEREOF |
| US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
| US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
| US12115360B2 (en) | 2018-07-24 | 2024-10-15 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
| MX2021000748A (es) | 2018-07-24 | 2021-03-26 | Amgen Inc | Dispositivos de suministro para administrar farmacos. |
| US12303677B2 (en) | 2018-07-24 | 2025-05-20 | Amgen Inc. | Hybrid drug delivery devices with optional grip portion and related method of preparation |
| CN112351804A (zh) | 2018-07-24 | 2021-02-09 | 安进公司 | 用于施用药物的输送装置 |
| US12109389B2 (en) | 2018-07-31 | 2024-10-08 | Amgen Inc. | Fluid path assembly for a drug delivery device |
| CA3106452A1 (en) | 2018-09-24 | 2020-04-02 | Amgen Inc. | Interventional dosing systems and methods |
| US12042642B2 (en) | 2018-09-28 | 2024-07-23 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
| CA3110529A1 (en) | 2018-10-02 | 2020-04-09 | Amgen Inc. | Injection systems for drug delivery with internal force transmission |
| TWI824026B (zh) | 2018-10-05 | 2023-12-01 | 美商安進公司 | 具有劑量指示器之藥物遞送裝置 |
| EA202191038A1 (ru) | 2018-10-15 | 2021-07-06 | Эмджен Инк. | Способ платформенной сборки для устройства доставки лекарственного средства |
| IL313960B2 (en) | 2018-10-15 | 2025-10-01 | Amgen Inc | Drug delivery device with a suppression mechanism |
| TWI831847B (zh) | 2018-11-01 | 2024-02-11 | 美商安進公司 | 部分針頭縮回之藥物遞送裝置及其操作方法 |
| EP3873563A1 (en) | 2018-11-01 | 2021-09-08 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| ES3010833T3 (en) | 2018-11-01 | 2025-04-04 | Amgen Inc | Drug delivery devices with partial drug delivery member retraction |
| CA3137360A1 (en) | 2019-04-24 | 2020-10-29 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
| WO2020234195A1 (en) | 2019-05-17 | 2020-11-26 | Universitaet Zuerich | Haptoglobin for use in treating an adverse secondary neurological outcome following a haemorrhagic stroke |
| US20220389082A1 (en) | 2019-07-04 | 2022-12-08 | CSL Behring Lengnau AG | A truncated von willebrand factor (vwf) for increasing the in vitro stability of coagulation factor viii |
| JP7608439B2 (ja) | 2019-08-23 | 2025-01-06 | アムジエン・インコーポレーテツド | 構成可能な針シールド係合構成要素を備えた薬物送達デバイス及び関連方法 |
| CU24704B1 (es) * | 2019-09-05 | 2024-04-08 | Ct Inmunologia Molecular | Método para la obtención de eritropoyetina humana recombinante hiposialilada para el tratamiento de alteraciones del sistema nervioso |
| JP7680442B2 (ja) | 2019-11-11 | 2025-05-20 | ツェー・エス・エル・ベーリング・レングナウ・アクチエンゲゼルシャフト | 第viii因子に対する寛容を誘導するためのポリペプチド |
| CN111499764B (zh) * | 2020-04-02 | 2022-02-08 | 北京翼方生物科技有限责任公司 | 一种具有促红细胞生成素活性的长效融合蛋白 |
| WO2021251438A1 (ja) * | 2020-06-10 | 2021-12-16 | 株式会社バイカ・セラピュティクス | エリスロポエチンポリペプチドを含む融合タンパク質 |
| CN116568327A (zh) | 2020-11-20 | 2023-08-08 | 德国杰特贝林生物制品有限公司 | 治疗抗体介导的排斥反应的方法 |
| EP4284407A1 (en) | 2021-02-01 | 2023-12-06 | CSL Behring AG | Method of treating or preventing an adverse secondary neurological outcome following a haemorrhagic stroke |
| CN117321074A (zh) | 2021-05-07 | 2023-12-29 | 瑞士杰特贝林生物制品有限公司 | 用于产生重组触珠蛋白(Hp)β链的表达系统 |
| BR112023024278A2 (pt) | 2021-05-21 | 2024-01-30 | Amgen Inc | Método de otimizar uma receita de enchimento para um recipiente de fármacos |
| WO2023211805A1 (en) * | 2022-04-26 | 2023-11-02 | The Regents Of The University Of California | Hhip-fc fusion proteins and uses thereof |
| CN117069825A (zh) * | 2022-05-17 | 2023-11-17 | 广州汉腾生物科技有限公司 | 重组促红细胞生成素及其应用 |
| TW202423475A (zh) | 2022-09-02 | 2024-06-16 | 瑞士商Csl貝林股份有限公司 | 用於治療或預防過度勃起反應或勃起功能障礙之血紅素結合蛋白 |
| WO2024094457A1 (en) | 2022-11-02 | 2024-05-10 | F. Hoffmann-La Roche Ag | Method for producing glycoprotein compositions |
| WO2025257801A1 (en) | 2024-06-13 | 2025-12-18 | CSL Innovation Pty Ltd | Heme-binding protein for the treatment of ischemia-reperfusion injury (iri) |
Family Cites Families (183)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4196265A (en) * | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
| US4469797A (en) * | 1982-09-23 | 1984-09-04 | Miles Laboratories, Inc. | Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives |
| US4816567A (en) * | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| 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 |
| US5082658A (en) * | 1984-01-16 | 1992-01-21 | Genentech, Inc. | Gamma interferon-interleukin-2 synergism |
| US5807715A (en) * | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| US4667016A (en) * | 1985-06-20 | 1987-05-19 | Kirin-Amgen, Inc. | Erythropoietin purification |
| US5679543A (en) | 1985-08-29 | 1997-10-21 | Genencor International, Inc. | DNA sequences, vectors and fusion polypeptides to increase secretion of desired polypeptides from filamentous fungi |
| US4676980A (en) * | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| US4935233A (en) * | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
| US5359035A (en) | 1985-12-21 | 1994-10-25 | Hoechst Aktiengesellschaft | Bifunctional proteins including interleukin-2 (IL-2) and granuloctyte macrophage colony stimulating factor (GM-CSF) |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5225539A (en) * | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| DK173067B1 (da) | 1986-06-27 | 1999-12-13 | Univ Washington | Humant erythropoietin-gen, fremgangsmåde til ekspression deraf i transficerede cellelinier, de transficerede cellelinier sa |
| US4954617A (en) | 1986-07-07 | 1990-09-04 | Trustees Of Dartmouth College | Monoclonal antibodies to FC receptors for immunoglobulin G on human mononuclear phagocytes |
| US4946778A (en) * | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5019368A (en) * | 1989-02-23 | 1991-05-28 | Cancer Biologics, Inc. | Detection of necrotic malignant tissue and associated therapy |
| EP0275636B1 (en) * | 1987-01-19 | 1993-07-21 | Canon Kabushiki Kaisha | Color toner and two-component developer containing same |
| EP0307434B2 (en) * | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| US5091513A (en) * | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| ATE120761T1 (de) | 1987-05-21 | 1995-04-15 | Creative Biomolecules Inc | Multifunktionelle proteine mit vorbestimmter zielsetzung. |
| ATE122238T1 (de) | 1987-06-10 | 1995-05-15 | Dana Farber Cancer Inst Inc | Bifunktionelle antikörperkonstruktionen und verfahren zur selektiven tötung von zellbeständen. |
| US5064646A (en) | 1988-08-02 | 1991-11-12 | The University Of Maryland | Novel infectious bursal disease virus |
| PH26813A (en) | 1987-09-02 | 1992-11-05 | Ciba Geigy Ag | Conjugates of cytokines with immunoglobulins |
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| DE3850542T2 (de) | 1987-09-23 | 1994-11-24 | Bristol Myers Squibb Co | Antikörper-Heterokonjugate zur Töting von HIV-infizierten Zellen. |
| NZ226414A (en) | 1987-10-02 | 1992-07-28 | Genentech Inc | Cd4 peptide adhesion variants and their preparation and use |
| WO1989006692A1 (en) * | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| CA1341588C (en) | 1988-01-26 | 2009-01-06 | Michel Revel | Human ifn-beta2/i1-6, its purification and use |
| US5120525A (en) * | 1988-03-29 | 1992-06-09 | Immunomedics, Inc. | Radiolabeled antibody cytotoxic therapy of cancer |
| DE3812605A1 (de) | 1988-04-15 | 1990-06-07 | Leskovar Peter Dipl Ing Dr Hab | Immunregulative stoffe und stoffgemische zur aktiven beeinflussung des krankheitsverlaufes |
| US4975369A (en) | 1988-04-21 | 1990-12-04 | Eli Lilly And Company | Recombinant and chimeric KS1/4 antibodies directed against a human adenocarcinoma antigen |
| IT1217724B (it) | 1988-05-26 | 1990-03-30 | Ist Naz Ric Sul Cancro | Anticorpo monoclonale specifico per una sequenza di fibronettina espressa in cellule trasformate ibridoma secernente tale anticorpo e impiego dell'anticorpo monoclonale per la diagnosi di tumori |
| IE62463B1 (en) | 1988-07-07 | 1995-02-08 | Res Dev Foundation | Immunoconjugates for cancer diagnosis and therapy |
| US5601819A (en) * | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
| US5242824A (en) | 1988-12-22 | 1993-09-07 | Oncogen | Monoclonal antibody to human carcinomas |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5116964A (en) * | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| US6750329B1 (en) * | 1989-05-05 | 2004-06-15 | Research Development Foundation | Antibody delivery system for biological response modifiers |
| IE63847B1 (en) | 1989-05-05 | 1995-06-14 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
| US6291158B1 (en) * | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
| US5399346A (en) * | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
| AU641673B2 (en) | 1989-06-29 | 1993-09-30 | Medarex, Inc. | Bispecific reagents for aids therapy |
| EP0406857B1 (en) * | 1989-07-07 | 1995-05-24 | Takeda Chemical Industries, Ltd. | Proteins and production thereof |
| DE69034022T2 (de) | 1989-09-20 | 2003-07-10 | Abbott Laboratories, Abbott Park | Verfahren zur Herstellung von Fusionsproteinen |
| US5856298A (en) | 1989-10-13 | 1999-01-05 | Amgen Inc. | Erythropoietin isoforms |
| AU646822B2 (en) | 1989-10-13 | 1994-03-10 | Kirin-Amgen Inc. | Erythropoietin isoforms |
| US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
| WO1991013166A1 (en) | 1990-03-02 | 1991-09-05 | Abbott Biotech, Inc. | Antibody constructs with enhanced binding affinity |
| JP3319594B2 (ja) | 1990-03-20 | 2002-09-03 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | 定常領域の代わりに受容体結合性リガンドを有するキメラ抗体 |
| US5349053A (en) * | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
| US7253264B1 (en) | 1990-06-28 | 2007-08-07 | Sanofi-Arentideutschland GmbH | Immunoglobulin fusion proteins, their production and use |
| CA2082804A1 (en) | 1990-07-27 | 1992-01-28 | Theodore Maione | Methods and compositions for treatment of angiogenic diseases |
| US5650150A (en) | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
| EP0556328A4 (en) | 1990-11-09 | 1994-06-08 | Abbott Lab | Bridging antibody fusion constructs |
| ATE218889T1 (de) | 1990-11-09 | 2002-06-15 | Stephen D Gillies | Cytokine immunokonjugate |
| WO1992010755A1 (en) | 1990-12-05 | 1992-06-25 | Novo Nordisk A/S | Proteins with changed epitopes and methods for the production thereof |
| US5709859A (en) * | 1991-01-24 | 1998-01-20 | Bristol-Myers Squibb Company | Mixed specificity fusion proteins |
| GB9105245D0 (en) | 1991-03-12 | 1991-04-24 | Lynxvale Ltd | Binding molecules |
| US6072039A (en) | 1991-04-19 | 2000-06-06 | Rohm And Haas Company | Hybrid polypeptide comparing a biotinylated avidin binding polypeptide fused to a polypeptide of interest |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| WO1993003157A1 (en) | 1991-07-29 | 1993-02-18 | Dana Farber Cancer Institute | Plasmids for the rapid preparation of modified proteins |
| CA2116533A1 (en) | 1991-08-30 | 1993-03-18 | George J. Todaro | Hybrid cytokines |
| EP0531562A1 (de) * | 1991-09-11 | 1993-03-17 | Doerr, Hans-Wilhelm, Prof. Dr. med. | Kultivierung von Säugetierzellen |
| US20020037558A1 (en) * | 1991-10-23 | 2002-03-28 | Kin-Ming Lo | E.coli produced immunoglobulin constructs |
| US5335176A (en) * | 1991-12-02 | 1994-08-02 | Koyo Seiko Co., Ltd. | Safety system for vehicles |
| US6627615B1 (en) | 1991-12-17 | 2003-09-30 | The Regents Of The University Of California | Methods and compositions for in vivo gene therapy |
| GB9206422D0 (en) | 1992-03-24 | 1992-05-06 | Bolt Sarah L | Antibody preparation |
| DK0615451T3 (da) * | 1992-05-26 | 2006-04-24 | Immunex Corp | Hidtil ukendt cytokin der binder til CD30 |
| IL105914A0 (en) | 1992-06-04 | 1993-10-20 | Univ California | Methods and compositions for in vivo gene therapy |
| US5614184A (en) * | 1992-07-28 | 1997-03-25 | New England Deaconess Hospital | Recombinant human erythropoietin mutants and therapeutic methods employing them |
| DE69332485T2 (de) | 1992-08-11 | 2003-11-13 | The President And Fellows Of Harvard College, Cambridge | Immunmodulierende peptide |
| DE4228839A1 (de) | 1992-08-29 | 1994-03-03 | Behringwerke Ag | Verfahren zum Nachweis und zur Bestimmung von Mediatoren |
| WO1994009817A1 (en) | 1992-11-04 | 1994-05-11 | City Of Hope | Novel antibody construct |
| AU6709794A (en) | 1993-04-21 | 1994-11-08 | Brigham And Women's Hospital | Erythropoietin muteins with enhanced activity |
| AU6776194A (en) | 1993-04-28 | 1994-11-21 | Hybritech Incorporated | Method for creating optimized regulatory regions affecting protein expression and protein trafficking |
| AU697453B2 (en) * | 1993-04-29 | 1998-10-08 | Abbott Laboratories | Erythropoietin analog compositions and methods |
| US5554512A (en) | 1993-05-24 | 1996-09-10 | Immunex Corporation | Ligands for flt3 receptors |
| GB9316989D0 (en) | 1993-08-16 | 1993-09-29 | Lynxvale Ltd | Binding molecules |
| IL110669A (en) | 1993-08-17 | 2008-11-26 | Kirin Amgen Inc | Erythropoietin analogs |
| ATE203274T1 (de) | 1994-02-01 | 2001-08-15 | Nasa | Fusionierte proteine die antikörper-teile und nicht-antikörper-teile enthalten |
| CA2190101A1 (en) | 1994-05-13 | 1995-11-23 | Donald Leonard Nicholas Cardy | Improvements in or relating to peptide delivery |
| CU22615A1 (es) | 1994-06-30 | 2000-02-10 | Centro Inmunologia Molecular | Procedimiento de obtención de anticuerpos monoclonales murinos menos inmunogénicos. anticuerpos monoclonales obtenidos |
| JPH10503371A (ja) | 1994-07-29 | 1998-03-31 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 新規化合物 |
| US5888773A (en) * | 1994-08-17 | 1999-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Method of producing single-chain Fv molecules |
| US5514087A (en) * | 1994-08-26 | 1996-05-07 | Karl Storz Gmbh & Co. | Self-regulating insufflator |
| US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
| PT706799E (pt) | 1994-09-16 | 2002-05-31 | Merck Patent Gmbh | Imunoconjugados ii |
| JPH11501506A (ja) | 1994-12-12 | 1999-02-09 | ベス イスラエル デアコネス メディカル センター | キメラ型サイトカインおよびその利用 |
| US6086875A (en) * | 1995-01-17 | 2000-07-11 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of immunogens |
| US6485726B1 (en) | 1995-01-17 | 2002-11-26 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of therapeutics |
| EP0815224B1 (en) * | 1995-03-10 | 2004-07-21 | Genentech, Inc. | Receptor activation by gas6 |
| US6281010B1 (en) * | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
| WO1996040792A1 (en) | 1995-06-07 | 1996-12-19 | Novo Nordisk A/S | Modification of polypeptides |
| WO1997000317A1 (en) | 1995-06-07 | 1997-01-03 | Osteosa Inc. | Osteoclast growth regulatory factor |
| GB9511935D0 (en) | 1995-06-13 | 1995-08-09 | Smithkline Beecham Plc | Novel compound |
| WO1997024440A1 (en) | 1995-12-27 | 1997-07-10 | Genentech, Inc. | Ob protein derivatives having prolonged half-life |
| US6620413B1 (en) * | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
| US5723125A (en) * | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
| US6750334B1 (en) * | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
| WO1997030089A1 (en) | 1996-02-13 | 1997-08-21 | Regents Of The University Of California | Novel antibody-cytokine fusion protein, and methods of making and using the same |
| US5756541A (en) | 1996-03-11 | 1998-05-26 | Qlt Phototherapeutics Inc | Vision through photodynamic therapy of the eye |
| US6046310A (en) | 1996-03-13 | 2000-04-04 | Protein Design Labs., Inc. | FAS ligand fusion proteins and their uses |
| AU728657B2 (en) | 1996-03-18 | 2001-01-18 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| WO1997043316A1 (en) | 1996-05-10 | 1997-11-20 | Beth Israel Deaconess Medical Center, Inc. | Physiologically active molecules with extended half-lives and methods of using same |
| EP0927033A1 (en) | 1996-07-02 | 1999-07-07 | Bar-Ilan University | Retinoyloxy(substituted)alkylene butyrates useful for the treatment of cancer and other proliferative diseases |
| US5856293A (en) * | 1996-08-08 | 1999-01-05 | Colgate Palmolive Company | Light duty liquid cleaning compositions |
| ATE218143T1 (de) * | 1996-09-03 | 2002-06-15 | Gsf Forschungszentrum Umwelt | Verwendung bi-und trispezifischer antikörper zur induktion einer tumorimmunität |
| DE19649828A1 (de) | 1996-12-02 | 1998-06-04 | Bayer Ag | Verfahren zur diskontinuierlichen Herstellung von weichelastischen, offenzelligen Polyurethanschaumstoffen |
| US6737057B1 (en) | 1997-01-07 | 2004-05-18 | The University Of Tennessee Research Corporation | Compounds, compositions and methods for the endocytic presentation of immunosuppressive factors |
| US6100387A (en) * | 1997-02-28 | 2000-08-08 | Genetics Institute, Inc. | Chimeric polypeptides containing chemokine domains |
| US6277375B1 (en) * | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| ES2183351T3 (es) | 1997-04-17 | 2003-03-16 | Amgen Inc | Composicones que comprenden conjugados de proteina ob humana activa estable con una cadena fc de inmunoglobulinas y metodos. |
| EP0983303B1 (en) | 1997-05-21 | 2006-03-08 | Biovation Limited | Method for the production of non-immunogenic proteins |
| GB9712892D0 (en) | 1997-06-20 | 1997-08-20 | Eclagen Ltd | Identification of mhc binding peptides |
| WO1999002709A1 (en) | 1997-07-10 | 1999-01-21 | Beth Israel Deaconess Medical Center | Recombinant erythropoietin / immunoglobulin fusion proteins |
| US6165476A (en) | 1997-07-10 | 2000-12-26 | Beth Israel Deaconess Medical Center | Fusion proteins with an immunoglobulin hinge region linker |
| ATE375363T1 (de) | 1997-07-14 | 2007-10-15 | Bolder Biotechnology Inc | Derivate des wachstumshormons und verwandte proteine |
| PT1037927E (pt) * | 1997-12-08 | 2004-10-29 | Emd Lexigen Res Ct Corp | Proteinas de fusao heterodimericas uteis para imunoterapia de abordagem selectiva e estimulacao imunologica geral |
| PL199659B1 (pl) | 1998-02-25 | 2008-10-31 | Merck Patent Gmbh | Białko fuzyjne przeciwciała hu-KS IL2, cząsteczka DNA kodująca białko fuzyjne przeciwciała hu-KS IL2 i sposób wytwarzania białka fuzyjnego przeciwciała hu-KS IL2 |
| US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
| WO1999052562A2 (en) | 1998-04-15 | 1999-10-21 | Lexigen Pharmaceuticals Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor |
| WO1999053958A2 (en) * | 1998-04-17 | 1999-10-28 | Lexigen Pharmaceuticals Corporation | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with prostaglandin inhibitor |
| WO1999054484A1 (en) * | 1998-04-20 | 1999-10-28 | The Regents Of The University Of California | Modified immunoglobulin molecules and methods for use thereof |
| AU751823B2 (en) | 1998-05-14 | 2002-08-29 | Merck Patent Gmbh | Fused protein |
| CA2330527A1 (en) | 1998-06-15 | 1999-12-23 | Genzyme Transgenics Corporation | Erythropoietin analog-human serum albumin fusion |
| GB9814383D0 (en) | 1998-07-02 | 1998-09-02 | Cambridge Antibody Tech | Improvements relating to antibodies |
| US5946778A (en) * | 1998-08-11 | 1999-09-07 | Mcgarity; Ronald M. | Clip with retractable operating levers |
| WO2000009560A2 (en) | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
| ES2342239T3 (es) | 1998-08-25 | 2010-07-02 | Merck Patent Gmbh | Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. |
| US6419644B1 (en) * | 1998-09-08 | 2002-07-16 | Scimed Life Systems, Inc. | System and method for intraluminal imaging |
| US6646113B1 (en) | 1998-09-17 | 2003-11-11 | The Trustees Of The University Of Pennsylvania | Nucleic acid molecule encoding human survival of motor neuron-interacting protein 1 (SIP1) deletion mutants |
| US6335176B1 (en) * | 1998-10-16 | 2002-01-01 | Pharmacopeia, Inc. | Incorporation of phosphorylation sites |
| HK1040944B (en) | 1998-10-23 | 2007-09-07 | Amgen Inc. | Methods and compositions for the prevention and treatment of anemia |
| ES2278463T3 (es) | 1998-12-08 | 2007-08-01 | Biovation Limited | Metodo para reducir la inmunogenicidad de proteinas. |
| EP1141013A2 (en) * | 1999-01-07 | 2001-10-10 | Lexigen Pharmaceuticals Corp. | EXPRESSION AND EXPORT OF ANTI-OBESITY PROTEINS AS Fc FUSION PROTEINS |
| SG143935A1 (en) | 1999-05-06 | 2008-07-29 | Univ Wake Forest | Compositions and methods for identifying antigens which elicit an immune response |
| IL145785A0 (en) | 1999-05-07 | 2002-07-25 | Genentech Inc | Novel chimpanzee erythropoietin (chepo) polypeptides and nucleic acids encoding the same |
| CN1361793A (zh) * | 1999-05-19 | 2002-07-31 | 利思进药品公司 | 干扰素-α蛋白作为Fc融合蛋白的表达和运输 |
| CZ299516B6 (cs) * | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem |
| PE20010288A1 (es) * | 1999-07-02 | 2001-03-07 | Hoffmann La Roche | Derivados de eritropoyetina |
| SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| US7067110B1 (en) * | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| DE59913565D1 (de) * | 1999-08-05 | 2006-07-27 | Baxter Ag | Rekombinanter stabiler zellklon, seine herstellung und verwendung |
| DE60025832T2 (de) | 1999-08-09 | 2006-08-31 | Emd Lexigen Research Center Corp., Billerica | Mehrere zytokin-antikörper komplexen |
| US20050202538A1 (en) | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
| AU2154401A (en) * | 1999-11-12 | 2001-05-30 | Merck Patent Gmbh | Erythropoietin forms with improved properties |
| HUP0204475A2 (en) * | 2000-02-11 | 2003-04-28 | Merck Patent Gmbh | Enhancing the circulating half-life of antibody-based fusion proteins |
| ATE333900T1 (de) * | 2000-02-24 | 2006-08-15 | Philogen Spa | Zusamensetzungen und verfahren zur behandlung von angiogenese in pathologischen schädigungen |
| US6586398B1 (en) * | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| EP2292651A1 (en) * | 2000-04-21 | 2011-03-09 | Amgen Inc. | Methods and compositions for the prevention and treatment of anemia |
| JP2004528001A (ja) * | 2000-05-12 | 2004-09-16 | ネオーズ テクノロジーズ, インコーポレイテッド | インビトロにおけるフコシル化組換えグリコペプチド |
| EP1294401B1 (en) * | 2000-06-29 | 2007-08-01 | EMD Lexigen Research Center Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents |
| CN1630720A (zh) * | 2001-01-18 | 2005-06-22 | 默克专利有限公司 | 具有葡糖脑苷脂酶活性的双功能融合蛋白 |
| CA2438628A1 (en) | 2001-02-19 | 2002-08-29 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Artificial proteins with reduced immunogenicity |
| MXPA03007316A (es) | 2001-02-19 | 2003-12-04 | Merck Patent Gmbh | Metodo para la identificacion de epitopes de celulas t y el uso para la preparacion de moleculas con inmunogenicidad reducida. |
| RU2003129528A (ru) | 2001-03-07 | 2005-04-10 | Мерк Патент ГмбХ (DE) | Способ экспрессии белков, содержащих в качестве компонента гибридный изотип антитела |
| WO2002079415A2 (en) * | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| DE60239454D1 (de) | 2001-05-03 | 2011-04-28 | Merck Patent Gmbh | Rekombinanter, tumorspezifischer antikörper und dessen verwendung |
| JP2005507870A (ja) | 2001-08-13 | 2005-03-24 | ユニバーシティ・オブ・サザン・カリフォルニア | 低毒性のインターロイキン−2突然変異体 |
| US6900292B2 (en) * | 2001-08-17 | 2005-05-31 | Lee-Hwei K. Sun | Fc fusion proteins of human erythropoietin with increased biological activities |
| EP1454138B1 (en) | 2001-12-04 | 2012-01-18 | Merck Patent GmbH | Immunocytokines with modulated selectivity |
| CN101143221A (zh) | 2002-03-15 | 2008-03-19 | 布赖汉姆妇女医院 | 适合治疗剂全身性递送的中央气道给药 |
| WO2003106484A1 (en) * | 2002-06-17 | 2003-12-24 | Chr. Hansen A/S | Improved method of producing an aspartic protease in a recombinant host organism |
| CA2510180C (en) * | 2002-12-17 | 2012-09-11 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2 |
| US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
| CN100467488C (zh) * | 2003-12-30 | 2009-03-11 | 默克专利有限公司 | Il-7融合蛋白 |
| RU2370276C2 (ru) | 2003-12-31 | 2009-10-20 | Мерк Патент Гмбх | Fc-ЭРИТРОПОЭТИН СЛИТЫЙ БЕЛОК С УЛУЧШЕННОЙ ФАРМАКОКИНЕТИКОЙ |
| CA2553883C (en) | 2004-01-22 | 2013-04-02 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Anti-cancer antibodies with reduced complement fixation |
| US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| US7589179B2 (en) * | 2004-12-09 | 2009-09-15 | Merck Patent Gmbh | IL-7 variants with reduced immunogenicity |
| US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
| PL1966244T3 (pl) * | 2005-12-30 | 2012-08-31 | Merck Patent Gmbh | Przeciwciała anty-il-6 zapobiegające wiązaniu il-6 skompleksowanego z il-6ralpha do gp130 |
| ATE509954T1 (de) * | 2005-12-30 | 2011-06-15 | Merck Patent Gmbh | Anti-cd19-antikörper mit reduzierter immunogenität |
| ES2384055T3 (es) | 2005-12-30 | 2012-06-28 | Merck Patent Gmbh | Variantes de la interleucina-12p40 con estabilidad mejorada |
| EP1999154B1 (en) | 2006-03-24 | 2012-10-24 | Merck Patent GmbH | Engineered heterodimeric protein domains |
| CA2656700A1 (en) * | 2006-07-06 | 2008-01-10 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Compositions and methods for enhancing the efficacy of il-2 mediated immune responses |
-
2004
- 2004-12-22 RU RU2006127554/15A patent/RU2370276C2/ru not_active IP Right Cessation
- 2004-12-22 AU AU2004309063A patent/AU2004309063B2/en not_active Ceased
- 2004-12-22 JP JP2006546058A patent/JP2008504008A/ja active Pending
- 2004-12-22 ES ES04804204T patent/ES2387028T3/es not_active Expired - Lifetime
- 2004-12-22 KR KR1020067012656A patent/KR20060124656A/ko not_active Withdrawn
- 2004-12-22 WO PCT/EP2004/014608 patent/WO2005063808A1/en not_active Ceased
- 2004-12-22 CA CA2551916A patent/CA2551916C/en not_active Expired - Fee Related
- 2004-12-22 BR BRPI0417916-1A patent/BRPI0417916A/pt not_active IP Right Cessation
- 2004-12-22 EP EP04804204A patent/EP1699821B1/en not_active Expired - Lifetime
- 2004-12-22 DK DK04804204.8T patent/DK1699821T3/da active
- 2004-12-22 CN CNA2004800396709A patent/CN1902222A/zh active Pending
- 2004-12-22 PT PT04804204T patent/PT1699821E/pt unknown
- 2004-12-30 US US11/026,998 patent/US7465447B2/en not_active Expired - Fee Related
-
2008
- 2008-09-26 US US12/238,840 patent/US20090092607A1/en not_active Abandoned
-
2012
- 2012-02-17 JP JP2012032557A patent/JP2012107042A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008504008A (ja) | 2008-02-14 |
| CN1902222A (zh) | 2007-01-24 |
| US7465447B2 (en) | 2008-12-16 |
| AU2004309063A1 (en) | 2005-07-14 |
| RU2370276C2 (ru) | 2009-10-20 |
| RU2006127554A (ru) | 2008-02-10 |
| BRPI0417916A (pt) | 2007-04-10 |
| ES2387028T3 (es) | 2012-09-12 |
| PT1699821E (pt) | 2012-08-23 |
| DK1699821T3 (da) | 2012-07-16 |
| KR20060124656A (ko) | 2006-12-05 |
| EP1699821B1 (en) | 2012-06-20 |
| EP1699821A1 (en) | 2006-09-13 |
| JP2012107042A (ja) | 2012-06-07 |
| US20050192211A1 (en) | 2005-09-01 |
| AU2004309063B2 (en) | 2010-10-28 |
| US20090092607A1 (en) | 2009-04-09 |
| CA2551916A1 (en) | 2005-07-14 |
| WO2005063808A1 (en) | 2005-07-14 |
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