KR101227278B1 - 동결건조된 치료 펩티바디 제제 - Google Patents
동결건조된 치료 펩티바디 제제 Download PDFInfo
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- KR101227278B1 KR101227278B1 KR1020087028391A KR20087028391A KR101227278B1 KR 101227278 B1 KR101227278 B1 KR 101227278B1 KR 1020087028391 A KR1020087028391 A KR 1020087028391A KR 20087028391 A KR20087028391 A KR 20087028391A KR 101227278 B1 KR101227278 B1 KR 101227278B1
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79399706P | 2006-04-21 | 2006-04-21 | |
| US60/793,997 | 2006-04-21 | ||
| US11/788,697 US9283260B2 (en) | 2006-04-21 | 2007-04-19 | Lyophilized therapeutic peptibody formulations |
| US11/788,697 | 2007-04-19 | ||
| PCT/US2007/009712 WO2007124090A2 (en) | 2006-04-21 | 2007-04-20 | Lyophilized therapeutic peptibody formulations |
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| KR1020127022549A Division KR101236042B1 (ko) | 2006-04-21 | 2007-04-20 | 동결건조된 치료 펩티바디 제제 |
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| KR20090005204A KR20090005204A (ko) | 2009-01-12 |
| KR101227278B1 true KR101227278B1 (ko) | 2013-01-28 |
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| KR1020087028391A Active KR101227278B1 (ko) | 2006-04-21 | 2007-04-20 | 동결건조된 치료 펩티바디 제제 |
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| KR1020127022549A Active KR101236042B1 (ko) | 2006-04-21 | 2007-04-20 | 동결건조된 치료 펩티바디 제제 |
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Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1783222T3 (da) | 1998-10-23 | 2012-07-09 | Kirin Amgen Inc | Dimere trombopoietiske peptidomimetika, der binder til MPL-receptor og har trombopoietisk aktivitet |
| US7658938B2 (en) | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
| DK2130554T3 (da) | 1999-02-22 | 2012-12-03 | Univ Connecticut | Albuminfrie faktor VIII-præparater |
| JP4817503B2 (ja) | 1999-06-01 | 2011-11-16 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Ｖｌａ−１に対するブロッキングモノクローナル抗体および炎症性障害の処置のためのその使用 |
| EE200300509A (et) | 2001-04-13 | 2004-08-16 | Biogen, Inc. | Antikehad VLA-1 vastu |
| WO2007093042A1 (en) | 2006-02-13 | 2007-08-23 | Alethia Biotherapeutics Inc. | Polynucleotides and polypeptide sequences involved in the process of bone remodeling |
| US8168181B2 (en) | 2006-02-13 | 2012-05-01 | Alethia Biotherapeutics, Inc. | Methods of impairing osteoclast differentiation using antibodies that bind siglec-15 |
| US7704977B2 (en) | 2006-04-07 | 2010-04-27 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
| AU2011265555B2 (en) * | 2006-04-21 | 2016-03-10 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
| US9283260B2 (en) * | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
| CN105381459A (zh) | 2006-05-25 | 2016-03-09 | 比奥根Ma公司 | 治疗中风的方法 |
| JP5671451B2 (ja) * | 2008-05-07 | 2015-02-18 | メリオン・リサーチ・Ｉｉｉ・リミテッド | ＧｎＲＨ関連化合物の組成物および調製プロセス |
| KR101752508B1 (ko) * | 2008-11-07 | 2017-06-29 | 백스터 인터내셔널 인코포레이티드 | 제8 인자 제형 |
| US20120183546A1 (en) | 2009-09-23 | 2012-07-19 | Amgen Inc. | Treatment of ovarian cancer using a specific binding agent of human angiopoietin-2 in combination with a taxane |
| ES2700925T3 (es) * | 2010-01-19 | 2019-02-20 | Hanmi Science Co Ltd | Formulaciones líquidas para conjugado de eritropoyetina de acción prolongada |
| WO2011120033A1 (en) | 2010-03-26 | 2011-09-29 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor xa inhibitors for oral administration |
| EA201390810A1 (ru) | 2010-12-02 | 2013-09-30 | Онколитикс Байотек Инк. | Жидкие вирусные составы |
| WO2012075376A2 (en) | 2010-12-02 | 2012-06-07 | Oncolytics Biotech Inc. | Lyophilized viral formulations |
| JP5759211B2 (ja) * | 2011-03-11 | 2015-08-05 | 三洋化成工業株式会社 | 凍結乾燥方法 |
| CA2840212A1 (en) | 2011-06-29 | 2013-01-03 | Amgen Inc. | Predictive biomarker of survival in the treatment of renal cell carcinoma |
| DE102011055889B4 (de) * | 2011-11-30 | 2013-08-01 | Otc Gmbh | Verfahren zur Herstellung eines Protein-Hydrolysates |
| CN102586217A (zh) * | 2011-12-16 | 2012-07-18 | 深圳市海普瑞药业股份有限公司 | 肝素黄杆菌肝素酶ⅰ、ⅱ、ⅲ的冻干保存方法 |
| RU2482128C1 (ru) * | 2011-12-28 | 2013-05-20 | Замертон Холдингс Лимитед | Пептиды, обладающие цитопротекторной активностью |
| US10316095B2 (en) * | 2012-02-16 | 2019-06-11 | Santarus, Inc. | Antibody formulations |
| EP2644186A1 (en) | 2012-03-26 | 2013-10-02 | OTC GmbH | Hair conditioning composition for permanent and semi-permanent hair coloration applications |
| KR20150034170A (ko) * | 2012-06-25 | 2015-04-02 | 이머전트 프로덕트 디벨롭먼트 게이더스버그 인코포레이티드 | 온도 안정성 백신 제형 |
| CA2928851A1 (en) | 2012-07-19 | 2014-01-23 | Alethia Biotherapeutics Inc. | Anti-siglec-15 antibodies |
| EP2698162A1 (en) * | 2012-08-15 | 2014-02-19 | Credentis AG | Method for producing a composition for treating a tooth lesion |
| AU2014228423A1 (en) * | 2013-03-15 | 2015-11-05 | Amgen Inc. | Myostatin antagonism in human subjects |
| CN104274827B (zh) * | 2013-07-01 | 2020-07-14 | 上海贺普药业股份有限公司 | 贺普拉肽的制剂 |
| WO2015035405A1 (en) * | 2013-09-09 | 2015-03-12 | Pinta Biotherapeutics, Inc. | Myostatin antagonist for treatment of pew in esrd patients |
| TR201902755T4 (tr) * | 2013-11-07 | 2019-03-21 | Dr August Wolff Gmbh & Co Kg Arzneimittel | Depolama kararliliğina sahi̇p li̇yofi̇li̇ze tri̇pepti̇t formülasyonlari. |
| WO2015077717A1 (en) | 2013-11-25 | 2015-05-28 | The Broad Institute Inc. | Compositions and methods for diagnosing, evaluating and treating cancer by means of the dna methylation status |
| WO2015085147A1 (en) | 2013-12-05 | 2015-06-11 | The Broad Institute Inc. | Polymorphic gene typing and somatic change detection using sequencing data |
| CA2932798C (en) * | 2013-12-06 | 2022-09-20 | The Broad Institute, Inc. | Formulations for neoplasia vaccines |
| EP3082853A2 (en) | 2013-12-20 | 2016-10-26 | The Broad Institute, Inc. | Combination therapy with neoantigen vaccine |
| WO2015100344A1 (en) | 2013-12-27 | 2015-07-02 | Emergent Product Development Gaithersburg Inc. | Temperature stable vaccine formulations |
| US11299528B2 (en) | 2014-03-11 | 2022-04-12 | D&D Pharmatech Inc. | Long acting TRAIL receptor agonists for treatment of autoimmune diseases |
| CA2943919A1 (en) * | 2014-03-29 | 2015-10-08 | Intas Pharmaceuticals Ltd. | Lyophilized pharmaceutical composition of fc-peptide fusion protein |
| EP3757134B1 (en) * | 2014-05-28 | 2024-03-06 | NoNO Inc. | Chloride salt of tat-nr2b9c |
| EP3155008B1 (en) * | 2014-06-13 | 2020-08-26 | Atara Biotherapeutics, Inc. | Formulated receptor polypeptides and related methods |
| ES2814157T3 (es) * | 2014-08-20 | 2021-03-26 | Portola Pharm Inc | Formulaciones liofilizadas para antídoto del factor Xa |
| JP6671141B2 (ja) * | 2014-10-21 | 2020-03-25 | 大日本住友製薬株式会社 | 懸濁液剤 |
| EP3234193B1 (en) | 2014-12-19 | 2020-07-15 | Massachusetts Institute of Technology | Molecular biomarkers for cancer immunotherapy |
| ES3049406T3 (en) | 2014-12-19 | 2025-12-16 | Broad Inst Inc | Methods for profiling the t-cell-receptor repertoire |
| CN107205948B (zh) | 2015-01-29 | 2021-12-14 | 诺和诺德股份有限公司 | 包含glp-1激动剂和肠溶衣的片剂 |
| US10857229B2 (en) | 2015-04-30 | 2020-12-08 | Amgen Inc. | Treatment of ovarian cancer in patients with ascites using a specific binding agent of human angiopoietin-2 in combination with a taxane |
| CN108025048B (zh) | 2015-05-20 | 2022-10-25 | 博德研究所 | 共有的新抗原 |
| CN108601819B (zh) | 2015-12-17 | 2022-03-15 | 约翰霍普金斯大学 | 用死亡受体激动剂改善系统性硬化症 |
| US11389510B2 (en) | 2016-01-08 | 2022-07-19 | Ascendis Pharma Growth Disorders A/S | Controlled-release CNP agonists with low initial NPR-B activity |
| EP3400018A1 (en) | 2016-01-08 | 2018-11-14 | Ascendis Pharma Growth Disorders A/S | Controlled-release cnp agonists with increased nep stability |
| PL3400019T3 (pl) | 2016-01-08 | 2023-01-23 | Ascendis Pharma Growth Disorders A/S | Proleki cnp z przyłączeniem nośnika w ugrupowaniu pierścieniowy |
| JP6992262B2 (ja) * | 2016-03-31 | 2022-02-15 | 東ソー株式会社 | 変性抗体測定試薬の製造方法 |
| JP7281795B2 (ja) | 2016-04-07 | 2023-05-26 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 膵炎および疼痛をデス受容体アゴニストで処置するための組成物および方法 |
| GB201608323D0 (en) | 2016-05-12 | 2016-06-29 | Ucb Biopharma Sprl | Pharmaceutical compositions |
| US10654922B2 (en) * | 2016-05-13 | 2020-05-19 | Askgene Pharma Inc. | Angiopoietin 2, VEGF dual antagonists |
| IL308416B2 (en) | 2016-12-02 | 2025-08-01 | Bioverativ Therapeutics Inc | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| US11549149B2 (en) | 2017-01-24 | 2023-01-10 | The Broad Institute, Inc. | Compositions and methods for detecting a mutant variant of a polynucleotide |
| JP2017155046A (ja) * | 2017-04-05 | 2017-09-07 | イーストポンド・ラボラトリーズ・リミテッド | シクロデキストリンを含有する細胞水和組成物 |
| AU2018334502A1 (en) | 2017-09-15 | 2020-03-12 | Amgen Inc. | Process for lyophilized pharmaceutical formulation of a therapeutic protein |
| US20200255496A1 (en) * | 2017-09-18 | 2020-08-13 | Amgen Inc. | Vegfr-fc fusion protein formulations |
| CA3189025A1 (en) * | 2017-12-22 | 2019-06-27 | Samsung Bioepis Co., Ltd. | Liquid composition comprising vegf antagonist |
| CN108159413B (zh) * | 2018-01-10 | 2021-07-06 | 杭州洪桥中科基因技术有限公司 | 一种动物用冻干活疫苗及其制备方法 |
| GB201804835D0 (en) * | 2018-03-26 | 2018-05-09 | Ge Healthcare As | Formulation and method of preparation |
| MA52630B1 (fr) | 2018-05-18 | 2025-07-31 | Bioverativ Therapeutics Inc. | Procédés de traitement de l'hémophilie a |
| US20210236636A1 (en) * | 2018-07-31 | 2021-08-05 | Amgen Inc. | Pharmaceutical formulations of masked antibodies |
| KR102893903B1 (ko) | 2019-02-11 | 2025-12-01 | 아센디스 파마 그로우쓰 디스오더스 에이/에스 | Cnp 접합체의 건조 약학 제제 |
| JP7266108B2 (ja) | 2019-02-18 | 2023-04-27 | イーライ リリー アンド カンパニー | 治療用抗体製剤 |
| CN113660953A (zh) * | 2019-04-01 | 2021-11-16 | 豪夫迈·罗氏有限公司 | 用于稳定含蛋白质制剂的组合物和方法 |
| EP3736574A1 (en) * | 2019-05-07 | 2020-11-11 | Atlas Antibodies AB | A formulation comprising an isotope labeled fusion polypeptide |
| EP3744319B1 (en) * | 2019-05-28 | 2022-10-19 | Ilkogen Ilac Sanayi Ve Ticaret A.S. | A stable lyophilized formulation for hybrid fc fused g-csf |
| JP2019178154A (ja) * | 2019-06-18 | 2019-10-17 | イーストポンド・ラボラトリーズ・リミテッド | シクロデキストリンを含有する細胞水和組成物 |
| GB201911461D0 (en) * | 2019-08-09 | 2019-09-25 | Arecor Ltd | Novel composition |
| CN115427569A (zh) * | 2019-12-02 | 2022-12-02 | 奥特万科学有限公司 | 下气道疾病的治疗 |
| KR20220122648A (ko) * | 2019-12-03 | 2022-09-02 | 차이나 메디칼 유니버시티 | 올리고펩티드, 이의 테스트 키트, 및 이의 의약 조성물 |
| US11767353B2 (en) | 2020-06-05 | 2023-09-26 | Theraly Fibrosis, Inc. | Trail compositions with reduced immunogenicity |
| EP4314083A4 (en) * | 2021-03-31 | 2025-04-09 | Hangzhou Exegenesis Bio Ltd. | Fusion molecules targeting VEGF and angiopoietin and uses thereof |
| KR20240109277A (ko) | 2021-12-01 | 2024-07-10 | 유씨비 바이오파마 에스알엘 | Fab-peg를 포함하는 제제 |
| US20240076597A1 (en) * | 2022-09-02 | 2024-03-07 | Terumo Bct, Inc. | Methods for cell expansion, differentiation, and/or harvesting of natural killer cells using hollow-fiber membranes |
| WO2024133908A1 (en) * | 2022-12-23 | 2024-06-27 | Syna Therapeutics, S.L. | Stable pharmaceutical compositions comprising romiplostim |
| WO2024263570A1 (en) * | 2023-06-23 | 2024-12-26 | The Regents Of The University Of Michigan | Nanoparticle compositions associated with peptides |
| CN118126120B (zh) * | 2023-09-14 | 2024-12-06 | 海南大学 | 抑制Aβ42聚集并降低其细胞毒作用的三肽化合物 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001083525A2 (en) * | 2000-05-03 | 2001-11-08 | Amgen Inc. | Modified peptides, comprising an fc domain, as therapeutic agents |
Family Cites Families (109)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3691016A (en) * | 1970-04-17 | 1972-09-12 | Monsanto Co | Process for the preparation of insoluble enzymes |
| CA1023287A (en) * | 1972-12-08 | 1977-12-27 | Boehringer Mannheim G.M.B.H. | Process for the preparation of carrier-bound proteins |
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US3941763A (en) * | 1975-03-28 | 1976-03-02 | American Home Products Corporation | PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates |
| US4002531A (en) * | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| US4195128A (en) * | 1976-05-03 | 1980-03-25 | Bayer Aktiengesellschaft | Polymeric carrier bound ligands |
| US4330440A (en) * | 1977-02-08 | 1982-05-18 | Development Finance Corporation Of New Zealand | Activated matrix and method of activation |
| CA1093991A (en) * | 1977-02-17 | 1981-01-20 | Hideo Hirohara | Enzyme immobilization with pullulan gel |
| US4229537A (en) * | 1978-02-09 | 1980-10-21 | New York University | Preparation of trichloro-s-triazine activated supports for coupling ligands |
| DE3244265A1 (de) | 1982-11-30 | 1984-05-30 | Cassella Ag, 6000 Frankfurt | Weichmacheremulsion, verfahren zu ihrer herstellung und ihre anwendung |
| US4503235A (en) | 1983-03-11 | 1985-03-05 | Warner-Lambert Company | Process for producing 4-carbamoyl-1H-imidazolium-5-olate |
| DE3572982D1 (en) | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
| EP0315456B1 (en) | 1987-11-05 | 1994-06-01 | Hybritech Incorporated | Polysaccharide-modified immunoglobulins having reduced immunogenic potential or improved pharmacokinetics |
| US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US5223409A (en) * | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| GB8824591D0 (en) | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Fractionation process |
| CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
| US5089261A (en) * | 1989-01-23 | 1992-02-18 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US4902502A (en) | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US5627262A (en) | 1989-07-05 | 1997-05-06 | The Board Of Regents Of The University Of Oklahoma | Method and composition for the treatment of septic shock |
| DK0939121T4 (da) | 1989-09-12 | 2008-02-04 | Ahp Mfg B V | TNF-bindende proteiner |
| JPH04218000A (ja) | 1990-02-13 | 1992-08-07 | Kirin Amgen Inc | 修飾ポリペプチド |
| US5723286A (en) * | 1990-06-20 | 1998-03-03 | Affymax Technologies N.V. | Peptide library and screening systems |
| US5252714A (en) * | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| ATE240740T1 (de) | 1991-03-15 | 2003-06-15 | Amgen Inc | Pegylation von polypeptiden |
| US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5281698A (en) * | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
| US5362852A (en) * | 1991-09-27 | 1994-11-08 | Pfizer Inc. | Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties |
| US5733731A (en) * | 1991-10-16 | 1998-03-31 | Affymax Technologies N.V. | Peptide library and screening method |
| US5270170A (en) * | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| NZ244778A (en) | 1991-10-21 | 1994-03-25 | Ortho Pharma Corp | Peg imidates and protein derivatives thereof |
| DK0615451T3 (da) | 1992-05-26 | 2006-04-24 | Immunex Corp | Hidtil ukendt cytokin der binder til CD30 |
| DE69332485T2 (de) | 1992-08-11 | 2003-11-13 | The President And Fellows Of Harvard College, Cambridge | Immunmodulierende peptide |
| GB9225448D0 (en) | 1992-12-04 | 1993-01-27 | Erba Carlo Spa | Improved synthesis of polymer bioactive conjugates |
| US5922545A (en) * | 1993-10-29 | 1999-07-13 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
| US5773569A (en) * | 1993-11-19 | 1998-06-30 | Affymax Technologies N.V. | Compounds and peptides that bind to the erythropoietin receptor |
| US5981478A (en) | 1993-11-24 | 1999-11-09 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
| US5880096A (en) * | 1994-02-02 | 1999-03-09 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
| US5786331A (en) * | 1994-02-02 | 1998-07-28 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
| US5608035A (en) * | 1994-02-02 | 1997-03-04 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
| US5844929A (en) * | 1994-02-24 | 1998-12-01 | British Telecommunications Public Limited Company | Optical device with composite passive and tapered active waveguide regions |
| 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 |
| US20030053982A1 (en) * | 1994-09-26 | 2003-03-20 | Kinstler Olaf B. | N-terminally chemically modified protein compositions and methods |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| AU693478B2 (en) | 1994-11-10 | 1998-07-02 | Metabolic Pharmaceuticals Limited | Treatment of obesity |
| IL116026A (en) | 1994-11-22 | 2005-08-31 | Rhone Poulenc Rorer Sa | Peptides capable of linking to the sh3 domain of gap, nucleotide sequences encoding the same, their preparation and uses |
| US5888763A (en) | 1994-12-30 | 1999-03-30 | The Rockefeller University | Peptides specific for the first Crk-SH3 domain |
| AU695129B2 (en) * | 1995-02-06 | 1998-08-06 | Genetics Institute, Llc | Formulations for IL-12 |
| IL113159A0 (en) | 1995-03-28 | 1995-06-29 | Yeda Res & Dev | Synthetic peptides and pharmaceutical compositions comprising them |
| US5739277A (en) * | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
| US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
| US5869451A (en) * | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
| US5767078A (en) | 1995-06-07 | 1998-06-16 | Johnson; Dana L. | Agonist peptide dimers |
| MX9800684A (es) * | 1995-07-27 | 1998-04-30 | Genentech Inc | Formulacion de proteinas liofilizadas isotonicas estables. |
| US5746516A (en) | 1995-08-11 | 1998-05-05 | Hitachi Powdered Metals Co., Ltd. | Porous bearing system having internal grooves and electric motor provided with the same |
| US5817750A (en) | 1995-08-28 | 1998-10-06 | La Jolla Cancer Research Foundation | Structural mimics of RGD-binding sites |
| JPH09151200A (ja) | 1995-09-29 | 1997-06-10 | Ajinomoto Co Inc | ヒト胃癌に対する免疫応答を誘導できるペプチド及び該ペプチドを含むヒト胃癌治療、予防剤 |
| US6369027B1 (en) | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
| US5714577A (en) | 1996-01-26 | 1998-02-03 | University Of Pittsburgh | Antimicrobial peptides |
| IL117223A0 (en) | 1996-02-22 | 1996-06-18 | Yeda Res & Dev | Antipathogenic polypeptides and compositions comprising them |
| AU728657B2 (en) | 1996-03-18 | 2001-01-18 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| AU2597897A (en) | 1996-03-28 | 1997-10-17 | Brigham And Women's Hospital | Peptide ligands of the urokinase receptor |
| IL118003A0 (en) | 1996-04-23 | 1996-08-04 | Yeda Res & Dev | Novel vip fragments and pharmaceutical compositions comprising them |
| FR2748028B1 (fr) | 1996-04-30 | 1998-08-14 | Lab Francais Du Fractionnement | Peptides derives du facteur von willebrand et leur utilisation comme anticoagulant |
| EP0911393B1 (en) | 1996-06-07 | 2007-01-10 | Takeda Pharmaceutical Company Limited | Peptide having cortistatin or somatostatin activity, process for the production of the same, and use of the same |
| US6126939A (en) | 1996-09-03 | 2000-10-03 | Yeda Research And Development Co. Ltd. | Anti-inflammatory dipeptide and pharmaceutical composition thereof |
| JP2001501600A (ja) | 1996-09-10 | 2001-02-06 | ザ バーナム インスティテュート | 腫瘍ホーミング分子、それに由来する結合体、およびその使用方法 |
| JP2001501619A (ja) * | 1996-10-04 | 2001-02-06 | アムジェン インコーポレーテッド | ｍｐｌリガンドを含有する医薬組成物 |
| CA2267139A1 (en) | 1996-10-08 | 1998-04-16 | Ton Logtenberg | Methods and means for selecting peptides and proteins having specific affinity for a target |
| WO1998033812A1 (en) | 1997-02-05 | 1998-08-06 | Brigham And Women's Hospital, Inc. | Mast cell protease peptide inhibitors |
| ES2284203T5 (es) | 1997-04-16 | 2016-03-11 | Amgen Inc. | Proteínas de unión a osteoprotegerina y sus receptores |
| US6265535B1 (en) | 1997-05-30 | 2001-07-24 | The Trustees Of The University Of Pennsylvania | Peptides and peptide analogues designed from binding sites of tumor necrosis factor receptor superfamily and their uses |
| US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| IL135835A0 (en) | 1997-11-07 | 2001-05-20 | Conjuchem Inc | Novel conjugates of opioids and endogenous carriers |
| WO1999038526A1 (en) | 1998-01-29 | 1999-08-05 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Variant peptide ligands that selectively induce apoptosis |
| US6423685B1 (en) | 1998-03-05 | 2002-07-23 | Chiron Corporation | Method for increasing the serum half-life of a biologically active molecule |
| US6235872B1 (en) | 1998-03-12 | 2001-05-22 | The Burnham Institute | Proapoptotic peptides dependence polypeptides and methods of use |
| WO1999047151A1 (en) | 1998-03-20 | 1999-09-23 | Chugai Pharmaceutical Co., Ltd. | Peptide ligands for the erythropoietin receptor |
| EP0947524A1 (en) | 1998-03-30 | 1999-10-06 | Upither B.V. | Novel peptides for the treatment of autoimmune diseases |
| CA2327811A1 (en) | 1998-04-06 | 1999-10-14 | Advanced Immunit, Inc. | Short peptides for treatment of neurological degenerative diseases |
| ATE399567T1 (de) * | 1998-04-28 | 2008-07-15 | Serono Lab | Peg konjugate von lhrh analogen |
| EP0972780A1 (en) | 1998-05-18 | 2000-01-19 | Applied Research Systems ARS Holding N.V. | Il-6 antagonist peptides |
| DE69938782D1 (de) | 1998-05-22 | 2008-07-03 | Abbott Lab | Peptide als antiangiogene arzneimittel |
| US5932548A (en) | 1998-06-03 | 1999-08-03 | Deghenghi; Romano | Lysine containing peptides for treatment of heart disease |
| WO2000001402A1 (en) | 1998-07-02 | 2000-01-13 | Envision Biomedical Consulting | Antiproliferative and antiviral proteins and peptides |
| US6168785B1 (en) | 1998-07-16 | 2001-01-02 | Institut Pasteur | Biological applications of new peptides of IL-2 and derivatives and use as therapeutic agents |
| US6906170B1 (en) | 1998-08-21 | 2005-06-14 | Yeda Research And Development Co. Ltd. | Anti-inflammatory peptides derived from IL-2 and analogues thereof |
| MXPA01003790A (es) | 1998-10-16 | 2002-09-18 | Biogen Inc | Proteinas de fusion beta - interferon y sus usos. |
| DK1783222T3 (da) * | 1998-10-23 | 2012-07-09 | Kirin Amgen Inc | Dimere trombopoietiske peptidomimetika, der binder til MPL-receptor og har trombopoietisk aktivitet |
| US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| AU2880400A (en) | 1999-02-12 | 2000-08-29 | Amgen, Inc. | Tnf-related proteins |
| US6635646B1 (en) * | 1999-05-04 | 2003-10-21 | Schering Corporation | Pegylated interferon alfa-CCR5 antagonist combination HIV therapy |
| US6586398B1 (en) * | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| US6853809B2 (en) | 2001-01-30 | 2005-02-08 | Koninklijke Philips Electronics N.V. | Camera system for providing instant switching between wide angle and full resolution views of a subject |
| CN100448891C (zh) * | 2001-05-11 | 2009-01-07 | 安姆根有限公司 | 与tall-1结合的肽和相关分子 |
| RU2180233C1 (ru) | 2001-06-26 | 2002-03-10 | Общество с ограниченной ответственностью "Протеиновый контур" | Способ получения жидких лекарственных форм рекомбинантных белков |
| US7332474B2 (en) * | 2001-10-11 | 2008-02-19 | Amgen Inc. | Peptides and related compounds having thrombopoietic activity |
| US7138370B2 (en) * | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| US7205275B2 (en) | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
| WO2004019860A2 (en) | 2002-08-28 | 2004-03-11 | Pharmacia Corporation | Formulations of modified antibodies and methods of making the same |
| US6919426B2 (en) | 2002-09-19 | 2005-07-19 | Amgen Inc. | Peptides and related molecules that modulate nerve growth factor activity |
| WO2004039337A2 (en) | 2002-10-31 | 2004-05-13 | Protein Design Labs, Inc. | Stable liquid pharmaceutical formulation of antibodies that are prone to isomerization |
| WO2004058988A2 (en) * | 2002-12-20 | 2004-07-15 | Amgen, Inc. | Binding agents which inhibit myostatin |
| EP1773400A2 (en) | 2004-07-08 | 2007-04-18 | Amgen Inc. | Therapeutic peptides |
| MX2007003320A (es) * | 2004-09-24 | 2007-05-18 | Amgen Inc | Moleculas fc modificadas. |
| US9283260B2 (en) * | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
| EP3035305B1 (en) | 2014-12-18 | 2016-11-16 | Axis AB | Enclosure and arrangement for recess mounting of a camera or camera head |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001083525A2 (en) * | 2000-05-03 | 2001-11-08 | Amgen Inc. | Modified peptides, comprising an fc domain, as therapeutic agents |
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| ES2299278T5 (es) | Péptidos modificados que actúan como agentes terapéuticos | |
| US20080254020A1 (en) | Therapeutic Peptides | |
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