JP6868617B2 - 低ホスファターゼ血症の組織非特異的アルカリホスファターゼ(tnsalp)酵素補充療法に有効な投薬計画の特定 - Google Patents
低ホスファターゼ血症の組織非特異的アルカリホスファターゼ(tnsalp)酵素補充療法に有効な投薬計画の特定 Download PDFInfo
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| PCT/US2016/054013 WO2017058822A1 (en) | 2015-09-28 | 2016-09-27 | Identifying effective dosage regimens for tissue non-specific alkaline phosphatase (tnsalp)-enzyme replacement therapy of hypophosphatasia |
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| EP3226891B1 (en) | 2014-12-05 | 2025-06-25 | Alexion Pharmaceuticals, Inc. | Treating seizure with recombinant alkaline phosphatase |
| JP6868561B2 (ja) | 2015-01-28 | 2021-05-12 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | アルカリホスファターゼ欠損を有する被験者を治療する方法 |
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| EP3426286A4 (en) | 2016-03-08 | 2019-12-04 | Alexion Pharmaceuticals, Inc. | PROCESS FOR TREATING HYPOPHOSPHATASIA IN CHILDREN |
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| US12268733B2 (en) | 2018-08-10 | 2025-04-08 | Alexion Pharmaceuticals, Inc. | Methods of treating neurofibromatosis type 1 and related conditions with alkaline phosphatase |
| CN113993541A (zh) | 2019-05-06 | 2022-01-28 | 合成生物制品有限公司 | 基于碱性磷酸酶的肿瘤学治疗 |
| JP7268148B2 (ja) * | 2019-05-30 | 2023-05-02 | 富士フイルム富山化学株式会社 | 医療情報登録支援装置、医療情報登録支援装置の作動方法、及びプログラム |
| AU2020398898A1 (en) | 2019-12-09 | 2022-07-21 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| EP4084819A1 (en) | 2020-01-03 | 2022-11-09 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Tnap locally administered for promoting periodontal health |
| CN113496072B (zh) * | 2020-03-22 | 2024-07-02 | 杭州环特生物科技股份有限公司 | 用于安全性评价的斑马鱼转换人用剂量的换算方法 |
| CN117042791A (zh) | 2021-02-12 | 2023-11-10 | 阿雷克森制药公司 | 碱性磷酸酶多肽及其使用方法 |
| WO2024163665A1 (en) * | 2023-01-31 | 2024-08-08 | Unlearn.AI, Inc. | Systems and methods for prognostic covariate adjustment in logistic regression for randomized controlled trial design |
Family Cites Families (180)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1339210C (en) | 1988-05-31 | 1997-08-05 | John Lewicki | Recombinant techniques for production of novel natriuretic and vasodilator peptides |
| US6406697B1 (en) | 1989-02-23 | 2002-06-18 | Genentech, Inc. | Hybrid immunoglobulins |
| US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US6541610B1 (en) | 1989-09-05 | 2003-04-01 | Immunex Corporation | Fusion proteins comprising tumor necrosis factor receptor |
| ATE121102T1 (de) | 1990-04-20 | 1995-04-15 | Hisayuki Matsuo | Neue im schwein vorkommende physiologisch aktive peptide. |
| JP3026351B2 (ja) | 1990-07-13 | 2000-03-27 | 壽之 松尾 | ブタcnp遺伝子及び前駆体蛋白 |
| JP2930380B2 (ja) | 1990-07-13 | 1999-08-03 | 壽之 松尾 | ブタ由来新規生理活性ペプチド(cnp―53) |
| JP2977159B2 (ja) | 1990-09-07 | 1999-11-10 | 壽之 松尾 | カエル由来新規生理活性ペプチド(カエルcnp) |
| JP2977158B2 (ja) | 1990-09-07 | 1999-11-10 | 壽之 松尾 | トリ由来新規生理活性ペプチド(ニワトリcnp) |
| JP3026352B2 (ja) | 1990-09-11 | 2000-03-27 | 壽之 松尾 | ラットCNPcDNA及び前駆体蛋白 |
| JP3026354B2 (ja) | 1990-09-27 | 2000-03-27 | 壽之 松尾 | ヒトcnp遺伝子及び前駆体蛋白 |
| JP2809533B2 (ja) | 1991-01-31 | 1998-10-08 | 壽之 松尾 | Cnp類似体ペプチド |
| CA2102808A1 (en) | 1991-05-10 | 1992-11-11 | Hanne Bentz | Targeted delivery of bone growth factors |
| AU6360394A (en) | 1993-03-03 | 1994-09-26 | Mayo Foundation For Medical Education And Research | Vasonatrin peptide and analogs thereof |
| AU4835693A (en) | 1993-08-13 | 1995-03-14 | Rijksuniversiteit Te Groningen | Pharmaceutical composition comprising phosphatase or a derivative thereof |
| US5846932A (en) | 1993-11-12 | 1998-12-08 | Genentech, Inc. | Receptor specific atrial natriuretic peptides |
| US5665704A (en) | 1993-11-12 | 1997-09-09 | Genentech, Inc. | Receptor specific atrial natriuretic peptides |
| US6525022B1 (en) | 1993-11-12 | 2003-02-25 | Genentech, Inc. | Receptor specific atrial natriuretic peptides |
| CA2174517C (en) | 1993-11-12 | 2007-01-02 | David Lowe | Receptor specific atrial natriuretic peptides |
| AU2671795A (en) | 1994-06-02 | 1996-01-04 | Boehringer Mannheim Gmbh | Process and intermediate products for preparing cardiodilatin fragments, and highly purified cardiodilatin fragments |
| JPH0870875A (ja) | 1994-09-05 | 1996-03-19 | Tosoh Corp | 組換えアルカリフォスファタ−ゼ融合タンパク質 |
| US5863782A (en) | 1995-04-19 | 1999-01-26 | Women's And Children's Hospital | Synthetic mammalian sulphamidase and genetic sequences encoding same |
| EP0939770A1 (en) | 1996-10-22 | 1999-09-08 | Genentech, Inc. | Receptor specific brain natriuretic peptide (bnp) |
| US6028055A (en) | 1996-10-22 | 2000-02-22 | Genetech, Inc. | Receptor selective BNP |
| CA2280957A1 (en) | 1997-02-14 | 1998-08-20 | Leslie Orgel | Methods and compositions for delivery of therapeutic agents to bone tissue employing conjugates of negatively charged peptide oligomers with therapeutic agents |
| IL138214A0 (en) | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| CA2245903A1 (en) | 1998-09-28 | 2000-03-28 | Mcgill University | Use of pex in the treatment of metabolic bone diseases |
| CA2260376A1 (en) | 1999-02-11 | 2000-08-11 | Universite De Montreal | New metalloproteases of the neprilysin family |
| CA2262056A1 (en) | 1999-02-24 | 2000-08-24 | Guy Boileau | Composition, methods and reagents for the synthesis of a soluble form of human pex |
| AU2495200A (en) | 1999-03-08 | 2000-09-28 | Genentech Inc. | Compositions and methods for the treatment of tumor |
| JP2002542304A (ja) | 1999-04-28 | 2002-12-10 | ベクトレイムド インコーポレイテッド | 酵素的に活性化された重合薬物接合体 |
| US20040266673A1 (en) | 2002-07-31 | 2004-12-30 | Peter Bakis | Long lasting natriuretic peptide derivatives |
| US6887470B1 (en) | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| JP2000327583A (ja) | 1999-05-17 | 2000-11-28 | Medei Sci Puraningu:Kk | 骨指向性ホルモン誘導体 |
| EP1623994A3 (en) | 1999-05-17 | 2008-07-16 | ConjuChem Biotechnologies Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| US6849714B1 (en) | 1999-05-17 | 2005-02-01 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| DE19942230C2 (de) | 1999-09-03 | 2003-09-25 | Wolf-Georg Forssmann | Verwendung natriuretischer Peptide als antibiotisch wirksame Subsanzen zur Behandlung von bakteriellen Infektionen |
| ES2284545T3 (es) | 1999-11-16 | 2007-11-16 | Genzyme Corporation | Vectores y transgenes con elementos reguladores para la administracion de genes del higado. |
| US6407211B1 (en) | 1999-12-17 | 2002-06-18 | Mayo Foundation For Medical Education And Research | Chimeric natriuretic peptides |
| US6420384B2 (en) | 1999-12-17 | 2002-07-16 | Ariad Pharmaceuticals, Inc. | Proton pump inhibitors |
| JP4237375B2 (ja) | 2000-03-31 | 2009-03-11 | アスビオファーマ株式会社 | 虚血性疾患の処置又は予防に用いる医薬組成物 |
| AU5022101A (en) | 2000-04-26 | 2001-11-07 | Univ Kingston | Formulations and methods of using nitric oxide mimetics against a malignant cellphenotype |
| EP1502604A1 (en) | 2000-04-26 | 2005-02-02 | Cellegy Pharmaceuticals, Inc | Use of nitric oxide mimetics in cancer treatment |
| US20050142217A1 (en) | 2000-04-26 | 2005-06-30 | Adams Michael A. | Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype |
| US7678391B2 (en) | 2000-04-26 | 2010-03-16 | Queen's University At Kingston | Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype |
| US6830885B1 (en) | 2000-08-18 | 2004-12-14 | Phenogene Therapeutiques Inc. | Nucleic acid molecule, method and kit for selecting a nucleic acid having a desired feature |
| AU8742901A (en) | 2000-08-23 | 2002-03-04 | Biomep Inc | Method and compositions for promoting osteogenesis |
| US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
| ATE406384T1 (de) | 2000-12-07 | 2008-09-15 | Lilly Co Eli | Glp-1 fusion proteine |
| JP2002178279A (ja) | 2000-12-12 | 2002-06-25 | Ulvac Japan Ltd | 基板搬送方法 |
| AU2002255478A1 (en) | 2001-01-10 | 2002-09-12 | Pe Corporation (Ny) | Kits, such as nucleic acid arrays, comprising a majority of human exons or transcripts, for detecting expression and other uses thereof |
| JP2002246704A (ja) | 2001-02-16 | 2002-08-30 | Philips Japan Ltd | 電子装置及び回路装置 |
| IL142118A0 (en) | 2001-03-20 | 2002-03-10 | Prochon Biotech Ltd | Method and composition for treatment of skeletal dysplasias |
| US7888372B2 (en) | 2001-03-23 | 2011-02-15 | National Institutes Of Health (Nih) | Compositions and methods for modulating bone mineral deposition |
| AU2002258592A1 (en) | 2001-03-23 | 2002-11-25 | The Burnham Institute | Compositions and methods for modulating bone mineral deposition |
| US6808905B2 (en) | 2001-05-14 | 2004-10-26 | Cell Genesys, Inc. | Lentiviral vectors encoding clotting factors for gene therapy |
| EP2053406A3 (en) | 2001-07-16 | 2009-06-24 | caprotec bioanalytics GmbH | Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions |
| BRPI0203172B8 (pt) | 2001-09-28 | 2021-05-25 | Nakao Kazuwa | composição farmacêutica para acondroplasia |
| US20050202442A1 (en) | 2003-12-15 | 2005-09-15 | Morris David W. | Novel therapeutic targets in cancer |
| CA2469972A1 (en) | 2001-12-20 | 2003-07-03 | Phenogene Therapeutiques Inc. | Bone polypeptide-1 |
| US20080194481A1 (en) | 2001-12-21 | 2008-08-14 | Human Genome Sciences, Inc. | Albumin Fusion Proteins |
| AU2002364586A1 (en) | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| US20030158132A1 (en) | 2002-01-22 | 2003-08-21 | Genvec, Inc. | Method for enhancing bone density or formation |
| JP2005527510A (ja) | 2002-03-06 | 2005-09-15 | セレジー ファーマシューティカルズ インコーポレーティッド | 癌の治療において一酸化窒素模倣体を使用するための製剤および方法 |
| US20050113286A1 (en) | 2002-03-18 | 2005-05-26 | Schreiner George F. | Methods for treating congestive heart failure |
| AU2003214214A1 (en) | 2002-03-18 | 2003-10-08 | Scios Inc. | Method for treating congestive heart failure |
| IL149562A0 (en) | 2002-05-09 | 2002-11-10 | Prochon Ltd | Fgf variants and methods for use thereof |
| CA2433479A1 (en) | 2002-07-22 | 2004-01-22 | F. Hoffmann-La Roche Ag | Conjugate of a tissue non-specific alkaline phosphatase and dextran, process for its production and use thereof |
| AU2003246500A1 (en) | 2002-07-31 | 2004-02-16 | Conjuchem Biotechnologies Inc. | Long lasting natriuretic peptide derivatives |
| AU2003270427A1 (en) | 2002-09-06 | 2004-03-29 | University Of South Florida | Cellular delivery of natriuretic peptides |
| CA2511680A1 (en) | 2002-11-18 | 2004-06-03 | Syn X Pharma, Inc. | Polyclonal-monoclonal elisa assay for detecting n-terminus probnp |
| CN100558398C (zh) | 2002-11-26 | 2009-11-11 | 拜奥康有限公司 | 修饰的钠尿化合物、缀合物及其应用 |
| US7648962B2 (en) | 2002-11-26 | 2010-01-19 | Biocon Limited | Natriuretic compounds, conjugates, and uses thereof |
| AU2003291867A1 (en) | 2002-12-03 | 2004-06-23 | Biomep Inc. | Derivatives of succinic and glutaric acids and analogs thereof useful as inhibitors of phex |
| EP1583554A2 (en) | 2003-01-13 | 2005-10-12 | Gudrun Rappold-Hoerbrand | Use of natriuretic peptides for the treatment of stature disorders related to the shox gene |
| JP2009520459A (ja) | 2003-02-14 | 2009-05-28 | サイグレス ディスカバリー, インコーポレイテッド | 癌における治療標的 |
| US7488713B2 (en) | 2004-03-18 | 2009-02-10 | University Of South Florida | Cancer treatment using C-type natriuretic peptides |
| JP2006527190A (ja) | 2003-04-17 | 2006-11-30 | サイファージェン バイオシステムズ インコーポレイテッド | ナトリウム利尿ペプチドに関連したポリペプチド、並びにこれらの同定および使用法 |
| CA2527878A1 (en) | 2003-05-30 | 2005-01-27 | Alexion Pharmaceuticals, Inc. | Antibodies and fusion proteins that include engineered constant regions |
| EP1644740B1 (en) | 2003-06-17 | 2010-12-01 | Otago Innovation Limited | Assessment of skeletal growth using measurements of nt-cnp peptides |
| CN101208353B (zh) | 2003-06-20 | 2011-12-14 | 梅约医学教育与研究基金会 | 脑利尿钠肽的同种型 |
| WO2005052593A1 (en) | 2003-10-29 | 2005-06-09 | The University Of Leicester | Detection |
| US7431915B2 (en) | 2003-10-31 | 2008-10-07 | The Regents Of The University Of California | Peptides whose uptake by cells is controllable |
| US8110665B2 (en) | 2003-11-13 | 2012-02-07 | Hanmi Holdings Co., Ltd. | Pharmaceutical composition comprising an immunoglobulin FC region as a carrier |
| RU2356909C2 (ru) | 2003-11-13 | 2009-05-27 | Ханми Фарм. Инд. Ко., Лтд. | Белковый комплекс, полученный с использованием фрагмента иммуноглобулина, и способ получения такого комплекса |
| US20060019890A1 (en) | 2004-01-15 | 2006-01-26 | Kapoun Ann M | Method for treating cardiac remodeling following myocardial injury |
| US20080182299A1 (en) | 2004-01-27 | 2008-07-31 | Compugent Ltd. | Novel brain natriuretic peptide variants and methods of use thereof |
| CA2554599A1 (en) | 2004-01-27 | 2005-08-11 | Compugen Usa, Inc. | Novel brain natriuretic peptide variants and methods of use thereof |
| ES2465141T3 (es) | 2004-03-31 | 2014-06-05 | Kazuwa Nakao | Remedio o medicamento preventivo para la artritis |
| JP4972403B2 (ja) | 2004-03-31 | 2012-07-11 | 一和 中尾 | 身長増加用組成物 |
| JP2005292718A (ja) | 2004-04-05 | 2005-10-20 | Furukawa Electric Co Ltd:The | 光導波路、光導波路モジュールおよび光導波路の作成方法 |
| EP3404102B1 (en) | 2004-04-21 | 2021-08-11 | Alexion Pharmaceuticals, Inc. | Bone delivery conjugates and method of using same to target proteins to bone |
| CA2565410A1 (en) | 2004-05-04 | 2005-11-10 | National University Of Singapore | Method for expressing sialylated glycoproteins in mammalian cells and cells thereof |
| MXPA06013029A (es) | 2004-05-10 | 2007-02-12 | Novacea Inc | Prevencion de la restenosis arterial con compuestos de vitamina d activos. |
| US20070081984A1 (en) | 2005-10-11 | 2007-04-12 | Shunji Tomatsu | Compositions and methods for treating hypophosphatasia |
| US7863238B2 (en) | 2004-06-10 | 2011-01-04 | Saint Louis University | Proteins with an attached short peptide of acidic amino acids |
| US7972593B2 (en) | 2004-06-10 | 2011-07-05 | Saint Louis University | Delivery of therapeutic agents to the bone |
| US20070081986A1 (en) | 2005-10-07 | 2007-04-12 | Shunji Tomatsu | Beta-glucuronidase with an attached short peptide of acidic amino acids |
| WO2006005140A2 (en) | 2004-07-15 | 2006-01-19 | The University Of Queensland | Proteinaceous compounds and uses therefor |
| WO2006039480A2 (en) | 2004-09-29 | 2006-04-13 | The Burnham Institute For Medical Research | Tissue non-specific alkaline phosphate (tnap): a therapeutic target for arterial calcification |
| BRPI0515819A (pt) | 2004-12-01 | 2008-08-05 | Genzyme Corp | métodos para o fornecimento direcionado de material genético ao fìgado |
| WO2006110743A1 (en) | 2005-04-07 | 2006-10-19 | Cardiopep Pharma Gmbh | Use of natriuretic peptide for treating heart failure |
| WO2006116260A2 (en) | 2005-04-26 | 2006-11-02 | Medimmune, Inc. | Modulation of antibody effector function by hinge domain engineering |
| US20070042957A1 (en) | 2005-08-19 | 2007-02-22 | Mayo Foundation For Medical Education And Research | Type v phosphodiesterase inhibitors and natriuretic polypeptides |
| US7470668B2 (en) | 2005-08-24 | 2008-12-30 | Enobia Pharma Inc. | Method of use of specific natriuretic peptide receptor c ligands, transgenic non-human mammals expressing specific natriuretic peptide receptor c antagonists and cells thereof |
| US20070099831A1 (en) | 2005-09-06 | 2007-05-03 | Paul Morley | Parathyroid hormone analogues and methods of use |
| WO2007035600A2 (en) | 2005-09-16 | 2007-03-29 | Mayo Foundation For Education And Research | Natriuretic activities |
| US20080227713A1 (en) | 2005-10-03 | 2008-09-18 | Protter Andrew A | Oxidized Human Bnp |
| RU2316334C2 (ru) | 2005-12-19 | 2008-02-10 | Медитек Индастриз ЛЛС | Способ активации утраченных двигательных функций, а также определения эффективности их восстановления при повреждении центральной нервной системы |
| 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 |
| CA2638912A1 (en) | 2006-02-20 | 2007-08-30 | Phylogica Limited | Method of constructing and screening libraries of peptide structures |
| US8784833B2 (en) | 2006-06-27 | 2014-07-22 | Saint Louis University | Prenatal enzyme replacement therapy for hypophosphatasia |
| CA2656112A1 (en) | 2006-06-30 | 2008-05-08 | Hanje Chen | Bioresponsive polymers |
| US7825092B2 (en) | 2006-08-08 | 2010-11-02 | University Of South Florida | Dendroaspis natriuretic peptide for treatment of cancer |
| BRPI0716416A2 (pt) | 2006-08-08 | 2016-10-11 | Mayo Foundation | polipeptídeo substancialmente puro entre 37 e 47 besíduos de aminoácido de comprimento, ácido nucléico isolado, vetor: célula hospedeira e composição farmacêutica |
| WO2008031045A2 (en) | 2006-09-08 | 2008-03-13 | Mayo Foundation For Medical Education And Research | Aquaretic and natriuretic polypeptides lacking vasodilatory activity |
| CN104193815A (zh) | 2006-09-08 | 2014-12-10 | Ambrx公司 | 经修饰的人类血浆多肽或Fc骨架和其用途 |
| AU2007343796A1 (en) | 2006-10-25 | 2008-07-24 | Amgen Inc. | Toxin peptide therapeutic agents |
| WO2008058016A2 (en) | 2006-11-02 | 2008-05-15 | University Of Virginia Patent Foundation | Ethoid-containing compounds, methods for preparing ethoid-containing compounds, and methods for use |
| JP5645408B2 (ja) | 2006-11-16 | 2014-12-24 | カイ ファーマシューティカルズ インコーポレーティッド | 副甲状腺機能亢進症および高カルシウム血症性障害の治療のためのポリカチオン性カルシウムモジュレーターペプチド |
| US20080181903A1 (en) | 2006-12-21 | 2008-07-31 | Pdl Biopharma, Inc. | Conjugate of natriuretic peptide and antibody constant region |
| WO2008109903A1 (en) | 2007-03-12 | 2008-09-18 | Biomedica Medizinprodukte Gmbh & Co Kg | Diagnosis of septic complications |
| EP1985697A1 (en) | 2007-04-27 | 2008-10-29 | AM-Pharma B.V. | Modified phosphatases |
| KR20080098216A (ko) | 2007-05-04 | 2008-11-07 | 한미약품 주식회사 | 캐리어 물질을 이용한 나트륨 배설 펩타이드 약물 결합체 |
| JP5732603B2 (ja) * | 2007-05-11 | 2015-06-10 | アレクション ファーマ ホールディング | 骨標的アルカリホスファターゼ、キット及びその使用方法 |
| MX2009012343A (es) | 2007-05-14 | 2010-02-10 | Biogen Idec Inc | Regiones fc (sc fc) de cadena sencilla, polipeptidos de enlace que comprenden las mismas, y metodos relacionados con ello. |
| CA2689492A1 (en) | 2007-06-06 | 2008-12-18 | Boehringer Ingelheim International Gmbh | Natriuretic fusion proteins |
| WO2008154543A2 (en) | 2007-06-11 | 2008-12-18 | Abbott Biotechnology Ltd. | Methods for treating juvenile idiopathic arthritis |
| US20110077383A1 (en) | 2007-07-03 | 2011-03-31 | Medimmune, Llc | Hinge domain engineering |
| JP2010532323A (ja) | 2007-07-06 | 2010-10-07 | セラテクノロジーズ インコーポレイテッド | アルファ−メラニン細胞刺激ホルモン(アルファ−msh)および心房性ナトリウム利尿タンパク質(anp)の二機能性融合タンパク質ならびに高血圧および急性腎臓損傷における使用 |
| JP5718051B2 (ja) | 2007-07-20 | 2015-05-13 | メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ | ナトリウム利尿ポリペプチド |
| US20090053192A1 (en) | 2007-08-10 | 2009-02-26 | Burnham Institute For Medical Research | Tissue-nonspecific alkaline phosphatase (tnap) activators and uses thereof |
| US8933197B2 (en) | 2007-08-15 | 2015-01-13 | Amunix Operating Inc. | Compositions comprising modified biologically active polypeptides |
| US20100204090A1 (en) | 2007-09-11 | 2010-08-12 | Dorian Bevec | Use of a peptide as a therapeutic agent |
| WO2009043437A2 (en) | 2007-09-11 | 2009-04-09 | Mondobiotech Laboratories Ag | Use of a peptide as a therapeutic agent |
| WO2009033799A2 (en) | 2007-09-11 | 2009-03-19 | Mondobiotech Laboratories Ag | Use of a peptide as a therapeutic agent |
| RU2010114029A (ru) | 2007-09-11 | 2011-10-20 | Мондобайотек Лабораториз Аг (Li) | Астрессин и бета-эндорфин для применения в качестве терапевтических средств |
| WO2009034134A2 (en) | 2007-09-11 | 2009-03-19 | Pharis Biotec Gmbh | Use of natriuretic peptides for treating angioedema syndromes |
| WO2009033762A2 (en) | 2007-09-11 | 2009-03-19 | Mondobiotech Laboratories Ag | Use of endothelin-3 as a therapeutic agent |
| US8357656B2 (en) | 2007-09-15 | 2013-01-22 | Mayo Foundation For Medical Education And Research | Natriuretic peptide receptor-C agonists |
| US8377884B2 (en) | 2007-11-21 | 2013-02-19 | Biomarin Pharmaceutical Inc. | Variants of C-type natriuretic peptides |
| WO2009086126A2 (en) | 2007-12-21 | 2009-07-09 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptides |
| EP2080812A1 (en) | 2008-01-18 | 2009-07-22 | Transmedi SA | Compositions and methods of detecting post-stop peptides |
| WO2009142307A1 (ja) | 2008-05-23 | 2009-11-26 | アスビオファーマ株式会社 | 目的ペプチドの血漿中半減期延長作用を有するペプチド |
| KR20110020903A (ko) | 2008-06-06 | 2011-03-03 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 키메라 나트륨이뇨성 폴리펩티드 및 심장 리모델링 억제 방법 |
| WO2009156481A1 (en) | 2008-06-25 | 2009-12-30 | Ascendis Pharma As | Pegylated bnp |
| EP2315602A4 (en) | 2008-06-26 | 2011-11-02 | Acceleron Pharma Inc | METHOD OF DOSING AN ACTRIIB ANTAGONIST AND MONITORING TREATED PATIENTS |
| US8741842B2 (en) | 2008-07-02 | 2014-06-03 | Mayo Foundation For Medical Education And Research | Chimeric natriuretic polypeptides with unique pharmacologic profiles |
| NZ590358A (en) | 2008-07-23 | 2012-04-27 | Hanmi Holdings Co Ltd | A polypeptide complex comprising non-peptidyl polymer having three functional ends |
| US20100093678A1 (en) | 2008-10-10 | 2010-04-15 | The University Of Georgia Research Foundation, Inc | Compositions and methods of the treatment of obesity and osteoporosis |
| WO2010048308A2 (en) | 2008-10-24 | 2010-04-29 | Deborah Dickey | Natriuretic polypeptides |
| WO2010078325A2 (en) | 2008-12-29 | 2010-07-08 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptides for reducing or preventing restenosis |
| AR075029A1 (es) | 2009-01-19 | 2011-03-02 | Hanmi Pharm Ind Co Ltd | Metodo para producir una proteina o un peptido fisiologicamente activo usando un fragmento de inmunoglobulina |
| WO2010117760A2 (en) | 2009-03-30 | 2010-10-14 | Boehringer Ingelheim International Gmbh | Fusion proteins comprising canine fc portions |
| WO2010129655A2 (en) | 2009-05-05 | 2010-11-11 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptides having mutations within their disulfide rings |
| KR102033680B1 (ko) | 2009-05-20 | 2019-10-18 | 바이오마린 파머수티컬 인크. | 씨형 나트륨이뇨 펩티드의 변이체 |
| CN103153344A (zh) | 2010-04-30 | 2013-06-12 | 阿莱克森国际制药有限公司 | 用于治疗基质矿化障碍的方法、组合物、和试剂盒 |
| US9266939B2 (en) | 2010-12-27 | 2016-02-23 | Alexion Pharmaceuticals, Inc. | Compositions comprising natriuretic peptides and methods of use thereof |
| CA2852874A1 (en) | 2011-10-19 | 2013-04-25 | Alexion Pharma Holding | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
| MX355063B (es) | 2011-11-10 | 2018-04-04 | Kai Pharmaceuticals Inc | Calcimiméticos y métodos para su uso. |
| US10052366B2 (en) * | 2012-05-21 | 2018-08-21 | Alexion Pharmaceuticsl, Inc. | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
| KR20150073944A (ko) | 2012-07-25 | 2015-07-01 | 싸이오서스 테라퓨틱스 엘티디. | 악액질 및 근육감소증 치료를 위한 s핀돌롤의 사용 |
| WO2014186809A2 (en) | 2013-05-17 | 2014-11-20 | The Translational Genomics Research Institute | A genetic test to predict patient response to bone morphogenetic protein in arthrodesis |
| DK3097188T3 (en) | 2014-01-24 | 2018-10-08 | Am Pharma Bv | DOWNSTREAM PREPARATION OF AN ALKALIC PHOSPHATASE |
| LT3151859T (lt) | 2014-06-09 | 2021-03-25 | Ultragenyx Pharmaceutical Inc. | Veiksminga ir efektyvi serumo fosfatų kontrolė optimaliam kaulų formavimosi užtikrinimui |
| US10822596B2 (en) | 2014-07-11 | 2020-11-03 | Alexion Pharmaceuticals, Inc. | Compositions and methods for treating craniosynostosis |
| EP3226891B1 (en) | 2014-12-05 | 2025-06-25 | Alexion Pharmaceuticals, Inc. | Treating seizure with recombinant alkaline phosphatase |
| JP6868561B2 (ja) | 2015-01-28 | 2021-05-12 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | アルカリホスファターゼ欠損を有する被験者を治療する方法 |
| KR101867134B1 (ko) | 2015-03-23 | 2018-06-12 | 한양대학교 산학협력단 | 포유류 세포를 이용하여 목적 물질을 고효율로 생산하기 위한 세포 배양 배지, 이를 이용한 세포 배양 방법 및 목적 물질의 생산 방법 |
| HK1257341A1 (zh) | 2015-08-17 | 2019-10-18 | Alexion Pharmaceuticals, Inc. | 硷性磷酸酯的制造 |
| US11229686B2 (en) | 2015-09-28 | 2022-01-25 | Alexion Pharmaceuticals, Inc. | Reduced frequency dosage regimens for tissue non-specific alkaline phosphatase (TNSALP)-enzyme replacement therapy of hypophosphatasia |
| US11400140B2 (en) | 2015-10-30 | 2022-08-02 | Alexion Pharmaceuticals, Inc. | Methods for treating craniosynostosis in a patient |
| EP3426286A4 (en) | 2016-03-08 | 2019-12-04 | Alexion Pharmaceuticals, Inc. | PROCESS FOR TREATING HYPOPHOSPHATASIA IN CHILDREN |
| WO2017173395A1 (en) | 2016-04-01 | 2017-10-05 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
| WO2017171871A1 (en) | 2016-04-01 | 2017-10-05 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
| CN109152820A (zh) | 2016-04-01 | 2019-01-04 | 阿雷克森制药公司 | 用碱性磷酸酶治疗肌肉无力 |
| US10988744B2 (en) | 2016-06-06 | 2021-04-27 | Alexion Pharmaceuticals, Inc. | Method of producing alkaline phosphatase |
| ES2887573T3 (es) | 2016-06-27 | 2021-12-23 | Alexion Pharma Inc | Métodos para el tratamiento de la hipofosfatasia en niños y adolescentes |
| EP3500289B1 (en) | 2016-08-18 | 2024-10-09 | Alexion Pharmaceuticals, Inc. | Asfotase alfa for use in treating tracheobronchomalacia |
| WO2018164995A1 (en) | 2017-03-09 | 2018-09-13 | Alexion Pharmaceuticals, Inc . | Glycoprotein manufacturing process |
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| US20190298810A1 (en) | 2019-10-03 |
| EP3355904A1 (en) | 2018-08-08 |
| JP2018528252A (ja) | 2018-09-27 |
| WO2017058822A1 (en) | 2017-04-06 |
| EP3355904A4 (en) | 2019-06-12 |
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