ZA200207206B - Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates. - Google Patents
Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates. Download PDFInfo
- Publication number
- ZA200207206B ZA200207206B ZA200207206A ZA200207206A ZA200207206B ZA 200207206 B ZA200207206 B ZA 200207206B ZA 200207206 A ZA200207206 A ZA 200207206A ZA 200207206 A ZA200207206 A ZA 200207206A ZA 200207206 B ZA200207206 B ZA 200207206B
- Authority
- ZA
- South Africa
- Prior art keywords
- uricase
- poly
- conjugate
- peg
- ethylene glycol
- Prior art date
Links
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- 238000002360 preparation method Methods 0.000 title description 17
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- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 17
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 17
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- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 14
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0044—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7)
- C12N9/0046—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7) with oxygen as acceptor (1.7.3)
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
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US09/501,730 US6783965B1 (en) | 2000-02-10 | 2000-02-10 | Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates |
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Families Citing this family (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6057287A (en) | 1994-01-11 | 2000-05-02 | Dyax Corp. | Kallikrein-binding "Kunitz domain" proteins and analogues thereof |
CN101280293B (zh) | 1998-08-06 | 2013-09-11 | 杜克大学 | 尿酸氧化酶 |
US6783965B1 (en) | 2000-02-10 | 2004-08-31 | Mountain View Pharmaceuticals, Inc. | Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates |
PT1588716E (pt) | 1998-08-06 | 2011-05-25 | Mountain View Pharmaceuticals | Conjugados de peg-urato oxidase e sua utiliza??o |
KR100488848B1 (ko) * | 1998-08-06 | 2005-05-11 | 듀크 유니버서티 | 피이지-유레이트 옥시데이즈 접합체 및 그의 이용 |
US20060188971A1 (en) * | 1998-08-06 | 2006-08-24 | Duke University | Urate oxidase |
DK1421175T3 (da) | 2001-06-28 | 2009-03-23 | Mountain View Pharmaceuticals | Polymerstabiliserede proteinaser |
US6913915B2 (en) * | 2001-08-02 | 2005-07-05 | Phoenix Pharmacologics, Inc. | PEG-modified uricase |
ES2559927T3 (es) | 2002-06-07 | 2016-02-16 | Dyax Corp. | Prevención y reducción de pérdida de sangre y respuesta inflamatoria |
US7153829B2 (en) | 2002-06-07 | 2006-12-26 | Dyax Corp. | Kallikrein-inhibitor therapies |
US8129330B2 (en) * | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
EA008866B1 (ru) * | 2002-12-26 | 2007-08-31 | Маунтин Вью Фамэсьютикэлс, Инк. | ПОЛИМЕРНЫЙ КОНЪЮГАТ МОДИФИКАЦИЙ ИНТЕРФЕРОНА-β, ФАРМАЦЕВТИЧЕСКИЕ ПРОДУКТЫ НА ЕГО ОСНОВЕ И СПОСОБ ИХ ПОЛУЧЕНИЯ |
KR101160611B1 (ko) * | 2003-05-12 | 2012-06-28 | 아피맥스, 인크. | 폴리(에틸렌 글리콜)로 변형된 펩티드 기재 화합물용 신규 스페이서 부분 |
EA010099B1 (ru) * | 2003-05-12 | 2008-06-30 | Афимакс, Инк. | Пептиды, которые связываются с рецептором к эритропоэтину, и способы их применения |
BRPI0411160A (pt) * | 2003-05-12 | 2006-07-11 | Affymax Inc | novos compostos modificados com poli(glicol etilênico) e usos dos mesmos |
CA2536873C (en) * | 2003-08-29 | 2019-09-10 | Dyax Corp. | Poly-pegylated protease inhibitors |
US7235530B2 (en) | 2004-09-27 | 2007-06-26 | Dyax Corporation | Kallikrein inhibitors and anti-thrombolytic agents and uses thereof |
EA200700990A1 (ru) * | 2004-11-11 | 2008-04-28 | Афимакс, Инк. | Новые пептиды, которые связывают рецептор эритропоэтина |
WO2006062685A2 (en) * | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
CA2602654A1 (en) * | 2005-04-05 | 2006-10-12 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Method for shielding functional sites or epitopes on proteins |
LT3321359T (lt) * | 2005-04-11 | 2021-05-10 | Horizon Pharma Rheumatology Llc | Urato oksidazės variantinės formos ir jų panaudojimas |
US7811800B2 (en) | 2005-04-11 | 2010-10-12 | Savient Pharmaceuticals, Inc. | Variant form of urate oxidase and use thereof |
US8148123B2 (en) * | 2005-04-11 | 2012-04-03 | Savient Pharmaceuticals, Inc. | Methods for lowering elevated uric acid levels using intravenous injections of PEG-uricase |
US20080159976A1 (en) * | 2005-04-11 | 2008-07-03 | Jacob Hartman | Methods for lowering elevated uric acid levels using intravenous injections of PEG-uricase |
WO2006125452A1 (en) * | 2005-05-23 | 2006-11-30 | Universite De Geneve | Injectable superparamagnetic nanoparticles for treatment by hyperthermia and use for forming an hyperthermic implant |
US7550433B2 (en) | 2005-06-03 | 2009-06-23 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
US8324159B2 (en) * | 2005-06-03 | 2012-12-04 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
US7919461B2 (en) | 2005-06-03 | 2011-04-05 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
HU230758B1 (hu) * | 2006-04-12 | 2018-03-28 | Crealta Pharmaceuticals LLC 100% | Fehérjék tisztítása kationos felületaktív anyaggal |
CA2696208A1 (en) * | 2007-08-21 | 2009-02-26 | Genzyme Corporation | Treatment with kallikrein inhibitors |
AU2010203712A1 (en) | 2009-01-06 | 2010-07-15 | Dyax Corp. | Treatment of mucositis with kallikrein inhibitors |
RU2535038C2 (ru) | 2009-06-25 | 2014-12-10 | Криэлта Фармасьютикалз ЭлЭлСи | Способы и наборы для прогнозирования риска инфузионных реакций и опосредованной антителами потери ответа при терапии пэгилированной уриказой с помощью мониторинга содержания мочевой кислоты в сыворотке крови |
SI2521568T1 (sl) | 2010-01-06 | 2019-01-31 | Dyax Corp. | Proteini, ki vežejo plazemski kalikrein |
US8940861B2 (en) | 2010-04-08 | 2015-01-27 | Georgia Tech Research Corporation | Variants of ancestral uricases and uses thereof |
CN103635489B (zh) | 2011-01-06 | 2016-04-13 | 戴埃克斯有限公司 | 血浆前激肽释放酶结合蛋白 |
CN102827073A (zh) | 2011-06-17 | 2012-12-19 | 安吉奥斯医药品有限公司 | 治疗活性组合物和它们的使用方法 |
US9474779B2 (en) | 2012-01-19 | 2016-10-25 | Agios Pharmaceuticals, Inc. | Therapeutically active compositions and their methods of use |
WO2014197806A2 (en) | 2013-06-07 | 2014-12-11 | Allena Pharmaceuticals, Inc. | Compositions, methods, and devices for dialysis |
WO2015003355A2 (en) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
US10376510B2 (en) | 2013-07-11 | 2019-08-13 | Agios Pharmaceuticals, Inc. | 2,4- or 4,6-diaminopyrimidine compounds as IDH2 mutants inhibitors for the treatment of cancer |
WO2015003360A2 (en) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
US9579324B2 (en) | 2013-07-11 | 2017-02-28 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
US20150031627A1 (en) | 2013-07-25 | 2015-01-29 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
JP6564796B2 (ja) | 2014-03-14 | 2019-08-21 | アジオス ファーマシューティカルズ, インコーポレイテッド | 治療活性化合物の医薬組成物 |
US10428158B2 (en) | 2014-03-27 | 2019-10-01 | Dyax Corp. | Compositions and methods for treatment of diabetic macular edema |
CN107614007B (zh) | 2015-05-15 | 2022-03-25 | 免疫医疗有限责任公司 | 改进的尿酸酶序列和治疗方法 |
EP3362065B1 (de) | 2015-10-15 | 2024-04-03 | Les Laboratoires Servier | Kombinationstherapie mit ivosidenib, cytarabine und daunorubicin oder idarubicin zur behandlung von akuter myeloischer leukämie |
LT3362066T (lt) | 2015-10-15 | 2022-02-10 | Les Laboratoires Servier Sas | Kombinuota terapija, skirta piktybinių susirgimų gydymui |
EA201891388A1 (ru) | 2015-12-11 | 2018-11-30 | Дайэкс Корп. | Ингибиторы калликреина плазмы и их применение для лечения обострения наследственного ангионевротического отека |
US20230085022A1 (en) | 2016-11-11 | 2023-03-16 | Horizon Therapeutics Usa, Inc. | Combination therapies of prednisone and uricase molecules and uses thereof |
CN111373034A (zh) | 2017-07-07 | 2020-07-03 | 艾乐娜制药有限公司 | 重组尿酸酶 |
US20190309269A1 (en) | 2018-03-20 | 2019-10-10 | Rubius Therapeutics, Inc. | Therapeutic cell systems and methods for treating hyperuricemia and gout |
US10980788B2 (en) | 2018-06-08 | 2021-04-20 | Agios Pharmaceuticals, Inc. | Therapy for treating malignancies |
CN109055260B (zh) * | 2018-08-08 | 2021-11-09 | 淮海工学院 | 弯曲芽孢杆菌alkaAU及产尿酸氧化酶方法、产品与应用 |
CN114181917B (zh) * | 2022-02-14 | 2022-06-03 | 潍坊华卓生物科技有限公司 | 一种改造尿酸酶、基因序列、制备方法及应用 |
Family Cites Families (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE279486C (de) | ||||
US3616231A (en) | 1968-11-14 | 1971-10-26 | Boehringer Mannheim Gmbh | Process for the production of uricase |
US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
JPS5599189A (en) | 1979-01-22 | 1980-07-28 | Mihama Hisaharu | Modified uricase free from antigenicity and its preparation |
JPS55135590A (en) | 1979-04-05 | 1980-10-22 | Mihama Hisaharu | Modified asparaginase and uricase and their preparation |
CH657141A5 (de) | 1980-07-01 | 1986-08-15 | Hoffmann La Roche | Dns-sequenzen, rekombinante expressionsvektoren zur mikrobiellen herstellung von human-leukozyten-interferonen und transformierte mikroorganismen. |
JPS57192435A (en) | 1981-05-20 | 1982-11-26 | Toyobo Co Ltd | Modified polypeptide |
DE3126759A1 (de) | 1981-07-07 | 1983-01-27 | Boehringer Mannheim Gmbh, 6800 Mannheim | Loesliche leber-uricase, verfahren zu ihrer herstellung und verwendung |
US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
DE3676670D1 (de) * | 1985-06-26 | 1991-02-07 | Cetus Corp | Solubilisierung von proteinen fuer pharmazeutische zusammensetzungen mittels polymerkonjugierung. |
US4847079A (en) * | 1985-07-29 | 1989-07-11 | Schering Corporation | Biologically stable interferon compositions comprising thimerosal |
DD279486A1 (de) | 1986-03-10 | 1990-06-06 | Akad Wissenschaften Ddr | Verfahren zur aktivierung von hydroxylgruppenhaltigen polymeren verbindungen |
JPS6255079A (ja) * | 1986-04-23 | 1987-03-10 | Mihama Hisaharu | 修飾ウリカ−ゼ |
JPH085506B2 (ja) * | 1986-08-25 | 1996-01-24 | 日東製器株式会社 | 缶容器 |
DD279489A1 (de) | 1986-12-11 | 1990-06-06 | Leuna Werke Veb | Verfahren zur herstellung optisch transparenter epoxidharzformmassen |
US5080891A (en) * | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
US4847325A (en) | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
US5955336A (en) * | 1988-08-17 | 1999-09-21 | Toyo Boseki Kabushiki Kaisha | DNA sequence for uricase and manufacturing process of uricase |
US5349052A (en) | 1988-10-20 | 1994-09-20 | Royal Free Hospital School Of Medicine | Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor |
US5324844A (en) | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
NZ234453A (en) * | 1989-07-13 | 1993-01-27 | Sanofi Sa | Recombinant dna encoding urate oxidase, and vector, host, protein and pharmaceutical compositions associated therewith |
US5382518A (en) | 1989-07-13 | 1995-01-17 | Sanofi | Urate oxidase activity protein, recombinant gene coding therefor, expression vector, micro-organisms and transformed cells |
US5286637A (en) | 1989-08-07 | 1994-02-15 | Debiopharm, S.A. | Biologically active drug polymer derivatives and method for preparing same |
JPH03148298A (ja) | 1989-11-01 | 1991-06-25 | Sumitomo Pharmaceut Co Ltd | 修飾ペプチドおよびその製造方法 |
US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
US5653974A (en) | 1990-10-18 | 1997-08-05 | Board Of Regents,The University Of Texas System | Preparation and characterization of liposomal formulations of tumor necrosis factor |
JP3693671B2 (ja) * | 1991-03-15 | 2005-09-07 | アムゲン インコーポレーテッド | ポリペプチドのpeg化 |
DE69230613T2 (de) | 1991-07-02 | 2000-12-28 | Inhale Inc | Verfahren und vorrichtung zum abgeben von medikamenten in aerosolform |
WO1994019007A1 (en) | 1993-02-16 | 1994-09-01 | Enzon, Inc. | Ribosome inactivating protein compositions having reduced antigenicity |
AU6586394A (en) * | 1993-04-22 | 1994-11-08 | Celtrix Pharmaceuticals, Inc. | Conjugates of growth factor and bone resorption inhibitor |
AU7113594A (en) | 1993-06-21 | 1995-01-17 | Enzon, Inc. | Site specific synthesis of conjugated peptides |
IT1265101B1 (it) * | 1993-07-23 | 1996-10-30 | Erba Carlo Spa | Derivati dell'acido 2-ammino-4-fenil-4-osso butirrico |
US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
HUT75533A (en) * | 1993-11-10 | 1997-05-28 | Schering Corp | Improved interferon polymer conjugates |
US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
EP0796324A1 (de) * | 1994-12-07 | 1997-09-24 | Novo Nordisk A/S | Polypeptide mit verminderter allergener wirkung |
US5932462A (en) * | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
JP2758154B2 (ja) * | 1995-04-06 | 1998-05-28 | エフ・ホフマン−ラ ロシユ アーゲー | インターフェロンを含む液体製剤 |
FR2733914B1 (fr) * | 1995-05-11 | 1997-08-01 | Sanofi Sa | Composition de liquide stable contenant de l'urate oxydase et composition lyophilisee pour sa preparation |
US5853974A (en) | 1995-06-07 | 1998-12-29 | Chiron Corporation | Enhancement of alkaline phosphatase with SDS in chemiluminescent substrates |
JPH09154581A (ja) | 1995-12-05 | 1997-06-17 | Asahi Chem Ind Co Ltd | ウリカーゼを生産する実質上純粋な微生物 |
DK1007082T3 (da) | 1997-01-15 | 2007-02-19 | Phoenix Pharmacologics Inc | Modificeret tumor nekrose faktor |
PT1084136E (pt) * | 1998-06-01 | 2004-12-31 | Genentech Inc | Separacao de monomeros de anticorpos dos seus multimeros atraves da utilizacao de cromatografia de troca ionica |
CN101280293B (zh) | 1998-08-06 | 2013-09-11 | 杜克大学 | 尿酸氧化酶 |
PT1588716E (pt) * | 1998-08-06 | 2011-05-25 | Mountain View Pharmaceuticals | Conjugados de peg-urato oxidase e sua utiliza??o |
KR100488848B1 (ko) | 1998-08-06 | 2005-05-11 | 듀크 유니버서티 | 피이지-유레이트 옥시데이즈 접합체 및 그의 이용 |
US6783965B1 (en) * | 2000-02-10 | 2004-08-31 | Mountain View Pharmaceuticals, Inc. | Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates |
US6425448B1 (en) | 2001-01-30 | 2002-07-30 | Cdx Gas, L.L.P. | Method and system for accessing subterranean zones from a limited surface area |
US6913915B2 (en) * | 2001-08-02 | 2005-07-05 | Phoenix Pharmacologics, Inc. | PEG-modified uricase |
TWI538373B (zh) | 2013-05-24 | 2016-06-11 | 中心微電子德累斯頓股份公司 | 切換式功率轉換器以及用於控制切換式功率轉換器的方法 |
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