PT981607E - A deiminase modificada - Google Patents
A deiminase modificada Download PDFInfo
- Publication number
- PT981607E PT981607E PT98922197T PT98922197T PT981607E PT 981607 E PT981607 E PT 981607E PT 98922197 T PT98922197 T PT 98922197T PT 98922197 T PT98922197 T PT 98922197T PT 981607 E PT981607 E PT 981607E
- Authority
- PT
- Portugal
- Prior art keywords
- group
- adi
- polyethylene glycol
- succinimidyl
- compound
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- 108010082340 Arginine deiminase Proteins 0.000 title claims abstract description 106
- 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 title 1
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Classifications
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- 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
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
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- 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
- A61K47/51—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 the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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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
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Enzymes And Modification Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Chemical Or Physical Treatment Of Fibers (AREA)
Applications Claiming Priority (2)
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| US4620097P | 1997-05-12 | 1997-05-12 | |
| US09/023,809 US6183738B1 (en) | 1997-05-12 | 1998-02-13 | Modified arginine deiminase |
Publications (1)
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| PT981607E true PT981607E (pt) | 2006-11-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| PT98922197T PT981607E (pt) | 1997-05-12 | 1998-05-12 | A deiminase modificada |
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| JP (1) | JP4456184B2 (enExample) |
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| AT (1) | ATE335814T1 (enExample) |
| AU (1) | AU724907B2 (enExample) |
| CA (1) | CA2288948C (enExample) |
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| ES (1) | ES2270515T3 (enExample) |
| PT (1) | PT981607E (enExample) |
| TW (1) | TW368504B (enExample) |
| WO (1) | WO1998051784A1 (enExample) |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5545553A (en) * | 1994-09-26 | 1996-08-13 | The Rockefeller University | Glycosyltransferases for biosynthesis of oligosaccharides, and genes encoding them |
| US6183738B1 (en) | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| US6635462B1 (en) * | 1997-05-12 | 2003-10-21 | Phoenix Pharmacologies, Inc. | Mutated form of arginine deiminase |
| US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| CN1328152A (zh) * | 2000-06-14 | 2001-12-26 | 上海博德基因开发有限公司 | 一种新的多肽——人nrd转化酶10.01和编码这种多肽的多核苷酸 |
| WO2002009741A1 (en) * | 2000-07-27 | 2002-02-07 | Angiolab, Inc. | The pharmaceutical composition comprising arginine deiminase for inhibiting angiogenesis |
| US20040096437A1 (en) * | 2000-07-27 | 2004-05-20 | Bon-Hong Min | Pharmaceutical composition comprising arginine deiminasa for inhibiting angio-genesis |
| AU2001289132A1 (en) * | 2000-11-28 | 2002-06-11 | Phoenix Pharmacologics, Inc. | Modified arginine deiminase |
| US20050063942A1 (en) * | 2001-02-02 | 2005-03-24 | Clark Mike A. | Methods for predicting sensitivity of tumors to arginine deprivation |
| US7399613B2 (en) * | 2001-10-10 | 2008-07-15 | Neose Technologies, Inc. | Sialic acid nucleotide sugars |
| ES2561985T3 (es) * | 2001-10-10 | 2016-03-01 | Ratiopharm Gmbh | Remodelación y glicoconjugación de anticuerpos |
| US7173003B2 (en) * | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
| US7795210B2 (en) * | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| US7265084B2 (en) * | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| US7179617B2 (en) * | 2001-10-10 | 2007-02-20 | Neose Technologies, Inc. | Factor IX: remolding and glycoconjugation of Factor IX |
| US7214660B2 (en) * | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7696163B2 (en) * | 2001-10-10 | 2010-04-13 | Novo Nordisk A/S | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US8008252B2 (en) * | 2001-10-10 | 2011-08-30 | Novo Nordisk A/S | Factor VII: remodeling and glycoconjugation of Factor VII |
| US7473680B2 (en) | 2001-11-28 | 2009-01-06 | Neose Technologies, Inc. | Remodeling and glycoconjugation of peptides |
| MXPA04012496A (es) * | 2002-06-21 | 2005-09-12 | Novo Nordisk Healthcare Ag | Glicoformos del factor vii pegilados. |
| CN100405906C (zh) * | 2002-10-09 | 2008-07-30 | 尼奥斯技术有限公司 | 促红细胞生成素:促红细胞生成素的重构和糖缀合 |
| ES2477118T3 (es) * | 2002-11-18 | 2014-07-15 | Polaris Group | Método para inhibir la replicaci�n viral in vivo |
| KR101025143B1 (ko) * | 2002-12-31 | 2011-04-01 | 넥타르 테라퓨틱스 | 가수분해상으로 안정한 말레이미드－종결 중합체 |
| US7432331B2 (en) | 2002-12-31 | 2008-10-07 | Nektar Therapeutics Al, Corporation | Hydrolytically stable maleimide-terminated polymers |
| MXPA05007163A (es) * | 2002-12-31 | 2005-09-21 | Nektar Therapeutics Al Corp | Derivados polimericos de acido maleamico y sus bioconjugados. |
| CN102212019B (zh) * | 2003-03-14 | 2015-05-27 | 蔚所番有限公司 | 支化水溶性聚合物及其缀合物 |
| SG155777A1 (en) * | 2003-04-09 | 2009-10-29 | Neose Technologies Inc | Glycopegylation methods and proteins/peptides produced by the methods |
| CN100522988C (zh) * | 2003-04-09 | 2009-08-05 | 诺和诺德公司 | 糖peg化方法及由该方法生产的蛋白质/肽 |
| WO2004091499A2 (en) * | 2003-04-09 | 2004-10-28 | Neose Technologies, Inc. | Intracellular formation of peptide conjugates |
| US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
| EP1624847B1 (en) | 2003-05-09 | 2012-01-04 | BioGeneriX AG | Compositions and methods for the preparation of human growth hormone glycosylation mutants |
| WO2005012484A2 (en) | 2003-07-25 | 2005-02-10 | Neose Technologies, Inc. | Antibody-toxin conjugates |
| US20070254834A1 (en) * | 2003-11-24 | 2007-11-01 | Defrees Shawn | Glycopegylated Erythropoietin |
| US20080305992A1 (en) * | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
| US8633157B2 (en) * | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
| US7842661B2 (en) * | 2003-11-24 | 2010-11-30 | Novo Nordisk A/S | Glycopegylated erythropoietin formulations |
| RU2400490C2 (ru) * | 2003-12-03 | 2010-09-27 | Биодженерикс Аг | Гликопэгилированный гранулоцитарный колониестимулирующий фактор |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| US7790835B2 (en) * | 2003-12-03 | 2010-09-07 | Nektar Therapeutics | Method of preparing maleimide functionalized polymers |
| US20080318850A1 (en) * | 2003-12-03 | 2008-12-25 | Neose Technologies, Inc. | Glycopegylated Factor Ix |
| CN1897812B (zh) | 2003-12-03 | 2011-08-17 | 生物种属学股份公司 | 糖聚乙二醇化的粒细胞集落刺激因子 |
| US7956032B2 (en) * | 2003-12-03 | 2011-06-07 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
| JP5743368B2 (ja) * | 2004-01-08 | 2015-07-01 | ラショファーム ゲーエムベーハー | ペプチドのｏ結合型グリコシル化 |
| WO2005107815A2 (en) * | 2004-05-03 | 2005-11-17 | Nektar Therapeutics Al, Corporation | Polymer derivatives comprising an imide branching point |
| ES2339953T5 (es) * | 2004-05-04 | 2020-05-06 | Novo Nordisk Healthcare Ag | Glicoformas de factor VII ligadas a O y método de fabricación |
| US20080300173A1 (en) | 2004-07-13 | 2008-12-04 | Defrees Shawn | Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1] |
| CN1745847A (zh) * | 2004-09-08 | 2006-03-15 | 康达医药科技有限公司 | 用精氨酸酶治疗肝炎的药物组合物和方法 |
| US8268967B2 (en) * | 2004-09-10 | 2012-09-18 | Novo Nordisk A/S | Glycopegylated interferon α |
| WO2006035057A1 (en) * | 2004-09-29 | 2006-04-06 | Novo Nordisk Health Care Ag | Modified proteins |
| HUE026826T2 (en) | 2004-10-29 | 2016-07-28 | Ratiopharm Gmbh | Modeling and glycopegylation of fibroblast growth factor (FGF) |
| WO2006074279A1 (en) * | 2005-01-06 | 2006-07-13 | Neose Technologies, Inc. | Glycoconjugation using saccharyl fragments |
| US9029331B2 (en) | 2005-01-10 | 2015-05-12 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
| US20060246544A1 (en) * | 2005-03-30 | 2006-11-02 | Neose Technologies,Inc. | Manufacturing process for the production of peptides grown in insect cell lines |
| EP1871795A4 (en) * | 2005-04-08 | 2010-03-31 | Biogenerix Ag | COMPOSITIONS AND METHOD FOR PRODUCING GLYCOSYLATION MUTANTS OF A PROTEASE-RESISTANT HUMAN GROWTH HORMONE |
| FR2884717B1 (fr) * | 2005-04-25 | 2009-07-03 | Erytech Pharma Soc Par Actions | Erythrocytes renfermant de l'arginine deiminase |
| EP1891231A4 (en) | 2005-05-25 | 2011-06-22 | Novo Nordisk As | GLYCOPEGYLATED FACTOR IX |
| KR101334541B1 (ko) * | 2005-07-19 | 2013-11-28 | 넥타르 테라퓨틱스 | 중합체 말레이미드를 제조하는 방법 |
| JP2009515508A (ja) * | 2005-08-19 | 2009-04-16 | ネオス テクノロジーズ インコーポレイテッド | グリコｐｅｇ化因子ｖｉｉおよび因子ｖｉｉａ |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| US20090048440A1 (en) * | 2005-11-03 | 2009-02-19 | Neose Technologies, Inc. | Nucleotide Sugar Purification Using Membranes |
| 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 |
| US7982010B2 (en) * | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
| NZ572050A (en) | 2006-03-31 | 2011-09-30 | Baxter Int | Factor VIII conjugated to polyethylene glycol |
| US7985839B2 (en) * | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
| US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| US7534595B2 (en) * | 2006-06-12 | 2009-05-19 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US7531341B1 (en) | 2006-06-12 | 2009-05-12 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US20080248959A1 (en) * | 2006-07-21 | 2008-10-09 | Neose Technologies, Inc. | Glycosylation of peptides via o-linked glycosylation sequences |
| JP2010505874A (ja) * | 2006-10-03 | 2010-02-25 | ノヴォ ノルディスク アー／エス | ポリペプチドコンジュゲートの精製方法 |
| US20100041872A1 (en) * | 2006-10-04 | 2010-02-18 | Defrees Shawn | Glycerol linked pegylated sugars and glycopeptides |
| US20080207487A1 (en) * | 2006-11-02 | 2008-08-28 | Neose Technologies, Inc. | Manufacturing process for the production of polypeptides expressed in insect cell-lines |
| CN105838699A (zh) | 2006-12-15 | 2016-08-10 | 巴克斯艾尔塔公司 | 具有延长的体内半衰期的因子VIIa-聚唾液酸结合物 |
| RS52845B (sr) * | 2007-04-03 | 2013-12-31 | Biogenerix Ag | Postupci tretmana korišćenjem glikopegiliranog g-csf |
| US20090053167A1 (en) * | 2007-05-14 | 2009-02-26 | Neose Technologies, Inc. | C-, S- and N-glycosylation of peptides |
| US20080292609A1 (en) * | 2007-05-21 | 2008-11-27 | Ning Man Cheng | Use of Arginase in Combination with 5FU and Other Compounds for Treatment of Human Malignancies |
| JP2010531135A (ja) * | 2007-06-04 | 2010-09-24 | ノボ ノルディスク アクティーゼルスカブ | Ｎ−アセチルグルコサミニルトランスフェラーゼを使用したｏ結合型グリコシル化 |
| JP5876649B2 (ja) * | 2007-06-12 | 2016-03-02 | ラツィオファルム ゲーエムベーハーｒａｔｉｏｐｈａｒｍ ＧｍｂＨ | ヌクレオチド糖の改良製造法 |
| FR2919804B1 (fr) | 2007-08-08 | 2010-08-27 | Erytech Pharma | Composition et vaccin therapeutique anti-tumoral |
| US7537923B2 (en) * | 2007-08-17 | 2009-05-26 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof |
| US8207112B2 (en) * | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
| EP2242505A4 (en) * | 2008-01-08 | 2012-03-07 | Biogenerix Ag | GLYCOCONJUGATION OF POLYPEPTIDES USING OLIGOSACCHARYLTRANSFERASES |
| ES2476690T3 (es) | 2008-02-27 | 2014-07-15 | Novo Nordisk A/S | Moléculas conjugadas del Factor VIII |
| US20110201022A1 (en) * | 2008-07-30 | 2011-08-18 | Biomarin Pharmaceutical Inc. | Assays for detection of phenylalanine ammonia-lyase and antibodies to phenylalanine ammonia-lyase |
| WO2010023195A2 (en) | 2008-08-26 | 2010-03-04 | Kyon Biotech Ag | Compositions and methods for treating cancer |
| US20100150949A1 (en) * | 2008-12-16 | 2010-06-17 | Oncopharmacologics, Inc. | Methods and compositions for modulating proline levels |
| US8809501B2 (en) | 2009-07-27 | 2014-08-19 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| EP2459224B1 (en) * | 2009-07-27 | 2016-06-01 | Baxalta GmbH | Blood coagulation protein conjugates |
| PL2459224T3 (pl) | 2009-07-27 | 2017-08-31 | Baxalta GmbH | Koniugaty białka związanego z krzepnięciem krwi |
| EP2459226B1 (en) | 2009-07-27 | 2016-06-29 | Lipoxen Technologies Limited | Glycopolysialylation of proteins other than blood coagulation proteins |
| EP2295560A1 (en) | 2009-09-14 | 2011-03-16 | RWTH Aachen University | Directed evolution of arginine deiminase for increased activity at physiological pH |
| EP2531209B1 (en) | 2010-02-04 | 2016-04-20 | BioMarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase variants and methods of using compositions thereof |
| CN101812438B (zh) * | 2010-03-25 | 2014-08-27 | 江苏泰康生物医药有限公司 | 一种精氨酸脱亚氨酶突变体及其制备与应用 |
| WO2012075173A2 (en) | 2010-12-01 | 2012-06-07 | Board Of Regents The University Of Texas System | Compositions and method for deimmunization of proteins |
| ES2800983T3 (es) | 2010-12-22 | 2021-01-07 | Baxalta GmbH | Materiales y métodos para conjugar un derivado de ácido graso soluble en agua con una proteína |
| AU2012330497B2 (en) * | 2012-04-04 | 2016-08-04 | Polaris Group | Methods of treating with arginine deiminase |
| WO2014001956A2 (en) * | 2012-06-25 | 2014-01-03 | Ning Man Cheng | Combinational use of pegylated recombinant human arginase with chemotherapeutic/target therapeutic drug in cancer treatment |
| USRE48805E1 (en) | 2013-03-06 | 2021-11-02 | Vision Global Holdings Ltd. | Method for cancer targeting treatment and detection of arginine using albumin-binding arginine deiminase fusion protein |
| US9255262B2 (en) | 2013-03-06 | 2016-02-09 | Vision Global Holdings Ltd. | Albumin-binding arginine deminase and the use thereof |
| ES2805360T3 (es) * | 2013-03-15 | 2021-02-11 | Tdw Group | Arginina desiminasa con reactividad cruzada reducida hacia anticuerpos para ADI - PEG 20 para el tratamiento del cáncer |
| EP3052116B1 (en) | 2013-10-04 | 2021-05-05 | Ann, David K. | Arginase i, arginase ii, or adi in combiantion with doxorubicin for use in a treatmnt of a breast cancer |
| TWI676683B (zh) * | 2014-03-14 | 2019-11-11 | 開曼群島商瑞華藥業集團 | 用於癌症治療之對ａｄｉ－ｐｅｇ２０抗體交叉反應性降低之精胺酸去亞胺酶 |
| EP3119421B1 (en) * | 2014-03-18 | 2019-10-02 | TDW Group | Engineered chimeric pegylated adi and methods of use |
| CN103923898A (zh) * | 2014-04-17 | 2014-07-16 | 江南大学 | 一种peg修饰的重组精氨酸脱亚胺酶及其制备方法和应用 |
| CN114106186A (zh) | 2014-07-08 | 2022-03-01 | 瑞华药业集团 | 精氨基琥珀酸合成酶的抗体和相关方法 |
| SG10202002557SA (en) | 2014-09-16 | 2020-04-29 | Tdw Group | Arginine deiminase with reduced cross-reactivity toward adi - peg 20 antibodies for cancer treatment |
| CN104726478A (zh) * | 2015-03-09 | 2015-06-24 | 武汉远大弘元股份有限公司 | 表达精氨酸脱亚胺酶基因的重组大肠杆菌及其应用 |
| WO2017041051A1 (en) | 2015-09-04 | 2017-03-09 | Sqz Biotechnologies Company | Intracellular delivery of biomolecules to cells comprising a cell wall |
| KR102430856B1 (ko) | 2016-05-03 | 2022-08-08 | 에스큐지 바이오테크놀로지스 컴퍼니 | 관용을 유도하는 생체분자의 세포내 전달 |
| TWI847958B (zh) | 2016-07-05 | 2024-07-11 | 英屬開曼群島商北極星藥業集團股份有限公司 | 用精胺酸耗盡劑進行之組合癌症免疫療法 |
| WO2018085551A2 (en) | 2016-11-02 | 2018-05-11 | Polaris Group | Formulations of pegylated arginine deiminase |
| CN106591271B (zh) * | 2017-03-02 | 2019-07-16 | 江南大学 | 一株酶活和温度稳定性提高的精氨酸脱亚胺酶突变体及其应用 |
| WO2019042628A1 (en) | 2017-08-31 | 2019-03-07 | Erytech Pharma | ARGININE DEIMINASE ENCAPSULATED WITHIN ERYTHROCYTES AND THEIR USE IN THE TREATMENT OF CANCER AND ARGINASE-1 DEFICIENCY |
| EP3449935A1 (en) | 2017-08-31 | 2019-03-06 | Erytech Pharma | Arginine deiminase encapsulated inside erythrocytes and their use in treating cancer and arginase-1 deficiency |
| AU2019275733B2 (en) * | 2018-05-31 | 2025-07-31 | The Chinese University Of Hong Kong | Composition and application of arginine-depleting agents for cancer, obesity, metabolic disorders, and related complications and comorbidities |
| CN118497178A (zh) * | 2023-02-15 | 2024-08-16 | 重庆派金生物科技有限公司 | 精氨酸脱亚胺酶突变体、共价二聚体及其偶联物和应用 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4609546A (en) | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| US5447722A (en) | 1983-12-12 | 1995-09-05 | University Of Manitoba | Method for the suppression of an immune response with antigen-MPEG conjugates in nonsensitized individuals |
| DE3678702D1 (de) * | 1985-12-28 | 1991-05-16 | Ohgen Research Lab Ltd | Antitumorprotein-gen von streptococcus pyogenes su, plasmide, die das gen enthalten, transformantenzellen, die die plasmide beherbergen, und verfahren zur herstellung des antitumorproteins. |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| JPH0253490A (ja) | 1988-08-16 | 1990-02-22 | Agency Of Ind Science & Technol | アルギニン・デイミナーゼ遺伝子 |
| WO1990005534A1 (en) | 1988-11-23 | 1990-05-31 | Genentech, Inc. | Polypeptide derivatives |
| JP2900279B2 (ja) | 1989-08-02 | 1999-06-02 | 株式会社ジャパンエナジー | 新規なアルギニンデイミナーゼ、その製造法及び該酵素を有効成分とする制癌剤 |
| JP2736145B2 (ja) | 1990-01-11 | 1998-04-02 | 関東電化工業株式会社 | パーハロゲン化エチレンの製造法 |
| JPH04218000A (ja) * | 1990-02-13 | 1992-08-07 | Kirin Amgen Inc | 修飾ポリペプチド |
| JP3209338B2 (ja) | 1990-09-10 | 2001-09-17 | 株式会社ジャパンエナジー | ポリエチレングリコール修飾アルギニンデイミナーゼおよびその製造法 |
| US5372942A (en) * | 1992-02-10 | 1994-12-13 | Coriell Institute For Medical Research | Protease K resistant arginine deiminase, its method of preparation and its use as an anti-neoplastic agent |
| AU5098193A (en) | 1992-09-01 | 1994-03-29 | Berlex Laboratories, Inc. | Glycolation of glycosylated macromolecules |
| US5695760A (en) | 1995-04-24 | 1997-12-09 | Boehringer Inglehiem Pharmaceuticals, Inc. | Modified anti-ICAM-1 antibodies and their use in the treatment of inflammation |
| US5804183A (en) | 1997-01-31 | 1998-09-08 | Enzon, Inc. | Arginine deminase derived from mycoplasma arthritidis and polymer conjugates containing the same |
| US6183738B1 (en) | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| US6180387B1 (en) | 1997-08-11 | 2001-01-30 | Smithkline Beecham Corporation | Arginine deiminase |
-
1998
- 1998-02-13 US US09/023,809 patent/US6183738B1/en not_active Expired - Lifetime
- 1998-05-12 JP JP54937598A patent/JP4456184B2/ja not_active Expired - Lifetime
- 1998-05-12 DE DE69835515T patent/DE69835515T2/de not_active Expired - Lifetime
- 1998-05-12 AT AT98922197T patent/ATE335814T1/de active
- 1998-05-12 EP EP98922197A patent/EP0981607B1/en not_active Expired - Lifetime
- 1998-05-12 PT PT98922197T patent/PT981607E/pt unknown
- 1998-05-12 CN CNB988050668A patent/CN1169951C/zh not_active Expired - Lifetime
- 1998-05-12 CA CA002288948A patent/CA2288948C/en not_active Expired - Lifetime
- 1998-05-12 AU AU74798/98A patent/AU724907B2/en not_active Expired
- 1998-05-12 ES ES98922197T patent/ES2270515T3/es not_active Expired - Lifetime
- 1998-05-12 TW TW087107257A patent/TW368504B/zh not_active IP Right Cessation
- 1998-05-12 WO PCT/US1998/009575 patent/WO1998051784A1/en not_active Ceased
- 1998-05-12 DK DK98922197T patent/DK0981607T3/da active
-
2000
- 2000-11-28 US US09/723,546 patent/US6737259B1/en not_active Expired - Lifetime
-
2004
- 2004-01-15 US US10/757,843 patent/US7323167B2/en not_active Expired - Lifetime
-
2006
- 2006-11-03 CY CY20061101590T patent/CY1105758T1/el unknown
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|---|---|
| US20050129706A1 (en) | 2005-06-16 |
| US6737259B1 (en) | 2004-05-18 |
| CA2288948C (en) | 2007-10-30 |
| AU7479898A (en) | 1998-12-08 |
| DE69835515T2 (de) | 2007-08-09 |
| US7323167B2 (en) | 2008-01-29 |
| CN1169951C (zh) | 2004-10-06 |
| AU724907B2 (en) | 2000-10-05 |
| WO1998051784A1 (en) | 1998-11-19 |
| DE69835515D1 (de) | 2006-09-21 |
| EP0981607A4 (en) | 2004-09-01 |
| CY1105758T1 (el) | 2010-12-22 |
| JP2001524836A (ja) | 2001-12-04 |
| ES2270515T3 (es) | 2007-04-01 |
| EP0981607A1 (en) | 2000-03-01 |
| EP0981607B1 (en) | 2006-08-09 |
| US6183738B1 (en) | 2001-02-06 |
| JP4456184B2 (ja) | 2010-04-28 |
| TW368504B (en) | 1999-09-01 |
| CA2288948A1 (en) | 1998-11-19 |
| DK0981607T3 (da) | 2006-12-11 |
| CN1255944A (zh) | 2000-06-07 |
| ATE335814T1 (de) | 2006-09-15 |
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