ES2325877T3 - Moleculas de tipo factor vii o viia. - Google Patents
Moleculas de tipo factor vii o viia. Download PDFInfo
- Publication number
- ES2325877T3 ES2325877T3 ES01903611T ES01903611T ES2325877T3 ES 2325877 T3 ES2325877 T3 ES 2325877T3 ES 01903611 T ES01903611 T ES 01903611T ES 01903611 T ES01903611 T ES 01903611T ES 2325877 T3 ES2325877 T3 ES 2325877T3
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- polypeptide
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- amino acid
- conjugate
- fviia
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- 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
- A61K47/62—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 a protein, peptide or polyamino acid
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- 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)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK200000218 | 2000-02-11 | ||
| DKPA200000218 | 2000-02-11 | ||
| DKPA200001558 | 2000-10-18 | ||
| DK200001558 | 2000-10-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2325877T3 true ES2325877T3 (es) | 2009-09-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01903611T Expired - Lifetime ES2325877T3 (es) | 2000-02-11 | 2001-02-12 | Moleculas de tipo factor vii o viia. |
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| RU (1) | RU2278123C2 (enExample) |
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Families Citing this family (168)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7247708B2 (en) | 1997-10-23 | 2007-07-24 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6747003B1 (en) | 1997-10-23 | 2004-06-08 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| WO2001004287A1 (en) * | 1999-07-07 | 2001-01-18 | Maxygen Aps | A method for preparing modified polypeptides |
| WO2001058935A2 (en) * | 2000-02-11 | 2001-08-16 | Maxygen Aps | FACTOR VII OR VIIa-LIKE MOLECULES |
| US7220837B1 (en) | 2000-04-28 | 2007-05-22 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US7812132B2 (en) | 2000-04-28 | 2010-10-12 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6905683B2 (en) * | 2000-05-03 | 2005-06-14 | Novo Nordisk Healthcare A/G | Human coagulation factor VII variants |
| US7160540B2 (en) | 2000-06-30 | 2007-01-09 | Regents Of The University Of Minnesota | Methods for detecting activity of clottings factors |
| US6423826B1 (en) * | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
| US20030211094A1 (en) * | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| EP1319067A2 (en) * | 2000-09-13 | 2003-06-18 | Novo Nordisk A/S | Human coagulation factor vii variants |
| US7176288B2 (en) | 2000-09-13 | 2007-02-13 | Novo Nordisk Healthcare A/G | Human coagulation factor VII variants |
| US7173000B2 (en) * | 2000-11-09 | 2007-02-06 | The Scripps Research Institute | Modified factor VIIa |
| WO2002077218A1 (en) * | 2001-03-22 | 2002-10-03 | Novo Nordisk Health Care Ag | Coagulation factor vii derivatives |
| US7235638B2 (en) * | 2001-03-22 | 2007-06-26 | Novo Nordisk Healthcare A/G | Coagulation factor VII derivatives |
| US7052868B2 (en) * | 2001-09-27 | 2006-05-30 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| JP4537059B2 (ja) * | 2001-09-27 | 2010-09-01 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | ヒト凝固第vii因子ポリペプチド |
| US7795210B2 (en) | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
| US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
| ES2561985T3 (es) * | 2001-10-10 | 2016-03-01 | Ratiopharm Gmbh | Remodelación y glicoconjugación de anticuerpos |
| US7696163B2 (en) | 2001-10-10 | 2010-04-13 | Novo Nordisk A/S | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | 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 |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| JP2005512524A (ja) | 2001-11-02 | 2005-05-12 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | ヒト凝固第vii因子ポリペプチド |
| US6960657B2 (en) * | 2001-11-02 | 2005-11-01 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| US7125846B2 (en) | 2001-11-09 | 2006-10-24 | Novo Nordisk Healthcare A/G | Pharmaceutical composition comprising factor VII polypeptides and factor V polypeptides |
| KR20040065278A (ko) * | 2001-12-21 | 2004-07-21 | 노보 노르디스크 에이/에스 | 변경된 인자 ⅶ 폴리펩티드의 액체 조성물 |
| DE60232017D1 (de) | 2001-12-21 | 2009-05-28 | Novo Nordisk Healthcare Ag | Flüssige zusammensetzung aus faktor vii polypeptiden |
| US20050069551A1 (en) * | 2002-03-08 | 2005-03-31 | Emory University | Cytotoxic compound-protein conjugates as suppressors of tumor growth and angiogenesis |
| CA2478522A1 (en) * | 2002-03-08 | 2003-09-18 | Emory University | Novel curcuminoid-factor viia constructs as suppressors of tumor growth and angiogenesis |
| PL373728A1 (en) * | 2002-04-30 | 2005-09-05 | Maxygen Holdings Ltd. | Factor vii or viia polypeptide variants |
| US20040009918A1 (en) * | 2002-05-03 | 2004-01-15 | Hanne Nedergaard | Stabilised solid compositions of modified factor VII |
| MXPA04012496A (es) | 2002-06-21 | 2005-09-12 | Novo Nordisk Healthcare Ag | Glicoformos del factor vii pegilados. |
| PL207018B1 (pl) | 2002-06-21 | 2010-10-29 | Novo Nordisk Helth Care Ag | Kompozycja farmaceutyczna, sposób przygotowania stabilnego polipeptydu czynnika VII i zastosowanie polipeptydu czynnika VII |
| CN1671420A (zh) | 2002-06-21 | 2005-09-21 | 诺和诺德医疗保健公司 | Peg化因子ⅶ糖型 |
| ES2339393T3 (es) * | 2002-09-25 | 2010-05-19 | Novo Nordisk Health Care Ag | Polipeptidos del factor de coagulacion humano vii. |
| US6911323B2 (en) * | 2002-09-25 | 2005-06-28 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| ATE505487T1 (de) * | 2002-09-30 | 2011-04-15 | Bayer Healthcare Llc | Fvii- oder fviia-varianten mit erhöhter koagulationswirkung |
| 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 |
| EP1605968A2 (en) * | 2003-03-18 | 2005-12-21 | Novo Nordisk Health Care AG | Liquid, aqueous, pharmaceutical compositions of factor vii polypeptides |
| KR101204712B1 (ko) | 2003-03-18 | 2012-11-27 | 노보 노르디스크 헬스 케어 악티엔게젤샤프트 | Gla-잔기 함유 세린 프로테아제의 제조 방법 |
| DE602004021099D1 (de) | 2003-03-20 | 2009-06-25 | Bayer Healthcare Llc | Fvii oder fviia varianten |
| US7897734B2 (en) | 2003-03-26 | 2011-03-01 | Novo Nordisk Healthcare Ag | Method for the production of proteins |
| WO2004091499A2 (en) | 2003-04-09 | 2004-10-28 | Neose Technologies, Inc. | Intracellular formation of peptide conjugates |
| SG155777A1 (en) | 2003-04-09 | 2009-10-29 | Neose Technologies Inc | Glycopegylation methods and proteins/peptides produced by the methods |
| US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| US7348004B2 (en) | 2003-05-06 | 2008-03-25 | Syntonix Pharmaceuticals, Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
| DE602004031390D1 (de) | 2003-05-06 | 2011-03-24 | Syntonix Pharmaceuticals Inc | Gerinnungsfaktor VII-Fc chimäre Proteine zur Behandlung von hämostatischen Krankheiten |
| EP1624847B1 (en) | 2003-05-09 | 2012-01-04 | BioGeneriX AG | Compositions and methods for the preparation of human growth hormone glycosylation mutants |
| CN1780638B (zh) * | 2003-05-23 | 2010-04-14 | 诺和诺德医疗保健公司 | 氧化硅涂层玻璃作为容器内壁材料的用途及以该材料作内壁的容器 |
| WO2004111242A1 (en) * | 2003-06-19 | 2004-12-23 | Maxygen Holdings Ltd. | FACTOR VII OR VIIa GLA DOMAIN VARIANTS |
| JP4658041B2 (ja) | 2003-06-25 | 2011-03-23 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | Vii因子ポリペプチドの液体組成物 |
| EP1644030B1 (en) * | 2003-07-01 | 2009-10-28 | Novo Nordisk Health Care AG | Liquid, aqueous pharmaceutical composition of factor vii polypeptides |
| WO2005012484A2 (en) | 2003-07-25 | 2005-02-10 | Neose Technologies, Inc. | Antibody-toxin conjugates |
| WO2005025623A2 (en) * | 2003-07-28 | 2005-03-24 | Emory University | Ef-24-factor vii conjugates |
| EP1654004A2 (en) * | 2003-08-08 | 2006-05-10 | Novo Nordisk A/S | Synthesis and application of new structural well defined branched polymers as conjugating agents for peptides |
| US20060198819A1 (en) * | 2003-08-08 | 2006-09-07 | Novo Nordisk Healthcare A/G | Use of galactose oxidase for selective chemical conjugation of protractor molecules to proteins of therapeutic interest |
| RU2388460C2 (ru) | 2003-08-14 | 2010-05-10 | Ново Нордиск Хелс Кеа Аг | Жидкая водная фармацевтическая композиция, содержащая полипептид фактора vii |
| JP4824559B2 (ja) * | 2003-09-09 | 2011-11-30 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 凝固因子viiポリペプチド |
| WO2005024006A2 (en) * | 2003-09-09 | 2005-03-17 | Novo Nordisk Health Care Ag | Coagulation factor vii polypeptides |
| JP2007509843A (ja) * | 2003-10-07 | 2007-04-19 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 第VII/VIIa因子活性を有するハイブリッド分子 |
| US7842661B2 (en) | 2003-11-24 | 2010-11-30 | Novo Nordisk A/S | Glycopegylated erythropoietin formulations |
| US8633157B2 (en) | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
| US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
| PL1711513T3 (pl) | 2003-12-01 | 2014-12-31 | Novo Nordisk Healthcare Ag | Nanofiltracja roztworów czynnika vii w celu usunięcia wirusów |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| US7956032B2 (en) | 2003-12-03 | 2011-06-07 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
| EP2298287B1 (en) | 2003-12-19 | 2018-04-11 | Novo Nordisk Health Care AG | Stabilised compositions of factor VII polypeptides |
| 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 |
| CA2552043A1 (en) | 2004-01-21 | 2005-08-04 | Novo Nordisk A/S | Transglutaminase mediated conjugation of peptides |
| KR100545720B1 (ko) * | 2004-05-31 | 2006-01-24 | 메덱스젠 주식회사 | 당화된 면역글로불린 및 이를 포함하는 면역접합체 |
| WO2005123916A2 (en) * | 2004-06-21 | 2005-12-29 | Novo Nordisk Health Care Ag | Glycosylation-disrupted factor vii variants |
| US20080300173A1 (en) | 2004-07-13 | 2008-12-04 | Defrees Shawn | Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1] |
| US20090176967A1 (en) * | 2004-08-02 | 2009-07-09 | Novo Nordisk Healthcare A/G | Conjugation of FVII |
| JP2008509688A (ja) * | 2004-08-17 | 2008-04-03 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 改変ビタミンk依存性ポリペプチド |
| US8268967B2 (en) | 2004-09-10 | 2012-09-18 | Novo Nordisk A/S | Glycopegylated interferon α |
| HUE026826T2 (en) | 2004-10-29 | 2016-07-28 | Ratiopharm Gmbh | Modeling and glycopegylation of fibroblast growth factor (FGF) |
| SI1824988T1 (sl) * | 2004-11-12 | 2017-11-30 | Bayer Healthcare Llc | Usmerjena modifikacija FVIII |
| JP2008525381A (ja) | 2004-12-23 | 2008-07-17 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 関心のあるビタミンk依存性タンパク質を含んでなる組成物中におけるタンパク質混入物の量の減少 |
| US9029331B2 (en) | 2005-01-10 | 2015-05-12 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
| EP1871795A4 (en) | 2005-04-08 | 2010-03-31 | Biogenerix Ag | COMPOSITIONS AND METHOD FOR PRODUCING GLYCOSYLATION MUTANTS OF A PROTEASE-RESISTANT HUMAN GROWTH HORMONE |
| EP1893230A2 (en) * | 2005-04-26 | 2008-03-05 | Maxygen Holdings Ltd. | Use of modified factor vii for treating bleeding |
| EP1891231A4 (en) | 2005-05-25 | 2011-06-22 | Novo Nordisk As | GLYCOPEGYLATED FACTOR IX |
| WO2006134173A2 (en) | 2005-06-17 | 2006-12-21 | Novo Nordisk Health Care Ag | Selective reduction and derivatization of engineered proteins comprising at least one non-native cysteine |
| CN101262880A (zh) * | 2005-06-24 | 2008-09-10 | 德拉格雷丘尔公司 | 在影响呼吸道的炎症病状中气道施用组织因子途径抑制物 |
| ES2397851T3 (es) | 2005-07-13 | 2013-03-11 | Novo Nordisk Health Care Ag | Células de inactivación proteínica de la célula huésped para la producción de proteínas terapéuticas |
| US20070105755A1 (en) * | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| EP1919498A2 (en) * | 2005-08-26 | 2008-05-14 | Maxygen Holdings Ltd. | Liquid factor vii composition |
| CN101268185B (zh) | 2005-09-01 | 2013-03-27 | 诺沃-诺迪斯克保健股份有限公司 | 因子ⅶ多肽的疏水作用色谱纯化 |
| EP2316930A1 (en) | 2005-09-14 | 2011-05-04 | Novo Nordisk Health Care AG | Human coagulation factor VII polypeptides |
| WO2007039475A1 (en) * | 2005-09-21 | 2007-04-12 | Novo Nordisk Health Care Ag | Human coagulation factor vii polypeptides |
| US20090048440A1 (en) | 2005-11-03 | 2009-02-19 | Neose Technologies, Inc. | Nucleotide Sugar Purification Using Membranes |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| WO2007104317A1 (en) * | 2006-03-16 | 2007-09-20 | Drugrecure Aps | Methods for local treatment with factor vii |
| NZ572050A (en) | 2006-03-31 | 2011-09-30 | Baxter Int | Factor VIII conjugated to polyethylene glycol |
| US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| US7985839B2 (en) * | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
| US7982010B2 (en) * | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
| US20110040073A1 (en) * | 2006-04-07 | 2011-02-17 | Novo Nordisk Healthcare A/G | Covalent Factor VII-Tissue Factor Complex |
| DE602007007923D1 (de) * | 2006-04-11 | 2010-09-02 | Csl Behring Gmbh | Verfahren zur erhöhung der in-vivo-gewinnung therapeutischer polypeptide |
| BRPI0712008A2 (pt) | 2006-05-24 | 2012-01-10 | Novo Nordisk Healthcare Ag | derivados e análogos de fix prolongados |
| FR2901707B1 (fr) | 2006-05-31 | 2017-09-29 | Lab Francais Du Fractionnement | Composition de facteur vii recombinant ou transgenique, chaque molecule de facteur vii possedant deux sites de n-glycosylation a motifs glycanniques definis |
| WO2008003750A2 (en) | 2006-07-07 | 2008-01-10 | Novo Nordisk Health Care Ag | New protein conjugates and methods for their preparation |
| JP5122562B2 (ja) * | 2006-07-17 | 2013-01-16 | ノボ ノルディスク ヘルス ケア アーゲー | 増加した活性を有する第viia因子アナログの新規用途 |
| US20080248959A1 (en) | 2006-07-21 | 2008-10-09 | Neose Technologies, Inc. | Glycosylation of peptides via o-linked glycosylation sequences |
| FR2904558B1 (fr) * | 2006-08-01 | 2008-10-17 | Lab Francais Du Fractionnement | "composition de facteur vii recombinant ou transgenique, presentant majoritairement des formes glycanniques biantennees, bisialylees et non fucosylees" |
| ES2531934T3 (es) | 2006-09-01 | 2015-03-20 | Novo Nordisk Health Care Ag | Glicoproteínas modificadas |
| 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 |
| US8777971B2 (en) * | 2006-10-17 | 2014-07-15 | Amj Bv | Device and method for joining vessels in anastomosis |
| 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 |
| EP3231440A1 (en) | 2006-12-22 | 2017-10-18 | CSL Behring GmbH | Modified coagulation factors with prolonged in vivo half-life |
| EP2099475B1 (en) * | 2007-01-03 | 2016-08-24 | Novo Nordisk Health Care AG | Subcutaneous administration of coagulation factor viia-related polypeptides |
| EP1972687A1 (en) * | 2007-03-23 | 2008-09-24 | GenOdyssee | Polynucleotides and polypeptides of human factor VII gene, SNPs |
| RS52845B (sr) | 2007-04-03 | 2013-12-31 | Biogenerix Ag | Postupci tretmana korišćenjem glikopegiliranog g-csf |
| NZ579985A (en) * | 2007-04-13 | 2012-02-24 | Catalyst Biosciences Inc | Modified factor vii polypetides and uses thereof |
| CN104887620A (zh) | 2007-05-02 | 2015-09-09 | 诺沃—诺迪斯克保健股份有限公司 | 包括芳香族防腐剂和抗氧化剂的高浓度因子vii多肽制剂 |
| 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 |
| AU2008275911A1 (en) * | 2007-07-19 | 2009-01-22 | Arizona Board of Regents, a body corporate acting for and on behalf of Arizona State University | Self- anchoring MEMS intrafascicular neural electrode |
| US8207112B2 (en) | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
| CN104004739A (zh) * | 2007-10-15 | 2014-08-27 | 北卡罗来纳-查佩尔山大学 | 半衰期延长的人因子ix变体 |
| PL2235197T3 (pl) | 2007-12-27 | 2018-01-31 | Baxalta GmbH | Sposoby hodowli komórek |
| ES2476690T3 (es) | 2008-02-27 | 2014-07-15 | Novo Nordisk A/S | Moléculas conjugadas del Factor VIII |
| TWI538916B (zh) | 2008-04-11 | 2016-06-21 | 介控生化科技公司 | 經修飾的因子vii多肽和其用途 |
| EP2444491B1 (en) * | 2008-04-21 | 2016-11-16 | Novo Nordisk Healthcare Ag | Hyperglycosylated human coagulation factor IX |
| EP2280734B1 (en) * | 2008-04-24 | 2014-02-26 | Cantab Biopharmaceuticals Patents Limited | Factor ix conjugates with extended half-lives |
| WO2009141433A1 (en) * | 2008-05-23 | 2009-11-26 | Novo Nordisk Health Care Ag | Low viscosity compositions comprising a pegylated gla-domain containing protein |
| CN102065899A (zh) * | 2008-05-23 | 2011-05-18 | 诺沃-诺迪斯克保健股份有限公司 | 含有高浓度的芳香族防腐剂的peg-官能化的丝氨酸蛋白酶的制剂 |
| MX2011000847A (es) | 2008-08-06 | 2011-02-25 | Novo Nordisk Healthcare Ag | Proteinas conjugadas con eficacia prolongada in vivo. |
| CN102292349B (zh) | 2009-01-22 | 2016-04-13 | 诺沃—诺迪斯克保健股份有限公司 | 稳定的生长激素化合物 |
| WO2010091122A1 (en) | 2009-02-03 | 2010-08-12 | Amunix, Inc. | Extended recombinant polypeptides and compositions comprising same |
| SI2440239T1 (en) | 2009-06-09 | 2018-01-31 | Prolong Pharmaceuticals, LLC | Hemoglobin compositions |
| WO2010149172A2 (en) | 2009-06-24 | 2010-12-29 | Rigshospitalet | SYSTEMIC PRO-HEMOSTATIC EFFECT OF CLOTTING FACTORS IN COMBINATION WITH SYMPATHICOMIMETICS WITH AGONISTIC EFFECTS ON α-ADRENERGIC AND/OR β-ADRENERGIC RECEPTORS OF THE SYMPATHETIC NERVOUS SYSTEM, RELATED TO IMPROVED CLOT STRENGTH. |
| EP2459226B1 (en) | 2009-07-27 | 2016-06-29 | Lipoxen Technologies Limited | Glycopolysialylation of proteins other than blood coagulation proteins |
| US8809501B2 (en) | 2009-07-27 | 2014-08-19 | 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 |
| US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| CN102612376A (zh) | 2009-08-06 | 2012-07-25 | 诺沃-诺迪斯克保健股份有限公司 | 具有延长的体内功效的生长激素 |
| WO2011018515A1 (en) | 2009-08-14 | 2011-02-17 | Novo Nordisk Health Care Ag | Method of purifying pegylated proteins |
| BR112012004094A2 (pt) | 2009-08-24 | 2016-03-08 | Amunix Operating Inc | composições de fator vii de coagulação e métodos para fazer e usar as mesmas |
| US20110150843A1 (en) * | 2009-10-30 | 2011-06-23 | National Institute Of Immunology | Method for the therapeutic correction of hemophilia a by transplanting bone marrow cells |
| US9211342B2 (en) | 2010-01-22 | 2015-12-15 | Novo Nordisk Healthcare Ag | Stable growth hormone compounds resistant to proteolytic degradation |
| MX345736B (es) | 2010-01-22 | 2017-02-14 | Novo Nordisk Healthcare Ag | Hormonas de crecimiento con eficacia in vivo prolongada. |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| WO2011152694A2 (en) | 2010-06-04 | 2011-12-08 | Sk Chemicals Co., Ltd. | Fusion protein having factor vii activity |
| TWI595004B (zh) | 2010-11-03 | 2017-08-11 | 介控生化科技公司 | 經修飾之第九因子多胜肽及其用途 |
| WO2012071631A1 (en) * | 2010-12-03 | 2012-06-07 | Gene Stream Pty Ltd | Improved light-emitting molecules |
| 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 |
| DK2717898T3 (en) | 2011-06-10 | 2019-03-25 | Bioverativ Therapeutics Inc | COAGULATING COMPOUNDS AND PROCEDURES FOR USE THEREOF |
| CA2851223A1 (en) * | 2011-10-06 | 2013-04-11 | Hanmi Science Co., Ltd. | Blood coagulation factor vii and viia derivatives, conjugates and complexes comprising the same, and use thereof |
| HRP20221531T1 (hr) | 2012-02-15 | 2023-02-17 | Bioverativ Therapeutics Inc. | Pripravci faktora viii i postupci dobivanja i korištenja istih |
| LT2822577T (lt) | 2012-02-15 | 2019-03-25 | Bioverativ Therapeutics Inc. | Rekombinantiniai faktoriaus viii baltymai |
| EP2838566A2 (en) * | 2012-04-16 | 2015-02-25 | Cantab Biopharmaceuticals Patents Limited | Optimised subcutaneous therapeutic agents |
| WO2014060401A1 (en) * | 2012-10-15 | 2014-04-24 | Novo Nordisk Health Care Ag | Coagulation factor vii polypeptides |
| US20150259665A1 (en) | 2012-10-15 | 2015-09-17 | Novo Nordisk Health Care Ag | Factor vii conjugates |
| CA2896057C (en) | 2012-12-24 | 2023-03-14 | Maxine Bauzon | Short-acting factor vii polypeptides |
| CN105120887A (zh) | 2013-04-05 | 2015-12-02 | 诺和诺德保健股份有限公司 | 生长激素化合物制剂 |
| EP3033097B1 (en) | 2013-08-14 | 2021-03-10 | Bioverativ Therapeutics Inc. | Factor viii-xten fusions and uses thereof |
| MX2016004702A (es) * | 2013-10-15 | 2016-07-22 | Novo Nordisk Healthcare Ag | Polipeptidos del factor vii de coagulacion. |
| MX2018001497A (es) | 2015-08-03 | 2018-05-15 | Bioverativ Therapeutics Inc | Proteinas de fusion de factor ix y metodos para producirlas y usarlas. |
| RU2633588C2 (ru) * | 2015-11-03 | 2017-10-13 | Евгений Федорович Чередников | Способ эндоскопического лечения язвенного гастродуоденального кровотечения |
| WO2018102743A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| RS66972B1 (sr) | 2018-05-18 | 2025-07-31 | Bioverativ Therapeutics Inc | Metode lečenja hemofilije a |
| CN114728044A (zh) | 2019-08-15 | 2022-07-08 | 介控生化科技公司 | 用于皮下施用和按需求治疗的经修饰的因子vii多肽 |
| CA3157605A1 (en) | 2019-11-13 | 2021-05-20 | Volker Schellenberger | Barcoded xten polypeptides and compositions thereof, and methods for making and using the same |
| MX2024005230A (es) * | 2021-10-29 | 2024-08-27 | Sigilon Therapeutics Inc | Composiciones para terapias basadas en celulas y metodos relacionados. |
Family Cites Families (140)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4470461A (en) | 1982-09-30 | 1984-09-11 | Phillips Petroleum Company | Organic nitro compounds as cosurfactants in enhanced oil recovery processes |
| US4870008A (en) | 1983-08-12 | 1989-09-26 | Chiron Corporation | Secretory expression in eukaryotes |
| EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
| US4931373A (en) | 1984-05-25 | 1990-06-05 | Zymogenetics, Inc. | Stable DNA constructs for expression of α-1 antitrypsin |
| GB8430252D0 (en) | 1984-11-30 | 1985-01-09 | Beecham Group Plc | Compounds |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| GR860984B (en) | 1985-04-17 | 1986-08-18 | Zymogenetics Inc | Expression of factor vii and ix activities in mammalian cells |
| ZA862768B (en) * | 1985-04-17 | 1986-12-30 | Zymogenetics Inc | Expression of factor vii and ix activities in mammalian cells |
| DE3676670D1 (de) | 1985-06-26 | 1991-02-07 | Cetus Corp | Solubilisierung von proteinen fuer pharmazeutische zusammensetzungen mittels polymerkonjugierung. |
| DE3688920T4 (de) | 1985-07-03 | 1995-08-31 | Genencor Int | Hybride Polypeptide und Verfahren zu deren Herstellung. |
| US5679543A (en) | 1985-08-29 | 1997-10-21 | Genencor International, Inc. | DNA sequences, vectors and fusion polypeptides to increase secretion of desired polypeptides from filamentous fungi |
| HU206897B (en) | 1985-10-25 | 1993-01-28 | Zymogenetics Inc | Process for utilizing bar-1 gen for selecting strange proteins |
| US5180583A (en) | 1985-11-26 | 1993-01-19 | Hedner Ulla K E | Method for the treatment of bleeding disorders |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | METHOD FOR IMPROVING GLYCOPROTE INSTABILITY. |
| DK122686D0 (da) | 1986-03-17 | 1986-03-17 | Novo Industri As | Fremstilling af proteiner |
| US5258288A (en) | 1986-07-25 | 1993-11-02 | Genzyme Corporation | Vector containing DNA encoding mature human protein S |
| DK323587D0 (da) | 1987-06-25 | 1987-06-25 | Novo Industri As | Protein |
| PT87688B (pt) | 1987-06-12 | 1992-09-30 | Hoechst Japan | Processo para a preparacao de proteina hibrida c |
| US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US5648254A (en) | 1988-01-15 | 1997-07-15 | Zymogenetics, Inc. | Co-expression in eukaryotic cells |
| US4847325A (en) | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
| JPH0246296A (ja) | 1988-08-09 | 1990-02-15 | Hoechst Japan Ltd | 雑種プロテインc及びその製造方法 |
| JP2928287B2 (ja) * | 1988-09-29 | 1999-08-03 | 協和醗酵工業株式会社 | 新規ポリペプチド |
| US5218092A (en) * | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
| 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 |
| GB8824591D0 (en) | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Fractionation process |
| WO1990005783A1 (en) | 1988-11-18 | 1990-05-31 | Cetus Corporation | Insect signal peptide mediated secretion of recombinant proteins |
| US5041376A (en) | 1988-12-09 | 1991-08-20 | The Board Of Regents Of The University Of Texas System | Method for identifying or shielding functional sites or epitopes of proteins that enter the exocytotic pathway of eukaryotic cells, the mutant proteins so produced and genes encoding said mutant proteins |
| US5047335A (en) | 1988-12-21 | 1991-09-10 | The Regents Of The University Of Calif. | Process for controlling intracellular glycosylation of proteins |
| EP0401384B1 (en) | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| US4902502A (en) | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US5122614A (en) | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| AU5526690A (en) | 1989-04-19 | 1990-11-29 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| DE69026306T2 (de) | 1989-05-27 | 1996-10-17 | Seikagaku Kogyo Co Ltd | Verfahren für die Herstellung von Polyethylenglykolderivate und modifizierte Proteine. |
| US5093317A (en) | 1989-06-05 | 1992-03-03 | Cephalon, Inc. | Treating disorders by application of insulin-like growth factor |
| US5077214A (en) | 1989-07-07 | 1991-12-31 | The Texas A&M University System | Use of baculovirus early promoters for expression of foreign genes in stably transformed insect cells |
| US4973317A (en) | 1989-07-14 | 1990-11-27 | Bobrove Arthur M | Automatic sheath protection of hypodermic needle |
| US5023328A (en) | 1989-08-04 | 1991-06-11 | The Texas A&M University System | Lepidopteran AKH signal sequence |
| US5580560A (en) | 1989-11-13 | 1996-12-03 | Novo Nordisk A/S | Modified factor VII/VIIa |
| US5225537A (en) | 1989-12-29 | 1993-07-06 | Zymogenetics, Inc. | Methods for producing hybrid phospholipid-binding proteins |
| JP2549224B2 (ja) | 1990-01-26 | 1996-10-30 | イムノ・アクチェンゲゼルシャフト | 組換えにより産生される血液因子及びその血液因子の発現方法並びにその方法に使用されるワクシニアウイルス組換え体 |
| EP0521873B1 (en) | 1990-01-29 | 1999-06-02 | Zymogenetics, Inc. | Anticoagulant proteins |
| US5219564A (en) | 1990-07-06 | 1993-06-15 | Enzon, Inc. | Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon |
| US5583107A (en) | 1990-09-04 | 1996-12-10 | Cor Therapeutics, Inc. | Agents affecting thrombosis and hemostasis |
| US5531916A (en) | 1990-10-03 | 1996-07-02 | E. I. Du Pont De Nemours And Company | Hydrofluorocarbon cleaning compositions |
| EP0513332A4 (en) | 1990-11-14 | 1993-03-17 | Cargill, Incorporated | Conjugates of poly(vinylsaccharide) with proteins for the stabilization of proteins |
| IE914102A1 (en) | 1990-11-26 | 1992-06-03 | Genetics Inst | Expression of pace in host cells and methods of use thereof |
| US5817788A (en) | 1991-02-28 | 1998-10-06 | Zymogenetics, Inc. | Modified factor VII |
| US5788965A (en) | 1991-02-28 | 1998-08-04 | Novo Nordisk A/S | Modified factor VII |
| JP3459416B2 (ja) | 1991-02-28 | 2003-10-20 | ザイモジェネティクス,インコーポレイティド | 修飾されたファクター▲vii▼ |
| US5861374A (en) * | 1991-02-28 | 1999-01-19 | Novo Nordisk A/S | Modified Factor VII |
| US5833982A (en) | 1991-02-28 | 1998-11-10 | Zymogenetics, Inc. | Modified factor VII |
| WO1994027631A1 (en) | 1993-05-21 | 1994-12-08 | Zymogenetics, Inc. | Modified factor vii |
| CA2101918A1 (en) | 1991-03-18 | 1992-09-19 | Samuel Zalipsky | Hydrazine containing conjugates of polypeptides and glycopolypeptides with polymers |
| US5595732A (en) | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5504064A (en) | 1991-04-10 | 1996-04-02 | Oklahoma Medical Research Foundation | Treatment of bleeding with modified tissue factor in combination with an activator of FVII |
| DE4113487C1 (enExample) | 1991-04-25 | 1992-11-05 | Fleischgrosshandel Hans-Werner & Bernd Meixner Gmbh, 6301 Wettenberg, De | |
| US5281698A (en) | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
| ZA933926B (en) | 1992-06-17 | 1994-01-03 | Amgen Inc | Polyoxymethylene-oxyethylene copolymers in conjuction with blomolecules |
| WO1994004193A1 (en) | 1992-08-21 | 1994-03-03 | Enzon, Inc. | Novel attachment of polyalkylene oxides to bio-effecting substances |
| US5382657A (en) | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| NZ250375A (en) | 1992-12-09 | 1995-07-26 | Ortho Pharma Corp | Peg hydrazone and peg oxime linkage forming reagents and protein derivatives |
| US5298643A (en) | 1992-12-22 | 1994-03-29 | Enzon, Inc. | Aryl imidate activated polyalkylene oxides |
| US5349001A (en) | 1993-01-19 | 1994-09-20 | Enzon, Inc. | Cyclic imide thione activated polyalkylene oxides |
| US5321095A (en) | 1993-02-02 | 1994-06-14 | Enzon, Inc. | Azlactone activated polyalkylene oxides |
| IL104734A0 (en) | 1993-02-15 | 1993-06-10 | Univ Bar Ilan | Bioactive conjugates of cellulose with amino compounds |
| DK38293D0 (da) | 1993-03-31 | 1993-03-31 | Novo Nordisk As | Fremstilling af proteiner |
| US5871384A (en) * | 1993-04-20 | 1999-02-16 | Kichijo; Hiroshi | Block assembly and devices formed thereby |
| JPH0720127A (ja) | 1993-05-07 | 1995-01-24 | Eisai Co Ltd | 各種pivkaの測定方法および測定試薬 |
| AU7097094A (en) | 1993-06-01 | 1994-12-20 | Enzon, Inc. | Carbohydrate-modified polymer conjugates with erythropoietic activity |
| WO1995000162A1 (en) | 1993-06-21 | 1995-01-05 | Enzon, Inc. | Site specific synthesis of conjugated peptides |
| GB9317618D0 (en) | 1993-08-24 | 1993-10-06 | Royal Free Hosp School Med | Polymer modifications |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| ATE214940T1 (de) | 1993-11-10 | 2002-04-15 | Enzon Inc | Verbesserte interferon-polymerkonjugate |
| US5951974A (en) | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| DE4343591A1 (de) | 1993-12-21 | 1995-06-22 | Evotec Biosystems Gmbh | Verfahren zum evolutiven Design und Synthese funktionaler Polymere auf der Basis von Formenelementen und Formencodes |
| US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US5473034A (en) | 1994-03-18 | 1995-12-05 | Hyogo Prefectural Government | Method for producing protein-synthetic polymer conjugate and said conjugate produced thereby |
| US5629384A (en) | 1994-05-17 | 1997-05-13 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
| AU2826495A (en) | 1994-06-02 | 1996-01-04 | Enzon, Inc. | Method of solubilizing substantially water insoluble materials |
| US5730990A (en) | 1994-06-24 | 1998-03-24 | Enzon, Inc. | Non-antigenic amine derived polymers and polymer conjugates |
| WO1996000787A1 (en) | 1994-06-30 | 1996-01-11 | Novo Nordisk Biotech, Inc. | Non-toxic, non-toxigenic, non-pathogenic fusarium expression system and promoters and terminators for use therein |
| US5650234A (en) | 1994-09-09 | 1997-07-22 | Surface Engineering Technologies, Division Of Innerdyne, Inc. | Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| DE4437604A1 (de) | 1994-10-21 | 1996-04-25 | Basf Ag | Konjugate aus einem Poly- oder Oligopeptid und einer niedermolekularen lipophilen Verbindung |
| WO1996041813A2 (en) | 1994-11-09 | 1996-12-27 | Offord Robin E | Functionalized polymers for site-specific attachment |
| US5738846A (en) | 1994-11-10 | 1998-04-14 | Enzon, Inc. | Interferon polymer conjugates and process for preparing the same |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| WO1996040791A1 (en) | 1995-06-07 | 1996-12-19 | Novo Nordisk A/S | Modification of polypeptides |
| US5672662A (en) | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| EP0843725B1 (en) | 1995-08-11 | 2002-04-17 | Novozymes A/S | Method for preparing polypeptide variants |
| DE19531637A1 (de) | 1995-08-28 | 1997-03-06 | Immuno Ag | Pharmazeutische Zusammensetzung zur Behandlung von Blutgerinnungsstörugnen, Verfahren zur Herstellung derselben und deren Verwendung |
| US5747639A (en) | 1996-03-06 | 1998-05-05 | Amgen Boulder Inc. | Use of hydrophobic interaction chromatography to purify polyethylene glycols |
| TW517067B (en) | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
| DE69736780T2 (de) | 1996-08-02 | 2007-09-06 | Ortho-Mcneil Pharmaceutical, Inc. | Polypeptide mit einzelnem kovalent gebundenen n-terminalen wasserlöslichen polymer |
| DE69735597T2 (de) | 1996-11-08 | 2006-12-21 | Oklahoma Medical Research Foundation, Oklahoma | Verwendung eines modifizierten protein-c |
| US5837843A (en) | 1996-11-08 | 1998-11-17 | Oklahoma Medical Research Foundation | Modified protein C |
| JP2001527387A (ja) | 1997-01-24 | 2001-12-25 | ノボ ノルディスク アクティーゼルスカブ | 合成リーダーペプチド配列 |
| EP0921817B1 (en) | 1997-01-29 | 2001-03-28 | PolyMASC Pharmaceuticals plc | Pegylation process |
| EP1017794A1 (en) * | 1997-02-06 | 2000-07-12 | Novo Nordisk A/S | Polypeptide-polymer conjugates having added and/or removed attachment groups |
| WO1998048837A1 (en) | 1997-04-30 | 1998-11-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
| AU744085B2 (en) | 1997-06-06 | 2002-02-14 | Kyowa Hakko Kirin Co., Ltd. | Chemically modified polypeptides |
| AT407255B (de) | 1997-06-20 | 2001-02-26 | Immuno Ag | Rekombinanter zellklon mit erhöhter stabilität in serum- und proteinfreiem medium und verfahren zur gewinnung des stabilen zellklons |
| US6475725B1 (en) | 1997-06-20 | 2002-11-05 | Baxter Aktiengesellschaft | Recombinant cell clones having increased stability and methods of making and using the same |
| EP1012184B1 (en) * | 1997-07-14 | 2007-10-10 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
| JP2001510168A (ja) | 1997-07-18 | 2001-07-31 | ノボ ノルディスク アクティーゼルスカブ | FVIIa媒介性細胞内シグナル伝達経路に関連する反対条件の処理のためのFVIIa又はFVIIaiの使用 |
| US7247708B2 (en) | 1997-10-23 | 2007-07-24 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6017882A (en) | 1997-10-23 | 2000-01-25 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6747003B1 (en) | 1997-10-23 | 2004-06-08 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6693075B1 (en) | 1997-10-23 | 2004-02-17 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US5981709A (en) | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| US5985263A (en) | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| NZ507456A (en) | 1998-04-28 | 2003-10-31 | Applied Research Systems | Process and conjugated forms of PEGylated interferon- beta with polyethylene glycol (PEG) wherein the thiol reactive polyol agent is mono-methoxylated |
| AT408613B (de) | 1998-06-17 | 2002-01-25 | Immuno Ag | Pharmazeutisches faktor vii-präparat |
| ATE390441T1 (de) | 1998-10-30 | 2008-04-15 | Novozymes As | Niedrigallergene proteinvarianten |
| ATE365210T1 (de) | 1998-10-30 | 2007-07-15 | Novozymes As | Glykosylierte proteine mit reduzierter allergenität |
| AU1262900A (en) | 1998-11-06 | 2000-05-29 | Novo Nordisk A/S | Method for the production of fvii |
| JP2002534966A (ja) | 1999-01-19 | 2002-10-22 | マキシジェン, インコーポレイテッド | オリゴヌクレオチド媒介核酸組換え |
| WO2000054787A1 (en) | 1999-03-16 | 2000-09-21 | The Children's Hospital Of Philadelphia | Enhanced gamma-carboxylation of recombinant vitamin k-dependent clotting factors |
| US6432826B1 (en) * | 1999-11-29 | 2002-08-13 | Applied Materials, Inc. | Planarized Cu cleaning for reduced defects |
| WO2001058935A2 (en) | 2000-02-11 | 2001-08-16 | Maxygen Aps | FACTOR VII OR VIIa-LIKE MOLECULES |
| US7220837B1 (en) | 2000-04-28 | 2007-05-22 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| AU2001254624A1 (en) | 2000-05-03 | 2001-11-12 | Novo-Nordisk A/S | Human coagulation factor vii variants |
| US7160540B2 (en) | 2000-06-30 | 2007-01-09 | Regents Of The University Of Minnesota | Methods for detecting activity of clottings factors |
| US6423826B1 (en) | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
| US20030211094A1 (en) | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| EP1319067A2 (en) | 2000-09-13 | 2003-06-18 | Novo Nordisk A/S | Human coagulation factor vii variants |
| US7176288B2 (en) | 2000-09-13 | 2007-02-13 | Novo Nordisk Healthcare A/G | Human coagulation factor VII variants |
| AU2001291653A1 (en) | 2000-10-02 | 2002-04-15 | Novo-Nordisk A/S | Industrial-scale serum-free production of recombinant factor vii in mammalian cells |
| US7173000B2 (en) | 2000-11-09 | 2007-02-06 | The Scripps Research Institute | Modified factor VIIa |
| PL373728A1 (en) | 2002-04-30 | 2005-09-05 | Maxygen Holdings Ltd. | Factor vii or viia polypeptide variants |
| ATE505487T1 (de) | 2002-09-30 | 2011-04-15 | Bayer Healthcare Llc | Fvii- oder fviia-varianten mit erhöhter koagulationswirkung |
| DE602004021099D1 (de) | 2003-03-20 | 2009-06-25 | Bayer Healthcare Llc | Fvii oder fviia varianten |
| WO2004111242A1 (en) | 2003-06-19 | 2004-12-23 | Maxygen Holdings Ltd. | FACTOR VII OR VIIa GLA DOMAIN VARIANTS |
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