NZ319322A - Conjugates of factor viii and a biopolymer - Google Patents
Conjugates of factor viii and a biopolymerInfo
- Publication number
- NZ319322A NZ319322A NZ319322A NZ31932296A NZ319322A NZ 319322 A NZ319322 A NZ 319322A NZ 319322 A NZ319322 A NZ 319322A NZ 31932296 A NZ31932296 A NZ 31932296A NZ 319322 A NZ319322 A NZ 319322A
- Authority
- NZ
- New Zealand
- Prior art keywords
- factor
- polypeptide
- factor viii
- process according
- conjugate
- Prior art date
Links
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- 238000002741 site-directed mutagenesis Methods 0.000 description 1
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- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
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- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- 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)
- C12N9/48—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)
- C12N9/644—Coagulation factor IXa (3.4.21.22)
-
- 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)
- C12N9/48—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)
- C12N9/647—Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
-
- 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
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
- Y10S530/812—Peptides or proteins is immobilized on, or in, an organic carrier
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
- Y10S530/812—Peptides or proteins is immobilized on, or in, an organic carrier
- Y10S530/813—Carrier is a saccharide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
- Y10S530/812—Peptides or proteins is immobilized on, or in, an organic carrier
- Y10S530/815—Carrier is a synthetic polymer
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Toxicology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Polyesters Or Polycarbonates (AREA)
- Polyamides (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9503380A SE9503380D0 (sv) | 1995-09-29 | 1995-09-29 | Protein derivatives |
| PCT/SE1996/001215 WO1997011957A1 (en) | 1995-09-29 | 1996-09-27 | Conjugates of a polypeptide and a biocompatible polymer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ319322A true NZ319322A (en) | 1998-08-26 |
Family
ID=20399642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ319322A NZ319322A (en) | 1995-09-29 | 1996-09-27 | Conjugates of factor viii and a biopolymer |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6048720A (https=) |
| EP (3) | EP1260582B1 (https=) |
| JP (1) | JP3911023B2 (https=) |
| AT (3) | ATE283351T1 (https=) |
| AU (1) | AU706246B2 (https=) |
| BR (1) | BR9610695A (https=) |
| CA (1) | CA2231801C (https=) |
| DE (3) | DE69634373T2 (https=) |
| DK (3) | DK0871649T3 (https=) |
| ES (3) | ES2236396T3 (https=) |
| HU (1) | HU221208B1 (https=) |
| NO (2) | NO321096B1 (https=) |
| NZ (1) | NZ319322A (https=) |
| PL (1) | PL185821B1 (https=) |
| PT (3) | PT871649E (https=) |
| SE (1) | SE9503380D0 (https=) |
| WO (1) | WO1997011957A1 (https=) |
| ZA (1) | ZA968139B (https=) |
Families Citing this family (177)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AT405740B (de) * | 1996-12-13 | 1999-11-25 | Immuno Ag | Von willebrand-faktor-derivat sowie ein verfahren zur isolierung von proteinen |
| EE05214B1 (et) * | 1998-04-28 | 2009-10-15 | Applied Research Systems ARS Holding N.V. | Polool-IFN- β konjugaat, selle valmistamismeetod ja farmatseutiline kompositsioon |
| US7425541B2 (en) * | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
| DK1820516T3 (da) | 1999-02-22 | 2013-10-28 | Univ Connecticut | Nye albuminfrie faktor VIII-præparater |
| US7655252B2 (en) | 1999-04-28 | 2010-02-02 | The Regents Of The University Of Michigan | Antimicrobial nanoemulsion compositions and methods |
| US6635676B2 (en) * | 1999-04-28 | 2003-10-21 | Regents Of The University Of Michigan | Non-toxic antimicrobial compositions and methods of use |
| IT1318484B1 (it) * | 2000-04-21 | 2003-08-25 | Univ Roma | Derivati di colina per il trattamento della malattia di alzheimer. |
| 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 |
| CA2415158A1 (en) * | 2000-07-07 | 2002-01-17 | Gennady P. Samokhin | Biologically active protein conjugates formed by first protecting activesite |
| AU2002225681A1 (en) * | 2000-11-15 | 2002-05-27 | Globe Immune, Inc. | Yeast-dentritic cell vaccines and uses thereof |
| JP2010209109A (ja) * | 2001-06-25 | 2010-09-24 | Regents Of The Univ Of Michigan | 抗微生物ナノエマルジョンの組成物および方法 |
| EP1425304B9 (en) * | 2001-07-11 | 2010-09-08 | Maxygen, Inc. | G-csf conjugates |
| US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| ES2411007T3 (es) * | 2001-10-10 | 2013-07-04 | Novo Nordisk A/S | Remodelación y glicoconjugación de péptidos |
| US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
| 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 |
| SE0104186D0 (sv) * | 2001-12-12 | 2001-12-12 | Darcy Birse | Method and device |
| PT3025726T (pt) * | 2002-01-18 | 2020-01-09 | Biogen Ma Inc | Compostos do polímero polialquileno e utilizações dos mesmos |
| US20030149246A1 (en) * | 2002-02-01 | 2003-08-07 | Russell John C. | Macromolecular conjugates and processes for preparing the same |
| CA2475370A1 (en) * | 2002-03-02 | 2003-09-12 | F. Hoffmann-La Roche Ag | Conjugates of the c domain of human gelatinase a and polyethylene glycol, methods of purification and uses thereof |
| DE60336555D1 (de) * | 2002-06-21 | 2011-05-12 | Novo Nordisk Healthcare Ag | Pegylierte glykoformen von faktor vii |
| DK1545613T3 (da) | 2002-07-31 | 2011-11-14 | Seattle Genetics Inc | Auristatinkonjugater og deres anvendelse til behandling af cancer, en autoimmun sygdom eller en infektiøs sygdom |
| BRPI0407882B1 (pt) * | 2003-02-26 | 2021-07-27 | Nektar Therapeutics | Composição compreendendo conjugados de polímero-porção de fator viii e seu método de fabricação |
| US7217794B2 (en) * | 2003-04-02 | 2007-05-15 | Daiamed, Inc. | Compounds and methods for treatment of thrombosis |
| US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
| PL1615945T3 (pl) | 2003-04-09 | 2012-03-30 | Ratiopharm Gmbh | Sposoby glikopegylacji i białka/peptydy wytwarzane tymi sposobami |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| CN1820024B (zh) * | 2003-05-12 | 2011-06-22 | 阿费麦克斯公司 | 新的聚(乙二醇)修饰的化合物及其用途 |
| EP2644206B1 (en) * | 2003-05-23 | 2019-04-03 | Nektar Therapeutics | PEG derivatives containing two PEG chains |
| US7947261B2 (en) * | 2003-05-23 | 2011-05-24 | Nektar Therapeutics | Conjugates formed from polymer derivatives having particular atom arrangements |
| US9005625B2 (en) | 2003-07-25 | 2015-04-14 | Novo Nordisk A/S | Antibody toxin conjugates |
| EP2478912B1 (en) | 2003-11-06 | 2016-08-31 | Seattle Genetics, Inc. | Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy |
| US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| MXPA06006023A (es) * | 2003-12-03 | 2006-08-23 | Neose Technologies Inc | Factor ix glicopegilado. |
| US20050171002A1 (en) * | 2004-02-03 | 2005-08-04 | Mohanty Dillip K. | Polyoxyalkylene compound and method for making |
| EP1755652B1 (en) | 2004-03-19 | 2010-11-24 | Baxter International Inc. | Factor ixa for the treatment of bleeding disorders |
| KR20070027621A (ko) * | 2004-06-08 | 2007-03-09 | 알자 코포레이션 | 4-성분 축합 반응에 의한 고분자 콘쥬게이트의 제조 |
| AU2014280936B2 (en) * | 2004-06-30 | 2016-12-15 | Nektar Therapeutics | Polymer-factor ix moiety conjugates |
| CA2571292C (en) * | 2004-06-30 | 2013-05-21 | Nektar Therapeutics Al, Corporation | Polymer-factor ix moiety conjugates |
| US20080300173A1 (en) | 2004-07-13 | 2008-12-04 | Defrees Shawn | Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1] |
| PL1797112T3 (pl) * | 2004-09-29 | 2011-04-29 | The Administrators Of The Tulane Educational Fund | Inhibitory wirusa zapalenia wątroby typu C |
| WO2006050247A2 (en) | 2004-10-29 | 2006-05-11 | Neose Technologies, Inc. | Remodeling and glycopegylation of fibroblast growth factor (fgf) |
| AU2013203348B2 (en) * | 2004-11-12 | 2016-03-03 | Bayer Healthcare Llc | Site-directed modification of FVIII |
| AU2016203693B2 (en) * | 2004-11-12 | 2018-08-23 | Bayer Healthcare Llc | Site-directed modification of FVIII |
| PT2363414T (pt) | 2004-11-12 | 2022-08-04 | Bayer Healthcare Llc | Modificação de fviii direcionada a sítio |
| AU2012203813B2 (en) * | 2004-11-12 | 2013-10-24 | Bayer Healthcare Llc | Site-directed modification of FVIII |
| US8288352B2 (en) * | 2004-11-12 | 2012-10-16 | Seattle Genetics, Inc. | Auristatins having an aminobenzoic acid unit at the N terminus |
| CN101163506B (zh) | 2004-12-27 | 2012-09-26 | 巴克斯特国际公司 | 聚合物-von Willebrand因子偶联物 |
| US9029331B2 (en) | 2005-01-10 | 2015-05-12 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
| WO2006076471A2 (en) * | 2005-01-12 | 2006-07-20 | Nobex Corporation | Bnp conjugates and methods of use |
| WO2006121569A2 (en) * | 2005-04-08 | 2006-11-16 | Neose Technologies, Inc. | Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants |
| EP2975135A1 (en) * | 2005-05-25 | 2016-01-20 | Novo Nordisk A/S | Glycopegylated factor IX |
| WO2007008848A2 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus |
| ES2708763T3 (es) | 2005-07-07 | 2019-04-11 | Seattle Genetics Inc | Compuestos de monometilvalina que tienen modificaciones de la cadena lateral de fenilalanina en el extremo C |
| US7395967B2 (en) * | 2005-07-21 | 2008-07-08 | University Of Washington | Methods and systems for counterbalancing a scanning beam device |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| US7855279B2 (en) | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| WO2007056191A2 (en) | 2005-11-03 | 2007-05-18 | 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 |
| US7750116B1 (en) * | 2006-02-18 | 2010-07-06 | Seattle Genetics, Inc. | Antibody drug conjugate metabolites |
| US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| AU2007245190B2 (en) * | 2006-03-31 | 2011-07-21 | Takeda Pharmaceutical Company Limited | Pegylated factor VIII |
| US7982010B2 (en) | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
| US7985839B2 (en) | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
| EP2049144B8 (en) * | 2006-07-21 | 2015-02-18 | ratiopharm GmbH | Glycosylation of peptides via o-linked glycosylation sequences |
| EP2054521A4 (en) | 2006-10-03 | 2012-12-19 | Novo Nordisk As | PROCESS FOR CLEANING POLYPEPTIDE CONJUGATES |
| ES2655734T3 (es) * | 2006-10-04 | 2018-02-21 | Novo Nordisk A/S | Glicopéptidos y azúcares pegilados unidos a glicerol |
| PT2101821E (pt) | 2006-12-15 | 2014-10-03 | Baxter Int | Fator conjugado viia-ácido (poli)siálico com prolongamento do tempo de meia vida in vivo |
| CA2673459C (en) | 2006-12-22 | 2016-09-13 | Stefan Schulte | Modified coagulation factors with prolonged in vivo half-life |
| EP2114458B1 (en) | 2006-12-27 | 2014-02-26 | Nektar Therapeutics | Von willebrand factor- and factor viii-polymer conjugates having a releasable linkage |
| JP5606738B2 (ja) * | 2006-12-27 | 2014-10-15 | ウェルズ ファーゴ バンク ナショナル アソシエイション | 解離可能な連結を有する第ｉｘ因子部分−ポリマー共役体 |
| HRP20130382T1 (hr) | 2007-04-03 | 2013-05-31 | Biogenerix Ag | Postupci lijeäśenja pomoä†u glikopegiliranog g-csf |
| CA2683317C (en) * | 2007-04-26 | 2014-12-16 | Bayer Healthcare Llc | Stabilization of liquid solutions of recombinant protein for frozen storage |
| WO2008137747A1 (en) | 2007-05-02 | 2008-11-13 | The Regents Of The University Of Michigan | Nanoemulsion therapeutic compositions and methods of using the same |
| CA2690611C (en) | 2007-06-12 | 2015-12-08 | Novo Nordisk A/S | Improved process for the production of nucleotide sugars |
| JP2010529155A (ja) * | 2007-06-13 | 2010-08-26 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 出血性疾患の治療及び予防的処置における血管外投与のためのｖｗｆ安定化ｆｖｉｉｉ製剤及びｆｖｉｉｉなしのｖｗｆ製剤の使用 |
| PE20090943A1 (es) | 2007-07-16 | 2009-08-05 | Genentech Inc | Anticuerpos anti-cd79b e inmunoconjugados |
| EP2176295B1 (en) | 2007-07-16 | 2014-11-19 | Genentech, Inc. | Humanized anti-cd79b antibodies and immunoconjugates and methods of use |
| US20090035848A1 (en) * | 2007-08-03 | 2009-02-05 | Robert Hickey | Moving bed biofilm reactor (mbbr) system for conversion of syngas components to liquid products |
| KR20100095441A (ko) * | 2007-11-09 | 2010-08-30 | 백스터 인터내셔널 인코포레이티드 | 변형된 재조합 인자 ⅷ 및 폰 빌레브란트 인자 및 사용 방법 |
| KR101607346B1 (ko) | 2008-01-31 | 2016-03-29 | 제넨테크, 인크. | 항-ｃｄ７９ｂ 항체 및 면역접합체 및 사용 방법 |
| PL2257311T3 (pl) | 2008-02-27 | 2014-09-30 | Novo Nordisk As | Koniugaty cząsteczek czynnika VIII |
| EP2297330A4 (en) * | 2008-06-04 | 2012-03-14 | Bayer Healthcare Llc | FVII MUTINES FOR THE TREATMENT OF MORBUS WILLEBRAND |
| PL2291523T3 (pl) | 2008-06-24 | 2015-05-29 | Csl Behring Gmbh | Czynnik VIII, czynnik von Willebranda lub ich kompleksy o wydłużonym okresie półtrwania in vivo |
| DK2349341T3 (da) * | 2008-10-15 | 2014-01-06 | Baxter Int | Pegylering af rekombinante blodkoagulationsfaktorer i nærvær af bundne antistoffer |
| KR20110093775A (ko) * | 2008-11-03 | 2011-08-18 | 바이엘 헬스케어 엘엘씨 | 혈우병 치료 방법 |
| MX339060B (es) | 2008-11-07 | 2016-05-09 | Baxter Int | Formulaciones del factor viii. |
| CA2743904A1 (en) | 2008-11-17 | 2010-05-20 | The Regents Of The University Of Michigan | Cancer vaccine compositions and methods of using the same |
| ES2610356T3 (es) | 2009-02-03 | 2017-04-27 | Amunix Operating Inc. | Polipéptidos recombinantes extendidos y composiciones que comprenden los mismos |
| US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| ES2597954T3 (es) | 2009-07-27 | 2017-01-24 | Baxalta GmbH | Conjugados de proteína de la coagulación sanguínea |
| JP5909755B2 (ja) | 2009-07-27 | 2016-04-27 | リポクセン テクノロジーズ リミテッド | 非血液凝固タンパク質の糖ポリシアル酸化 |
| EP3093029A1 (en) | 2009-07-27 | 2016-11-16 | Baxalta GmbH | Blood coagulation protein conjugates |
| US8809501B2 (en) | 2009-07-27 | 2014-08-19 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| CA2771999A1 (en) | 2009-08-24 | 2011-03-10 | Amunix Operating Inc. | Coagulation factor vii compositions and methods of making and using same |
| SI2506868T1 (en) | 2009-12-06 | 2018-04-30 | Bioverativ Therapeutics Inc. | HYPER AND HYBRID POLYPETTIDES FACTOR VIII-FC AND METHODS FOR THEIR USE |
| ES2993140T3 (en) | 2010-04-02 | 2024-12-23 | Amunix Pharmaceuticals Inc | Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| TW201217527A (en) | 2010-07-09 | 2012-05-01 | Biogen Idec Hemophilia Inc | Processable single chain molecules and polypeptides made using same |
| EP3508573A1 (en) | 2010-07-09 | 2019-07-10 | Bioverativ Therapeutics Inc. | Systems for factor viii processing and methods thereof |
| CA2821945A1 (en) * | 2010-12-16 | 2012-06-21 | Novo Nordisk A/S | Aqueous factor viii solution |
| BR112013015898A2 (pt) | 2010-12-22 | 2018-06-26 | Baxter International Inc. | derivado de ácido graxo solúvel em água, e, métodos para preparar um derivado de ácido graxo e uma proteína terapêutica conjugada. |
| US9486507B2 (en) | 2011-06-10 | 2016-11-08 | Biogen Ma Inc. | Pro-coagulant compounds and methods of use thereof |
| PT3513804T (pt) | 2011-07-08 | 2022-06-02 | Bioverativ Therapeutics Inc | Polipéptidos fator viii híbridos e quiméricos, e métodos de utilização dos mesmos |
| WO2013016454A1 (en) | 2011-07-25 | 2013-01-31 | Biogen Idec Hemophilia Inc. | Assays to monitor bleeding disorders |
| CN104271150A (zh) | 2012-01-12 | 2015-01-07 | 比奥根艾迪克Ma公司 | 嵌合因子viii多肽及其用途 |
| EA038705B1 (ru) | 2012-01-12 | 2021-10-07 | Биовератив Терапьютикс Инк. | Способы снижения иммуногенности фактора свёртывания крови viii у пациентов, получающих лечение фактором viii |
| EP2822577B1 (en) | 2012-02-15 | 2019-02-06 | Bioverativ Therapeutics Inc. | Recombinant factor viii proteins |
| JP6256882B2 (ja) | 2012-02-15 | 2018-01-10 | アムニクス オペレーティング インコーポレイテッド | 第ｖｉｉｉ因子組成物、ならびに組成物の作製方法および用途 |
| WO2013120939A1 (en) | 2012-02-15 | 2013-08-22 | Csl Behring Gmbh | Von willebrand factor variants having improved factor viii binding affinity |
| JP6355563B2 (ja) | 2012-02-27 | 2018-07-11 | アムニクス オペレーティング インコーポレイテッド | Ｘｔｅｎ共役組成物およびそれを製造する方法 |
| MY190257A (en) * | 2012-04-16 | 2022-04-11 | Cantab Biopharmaceuticals Patents Ltd | Optimised subcutaneous therapeutic agents |
| JP2015515482A (ja) | 2012-04-24 | 2015-05-28 | ノヴォ ノルディスク アー／エス | 血友病の治療に適する化合物 |
| WO2013185113A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Procoagulant compounds |
| CA2875247A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Chimeric clotting factors |
| US10023628B2 (en) | 2012-07-06 | 2018-07-17 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor VIII polypeptides and uses thereof |
| CN104661674A (zh) | 2012-07-11 | 2015-05-27 | 阿穆尼克斯运营公司 | 具有xten和血管性血友病因子蛋白的因子viii复合物、及其用途 |
| US10001495B2 (en) | 2012-07-25 | 2018-06-19 | Bioverativ Therapeutics Inc. | Blood factor monitoring assay and uses thereof |
| HK1213767A1 (zh) | 2012-10-18 | 2016-07-15 | Bioverativ Therapeutics Inc. | 使用固定劑量凝血因子的方法 |
| HK1214539A1 (zh) | 2012-10-30 | 2016-07-29 | Bioverativ Therapeutics Inc. | 應用viii因子多肽的方法 |
| CA2891280C (en) | 2012-11-24 | 2018-03-20 | Hangzhou Dac Biotech Co., Ltd. | Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules |
| WO2014127215A1 (en) | 2013-02-15 | 2014-08-21 | Biogen Idec Ma Inc. | Optimized factor viii gene |
| WO2014144549A1 (en) | 2013-03-15 | 2014-09-18 | Biogen Idec Ma Inc. | Factor ix polypeptide formulations |
| EP4122487A1 (en) | 2013-03-15 | 2023-01-25 | Bioverativ Therapeutics Inc. | Factor viii polypeptide formulations |
| EP2796145B1 (en) | 2013-04-22 | 2017-11-01 | CSL Ltd. | A covalent complex of von willebrand factor and faktor viii linked by a disulphide bridge |
| CN113817069A (zh) | 2013-06-28 | 2021-12-21 | 比奥贝拉蒂治疗公司 | 具有xten的凝血酶可裂解连接子和其用途 |
| WO2015021423A2 (en) | 2013-08-08 | 2015-02-12 | Biogen Idec Ma Inc. | Purification of chimeric fviii molecules |
| TW202003554A (zh) | 2013-08-14 | 2020-01-16 | 美商百歐維拉提夫治療公司 | 因子ｖｉｉｉ－ｘｔｅｎ融合物及其用途 |
| EP3065769A4 (en) | 2013-11-08 | 2017-05-31 | Biogen MA Inc. | Procoagulant fusion compound |
| US10325687B2 (en) | 2013-12-06 | 2019-06-18 | Bioverativ Therapeutics Inc. | Population pharmacokinetics tools and uses thereof |
| AU2015204646B2 (en) | 2014-01-10 | 2020-08-27 | Bioverativ Therapeutics Inc. | Factor VIII chimeric proteins and uses thereof |
| WO2015120056A1 (en) | 2014-02-04 | 2015-08-13 | Biogen Ma Inc. | Use of cation-exchange chromatography in the flow-through mode to enrich post-translational modifications |
| US10464955B2 (en) | 2014-02-28 | 2019-11-05 | Hangzhou Dac Biotech Co., Ltd. | Charged linkers and their uses for conjugation |
| US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
| BR112016030950A2 (pt) | 2014-07-02 | 2018-03-27 | Csl Ltd | polipeptídeo modificado que se liga ao fator viii, complexo, composição farmacêutica, métodos para tratar uma coagulopatia, para produzir um polipeptídeo que compreende um vwf modificado e para aumentar a afinidade de ligação ao fator viii do vwf e a meia-vida do fator viii, uso de um polipeptídeo modificado ou de um complexo, polinucleotídeo, plasmídeo ou vetor, e, célula hospedeira. |
| HUE049175T2 (hu) | 2014-09-23 | 2020-09-28 | Hoffmann La Roche | Eljárás anti-CD79b immunkonjugátumok alkalmazására |
| MA40864A (fr) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | Hypotaurine, gaba, bêta-alanine et choline pour la régulation de l'accumulation de sous-produits résiduaires dans des procédés de culture de cellules mammifères |
| ES2772933T3 (es) | 2015-03-06 | 2020-07-08 | CSL Behring Lengnau AG | Factor de von Willebrand modificado que tiene una semivida mejorada |
| EP3297656B1 (en) | 2015-05-22 | 2020-01-08 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for treating hemophilia |
| JP6651548B2 (ja) | 2015-05-22 | 2020-02-19 | ツェー・エス・エル・ベーリング・レングナウ・アクチエンゲゼルシャフト | 改変フォン・ヴィルブランド因子を製造するための方法 |
| CA2989269C (en) | 2015-06-15 | 2020-09-22 | Robert Yongxin Zhao | Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule |
| NZ739830A (en) | 2015-07-12 | 2021-12-24 | Hangzhou Dac Biotech Co Ltd | Bridge linkers for conjugation of cell-binding molecules |
| US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
| EA201890423A1 (ru) | 2015-08-03 | 2018-07-31 | Биовератив Терапьютикс Инк. | Слитые белки фактора ix, способы их получения и применения |
| CA3005565A1 (en) | 2015-11-13 | 2017-05-18 | Baxalta Incorporated | Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a |
| EA202190827A1 (ru) | 2015-11-13 | 2021-11-30 | Баксалта Инкорпорейтед | Вирусные векторы, кодирующие рекомбинантные варианты fviii с повышенной экспрессией для генной терапии гемофилии a |
| DK3400002T3 (da) | 2016-01-07 | 2022-04-11 | CSL Behring Lengnau AG | Muteret, trunkeret von willebrand faktor |
| RU2018128613A (ru) | 2016-01-07 | 2020-02-07 | Цсл Беринг Ленгнау Аг | Мутированный фактор фон виллебранда |
| CA3012695A1 (en) | 2016-02-01 | 2017-08-10 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
| WO2017222337A1 (ko) | 2016-06-24 | 2017-12-28 | 재단법인 목암생명과학연구소 | Fviii 및 vwf 인자를 포함하는 키메라 단백질 및 그 용도 |
| US11814421B2 (en) | 2016-11-11 | 2023-11-14 | CSL Behring Lengnau AG | Truncated von Willebrand Factor polypeptides for treating hemophilia |
| SG11201903954WA (en) | 2016-11-11 | 2019-05-30 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder |
| KR20220150408A (ko) | 2016-11-14 | 2022-11-10 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| MX2019006444A (es) | 2016-12-02 | 2019-10-30 | Bioverativ Therapeutics Inc | Métodos de tratamiento de artropatía hemofílica utilizando factores de coagulación quiméricos. |
| JP2019536794A (ja) | 2016-12-02 | 2019-12-19 | バイオベラティブ セラピューティクス インコーポレイテッド | 凝固因子に対する免疫寛容を誘導する方法 |
| NZ762100A (en) | 2017-08-09 | 2025-12-19 | Bioverativ Therapeutics Inc | Nucleic acid molecules and uses thereof |
| AU2019215063B2 (en) | 2018-02-01 | 2025-10-16 | Bioverativ Therapeutics, Inc. | Use of lentiviral vectors expressing Factor VIII |
| BR112020020084A2 (pt) | 2018-04-04 | 2021-01-05 | Sigilon Therapeutics, Inc. | Partícula, preparação de uma pluralidade de partículas, método de preparação de uma partícula, e, composição de partículas. |
| PL3793588T3 (pl) | 2018-05-18 | 2025-09-01 | Bioverativ Therapeutics Inc. | Sposoby leczenia hemofilii a |
| US12091675B2 (en) | 2018-07-16 | 2024-09-17 | Takeda Pharmaceutical Company Limited | Gene therapy of hemophilia a using viral vectors encoding recombinant FVIII variants with increased expression |
| EP3833766A1 (en) | 2018-08-09 | 2021-06-16 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof for non-viral gene therapy |
| UY38389A (es) | 2018-09-27 | 2020-04-30 | Sigilon Therapeutics Inc | Dispositivos implantables para terapia celular y métodos relacionados |
| TWI851647B (zh) | 2019-01-16 | 2024-08-11 | 日商武田藥品工業股份有限公司 | 用於a型血友病基因治療之編碼表現增加之重組fviii變異體的病毒載體 |
| CN114007637A (zh) | 2019-06-19 | 2022-02-01 | 比奥维拉迪维治疗股份有限公司 | 用于治疗血友病和低骨矿物质密度的重组因子viii-fc |
| KR20220097891A (ko) | 2019-09-30 | 2022-07-08 | 바이오버라티브 테라퓨틱스 인크. | 렌티바이러스 벡터 제형 |
| WO2021119357A2 (en) | 2019-12-12 | 2021-06-17 | Baxalta Incorporated | Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression |
| MX2023000156A (es) | 2020-06-24 | 2023-02-16 | Bioverativ Therapeutics Inc | Metodos para la eliminacion de factor viii libre de preparaciones de vectores lentivirales modificados para expresar dicha proteina. |
| EP4355768A1 (en) | 2021-06-14 | 2024-04-24 | Takeda Pharmaceutical Company Limited | Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression |
| AU2022332276A1 (en) | 2021-08-23 | 2024-04-04 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
| TW202346327A (zh) | 2021-09-30 | 2023-12-01 | 美商百歐維拉提夫治療公司 | 編碼具有降低免疫原性的因子ｖｉｉｉ多肽之核酸 |
| EP4426727A2 (en) | 2021-11-03 | 2024-09-11 | Hangzhou Dac Biotech Co., Ltd. | Specific conjugation of an antibody |
| WO2024081309A1 (en) | 2022-10-11 | 2024-04-18 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
| WO2025008774A1 (en) | 2023-07-05 | 2025-01-09 | Takeda Pharmaceutical Company Limited | Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59172425A (ja) * | 1983-03-18 | 1984-09-29 | Nippon Chemiphar Co Ltd | 新規な血液凝固因子誘導体およびその製造法ならびにそれを含有する血液凝固促進剤 |
| US4970300A (en) * | 1985-02-01 | 1990-11-13 | New York University | Modified factor VIII |
| SE8501050D0 (sv) * | 1985-03-05 | 1985-03-05 | Kabivitrum Ab | Biologically active fragments of human antihemophilic factor and method for preparation thereof |
| DE3717210C2 (de) * | 1987-05-22 | 1993-11-25 | Diagen Inst Molekularbio | Verfahren zur Modifizierung von Nukleinsäuren |
| US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| SE465222C5 (sv) * | 1989-12-15 | 1998-02-10 | Pharmacia & Upjohn Ab | Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning |
| JPH06506217A (ja) * | 1991-03-18 | 1994-07-14 | エンゾン，インコーポレーテッド | ポリペプチドまたはグリコポリペプチドとポリマーとのヒドラジン含有結合体 |
| US5169627A (en) * | 1991-10-28 | 1992-12-08 | Mount Sinai School Of Medicine Of The City University Of New York | Oral pharmaceutical composition containing a polyethylene glycol-immunoglobulin G conjugate for reconstitution of secretory immunity and method of reconstituting secretory immunity |
| GB9225448D0 (en) * | 1992-12-04 | 1993-01-27 | Erba Carlo Spa | Improved synthesis of polymer bioactive conjugates |
| WO1994015625A1 (en) * | 1993-01-15 | 1994-07-21 | Enzon, Inc. | Factor viii - polymeric conjugates |
| US5621039A (en) * | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
-
1995
- 1995-09-29 SE SE9503380A patent/SE9503380D0/xx unknown
-
1996
- 1996-09-27 DK DK96932915T patent/DK0871649T3/da active
- 1996-09-27 ZA ZA968139A patent/ZA968139B/xx unknown
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- 1996-09-27 DK DK02013607T patent/DK1260582T3/da active
- 1996-09-27 EP EP02013607A patent/EP1260582B1/en not_active Expired - Lifetime
- 1996-09-27 HU HU9901203A patent/HU221208B1/hu unknown
- 1996-09-27 AT AT02013607T patent/ATE283351T1/de active
- 1996-09-27 ES ES02013607T patent/ES2236396T3/es not_active Expired - Lifetime
- 1996-09-27 EP EP96932915A patent/EP0871649B1/en not_active Expired - Lifetime
- 1996-09-27 NZ NZ319322A patent/NZ319322A/en not_active IP Right Cessation
- 1996-09-27 DE DE69634373T patent/DE69634373T2/de not_active Expired - Lifetime
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- 1996-09-27 US US09/029,672 patent/US6048720A/en not_active Expired - Lifetime
- 1996-09-27 AU AU71517/96A patent/AU706246B2/en not_active Expired
- 1996-09-27 PT PT02013607T patent/PT1260582E/pt unknown
- 1996-09-27 DE DE69633952T patent/DE69633952T2/de not_active Expired - Lifetime
- 1996-09-27 ES ES96932915T patent/ES2187676T3/es not_active Expired - Lifetime
- 1996-09-27 AT AT02013613T patent/ATE289321T1/de active
- 1996-09-27 BR BR9610695A patent/BR9610695A/pt unknown
- 1996-09-27 EP EP02013613A patent/EP1258497B1/en not_active Expired - Lifetime
- 1996-09-27 CA CA2231801A patent/CA2231801C/en not_active Expired - Lifetime
- 1996-09-27 WO PCT/SE1996/001215 patent/WO1997011957A1/en not_active Ceased
- 1996-09-27 AT AT96932915T patent/ATE228531T1/de active
- 1996-09-27 DE DE69625085T patent/DE69625085T2/de not_active Expired - Lifetime
- 1996-09-27 PL PL96325958A patent/PL185821B1/pl unknown
- 1996-09-27 DK DK02013613T patent/DK1258497T3/da active
- 1996-09-27 JP JP51336397A patent/JP3911023B2/ja not_active Expired - Lifetime
- 1996-09-27 PT PT02013613T patent/PT1258497E/pt unknown
-
1998
- 1998-03-27 NO NO19981408A patent/NO321096B1/no not_active IP Right Cessation
-
2005
- 2005-04-21 NO NO20051950A patent/NO20051950L/no not_active Application Discontinuation
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