CY1117880T1 - Συζυγη πρωτεϊνων πηξης αιματος - Google Patents
Συζυγη πρωτεϊνων πηξης αιματοςInfo
- Publication number
- CY1117880T1 CY1117880T1 CY20161100787T CY161100787T CY1117880T1 CY 1117880 T1 CY1117880 T1 CY 1117880T1 CY 20161100787 T CY20161100787 T CY 20161100787T CY 161100787 T CY161100787 T CY 161100787T CY 1117880 T1 CY1117880 T1 CY 1117880T1
- Authority
- CY
- Cyprus
- Prior art keywords
- soluble polymer
- coupling
- water
- oxidized carbohydrate
- concentration
- Prior art date
Links
- 102000004506 Blood Proteins Human genes 0.000 title 1
- 108010017384 Blood Proteins Proteins 0.000 title 1
- 229920003169 water-soluble polymer Polymers 0.000 abstract 4
- 230000008878 coupling Effects 0.000 abstract 3
- 238000010168 coupling process Methods 0.000 abstract 3
- 238000005859 coupling reaction Methods 0.000 abstract 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 abstract 2
- 150000001720 carbohydrates Chemical class 0.000 abstract 2
- 239000000463 material Substances 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 125000000539 amino acid group Chemical group 0.000 abstract 1
- 125000003277 amino group Chemical group 0.000 abstract 1
- 230000023555 blood coagulation Effects 0.000 abstract 1
- 125000000837 carbohydrate group Chemical group 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 230000000269 nucleophilic effect Effects 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
Classifications
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
-
- 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)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- 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
- A61K47/61—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 the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
-
- 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)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
-
- 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
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21021—Coagulation factor VIIa (3.4.21.21)
-
- 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)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Materials Engineering (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22882809P | 2009-07-27 | 2009-07-27 | |
| US34713610P | 2010-05-21 | 2010-05-21 | |
| PCT/US2010/043242 WO2011017055A2 (en) | 2009-07-27 | 2010-07-26 | Blood coagulation protein conjugates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CY1117880T1 true CY1117880T1 (el) | 2017-05-17 |
Family
ID=46582462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CY20161100787T CY1117880T1 (el) | 2009-07-27 | 2016-08-10 | Συζυγη πρωτεϊνων πηξης αιματος |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US8637640B2 (enExample) |
| EP (1) | EP2459224B1 (enExample) |
| JP (1) | JP5908401B2 (enExample) |
| KR (3) | KR101832937B1 (enExample) |
| CN (1) | CN102497884A (enExample) |
| AR (1) | AR077600A1 (enExample) |
| AU (1) | AU2010281453C1 (enExample) |
| BR (1) | BR112012001814A8 (enExample) |
| CA (1) | CA2769326A1 (enExample) |
| CY (1) | CY1117880T1 (enExample) |
| DK (1) | DK2459224T3 (enExample) |
| ES (1) | ES2597954T3 (enExample) |
| GB (1) | GB2472303A (enExample) |
| HR (1) | HRP20160916T1 (enExample) |
| MX (1) | MX2012001207A (enExample) |
| NZ (1) | NZ598056A (enExample) |
| RU (1) | RU2595442C2 (enExample) |
| SG (1) | SG178141A1 (enExample) |
| SM (1) | SMT201600314B (enExample) |
| TW (1) | TWI537006B (enExample) |
| WO (1) | WO2011017055A2 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2101821T3 (da) | 2006-12-15 | 2014-10-06 | Baxter Healthcare Sa | Faktor VIIA-(poly)sialinsyre-konjugat med forlænget halveringstid in vivo |
| RU2744370C2 (ru) | 2009-07-27 | 2021-03-05 | Баксалта Инкорпорейтед | Конъюгаты белков свертывания крови |
| BR112012001814A8 (pt) | 2009-07-27 | 2018-02-06 | Baxalta GmbH | Conjugados de proteína de coagulação sanguínea |
| EP3081233B1 (en) | 2009-07-27 | 2020-12-23 | Baxalta GmbH | Glycopolysialylation of proteins other than blood coagulation proteins |
| US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| US8809501B2 (en) | 2009-07-27 | 2014-08-19 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| LT2536399T (lt) * | 2010-02-21 | 2020-03-10 | Bayer Healthcare Llc | Biomolekulių aktyvinimo ir konjugavimo būdas |
| TWI534152B (zh) * | 2010-07-30 | 2016-05-21 | 巴克斯特國際公司 | 用於肟連接的親核性催化劑 |
| AU2015275284C1 (en) * | 2010-07-30 | 2018-04-05 | Takeda Pharmaceutical Company Limited | Nucleophilic Catalysts for Oxime Linkage |
| PL2710375T3 (pl) | 2011-05-18 | 2019-07-31 | Baxalta GmbH | Testy aktywności zależne od modyfikacji |
| WO2013123457A1 (en) * | 2012-02-15 | 2013-08-22 | Biogen Idec Ma Inc. | Recombinant factor viii proteins |
| HK1200695A1 (en) * | 2012-04-16 | 2015-08-14 | Cantab Biopharmaceuticals Patents Limited | Optimised subcutaneous therapeutic agents |
| AU2013204754C1 (en) * | 2012-05-16 | 2018-10-11 | Takeda Pharmaceutical Company Limited | Nucleophilic Catalysts for Oxime Linkage |
| EP2828088B1 (en) | 2012-07-03 | 2020-05-27 | Hewlett-Packard Development Company, L.P. | Fluid ejection apparatus |
| TW201731869A (zh) * | 2015-12-03 | 2017-09-16 | 百克莎塔股份有限公司 | 具有延長之半衰期及降低之配位體結合性質的因子viii |
| CN105801870B (zh) * | 2016-04-08 | 2018-08-21 | 北京华熙海御科技有限公司 | 一种聚唾液酸-透明质酸复合凝胶的制备方法及所得产品和应用 |
| WO2018017923A1 (en) * | 2016-07-22 | 2018-01-25 | Nektar Therapeutics | Conjugates of a factor viii moiety having an oxime-containing linkage |
| KR20190086269A (ko) * | 2018-01-12 | 2019-07-22 | 재단법인 목암생명과학연구소 | 체내 지속형 재조합 당단백질 및 이의 제조방법 |
| CA3126476A1 (en) | 2019-01-23 | 2020-07-30 | Regeneron Pharmaceuticals, Inc. | Treatment of ophthalmic conditions with angiopoietin-like 7 (angptl7) inhibitors |
| US11845989B2 (en) | 2019-01-23 | 2023-12-19 | Regeneron Pharmaceuticals, Inc. | Treatment of ophthalmic conditions with angiopoietin-like 7 (ANGPTL7) inhibitors |
| CN111450080A (zh) * | 2020-03-31 | 2020-07-28 | 天津大学 | 一种IgA肾病治疗纳米制剂的合成方法 |
| WO2022182768A1 (en) | 2021-02-26 | 2022-09-01 | Regeneron Pharmaceuticals, Inc. | Treatment of inflammation with glucocorticoids and angiopoietin-like 7 (angptl7) inhibitors |
Family Cites Families (133)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS54113492A (en) | 1978-02-24 | 1979-09-05 | Sanyo Chem Ind Ltd | Preparation of glucoprotein derivative |
| US4356170A (en) | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
| US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
| US4970300A (en) | 1985-02-01 | 1990-11-13 | New York University | Modified factor VIII |
| US5198349A (en) | 1986-01-03 | 1993-03-30 | Genetics Institute, Inc. | Method for producing factor VIII:C and analogs |
| US5250421A (en) | 1986-01-03 | 1993-10-05 | Genetics Institute, Inc. | Method for producing factor VIII:C-type proteins |
| JPH0387173A (ja) | 1987-09-10 | 1991-04-11 | Teijin Ltd | ヒト活性化天然型ファクター8cの製造方法及びそれに用いる形質転換体 |
| US5153265A (en) | 1988-01-20 | 1992-10-06 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| US4966999A (en) | 1988-06-07 | 1990-10-30 | Cytogen Corporation | Radiohalogenated compounds for site specific labeling |
| US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for 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 |
| SE466754B (sv) | 1990-09-13 | 1992-03-30 | Berol Nobel Ab | Saett att kovalent binda biopolymerer till hydrofila ytor |
| CA2073511A1 (en) | 1990-11-14 | 1992-05-29 | Matthew R. Callstrom | Conjugates of poly(vinylsaccharide) with proteins for the stabilization of proteins |
| AU1676992A (en) | 1991-03-18 | 1992-10-21 | Enzon, Inc. | Hydrazine containing conjugates of polypeptides and glycopolypeptides with polymers |
| US5846951A (en) | 1991-06-06 | 1998-12-08 | The School Of Pharmacy, University Of London | Pharmaceutical compositions |
| US6037452A (en) * | 1992-04-10 | 2000-03-14 | Alpha Therapeutic Corporation | Poly(alkylene oxide)-Factor VIII or Factor IX conjugate |
| WO1994005332A2 (en) | 1992-09-01 | 1994-03-17 | Berlex Laboratories, Inc. | Glycolation of glycosylated macromolecules |
| ATE198277T1 (de) | 1992-10-02 | 2001-01-15 | Genetics Inst | Zusammensetzung, welche den koagulationsfaktor viii beinhaltet; verfahren zu deren herstellung und die benutzung eines oberflächenaktiven stoffes als stabilisator |
| NZ250375A (en) | 1992-12-09 | 1995-07-26 | Ortho Pharma Corp | Peg hydrazone and peg oxime linkage forming reagents and protein derivatives |
| FI935485L (fi) * | 1992-12-09 | 1994-06-10 | Ortho Pharma Corp | PEG-hydratsoni- ja PEG-oksiimisidoksen muodostavat reagenssit ja niiden proteiinijohdannaiset |
| US5298643A (en) * | 1992-12-22 | 1994-03-29 | Enzon, Inc. | Aryl imidate activated polyalkylene oxides |
| WO1994015625A1 (en) * | 1993-01-15 | 1994-07-21 | Enzon, Inc. | Factor viii - polymeric conjugates |
| WO1994028024A1 (en) | 1993-06-01 | 1994-12-08 | Enzon, Inc. | Carbohydrate-modified polymer conjugates with erythropoietic activity |
| US5621039A (en) * | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
| SE504074C2 (sv) | 1993-07-05 | 1996-11-04 | Pharmacia Ab | Proteinberedning för subkutan, intramuskulär eller intradermal administrering |
| CA2204726A1 (en) | 1994-11-09 | 1996-12-27 | Robin E. Offord | Functionalized polymers for site-specific attachment |
| WO1996040731A1 (en) | 1995-06-07 | 1996-12-19 | Mount Sinai School Of Medicine Of The City University Of New York | Pegylated modified proteins |
| WO1996040662A2 (en) | 1995-06-07 | 1996-12-19 | Cellpro, Incorporated | Aminooxy-containing linker compounds and their application in conjugates |
| SE9503380D0 (sv) | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
| US6323322B1 (en) | 1997-04-30 | 2001-11-27 | Enzon, Inc. | Single-chain antigen-binding proteins capable of glycosylation, production and uses thereof |
| US6183738B1 (en) | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| PT1012259E (pt) | 1997-06-04 | 2009-11-06 | Oxford Biomedica Ltd | Vector dirigido a tumor |
| WO1999003496A1 (en) | 1997-07-21 | 1999-01-28 | The University Of North Carolina At Chapel Hill | Factor ix antihemophilic factor with increased clotting activity |
| WO1999028455A1 (de) | 1997-12-03 | 1999-06-10 | Roche Diagnostics Gmbh | Verfahren zur herstellung von polypeptiden mit geeigneter glykosilierung |
| US5985263A (en) | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| DE69914611T2 (de) | 1998-08-28 | 2004-12-23 | Gryphon Therapeutics, Inc., South San Francisco | Verfahren zur herstellung von polyamidketten von genauer länge und deren konjugate mit proteinen |
| DK1656952T3 (da) | 1998-10-16 | 2014-01-20 | Biogen Idec Inc | Polyalkylenglycolkonjugater af interferon beta-1A og anvendelser deraf |
| DE19852729A1 (de) | 1998-11-16 | 2000-05-18 | Werner Reutter | Rekombinante Glycoproteine, Verfahren zu ihrer Herstellung, sie enthaltende Arzneimittel und ihre Verwendung |
| EP1820516B1 (en) | 1999-02-22 | 2013-07-24 | University of Connecticut | Novel albumin-free factor VIII formulations |
| US6531122B1 (en) | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
| US7230081B1 (en) | 1999-11-12 | 2007-06-12 | Maxygen Holdings, Ltd. | Interferon gamma conjugates |
| US7074878B1 (en) | 1999-12-10 | 2006-07-11 | Harris J Milton | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
| WO2001058935A2 (en) | 2000-02-11 | 2001-08-16 | Maxygen Aps | FACTOR VII OR VIIa-LIKE MOLECULES |
| US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| JP5090605B2 (ja) | 2000-05-03 | 2012-12-05 | 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の皮下投与 |
| WO2001083725A1 (en) | 2000-05-03 | 2001-11-08 | Novo Nordisk A/S | Human coagulation factor vii variants |
| CA2414076A1 (en) * | 2000-06-08 | 2001-12-13 | La Jolla Pharmaceutical Company | Multivalent platform molecules comprising high molecular weight polyethylene oxide |
| US6423826B1 (en) | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
| US7118737B2 (en) | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| EP2226385B1 (en) | 2000-09-13 | 2013-07-10 | Novo Nordisk Health Care AG | 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 |
| ES2432967T3 (es) | 2001-03-22 | 2013-12-05 | Novo Nordisk Health Care Ag | Derivados del Factor VII de coagulación |
| US6913915B2 (en) | 2001-08-02 | 2005-07-05 | Phoenix Pharmacologics, Inc. | PEG-modified uricase |
| US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7265084B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| EP2292273A3 (en) | 2001-10-10 | 2011-11-23 | BioGeneriX AG | Remodeling and glycoconjugation of peptides |
| US7795210B2 (en) | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
| EP1446438A2 (en) | 2001-11-07 | 2004-08-18 | Nektar Therapeutics Al, Corporation | Branched polymers and their conjugates |
| JP2005535280A (ja) | 2001-11-28 | 2005-11-24 | ネオーズ テクノロジーズ, インコーポレイテッド | エンドグリカナーゼを用いる糖タンパク質のリモデリング |
| JP2005510229A (ja) | 2001-11-28 | 2005-04-21 | ネオーズ テクノロジーズ, インコーポレイテッド | アミダーゼを用いる糖タンパク質のリモデリング |
| ES2363205T3 (es) | 2002-06-21 | 2011-07-26 | Novo Nordisk Health Care Ag | Glicoformas del factor vii pegilado. |
| US7087229B2 (en) | 2003-05-30 | 2006-08-08 | Enzon Pharmaceuticals, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| US7122189B2 (en) | 2002-08-13 | 2006-10-17 | Enzon, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| MXPA05002594A (es) | 2002-09-11 | 2005-05-27 | Fresenius Kabi Gmbh | Derivados de polipeptidos con hidroxialquilalmidon, especialmente derivados de eritropoyetina con hidroxialquilalmidon. |
| US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| ATE444984T1 (de) | 2002-12-31 | 2009-10-15 | Nektar Therapeutics Al Corp | Hydrolysestabile maleimidendgruppen-enthaltende polymere |
| KR101031206B1 (ko) | 2002-12-31 | 2011-04-27 | 넥타르 테라퓨틱스 | 말레암산 중합체 유도체 및 이의 바이오컨쥬게이트 |
| EP1596887B1 (en) | 2003-02-26 | 2022-03-23 | Nektar Therapeutics | Polymer-factor viii moiety conjugates |
| WO2004089280A2 (en) | 2003-04-08 | 2004-10-21 | Yeda Research And Development Co. Ltd. | Reversible pegylated drugs |
| WO2005014024A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of a polymer and a protein linked by an oxime linking group |
| WO2005014035A2 (en) | 2003-08-08 | 2005-02-17 | Novo Nordisk Health Care Ag | Use of galactose oxidase for selective chemical conjugation of protractor molecules to proteins of therapeutic interest |
| EP1654290B1 (en) | 2003-08-12 | 2019-03-13 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| ES2294535T3 (es) | 2003-08-12 | 2008-04-01 | Lipoxen Technologies Limited | Derivados del acido polisialico. |
| PL1653994T3 (pl) * | 2003-08-12 | 2010-05-31 | Tigenix Nv | Zastosowanie chemokiny CXCL6 w profilaktyce lub naprawie ubytków chrząstki |
| US8633157B2 (en) | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
| ES2422187T3 (es) | 2003-12-03 | 2013-09-09 | Biogenerix Ag | Factor estimulante de colonias de granulocitos glicopegilados |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| JP4738346B2 (ja) | 2003-12-03 | 2011-08-03 | ノヴォ ノルディスク アー/エス | GlycoPEG化された第IX因子 |
| NZ548123A (en) | 2004-01-08 | 2010-05-28 | Novo Nordisk As | O-linked glycosylation of peptides |
| US20060109877A1 (en) * | 2004-06-21 | 2006-05-25 | Caton John W | External cavity laser with adaptive fiber bragg grating (FBG) for minimizing noise related to stimulated brillouin scattering (SBS) in dispersive fiber links |
| WO2006020372A2 (en) | 2004-07-23 | 2006-02-23 | Neose Technologies, Inc. | Enzymatic modification of glycopeptides |
| US20090176967A1 (en) | 2004-08-02 | 2009-07-09 | Novo Nordisk Healthcare A/G | Conjugation of FVII |
| EP1776389B1 (en) | 2004-08-12 | 2016-06-29 | Lipoxen Technologies Limited | Sialic acid derivatives |
| CN101039965A (zh) * | 2004-08-12 | 2007-09-19 | 利普生技术有限公司 | 唾液酸衍生物 |
| WO2006031811A2 (en) | 2004-09-10 | 2006-03-23 | Neose Technologies, Inc. | Glycopegylated interferon alpha |
| DK2371856T3 (en) | 2004-11-12 | 2022-08-08 | Bayer Healthcare Llc | Site-directed modifikation af FVIII |
| AU2005322067B8 (en) | 2004-12-27 | 2012-07-26 | Takeda Pharmaceutical Company Limited | Polymer-von Willebrand factor-conjugates |
| EP1838332A1 (en) | 2005-01-06 | 2007-10-03 | Neose Technologies, Inc. | Glycoconjugation using saccharyl fragments |
| US20080255026A1 (en) | 2005-05-25 | 2008-10-16 | Glycopegylated Factor 1X | Glycopegylated Factor Ix |
| CA2611823C (en) | 2005-06-16 | 2013-07-30 | Nektar Therapeutics Al, Corporation | Conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates |
| US8633300B2 (en) | 2005-06-17 | 2014-01-21 | Novo Nordisk Healthcare Ag | Selective reduction and derivatization of engineered proteins comprising at least one non-native cysteine |
| US20090017007A1 (en) | 2005-08-26 | 2009-01-15 | Maxygen Holdings Ltd. | Liquid factor vii composition |
| JP5405122B2 (ja) | 2005-12-21 | 2014-02-05 | ワイス・エルエルシー | 低粘度のタンパク質製剤およびその用途 |
| US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| WO2007126808A1 (en) | 2006-03-31 | 2007-11-08 | Baxter International Inc | Pegylated factor viii |
| WO2007140282A1 (en) | 2006-05-24 | 2007-12-06 | Peg Biosciences | Peg linker compounds and biologically active conjugates thereof |
| US7939632B2 (en) | 2006-06-14 | 2011-05-10 | Csl Behring Gmbh | Proteolytically cleavable fusion proteins with high molar specific activity |
| PL2049692T3 (pl) | 2006-07-13 | 2016-08-31 | Serum Inst India Ltd | Sposób wytwarzania poli(kwasu sialowego) o wysokiej czystości |
| CN103169984B (zh) | 2006-07-25 | 2016-08-03 | 利普生技术有限公司 | N末端聚唾液酸化 |
| US20100056428A1 (en) * | 2006-09-01 | 2010-03-04 | Novo Nordisk Health Care Ag | Modified proteins |
| US8969532B2 (en) | 2006-10-03 | 2015-03-03 | Novo Nordisk A/S | Methods for the purification of polypeptide conjugates comprising polyalkylene oxide using hydrophobic interaction chromatography |
| DK2101821T3 (da) | 2006-12-15 | 2014-10-06 | Baxter Healthcare Sa | Faktor VIIA-(poly)sialinsyre-konjugat med forlænget halveringstid in vivo |
| JP5558106B2 (ja) | 2007-01-03 | 2014-07-23 | ノボ ノルディスク ヘルス ケア アーゲー | 凝固第vii因子関連ポリペプチドの皮下投与 |
| WO2008119815A1 (en) | 2007-04-02 | 2008-10-09 | Novo Nordisk A/S | Subcutaneous administration of coagulation factor ix |
| TWI569810B (zh) * | 2007-06-26 | 2017-02-11 | 巴克斯歐塔公司 | 可水解之聚合茀基甲氧基羰基-連接劑 |
| CA2690440A1 (en) | 2007-07-03 | 2009-01-08 | Children's Hospital & Research Center At Oakland | Oligosialic acid derivatives, methods of manufacture, and immunological uses |
| US20100239517A1 (en) | 2007-10-09 | 2010-09-23 | Stephen Brocchini | Novel conjugated proteins and peptides |
| CN102037004A (zh) | 2008-01-08 | 2011-04-27 | 生物种属学股份公司 | 使用寡糖基转移酶的多肽的糖缀合 |
| US20130189239A1 (en) | 2008-02-27 | 2013-07-25 | Novo Nordisk A/S | Conjugated Factor VIII Molecules |
| KR20110016440A (ko) | 2008-04-24 | 2011-02-17 | 셀틱 파르마 피이지 엘티디. | 연장된 반감기를 가진 제 ⅰⅹ 인자 접합체 |
| EP2285412A1 (en) | 2008-05-23 | 2011-02-23 | Novo Nordisk Health Care AG | Formulations of peg-functionalised serine proteases with high concentrations of an aromatic preservative |
| US20110112029A1 (en) | 2008-05-23 | 2011-05-12 | Novo Nordisk Health Care Ag | Low viscosity compositions comprising a pegylated gla-domain containing protein |
| JP5674650B2 (ja) | 2008-06-04 | 2015-02-25 | バイエル・ヘルスケア・エルエルシー | フォン・ヴィレブランド病の処置のためのfviii変異タンパク質 |
| ES2560807T3 (es) | 2008-07-21 | 2016-02-22 | Polytherics Limited | Nuevos reactivos y procedimiento de conjugación de moléculas biológicas |
| EP2352515A4 (en) | 2008-11-03 | 2012-04-25 | Bayer Healthcare Llc | METHOD FOR TREATING HEMOPHILIA |
| CA2748662A1 (en) | 2009-01-19 | 2010-07-22 | Bayer Healthcare Llc | Protein conjugate having an endopeptidase-cleavable bioprotective moiety |
| US20110306551A1 (en) | 2009-02-19 | 2011-12-15 | Novo Nordisk A/S | Modification of Factor VIII |
| US9005598B2 (en) | 2009-03-04 | 2015-04-14 | Polytherics Limited | Conjugated proteins and peptides |
| WO2010120365A2 (en) | 2009-04-16 | 2010-10-21 | Wu Nian | Protein-carrier conjugates |
| GB0908393D0 (en) | 2009-05-15 | 2009-06-24 | Almac Sciences Scotland Ltd | Labelling method |
| BR112012001814A8 (pt) | 2009-07-27 | 2018-02-06 | Baxalta GmbH | Conjugados de proteína de coagulação sanguínea |
| EP3081233B1 (en) | 2009-07-27 | 2020-12-23 | Baxalta GmbH | Glycopolysialylation of proteins other than blood coagulation proteins |
| EA201290069A1 (ru) | 2009-07-31 | 2012-07-30 | Байер Хелскер Ллс | Модифицированные полипептиды фактора ix и их применения |
| DE102009028526A1 (de) | 2009-08-13 | 2011-02-24 | Leibniz-Institut Für Polymerforschung Dresden E.V. | Verfahren zur Modifikation und Funktionalisierung von Sacchariden |
| EP2480578A4 (en) | 2009-09-25 | 2013-04-17 | Vybion Inc | MODIFICATION OF POLYPEPTIDE |
| CN107383158A (zh) | 2009-11-24 | 2017-11-24 | 诺沃—诺迪斯克保健股份有限公司 | 纯化聚乙二醇化蛋白质的方法 |
| EP2536753B1 (en) | 2010-02-16 | 2017-12-20 | Novo Nordisk A/S | Factor viii molecules with reduced vwf binding |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| GB201007357D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIII |
| JP2014503495A (ja) | 2010-11-15 | 2014-02-13 | バイオジェン アイデック インコーポレイテッド | 過負荷結合および溶出クロマトグラフィによる選択生成物アイソフォームの富化および濃縮 |
| EP4169525A1 (en) | 2011-07-08 | 2023-04-26 | Bioverativ Therapeutics Inc. | Factor viii chimeric and hybrid polypeptides, and methods of use thereof |
-
2010
- 2010-07-26 BR BR112012001814A patent/BR112012001814A8/pt not_active Application Discontinuation
- 2010-07-26 GB GB1012482A patent/GB2472303A/en not_active Withdrawn
- 2010-07-26 ES ES10738119.6T patent/ES2597954T3/es active Active
- 2010-07-26 WO PCT/US2010/043242 patent/WO2011017055A2/en not_active Ceased
- 2010-07-26 RU RU2012106589/15A patent/RU2595442C2/ru not_active IP Right Cessation
- 2010-07-26 EP EP10738119.6A patent/EP2459224B1/en active Active
- 2010-07-26 JP JP2012522940A patent/JP5908401B2/ja active Active
- 2010-07-26 NZ NZ598056A patent/NZ598056A/en unknown
- 2010-07-26 AU AU2010281453A patent/AU2010281453C1/en active Active
- 2010-07-26 KR KR1020127003964A patent/KR101832937B1/ko active Active
- 2010-07-26 US US12/843,542 patent/US8637640B2/en active Active
- 2010-07-26 HR HRP20160916TT patent/HRP20160916T1/hr unknown
- 2010-07-26 TW TW099124493A patent/TWI537006B/zh active
- 2010-07-26 KR KR1020187005130A patent/KR102068133B1/ko active Active
- 2010-07-26 CN CN2010800370028A patent/CN102497884A/zh active Pending
- 2010-07-26 CA CA2769326A patent/CA2769326A1/en not_active Abandoned
- 2010-07-26 MX MX2012001207A patent/MX2012001207A/es active IP Right Grant
- 2010-07-26 SG SG2012006094A patent/SG178141A1/en unknown
- 2010-07-26 DK DK10738119.6T patent/DK2459224T3/en active
- 2010-07-26 KR KR1020127003344A patent/KR101759300B1/ko not_active Expired - Fee Related
- 2010-07-27 AR ARP100102720A patent/AR077600A1/es active IP Right Grant
-
2013
- 2013-12-20 US US14/136,266 patent/US20140107320A1/en not_active Abandoned
-
2016
- 2016-01-06 US US14/988,931 patent/US20160120994A1/en not_active Abandoned
- 2016-08-10 CY CY20161100787T patent/CY1117880T1/el unknown
- 2016-09-09 SM SM201600314T patent/SMT201600314B/it unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CY1121943T1 (el) | Πυρηνοφιλοι καταλυτες για συνδεση οξιμων | |
| MX2012001207A (es) | Conjugados proteicos de coagulacion sanguínea. | |
| Conroy et al. | Antibody production, design and use for biosensor-based applications | |
| AR081246A1 (es) | Proteinas de union a il-1 | |
| CY1124819T1 (el) | Ανθρωπινα αντισωματα αντι- fel d1 και μεθοδοι χρησης αυτων | |
| CY1119930T1 (el) | Λευκολεκτινες και χρησεις αυτων | |
| EA201790935A1 (ru) | Нуклеофильные катализаторы для оксимного связывания | |
| MX2012001000A (es) | Metodo y kit para la deteccion de un microorganismo. | |
| CY1121632T1 (el) | Η rv2386c πρωτεϊνη φυματιωσης, συνθεσεις και χρησεις αυτης | |
| CY1114736T1 (el) | Προερχομενες απο παπια εμβρυϊκες βλαστικες κυτταρικες σειρες για την παραγωγη ιικων εμβολιων | |
| ES2570731T3 (es) | Método de detección de cáncer | |
| AR078795A1 (es) | Inmunoglobulinas con dominio variable dual y usos de las mismas | |
| AR076508A1 (es) | Inmunoglobulina con dominio variable dual y usos de la misma | |
| ATE542903T1 (de) | Luciferase-biosensoren für camp | |
| MX349996B (es) | Metodos y composiciones para diagnostico y tratamiento del cancer. | |
| MA32766B1 (fr) | Membrane biomimetique formee a partir d'un conjugue vesicule-fil | |
| EP2582849A4 (en) | DETECTION OF NUCLEIC ACIDS AND PROTEINS | |
| EP3093029A8 (en) | Blood coagulation protein conjugates | |
| BRPI0913855A2 (pt) | novas proteínas de adesão do bacteriófago | |
| CO6430441A2 (es) | Medio de absorcion para retirar gases acidos de una corriente de fluidos | |
| EP4640716A3 (en) | Methods for detecting renal disease | |
| ES2693129T3 (es) | Detección de múltiples analitos | |
| CY1111618T1 (el) | Ανακτηση θειικου οξεος | |
| BRPI0912750A2 (pt) | método de teste ultra-sônico e sistema de detecção ultra-sônico. | |
| GB201205512D0 (en) | Active site probes |