Nothing Special   »   [go: up one dir, main page]

ATE406387T1 - Verfahren zur herstellung von hydroxyalkylstärkederivaten - Google Patents

Verfahren zur herstellung von hydroxyalkylstärkederivaten

Info

Publication number
ATE406387T1
ATE406387T1 AT03020424T AT03020424T ATE406387T1 AT E406387 T1 ATE406387 T1 AT E406387T1 AT 03020424 T AT03020424 T AT 03020424T AT 03020424 T AT03020424 T AT 03020424T AT E406387 T1 ATE406387 T1 AT E406387T1
Authority
AT
Austria
Prior art keywords
starch derivatives
hydroxyalkyl starch
producing hydroxyalkyl
producing
derivatives
Prior art date
Application number
AT03020424T
Other languages
English (en)
Inventor
Norbert Zander
Original Assignee
Fresenius Kabi De Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=31995520&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ATE406387(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from EP02020425A external-priority patent/EP1400533A1/de
Application filed by Fresenius Kabi De Gmbh filed Critical Fresenius Kabi De Gmbh
Application granted granted Critical
Publication of ATE406387T1 publication Critical patent/ATE406387T1/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C08B31/08—Ethers
    • C08B31/10—Alkyl or cycloalkyl ethers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C08B31/08—Ethers
    • C08B31/12—Ethers having alkyl or cycloalkyl radicals substituted by heteroatoms, e.g. hydroxyalkyl or carboxyalkyl starch
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • 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
    • 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
    • A61P7/06—Antianaemics
    • 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
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/505—Erythropoietin [EPO]
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5412—IL-6
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/55—IL-2
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/56—IFN-alpha
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/565—IFN-beta
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C07K17/10—Peptides being immobilised on, or in, an organic carrier the carrier being a carbohydrate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C08B31/003—Crosslinking of starch
    • C08B31/006—Crosslinking of derivatives of starch
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C08B31/08—Ethers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B31/00—Preparation of derivatives of starch
    • C08B31/18—Oxidised starch
    • C08B31/185—Derivatives of oxidised starch, e.g. crosslinked oxidised starch
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08H—DERIVATIVES OF NATURAL MACROMOLECULAR COMPOUNDS
    • C08H1/00—Macromolecular products derived from proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Materials Engineering (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
AT03020424T 2002-09-11 2003-09-11 Verfahren zur herstellung von hydroxyalkylstärkederivaten ATE406387T1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US40978102P 2002-09-11 2002-09-11
EP02020425A EP1400533A1 (de) 2002-09-11 2002-09-11 Hasylierte Polypeptide, besonders hasyliertes Erythropoietin
PCT/EP2003/008829 WO2004024776A1 (en) 2002-09-11 2003-08-08 Method of producing hydroxyalkyl starch derivatives

Publications (1)

Publication Number Publication Date
ATE406387T1 true ATE406387T1 (de) 2008-09-15

Family

ID=31995520

Family Applications (3)

Application Number Title Priority Date Filing Date
AT03020424T ATE406387T1 (de) 2002-09-11 2003-09-11 Verfahren zur herstellung von hydroxyalkylstärkederivaten
AT03020425T ATE449112T1 (de) 2002-09-11 2003-09-11 Hydroxyalkylstärke-derivate
AT03020423T ATE323723T1 (de) 2002-09-11 2003-09-11 Hasylierte polypeptide, besonders hasyliertes erythropoietin

Family Applications After (2)

Application Number Title Priority Date Filing Date
AT03020425T ATE449112T1 (de) 2002-09-11 2003-09-11 Hydroxyalkylstärke-derivate
AT03020423T ATE323723T1 (de) 2002-09-11 2003-09-11 Hasylierte polypeptide, besonders hasyliertes erythropoietin

Country Status (25)

Country Link
US (5) US8618266B2 (de)
EP (8) EP2017287A3 (de)
JP (4) JP2006516534A (de)
KR (3) KR101174510B1 (de)
CN (2) CN1681844A (de)
AR (3) AR041097A1 (de)
AT (3) ATE406387T1 (de)
AU (6) AU2003253399B2 (de)
BR (3) BR0314106A (de)
CA (2) CA2496317C (de)
CY (1) CY1109813T1 (de)
DE (7) DE20321836U1 (de)
DK (3) DK1398328T3 (de)
ES (4) ES2399006T3 (de)
HK (4) HK1063478A1 (de)
IL (5) IL166506A0 (de)
MX (4) MXPA05002591A (de)
NO (2) NO20051419L (de)
PL (3) PL216545B1 (de)
PT (3) PT1398328E (de)
RU (3) RU2326891C2 (de)
SI (2) SI1398328T1 (de)
TW (1) TW200418875A (de)
WO (3) WO2004024777A1 (de)
ZA (1) ZA200600651B (de)

Families Citing this family (158)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10112825A1 (de) * 2001-03-16 2002-10-02 Fresenius Kabi De Gmbh HESylierung von Wirkstoffen in wässriger Lösung
DE10209822A1 (de) 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung niedermolekularer Substanzen an ein modifiziertes Polysaccharid
DE10209821A1 (de) 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung von Proteinen an ein modifiziertes Polysaccharid
KR101174510B1 (ko) * 2002-09-11 2012-08-16 프레제니우스 카비 도이치란트 게엠베하 하이드록시알킬전분화 폴리펩티드, 특히 하이드록시알킬전분화 에리트로포이에틴
ES2214166T1 (es) * 2002-09-11 2004-09-16 Fresenius Kabi Deutschland Gmbh Polipeptidos has-ilados, especialmente, eriptropoyetina has-ilada.
DE10242076A1 (de) * 2002-09-11 2004-03-25 Fresenius Kabi Deutschland Gmbh HAS-Allergen-Konjugate
US7538092B2 (en) 2002-10-08 2009-05-26 Fresenius Kabi Deutschland Gmbh Pharmaceutically active oligosaccharide conjugates
DE10256558A1 (de) * 2002-12-04 2004-09-16 Supramol Parenteral Colloids Gmbh Ester von Polysaccharid Aldonsäuren, Verfahren zu ihrer Herstellung und Verwendung zur Kopplung an pharmazeutische Wirkstoffe
EP1653991A2 (de) * 2003-08-08 2006-05-10 Fresenius Kabi Deutschland GmbH Durch oxime als bindungsgruppe verbundene konjugate eines polymers mit einem protein
BRPI0413450A (pt) * 2003-08-08 2006-10-17 Fresenius Kabi De Gmbh conjugados de hidroxialquil amido e g-csf
WO2005014655A2 (en) * 2003-08-08 2005-02-17 Fresenius Kabi Deutschland Gmbh Conjugates of hydroxyalkyl starch and a protein
RU2370281C2 (ru) * 2003-08-08 2009-10-20 Фрезениус Каби Дойчланд Гмбх Конъюгаты гидроксиалкилкрахмала и g-csf
US8754031B2 (en) 2004-03-08 2014-06-17 Oncolix, Inc. Use of prolactin receptor antagonists in combination with an agent that inactivates the HER2/neu signaling pathway
JP5396019B2 (ja) * 2004-03-11 2014-01-22 フレゼニウス・カビ・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング ヒドロキシアルキルデンプンとタンパク質とのコンジュゲート
BRPI0508607A (pt) * 2004-03-11 2007-07-31 Fresenius Kabi De Gmbh conjugados de amido de hidroxialquila e uma proteìna, preparados pela aminação redutiva
AR048918A1 (es) * 2004-03-11 2006-06-14 Fresenius Kabi De Gmbh Conjugados de almidon de hidroxietilo y eritropoyetina
US7589063B2 (en) 2004-12-14 2009-09-15 Aplagen Gmbh Molecules which promote hematopoiesis
WO2006094826A2 (en) * 2005-03-11 2006-09-14 Fresenius Kabi Deutschland Gmbh Method for coupling enzymatically activated glycoconjugates to a hydroxyalkyl starch
KR20070110902A (ko) * 2005-03-11 2007-11-20 프레제니우스 카비 도이치란트 게엠베하 비활성 출발 물질로부터 생물활성 당단백질의 생산
EP1762250A1 (de) 2005-09-12 2007-03-14 Fresenius Kabi Deutschland GmbH Konjugate welche durch chemische Ligation zwischen Hydroxyalkylstärken und aktiven Substanzen mit Bildung eines Thiazolidin-Ringes entstehen
EP2035041B1 (de) 2006-06-30 2020-01-08 Syntab Therapeutics GmbH Konjugate für die immanente immuntherapie bei krebs
US8394921B2 (en) * 2006-07-25 2013-03-12 Lipoxen Technologies Limited N-terminal derivatisation of proteins with polysaccharides
JP2010510794A (ja) 2006-11-28 2010-04-08 ハナル ファーマシューティカル カンパニー リミテッド 修飾型エリスロポエチンポリペプチド及びこの治療用用途
EP3323430A1 (de) * 2006-12-15 2018-05-23 Baxalta GmbH Faktor-viia-(poly)sialsäure-konjugat mit verlängerter in-vivo-halbwertszeit
PT2457919T (pt) 2007-01-18 2019-09-20 Genzyme Corp Oligossacáridos compreendendo um grupo amino-oxi e os seus conjugados
WO2009043049A2 (en) 2007-09-27 2009-04-02 Amgen Inc. Pharmaceutical formulations
WO2009064838A1 (en) 2007-11-15 2009-05-22 Amgen, Inc. Aqueous formulation of erythropoiesis stimulating protein stablised by antioxidants for parenteral administration
EP2070950A1 (de) * 2007-12-14 2009-06-17 Fresenius Kabi Deutschland GmbH Hydroxyalkylstärkederivate und deren Herstellungsverfahren
EP2070951A1 (de) 2007-12-14 2009-06-17 Fresenius Kabi Deutschland GmbH Verfahren zur Herstellung eines Hydroxyalkylstärkederivats mit zwei Linkern
CN104888264B (zh) 2008-01-14 2018-01-09 北京环球利康科技有限公司 生物相容性止血、防粘连、促愈合、外科封闭的变性淀粉材料
ES2500066T3 (es) 2008-01-25 2014-09-30 Amgen, Inc Anticuerpos frente a ferroportina y métodos de uso
EP2310423A1 (de) * 2008-04-28 2011-04-20 SurModics, Inc. Auf poly(1;4)glucopyranose basierende matrizes mit hydrazidvernetzung
AU2009246946B2 (en) 2008-05-01 2013-09-26 Amgen Inc. Anti-hepcidin antibodies and methods of use
EP2166085A1 (de) 2008-07-16 2010-03-24 Suomen Punainen Risti Veripalvelu Divalente modifizierte Zellen
NZ591235A (en) 2008-07-23 2012-07-27 Ambrx Inc Modified bovine g-csf polypeptides comprising non natural amino acid and their uses treating infections such as mastitis
EP2350118B1 (de) 2008-09-19 2016-03-30 Nektar Therapeutics Kohlenhydratbasisierte polymere zur wirkstoffabgabe und konjugate davon
CN102215869B (zh) 2008-11-13 2015-05-13 通用医疗公司 用于通过调整bmp-6来调节铁稳态的方法和组合物
BRPI0920896B8 (pt) 2008-12-06 2021-05-25 Braun Melsungen Ag composto de fórmula geral (i) (t-z)n-p (i), formulação farmacêutica e processo para preparar um composto de fórmula geral (i)
US8648046B2 (en) 2009-02-26 2014-02-11 Oncolix, Inc. Compositions and methods for visualizing and eliminating cancer stem cells
US8754035B2 (en) 2009-02-26 2014-06-17 Oncolix, Inc. Compositions and methods for visualizing and eliminating cancer stem cells
CN102365099A (zh) 2009-03-31 2012-02-29 B·布朗·梅尔松根有限公司 胺化多糖粘合制品
US8809501B2 (en) 2009-07-27 2014-08-19 Baxter International Inc. Nucleophilic catalysts for oxime linkage
HUE028056T2 (en) * 2009-07-27 2016-11-28 Baxalta GmbH Blood coagulation protein conjugates
US8642737B2 (en) 2010-07-26 2014-02-04 Baxter International Inc. Nucleophilic catalysts for oxime linkage
CA2769326A1 (en) 2009-07-27 2011-02-10 Baxter International Inc. Blood coagulation protein conjugates
CN102573920B (zh) * 2009-07-27 2015-01-14 利普森技术有限公司 非凝血蛋白的糖基多唾液酸化
WO2011050333A1 (en) 2009-10-23 2011-04-28 Amgen Inc. Vial adapter and system
EA201290541A1 (ru) 2009-12-21 2013-05-30 Амбркс, Инк. Модифицированные бычьи соматотропиновые полипептиды и их применение
AU2010341518B2 (en) 2009-12-21 2014-01-09 Ambrx, Inc. Modified porcine somatotropin polypeptides and their uses
WO2011098095A1 (en) 2010-02-09 2011-08-18 Aplagen Gmbh Peptides binding the tpo receptor
AU2011265005B2 (en) 2010-06-07 2015-04-09 Amgen Inc. Drug delivery device
EP2591009A1 (de) 2010-07-09 2013-05-15 Fresenius Kabi Deutschland GmbH Stickoxidfreisetzende hydroxyalkylstärkederivate
US20140088298A9 (en) * 2010-07-09 2014-03-27 Fresenius Kabi Deutschland Gmbh Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation
EP2590680A1 (de) * 2010-07-09 2013-05-15 Fresenius Kabi Deutschland GmbH Konjugate mit hydroxyalkylstärke und einem zytotoxischen mittel sowie verfahren zu ihrer herstellung
US20130217871A1 (en) * 2010-07-09 2013-08-22 Helmut Knoller Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation
US8945897B2 (en) 2010-07-26 2015-02-03 Baxter International Inc. Materials and methods for conjugating a water soluble fatty acid derivative to a protein
PT2598172T (pt) 2010-07-30 2019-06-25 Baxalta Inc Catalisadores nucleofílicos para ligação oxima
TWI480288B (zh) 2010-09-23 2015-04-11 Lilly Co Eli 牛顆粒細胞群落刺激因子及其變體之調配物
CA2831100C (en) 2011-03-31 2020-02-18 Mark Dominis Holt Vial adapter and system
LT2699293T (lt) 2011-04-20 2019-04-25 Amgen Inc. Automatinio purškimo prietaisas
AU2012262428C1 (en) 2011-05-27 2018-10-11 Takeda Pharmaceutical Company Limited Therapeutic proteins with increased half-life and methods of preparing same
US20150044714A1 (en) * 2011-06-07 2015-02-12 Philadelphia Health & Education Corporation D/B/A Drexel University College Of Medicine sPLA2 MONITORING STRIP
US20140371292A1 (en) 2011-08-10 2014-12-18 Ludwig-Maximilians-Universitat Munchen Method for the controlled intracellular delivery of nucleic acids
PL3045187T3 (pl) 2011-10-14 2019-09-30 Amgen Inc. Wstrzykiwacz i sposób montażu
WO2013113503A1 (en) 2012-01-31 2013-08-08 Fresenius Kabi Deutschland Gmbh Conjugates of hydroxyalkyl starch and an oligonucleotide
AU2013204754C1 (en) 2012-05-16 2018-10-11 Takeda Pharmaceutical Company Limited Nucleophilic Catalysts for Oxime Linkage
US12115341B2 (en) 2012-11-21 2024-10-15 Amgen Inc. Drug delivery device
EP2926829B1 (de) * 2012-11-30 2018-07-25 Glytech, Inc. An zuckerkette angehängter linker, verbindung mit an zuckerkette angehängtem linker und physiologisch aktiver stoff oder salz davon und verfahren zur herstellung davon
CN110041427B (zh) 2013-03-15 2023-05-23 本质生命科学有限公司 抗铁调素抗体及其用途
TWI639453B (zh) 2013-03-15 2018-11-01 美商安美基公司 用於注射器之匣盒
WO2014144096A1 (en) 2013-03-15 2014-09-18 Amgen Inc. Drug cassette, autoinjector, and autoinjector system
EP2968736A4 (de) 2013-03-15 2016-11-09 Amgen Inc An eine körperform anpassbare autoinjektorvorrichtung
CA2907378A1 (en) * 2013-03-20 2014-09-25 Fresenius Kabi Deutschland Gmbh Process for the preparation of thiol functionalized hydroxyalkyl starch derivatives
US20160311934A1 (en) * 2013-03-20 2016-10-27 Fresenius Kabi Deutschland Gmbh Hydroxyalkyl starch derivatives as reactants for coupling to thiol groups
CA2907371A1 (en) * 2013-03-20 2014-09-25 Fresenius Kabi Deutschland Gmbh Hydroxyalkyl starch derivatives as reactants for coupling to thiol groups
AU2014238267B2 (en) 2013-03-22 2019-08-15 Amgen Inc. Injector and method of assembly
JP6520712B2 (ja) 2013-09-24 2019-05-29 味の素株式会社 糖アミノ酸およびその用途
CA2926110C (en) 2013-10-24 2023-05-23 Amgen Inc. Drug delivery system with temperature-sensitive control
ES2744837T3 (es) 2013-10-24 2020-02-26 Amgen Inc Inyector y procedimiento de ensamblaje
US10994112B2 (en) 2014-02-05 2021-05-04 Amgen Inc. Drug delivery system with electromagnetic field generator
US20150225315A1 (en) * 2014-02-10 2015-08-13 Honeywell International Inc. Reactor design for liquid phase fluorination
WO2015132724A1 (en) 2014-03-05 2015-09-11 Pfizer Inc. Improved muteins of clotting factor viii
CA2945026C (en) 2014-05-07 2023-10-10 Amgen Inc. Autoinjector with shock reducing elements
CN113990437A (zh) 2014-06-03 2022-01-28 安姆根有限公司 用于远程处理由药物递送装置收集的数据的系统和方法
CN104072608A (zh) * 2014-06-23 2014-10-01 山东齐都药业有限公司 含羧基羟乙基淀粉衍生物修饰的牛血清白蛋白偶联物及其制备方法
AU2015321462B2 (en) 2014-09-22 2020-04-30 Intrinsic Lifesciences Llc Humanized anti-hepcidin antibodies and uses thereof
MX2017004836A (es) 2014-10-14 2017-07-20 Amgen Inc Dispositivo de inyeccion de farmaco con indicadores visuales y audibles.
US11357916B2 (en) 2014-12-19 2022-06-14 Amgen Inc. Drug delivery device with live button or user interface field
EP3848072A1 (de) 2014-12-19 2021-07-14 Amgen Inc. Medikamentenabgabevorrichtung mit näherungssensor
CA2976935C (en) 2015-02-17 2020-03-10 Amgen Inc. Drug delivery device with vacuum assisted securement and/or feedback
JP2018512184A (ja) 2015-02-27 2018-05-17 アムジエン・インコーポレーテツド 針ガードの移動に対する抵抗力の閾値が調整可能な針ガード機構を備えた薬物送達装置
WO2017039786A1 (en) 2015-09-02 2017-03-09 Amgen Inc. Syringe assembly adapter for a syringe
JP7082568B2 (ja) 2015-12-09 2022-06-08 アムジエン・インコーポレーテツド 信号伝達キャップ付き自動注射器
US11154661B2 (en) 2016-01-06 2021-10-26 Amgen Inc. Auto-injector with signaling electronics
EP3721922B1 (de) 2016-03-15 2022-05-04 Amgen Inc. Verringerung der wahrscheinlichkeit auf glasbruch in arzneimittelabgabevorrichtungen
WO2017189089A1 (en) 2016-04-29 2017-11-02 Amgen Inc. Drug delivery device with messaging label
WO2017192287A1 (en) 2016-05-02 2017-11-09 Amgen Inc. Syringe adapter and guide for filling an on-body injector
US10988284B2 (en) 2016-05-13 2021-04-27 Amgen Inc. Vial sleeve assembly
EP3458988B1 (de) 2016-05-16 2023-10-18 Amgen Inc. Datenverschlüsselung in medizinischen vorrichtungen mit eingeschränkter rechenfähigkeit
DK3458085T5 (da) 2016-05-20 2024-09-09 Octapharma Ag Glykosyleret vwf-fusionsproteiner med forbedret farmakokinetik
GB201609083D0 (en) 2016-05-24 2016-07-06 Syntab Therapeutics Gmbh Synthetic compound
WO2017209899A1 (en) 2016-06-03 2017-12-07 Amgen Inc. Impact testing apparatuses and methods for drug delivery devices
WO2018004842A1 (en) 2016-07-01 2018-01-04 Amgen Inc. Drug delivery device having minimized risk of component fracture upon impact events
US20190328965A1 (en) 2016-08-17 2019-10-31 Amgen Inc. Drug delivery device with placement detection
EP3532127A1 (de) 2016-10-25 2019-09-04 Amgen Inc. Injektor am körper
MX2019008432A (es) 2017-01-17 2019-11-18 Amgen Inc Dispositivos de inyeccion y metodos relacionados de uso y ensamblaje.
EP3582829A1 (de) 2017-02-17 2019-12-25 Amgen Inc. Einführmechanismus für eine arzneimittelabgabevorrichtung
MX2019009625A (es) 2017-02-17 2019-10-09 Amgen Inc Dispositivo de administracion de farmacos con trayectoria de flujo de fluido esteril y metodo relacionado de ensamblaje.
EP3592403A1 (de) 2017-03-06 2020-01-15 Amgen Inc. Wirkstofffreisetzungsvorrichtung mit aktivierungsverhinderungsfunktion
JP2020509839A (ja) 2017-03-07 2020-04-02 アムジエン・インコーポレーテツド 超過圧力による針の挿入
IL303449B2 (en) 2017-03-09 2024-08-01 Amgen Inc Insertion mechanism for a drug delivery device
EP3570871B1 (de) 2017-03-20 2020-11-18 H. Hoffnabb-La Roche Ag Verfahren für in-vitro-glyco-engineering eines erythropoiesestimulierenden proteins
CN114588404B (zh) 2017-03-28 2024-07-09 美国安进公司 柱塞杆和注射器组件系统以及方法
US11904143B2 (en) 2017-06-08 2024-02-20 Amgen Inc. Torque driven drug delivery device
EP3634539A1 (de) 2017-06-08 2020-04-15 Amgen Inc. Spritzenanordnung für eine wirkstofffreisetzungsvorrichtung und verfahren zur montage
MX2019015472A (es) 2017-06-22 2020-02-19 Amgen Inc Reduccion del impacto/choque de la activacion del mecanismo.
MA49461A (fr) 2017-06-23 2020-04-29 Amgen Inc Dispositif électronique d'administration de médicament comprenant un bouchon activé par un ensemble commutateur
ES2972207T3 (es) 2017-07-14 2024-06-11 Amgen Inc Sistema de inserción-retracción de agujas con sistema de resorte de torsión doble
EP3655063A1 (de) 2017-07-21 2020-05-27 Amgen Inc. Gasdurchlässiges dichtelement für arzneimittelbehälter und verfahren zur montage
WO2019022950A1 (en) 2017-07-25 2019-01-31 Amgen Inc. DRUG DELIVERY DEVICE WITH CONTAINER ACCESS SYSTEM AND ASSEMBLY METHOD THEREOF
WO2019022951A1 (en) 2017-07-25 2019-01-31 Amgen Inc. DRUG DELIVERY DEVICE WITH GEAR MODULE AND ASSEMBLY METHOD THEREOF
MA49838A (fr) 2017-08-09 2020-06-17 Amgen Inc Systèm de administration de médicaments avec pression hydraulique-pneumatique de chambre
US11077246B2 (en) 2017-08-18 2021-08-03 Amgen Inc. Wearable injector with sterile adhesive patch
US11103636B2 (en) 2017-08-22 2021-08-31 Amgen Inc. Needle insertion mechanism for drug delivery device
ES2939292T3 (es) 2017-10-04 2023-04-20 Amgen Inc Adaptador de flujo para dispositivo de administración de fármacos
CN111132711B (zh) 2017-10-06 2022-07-01 安进公司 带有联锁组件的药物递送装置及相关组装方法
IL273323B2 (en) 2017-10-09 2024-10-01 Amgen Inc Drug delivery device with drive assembly and related assembly method
MA50527A (fr) 2017-11-03 2020-09-09 Amgen Inc Système et approches pour stériliser un dispositif d'administration de médicament
WO2019090303A1 (en) 2017-11-06 2019-05-09 Amgen Inc. Fill-finish assemblies and related methods
US20200261648A1 (en) 2017-11-06 2020-08-20 Amgen Inc. Drug delivery device with placement and flow sensing
MX2020004736A (es) 2017-11-10 2020-08-13 Amgen Inc Embolos para dispositivos de administracion de farmacos.
WO2019099322A1 (en) 2017-11-16 2019-05-23 Amgen Inc. Autoinjector with stall and end point detection
MX2020004996A (es) 2017-11-16 2020-08-27 Amgen Inc Un mecanismo de pestillo de puerta para un dispositivo de administracion de farmacos.
CN108503718B (zh) * 2018-02-08 2020-03-20 华中科技大学 一种羟烷基淀粉偶联物及其制备方法和应用
CN108219019B (zh) * 2018-02-08 2020-03-20 华中科技大学 一种巯基化羟乙基淀粉及其修饰的纳米材料和制备方法
CN108403641B (zh) * 2018-02-08 2020-03-20 华中科技大学 一种载药纳米材料及其制备方法
WO2019212377A1 (ru) * 2018-05-04 2019-11-07 Farber Boris Slavinovich Фармацевтическая композиция на основе полимиксина для лечения инфекционных заболеваний
US10835685B2 (en) 2018-05-30 2020-11-17 Amgen Inc. Thermal spring release mechanism for a drug delivery device
US11083840B2 (en) 2018-06-01 2021-08-10 Amgen Inc. Modular fluid path assemblies for drug delivery devices
WO2020023336A1 (en) 2018-07-24 2020-01-30 Amgen Inc. Hybrid drug delivery devices with grip portion
US12042645B2 (en) 2018-07-24 2024-07-23 Amgen Inc. Delivery devices for administering drugs
US20210260279A1 (en) 2018-07-24 2021-08-26 Amgen Inc. Hybrid drug delivery devices with optional grip portion and related method of preparation
MA53375A (fr) 2018-07-24 2021-06-02 Amgen Inc Dispositifs d'administration pour l'administration de médicaments
US12109389B2 (en) 2018-07-31 2024-10-08 Amgen Inc. Fluid path assembly for a drug delivery device
WO2020068623A1 (en) 2018-09-24 2020-04-02 Amgen Inc. Interventional dosing systems and methods
EP3856283A1 (de) 2018-09-28 2021-08-04 Amgen Inc. Anordnung zur aktivierung des muskeldrahtvorschubs für eine medikamentenabgabevorrichtung
JP2022503983A (ja) 2018-10-02 2022-01-12 アムジエン・インコーポレーテツド 内力伝達を伴う薬物送達用の注入システム
AU2019355979A1 (en) 2018-10-05 2021-03-18 Amgen Inc. Drug delivery device having dose indicator
AR116703A1 (es) 2018-10-15 2021-06-02 Amgen Inc Proceso de ensamblaje de plataforma para un dispositivo de administración de fármacos
EA202191037A1 (ru) 2018-10-15 2021-08-05 Эмджен Инк. Устройство доставки лекарственного средства, имеющее демпферный механизм
WO2020091981A1 (en) 2018-11-01 2020-05-07 Amgen Inc. Drug delivery devices with partial drug delivery member retraction
WO2020091956A1 (en) 2018-11-01 2020-05-07 Amgen Inc. Drug delivery devices with partial drug delivery member retraction
TWI831847B (zh) 2018-11-01 2024-02-11 美商安進公司 部分針頭縮回之藥物遞送裝置及其操作方法
CN111157736A (zh) * 2018-11-08 2020-05-15 中国科学院大连化学物理研究所 一种基于化学酶促的人血清o糖基化鉴定方法
JP7510952B2 (ja) 2019-04-24 2024-07-04 アムジエン・インコーポレーテツド シリンジ滅菌確認アセンブリ及び方法
JP2022545227A (ja) 2019-08-23 2022-10-26 アムジエン・インコーポレーテツド 構成可能な針シールド係合構成要素を備えた薬物送達デバイス及び関連方法
WO2022246055A1 (en) 2021-05-21 2022-11-24 Amgen Inc. Method of optimizing a filling recipe for a drug container
WO2024094457A1 (en) 2022-11-02 2024-05-10 F. Hoffmann-La Roche Ag Method for producing glycoprotein compositions

Family Cites Families (157)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE279486C (de)
US3191291A (en) * 1959-01-21 1965-06-29 Continental Can Co Art of producing very thin steel and like sheets in wide strips
CH397115A (de) * 1960-10-04 1965-08-15 Hoechst Ag Verfahren zur Herstellung wasserunlöslicher Farbstoffe
DE2233977A1 (de) 1971-07-14 1973-02-01 Unilever Nv Verfahren zur herstellung oxydierter kohlenhydrate
GB1419080A (en) 1972-12-29 1975-12-24 Cheminova As Chemical compounds having juvenile hormone activity
US4179337A (en) * 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US4125492A (en) * 1974-05-31 1978-11-14 Pedro Cuatrecasas Affinity chromatography of vibrio cholerae enterotoxin-ganglioside polysaccharide and the biological effects of ganglioside-containing soluble polymers
US4001200A (en) * 1975-02-27 1977-01-04 Alza Corporation Novel polymerized, cross-linked, stromal-free hemoglobin
US4061736A (en) * 1975-02-02 1977-12-06 Alza Corporation Pharmaceutically acceptable intramolecularly cross-linked, stromal-free hemoglobin
US4001401A (en) * 1975-02-02 1977-01-04 Alza Corporation Blood substitute and blood plasma expander comprising polyhemoglobin
US4053590A (en) * 1975-02-27 1977-10-11 Alza Corporation Compositions of matter comprising macromolecular hemoglobin
CA1055932A (en) 1975-10-22 1979-06-05 Hematech Inc. Blood substitute based on hemoglobin
DE2616086C2 (de) * 1976-04-13 1986-04-03 Dr. Eduard Fresenius, Chemisch-pharmazeutische Industrie KG, 6380 Bad Homburg Substanz zur Verwendung in einem kolloidalen Blutvolumenersatzmittel aus Hydroxyethylstärke und Hämoglobin
GB1578348A (en) * 1976-08-17 1980-11-05 Pharmacia Ab Products and a method for the therapeutic suppression of reaginic antibodies responsible for common allergic
FR2378094A2 (fr) 1977-01-24 1978-08-18 Inst Nat Sante Rech Med Nouveaux reactifs biologiques constitues par des supports solides sur lesquels sont couples des composes organiques comportant un residu glucidique
EP0019403B1 (de) * 1979-05-10 1985-07-31 American Hospital Supply Corporation Arzneimittelträger auf der Basis von Hydroxyalkyl-Stärke
DE3029307A1 (de) * 1980-08-01 1982-03-04 Dr. Eduard Fresenius, Chemisch-pharmazeutische Industrie KG, 6380 Bad Homburg Haemoglobin enthaltendes blutersatzmittel
US4454161A (en) * 1981-02-07 1984-06-12 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Process for the production of branching enzyme, and a method for improving the qualities of food products therewith
JPS57206622A (en) * 1981-06-10 1982-12-18 Ajinomoto Co Inc Blood substitute
IE56026B1 (en) 1982-10-19 1991-03-27 Cetus Corp Cysteine-depleted muteins of biologically active proteins
ATE78293T1 (de) 1983-05-27 1992-08-15 Texas A & M Univ Sys Verfahren zur herstellung eines rekombinanten baculovirus-expressionsvektors.
DK171029B1 (da) 1983-10-11 1996-04-22 Fidia Spa Hyaluronsyrefraktion, fremgangsmåde til fremstilling deraf samt ophthalmiske præparater indeholdende hyaluronsyrefraktion
NZ210501A (en) 1983-12-13 1991-08-27 Kirin Amgen Inc Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence
US4703008A (en) 1983-12-13 1987-10-27 Kiren-Amgen, Inc. DNA sequences encoding erythropoietin
US4496689A (en) * 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4952496A (en) * 1984-03-30 1990-08-28 Associated Universities, Inc. Cloning and expression of the gene for bacteriophage T7 RNA polymerase
IL77081A (en) 1984-12-04 1999-10-28 Genetics Inst AND sequence encoding human erythropoietin, a process for its preparation and a pharmacological preparation of human erythropoietin
DE3501616A1 (de) 1985-01-17 1986-07-17 Schering AG, 1000 Berlin und 4709 Bergkamen Verfahren zur herstellung von hydroxylamin-derivaten
US4667016A (en) 1985-06-20 1987-05-19 Kirin-Amgen, Inc. Erythropoietin purification
US4766106A (en) * 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
US5217998A (en) * 1985-07-02 1993-06-08 Biomedical Frontiers, Inc. Composition for the stabilization of deferoxamine to chelate free ions in physiological fluid
US4863964A (en) 1985-07-02 1989-09-05 Biomedical Frontiers, Inc. Method for the stabilization of deferoxamine to chelate free ions in physiological fluid
GB8610551D0 (en) 1986-04-30 1986-06-04 Hoffmann La Roche Polypeptide & protein derivatives
IT1203814B (it) 1986-06-30 1989-02-23 Fidia Farmaceutici Esteri dell'acido alginico
FR2600894B1 (fr) * 1986-07-02 1989-01-13 Centre Nat Rech Scient Conjugues macromoleculaires d'hemoglobine, leur procede de preparation et leurs applications
US5214132A (en) * 1986-12-23 1993-05-25 Kyowa Hakko Kogyo Co., Ltd. Polypeptide derivatives of human granulocyte colony stimulating factor
US5362853A (en) * 1986-12-23 1994-11-08 Kyowa Hakko Kogyo Co., Ltd. Polypeptide derivatives of human granulocyte colony stimulating factor
JP2594123B2 (ja) * 1987-09-12 1997-03-26 株式会社林原生物化学研究所 減感作剤
EP0307827A3 (de) 1987-09-15 1989-12-27 Kuraray Co., Ltd. Makromolekulare Komplexe, ihre Herstellung und Verwendung in der Medizin
IL84252A (en) 1987-10-23 1994-02-27 Yissum Res Dev Co Phospholipase inhibiting compositions
US4904584A (en) * 1987-12-23 1990-02-27 Genetics Institute, Inc. Site-specific homogeneous modification of polypeptides
US4847325A (en) * 1988-01-20 1989-07-11 Cetus Corporation Conjugation of polymer to colony stimulating factor-1
DK110188D0 (da) 1988-03-02 1988-03-02 Claus Selch Larsen High molecular weight prodrug derivatives of antiinflammatory drugs
FR2630329B1 (fr) * 1988-04-20 1991-07-05 Merieux Inst Conjugues macromoleculaires d'hemoglobine, leur procede de preparation et leurs applications
IT1219942B (it) 1988-05-13 1990-05-24 Fidia Farmaceutici Esteri polisaccaridici
US4900780A (en) * 1988-05-25 1990-02-13 Masonic Medical Research Laboratory Acellular resuscitative fluid
US4925677A (en) * 1988-08-31 1990-05-15 Theratech, Inc. Biodegradable hydrogel matrices for the controlled release of pharmacologically active agents
US5420105A (en) * 1988-09-23 1995-05-30 Gustavson; Linda M. Polymeric carriers for non-covalent drug conjugation
US5218092A (en) * 1988-09-29 1993-06-08 Kyowa Hakko Kogyo Co., Ltd. Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains
DE3836600A1 (de) 1988-10-27 1990-05-03 Wolff Walsrode Ag Kohlensaeureester von polysacchariden und verfahren zu ihrer herstellung
CA2006596C (en) * 1988-12-22 2000-09-05 Rika Ishikawa Chemically-modified g-csf
US6261800B1 (en) * 1989-05-05 2001-07-17 Genentech, Inc. Luteinizing hormone/choriogonadotropin (LH/CG) receptor
DE3919729C3 (de) * 1989-06-16 1997-06-19 Fresenius Ag Hydroxyethylstärke als Plasmaexpander, Verfahren zu ihrer Herstellung und Verwendung als kolloidales Plasmaersatzmittel
JP2896580B2 (ja) 1989-08-25 1999-05-31 チッソ株式会社 アミロース―リゾチームハイブリッドと活性化糖およびその製造法
JP2838800B2 (ja) * 1989-09-02 1998-12-16 株式会社林原生物化学研究所 減感作剤
WO1991005867A1 (en) 1989-10-13 1991-05-02 Amgen Inc. Erythropoietin isoforms
JP2975632B2 (ja) 1990-03-30 1999-11-10 生化学工業株式会社 グリコサミノグリカン修飾プロテイン
US5169784A (en) 1990-09-17 1992-12-08 The Texas A & M University System Baculovirus dual promoter expression vector
DK130991D0 (da) * 1991-07-04 1991-07-04 Immunodex K S Polymere konjugater
US5281698A (en) * 1991-07-23 1994-01-25 Cetus Oncology Corporation Preparation of an activated polymer ester for protein conjugation
DE4130807A1 (de) 1991-09-17 1993-03-18 Wolff Walsrode Ag Verfahren zur herstellung von polysaccharidcarbonaten
US6172208B1 (en) * 1992-07-06 2001-01-09 Genzyme Corporation Oligonucleotides modified with conjugate groups
WO1994005332A2 (en) * 1992-09-01 1994-03-17 Berlex Laboratories, Inc. Glycolation of glycosylated macromolecules
GB2270920B (en) * 1992-09-25 1997-04-02 Univ Keele Alginate-bioactive agent conjugates
NZ250375A (en) 1992-12-09 1995-07-26 Ortho Pharma Corp Peg hydrazone and peg oxime linkage forming reagents and protein derivatives
NO934477L (no) 1992-12-09 1994-06-10 Ortho Pharma Corp PEG hydrazon- og PEG oksim-bindingdannende reagenser og proteinderivater derav
CA2110543A1 (en) 1992-12-09 1994-06-10 David E. Wright Peg hydrazone and peg oxime linkage forming reagents and protein derivatives thereof
EP0601417A3 (de) * 1992-12-11 1998-07-01 Hoechst Aktiengesellschaft Physiologisch verträglicher und physiologisch abbaubarer, Kohlenhydratrezeptorblocker auf Polymerbasis, ein Verfahren zu seiner Herstellung und seine Verwendung
US5581476A (en) * 1993-01-28 1996-12-03 Amgen Inc. Computer-based methods and articles of manufacture for preparing G-CSF analogs
ATE146189T1 (de) 1993-03-16 1996-12-15 Hemosol Inc Selektive vernetzung von hemoglobin mittels oxidierten, ringgeöffneten sacchariden
WO1994028024A1 (en) * 1993-06-01 1994-12-08 Enzon, Inc. Carbohydrate-modified polymer conjugates with erythropoietic activity
ZA946122B (en) 1993-08-17 1995-03-20 Amgen Inc Erythropoietin analogs
US5840900A (en) * 1993-10-20 1998-11-24 Enzon, Inc. High molecular weight polymer-based prodrugs
JPH07188291A (ja) 1993-12-27 1995-07-25 Hayashibara Biochem Lab Inc 蛋白質とその製造方法並びに用途
US5876980A (en) * 1995-04-11 1999-03-02 Cytel Corporation Enzymatic synthesis of oligosaccharides
US6214331B1 (en) * 1995-06-06 2001-04-10 C. R. Bard, Inc. Process for the preparation of aqueous dispersions of particles of water-soluble polymers and the particles obtained
WO1996040662A2 (en) * 1995-06-07 1996-12-19 Cellpro, Incorporated Aminooxy-containing linker compounds and their application in conjugates
US5736533A (en) * 1995-06-07 1998-04-07 Neose Technologies, Inc. Bacterial inhibition with an oligosaccharide compound
US5981507A (en) * 1995-12-14 1999-11-09 Advanced Magnetics, Inc. Polymeric carriers linked to nucleotide analogues via a phosphoramide bond
US5723589A (en) * 1995-12-21 1998-03-03 Icn Pharmaceuticals Carbohydrate conjugated bio-active compounds
PL189698B1 (pl) * 1996-03-12 2005-09-30 Pg Txl Co Kompozycja farmaceutyczna zawierająca lek przeciwnowotworowy i jej zastosowania
US5696152A (en) 1996-05-07 1997-12-09 Wisconsin Alumni Research Foundation Taxol composition for use as organ preservation and cardioplegic agents
TW517067B (en) * 1996-05-31 2003-01-11 Hoffmann La Roche Interferon conjugates
DE19628705A1 (de) * 1996-07-08 1998-01-15 Fresenius Ag Neue Sauerstoff-Transport-Mittel, diese enthaltende Hämoglobin-Hydroxyethylstärke-Konjugate, Verfahren zu deren Herstellung, sowie deren Verwendung als Blutersatzstoffe
US5770645A (en) * 1996-08-02 1998-06-23 Duke University Medical Center Polymers for delivering nitric oxide in vivo
US5851984A (en) * 1996-08-16 1998-12-22 Genentech, Inc. Method of enhancing proliferation or differentiation of hematopoietic stem cells using Wnt polypeptides
US6011008A (en) * 1997-01-08 2000-01-04 Yissum Research Developement Company Of The Hebrew University Of Jerusalem Conjugates of biologically active substances
US5952347A (en) * 1997-03-13 1999-09-14 Merck & Co., Inc. Quinoline leukotriene antagonists
US6299881B1 (en) * 1997-03-24 2001-10-09 Henry M. Jackson Foundation For The Advancement Of Military Medicine Uronium salts for activating hydroxyls, carboxyls, and polysaccharides, and conjugate vaccines, immunogens, and other useful immunological reagents produced using uronium salts
US5990237A (en) * 1997-05-21 1999-11-23 Shearwater Polymers, Inc. Poly(ethylene glycol) aldehyde hydrates and related polymers and applications in modifying amines
DE69835308T2 (de) * 1997-08-07 2007-08-09 University Of Utah Research Foundation, Salt Lake City Prodrugs und Konjugate von Selenoenthaltenden Verbindungen und ihre Verwendung
US5847110A (en) * 1997-08-15 1998-12-08 Biomedical Frontiers, Inc. Method of reducing a schiff base
US6875594B2 (en) * 1997-11-13 2005-04-05 The Rockefeller University Methods of ligating expressed proteins
US6624142B2 (en) 1997-12-30 2003-09-23 Enzon, Inc. Trimethyl lock based tetrapartate prodrugs
DE19808079A1 (de) 1998-02-20 1999-08-26 Schering Ag Hydroxyethylstärke-Konjugate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel
EP1063317B1 (de) 1998-03-05 2003-07-30 Asahi Glass Company Ltd. Sputtertarget, transparenter leitender film und verfahren zu dessen herstellung
CA2233725A1 (en) 1998-03-31 1999-09-30 Hemosol Inc. Hemoglobin-hydroxyethyl starch complexes
US6153655A (en) * 1998-04-17 2000-11-28 Enzon, Inc. Terminally-branched polymeric linkers and polymeric conjugates containing the same
US6660843B1 (en) * 1998-10-23 2003-12-09 Amgen Inc. Modified peptides as therapeutic agents
US6261594B1 (en) * 1998-11-25 2001-07-17 The University Of Akron Chitosan-based nitric oxide donor compositions
EP1035137A1 (de) * 1999-03-12 2000-09-13 Pasteur Merieux Serums Et Vaccins Verfahren zur reduktiven aminierung von polysacchariden
CZ299516B6 (cs) 1999-07-02 2008-08-20 F. Hoffmann-La Roche Ag Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem
US7279176B1 (en) 1999-09-02 2007-10-09 Rice University Nitric oxide-producing hydrogel materials
US20020065410A1 (en) * 1999-12-02 2002-05-30 Antrim Richard L. Branched starches and branched starch hydrolyzates
US6555660B2 (en) * 2000-01-10 2003-04-29 Maxygen Holdings Ltd. G-CSF conjugates
US6749865B2 (en) * 2000-02-15 2004-06-15 Genzyme Corporation Modification of biopolymers for improved drug delivery
US6586398B1 (en) * 2000-04-07 2003-07-01 Amgen, Inc. Chemically modified novel erythropoietin stimulating protein compositions and methods
JP2001294601A (ja) 2000-04-11 2001-10-23 Akita Prefecture 高度分岐澱粉と該高度分岐澱粉の製造方法
JP2002003398A (ja) 2000-04-17 2002-01-09 Ltt Institute Co Ltd 徐放製剤、その製造法及びワクチン
DE10023051B4 (de) * 2000-05-11 2004-02-19 Roche Diagnostics Gmbh Verfahren zur Herstellung von Fluoresceinisothiocyanat-Sinistrin, dessen Verwendung und Fluoresceinisothiocyanat-Sinistrin enthaltende diagnostische Zubereitung
FR2811967B1 (fr) 2000-07-24 2002-12-13 Cebal Tube muni d'une tete de fixation pour divers bouchages et les divers bouchages munis de moyens de fixation sur ledit tube
US6417347B1 (en) * 2000-08-24 2002-07-09 Scimed Life Systems, Inc. High yield S-nitrosylation process
DE10041541A1 (de) 2000-08-24 2002-03-14 Michael Duchene Rekombinante Allergene aus der Motte Plodia interpunctella
US7030218B2 (en) 2000-09-08 2006-04-18 Gryphon Therapeutics Pseudo native chemical ligation
DE10105921A1 (de) 2001-02-09 2002-08-14 Braun Melsungen Ag An Kolloide gebundene Arzneiwirkstoffe
DE10112825A1 (de) * 2001-03-16 2002-10-02 Fresenius Kabi De Gmbh HESylierung von Wirkstoffen in wässriger Lösung
DE10126158A1 (de) 2001-05-30 2002-12-12 Novira Chem Gmbh Eine Methode zur Synthese von Gemischen einfach aktivierter und nicht aktivierter Polyoxyalkylene zur Modifizierung von Proteinen
DE10129369C1 (de) * 2001-06-21 2003-03-06 Fresenius Kabi De Gmbh Wasserlösliches, einen Aminozucker aufweisendes Antibiotikum in Form eines Pol ysaccharid-Konjugats
DE10135694A1 (de) 2001-07-21 2003-02-06 Supramol Parenteral Colloids Amphiphile Stärke-und Hydroxyethylstärke-Konjugate
US7179617B2 (en) * 2001-10-10 2007-02-20 Neose Technologies, Inc. Factor IX: remolding and glycoconjugation of Factor IX
US7125843B2 (en) * 2001-10-19 2006-10-24 Neose Technologies, Inc. Glycoconjugates including more than one peptide
WO2003035665A1 (de) 2001-10-26 2003-05-01 Noxxon Pharma Ag Modifizierte l-nukleinsäure
US6375846B1 (en) * 2001-11-01 2002-04-23 Harry Wellington Jarrett Cyanogen bromide-activation of hydroxyls on silica for high pressure affinity chromatography
DE10155098A1 (de) 2001-11-09 2003-05-22 Supramol Parenteral Colloids Mittel zur Prävention von mykotischen Kontaminationen bei der Zell- und Gewebekultur bakteriellen, pflanzlichen, animalischen und humanen Ursprungs, bestehend aus Polyen-Makrolid-Konjugaten mit Polysacchariden
US6916962B2 (en) 2001-12-11 2005-07-12 Sun Bio, Inc. Monofunctional polyethylene glycol aldehydes
DE10207072A1 (de) * 2002-02-20 2003-08-28 Supramol Parenteral Colloids Stärkederivate, ihre Konjugate und Verfahren zur Herstellung derselben
DE10209822A1 (de) * 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung niedermolekularer Substanzen an ein modifiziertes Polysaccharid
DE10209821A1 (de) * 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung von Proteinen an ein modifiziertes Polysaccharid
EP1496076B1 (de) 2002-03-13 2007-07-25 Beijing Jiankai Technology Co., Ltd. Hydrophiles polymerderivat mit y-verzweigung und herstellungsverfahren dafür; obige verbindung enthaltender medizinischer verbundwerkstoff
DE10217994A1 (de) 2002-04-23 2003-11-06 Supramol Parenteral Colloids Konjugate von hyperverzweigten Polysacchariden
AU2003249692B2 (en) * 2002-06-03 2008-07-31 The Institute For Systems Biology Methods for quantitative proteome analysis of glycoproteins
US20040101546A1 (en) 2002-11-26 2004-05-27 Gorman Anne Jessica Hemostatic wound dressing containing aldehyde-modified polysaccharide and hemostatic agents
EP1591467A1 (de) 2002-09-09 2005-11-02 Nektar Therapeutics Al, Corporation Konjugat aus einem Polyethylene Glykol mit einer Alkanal Endgruppe und einem menschlichen Wachstumshormon
CA2498167C (en) 2002-09-09 2012-03-20 Nektar Therapeutics Al, Corporation Water-soluble polymer alkanals
KR101174510B1 (ko) * 2002-09-11 2012-08-16 프레제니우스 카비 도이치란트 게엠베하 하이드록시알킬전분화 폴리펩티드, 특히 하이드록시알킬전분화 에리트로포이에틴
DE10242076A1 (de) * 2002-09-11 2004-03-25 Fresenius Kabi Deutschland Gmbh HAS-Allergen-Konjugate
ES2214166T1 (es) 2002-09-11 2004-09-16 Fresenius Kabi Deutschland Gmbh Polipeptidos has-ilados, especialmente, eriptropoyetina has-ilada.
US7538092B2 (en) * 2002-10-08 2009-05-26 Fresenius Kabi Deutschland Gmbh Pharmaceutically active oligosaccharide conjugates
DE10254745A1 (de) 2002-11-23 2004-06-03 Supramol Parenteral Colloids Gmbh Imidazolide von Polysaccharid Aldonsäuren, Verfahren zu ihrer Herstellung und Verwendung zur Kopplung an pharmazeutische Wirkstoffe
DE10256558A1 (de) 2002-12-04 2004-09-16 Supramol Parenteral Colloids Gmbh Ester von Polysaccharid Aldonsäuren, Verfahren zu ihrer Herstellung und Verwendung zur Kopplung an pharmazeutische Wirkstoffe
EP1653991A2 (de) * 2003-08-08 2006-05-10 Fresenius Kabi Deutschland GmbH Durch oxime als bindungsgruppe verbundene konjugate eines polymers mit einem protein
BRPI0413450A (pt) 2003-08-08 2006-10-17 Fresenius Kabi De Gmbh conjugados de hidroxialquil amido e g-csf
WO2005014655A2 (en) * 2003-08-08 2005-02-17 Fresenius Kabi Deutschland Gmbh Conjugates of hydroxyalkyl starch and a protein
RU2370281C2 (ru) 2003-08-08 2009-10-20 Фрезениус Каби Дойчланд Гмбх Конъюгаты гидроксиалкилкрахмала и g-csf
WO2005072778A2 (en) 2004-01-29 2005-08-11 Biosynexus, Inc. Use of amino-oxy functional groups in the preparation of vaccines conjugates
DE102004009783A1 (de) 2004-02-28 2005-09-15 Supramol Parenteral Colloids Gmbh Hyperverzweigte Stärkefraktion, Verfahren zu ihrer Herstellung und ihre Konjugate mit pharmazeutischen Wirkstoffen
AR048918A1 (es) * 2004-03-11 2006-06-14 Fresenius Kabi De Gmbh Conjugados de almidon de hidroxietilo y eritropoyetina
BRPI0508607A (pt) 2004-03-11 2007-07-31 Fresenius Kabi De Gmbh conjugados de amido de hidroxialquila e uma proteìna, preparados pela aminação redutiva
JP5396019B2 (ja) * 2004-03-11 2014-01-22 フレゼニウス・カビ・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング ヒドロキシアルキルデンプンとタンパク質とのコンジュゲート
US20050265958A1 (en) 2004-05-14 2005-12-01 West Jennifer L Nitric oxide releasing compositions and associated methods
KR20070110902A (ko) * 2005-03-11 2007-11-20 프레제니우스 카비 도이치란트 게엠베하 비활성 출발 물질로부터 생물활성 당단백질의 생산
EP1762250A1 (de) * 2005-09-12 2007-03-14 Fresenius Kabi Deutschland GmbH Konjugate welche durch chemische Ligation zwischen Hydroxyalkylstärken und aktiven Substanzen mit Bildung eines Thiazolidin-Ringes entstehen
AU2006309212B2 (en) 2005-10-31 2011-09-15 Government Of The United States Of America, Represented By The Secretary Department Of Health And Human Services Polysaccharide-derived nitric oxide-releasing carbon-bound diazeniumdiolates
JP2009093397A (ja) 2007-10-09 2009-04-30 Panasonic Corp タッチパネル及びこれを用いた入力装置
EP2070951A1 (de) * 2007-12-14 2009-06-17 Fresenius Kabi Deutschland GmbH Verfahren zur Herstellung eines Hydroxyalkylstärkederivats mit zwei Linkern
EP2070950A1 (de) 2007-12-14 2009-06-17 Fresenius Kabi Deutschland GmbH Hydroxyalkylstärkederivate und deren Herstellungsverfahren
CA2739757C (en) 2008-10-07 2016-07-05 Rexahn Pharmaceuticals, Inc. Hpma - docetaxel or gemcitabine conjugates and uses therefore

Also Published As

Publication number Publication date
IL166930A (en) 2012-08-30
JP2011089125A (ja) 2011-05-06
RU2328505C2 (ru) 2008-07-10
US20050234230A1 (en) 2005-10-20
HK1136226A1 (en) 2010-06-25
AU2003255406A1 (en) 2004-04-30
CY1109813T1 (el) 2014-09-10
AU2003253399A1 (en) 2004-04-30
ES2213507T1 (es) 2004-09-01
DE03020423T1 (de) 2004-07-15
KR101045401B1 (ko) 2011-06-30
ES2399006T3 (es) 2013-03-25
ES2213507T3 (es) 2010-04-15
EP2143736A1 (de) 2010-01-13
IL166506A (en) 2010-02-17
ES2213505T1 (es) 2004-09-01
AU2003253399B2 (en) 2010-10-14
PL374490A1 (en) 2005-10-31
EP1398322A1 (de) 2004-03-17
US7815893B2 (en) 2010-10-19
IL166506A0 (en) 2006-01-15
US20100317609A1 (en) 2010-12-16
US8618266B2 (en) 2013-12-31
KR20050061466A (ko) 2005-06-22
SI1398328T1 (sl) 2010-02-26
SI1398327T1 (sl) 2009-02-28
IL166931A (en) 2012-06-28
RU2329274C2 (ru) 2008-07-20
HK1063477A1 (en) 2004-12-31
EP1398328B1 (de) 2009-11-18
CN1681844A (zh) 2005-10-12
MXPA05002594A (es) 2005-05-27
NO20051427L (no) 2005-05-31
ES2213505T3 (es) 2006-11-16
HK1063475A1 (en) 2004-12-31
RU2005110423A (ru) 2006-01-20
US20110054152A1 (en) 2011-03-03
ES2213506T1 (es) 2004-09-01
HK1063478A1 (en) 2004-12-31
EP2017287A3 (de) 2009-11-04
AU2003260393A1 (en) 2004-04-30
DE60330098D1 (de) 2009-12-31
US20050238723A1 (en) 2005-10-27
IL200150A0 (en) 2011-07-31
MXPA05002593A (es) 2005-05-27
CA2496317C (en) 2014-02-18
JP2010265464A (ja) 2010-11-25
MX2010006175A (es) 2010-07-05
WO2004024761A1 (en) 2004-03-25
DK1398327T3 (da) 2008-11-10
BR0314107A (pt) 2005-07-19
EP2272865A3 (de) 2014-06-18
WO2004024777A8 (en) 2005-03-24
AU2003260393B2 (en) 2009-10-01
AU2011200219A1 (en) 2011-02-10
EP1398322B1 (de) 2006-04-19
MXPA05002591A (es) 2005-09-20
KR101045422B1 (ko) 2011-06-30
PT1398327E (pt) 2008-10-31
EP2017287A2 (de) 2009-01-21
PL374969A1 (en) 2005-11-14
EP1398327A1 (de) 2004-03-17
PL375037A1 (en) 2005-11-14
CN1681846A (zh) 2005-10-12
DE03020425T1 (de) 2004-07-15
DE60304640D1 (de) 2006-05-24
RU2005110415A (ru) 2006-08-27
PT1398322E (pt) 2006-08-31
US20060019877A1 (en) 2006-01-26
AR045235A1 (es) 2005-10-19
PL216545B1 (pl) 2014-04-30
DK1398322T3 (da) 2006-08-21
PL217085B1 (pl) 2014-06-30
US8475765B2 (en) 2013-07-02
JP5275293B2 (ja) 2013-08-28
JP2010248528A (ja) 2010-11-04
AU2009238372A1 (en) 2009-12-17
JP5455821B2 (ja) 2014-03-26
DE03020424T1 (de) 2004-07-15
EP2154160A1 (de) 2010-02-17
DE20321836U1 (de) 2011-04-07
ATE449112T1 (de) 2009-12-15
PT1398328E (pt) 2010-02-19
KR20050072417A (ko) 2005-07-11
US20120046240A9 (en) 2012-02-23
EP1398327B1 (de) 2008-08-27
DE60323192D1 (de) 2008-10-09
AU2009238372B2 (en) 2012-08-23
RU2326891C2 (ru) 2008-06-20
EP2316850A3 (de) 2011-11-09
AU2011200158B2 (en) 2012-08-02
TW200418875A (en) 2004-10-01
RU2005110412A (ru) 2006-01-20
AR045234A1 (es) 2005-10-19
ZA200600651B (en) 2007-04-25
AU2011200158A1 (en) 2011-02-03
ES2213506T3 (es) 2009-02-16
CA2496317A1 (en) 2004-03-25
WO2004024776A1 (en) 2004-03-25
AU2003255406B2 (en) 2009-09-10
CA2495242A1 (en) 2004-03-25
NO20051419L (no) 2005-05-30
BR0314106A (pt) 2005-07-19
EP2272865A2 (de) 2011-01-12
EP2143736B1 (de) 2012-11-07
EP2316850A2 (de) 2011-05-04
KR101174510B1 (ko) 2012-08-16
AU2011200219B2 (en) 2012-05-17
EP1398328A1 (de) 2004-03-17
ATE323723T1 (de) 2006-05-15
KR20050075336A (ko) 2005-07-20
BR0314227A (pt) 2005-10-25
JP2006516534A (ja) 2006-07-06
WO2004024777A1 (en) 2004-03-25
DE60304640T2 (de) 2007-05-16
AR041097A1 (es) 2005-05-04
CN100348618C (zh) 2007-11-14
DK1398328T3 (da) 2010-03-08

Similar Documents

Publication Publication Date Title
ATE406387T1 (de) Verfahren zur herstellung von hydroxyalkylstärkederivaten
ATE386736T1 (de) Verfahren zur herstellung von benzimidazol-2-yl - chinolinonderivaten
DE60221399D1 (de) Verfahren zur herstellung von mitteldistillaten
ATE403641T1 (de) Verfahren zur herstellung von o- desmethylvenlafaxin
ATE414077T1 (de) Verfahren zur herstellung von 1-ä(benzimidazol-1- yl)chinolin-8-ylüpiperidin-4-ylaminderivaten
DE60324720D1 (de) Verfahren zur Herstellung dekorativer Gegenstände
DE60230908D1 (de) Verfahren zur herstellung von polyarylenethern
DE60317690D1 (de) Verfahren zur herstellung von valsartan
ATE286011T1 (de) Verfahren zur herstellung von 1-octen
DE60327788D1 (de) Verfahren zur herstellung von polytrimethylenterephthalt-fasern
ATE448209T1 (de) Verfahren zur herstellung von pyrimidinverbindungen
DE50308650D1 (de) Verfahren zur herstellung von cellulosecarbamatformkörpern
ATE456569T1 (de) Verfahren zur herstellung von 6-alkyliden- penemderivaten
ATE376997T1 (de) Verfahren zur herstellung von 1,4- diphenylazetidinon-derivaten
ATE441662T1 (de) Verfahren zur herstellung von echinocandinderivaten
ATE553103T1 (de) Verfahren zur herstellung von (s)-pantoprazol
ATE284875T1 (de) Verfahren zur herstellung von mesylaten von piperazinderivaten
ATE287870T1 (de) Verfahren zur herstellung von phenethylamin- derivaten
DE50303611D1 (de) Verfahren zur herstellung von polyisobuten
ATE424892T1 (de) Verfahren zur herstellung von derivaten des 4a,5, 9,10,11,12-hexahydrobenzofuro ä3a,3,2üä 2 ü- benzazepins
DE50200870D1 (de) Verfahren zur herstellung von hydroxyalkylpolysiloxanen
ATE402138T1 (de) Verfahren zur herstellung von 2- aminoindanderivaten
ATE371642T1 (de) Verfahren zur herstellung von 3- methylthiopropanal
ATE374757T1 (de) Verfahren zur herstellung von (1,4,5)- oxadiazepinderivaten
ATE471941T1 (de) Verfahren zur herstellung von thiazolopyrimidinen

Legal Events

Date Code Title Description
UEP Publication of translation of european patent specification

Ref document number: 1398327

Country of ref document: EP