MX350293B - Modificacion dirigida al sitio del factor viii. - Google Patents

Modificacion dirigida al sitio del factor viii.

Info

Publication number
MX350293B
MX350293B MX2014005051A MX2014005051A MX350293B MX 350293 B MX350293 B MX 350293B MX 2014005051 A MX2014005051 A MX 2014005051A MX 2014005051 A MX2014005051 A MX 2014005051A MX 350293 B MX350293 B MX 350293B
Authority
MX
Mexico
Prior art keywords
site
fviii
directed modification
polyethylene glycol
factor viii
Prior art date
Application number
MX2014005051A
Other languages
English (en)
Inventor
Q Pan Clark
E Murphy John
Mei Baisong
S Strauss Jonathan
Tjandra Hendri
Chen Jianmin
Barnett Thomas
Tang Liang
Wang Deqian
Original Assignee
Bayer Healthcare Llc
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=36337298&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MX350293(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Healthcare Llc filed Critical Bayer Healthcare Llc
Publication of MX350293B publication Critical patent/MX350293B/es

Links

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
    • A61K38/37—Factors VIII
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07K17/08—Peptides being immobilised on, or in, an organic carrier the carrier being a synthetic polymer
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Materials For Medical Uses (AREA)
  • Orthopedics, Nursing, And Contraception (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)

Abstract

La presente invención se refiere a un conjugado que tiene actividad procoagulante de factor VIII que comprende un polipéptido de factor VIII funcional unido covalentemente a uno o más polímeros biocompatibles para usarse en el tratamiento de la hemofilia en un paciente que tiene anticuerpos inhibidores de factor VIII, en donde el polímero biocompatible está unido covalentemente al polipéptido de factor VIII funcional en un sitio que es o está dentro de 20 Angstrom de un sitio de unión para los anticuerpos inhibidores de factor VIII.
MX2014005051A 2004-11-12 2005-11-14 Modificacion dirigida al sitio del factor viii. MX350293B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62727704P 2004-11-12 2004-11-12
PCT/US2005/041205 WO2006053299A2 (en) 2004-11-12 2005-11-14 Site-directed modification of fviii

Publications (1)

Publication Number Publication Date
MX350293B true MX350293B (es) 2017-09-04

Family

ID=36337298

Family Applications (3)

Application Number Title Priority Date Filing Date
MX2014005051A MX350293B (es) 2004-11-12 2005-11-14 Modificacion dirigida al sitio del factor viii.
MX2007005466A MX2007005466A (es) 2004-11-12 2005-11-14 Modificacion dirigida al sitio del factor viii.
MX2017007144A MX392760B (es) 2004-11-12 2005-11-14 Modificacion dirigida al sitio del factor viii.

Family Applications After (2)

Application Number Title Priority Date Filing Date
MX2007005466A MX2007005466A (es) 2004-11-12 2005-11-14 Modificacion dirigida al sitio del factor viii.
MX2017007144A MX392760B (es) 2004-11-12 2005-11-14 Modificacion dirigida al sitio del factor viii.

Country Status (32)

Country Link
US (4) US7632921B2 (es)
EP (9) EP2371856B1 (es)
JP (5) JP2008524117A (es)
KR (7) KR101483917B1 (es)
CN (6) CN105148287B (es)
AU (1) AU2005304622B2 (es)
BE (1) BE2019C523I2 (es)
BR (2) BR122016022033B8 (es)
CA (1) CA2586379C (es)
CY (3) CY1119292T1 (es)
DK (3) DK2371856T3 (es)
ES (4) ES2930159T3 (es)
FR (1) FR19C1031I2 (es)
HN (1) HN2007015683A (es)
HR (2) HRP20180481B1 (es)
HU (5) HUE059193T2 (es)
IL (3) IL182903A (es)
LT (5) LT1824988T (es)
LU (1) LUC00118I2 (es)
MA (1) MA29663B1 (es)
MX (3) MX350293B (es)
NL (1) NL300989I2 (es)
NO (3) NO20210454A1 (es)
NZ (1) NZ555032A (es)
PH (2) PH12014500352B1 (es)
PL (3) PL2363414T3 (es)
PT (4) PT1824988T (es)
RU (1) RU2423380C2 (es)
SI (4) SI3130601T1 (es)
UA (1) UA95225C2 (es)
WO (1) WO2006053299A2 (es)
ZA (1) ZA200703696B (es)

Families Citing this family (107)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2522345A1 (en) 2003-04-09 2004-11-18 Neose Technologies, Inc. Glycopegylation methods and proteins/peptides produced by the methods
WO2005012484A2 (en) 2003-07-25 2005-02-10 Neose Technologies, Inc. Antibody-toxin conjugates
US20080305992A1 (en) 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
KR101100059B1 (ko) * 2004-06-30 2011-12-29 넥타르 테라퓨틱스 중합체­인자 ｉｘ 부분의 접합체
EP1771066A2 (en) 2004-07-13 2007-04-11 Neose Technologies, Inc. Branched peg remodeling and glycosylation of glucagon-like peptide-1 glp-1
EP3061461A1 (en) 2004-10-29 2016-08-31 ratiopharm GmbH Remodeling and glycopegylation of fibroblast growth factor (fgf)
LT1824988T (lt) 2004-11-12 2017-10-25 Bayer Healthcare Llc Nukreipta į užduotą saitą fviii modifikacija
NZ556436A (en) 2005-01-10 2010-11-26 Biogenerix Ag Glycopegylated granulocyte colony stimulating factor
US9187546B2 (en) 2005-04-08 2015-11-17 Novo Nordisk A/S Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants
EP2360170A3 (en) 2005-06-17 2012-03-28 Novo Nordisk Health Care AG Selective reduction and derivatization of engineered proteins comprinsing at least one non-native cysteine
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
US7855279B2 (en) 2005-09-27 2010-12-21 Amunix Operating, Inc. Unstructured recombinant polymers and uses thereof
US20090048440A1 (en) 2005-11-03 2009-02-19 Neose Technologies, Inc. Nucleotide Sugar Purification Using Membranes
RU2008145084A (ru) * 2006-05-24 2010-06-27 Ново Нордиск Хелс Кеа Аг (Ch) Аналоги фактора ix, имеющие пролонгированное время полужизни in vivo
US9187532B2 (en) 2006-07-21 2015-11-17 Novo Nordisk A/S Glycosylation of peptides via O-linked glycosylation sequences
WO2008057683A2 (en) 2006-10-03 2008-05-15 Novo Nordisk A/S Methods for the purification of polypeptide conjugates
JP5876208B2 (ja) 2006-12-15 2016-03-02 バクスター・インターナショナル・インコーポレイテッドＢａｘｔｅｒ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｉｎｃｏｒｐ０Ｒａｔｅｄ 延長されたｉｎｖｉｖｏ半減期を有する第ＶＩＩａ因子−（ポリ）シアル酸結合体
BRPI0809670A8 (pt) 2007-04-03 2018-12-18 Biogenerix Ag métodos para aumentar a produção de célula tronco, para aumentar o número de granulócitos em um indivíduo, para prevenir, tratar e aliviar a mielossupressão que resulta de uma terapia contra o câncer, para tratar uma condição em um indivíduo, para tratar neutropenia e trombocitopenia em um mamífero, para expandir células tronco hematopoiéticas em cultura, para aumentar a hematopoiese em um indivíduo, para aumentar o número de célulars progenitoras hematopoiéticas em um indivíduo, e para fornecer enxerto estável da medula óssea, e, forma de dosagem oral.
MX2009013259A (es) 2007-06-12 2010-01-25 Novo Nordisk As Proceso mejorado para la produccion de azucares de nucleotidos.
EP2222329A1 (en) * 2007-11-09 2010-09-01 Baxter International Inc. Modified recombinant factor viii and von willebrand factor and methods of use
RU2573587C2 (ru) * 2008-02-27 2016-01-20 Ново Нордиск А/С Конъюгированные молекулы фактора viii
KR101841870B1 (ko) * 2008-05-16 2018-03-23 바이엘 헬스케어 엘엘씨 표적화 응고 인자 및 그의 사용 방법
MX2010013219A (es) * 2008-06-04 2011-04-11 Bayer Healthcare Llc Muteínas de fviii para el tratamiento de la enfermedad de von willebrand.
AU2009262476C1 (en) 2008-06-24 2016-06-02 Csl Behring Gmbh Factor VIII, von Willebrand factor or complexes thereof with prolonged in vivo half-life
WO2010019263A2 (en) * 2008-08-15 2010-02-18 Genzyme Corporation Soluble flt constructs for treating cancers
SMT201800486T1 (it) * 2008-10-17 2018-11-09 Baxalta Inc Fattori sanguigni modificati comprendenti un grado basso di polimero solubile in acqua
WO2010062768A1 (en) * 2008-11-03 2010-06-03 Bayer Healthcare Llc Method for the treatment of hemophilia
WO2010060081A1 (en) * 2008-11-24 2010-05-27 Bayer Healthcare Llc Method of determining pegylated blood coagulation factor activity in a silica-based activated partial thromboplastin time assay
WO2010083536A1 (en) * 2009-01-19 2010-07-22 Bayer Healthcare Llc Protein conjugate having an endopeptidase-cleavable bioprotective moiety
PL2393828T3 (pl) 2009-02-03 2017-06-30 Amunix Operating Inc. Wydłużone rekombinowane polipeptydy i zawierające je kompozycje
US20110046060A1 (en) * 2009-08-24 2011-02-24 Amunix Operating, Inc., Coagulation factor IX compositions and methods of making and using same
US20110306551A1 (en) * 2009-02-19 2011-12-15 Novo Nordisk A/S Modification of Factor VIII
DK2408800T3 (en) * 2009-03-20 2016-08-29 Hanmi Science Co Ltd A process for the preparation of a site-specific conjugate of a physiologically active polypeptide
JP5739865B2 (ja) * 2009-03-24 2015-06-24 バイエル・ヘルスケア・エルエルシー 第ｖｉｉｉ因子変異体および使用の方法
SG178141A1 (en) 2009-07-27 2012-03-29 Baxter Int Blood coagulation protein conjugates
US8809501B2 (en) 2009-07-27 2014-08-19 Baxter International Inc. Nucleophilic catalysts for oxime linkage
JP5909755B2 (ja) 2009-07-27 2016-04-27 リポクセン テクノロジーズ リミテッド 非血液凝固タンパク質の糖ポリシアル酸化
US8642737B2 (en) 2010-07-26 2014-02-04 Baxter International Inc. Nucleophilic catalysts for oxime linkage
EP3093029A1 (en) 2009-07-27 2016-11-16 Baxalta GmbH Blood coagulation protein conjugates
AU2010325787B2 (en) 2009-12-06 2016-05-12 Bioverativ Therapeutics Inc. Factor VIII-Fc chimeric and hybrid polypeptides, and methods of use thereof
WO2011075185A1 (en) 2009-12-18 2011-06-23 Oligasis Targeted drug phosphorylcholine polymer conjugates
US20130040888A1 (en) 2010-02-16 2013-02-14 Novo Nordisk A/S Factor VIII Molecules With Reduced VWF Binding
EA201290804A1 (ru) * 2010-02-21 2013-03-29 БАЙЕР ХелсКер ЛЛСи Способ активации и сопряжения биомолекул
KR20130097636A (ko) 2010-04-15 2013-09-03 올리가시스 고분자량 쌍성이온-함유 중합체
GB201007357D0 (en) * 2010-04-30 2010-06-16 Leverton Licence Holdings Ltd Conjugated factor VIII
GB201007356D0 (en) 2010-04-30 2010-06-16 Leverton Licence Holdings Ltd Conjugated factor VIIa
US9611310B2 (en) 2010-07-09 2017-04-04 Bioverativ Therapeutics Inc. Systems for factor VIII processing and methods thereof
EP2635297B1 (en) 2010-11-05 2019-02-27 Baxalta GmbH A new variant of antihemophilic factor viii having increased specific activity
RU2013131911A (ru) * 2010-12-16 2015-01-27 Ново Нордиск А/С Водный раствор фактора viii
DK2654794T3 (da) 2010-12-22 2020-06-08 Baxalta GmbH Materialer og fremgangsmåder til konjugering af et vandopløseligt fedtsyrederivat til et protein
AU2012262428C1 (en) 2011-05-27 2018-10-11 Takeda Pharmaceutical Company Limited Therapeutic proteins with increased half-life and methods of preparing same
PT2717898T (pt) 2011-06-10 2019-05-20 Bioverativ Therapeutics Inc Compostos pró-coagulantes e processos para a sua utilização
CN103930440A (zh) 2011-07-01 2014-07-16 拜耳知识产权有限责任公司 松弛素融合多肽及其用途
KR102110736B1 (ko) 2011-07-08 2020-05-14 바이오버라티브 테라퓨틱스 인크. Viii 인자 키메라 및 하이브리드 폴리펩타이드, 그리고 이들의 사용 방법
CN104093735B (zh) 2011-09-23 2018-07-06 诺沃—诺迪斯克有限公司 新的胰高血糖素类似物
KR20130049671A (ko) * 2011-11-04 2013-05-14 한미사이언스 주식회사 생리활성 폴리펩타이드 결합체 제조 방법
PL2814502T3 (pl) 2012-02-15 2018-02-28 Csl Behring Gmbh Warianty czynnika von Willebranda mające ulepszone powinowactwo do wiązania czynnika VIII
CN119192402A (zh) 2012-02-15 2024-12-27 比奥贝拉蒂治疗公司 因子viii组合物及其制备和使用方法
WO2013123457A1 (en) 2012-02-15 2013-08-22 Biogen Idec Ma Inc. Recombinant factor viii proteins
EP2666782A1 (en) * 2012-05-22 2013-11-27 Imnate Sarl Coagulation factor VIII with reduced immunogenicity.
EP3693000B1 (en) 2012-06-08 2022-03-02 Bioverativ Therapeutics Inc. Procoagulant compounds
EP3404105A1 (en) 2012-07-06 2018-11-21 Bioverativ Therapeutics Inc. Cell line expressing single chain factor viii polypeptides and uses thereof
CA2888806A1 (en) 2012-10-18 2014-04-24 Biogen Idec Ma Inc. Methods of using a fixed dose of a clotting factor
EP2914293A4 (en) 2012-10-30 2016-04-20 Biogen Ma Inc METHOD OF USE OF FVIII POLYPEPTIDE
RU2015144076A (ru) * 2013-03-15 2017-04-24 БАЙЕР ХелсКер ЛЛСи Композиции рекомбинантного фактора viii
WO2014144549A1 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Factor ix polypeptide formulations
EA201890671A1 (ru) 2013-03-15 2019-01-31 Биовератив Терапьютикс Инк. Препараты полипептида фактора viii
WO2014170496A1 (en) 2013-04-18 2014-10-23 Novo Nordisk A/S Stable, protracted glp-1/glucagon receptor co-agonists for medical use
ES2657291T3 (es) 2013-04-22 2018-03-02 Csl Ltd. Un complejo covalente de factor de von Willebrand y factor VIII asociado por un puente disulfuro
TW201519900A (zh) * 2013-04-28 2015-06-01 Bayer Healthcare Llc 用於誘導對凝血因子蛋白之免疫耐受性的組成物及方法
EP4108254A1 (en) 2013-08-14 2022-12-28 Bioverativ Therapeutics Inc. Recombinant factor viii proteins
WO2015023891A2 (en) 2013-08-14 2015-02-19 Biogen Idec Ma Inc. Factor viii-xten fusions and uses thereof
DK3041513T3 (da) 2013-09-08 2020-10-26 Kodiak Sciences Inc Zwitterioniske faktor viii-polymerkonjugater
BR112016009064A2 (pt) * 2013-10-22 2017-09-19 Inst Nat Sante Rech Med Dispositivo de emplastro cutâneo; sistema de liberação de fármaco; kit; e método de tratamento da hemofilia em um indivíduo em necessidade do mesmo
US10584147B2 (en) 2013-11-08 2020-03-10 Biovertiv Therapeutics Inc. Procoagulant fusion compound
RU2546297C1 (ru) * 2013-11-19 2015-04-10 Федеральное государственное бюджетное учреждение "Научно-исследовательский институт фармакологии" Сибирского отделения Российской академии медицинских наук Средство, улучшающее реологические свойства крови
ES2967617T3 (es) 2013-12-06 2024-05-03 Bioverativ Therapeutics Inc Herramientas de farmacocinética poblacional y sus usos
CA2934705C (en) 2014-01-20 2020-03-31 Octapharma Ag A process for manufacturing factor viii having an improved ratio of fviii:c/fviii:ag
EP3102589A1 (en) 2014-02-04 2016-12-14 Biogen MA Inc. Use of cation-exchange chromatography in the flow-through mode to enrich post-translational modifications
WO2015132724A1 (en) 2014-03-05 2015-09-11 Pfizer Inc. Improved muteins of clotting factor viii
SG10201913735SA (en) 2014-03-24 2020-03-30 Bioverativ Therapeutics Inc Lyophilized factor ix formulations
WO2015154090A1 (en) * 2014-04-04 2015-10-08 Bloodworks Routine laboratory and point-of-care (poc) testing for hemostasis
AU2015243961A1 (en) 2014-04-10 2016-10-27 Bayer Healthcare Llc Compounded media powder formulation and method of preparation of liquid medium for cell culture
US10570184B2 (en) 2014-06-04 2020-02-25 Novo Nordisk A/S GLP-1/glucagon receptor co-agonists for medical use
BR112016030950A2 (pt) 2014-07-02 2018-03-27 Csl Ltd polipeptídeo modificado que se liga ao fator viii, complexo, composição farmacêutica, métodos para tratar uma coagulopatia, para produzir um polipeptídeo que compreende um vwf modificado e para aumentar a afinidade de ligação ao fator viii do vwf e a meia-vida do fator viii, uso de um polipeptídeo modificado ou de um complexo, polinucleotídeo, plasmídeo ou vetor, e, célula hospedeira.
MA40864A (fr) 2014-10-31 2017-09-05 Biogen Ma Inc Hypotaurine, gaba, bêta-alanine et choline pour la régulation de l'accumulation de sous-produits résiduaires dans des procédés de culture de cellules mammifères
CN107406493B (zh) 2015-03-06 2021-08-13 康诺贝林伦瑙有限公司 具有改善的半衰期的经修饰的血管性血友病因子
RU2017145002A (ru) 2015-05-22 2019-06-24 Цсл Беринг Ленгнау Аг Способы получения модифицированного фактора фон виллебранда
JP6573989B2 (ja) 2015-05-22 2019-09-11 ツェー・エス・エル・ベーリング・レングナウ・アクチエンゲゼルシャフト 血友病を処置するための切断型フォン・ヴィルブランド因子ポリペプチド
CA2994547A1 (en) 2015-08-03 2017-02-09 Bioverativ Therapeutics Inc. Factor ix fusion proteins and methods of making and using same
US9849125B1 (en) 2015-11-03 2017-12-26 Banner Lifie Sciences LLC Anti-overingestion dosage forms
CN108779165B (zh) 2016-01-07 2022-12-02 康诺贝林伦瑙有限公司 突变的冯·维勒布兰德因子
JP6851381B6 (ja) 2016-01-07 2021-04-21 ツェー・エス・エル・ベーリング・レングナウ・アクチエンゲゼルシャフト 変異切断型フォンウィルブランド因子
CN109689683A (zh) * 2016-06-24 2019-04-26 财团法人牧岩生命科学研究所 重组单链fvⅲ及其化学缀合物
EP3538133B1 (en) 2016-11-11 2021-02-17 CSL Behring Lengnau AG Truncated von willebrand factor polypeptides for treating hemophilia
ES2908008T3 (es) 2016-11-11 2022-04-27 CSL Behring Lengnau AG Polipéptidos truncados del Factor de von Willebrand para su administración extravascular en el tratamiento o profilaxis de un trastorno de la coagulación sanguínea
EP3541834A1 (en) 2016-11-16 2019-09-25 Bayer Healthcare LLC Red blood cell targeted factor viii and method of using the same
BR112019011198A2 (pt) 2016-12-02 2019-12-17 Bioverativ Therapeutics Inc métodos de indução de tolerância imune a fatores de coagulação
US12161696B2 (en) 2016-12-02 2024-12-10 Bioverativ Therapeutics Inc. Methods of treating hemophilic arthropathy using chimeric clotting factors
CR20190389A (es) 2017-01-31 2019-11-26 Bioverativ Therapeutics Inc Proteínas de fusión del factor ix y procedimientos de preparación y utilización de las mismas
US10335375B2 (en) 2017-05-30 2019-07-02 Patheon Softgels, Inc. Anti-overingestion abuse deterrent compositions
KR20190086269A (ko) * 2018-01-12 2019-07-22 재단법인 목암생명과학연구소 체내 지속형 재조합 당단백질 및 이의 제조방법
TW202015723A (zh) 2018-05-18 2020-05-01 美商百歐維拉提夫治療公司 治療ａ型血友病的方法
KR102575788B1 (ko) 2018-05-18 2023-09-08 정저우 젠사이언시스 인코포레이티드 개선된 fviii 융합 단백질 및 이의 용도
CN114786731A (zh) 2019-10-10 2022-07-22 科达制药股份有限公司 治疗眼部病症的方法
WO2021091881A1 (en) * 2019-11-04 2021-05-14 The Trustees Of Columbia University In The City Of New York High concentration cell penetrating caspase inhibitor conjugates compositions and methods thereof
CA3159985A1 (en) * 2019-12-06 2021-06-10 The Children's Hospital Of Philadelphia Compositions and methods for modulating factor viii function

Family Cites Families (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59172425A (ja) * 1983-03-18 1984-09-29 Nippon Chemiphar Co Ltd 新規な血液凝固因子誘導体およびその製造法ならびにそれを含有する血液凝固促進剤
US7138505B1 (en) 1984-01-12 2006-11-21 Novartis Vaccines And Diagnostics, Inc. Factor VIII:C nucleic acid molecules
US4970300A (en) 1985-02-01 1990-11-13 New York University Modified factor VIII
US5451521A (en) 1986-05-29 1995-09-19 Genetics Institute, Inc. Procoagulant proteins
US5422260A (en) 1986-05-29 1995-06-06 Genetics Institute, Inc. -Legal Affairs Human factor VIII:c muteins
US6346513B1 (en) 1987-06-12 2002-02-12 Baxter Trading Gmbh Proteins with factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them
EP0294910B1 (en) 1987-06-12 1996-09-11 Immuno Ag Novel proteins with factor VIII activity, process for their preparation using genetically engineered cells and pharmaceutical compositions containing them
US5171844A (en) 1987-06-12 1992-12-15 Gist-Brocades N.W. Proteins with factor viii activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them
AU2473388A (en) * 1987-11-16 1989-06-22 Scripps Clinic And Research Foundation Treatment of factor viii inhibitors
US5166322A (en) 1989-04-21 1992-11-24 Genetics Institute Cysteine added variants of interleukin-3 and chemical modifications thereof
SE465222C5 (sv) 1989-12-15 1998-02-10 Pharmacia & Upjohn Ab Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning
US5766897A (en) 1990-06-21 1998-06-16 Incyte Pharmaceuticals, Inc. Cysteine-pegylated proteins
US6376463B1 (en) 1992-04-07 2002-04-23 Emory University Modified factor VIII
US6037452A (en) 1992-04-10 2000-03-14 Alpha Therapeutic Corporation Poly(alkylene oxide)-Factor VIII or Factor IX conjugate
CZ290342B6 (cs) 1992-10-02 2002-07-17 Genetics Institute Inc. Kompozice stabilní při skladování, obsahující koagulační faktor VIII a neiontovou povrchově aktivní látku a způsob její výroby
AU6029594A (en) 1993-01-15 1994-08-15 Enzon, Inc. Factor viii - polymeric conjugates
SE504074C2 (sv) 1993-07-05 1996-11-04 Pharmacia Ab Proteinberedning för subkutan, intramuskulär eller intradermal administrering
AU685187B2 (en) 1993-10-29 1998-01-15 Incyte Pharmaceuticals, Inc. Chimeric proteins including protease nexin-1 variants
IL113010A (en) 1994-03-31 1999-10-28 Pharmacia & Upjohn Ab Pharmaceutical formulation comprising factor viii with an activity of at least 500iu/ml and an enhancer for improved subcutaneous intramuscular or intradermal administration
BE1008491A3 (fr) * 1994-07-14 1996-05-07 Croix Rouge De Belgique Depart Sequence polypeptidique antigenique du facteur viii, fragments et/ou epitopes de celle-ci.
WO1996041813A2 (en) 1994-11-09 1996-12-27 Offord Robin E Functionalized polymers for site-specific attachment
AU691111B2 (en) * 1995-06-21 1998-05-07 Google Technology Holdings LLC Method and antenna for providing an omnidirectional pattern
WO1997003195A1 (en) 1995-07-11 1997-01-30 Chiron Corporation Novel factor viii:c polypeptide analogs with altered protease sites
SE9503380D0 (sv) * 1995-09-29 1995-09-29 Pharmacia Ab Protein derivatives
AT403438B (de) 1996-05-24 1998-02-25 Immuno Ag Pharmazeutische präparation mit faktor viii prokoagulationsaktivität und vwf-bindungsaktivität
US6458563B1 (en) * 1996-06-26 2002-10-01 Emory University Modified factor VIII
ES2273373T3 (es) * 1996-08-02 2007-05-01 Ortho-Mcneil Pharmaceutical, Inc. Polipeptidos que tienen unido a su extremo n un unico polimero soluble al agua.
CA2225189C (en) 1997-03-06 2010-05-25 Queen's University At Kingston Canine factor viii gene, protein and methods of use
IL133974A0 (en) 1997-07-14 2001-04-30 Bolder Biotechnology Inc Derivatives of growth hormone and related proteins
US6753165B1 (en) * 1999-01-14 2004-06-22 Bolder Biotechnology, Inc. Methods for making proteins containing free cysteine residues
CA2306629A1 (en) * 1997-10-17 1999-04-29 Harvest Technologies Corporation Precipitation of growth-factor-enriched fibrinogen concentrate from platelet rich plasma
EP0922446A1 (en) 1997-12-03 1999-06-16 Applied Research Systems Ars Holding N.V. Solution-phase site-specific preparation of GRF-PEG conjugates
AU747391B2 (en) 1998-04-27 2002-05-16 Cantab Biopharmaceuticals Patents Limited Pharmaceutical composition comprising factor VIII and neutral liposomes
US6759216B1 (en) 1998-11-06 2004-07-06 Emory University Glycosylated, low antigenicity low immunogenicity factor VIII
AU775529B2 (en) 1998-11-10 2004-08-05 Stichting Sanquin Bloedvoorziening A factor VIII-polypeptide with factor VIII:C-activity
US6136599A (en) 1998-12-10 2000-10-24 Bayer Corporation Human hybrid host cell for mammalian gene expression
US6358703B1 (en) 1998-12-10 2002-03-19 Bayer Corporation Expression system for factor VIII
NZ513077A (en) 1999-01-14 2004-03-26 Bolder Biotechnology Inc Methods for making proteins containing free cysteine residues
WO2000071714A2 (en) 1999-05-24 2000-11-30 The American National Red Cross Methods of reducing factor viii clearance and compositions therefor
PL206148B1 (pl) * 2000-02-11 2010-07-30 Bayer HealthCare LLCBayer HealthCare LLC Koniugat polipeptydowy, polipeptyd, sekwencja nukleotydowa, wektor ekspresyjny, komórka gospodarz, sposób wytwarzania koniugatu polipeptydowego, środek farmaceutyczny i zastosowanie koniugatu polipeptydowego
MXPA03002256A (es) 2000-09-19 2003-09-10 Univ Emory Factor viii modificado.
AU2002248329B2 (en) 2001-01-12 2007-06-28 The American National Red Cross Methods and compositions for reducing heparan sulfate proteoglycan-mediated clearance of factor VIII
AU2002249096B2 (en) * 2001-03-22 2007-06-28 Novo Nordisk Health Care Ag Coagulation factor VII derivatives
WO2002096454A1 (en) 2001-05-31 2002-12-05 D. Collen Research Foundation Vzw Recombinant molecules with reduced immunogenicity, methods and intermediates for obtaining them and their use in pharmaceutical compositions and diagnostic tools
WO2002098454A2 (en) 2001-05-31 2002-12-12 D. Collen Research Foundation Vzw Onderwijsen Navorsing Campus Gasthuisberg K.U. Leuven Recombinant molecules with reduced immunogenicity, methods and intermediates for obtaining them and their use in pharmaceutical compositions and diagnostic tools
AU2002310438B2 (en) 2001-06-14 2008-05-01 The Scripps Research Institute Stabilized proteins with engineered disulfide bonds
EP1572889B1 (en) 2001-10-05 2008-12-17 Expression Therapeutics, LLC Nucleic acid and amino acid sequences encoding high-level expressor factor viii polypeptides and methods of use
CA2482926A1 (en) 2002-04-18 2003-10-23 Merck Patent Gesellschaft Mit Beschraenkter Haftung Modified factor viii
US8003117B2 (en) 2002-11-20 2011-08-23 Nof Corporation Polyalkylene glycol derivative and modified bio-related substance
JP4412461B2 (ja) 2002-11-20 2010-02-10 日油株式会社 修飾された生体関連物質、その製造方法および中間体
AU2003300139B2 (en) 2002-12-31 2008-08-28 Nektar Therapeutics Maleamic acid polymer derivatives and their bioconjugates
KR101025143B1 (ko) 2002-12-31 2011-04-01 넥타르 테라퓨틱스 가수분해상으로 안정한 말레이미드－종결 중합체
MXPA05007348A (es) 2003-01-06 2005-10-05 Nektar Therapeutics Al Corp Derivados de polimeros solubles en agua tiol-selectivos.
EP2572733A1 (en) * 2003-02-26 2013-03-27 Nektar Therapeutics Polymer-factor VIII moiety conjugates
US20050176108A1 (en) * 2003-03-13 2005-08-11 Young-Min Kim Physiologically active polypeptide conjugate having prolonged in vivo half-life
US20040180054A1 (en) * 2003-03-13 2004-09-16 Hanmi Pharm. Co., Ltd. Physiologically active polypeptide conjugate having prolonged in vivo half-life
EA010016B1 (ru) * 2003-05-12 2008-06-30 Афимакс, Инк. Новые модифицированные полиэтиленгликолем соединения и их применение
NZ541374A (en) 2003-05-23 2008-09-26 Nektar Therapeutics Al Corp PEG derivatives having an amidocarbonate linkage
EP1502921A1 (en) 2003-07-29 2005-02-02 ZLB Behring GmbH Recombinant mutated human factor VIII (FVIII) with improved stability
US20050123997A1 (en) 2003-10-30 2005-06-09 Lollar John S. Modified fVIII having reduced immunogenicity through mutagenesis of A2 and C2 epitopes
US7211559B2 (en) 2003-10-31 2007-05-01 University Of Maryland, Baltimore Factor VIII compositions and methods
WO2005055930A2 (en) 2003-12-03 2005-06-23 University Of Rochester Recombinant factor viii having increased specific activity
WO2006027111A1 (en) 2004-09-06 2006-03-16 Zlb Behring Gmbh Modified coagulation factor viii with enhanced stability
LT1824988T (lt) 2004-11-12 2017-10-25 Bayer Healthcare Llc Nukreipta į užduotą saitą fviii modifikacija
US20080227691A1 (en) 2005-04-01 2008-09-18 Novo Nordisk Health Care Ag Blood Coagulation FVIII Analogues
CA2647314A1 (en) * 2006-03-31 2007-11-08 Baxter International Inc. Pegylated factor viii
US7645860B2 (en) * 2006-03-31 2010-01-12 Baxter Healthcare S.A. Factor VIII polymer conjugates

Also Published As

Publication number Publication date
CY2019024I2 (el) 2019-11-27
LTPA2019509I1 (lt) 2019-08-26
EP3243833A1 (en) 2017-11-15
BRPI0517795A (pt) 2008-10-21
PT2371856T (pt) 2022-08-12
KR20160105928A (ko) 2016-09-07
RU2423380C2 (ru) 2011-07-10
NO344606B1 (no) 2020-02-10
HUE060016T2 (hu) 2023-01-28
EP3130601B1 (en) 2020-07-15
KR20140019489A (ko) 2014-02-14
PH12014500352A1 (en) 2015-07-20
DK1824988T3 (en) 2017-08-07
EP2772500B1 (en) 2019-12-25
HN2007015683A (es) 2011-07-11
ZA200703696B (en) 2008-08-27
EP1824988A2 (en) 2007-08-29
EP1824988A4 (en) 2008-12-31
ES2930159T3 (es) 2022-12-07
PH12014500352B1 (en) 2019-09-25
HK1218718A1 (zh) 2017-03-10
MA29663B1 (fr) 2008-08-01
US20160051633A1 (en) 2016-02-25
BRPI0517795B8 (pt) 2021-05-25
IL232540A (en) 2017-08-31
CN105753968A (zh) 2016-07-13
PL2371856T3 (pl) 2022-08-22
KR101654011B1 (ko) 2016-09-05
WO2006053299A2 (en) 2006-05-18
LUC00118I2 (es) 2019-12-27
IL182903A0 (en) 2007-08-19
JP2008524117A (ja) 2008-07-10
JP2017105773A (ja) 2017-06-15
RU2007121517A (ru) 2008-12-20
KR101483917B1 (ko) 2015-01-16
PT1824988T (pt) 2017-07-21
JP2013067621A (ja) 2013-04-18
KR101243564B1 (ko) 2013-03-27
LT2363414T (lt) 2022-10-25
US20130274445A1 (en) 2013-10-17
IL234433B (en) 2019-11-28
PT2363414T (pt) 2022-08-04
ES2930143T3 (es) 2022-12-07
SI2371856T1 (sl) 2022-09-30
EP3130601A1 (en) 2017-02-15
EP2363414A2 (en) 2011-09-07
ES2633916T3 (es) 2017-09-26
EP2371856A2 (en) 2011-10-05
BRPI0517795A8 (pt) 2018-12-26
CN103102406A (zh) 2013-05-15
NO20210454A1 (no) 2007-06-27
SI2363414T1 (sl) 2022-09-30
BR122016022033B8 (pt) 2021-05-25
MX392760B (es) 2025-03-24
HUE059193T2 (hu) 2022-10-28
HK1182121A1 (en) 2013-11-22
CN101124331A (zh) 2008-02-13
EP2772500A1 (en) 2014-09-03
KR101904630B1 (ko) 2018-10-04
CN105148287B (zh) 2019-07-09
DK2371856T3 (en) 2022-08-08
CN107082806A (zh) 2017-08-22
CA2586379C (en) 2012-04-03
JP6018238B2 (ja) 2016-11-02
PL2363414T3 (pl) 2022-09-05
DK2363414T3 (da) 2022-08-08
EP2363414B1 (en) 2022-05-18
CN103102406B (zh) 2015-05-27
BRPI0517795B1 (pt) 2020-03-31
ES2821832T3 (es) 2021-04-27
KR20140091618A (ko) 2014-07-21
US20060115876A1 (en) 2006-06-01
PH12019501613A1 (en) 2020-09-14
LUC00118I1 (es) 2019-05-13
PT3130601T (pt) 2020-10-01
LT3130601T (lt) 2020-09-10
KR20180110192A (ko) 2018-10-08
EP3323829B1 (en) 2020-07-15
BE2019C523I2 (es) 2025-02-10
EP1824988B1 (en) 2017-04-19
CY2019024I1 (el) 2019-11-27
JP6109523B2 (ja) 2017-04-05
NZ555032A (en) 2010-02-26
JP2015134780A (ja) 2015-07-27
LTC1824988I2 (lt) 2021-02-25
HUS1900026I1 (hu) 2022-04-28
MX2007005466A (es) 2007-10-19
US9364520B2 (en) 2016-06-14
WO2006053299A3 (en) 2006-08-24
EP2363414A3 (en) 2012-03-21
KR101468345B1 (ko) 2014-12-03
JP2017101028A (ja) 2017-06-08
CA2586379A1 (en) 2006-05-18
EP3153181A1 (en) 2017-04-12
EP2371856A3 (en) 2012-03-14
JP6487895B2 (ja) 2019-03-20
EP2371856B1 (en) 2022-05-18
HRP20180481A2 (hr) 2018-06-29
FR19C1031I1 (es) 2019-06-28
NO20072997L (no) 2007-06-27
CN103214569B (zh) 2016-12-28
EP3323829A1 (en) 2018-05-23
CY1119292T1 (el) 2018-02-14
EP3243833B1 (en) 2020-06-17
NO345800B1 (no) 2021-08-09
CN103214569A (zh) 2013-07-24
US9096656B2 (en) 2015-08-04
LT2371856T (lt) 2022-08-25
HK1117875A1 (en) 2009-01-23
NL300989I1 (nl) 2019-05-22
LT1824988T (lt) 2017-10-25
IL232540A0 (en) 2014-06-30
FR19C1031I2 (fr) 2020-06-05
US7632921B2 (en) 2009-12-15
KR20120136413A (ko) 2012-12-18
HRP20070268A2 (en) 2007-09-30
CN101124331B (zh) 2013-04-24
SI3130601T1 (sl) 2020-11-30
UA95225C2 (ru) 2011-07-25
IL182903A (en) 2014-09-30
US20100081615A1 (en) 2010-04-01
AU2005304622B2 (en) 2012-03-29
KR20070110260A (ko) 2007-11-16
HUE033776T2 (en) 2018-01-29
CN105148287A (zh) 2015-12-16
NL300989I2 (nl) 2019-11-28
NO20200044A1 (no) 2007-06-27
KR20130036780A (ko) 2013-04-12
BR122016022033B1 (pt) 2021-03-02
AU2005304622A1 (en) 2006-05-18
SI1824988T1 (sl) 2017-11-30
HRP20180481B1 (hr) 2022-02-18
HRP20070268B1 (hr) 2018-04-20
CY1123384T1 (el) 2021-12-31
PL1824988T3 (pl) 2018-01-31
EP3243834A1 (en) 2017-11-15
JP6559642B2 (ja) 2019-08-14
HUE050542T2 (hu) 2020-12-28

Similar Documents

Publication Publication Date Title
PH12019501613A1 (en) Site-directed modification of fviii
WO2006047419A3 (en) Heterobifunctional poly(ethylene glycol) and uses thereof
DE50306232D1 (de) Ampholytisches copolymer und dessen verwendung
CY1121314T1 (el) Παραγωγο ραπαμυκινης για την θεραπευτικη αντιμετωπιση του καρκινου του πνευμονα
WO2005091944A3 (en) Glycol linked fgf-21 compounds
NO20031179D0 (no) Chemokin-reseptorbindende heterocykliske forbindelser
MX2008001706A (es) Conjugados de una porcion g-csf y un polimero.
TR200400295T2 (tr) Kimyasal olarak modifiye edilmiş ensülin'in akçiğer yoluyla verilmesi
PL374523A1 (en) Calicheamicin derivative-carrier conjugates
GEP20074016B (en) Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof
ATE455561T1 (de) Konjugate von zytotoxischen mitteln und biologisch aktiven peptiden
MXPA04003597A (es) Conjugados polimericos de antagonistas opiaceos.
ATE531374T1 (de) Vorrichtung auf polymerbasis mit verzögerter freisetzung
EP1663171A4 (en) HETEROFUNCTIONAL COPOLYMERS OF GLYCEROL AND POLYETHYLENE GLYCOL, CONJUGATES AND COMPOSITIONS THEREOF
BRPI0507680A (pt) partìculas de fosfato de cálcio terapêuticas e métodos de fabricação e uso das mesmas
CY1116415T1 (el) Φαρμακευτικες συνθεσεις που περιλαμβανουν l-733060 για χρηση στη θεραπευτικη αγωγη καρκινικων ογκων
UA82983C2 (ru) Полимерные коньюгаты найбластина и способы их использования
MY181129A (en) Site-directed modification of fviii
MY151329A (en) Site-directed modification of fviii
MY173864A (en) Site-directed modification of fviii
CY1125477T1 (el) Κατευθυνομενη απο θεση τροποποιηση του fviii
WO2006065867A3 (en) Polymer-linked pseudomonas exotoxin immunotoxin
SV2007002756A (es) Modificacion dirigida al sitio del fviii
GT200700040A (es) Modificacion dirigida al sitio del fviii
UA90805C2 (en) Polyethylene glycol-interferon alpha conjugate