RU 2214419 С2, 20.10.2003. US 6514500 B1, (CONJUCHEM INC), 04.02.2003. WO 0069911 A1, (CONJUCHEM INC), 23.11.2000. WO 9946283 A1, (ZEALAND PHARMACEUTICALS A S), 16.09.1999. WO 2004060404 A1, (CHUGAI PHARMACEUTICAL CO LTD), 22.07.2004. BUIJSMAN, ROGIER C. ET AL: "Synthesis of a pentasaccharide-oligodeoxyribonucleotide conjugate: a novelantithrombotic agent" CHEMISTRY - A EUROPEAN JOURNAL, vol.2, no.12, 1996, pages 1572-1577. BAUDYS MIROSLAV ET AL: "Extending insulin action in vivo by conjugation to carboxymethyl dextran" BIOCONJUGATE CHEMISTRY, vol.9, no.2, March 1998 (1998-03), pages 176-183. UCHIO Т ET AL: "Site-specific insulin conjugates with enhanced stability and extended action profile" ADVANCED DRUG DELIVERY REVIEWS 1999 NETHERLANDS, vol.35, no.2-3, 1999, pages 289-306. ARNARP J ET AL: "Synthesis of oligosaccharides that form parts of the complex type of carbohydrate moieties of glycoproteins. Three glycosides prepared for conjugation to proteins." ACTA CHEMICA SCANDINAVICA. SERIES B: ORGANIC CHEMISTRY AND BIOCHEMISTRY. 1983, vol.37, no.4, 1983, pages 329-334. ZOU WEI ET AL: "Synthesis and NMR assignments of galactosylgloboside and its beta-D-GalNAc-(1 fwdarw 4)-alpha-D-Gal-linked positional isomer in a conjugatable form" CARBOHYDRATE RESEARCH, vol.315, no.3-4, 28 February 1999 (1999-02-28), pages 251-261. HARD К ET AL: "O-Mannosylation of recombinant human insulin-like growth factor I (IGF-I) produced in Saccharomyces cerevisiae" FEBS LETTERS, vol.248, no.1-2, 1989, pages 111-114. WESTERDUIN P ET AL: "Synthesis of tailor-made glycoconjugates showing ATIII-metidated inhibition of blood coagulation factors Xa and Thrombin". ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, WILEY VCH VERLAG, WEINHEIM, DE, vol.35, no.3, 1996, pages 331-333. AMSTERDAM VAN R G M ET AL: "SYNTHETIC ANALOGUES OF THE ANTITRHOMBIN III-BINDING PENTASACCHARIDE SEQUENCE OF HEPARIN PREDICTION OF IN VIVO RESIDENCE TIMES" ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol.15, no.4, 1995, pages 495-503. WALENGA J M ET AL: "ANTITHROMBOTIC ACTIVITY OF A SYNTHETIC HEPARIN PENTASACCHARIDE IN ARABBIT STASIS THROMBOSIS MODEL USING DIFFERENT THROMBOGENIC CHALLENGES" THROMBOSIS RESEARCH, TARRYTOWN, NY, US, vol.46, no.2, 1987, pages 187-198. BUIJSMAN R С ET AL: "Design and synthesis of a novel synthetic NAPAP-penta-saccharide conjugate displaying a dual antithrombotic action" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol.9, no.14, 19 July 1999 (1999-07-19), pages 2013-2018. VOGEL G M Т ET AL: "ANTITHROMBOTIC PROPERTIES OF A DIRECT THROMBIN INHIBITOR WITH A PROLONGED HALF LIFE AND ATMEDIATED FACTOR XA INHIBITORY ACTIVITY" JOURNAL OF THROMBOSIS AND HAEMOSTASIS, BLACKWELL PUBLISHING, OXFORD, GB, vol.1, no.9, September 2003 (2003-09), pages 1945-1954. LAHMANN M ET AL: "Synthesis of a polyphosphorylated GPI-anchor core structure" CANADIAN JOURNAL OF CHEMISTRY 2002 CANADA, vol.80, no.8, 2002, pages 1105-1111. EKWALL E ET AL: "IDENTIFICATION OF SALMONELLAE OF SEROGROUP C-1 BY IMMUNO FLUORESCENCE AND CO AGGLUTINATION WITH ANTI SERUM AGAINST AND OLIGO SACCHARIDE PROTEIN CONJUGATE" JOURNAL OF MEDICAL MICROBIOLOGY, vol.15, no.2, 1982. SABBATINI PAUL J ET AL: "Immunization of ovarian cancer patients with a synthetic Lewisy-protein conjugate vaccine: A phase 1 trial" INTERNATIONAL JOURNAL OF CANCER, vol.87, no.1, 1 July 2000 (2000-07-01), pages 79-85. KUDRYASHOV VALERY ET AL: "Immunogenicity of synthetic conjugates of Lewisy oligosaccharide with proteins in mice: Towards the design of anticancer vaccines" CANCER IMMUNOLOGY IMMUNOTHERAPY, vol.45, no.6, February 1998 (1998-02), pages 281-286. NILSSON ULF ET AL: "Synthesis of the saccharide moiety of galactosylgloboside (SSEA-3) and its conjugation to bovine serum albumin and Sepharose" CARBOHYDRATE RESEARCH, vol.272, no.1, 1995. ALBAN S: "The precautionary principle and its impact on medicine" KRANKENHAUSPHARMAZIE, vol.24, no.9, 1 September 2003 (2003-09-01), pages 367-373. MEURER J A ET AL: "Properties of native and in vitro glycosylated forms of the glucagon-like peptide-1 receptor antagonist exendin (9-39)" METABOLISM, CLINICAL AND EXPERIMENTAL, vol.48, no.6, June 1999 (1999-06), pages 716-724.
Имя заявителя:
Н.В. ОРГАНОН (NL)
Изобретатели:
БОС Эбо Сибрен (NL) ДЕ КОРТ Мартин (NL) СМИТ Мертинус Ян (NL) ВАН БУККЕЛ Констант Адриан Антон (NL)
Патентообладатели:
Н.В. ОРГАНОН (NL)
Приоритетные данные:
01.02.2005 EP 05100688.0
Реферат
Настоящее изобретение относится к коньюгатам полипептида и олигосахарида или его фармацевтически приемлемой соли, в которых полипептид коньюгирован по меньшей мере к одному олигосахаридно-спейсерному остатку, олигосахарид представляет собой синтетический сульфатированный пентасахаридный остаток и по существу обладает аффинностью к антитромбину III, и спейсер является связью или по существу фармакологически неактивным гибким сшивающим остатком. Коньюгаты настоящего изобретения имеют улучшенные фармакокинетические свойства по сравнению с соответствующими неконъюгированными полипептидами. 2 н. и 11 з.п. ф-лы, 24 ил., 7 табл., 28 пр.
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