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IN VIVO CONJUGATED PROTEINS WITH LONG-TERM ACTION
专利权人:
НОВО НОРДИСК ХЕЛС КЕА АГ (CH)
发明人:
БЕРЕНС Карстен (DK),ГЭРИБЭЙ Патрик Уилльям (DK),ЭСТЕРГААРД Сёрен (DK),АНДЕРСЕН Хенрик Сун (DK),ЙОХАНСЕН Нильс Лангеланд (DK),ПЕШКЕ Бернд (DK),БАК Сонья (DK)
申请号:
RU2011106573/15
公开号:
RU2011106573A
申请日:
2009.08.06
申请国别(地区):
RU
年份:
2012
代理人:
摘要:
1. A method for producing a conjugated protein or glycoprotein, which comprises the steps of reacting a protein or glycoprotein with a water-insoluble albumin binding agent in the presence of a possibly substituted cyclodextrin molecule. ! 2. The method according to claim 1, where the cyclodextrin molecule comprises cyclodextrin, such as β-cyclodextrin, optionally substituted with one or more C1-6 alkyl, such as methyl, ethyl or propyl, each of which may be optionally substituted by one or more than one hydroxy group such as hydroxyethylcyclodextrin or hydroxypropylcyclodextrin, in particular, a possibly substituted cyclodextrin includes 2-hydroxyethyl-β-cyclodextrin. ! 3. The method according to claim 1 or claim 2, where a molecule of possibly substituted cyclodextrin is added in a concentration of from 1% to 10%, for example 5%. ! 4. The method according to claim 1 or 2, which includes the interaction in an aqueous buffer solution, such as Hepes buffer, in particular 50 mm Hepes, 100 mm NaCl and 10 mm CaCl2. !5. The method according to claim 1 or 2, wherein the albumin binding agent has cLog P of>; 1, for example>; 2, for example>; 3, in particular>; 4, for example>; 5, in any of octan-1-ol, chloroform, cyclohexane and propylene glycol dipelargonate (PGDP). ! 6. The method according to claim 1 or 2, where the protein conjugate is a protein conjugate of the formula (I):! ! where P is a protein or glycoprotein; ! B is a hydrophilic spacer; ! W represents a chemical group linking A and B; ! A is an albumin binding moiety; and! y is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; ! or a pharmaceutically acceptable salt, solvate or prodrug thereof, such that the A-W-B- moiety includes nera1. Способ получения конъюгированного белка или гликопротеина, который включает стадии взаимодействия белка или гликопротеина с нерастворимым в воде альбумин-связывающим веществом в присутствии молекулы возможно замещенного циклодекстрина. ! 2. Способ по п.1, где
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