NOE, Christian R.,DIRIN, Mehrdad,WINKLER, Johannes,LACHMANN, Bodo,URBAN, Ernst
申请号：
EPEP2014/069174
公开号：
WO2015/032968A1
申请日:
2014.09.09
申请国别(地区):
WO
年份:
2015
代理人:
摘要：
The invention relates to an antisense or siRNA oligonucleotide or conjugate with improved pharmacokinetic properties, methods of producing the same as well as the use of such compounds and conjugates, e.g. as pharmaceutical composition, a pharmaceutical kit, a medicament or a tool in biomedical research. The conjugates of the invention have the formula I being P - (L - S - S - Y - X)n, wherein P represents a natural, artificial and/or modified oligonucleotide, L represents a linker group attached to one or more nucleosides at any position within the oligonucleotides sequence S represents sulfur X represents a ligand Y represents a spacer and n is an integer ranging from 1 to the oligonucleotide length of P. The oligonucleotides of the invention have the formula II being P- (L - S - R)n, wherein P represents a natural, artificial and /or modified oligonucleotide, L represents a linker group attached to one or more nucleosides at any position within the oligonucleotides sequence, S represents sulfur, R represents either hydrogen or a thiol protecting group, preferably trityl or tertiary butyl, and n is an integer ranging from 1 to the oligonucleotide length of P. In addition, the pharmaceutical composition or pharmaceutical kit or conjugate can be used for the treatment of a disease or disorder that can be at least in part alleviated by therapy, wherein the disease or disorder is selected from the group consisting of bacterial infections, viral infections, cancer, metabolic diseases and immunological disorders and preferably cancer.Linvention concerne un oligonucléotide antisens ou ARNsi ou un conjugué ayant des propriétés pharmacocinétiques améliorées, ses procédés dobtention ainsi que lutilisation de tels composés et conjugués, par exemple comme composition pharmaceutique, nécessaire pharmaceutique, médicament ou outil en recherche biomédicale. Les conjuguées de linvention ont la formule I suivante P - (L - S - S - Y - X)n, où P représente un oligonucléotide naturel
