Title:
CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES
Document Type and Number:
Japanese Patent JP2021080299
Kind Code:
A
Abstract:
To provide new receptor specific ligand conjugated iRNA agents and methods for their preparation that address shortcomings of in vivo delivery of oligonucleotide therapeutics.SOLUTION: The present invention provides iRNA agents comprising at least one subunit of the formula (I). In the formula, A and B are each independently O, N(RN) or S; X and Y are each independently for each occurrence H, OH, a hydroxy protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, -P(Z')(Z'')O-nucleoside, -P(Z')(Z'')O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, -P(Z')(Z'')O-Linker-OP(Z''')(Z'''')O-oligonucleotide, a nucleotide, an oligonucleotide, -P(Z')(Z'')-formula(I), -P(Z')(Z'')- or -Linker-R; R is LG or -Linker-LG, or has the structure including a plurality of -Linker-LG as branched chains shown in the chemical formula 7 herein, where LG is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, or polysaccharide; RN is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z', Z'', Z''' and Z'''' are each independently for each occurrence O or S.SELECTED DRAWING: None
More Like This:
Inventors:
MUTHIAH MANOHARAN
KALLANTHOTTATHIL G RAJEEV
NARAYANANNAIR K JAYAPRAKASH
MARTIN MAIER
KALLANTHOTTATHIL G RAJEEV
NARAYANANNAIR K JAYAPRAKASH
MARTIN MAIER
Application Number:
JP2021036082A
Publication Date:
May 27, 2021
Filing Date:
March 08, 2021
Export Citation:
Assignee:
ALNYLAM PHARMACEUTICALS INC
International Classes:
C07H21/02; A61K31/7105; A61K31/713; A61K47/54; A61K48/00; A61P3/06; A61P7/02; A61P35/00; A61P43/00; C07J31/00
Domestic Patent References:
| JP5519523B2 | 2014-06-11 |
Foreign References:
| WO2006020768A2 | 2006-02-23 | |||
| WO2006078278A2 | 2006-07-27 |
Other References:
NATURE BIOTECHNOLOGY,2007VOL.25,NO.10,P.1149-1157, JPN6013038197, ISSN: 0004980205
JOURNAL OF MEDICINAL CHEMISTRY,2004,VOL.47,NO.23,P.5798-5808, JPN6013038199, ISSN: 0004980206
JOURNAL OF MEDICINAL CHEMISTRY,1999,VOL.42,NO.4,P.609-618, JPN6013038200, ISSN: 0004980207
BIOCONJUGATE CHEM.,2003,VOL.14,NO.1,P.239-246, JPN6013038202, ISSN: 0004980208
JOURNAL OF MEDICINAL CHEMISTRY,2004,VOL.47,NO.23,P.5798-5808, JPN6013038199, ISSN: 0004980206
JOURNAL OF MEDICINAL CHEMISTRY,1999,VOL.42,NO.4,P.609-618, JPN6013038200, ISSN: 0004980207
BIOCONJUGATE CHEM.,2003,VOL.14,NO.1,P.239-246, JPN6013038202, ISSN: 0004980208
Attorney, Agent or Firm:
Hiroshi Higuchi