公开(公告)号：WO2022101512A1

公开(公告)日：2022-05-19

申请号：PCT/EP2021/081891

申请日：2021-11-16

申请人： HERNANDEZ, Frank J.

发明人： HERNANDEZ, Luiza Iuliana ,  BORSA, Baris Ata

IPC分类号： A61K47/50 ,  C07H21/02 ,  C12Q1/6806

摘要： The present invention refers to a drug delivery system which comprises a polynucleotide sequence susceptible of being cleaved by a specific nuclease derived from a bacterium or a mammalian cell, wherein the polynucleotide sequence, from (upstream to downstream) 5' to 3', comprises i) an oligonucleotide sequence of RNase-resistant modified RNA bases and/or nuclease-resistant DNA bases, acting as a resistant moiety, directly linked to ii) a polynucleotide sequence susceptible of being cleaved by a specific nuclease derived from a bacterium or a mammalian cell which is in turn directly linked to iii) a pharmacological active ingredient, wherein the polynucleotide sequence when cleaved at the cleaving site, releases the pharmacological active ingredient.

公开(公告)号：WO2022056127A2

公开(公告)日：2022-03-17

申请号：PCT/US2021/049663

申请日：2021-09-09

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： MCININCH, James D. ,  DEATON, Aimee ,  BONDURANT, Lucas ,  SCHLEGEL, Mark K. ,  CASTORENO, Adam

IPC分类号： A61K31/713 ,  A61P3/10 ,  A61K31/7088 ,  C12N15/113 ,  C07H21/02 ,  C12N15/11

摘要： The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the GRB10 or GRB14 gene, as well as methods of inhibiting expression of GRB10 or GRB14, and methods of treating subjects that would benefit from reduction in expression of GRB10 or GRB14, such as subjects having a GRB10- or GRB14-associated disease, disorder, or condition, such as diabetes, using such dsRNA compositions.

公开(公告)号：WO2022035917A1

公开(公告)日：2022-02-17

申请号：PCT/US2021/045465

申请日：2021-08-11

申请人： MERCK SHARP & DOHME CORP. ,  CHUNG, Cheol Keun ,  LIU, Zhijian ,  MALIGRES, Peter, E. ,  MAO, Edna ,  OBLIGACION, Jennifer, V. ,  PHILLIPS, Eric, M. ,  PIRNOT, Michael ,  POIRIER, Marc ,  SONG, Zhiguo Jake ,  WANG, Tao

发明人： CHUNG, Cheol Keun ,  LIU, Zhijian ,  MALIGRES, Peter, E. ,  MAO, Edna ,  OBLIGACION, Jennifer, V. ,  PHILLIPS, Eric, M. ,  PIRNOT, Michael ,  POIRIER, Marc ,  SONG, Zhiguo Jake ,  WANG, Tao

IPC分类号： A61K31/7084 ,  C07H21/00 ,  C07H21/02

摘要： The present invention relates to efficient processes useful in the preparation of fluorinated nucleosides, such as (O-{[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl}O,O-dihydrogen phosphorothioate, also known as 2'-(S)-fluoro-thio-adenosine monophosphate or 2'-F-thio-AMP. Such fluorinated nucleosides may be useful as a biologically active compound and or as an intermediate for the synthesis of more complex biologically active compounds. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

公开(公告)号：WO2021260107A1

公开(公告)日：2021-12-30

申请号：PCT/EP2021/067342

申请日：2021-06-24

申请人： STEALTH LABELS BIOTECH AB

发明人： WILHELMSSON, Marcus ,  ESBJÖRNER, Elin ,  BALADI, Tom

IPC分类号： C07H19/24 ,  C07H1/00 ,  C07H21/02 ,  C12N15/10 ,  C12Q1/68 ,  G01N33/58 ,  C12P19/34 ,  C12Q1/6809 ,  G01N33/582

摘要： This specification discloses a novel methodology for labelling RNA via enzymatic incorporation of a minimally perturbing fluorescent tricyclic cytosine analogue. This analogue is shown to be 100% incorporated in example transcripts and is fully compatible with both in vitro and in cell transcription. Spectroscopic characterization shows that the incorporation rate of the cytosine analogue is on par with its natural counterpart. Using live cell imaging and flow cytometry, labelled mRNAs are efficiently and correctly translated upon transfection into living cells and cell-free systems. The spectral properties of the modified transcripts and their correct translation product allow for their straightforward and simultaneous visualization. This technology therefore offers a general route to understanding the biological behaviour of RNA of interest, including RNA based drugs. The fluorescent tricyclic cytosine analogue has formula (I):

公开(公告)号：WO2021234459A2

公开(公告)日：2021-11-25

申请号：PCT/IB2021/000351

申请日：2021-05-24

申请人： WAVE LIFE SCIENCES LTD.

发明人： VARGEESE, Chandra ,  IWAMOTO, Naoki ,  APPONI, Luciano, H. ,  BUTLER, David, Charles Donnell ,  KANDASAMY, Pachamuthu ,  MARAPPAN, Subramanian ,  TRIPATHI, Snehlata ,  LIU, Wei ,  BEDEKAR, Mugdha ,  VATHIPADIEKAL, Vinod

IPC分类号： C12N15/113 ,  C12N15/11 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/3233 ,  C12N2310/343 ,  C12N2310/345 ,  C12N2310/346 ,  C12N2320/32

摘要： The present disclosure provides double stranded oligonucleotides, compositions, and methods relating thereto. The present disclosure encompasses the recognition that structural elements of double stranded oligonucleotides, such as base sequence, chemical modifications (e.g, modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, and/or stereochemistry (e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)), and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g, RNA interference (RNAi) activity, stability, delivery, etc. The present disclosure also provides methods for treatment of diseases using provided double stranded oligonucleotide compositions, for example, in RNA interference.

公开(公告)号：WO2021216556A2

公开(公告)日：2021-10-28

申请号：PCT/US2021/028166

申请日：2021-04-20

申请人： UNIVERSITY OF MASSACHUSETTS ,  KHVOROVA, Anastasia

发明人： FERGUSON, Chantal

IPC分类号： A61K31/713 ,  C07H21/02 ,  C12N15/09 ,  C12N15/11 ,  C12N15/113 ,  C12Q1/68 ,  A61K48/005 ,  A61P25/28 ,  C12N15/86 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/343 ,  C12N2310/346 ,  C12N2310/3515 ,  C12N2320/32 ,  C12N2750/14143

摘要： This disclosure relates to novel MSH3 targeting sequences. Novel MSH3 targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.

公开(公告)号：WO2021195533A2

公开(公告)日：2021-09-30

申请号：PCT/US2021/024425

申请日：2021-03-26

申请人： UNIVERSITY OF MASSACHUSETTS

发明人： KHVOROVA, Anastasia ,  ROUX, Loïc Maurice René Jean ,  YAMADA, Ken

IPC分类号： A61K48/00 ,  C07H19/06 ,  C07H19/16 ,  C07H19/067 ,  C07H21/02 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/31 ,  C12N2310/312 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3515 ,  C12N2320/51

摘要： This disclosure relates to the synthesis of novel modified oligonucleotides. The synthesis of novel phosphoramidites are also provided.

公开(公告)号：WO2021172204A1

公开(公告)日：2021-09-02

申请号：PCT/JP2021/006360

申请日：2021-02-19

申请人： 国立研究開発法人科学技術振興機構

发明人： 阿部　洋 ,  木村　康明 ,  阿部　奈保子

IPC分类号： C07H21/02

摘要： ５’末端がキャップ修飾されたＲＮＡであるキャップ化ＲＮＡの製造方法であって、下記式（１）で示される活性化キャップ化合物と、５’末端がモノリン酸化されたモノリン酸ＲＮＡとを反応させることを特徴とするキャップ化ＲＮＡの製造方法である。（ここで、Ｌは脱離基を示す。）　ここで、前記活性化キャップ化合物が下記式（２）で示される化合物であることが好ましい。

公开(公告)号：WO2021151099A1

公开(公告)日：2021-07-29

申请号：PCT/US2021/014967

申请日：2021-01-25

申请人： AIM IMMUNOTECH INC.

发明人： EQUELS, Thomas, K. ,  ATODARIA, Vishwajeetsinh, M. ,  SCOTT, Victoria, G. ,  STRAYER, David, R. ,  RODINO, Peter, W.

IPC分类号： A61K31/7105 ,  A61K31/713 ,  C07H21/02

摘要： Disclosed is a method for the synthesis of a therapeutic double-stranded RNA (tdsRNA), comprising: a) synthesizing a first single-stranded RNA (first ssRNA) in a first synthesis reaction with PNPase as the only RNA polymerase; b) synthesizing a second single- stranded RNA (second ssRNA) in a second synthesis reaction with PNPase as the only RNA polymerase; and c) hybridizing the first ssRNA with the second ssRNA to form the tdsRNA; wherein step a) and step b) are performed in any order. Also disclosed is a product produced by the method.

公开(公告)号：WO2021146488A1

公开(公告)日：2021-07-22

申请号：PCT/US2021/013525

申请日：2021-01-15

申请人： DICERNA PHARMACEUTICALS, INC.

发明人： WANG, Weimin ,  YU, Hongchuan

IPC分类号： C07H19/10 ,  C07H19/20 ,  C07H21/02 ,  C07H21/04 ,  A61P43/00 ,  C07H21/00

摘要： The present invention relates to nucleic acids and analogues thereof useful as potent and stable RNA interference agents.