公开(公告)号：WO2016079181A1

公开(公告)日：2016-05-26

申请号：PCT/EP2015/076967

申请日：2015-11-18

Applicant: ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： ALBÆK, Nanna ,  HANSEN, Henrik Frydenlund ,  KOCH, Troels ,  RAVN, Jacob ,  ROSENBOHM, Christoph ,  HAGEDORN, Peter ,  SEWING, Sabine ,  MOISAN, Annie

IPC: C07H21/00 ,  A61K31/712 ,  A61K31/7125

CPC classification number: C12N15/117 ,  C07H21/00 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/33 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/53 ,  C12N2330/30

Abstract: The present relates to LNA gapmer antisense oligonucleotides which comprise stereodefined phosphoramidite linkages. The use of stereodefined phosphoramidite linkages in LNA gapmers has been found to provide enhanced RNaseH activity, and modifying stereospecificity enables the reduced toxicity, altered biodistribution, and enhanced mismatch discrimination.

Abstract translation: 本发明涉及包含立体定向亚磷酰胺键的LNA gapmer反义寡核苷酸。 已经发现在LNA间隙物中使用立体定向亚磷酰胺键可提供增强的RNA酶H活性，并且改变立体定向性使得能够降低毒性，改变生物分布和增强错配鉴别。

公开(公告)号：WO2016096938A1

公开(公告)日：2016-06-23

申请号：PCT/EP2015/079915

申请日：2015-12-16

Applicant: ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： ALBAEK, Nanna ,  GUBLER, Marcel ,  HAGEDORN, Peter ,  HANSEN, Henrik, Frydenlund ,  KOCH, Troels ,  MOISAN, Annie ,  RAVN, Jacob ,  ROSENBOHM, Christoph ,  SEWING, Sabine

IPC: C12N15/11 ,  C12N15/113

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/345 ,  C12N2310/346 ,  C12N2320/53 ,  C12N2330/31 ,  G01N33/5014 ,  G01N33/5088

Abstract: The invention relates to a method of identifying stereodefined phosphrothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

Abstract translation: 本发明涉及通过在体外或体内产生和筛选具有降低的毒性的化合物的立体定向手性硫代磷酸酯变体文库来鉴定具有降低的毒性的立体定向磷酸硫酸酯寡核苷酸变体的方法。

公开(公告)号：WO2019224172A1

公开(公告)日：2019-11-28

申请号：PCT/EP2019/063044

申请日：2019-05-21

Applicant: ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： RAVN, Jacob ,  ROSENBOHM, Christoph ,  REDDY, Prasad

IPC: C07H9/04 ,  C07H19/06 ,  C07H19/16

Abstract: The present invention relates to the manufacture of allofuranose from glucofuranose as defined in the description and in the claim. Allofuranos is an intermediate in the manufacture of oligonucleotides which can be used as a medicament.

公开(公告)号：WO2016079183A1

公开(公告)日：2016-05-26

申请号：PCT/EP2015/076971

申请日：2015-11-18

Applicant: ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： ALBÆK, Nanna ,  HANSEN, Henrik Frydenlund ,  KOCH, Troels ,  RAVN, Jacob ,  ROSENBOHM, Christoph ,  HAGEDORN, Peter ,  SEWING, Sabine ,  MOISAN, Annie

IPC: A61K31/7125 ,  C07H21/00

CPC classification number: C12N15/117 ,  C07H21/00 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/33 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/53 ,  C12N2330/30

Abstract: The present invention provides stereodefined phosphorothioate LNA oligonucleotide, comprising at least one stereodefined phosphorothioate linkage between a LNA nucleoside and a subsequent (3') nucleoside.

Abstract translation: 本发明提供立体定向硫代磷酸酯LNA寡核苷酸，其包含LNA核苷和随后的（3'）核苷之间的至少一种立体定向的硫代磷酸酯键。

公开(公告)号：WO2017055423A1

公开(公告)日：2017-04-06

申请号：PCT/EP2016/073224

申请日：2016-09-29

Applicant: ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： HANSEN, Dennis Jul ,  ROSENBOHM, Christoph ,  MELDGAARD, Michael

IPC: A61K47/54 ,  A61K47/55

CPC classification number: C07H21/00 ,  A61K47/549 ,  A61K47/55 ,  C07H1/00 ,  C07H19/06 ,  C07H19/16

Abstract: The present invention relates to the field of oligonucleotide conjugates and to methods of synthesis thereof. In the present method a low-water content solvent environment allows a more efficient conjugation, reducing the amount of conjugate moiety needed and increasing the conjugation reaction speed.

Abstract translation: 本发明涉及寡核苷酸共轭物的领域及其合成方法。 在本方法中，低水含量的溶剂环境允许更有效的缀合，减少所需的缀合物部分的量并增加共轭反应速度。

公开(公告)号：WO2017032726A1

公开(公告)日：2017-03-02

申请号：PCT/EP2016/069765

申请日：2016-08-22

Applicant: ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： HANSEN, Dennis Jul ,  HOERNSCHEMEYER, Joerg ,  RAVN, Jacob ,  ROSENBOHM, Christoph

IPC: C12N15/11 ,  C07D473/18

CPC classification number: C12N15/111 ,  A61K31/7088 ,  C07H1/00 ,  C07H21/00 ,  C12N2310/3231 ,  C12N2310/336 ,  C12N2310/351 ,  C12N2330/30

Abstract: Recent advancements in LNA oligonucleotides include the use of amine linkers to link an LNA antisense oligonucleotide to a conjugate group. For example please see WO2014/118267. The present invention originates from the identification of a problem when de-protecting LNA oligonucleotides which comprise an aliphatic amine group and DMF protected LNA G nucleoside, which results in the production of a +28 Da impurity. This problem is solved by using acyl protection groups on the exocyclic nitrogen of the LNA-G residue, rather than the standard DMF protection group.

Abstract translation: LNA寡核苷酸的最新进展包括使用胺连接体将LNA反义寡核苷酸连接至缀合基团。 例如，请参见WO2014 / 118267。 本发明源于鉴定当包含脂族胺基和DMF保护的LNA G核苷的LNA寡核苷酸脱保护时导致产生+ 28Da杂质的问题。 通过在LNA-G残基的环外氮上使用酰基保护基，而不是标准的DMF保护基来解决这个问题。