公开(公告)号：US20210198305A1

公开(公告)日：2021-07-01

申请号：US16618003

申请日：2018-06-01

Applicant: WAVE LIFE SCIENCES LTD. ,  Pfizer Inc.

Inventor： Chandra Vargeese ,  Naoki Iwamoto ,  David Charles Donnell Butler ,  Subramanian Marappan ,  Genliang Lu ,  Jason Jingxin Zhang ,  Vinod Vathipadiekal ,  Maria David Frank-Kamenetsky ,  Luciano Henrique Apponi ,  Hanna Maria Wisniewska ,  Xiayun Cheng ,  Young Jin Cho

IPC: C07H17/04 ,  C07H19/04 ,  C12N15/113

Abstract: Among other things, the present disclosure provides designed APOC3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, 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. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.

公开(公告)号：US20210130821A1

公开(公告)日：2021-05-06

申请号：US16717986

申请日：2019-12-17

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Charles Donnell Butler ,  Naoki Iwamoto ,  Meena . ,  Nenad Svrzikapa ,  Gregory L. Verdine ,  Ivan Zlatev

IPC: C12N15/113 ,  C07H21/00 ,  C07C317/28 ,  C07D295/088 ,  C12N15/11 ,  C12Q1/6876

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

公开(公告)号：US20200299692A1

公开(公告)日：2020-09-24

申请号：US16782021

申请日：2020-02-04

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Maria David Frank-Kamenetsky ,  Hailin Yang ,  Aaron Jay Morris ,  Chandra Vargeese ,  Christopher J. Francis

IPC: C12N15/113 ,  C12N15/115 ,  A61P25/28

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

公开(公告)号：US20200056173A1

公开(公告)日：2020-02-20

申请号：US16098836

申请日：2017-05-03

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Chandra Vargeese ,  Meena . ,  Nenad Svrzikapa ,  Susovan Mohapatra ,  Christopher J. Francis ,  Gregory L. Verdine ,  Anna Sokolovska

IPC: C12N15/11 ,  C12N15/113

Abstract: Among other things, the present disclosure relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer. In some embodiments, a chirally controlled oligonucleotide composition has any sequence of bases, and/or pattern or base modifications, sugar modifications, backbone modifications and/or stereochemistry, or combination of these elements, described herein.

公开(公告)号：US20190390197A1

公开(公告)日：2019-12-26

申请号：US16087577

申请日：2017-10-06

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Charles Donnell Butler ,  Sethumadhavan Divakaramenon ,  Christopher J. Francis ,  Maria David Frank-Kamenetsky ,  Naoki Iwamoto ,  Genliang Lu ,  Subramanian Marappan ,  Meena . ,  Chandra Vargeese ,  Gregory L. Verdine ,  Hailin Yang ,  Jason Jingxin Zhang

IPC: C12N15/113 ,  A61P25/14 ,  A61P21/00 ,  A61K48/00 ,  A61K31/7125

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

公开(公告)号：US10450568B2

公开(公告)日：2019-10-22

申请号：US16139091

申请日：2018-09-23

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Charles Donnell Butler ,  Sethumadhavan Divakaramenon ,  Christopher J. Francis ,  Maria David Frank-Kamenetsky ,  Naoki Iwamoto ,  Genliang Lu ,  Subramanian Marappan ,  Meena ,  Chandra Vargeese ,  Gregory L. Verdine ,  Hailin Yang ,  Jason Jingxin Zhang

IPC: A61K31/712 ,  A61K31/7125 ,  C12N15/113 ,  C07H21/02 ,  C07H21/00 ,  A61P25/14 ,  A61P21/00 ,  A61K31/7115 ,  A61K48/00 ,  A61P27/00 ,  C07F9/59

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

公开(公告)号：US10307434B2

公开(公告)日：2019-06-04

申请号：US15167669

申请日：2016-05-27

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Gregory L. Verdine ,  Meena ,  Naoki Iwamoto

IPC: C07H21/00 ,  A61K31/70 ,  C07F9/655

Abstract: Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.

公开(公告)号：US09885037B2

公开(公告)日：2018-02-06

申请号：US14414614

申请日：2013-07-12

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Butler ,  Naoki Iwamoto ,  Meena ,  Nenad Svrzikapa ,  Gregory L. Verdine ,  Ivan Zlatev

IPC: C07H21/04 ,  C12N15/113 ,  C07H21/00 ,  C07C317/28 ,  C07D295/088 ,  C12Q1/68 ,  C12N15/11

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

公开(公告)号：US12180472B2

公开(公告)日：2024-12-31

申请号：US17016313

申请日：2020-09-09

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Meena Meena ,  David Butler ,  Naoki Iwamoto ,  Nenad Svrzikapa ,  Gregory L. Verdine ,  Ivan Zlatev

IPC: C12N15/113

Abstract: The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

公开(公告)号：US20240175016A1

公开(公告)日：2024-05-30

申请号：US17766680

申请日：2020-10-05

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Yuanjing Liu ,  Naoki Iwamoto ,  Chandra Vargeese ,  Zhong Zhong ,  Amy Jada Andreucci ,  Susovan Mohapatra

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341

Abstract: Among other things, the present disclosure provides C9orf72 oligonucleotides, compositions, and methods thereof. In some embodiments, the present disclosure provides methods for treating C9orf72-associated conditions, disorders or diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia.