公开(公告)号：US10329318B2

公开(公告)日：2019-06-25

申请号：US15608123

申请日：2017-05-30

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Takeshi Wada ,  Mamoru Shimizu

IPC: C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C07H1/00

Abstract: Described herein are methods of syntheses of phosphorous atom-modified nucleic acids comprising chiral X-phosphonate moieties. The methods described herein provide backbone-modified nucleic acids in high diasteteomeric purity via an asymmetric reaction of an achiral molecule comprising a chemically stable H-phophonate moiety with a nucleoside/nucleotide.

公开(公告)号：US20190127733A1

公开(公告)日：2019-05-02

申请号：US15766578

申请日：2016-10-07

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 ,  C07H21/02 ,  C07F9/59 ,  A61P27/00 ,  A61K48/00 ,  A61P21/00

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：US20190077817A1

公开(公告)日：2019-03-14

申请号：US16084556

申请日：2017-03-13

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Charles Donnell Butler ,  Subramanian Marappan

IPC: C07F9/6584 ,  C07H19/16 ,  C07H19/06 ,  C07H1/06

Abstract: The present disclosure, among other things, provides technologies for preparing and purifying phosphoramidites for oligonucleotide synthesis.

公开(公告)号：US10167309B2

公开(公告)日：2019-01-01

申请号：US15294602

申请日：2016-10-14

Applicant: WAVE LIFE SCIENCES LTD

Inventor： Mamoru Shimizu ,  Takeshi Wada

IPC: C07D207/08 ,  C07F7/08 ,  C07H19/10 ,  C07H19/207 ,  C07H1/00 ,  C07H23/00 ,  C07B53/00 ,  C07H19/11 ,  C07H19/213 ,  C07H21/04 ,  C07D405/04 ,  C07D473/18 ,  C07D473/34

Abstract: To provide a chiral reagent or a salt thereof.The chiral reagent has following chemical formula (I). In the formula (I), G1 and G2 are independently a hydrogen atom, a nitro group (—NO2), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G1 and G2 taken together to form a group of formula (IV).

公开(公告)号：US09982257B2

公开(公告)日：2018-05-29

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

CPC classification number: C12N15/113 ,  C07C317/28 ,  C07D295/088 ,  C07H21/00 ,  C12N15/11 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2330/30 ,  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：US20170037399A1

公开(公告)日：2017-02-09

申请号：US15112146

申请日：2015-01-16

Applicant: WAVE LIFE SCIENCES LTD.

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

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2320/30

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.

Abstract translation: 本发明涉及选择性设计的手性控制寡核苷酸，手性控制寡核苷酸组合物及其制备和使用方法。 在一些实施方案中，提供的手性控制的寡核苷酸组合物提供核酸聚合物与参考寡核苷酸组合物不同的切割模式。 在一些实施方案中，提供的手性控制寡核苷酸组合物在核酸聚合物的互补序列内提供单位切割。

公开(公告)号：US20240368207A1

公开(公告)日：2024-11-07

申请号：US18522146

申请日：2023-11-28

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Charles Donnell Butler ,  Pachamuthu Kandasamy ,  Subramanian Marappan ,  Ik-Hyeon Paik ,  Jayakanthan Kumarasamy ,  Gopal Reddy Bommineni

IPC: C07H1/06 ,  C07H19/10 ,  C07H19/207 ,  C07H21/00

Abstract: The present disclosure, among other things, provides technologies for oligonucleotide synthesis. In some embodiments, the present disclosure provides phosphoramidites and methods for synthesis thereof. In some embodiments, provided methods provides higher yields and/or purities. In some embodiments, provided methods remove byproducts without contact with an aqueous solution.

公开(公告)号：US20240174710A1

公开(公告)日：2024-05-30

申请号：US18316932

申请日：2023-05-12

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： David Charles Donnell Butler ,  Christopher P. Hencken ,  Naoki Iwamoto ,  Pachamuthu Kandasamy ,  Alvaro Andres Lanao ,  Genliang Lu ,  Mamoru Shimizu ,  Sethumadhavan Divakaramenon ,  Chandra Vargeese ,  Gopal Reddy Bommineni ,  Subramanian Marappan

IPC: C07H21/04 ,  C07C213/00 ,  C07C215/20 ,  C07C215/44 ,  C07D207/08 ,  C07D211/22 ,  C07F7/08 ,  C07F9/6564 ,  C07H19/06

CPC classification number: C07H21/04 ,  C07C213/00 ,  C07C215/20 ,  C07C215/44 ,  C07D207/08 ,  C07D211/22 ,  C07F7/0812 ,  C07F7/083 ,  C07F9/6564 ,  C07H19/06 ,  C07C2601/14

Abstract: The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

公开(公告)号：US20240132894A1

公开(公告)日：2024-04-25

申请号：US17956741

申请日：2022-09-29

Applicant: WAVE LIFE SCIENCES LTD.

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 ,  Young Jin Cho

IPC: C12N15/113 ,  A61K31/712

CPC classification number: C12N15/1137 ,  A61K31/712 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/343

Abstract: Among other things, the present disclosure provides designed 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：US20230329201A1

公开(公告)日：2023-10-19

申请号：US18022509

申请日：2021-08-23

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Hailin Yang ,  Prashant Monian ,  Chikdu Shakti Shivalila ,  Subramanian Marappan ,  Chandra Vargeese ,  Pachamuthu Kandasamy ,  Genliang Lu ,  Hui Yu ,  David Charles Donnell Butler ,  Luciano Henrique Apponi ,  Mamoru Shimizu ,  Stephany Michelle Standley ,  David John Boulay ,  Jack David Godfrey ,  Naoki Iwanmoto

IPC: A01K67/027 ,  C12N15/85 ,  C12N9/78 ,  A61K49/00

CPC classification number: A01K67/0275 ,  A61K49/0008 ,  C12N9/78 ,  C12N15/8509 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/01 ,  C12N2015/8518

Abstract: Among other things, the present disclosure provides cells and non-human animals engineered to express an ADAR1 polypeptide or a characteristic portion thereof. In some embodiments, the present disclosure provides cells and non-human animals engineered to express a human ADAR1 polypeptide or a characteristic portion thereof. In some embodiments, non-human animals are genetically modified rodents such as mice, rat, etc. In some embodiments, non-human animals are mice. In some embodiments, the present disclosure provides technologies for assessing an agent comprising administering the agent to a cell or non-human animal engineered to express an ADAR1 polypeptide or a characteristic portion thereof. In some embodiments, such a cell or non-human animal is engineered to express a human ADAR1 polypeptide or a characteristic portion thereof. In some embodiments, an agent is a pharmaceutical agent. In some embodiments, an agent is or comprises an oligonucleotide.