公开(公告)号：US20210228615A1

公开(公告)日：2021-07-29

申请号：US16755544

申请日：2018-10-12

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Jason Jingxin Zhang ,  Chikdu Shakti Shivalila ,  Chandra Vargeese ,  Naoki Iwamoto

IPC: A61K31/7125 ,  C12N15/113

Abstract: Among other things, the present disclosure provides technologies for altering splicing, particularly for increasing inclusion of exons in splicing products. In some embodiments, the present disclosure provides SMN2 oligonucleotides, compositions, and methods thereof. In some embodiments, the present disclosure provides chirally controlled SMN2 oligonucleotide compositions. In some embodiments, provided oligonucleotides and compositions can increase level of an exon 7-containing SMN2 splicing product and/or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of splicing-related conditions, disorders and diseases. In some embodiments, the present disclosure provides methods for treating SMN2-related conditions, disorders and diseases such as SMA (spinal muscular atrophy) and ALS (amyotrophic lateral sclerosis).

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：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.

公开(公告)号：US20230295619A1

公开(公告)日：2023-09-21

申请号：US17907895

申请日：2021-02-26

Applicant: Abbie Madeline MAGUIRE ,  Priyanka Shiva PRAKASHA ,  Naoki IWAMOTO ,  Kenneth Allan LONGO ,  Chandra VARGEESE ,  Kevin KIM ,  Elena DALE ,  Pachamuthu KANDASAMY ,  Mamoru SHIMIZU ,  WAVE LIFE SCIENCES LTD.

Inventor： Abbie Madeline Maguire ,  Priyanka Shiva Prakasha ,  Naoki Iwamoto ,  Kenneth Allan Longo ,  Chandra Vargeese ,  Kevin Kim ,  Elena Dale ,  Pachamuthu Kandasamy ,  Mamoru Shimizu

IPC: C12N15/113 ,  A61P25/28

CPC classification number: C12N15/113 ,  A61P25/28 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods for preventing and/ or treating various conditions, disorders or diseases. In some embodiments, provided technologies comprise nucleobase modifications, sugar modifications, intemucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, provided technologies target MAPT. In some embodiments, the present disclosure provides MAPT oligonucleotides, compositions and methods for preventing and/or treating MAPT-associated conditions, disorders or diseases, such as Alzheimer’s Disease (AD) or Frontotemporal Dementia (FTD).

公开(公告)号：US11739325B2

公开(公告)日：2023-08-29

申请号：US16636902

申请日：2018-08-07

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Chandra Vargeese ,  Zhong Zhong ,  Naoki Iwamoto ,  Jason Jingxin Zhang ,  Jean-Cosme Dodart ,  Yuanjing Liu ,  Pachamuthu Kandasamy ,  Sethumadhavan Divakaramenon ,  Genliang Lu ,  Subramanian Marappan

IPC: C12N15/113 ,  C12N15/11 ,  C12Q1/68

CPC classification number: C12N15/113 ,  C12N15/11 ,  C12N2310/11 ,  C12N2310/12 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/33 ,  C12N2310/341 ,  C12N2310/346

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. 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., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.