公开(公告)号：US20230392137A1

公开(公告)日：2023-12-07

申请号：US17953292

申请日：2022-09-26

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： 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 ,  Andrew Guzior Hoss ,  Jigar Desai ,  Jack David Godfrey ,  Hailin Yang ,  Naoki Iwamoto ,  Jayakanthan Kumarasamy ,  Anthony Lamattina ,  Tom Liantang Pu

IPC: C12N15/10 ,  C12N15/113

CPC classification number: C12N15/102 ,  C12N15/1135

Abstract: Among other things, the present disclosure provides oligonucleotides and compositions thereof. In some embodiments, provided oligonucleotides and compositions are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.

公开(公告)号：US20230203087A1

公开(公告)日：2023-06-29

申请号：US17926987

申请日：2021-05-24

Applicant: Pachamuthu Kandasamy ,  Jayakanthan Kumarasamy ,  Chandra Vargeese ,  Subramanian Marappan ,  Gopal Bommineni ,  Mamoru Shimizu ,  Naoki Iwamoto ,  Stephany Standley ,  Yuanjing Liu ,  Amy Jada Andreucci ,  Genliang LU ,  Onanong Chivatakarn ,  Akbar Husain Khan ,  WAVE LIFE SCIENCES LTD.

Inventor： Pachamuthu Kandasamy ,  Jayakanthan Kumarasamy ,  Chandra Vargeese ,  Subramanian Marappan ,  Gopal Reddy Bommineni ,  Mamoru Shimizu ,  Naoki Iwamoto ,  Stephany Michelle Standley ,  Yuanjing Liu ,  Amy Jada Andreucci ,  Genliang Lu ,  Onanong Chivatakarn ,  Akbar Husain Khan

IPC: C07H21/04 ,  C07F9/165 ,  C07D295/02

CPC classification number: C07H21/04 ,  C07F9/165 ,  C07D295/02

Abstract: The present disclosure provides modified oligonucleotides and compositions and methods thereof. In some embodiments, provided technologies comprise modified sugars and/or modified internucleotidic linkages. In some embodiments, the present disclosure provides technologies for preparing modified oligonucleotides. In some embodiments, the present disclosure provides chirally controlled oligonucleotide compositions and methods for their preparation and uses.

公开(公告)号：US11603532B2

公开(公告)日：2023-03-14

申请号：US16618010

申请日：2018-06-01

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: C12N15/11 ,  C12N15/113 ,  A61K31/712

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：US20220401467A1

公开(公告)日：2022-12-22

申请号：US17177111

申请日：2021-02-16

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Jason Jingxin Zhang ,  Naoki Iwamoto ,  Christopher J. Francis ,  Chandra Vargeese ,  David Charles Donnell Butler ,  Sethumadhavan Divakaramenon ,  Genliang Lu ,  Subramanian Marappan

IPC: A61K31/7125 ,  A61P21/00 ,  C12N15/117 ,  A61K31/7088

Abstract: The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.

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：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：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.