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.

公开(公告)号：US20220186217A1

公开(公告)日：2022-06-16

申请号：US17311285

申请日：2019-12-06

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Jason Jingxin Zhang ,  Chandra Vargeese ,  Naoki Iwamoto ,  Chikdu Shakti Shivalila ,  Nayantara Kothari ,  Ann Fiegen Durbin ,  Selvi Ramasamy ,  Pachamuthu Kandasamy ,  Jayakanthan Kumarasamy ,  Gopal Reddy Bommineni ,  Subramanian Marappan ,  Sethumadhavan Divakaramenon ,  David Charles Donnell Butler ,  Genliang Lu ,  Hailin Yang ,  Mamoru Shimizu ,  Prashant Monian ,  Khoa Ngoc Dang Luu

IPC: C12N15/113 ,  C12N15/11

Abstract: Among other things, the present disclosure provides designed DMD oligonucleotides, compositions, and methods of use thereof. In some embodiments, the present disclosure provides technologies useful for repairing mutant DMD transcripts by skipping exon 51, so that the transcript can be translated into an internally truncated but at least partially functional Dystrophin protein variant. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) DMD transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as muscular dystrophy, including but not limited to Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

公开(公告)号：US20210254062A1

公开(公告)日：2021-08-19

申请号：US17054452

申请日：2019-05-10

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Jason Jingxin Zhang ,  Chandra Vargeese ,  Naoki Iwamoto ,  Chikdu Shakti Shivalila ,  Nayantara Kothari ,  Ann Fiegen Durbin ,  Selvi Ramasamy ,  Pachamuthu Kandasamy ,  Jayakanthan Kumarasamy ,  Gopal Reddy Bommineni ,  Subramanian Marappan ,  Sethumadhavan Divakaramenon ,  David Charles Donnell Butler ,  Genliang Lu ,  Hailin Yang ,  Mamoru Shimizu ,  Prashant Monian

IPC: C12N15/113

Abstract: Among other things, the present disclosure provides designed DMD oligonucleotides, compositions, and methods of use GC thereof. In some embodiments, the present disclosure provides technologies useful for repairing mutant DMD transcripts by skipping exon 51 or exon 53, so that the transcript can be translated into an internally truncated but at least partially functional Dystrophin protein variant. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) DMD transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as muscular dystrophy, including but not limited to Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

公开(公告)号：US11013757B2

公开(公告)日：2021-05-25

申请号：US16305937

申请日：2017-06-02

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 ,  C12N15/117 ,  A61K31/7088 ,  A61P21/00

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：US20250066775A1

公开(公告)日：2025-02-27

申请号：US18613034

申请日：2024-03-21

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

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.

公开(公告)号：US20230295617A1

公开(公告)日：2023-09-21

申请号：US18072296

申请日：2022-11-30

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Chandra Vargeese ,  Jason Jingxin Zhang ,  Sethumadhavan Divakaramenon ,  David Charles Donnell Butler ,  Genliang Lu ,  Naoki Iwamoto ,  Hailin Yang ,  Maria David Frank-Kamenetsky ,  Subramanian Marappan

IPC: C12N15/11 ,  A61K47/54 ,  A61K31/7088

CPC classification number: C12N15/111 ,  A61K47/542 ,  A61K31/7088 ,  C12N2310/141 ,  C12N2310/14 ,  C12N2310/20 ,  C12N2320/32 ,  C12N2310/11 ,  C12N2310/16 ,  C12N2310/315 ,  C12N2310/3515

Abstract: In some embodiments, the present disclosure pertains to compositions and methods related to delivery of a biologically active agent, wherein the compositions comprise a biologically active agent and a lipid. In various embodiments, the lipid is selected from: lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, docosahexaenoic acid (cis-DHA), turbinaric acid and dilinoleyl. In some embodiments, a composition and method are useful for delivery of a biologically active agent to a particular cell or tissue, e.g., a muscle cell or tissue.

公开(公告)号：US11596646B2

公开(公告)日：2023-03-07

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: C07H21/04 ,  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：US20210032620A1

公开(公告)日：2021-02-04

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: C12N15/11

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.

公开(公告)号：US20200157545A1

公开(公告)日：2020-05-21

申请号：US16618010

申请日：2018-06-01

Applicant: Chandra VARGEESE ,  Naoki IWAMOTO ,  David Charles Donnell BUTLER ,  Subramanian MARAPPAN ,  Genliang LU ,  Jason Jingxin ZHANG ,  Vinod VATHIPADIEKAL ,  Maria David FRANK-KAMENETSKY ,  Luciano Henrique APPONI ,  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

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：US20190209604A1

公开(公告)日：2019-07-11

申请号：US16305937

申请日：2017-06-02

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 ,  C12N15/117 ,  A61P21/00

CPC classification number: A61K31/7125 ,  A61K31/7088 ,  A61P21/00 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/351 ,  C12N2310/3515

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.