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：US20220098585A1

公开(公告)日：2022-03-31

申请号：US17426511

申请日：2020-01-30

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Jeffrey Matthew Brown ,  Shaunna Syu-Mei Berkovitch ,  Naoki Iwamoto ,  Chandra Vargeese ,  Kidist M. Aklilu ,  Maria David Frank-Kamenetsky ,  Duncan Parley Brown

IPC: C12N15/113

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 oligonucleotides comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, the present disclosure provides oligonucleotides, compositions and methods for HTT-related conditions, disorders or diseases, such as Huntington's disease.

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：US10590413B2

公开(公告)日：2020-03-17

申请号：US15462787

申请日：2017-03-17

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：US10160969B2

公开(公告)日：2018-12-25

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

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：US20170275621A1

公开(公告)日：2017-09-28

申请号：US15462787

申请日：2017-03-17

Applicant: WAVE LIFE SCIENCES LTD.

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

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

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：US20170029457A1

公开(公告)日：2017-02-02

申请号：US15222910

申请日：2016-07-28

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Gregory L. Verdine ,  Meena ,  Naoki Iwamoto ,  David Charles Donnell Butler

IPC: C07H21/04

CPC classification number: C07H21/04 ,  A61K31/66 ,  A61K31/70 ,  C07C309/66 ,  C07D295/108 ,  C07H13/04

Abstract: Described herein are methods for the synthesis of derivatives of thiosulfonate reagents. Said reagents have utility for the synthesis of phosphorothiotriesters from H-phosphonates in a stereospecific fashion.

Abstract translation: 本文描述了合成硫代磺酸盐试剂衍生物的方法。 所述试剂可用于以立体特异性方式从H-膦酸盐合成磷酰化产物。