公开(公告)号：US11136346B2

公开(公告)日：2021-10-05

申请号：US16878461

申请日：2020-05-19

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Mamoru Shimizu ,  Takeshi Wada

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

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：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：US10479995B2

公开(公告)日：2019-11-19

申请号：US15746220

申请日：2016-07-22

Applicant: WAVE LIFE SCIENCES LTD.

Inventor： Chandra Vargeese ,  Meena ,  Nenad Svrzikapa ,  Susovan Mohapatra ,  Christopher J. Francis ,  Gregory L. Verdine ,  Anna Sokolovska

IPC: C12N15/113 ,  C12N15/115 ,  A61P25/28

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：US20190264267A1

公开(公告)日：2019-08-29

申请号：US16320379

申请日：2017-07-24

Applicant: Hailin Yang ,  Aaron Jay Morris ,  Vinod Vathipadiekal ,  WAVE LIFE SCIENCES LTD.

Inventor： Hailin YANG ,  Aaron Jay MORRIS ,  Vinod VATHIPADIEKAL

IPC: C12Q1/6827 ,  C12Q1/6853 ,  C12Q1/6858 ,  C12Q1/686

Abstract: Among other things, the present disclosure pertains to methods and compositions related to phasing of allelic variants of genetic loci. Phasing of allelic variants of genetic loci on an individual patient's chromosomes is highly valuable for many purposes, including patient stratification for allele-specific therapeutics.

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。