公开(公告)号：US09150603B2

公开(公告)日：2015-10-06

申请号：US14111688

申请日：2012-04-11

Applicant: Vinay Girijavallabhan ,  F. George Njoroge ,  Stephane Bogen ,  Angela Kerekes ,  Frank Bennett ,  Ying Huang ,  Latha Nair ,  Dmitri Pissarnitski ,  Vishal Verma ,  Qun Dang ,  Ian Davies ,  David B. Olsen ,  Andrew Stamford ,  Joseph P. Vacca

Inventor： Vinay Girijavallabhan ,  F. George Njoroge ,  Stephane Bogen ,  Angela Kerekes ,  Frank Bennett ,  Ying Huang ,  Latha Nair ,  Dmitri Pissarnitski ,  Vishal Verma ,  Qun Dang ,  Ian Davies ,  David B. Olsen ,  Andrew Stamford ,  Joseph P. Vacca

IPC: C07H19/06 ,  C07H19/20 ,  C07H19/10 ,  C07H19/12 ,  C07H19/16 ,  C07H19/04 ,  C07H19/207 ,  C07H19/11 ,  C07H19/213 ,  A61K31/7056 ,  A61K31/7068 ,  A61K31/7076 ,  A61K45/06

CPC classification number: C07H19/16 ,  A61K31/7056 ,  A61K31/7068 ,  A61K31/7076 ,  A61K45/06 ,  C07H19/06 ,  C07H19/10 ,  C07H19/11 ,  C07H19/20 ,  C07H19/207 ,  C07H19/213 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/395

Abstract: The present invention relates to 2′-Cyano Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Cyano Substituted Nucleoside Derivative, and methods of using the 2′-Cyano Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

Abstract translation: 本发明涉及式（I）的2'-氰基取代的核苷衍生物及其药学上可接受的盐，其中B，X，R 1，R 2和R 3如本文所定义。 本发明还涉及包含至少一种2'-氰基取代的核苷衍生物的组合物，以及使用2'-氰基取代的核苷衍生物治疗或预防患者HCV感染的方法。

公开(公告)号：US08993529B2

公开(公告)日：2015-03-31

申请号：US12987929

申请日：2011-01-10

Applicant: C. Frank Bennett ,  Kenneth W. Dobie

Inventor： C. Frank Bennett ,  Kenneth W. Dobie

IPC: A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  A61K38/00

CPC classification number: C12N15/1137 ,  A61K38/00 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525 ,  C12Y115/01001 ,  Y02P20/582

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of superoxide dismutase 1, soluble. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding superoxide dismutase 1, soluble. Methods of using these compounds for modulation of superoxide dismutase 1, soluble expression and for treatment of diseases associated with expression of superoxide dismutase 1, soluble are provided.

Abstract translation: 提供反义化合物，组合物和方法用于调节超氧化物歧化酶1的表达，可溶性。 组合物包含靶向编码超氧化物歧化酶1的核酸的可反应化合物，特别是反义寡核苷酸。 提供了使用这些化合物调节超氧化物歧化酶1，可溶性表达和治疗与超氧化物歧化酶1表达相关的疾病的方法。

公开(公告)号：US08980853B2

公开(公告)日：2015-03-17

申请号：US13380021

申请日：2010-06-17

Applicant: C. Frank Bennett ,  Gene Hung ,  Frank Rigo ,  Adrian R. Krainer ,  Yimin Hua ,  Marco A. Passini ,  Lamya Shihabuddin ,  Seng H. Cheng ,  Katherine W. Klinger

Inventor： C. Frank Bennett ,  Gene Hung ,  Frank Rigo ,  Adrian R. Krainer ,  Yimin Hua ,  Marco A. Passini ,  Lamya Shihabuddin ,  Seng H. Cheng ,  Katherine W. Klinger

IPC: A61K31/70 ,  C07H21/02 ,  C07H21/04 ,  A61K31/7088 ,  C12N15/113 ,  C12Q1/68 ,  A61K31/712

CPC classification number: A61K31/7088 ,  A61K31/712 ,  C12N15/113 ,  C12N2310/11 ,  C12N2320/33

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract translation: 本文公开了用于调节受试者中SMN2 mRNA的剪接的化合物，组合物和方法。 还提供了所公开的化合物和组合物在制备用于治疗疾病和病症（包括脊髓性肌肉萎缩）的药物中的用途。

公开(公告)号：US08916531B2

公开(公告)日：2014-12-23

申请号：US12743797

申请日：2008-11-20

Applicant: C. Frank Bennett ,  Lex M. Cowsert ,  Susan M. Freier

Inventor： C. Frank Bennett ,  Lex M. Cowsert ,  Susan M. Freier

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525

Abstract: Disclosed herein are antisense compounds and methods for decreasing CD40. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to CD40 include hyperproliferative disorders, graft versus host disease (GVHD), graft rejection, asthma, airway hyperresponsiveness, chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and certain forms of arthritis.

Abstract translation: 本文公开了用于减少CD40的反义化合物和方法。 通过施用靶向CD40的反义化合物可以改善的疾病状况的实例包括过度增殖性疾病，移植物抗宿主病（GVHD），移植物排斥反应，哮喘，气道高反应性，慢性阻塞性肺疾病（COPD），多发性硬化（MS） ，系统性红斑狼疮（SLE）和某些形式的关节炎。

公开(公告)号：US20140114057A1

公开(公告)日：2014-04-24

申请号：US14009782

申请日：2012-05-02

Applicant: Michelle L. Hastings ,  Frank Rigo ,  C. Frank Bennett

Inventor： Michelle L. Hastings ,  Frank Rigo ,  C. Frank Bennett

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C07H21/04 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3233 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3525

Abstract: The present invention provides compounds comprising oligonucleotides complementary to an Usher transcript. Certain such compounds are useful for hybridizing to an Usher transcript, including but not limited, to an Usher transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the Usher transcript. In certain such embodiments, the Usher transcript includes a mutation that results in cryptic splicing and hybridization of the oligonucleotide results in a decrease in the amount of cryptic splicing. In certain embodiments, such compounds are used to treat Usher Syndrome.

Abstract translation: 本发明提供了包含与Usher转录物互补的寡核苷酸的化合物。 某些这样的化合物可用于与Usher转录物杂交，包括但不限于细胞中的Usher转录物。 在某些实施方案中，这种杂交导致Usher转录物的剪接的调节。 在某些这样的实施方案中，Usher转录物包括导致隐含剪接的突变，并且寡核苷酸的杂交导致隐形剪接的量的减少。 在某些实施方案中，这些化合物用于治疗Usher综合征。

公开(公告)号：US08680294B2

公开(公告)日：2014-03-25

申请号：US13387619

申请日：2010-07-27

Applicant: John Traverse ,  William M. Leong ,  Steven P. Miller ,  Jennifer Albaneze-Walker ,  Thomas J. Hunter ,  Lijun Wang ,  Hongbiao Liao ,  Ashok Arasappan ,  Scott T. Trzaska ,  Randi M. Smith ,  Azzeddine Lekhal ,  Stephane L. Bogen ,  Jianshe Kong ,  Frank Bennett ,  F. George Njoroge ,  Marc Poirier ,  Shen-Chun Kuo ,  Yonggang Chen ,  Kenneth S. Matthews ,  Patrice Demonchaux ,  Amadeo Ferreira

Inventor： John Traverse ,  William M. Leong ,  Steven P. Miller ,  Jennifer Albaneze-Walker ,  Thomas J. Hunter ,  Lijun Wang ,  Hongbiao Liao ,  Ashok Arasappan ,  Scott T. Trzaska ,  Randi M. Smith ,  Azzeddine Lekhal ,  Stephane L. Bogen ,  Jianshe Kong ,  Frank Bennett ,  F. George Njoroge ,  Marc Poirier ,  Shen-Chun Kuo ,  Yonggang Chen ,  Kenneth S. Matthews ,  Patrice Demonchaux ,  Amadeo Ferreira

IPC: C07D207/06

CPC classification number: C07D209/52 ,  C07C51/353 ,  C07C67/04 ,  C07C237/04 ,  C07C315/02 ,  C07C315/04 ,  C07C317/28 ,  C07C319/14 ,  C07C319/20 ,  C07C2601/02 ,  C07C2601/14 ,  C07K5/0202 ,  C07K5/06034 ,  C07C323/53 ,  C07C317/44 ,  C07C57/03 ,  C07C69/533

Abstract: Processes useful for the preparation of a Compound of Formula I: Formula (I). Intermediates useful for the preparation of the compound of Formula I, and processes useful for preparing said intermediates are disclosed.

Abstract translation: 用于制备式I化合物的方法：式（I）。 公开了可用于制备式I化合物的中间体和用于制备所述中间体的方法。

公开(公告)号：US20140005252A1

公开(公告)日：2014-01-02

申请号：US13988296

申请日：2011-11-17

Applicant: C. Frank Bennett ,  Susan M. Freier ,  Jyothi Mallajosyula

Inventor： C. Frank Bennett ,  Susan M. Freier ,  Jyothi Mallajosyula

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/323 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/321 ,  C12N2310/3525

Abstract: Disclosed herein are antisense compounds and methods for decreasing alpha-synuclein mRNA and protein expression. Also disclosed herein are methods for treating, preventing, and ameliorating neurodegenerative diseases in an individual in need thereof.

Abstract translation: 本文公开了用于降低α-突触核蛋白mRNA和蛋白质表达的反义化合物和方法。 本文还公开了在有需要的个体中治疗，预防和改善神经变性疾病的方法。

公开(公告)号：US08501703B2

公开(公告)日：2013-08-06

申请号：US12065250

申请日：2006-08-29

Applicant: C. Frank Bennett ,  Nicholas M. Dean ,  Ryszard Kole ,  Casey C. Kopczynski

Inventor： C. Frank Bennett ,  Nicholas M. Dean ,  Ryszard Kole ,  Casey C. Kopczynski

IPC: A61K48/00

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2310/3531

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of a selected target mRNA. Further provided are uses of the disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Methods of enhancing cellular uptake, modulating tissue distribution and enhancing pharmacological activity of RNase H-independent antisense oligonucleotides are also provided.

公开(公告)号：US20130046008A1

公开(公告)日：2013-02-21

申请号：US13577622

申请日：2011-02-08

Applicant: C. Frank Bennett ,  Michael Hayden ,  Susan M. Freier ,  Sarah Greenlee ,  Jeffrey Carroll ,  Simon Warby ,  Eric E. Swayze

Inventor： C. Frank Bennett ,  Michael Hayden ,  Susan M. Freier ,  Sarah Greenlee ,  Jeffrey Carroll ,  Simon Warby ,  Eric E. Swayze

IPC: A61K31/7088 ,  A61P25/28 ,  A61K31/7115 ,  A61K31/7125 ,  C12N5/071 ,  A61K31/712

CPC classification number: C12Q1/6883 ,  C12N15/113 ,  C12N2310/11 ,  C12N2320/34 ,  C12Q1/6811 ,  C12Q1/6897 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2525/207 ,  C12Q2535/131 ,  C12Q2539/107 ,  C12Q2521/327 ,  C12Q2525/121 ,  C12Q2525/185

Abstract: Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).

公开(公告)号：US20130046007A1

公开(公告)日：2013-02-21

申请号：US13577616

申请日：2011-02-08

Applicant: C. Frank Bennett ,  Susan M. Freier ,  Sarah Greenlee ,  Eric E. Swayze

Inventor： C. Frank Bennett ,  Susan M. Freier ,  Sarah Greenlee ,  Eric E. Swayze

IPC: C12N15/113 ,  A61K31/7088 ,  A61P25/28 ,  A61P25/00 ,  A61P25/16 ,  A61P11/00 ,  A61P1/16 ,  A61P11/06 ,  A61P29/00 ,  A61P27/12 ,  A61P3/10 ,  A61P9/10 ,  A61P27/02 ,  A61P9/12 ,  A61P3/04 ,  A61P25/24 ,  A61P35/00 ,  C12N5/07

CPC classification number: C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/34

Abstract: Disclosed herein are antisense compounds and methods for selectively of reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative, such as Huntington's Disease (HD).

Abstract translation: 本文公开了用于选择性降低含有单核苷酸多态性（SNP）的基因的等位变体的表达的反义化合物和方法。 这些方法，化合物和组合物可用于治疗，预防或改善疾病，包括神经变性如亨廷顿病（HD）。