公开(公告)号：US20170189441A1

公开(公告)日：2017-07-06

申请号：US15033715

申请日：2014-11-03

申请人： Steven L. COLLETTI ,  Thomas J. TUCKER ,  David M. TELLERS ,  Boyoung KIM ,  Rob BURKE ,  Kathleen B. CALATI ,  Matthew G. STANTON ,  Rubina G. PARMAR ,  Jeffrey G. AARONSON ,  Weimin WANG ,  MERCK SHARP & DOHME CORP.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffery G. Aaronson ,  Weimin Wang

IPC分类号： A61K31/7125 ,  A61K38/10 ,  A61K38/16 ,  A61K31/713

CPC分类号： A61K31/7125 ,  A61K31/713 ,  A61K38/10 ,  A61K38/16 ,  C07K2319/10 ,  C12N15/111 ,  C12N15/113 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2320/31

摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

公开(公告)号：US09067882B2

公开(公告)日：2015-06-30

申请号：US13883487

申请日：2011-10-31

申请人： Matthew G. Stanton ,  Gregory L. Beutner

发明人： Matthew G. Stanton ,  Gregory L. Beutner

IPC分类号： C07D207/12 ,  A61K9/51

CPC分类号： C12N15/1137 ,  A61K9/5123 ,  C07D207/12 ,  C07D211/40 ,  C07D223/08 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/32

摘要： The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids comprising at least one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

摘要翻译： 本发明提供了可以与其它脂质组分如胆固醇和PEG-脂质组合使用以与寡核苷酸形成脂质纳米颗粒的新型阳离子脂质。 本发明的目的是提供一种阳离子脂质支架，由于肝中脂质水平降低，其表现出增强的功效以及较低的肝毒性。 本发明使用包含至少一个短脂链的低分子量阳离子脂质，以提高siRNA的体内递送的效率和耐受性。

公开(公告)号：US08518911B2

公开(公告)日：2013-08-27

申请号：US13057510

申请日：2009-07-27

申请人： Jason D. Katz ,  Sandra L. Knowles ,  James P. Jewell ,  David L. Sloman ,  Matthew G. Stanton ,  Njamkou Noucti

发明人： Jason D. Katz ,  Sandra L. Knowles ,  James P. Jewell ,  David L. Sloman ,  Matthew G. Stanton ,  Njamkou Noucti

IPC分类号： A61K31/675 ,  A61K31/437 ,  A61K31/496 ,  A61K31/397

CPC分类号： A61K31/425 ,  C07D417/04 ,  C07D417/14

摘要： The invention encompasses pyrazolo[1,5-a]pyridine derivatives which selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer's disease. Pharmaceutical compositions and methods of use are also included.

摘要翻译： 本发明包括选择性抑制微管亲和调节激酶（MARK）的吡唑并[1,5-a]吡啶衍生物，因此可用于治疗或预防阿尔茨海默氏病。 还包括药物组合物和使用方法。

公开(公告)号：US08518907B2

公开(公告)日：2013-08-27

申请号：US13813465

申请日：2011-08-02

申请人： Duncan Brown ,  James J. Cunningham ,  Marian Gindy ,  Victoria Pickering ,  Matthew G. Stanton ,  Steven M. Stirdivant ,  Walter R. Strapps

发明人： Duncan Brown ,  James J. Cunningham ,  Marian Gindy ,  Victoria Pickering ,  Matthew G. Stanton ,  Steven M. Stirdivant ,  Walter R. Strapps

IPC分类号： C12N15/11 ,  A61K48/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/1138 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/332 ,  C12N2310/346 ,  C12N2310/3521 ,  C12N2320/32

摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.

摘要翻译： 本发明涉及用于研究，诊断和治疗对CTNNB1基因表达和/或活性的调节作用和/或调节β-连环蛋白基因表达途径的性状，疾病和病症的化合物，组合物和方法 。 具体地说，本发明涉及包括小核酸分子，如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）等双链核酸分子， 和能够介导或介导针对CTNNB1基因表达的RNA干扰（RNAi）的短发夹RNA（shRNA）分子。

公开(公告)号：US20130053572A1

公开(公告)日：2013-02-28

申请号：US13574315

申请日：2011-01-19

申请人： Steven L. Colletti ,  Zhengwu James Deng ,  Matthew G. Stanton ,  Weimin Wang ,  Ivory Hills

发明人： Steven L. Colletti ,  Zhengwu James Deng ,  Matthew G. Stanton ,  Weimin Wang ,  Ivory Hills

IPC分类号： C07C217/40 ,  C07D211/44 ,  C07D211/32 ,  C07C217/52 ,  C07D211/46 ,  C07D207/08 ,  C07D207/12

CPC分类号： C12N15/113 ,  C07C217/40 ,  C07C217/52 ,  C07C2601/02 ,  C07D207/08 ,  C07D207/12 ,  C07D209/48 ,  C07D211/22 ,  C07D211/44 ,  C07D211/46 ,  C07D295/088 ,  C07H21/02 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/321 ,  C12N2330/30

摘要： The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that is susceptible to hydrolytic instability that may translate into reduced liver residence times and reduced hepatocellular toxicity. The present invention employs acetals and ketals to provide a low pH sensitive chemical handle for degradation.

摘要翻译： 本发明提供了可以与其它脂质组分如胆固醇和PEG-脂质组合使用以与寡核苷酸形成脂质纳米颗粒的新型阳离子脂质。 本发明的目的是提供一种易于水解不稳定性的阳离子脂质支架，其可能转化为减少的肝停留时间和降低的肝细胞毒性。 本发明使用缩醛和缩酮来提供用于降解的低pH敏感化学手柄。

公开(公告)号：US08026260B2

公开(公告)日：2011-09-27

申请号：US12084268

申请日：2006-10-30

申请人： Joshua Close ,  Richard W. Heidebrecht, Jr. ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G Stanton ,  Paul Tempest ,  David J. Witter

发明人： Joshua Close ,  Richard W. Heidebrecht, Jr. ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G Stanton ,  Paul Tempest ,  David J. Witter

IPC分类号： A61K31/4439 ,  A61K31/415 ,  A61K31/423 ,  A61K31/425 ,  A61K31/4245 ,  C07D401/02 ,  C07D271/10 ,  C07D277/20 ,  C07D231/10

CPC分类号： C07D401/12 ,  C07D231/40 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

摘要翻译： 本发明涉及新一类具有芳基 - 吡唑基基序的组蛋白脱乙酰酶抑制剂。 本发明的化合物可用于治疗癌症。 本发明的化合物适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明进一步提供包含本发明化合物和这些药物组合物的安全给药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的本发明化合物。

公开(公告)号：US20100010041A1

公开(公告)日：2010-01-14

申请号：US12439010

申请日：2007-08-31

申请人： Matthew G. Stanton ,  Benito Munoz ,  David L. Sloman ,  Jed Hubbs ,  Christopher Hamblett

发明人： Matthew G. Stanton ,  Benito Munoz ,  David L. Sloman ,  Jed Hubbs ,  Christopher Hamblett

IPC分类号： A61K31/445 ,  C07D211/38

CPC分类号： C07D211/38

摘要： Compounds of formula (I). Selectively inhibit production of Aβ(1-42) and hence find use in treatment of diseases associated with deposition of β-amyloid in the brain.

摘要翻译： 式（I）化合物。 选择性地抑制Abeta（1-42）的产生，因此可用于治疗与脑中沉淀β-淀粉样蛋白相关的疾病。

公开(公告)号：US07550481B2

公开(公告)日：2009-06-23

申请号：US10582856

申请日：2004-12-15

申请人： James C. Barrow ,  Craig A. Coburn ,  Philippe G. Nantermet ,  Harold G. Selnick ,  Shawn J. Stachel ,  Matthew G. Stanton ,  Shaun R. Stauffer ,  Linghang Zhuang ,  Jennifer R. Davis

发明人： James C. Barrow ,  Craig A. Coburn ,  Philippe G. Nantermet ,  Harold G. Selnick ,  Shawn J. Stachel ,  Matthew G. Stanton ,  Shaun R. Stauffer ,  Linghang Zhuang ,  Jennifer R. Davis

IPC分类号： C07D401/02 ,  A61K31/44

CPC分类号： C07D213/81 ,  C07D213/75 ,  C07D257/04 ,  C07D401/04 ,  C07D409/12 ,  C07D413/12

摘要： The present invention is directed to phenylamide and pyridylamide derivative compounds of which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

摘要翻译： 本发明涉及苯酰胺和吡啶酰胺衍生物化合物，其是β-分泌酶的抑制剂，可用于治疗其中涉及β-分泌酶的疾病，例如阿尔茨海默氏病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在治疗涉及β-分泌酶的疾病中的用途。

公开(公告)号：US6147078A

公开(公告)日：2000-11-14

申请号：US315195

申请日：1999-05-19

申请人： Philip E. Sanderson ,  Matthew G. Stanton ,  Suresh K. Balani

发明人： Philip E. Sanderson ,  Matthew G. Stanton ,  Suresh K. Balani

IPC分类号： C07D241/20 ,  C07D401/12 ,  A61K31/497

CPC分类号： C07D401/12 ,  C07D241/20

摘要： Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: ##STR1## wherein ##STR2##

摘要翻译： 本发明的化合物可用于抑制具有以下结构的凝血酶和相关的血栓闭塞：其中

公开(公告)号：US09669097B2

公开(公告)日：2017-06-06

申请号：US13823830

申请日：2011-09-20

申请人： Matthew G. Stanton ,  Brian W. Budzik ,  Gregory L. Beutner ,  Hongbiao Liao

发明人： Matthew G. Stanton ,  Brian W. Budzik ,  Gregory L. Beutner ,  Hongbiao Liao

IPC分类号： C07C211/04 ,  C07C211/08 ,  C07C211/21 ,  A61K48/00 ,  A61K47/18 ,  C12N15/88 ,  C07D207/06 ,  C07C211/17 ,  A61K45/00

CPC分类号： A61K47/18 ,  A61K45/00 ,  A61K48/00 ,  C07C211/04 ,  C07C211/08 ,  C07C211/17 ,  C07C211/21 ,  C07D207/06 ,  C12N15/88

摘要： The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.