公开(公告)号：WO2014134255A2

公开(公告)日：2014-09-04

申请号：PCT/US2014018873

申请日：2014-02-27

Applicant: NOVARTIS AG ,  BETTENCOURT BRIAN ,  GANESH SHANTHI ,  GEORGE ELIZABETH ,  HUESKEN DIETER ,  MILSTEIN STUART ,  SOLOMON JONATHAN ,  THOMAS EMILY ,  TOUDJARSKA IVANKA ,  TULLAI JENNIFER ,  WEILER JAN

Inventor： BETTENCOURT BRIAN ,  GANESH SHANTHI ,  GEORGE ELIZABETH ,  HUESKEN DIETER ,  MILSTEIN STUART ,  SOLOMON JONATHAN ,  THOMAS EMILY ,  TOUDJARSKA IVANKA ,  TULLAI JENNIFER ,  WEILER JAN

IPC: C12N15/113

CPC classification number: C12N15/113 ,  A61K31/7105 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61K31/713 ,  A61K45/06 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/342 ,  C12N2310/351 ,  C12N2320/30 ,  A61K2300/00

Abstract: The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preemclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.

Abstract translation: 本发明涉及治疗EPAS1相关疾病例如癌症，转移瘤，星形细胞瘤，膀胱癌，乳腺癌，软骨肉瘤，结肠直肠癌，胃癌，成胶质细胞瘤，头颈部鳞状细胞癌，肝细胞癌，肺腺癌，神经母细胞瘤 ，非小细胞肺癌，黑素瘤，多发性骨髓瘤，卵巢癌，直肠癌，肾癌，透明细胞肾细胞癌（以及这种和其他癌症的转移），牙龈炎，牛皮癣，卡波西肉瘤相关疱疹病毒，先兆子痫，炎症 ，慢性炎症，新血管疾病和类风湿性关节炎，使用治疗有效量的针对EPAS1的RNAi剂。

公开(公告)号：WO2012079046A2

公开(公告)日：2012-06-14

申请号：PCT/US2011/064275

申请日：2011-12-09

Applicant: ALNYLAM PHARMACEUTICALS, INC. ,  NOVOBRANTSEVA, Tatiana ,  BETTENCOURT, Brian ,  MILSTEIN, Stuart ,  BORODOVSKY, Anna

Inventor： NOVOBRANTSEVA, Tatiana ,  BETTENCOURT, Brian ,  MILSTEIN, Stuart ,  BORODOVSKY, Anna

IPC: A61K48/00

CPC classification number: C12N15/113 ,  C12N2310/14 ,  C12N2310/344 ,  C12N2310/321 ,  C12N2310/3521

Abstract: The invention relates to double- stranded ribonucleic acid (dsRNA) compositions targeting the KLF1 gene and the BCL11A gene, and methods of using such dsRNA compositions to inhibit expression of KLF1 and BCL11 A, respectively.

Abstract translation: 本发明涉及靶向KLF1基因和BCL11A基因的双链核糖核酸（dsRNA）组合物，以及使用这种dsRNA组合物分别抑制KLF1和BCL11A表达的方法。 p>

公开(公告)号：WO2011131707A1

公开(公告)日：2011-10-27

申请号：PCT/EP2011056299

申请日：2011-04-20

Applicant: NOVARTIS AG ,  DE FOUGEROLLES ANTONIN ,  DIENER JOHN L ,  HICKMAN EMMA ,  HINKLE GREGORY ,  MILSTEIN STUART ,  PULICHINO ANNE-MARIE ,  SPRAGUE ANDREW

Inventor： DE FOUGEROLLES ANTONIN ,  DIENER JOHN L ,  HICKMAN EMMA ,  HINKLE GREGORY ,  MILSTEIN STUART ,  PULICHINO ANNE-MARIE ,  SPRAGUE ANDREW

IPC: C12N15/113 ,  A61P3/12

CPC classification number: C12N15/1138 ,  A61K31/713 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2310/3517 ,  C12N2310/3521

Abstract: The present disclosure relates to RNAi agents useful in methods of treating Beta-ENaC-related diseases such as cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and obesity-associated hypertension, using a therapeutically effective amount of a RNAi agent to Beta-ENaC.

Abstract translation: 本公开涉及可用于使用治疗有效量治疗β-ENAC相关疾病如囊性纤维化，1型假性醛固酮增多症（1例（PHA1），跛行综合征，高血压，碱中毒，低钾血症和肥胖相关性高血压）的方法中的RNAi剂 的RNAi试剂到β-ENaC。

公开(公告)号：WO2011073326A2

公开(公告)日：2011-06-23

申请号：PCT/EP2010069917

申请日：2010-12-16

Applicant: NOVARTIS AG ,  HINKLE GREGORY ,  KUCHIMANCHI SATYANARAYANA ,  MILSTEIN STUART ,  WARMUTH MARKUS ,  ZHOU WENLAI ,  ZHU PING ,  ZIMMERMANN TRACY S

Inventor： HINKLE GREGORY ,  KUCHIMANCHI SATYANARAYANA ,  MILSTEIN STUART ,  WARMUTH MARKUS ,  ZHOU WENLAI ,  ZHU PING ,  ZIMMERMANN TRACY S

IPC: C12N15/113

CPC classification number: C12N15/113 ,  A61K31/713 ,  A61K45/06 ,  C07H21/02 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2320/31 ,  C12N2320/51 ,  C12N2320/53 ,  C12N2310/3521

Abstract: The present disclosure relates to methods of treating heat shock factor 1 (HSF1)-related diseases such as cancer and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

Abstract translation: 本公开涉及使用治疗有效量的针对HSF的RNAi剂治疗热休克因子1（HSF1）相关疾病例如癌症和病毒性疾病的方法。

公开(公告)号：WO2013166004A2

公开(公告)日：2013-11-07

申请号：PCT/US2013/038847

申请日：2013-04-30

Applicant: NOVARTIS AG ,  BETTENCOURT, Brian ,  MILSTEIN, Stuart ,  TOUDJARSKA, Ivanka ,  MCDONALD, Earl ,  SCHLABACH , Michael Jr. ,  STEGMEIER, Frank P. ,  WARMUTH, Markus ,  GAMPA, Kalyani ,  HUESKEN, Dieter ,  STUMP, Mark ,  WEILER, Jan ,  JAGANI, Zainab

Inventor： BETTENCOURT, Brian ,  MILSTEIN, Stuart ,  TOUDJARSKA, Ivanka ,  MCDONALD, Earl ,  SCHLABACH , Michael Jr. ,  STEGMEIER, Frank P. ,  WARMUTH, Markus ,  GAMPA, Kalyani ,  HUESKEN, Dieter ,  STUMP, Mark ,  WEILER, Jan ,  JAGANI, Zainab

IPC: C12N15/113 ,  A61P35/00

CPC classification number: A61K31/713 ,  A61K45/06 ,  A61K47/549 ,  C12N15/113 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2310/321 ,  C12N2310/3521

Abstract: The present disclosure relates to RNAi agents useful in methods of treating KRAS-related diseases such as a proliferative disease, including without limitation a solid or liquid cancer, adenocarcinoma, colorectal cancer, advanced and/or metastatic colorectal cancer, colon cancer, lung, non-small cell lung cancer and lung adenocarcinoma, acute myelogenous lung, bladder, brain, breast, cervical, endometrial, gastric, head and neck, kidney, leukemia, myelodysplastic syndrome, myeloid leukemia, liver, melanoma, ovarian, pancreatic, prostate, testicular, thyroid cancers, and cardio-facio-cutaneous (CFC) syndrome and Noonan syndrome, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to KRAS.

Abstract translation: 本公开涉及可用于治疗KRAS相关疾病如增殖性疾病的方法中的RNAi剂，所述方法包括但不限于固体或液体癌症，腺癌，结肠直肠癌，晚期和/或转移性结肠直肠癌，结肠癌，肺，非 - - 小细胞肺癌和肺腺癌，急性髓细胞肺，膀胱，脑，乳腺，子宫颈，子宫内膜，胃，头颈部，肾，白血病，骨髓增生异常综合征，骨髓性白血病，肝，黑素瘤，卵巢，胰腺，前列腺，睾丸 ，甲状腺癌和心脏表皮（CFC）综合征和Noonan综合征以及类似和相关疾病，使用治疗有效量的RNAi剂给KRAS。

公开(公告)号：WO2012177947A2

公开(公告)日：2012-12-27

申请号：PCT/US2012/043642

申请日：2012-06-21

Applicant: ALNYLAM PHARMACEUTICALS, INC. ,  BETTENCOURT, Brian ,  FITZGERALD, Kevin ,  MILSTEIN, Stuart ,  MAIER, Martin ,  CHARISSE, Klaus ,  KALLANTHOTTATHIL, Rajeev ,  KUCHIMANCHI, Satya ,  MANOHARAN, Muthiah ,  NGUYEN, Tuyen

Inventor： BETTENCOURT, Brian ,  FITZGERALD, Kevin ,  MILSTEIN, Stuart ,  MAIER, Martin ,  CHARISSE, Klaus ,  KALLANTHOTTATHIL, Rajeev ,  KUCHIMANCHI, Satya ,  MANOHARAN, Muthiah ,  NGUYEN, Tuyen

IPC: A61K48/00 ,  A61K38/17

CPC classification number: C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/344 ,  C12N2310/3515 ,  C12N2310/3521

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) targeting an APOC3 gene, and methods of using the dsRNA to inhibit expression of APOC3.

Abstract translation: 本发明涉及靶向APOC3基因的双链核糖核酸（dsRNA），以及使用dsRNA抑制APOC3表达的方法。

公开(公告)号：WO2010148013A2

公开(公告)日：2010-12-23

申请号：PCT/US2010/038707

申请日：2010-06-15

Applicant: ALNYLAM PHARMACEUTICALS, INC. ,  FITZGERALD, Kevin ,  HINKLE, Gregory ,  AKINC, Akin ,  MILSTEIN, Stuart

Inventor： FITZGERALD, Kevin ,  HINKLE, Gregory ,  AKINC, Akin ,  MILSTEIN, Stuart

IPC: A61K31/713 ,  A61P9/10

CPC classification number: A61K31/713 ,  A61K9/0019 ,  A61K9/1272 ,  A61K9/1273 ,  A61K38/1709 ,  A61K47/545 ,  A61K47/55 ,  A61K47/6911 ,  C12N15/1137 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3515

Abstract: This invention relates to composition and methods using lipid formulated siRNA targeted to a PCSK9 gene.

Abstract translation: 本发明涉及使用针对PCSK9基因的脂质配制的siRNA的组合物和方法。

公开(公告)号：WO9966323A9

公开(公告)日：2000-04-06

申请号：PCT/US9913650

申请日：1999-06-18

Applicant: COLD SPRING HARBOR LAB ,  HENGARTNER MICHAEL O ,  GARTNER ANTON ,  MILSTEIN STUART

Inventor： HENGARTNER MICHAEL O ,  GARTNER ANTON ,  MILSTEIN STUART

IPC: G01N33/15 ,  G01N33/50

CPC classification number: G01N33/5091

Abstract: The present invention relates to methods and kits for detecting apoptotic cells in a live nematode by exposing the live nematode to a vital dye that stains apoptotic cells, and detecting the apoptotic cells. Applications of this assay include methods of identifying agents, conditions or genes that modulate apoptosis. The present invention also includes methods of screening for mutated nematodes that exhibit altered apoptotic cell death.

Abstract translation: 本发明涉及通过将活线虫暴露于污染凋亡细胞的重要染料和检测凋亡细胞来检测活线虫中的凋亡细胞的方法和试剂盒。 该测定法的应用包括鉴定调节凋亡的药剂，条件或基因的方法。 本发明还包括筛选显示改变的凋亡细胞死亡的突变的线虫的方法。

公开(公告)号：WO2022159158A1

公开(公告)日：2022-07-28

申请号：PCT/US2021/057016

申请日：2021-10-28

Applicant: ALNYLAM PHARMACEUTICALS, INC. ,  SCHLEGEL, Mark, K. ,  CASTORENO, Adam ,  BROWN, Christopher ,  BONDURANT, Lucas, D. ,  BORODOVSKY, Anna ,  CANTLEY, William ,  CASTELLANOS-RIZALDOS, Elena ,  DEATON, Aimee, M. ,  FARLEY, Jonathan, Edward ,  FISHILEVICH, Elane ,  GANSNER, John, Michael ,  GILBERT, Jason ,  JADHAV, Vasant, R. ,  KAITTANIS, Charalambos ,  KEATING, Mark ,  LIU, Jingxuan ,  MCININCH, James, D. ,  MILSTEIN, Stuart ,  PANDYA, Bhaumik, A. ,  SOUNDARAPANDIAN, Mangala, Meenakshi ,  ZUBER, Jeffrey

Inventor： SCHLEGEL, Mark, K. ,  CASTORENO, Adam ,  BROWN, Christopher ,  BONDURANT, Lucas, D. ,  BORODOVSKY, Anna ,  CANTLEY, William ,  CASTELLANOS-RIZALDOS, Elena ,  DEATON, Aimee, M. ,  FARLEY, Jonathan, Edward ,  FISHILEVICH, Elane ,  GANSNER, John, Michael ,  GILBERT, Jason ,  JADHAV, Vasant, R. ,  KAITTANIS, Charalambos ,  KEATING, Mark ,  LIU, Jingxuan ,  MCININCH, James, D. ,  MILSTEIN, Stuart ,  PANDYA, Bhaumik, A. ,  SOUNDARAPANDIAN, Mangala, Meenakshi ,  ZUBER, Jeffrey

IPC: A61K31/713 ,  C12N15/11 ,  C12N15/113

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

公开(公告)号：WO2014134255A3

公开(公告)日：2014-09-04

申请号：PCT/US2014/018873

申请日：2014-02-27

Applicant: NOVARTIS AG ,  BETTENCOURT, Brian ,  GANESH, Shanthi ,  GEORGE, Elizabeth ,  HUESKEN, Dieter ,  MILSTEIN, Stuart ,  SOLOMON, Jonathan ,  THOMAS, Emily ,  TOUDJARSKA, Ivanka ,  TULLAI, Jennifer ,  WEILER, Jan

Inventor： BETTENCOURT, Brian ,  GANESH, Shanthi ,  GEORGE, Elizabeth ,  HUESKEN, Dieter ,  MILSTEIN, Stuart ,  SOLOMON, Jonathan ,  THOMAS, Emily ,  TOUDJARSKA, Ivanka ,  TULLAI, Jennifer ,  WEILER, Jan

IPC: C12N15/113 ,  A61K31/7088

Abstract: The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preemclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.