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1. 发明授权

US09745585B2 RNAi-mediated inhibition of histamine receptor H1-related conditions 有权
公开(公告)号：US09745585B2
公开(公告)日：2017-08-29
申请号：US14929486
申请日：2015-11-02
申请人： Arrowhead Research Corporation
发明人： John M. Yanni , Jon E. Chatterton , Daniel A. Gamache , Steven T. Miller
IPC分类号： C12N15/11 , C12N15/113
CPC分类号： C12N15/1138 , C12N2310/111 , C12N2310/14 , C12N2310/141
摘要： RNA interference is provided for inhibition of histamine receptor H1 mRNA expression, in particular, for treating patients having an HRH1-related condition or at risk of developing an HRH1-related condition such as allergic conjunctivitis, ocular inflammation, dermatitis, rhinitis, asthma, or allergy.

2. 发明申请

US20160002638A1 RNAi-MEDIATED INHIBITION OF CONNEXIN 43 FOR TREATMENT OF IOP-RELATED CONDITIONS 有权
公开(公告)号：US20160002638A1
公开(公告)日：2016-01-07
申请号：US14859484
申请日：2015-09-21
申请人： Arrowhead Research Corporation
发明人： Jon E. Chatterton , Abbot F. Clark , Martin B. Wax
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , A61K31/713 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2320/30
摘要： RNA interference is provided for inhibition of connexin 43 (Cx43) in intraocular pressure-related conditions, including ocular hypertension and glaucoma such as normal tension glaucoma and open angle glaucoma.

3. 发明申请

US20150344886A1 RNAi-Related Inhibition of TNF-alpha Signaling Pathway for Treatment of Ocular Angiogenesis 有权
标题翻译： RNAi相关抑制肿瘤坏死因子-α信号通路治疗眼血管生成
公开(公告)号：US20150344886A1
公开(公告)日：2015-12-03
申请号：US14827418
申请日：2015-08-17
申请人： Arrowhead Research Corporation
发明人： Jon E. Chatterton , Abbot F. Clark , David P. Bingaman , Martin B. Wax , Adrian M. Timmers
IPC分类号： C12N15/113
CPC分类号： C12N15/1138 , C12N15/113 , C12N15/1136 , C12N15/1137 , C12N2310/111 , C12N2310/14 , C12N2310/141 , C12N2310/31 , C12N2310/319 , C12N2310/32 , C12N2310/321 , C12N2310/53 , C12N2310/531
摘要： RNA interference is provided for inhibition of tumor necrosis factor α (TNFα) by silencing TNFα cell surface receptor TNF receptor-1 (TNFR1) mRNA expression, or by silencing TNFα converting enzyme (TACE/ADAM17) mRNA expression. Silencing such TNFα targets, in particular, is useful for treating patients having a TNFα-related condition or at risk of developing a TNFα-related condition, such as ocular angiogenesis, retinal ischemia, and diabetic retinopathy.
摘要翻译：通过沉默TNFα细胞表面受体TNF受体-1（TNFR1）mRNA表达或沉默TNFα转化酶（TACE / ADAM17）mRNA表达，提供RNA干扰抑制肿瘤坏死因子α（TNFα）。特别是使TNFα靶标沉默可用于治疗患有TNFα相关病症或出现TNFα相关病症如眼血管生成，视网膜缺血和糖尿病性视网膜病变的风险的患者。

4. 发明申请

US20150238515A1 ORGANIC COMPOSITIONS TO TREAT KRAS-RELATED DISEASES 审中-公开
标题翻译：有机组合物治疗与KRAS相关的疾病
公开(公告)号：US20150238515A1
公开(公告)日：2015-08-27
申请号：US14397815
申请日：2013-04-30
申请人： Arrowhead Research Corporation
发明人： Brian Bettencourt , Stuart Milstein , Ivanka Jarska , Earl McDonald , Michael Schlabach, JR. , Frank P. Stegmeier , Markus Warmuth , Kalyani Gampa , Dieter Huesken , Mark Stump , Jan Weiler , Zainab Jagani
IPC分类号： A61K31/713 , A61K45/06 , A61K47/48 , C12N15/113
CPC分类号： A61K31/713 , A61K45/06 , A61K47/549 , C12N15/113 , C12N15/1135 , C12N2310/14 , C12N2310/344 , C12N2310/351 , C12N2310/321 , C12N2310/3521
摘要： 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.
摘要翻译：本公开涉及可用于治疗KRAS相关疾病如增殖性疾病（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，肺癌，非结肠癌）的方法中的RNAi剂 - 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。

5. 发明授权

US09540643B2 Organic compositions to treat HSF1-related diseases 有权
标题翻译：治疗HSF1相关疾病的有机组合物
公开(公告)号：US09540643B2
公开(公告)日：2017-01-10
申请号：US14746148
申请日：2015-06-22
申请人： ARROWHEAD RESEARCH CORPORATION
发明人： Gregory Hinkle , Satyanarayana Kuchimanchi , Stuart Milstein , Markus Warmuth , Wenlai Zhou , Ping Zhu , Tracy S. Zimmermann
IPC分类号： C12N15/11 , C12N15/113 , A61K31/713 , A61K45/06 , A61K47/48 , C07H21/02
CPC分类号： C12N15/113 , A61K31/713 , A61K45/06 , C07H21/02 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2320/31 , C12N2320/51 , C12N2320/53 , Y02A50/467 , C12N2310/3521
摘要： 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.
摘要翻译：本公开涉及使用治疗有效量的RNAi剂对HSF治疗热休克因子1（HSF1）相关疾病如癌症和病毒性疾病的方法。

6. 发明授权

US09476052B2 RNAi inhibition of alpha-ENaC expression 有权
公开(公告)号：US09476052B2
公开(公告)日：2016-10-25
申请号：US14729104
申请日：2015-06-03
申请人： Arrowhead Research Corporation
发明人： Gino Van Heeke , Emma Hickman , Henry Luke Danahay , Pamela Tan , Anke Geick , Hans-Peter Vornlocher
IPC分类号： C12N15/11 , C12N15/113
CPC分类号： C12N15/1138 , A61K31/713 , A61K45/06 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/351 , C12N2310/3513 , C12N2310/3515 , C12N2310/3521
摘要： The invention relates to compositions and methods for modulating the expression of alpha-ENaC, and more particularly to the downregulation of alpha-ENaC expression by chemically modified oligonucleotides.

7. 发明授权

US09476047B2 RNAi-mediated inhibition of connexin 43 for treatment of IOP-related conditions 有权
公开(公告)号：US09476047B2
公开(公告)日：2016-10-25
申请号：US14859484
申请日：2015-09-21
申请人： Arrowhead Research Corporation
发明人： Jon E. Chatterton , Abbot F. Clark , Martin B. Wax
IPC分类号： C12N15/11 , A61K48/00 , C12N15/113 , A61K31/713
CPC分类号： C12N15/113 , A61K31/713 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2320/30
摘要： RNA interference is provided for inhibition of connexin 43 (Cx43) in intraocular pressure-related conditions, including ocular hypertension and glaucoma such as normal tension glaucoma and open angle glaucoma.

8. 发明授权

US09376683B2 Organic compositions to treat beta-ENaC-related diseases 有权
标题翻译：治疗β-ENAC相关疾病的有机组合物
公开(公告)号：US09376683B2
公开(公告)日：2016-06-28
申请号：US14723555
申请日：2015-05-28
申请人： Arrowhead Research Corporation
发明人： Antonin De Fougerolles , John Louis Diener , Emma Hickman , Gregory Hinkle , Stuart Milstein , Anne-Marie Pulichino , Andrew Griffin Sprague
IPC分类号： C07H21/02 , C07H21/04 , A61K48/00 , C12N15/113 , A61K31/713
CPC分类号： 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
摘要： The present disclosure relates to RNAi agents useful in methods of treating BetaENaC-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.
摘要翻译：本公开内容涉及可用于使用治疗有效量的β-半乳糖苷酶治疗β-肾上腺素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） RNAi试剂至β-ENaC。

9. 发明申请

US20160010089A1 ORGANIC COMPOSITIONS TO TREAT EPASI-RELATED DISEASES 有权
标题翻译：有机组合物治疗与EPAS相关的疾病
公开(公告)号：US20160010089A1
公开(公告)日：2016-01-14
申请号：US14770765
申请日：2014-02-27
申请人： ARROWHEAD RESEARCH CORPORATION
发明人： Brian Bettencourt , Shanthi Ganesh , Elizabeth George , Dieter Huesken , Stuart Milstein , Jonathan Solomon , Emily Thomas , Ivanka Toudjarska , Jennifer Tullai , Jan Weiler
IPC分类号： C12N15/113 , A61K45/06 , A61K31/713
CPC分类号： 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
摘要： 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.
摘要翻译：本公开涉及治疗EPAS1相关疾病如癌症，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，胶质母细胞瘤，头颈鳞状细胞癌，肝细胞癌，肺腺癌，成神经细胞瘤，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，新生血管性疾病和类风湿性关节炎，使用治疗有效量的RNAi剂给EPAS1。

10. 发明申请

US20150361432A1 MODIFIED SMALL INTERFERING RNA MOLECULES AND METHODS OF USE 审中-公开
标题翻译：改良的小干扰RNA分子及其使用方法
公开(公告)号：US20150361432A1
公开(公告)日：2015-12-17
申请号：US14819606
申请日：2015-08-06
申请人： Arrowhead Research Corporation
发明人： Jang Han , Mi-Young Seo , Michael Houghton
IPC分类号： C12N15/113
CPC分类号： C12N15/1131 , A61K31/711 , A61K38/00 , C12N2310/111 , C12N2310/14 , C12N2310/322 , C12N2310/33 , C12N2310/334 , C12N2310/335 , C12N2310/3515 , C12N2310/53 , C12N2320/30 , Y02A50/463 , Y02A50/465
摘要： The present invention provides double-stranded RNA molecules that mediate RNA interference in target cells, preferably hepatic cells. The invention also provides double-stranded RNA (dsRNA) molecules that are modified to be resistant to nuclease degradation, which inactivates a virus, and more specifically, hepatitis C virus (HCV). The invention also provides a method of using these modified RNA molecules to inactivate virus in mammalian cells and a method of making modified small interfering RNAs (siRNAs) using human Dicer. The invention provides modified RNA molecules that are modified to include a dsRNA or siRNA wherein one or more of the pyrimidines in the RNA molecule are modified to include 2′-Fluorine. The invention also provides dsRNA or siRNA in which all pyrimidines are modified to include a 2′-Fluorine. The invention provides that the 2′-Fluorine dsRNA or siRNA molecule is further modified to include a two base deoxynucleotide “TT” sequence at the 3′ end of the molecule.
摘要翻译：本发明提供了介导靶细胞，优选肝细胞中的RNA干扰的双链RNA分子。本发明还提供被修饰为对核酸酶降解具有抗性的双链RNA（dsRNA）分子，其使病毒失活，更具体地，丙型肝炎病毒（HCV）。本发明还提供了使用这些修饰的RNA分子来灭活哺乳动物细胞中的病毒的方法和使用人Dicer制备修饰的小干扰RNA（siRNA）的方法。本发明提供经修饰以包括dsRNA或siRNA的修饰的RNA分子，其中RNA分子中的一个或多个嘧啶被修饰为包括2'-氟。本发明还提供dsRNA或siRNA，其中所有嘧啶被修饰以包括2'-氟。本发明提供了2'-氟dsRNA或siRNA分子被进一步修饰，以在分子的3'端包括两碱基脱氧核苷酸“TT”序列。

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