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1. 发明申请

US20130211063A1 MODIFIED iRNA AGENTS 有权
标题翻译：改性iRNA代理
公开(公告)号：US20130211063A1
公开(公告)日：2013-08-15
申请号：US13849003
申请日：2013-03-22
申请人： Alnylam Pharmaceuticals, Inc.
发明人： Muthiah MANOHARAN , Venkitasamy KESAVAN , Kallanthottathil RAJEEV
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , A61K47/48123 , A61K47/554 , C07H21/02 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/323 , C12N2310/3515 , C12N2320/32 , C12N2320/51 , C12N2330/30
摘要： The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.
摘要翻译：本发明涉及iRNA试剂，其优选包括其中核糖部分被除核糖以外的部分替代的单体。包含这样的单体可以允许调节掺入其中的iRNA试剂的性质，例如通过使用非核糖部分作为配体或其它实体例如亲油部分的点。例如胆固醇是直接或间接的系链。本发明还涉及制备和使用这种修饰的iRNA试剂的方法。

2. 发明申请

US20130196903A1 Multimeric Inhibitors of Viral Fusion and Uses Thereof 审中-公开
标题翻译：多聚体抑制剂的病毒融合及其用途
公开(公告)号：US20130196903A1
公开(公告)日：2013-08-01
申请号：US13816163
申请日：2011-08-11
申请人： Antonello Pessi
发明人： Antonello Pessi
IPC分类号： A61K47/48
CPC分类号： A61K47/48123 , A61K38/00 , A61K47/554 , A61K47/60 , C12N2740/16063 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393
摘要： The present invention relates to novel multimeric inhibitors of viral entry into cells and their use for the prophylaxis and treatment of viral infections.
摘要翻译：本发明涉及病毒进入细胞的新型多聚体抑制剂及其用于预防和治疗病毒感染的用途。

3. 发明授权

US08445665B2 Therapeutic compositions 有权
标题翻译：治疗组合物
公开(公告)号：US08445665B2
公开(公告)日：2013-05-21
申请号：US12755252
申请日：2010-04-06
申请人： Muthiah Manoharan , David Bumcrot
发明人： Muthiah Manoharan , David Bumcrot
IPC分类号： C07H21/04 , C07H21/02
CPC分类号： C12N15/113 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0362 , A61K31/713 , A61K47/48123 , C07H21/02 , C07K14/775 , C12N15/111 , C12N15/1137 , C12N15/1138 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/344 , C12N2310/3515 , C12N2310/533 , C12N2320/32 , C12N2320/51 , C12N2320/53 , C12N2330/30
摘要： This application relates to iRNA agents and methods of making and using the agents. The iRNA agent comprises a sense sequence and an antisense sequence. The antisense strand and/or the sense strand may contain formula (8) or its L-nucleoside or 2′-5′ linkage isomer: The iRNA agents of the invention can present increased nuclease resistance.
摘要翻译：本申请涉及制备和使用该试剂的iRNA试剂和方法。 iRNA试剂包括有义序列和反义序列。反义链和/或有义链可以含有式（8）或其L-核苷或2'-5'连锁异构体。本发明的iRNA试剂可以呈现增加的核酸酶抗性。

4. 发明申请

US20120214872A1 BILE ACID OR BILE SALT FATTY ACID CONJUGATES 有权
标题翻译：酸或酸盐酸脂肪酸混合物
公开(公告)号：US20120214872A1
公开(公告)日：2012-08-23
申请号：US13366796
申请日：2012-02-06
申请人： Tuvia Gilat , Beatrice Gilat
发明人： Tuvia Gilat , Beatrice Gilat
IPC分类号： A61K31/20 , A61P3/10 , A61P3/04
CPC分类号： A61K31/575 , A61K47/48123 , A61K47/554 , C07J9/00 , C07J41/005 , C07J41/0055
摘要： A method for treating a disease or disorder associated with altered glucose metabolism or insulin action in a subject in need thereof. The method includes administering to the subject a BAFAC (bile acid or bile salt fatty acid conjugate) of general formula II: W-X-G in which G is a bile acid or bile salt radical, which is optionally conjugated in position 24 with a suitable amino acid, W stands for one or two fatty acid radicals, each having from 14-22 carbon atoms, and X is a suitable bonding member or a direct C═C bond between G and each W, said suitable bonding member being selected from the group consisting of NH, O, P and S. The disease or disorder associated with altered glucose metabolism is selected from the group consisting of hyperglycemia, diabetes, insulin resistance and obesity.
摘要翻译：用于治疗有需要的受试者中与葡萄糖代谢改变或胰岛素作用相关的疾病或病症的方法。该方法包括向受试者施用通式II：WXG的BAFAC（胆汁酸或胆汁盐脂肪酸缀合物），其中G是胆汁酸或胆汁盐基，其任选地在第24位与合适的氨基酸缀合， W表示一个或两个脂肪酸基团，每个具有14-22个碳原子，X是G和每个W之间的合适的结合部件或直接的C = C键，所述合适的粘结部件选自 NH，O，P和S.与葡萄糖代谢改变相关的疾病或病症选自高血糖症，糖尿病，胰岛素抵抗和肥胖症。

5. 发明授权

US08110674B2 Therapeutic compositions 有权
标题翻译：治疗组合物
公开(公告)号：US08110674B2
公开(公告)日：2012-02-07
申请号：US10548611
申请日：2004-03-08
申请人： Muthiah Manoharan , David Bumcrot
发明人： Muthiah Manoharan , David Bumcrot
IPC分类号： C07H21/04 , A61K31/70
CPC分类号： C12N15/113 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0362 , A61K31/713 , A61K47/48123 , C07H21/02 , C07K14/775 , C12N15/111 , C12N15/1137 , C12N15/1138 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/344 , C12N2310/3515 , C12N2310/533 , C12N2320/32 , C12N2320/51 , C12N2320/53 , C12N2330/30
摘要： Therapeutic sRNA agents and methods of making and using are enclosed.
摘要翻译：封闭了治疗性sRNA药剂和制备和使用方法。

6. 发明授权

US6127170A Multifunctional complexes for gene transfer into cells comprising a nucleic acid bound to a polyamine and having a endosome disruption agent 失效
标题翻译：用于将基因转移到细胞中的多功能复合物，其包含与多胺结合并具有内体破坏剂的核酸
公开(公告)号：US6127170A
公开(公告)日：2000-10-03
申请号：US809397
申请日：1997-03-21
申请人： Raymond H. Boutin
发明人： Raymond H. Boutin
IPC分类号： C12N15/09 , A61K47/48 , A61K48/00 , C07C211/14 , C07C233/35 , C07C271/22 , C07K7/08 , C07K14/005 , C07K14/11 , C12N15/64 , C12N15/86 , C12N15/87 , C12N15/88 , C12N15/00 , C12N5/00
CPC分类号： C07K14/005 , A61K47/48046 , A61K47/48123 , C12N15/64 , C12N15/87 , A61K48/00 , C12N2760/16022
摘要： A multifunctional molecular complex for the transfer of a nucleic acid composition to a target cell is provided. The complex is comprised of A) said nucleic acid composition and B) a transfer moiety comprising 1) one or more cationic polyamines bound to said nucleic acid composition, 2) one or more endosome membrane disrupting components attached to at least one nitrogen of the polyamine and 3) one or more receptor specific binding components.
摘要翻译： PCT No.PCT / US95 / 12502 Sec。 371日期1997年3月21日 102（e）1997年3月21日PCT PCT 1995年9月28日PCT公布。 WO96 / 10038 PCT出版物日期1996年4月4日提供了用于将核酸组合物转移至靶细胞的多功能分子复合物。所述复合物由A）所述核酸组合物和B）转移部分组成，所述转移部分包含1）与所述核酸组合物结合的一种或多种阳离子多胺，2）一种或多种内连体膜破坏连接至所述多胺的至少一个氮的组分和3）一种或多种受体特异性结合组分。

7. 发明授权

US6071890A Organ-specific targeting of cationic amphiphile/DNA complexes for gene therapy 失效
标题翻译：用于基因治疗的阳离子两亲物/ DNA复合物的器官特异性靶向
公开(公告)号：US6071890A
公开(公告)日：2000-06-06
申请号：US545473
申请日：1995-10-19
申请人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , Nelson S. Yew , David J. Harris , Edward R. Lee , Craig S. Siegel
发明人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , Nelson S. Yew , David J. Harris , Edward R. Lee , Craig S. Siegel
IPC分类号： C12N15/09 , A61K9/127 , A61K47/28 , A61K47/48 , A61K48/00 , A61P29/00 , A61P43/00 , C07C211/13 , C07C217/28 , C07C237/06 , C07C271/20 , C07C271/34 , C07C275/14 , C07C279/12 , C07C323/25 , C07C327/42 , C07C333/04 , C07J41/00 , C07J43/00 , C12N15/88 , A01N43/04
CPC分类号： A61K47/48023 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , A61K9/1272 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003 , C12N15/88
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译：提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

8. 发明授权

US5882941A Programmable genotoxic agents and uses therefor 失效
公开(公告)号：US5882941A
公开(公告)日：1999-03-16
申请号：US239428
申请日：1994-05-04
申请人： John M. Essigmann , Robert G. Croy , Zhenghuan Chen
发明人： John M. Essigmann , Robert G. Croy , Zhenghuan Chen
IPC分类号： A61K47/48 , C12N15/01 , C07J53/00 , C07K14/00 , C12N15/11
CPC分类号： A61K47/481 , A61K47/48023 , A61K47/48123 , A61K47/48146 , A61K47/48246
摘要： The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.

9. 发明授权

US5059591A Drug preparations of reduced toxicity 失效
标题翻译：药物制剂毒性降低
公开(公告)号：US5059591A
公开(公告)日：1991-10-22
申请号：US405623
申请日：1989-09-12
申请人： Andrew S. Janoff , Mircea C. Popescu , Carl R. Alving , Michael W. Fountain , Robert P. Lenk , Marc J. Ostro , Paul A. Tremblay , Alan L. Weiner
发明人： Andrew S. Janoff , Mircea C. Popescu , Carl R. Alving , Michael W. Fountain , Robert P. Lenk , Marc J. Ostro , Paul A. Tremblay , Alan L. Weiner
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K47/48215 , A61K47/48053 , A61K47/48123 , A61K9/127
摘要： Preparations of drugs in admixture with certain ligands are described which, when administered to animals or humans, are less toxic than conventional drug preparations. Although the toxicity of the drug-ligand preparations described is greatly reduced, the drug retains pharmacological activity.
摘要翻译：描述了与某些配体混合的药物的制备，其当施用于动物或人时比常规药物制剂毒性低。虽然所述药物 - 配体制剂的毒性大大降低，但药物保留药理活性。

10. 发明授权

US4897384A Drug preparations of reduced toxicity 失效
标题翻译：药物制剂毒性降低
公开(公告)号：US4897384A
公开(公告)日：1990-01-30
申请号：US844248
申请日：1986-03-24
申请人： Andrew S. Janoff , Carl R. Alving , Michael W. Fountain , Robert P. Lenk , Marc J. Ostro , Mircea C. Popescu , Paul A. Tremblay , Alan L. Weiner
发明人： Andrew S. Janoff , Carl R. Alving , Michael W. Fountain , Robert P. Lenk , Marc J. Ostro , Mircea C. Popescu , Paul A. Tremblay , Alan L. Weiner
IPC分类号： A61K20060101 , A61K9/127 , A61K31/00 , A61K31/66 , A61K31/665 , A61K31/70 , A61K47/00 , A61K47/48
CPC分类号： A61K9/127 , A61K47/48053 , A61K47/48123 , A61K47/48215
摘要： Preparations of drugs in admixture with certain ligands are described which, when administered to animals or humans, are less toxic than conventional drug preparations. Although the toxicity of the drug-ligand preparations described is greatly reduced, the drug retains pharmacological activity.
摘要翻译：描述了与某些配体混合的药物的制备，其当施用于动物或人时比常规药物制剂毒性低。虽然所述药物 - 配体制剂的毒性大大降低，但药物保留药理活性。

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