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公开(公告)号：US10519446B2
公开(公告)日：2019-12-31
申请号：US15025852
申请日：2014-09-30
申请人： Novartis AG , Jeremy Lee Baryza , Marcel Blommers , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu , Meghan Holdorf
发明人： Jeremy Lee Baryza , Marcel Blommers , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu , Meghan Holdorf
IPC分类号： C12N15/113
摘要： The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3′ end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. In some embodiments, the 3′ end of both the sense and anti-sense strand further comprise, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3′ end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the RNAi agent can be modified on one or both 5′ end. Optionally, the sense strand can comprise a 5′ end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference. The disclosure also pertains to methods of treating, ameliorating and preventing HBV in a patient involving the step of administering to the patient a therapeutic amount of a HBV RNAi agent.
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公开(公告)号：US20160304863A1
公开(公告)日：2016-10-20
申请号：US15025779
申请日：2014-10-01
申请人： Jeremy Lee BARYZA , Marcel BLOMMERS , Cesar FERNANDEZ , Erin GENO , Alvar GOSSERT , Paulette GREENIDGE , Dieter HUESKEN , Juerg HUNZIKER , Francois Jean-Charles NATT , Anup PATNAIK , Andrew PATTERSON , Jean-Michel Rene RONDEAU , Jan WEILER , Meicheng ZHU
发明人： Jeremy Lee Baryza , Marcel Blommers , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu
IPC分类号： C12N15/11 , C07C233/01 , C07D217/18 , C07D215/14 , C07D217/16
CPC分类号： C12N15/111 , C07C43/23 , C07C69/40 , C07C233/01 , C07D213/30 , C07D215/12 , C07D215/14 , C07D217/14 , C07D217/16 , C07D217/18 , C07D311/80 , C07D401/04 , C12N2310/14 , C12N2310/344 , C12N2310/351 , C12N2320/51
摘要： The disclosure relates to novel compounds and compositions comprising a RNAi agent comprising a novel compound as a 3′ end cap. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.
摘要翻译： 本公开涉及包含含有作为3'端帽的新化合物的RNAi剂的新化合物和组合物。 本公开还涉及制备这种组合物的方法，以及这种组合物的方法和用途，例如介导RNA干扰。
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公开(公告)号：US09988627B2
公开(公告)日：2018-06-05
申请号：US15025826
申请日：2014-10-06
申请人： Jeremy Lee Baryza , Marcel Blommers , William Chutkow , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu
发明人： Jeremy Lee Baryza , Marcel Blommers , William Chutkow , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/14 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/341 , C12N2310/351 , C12N2310/3515 , C12N2310/3521 , C12N2310/3525 , C12N2310/3533
摘要： The disclosure relates to compositions comprising a RNAi agent having a novel format including a spacer subunit. The disclosure relates to compositions comprising a RNAi agent having a novel format: an 18-mer format with at least one internal spacer. These RNAi agents comprise a first and a second 18-mer strand, wherein the first strand is 18 ribonucleotides or 18 total ribonucleotides and spacer subunit(s), and the second strand is 18 total ribonucleotides and spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand; the two strands form a duplex with at least one blunt end; and the 3 end of one or both strands terminates in a phosphate or modified internucleoside linker and further comprises, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker, and a 3 end cap. In various embodiments, the RNAi agents comprise a first and a second strand, wherein each strand is a 30-mer or shorter, the first strand comprises ribonucleotides, and the second strand comprises ribonucleotides and one or more spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand. In some embodiments, the 3 end of both strands further comprise, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker; and a 3 end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3 end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the first two base-pairing nucleotides on the 3 end of the one or both strand are 2-MOE. Optionally, the RNAi agent can be modified on one or both 5 end. Optionally, the first or second strand is the sense strand, and the sense strand can comprise a 5 end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.
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公开(公告)号：US07827914B2
公开(公告)日：2010-11-09
申请号：US10974897
申请日：2004-10-27
申请人： Cesar Fernandez , David Florez
发明人： Cesar Fernandez , David Florez
IPC分类号： B41F1/34
CPC分类号： B41J11/46
摘要： In one embodiment, a method includes applying at least one invisible mark to media, sensing the at least one invisible mark with separate sensors, and determining a speed of the media from signals of the separate sensors.
摘要翻译： 在一个实施例中，一种方法包括将至少一个不可见标记应用于介质，用单独的传感器感测至少一个不可见标记，以及根据分离的传感器的信号确定介质的速度。
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公开(公告)号：US5676332A
公开(公告)日：1997-10-14
申请号：US632061
申请日：1996-04-15
CPC分类号： B65H75/22 , G03B21/321 , B65H2701/5122 , B65H2701/5136
摘要： A motion picture film reel is comprised of a pair of identical retaining members each formed with a flat, side cheek-plate member having a central axis of rotation and a hub-engaging region. An axially extending portion projects from each central, hub-engaging region in generally perpendicular alignment therewith. Each axially extending portion includes a base with a pair of diametrically opposed channels extending lengthwise along the base and a pair of resilient, diametrically opposed prongs. The prongs both have radially outwardly directed catches thereon. The prongs are inserted through a central, axial opening in a disk-shaped hub from the opposite sides thereof. The opposite edges of the core on the opposite sides of the hub form latching ledges so that the catches on the prongs releasably engage the latching ledges on the two opposite sides of the hub. The retaining members are thereby held releasably engaged to the central hub located therebetween. One or both retaining members can be removed simply by pressing the catches at the ends of the prongs together and pulling the retaining members apart from each other.
摘要翻译： 电影胶片卷轴由一对相同的保持构件组成，每个保持构件形成有具有中心旋转轴线的平坦侧面颊板构件和毂接合区域。 轴向延伸部分从每个中心的轮毂接合区域以与其大致垂直对准的方式突出。 每个轴向延伸部分包括具有沿着基部沿纵向延伸的一对直径相对的通道的底座和一对弹性的直径相对的插脚。 插脚在其上具有径向向外的卡扣。 插脚从圆形轮毂的相对侧的中心轴向开口插入。 在轮毂的相对侧上的芯的相对边缘形成闩锁凸缘，使得叉头上的卡扣可释放地接合在毂的两个相对侧上的闩锁凸缘。 因此，保持构件被可释放地接合到位于其间的中心毂。 一个或两个保持构件可以简单地通过将叉子的端部处的卡扣压在一起并将保持构件彼此分开来移除。
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公开(公告)号：USD741071S1
公开(公告)日：2015-10-20
申请号：US29511234
申请日：2014-12-09
申请人： Cesar Fernandez , Gary Neil
设计人： Cesar Fernandez , Gary Neil
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公开(公告)号：US20060139392A1
公开(公告)日：2006-06-29
申请号：US11026164
申请日：2004-12-28
申请人： Cesar Fernandez , Antoni Murcia , David Florez
发明人： Cesar Fernandez , Antoni Murcia , David Florez
IPC分类号： B41J29/393
CPC分类号： B41J2/125
摘要： Systems, methods, and devices are provided for detecting an ink drop crossing a plane of light.
摘要翻译： 提供了用于检测穿过光平面的墨滴的系统，方法和装置。
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8.发明授权Method of adjusting printing resolution to avoid conditions of poor pen performance in an inkjet printing system, and systems 有权调整打印分辨率以避免在喷墨打印系统和系统中笔性能差的条件的方法公开(公告)号：US07255413B2
公开(公告)日：2007-08-14
申请号：US11047075
申请日：2005-01-31
CPC分类号： G06K15/02 , B41J2/5056
摘要： Exemplary embodiments of the invention include methods of adjusting the print resolution of an inkjet printhead having a region of poor performance such that printing occurs outside the region of poor performance. Exemplary embodiments also include systems utilizing the methods.
摘要翻译： 本发明的示例性实施例包括调整具有差性能区域的喷墨打印头的打印分辨率的方法，使得在不良性能区域之外进行打印。 示例性实施例还包括利用该方法的系统。
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公开(公告)号：USD741072S1
公开(公告)日：2015-10-20
申请号：US29511238
申请日：2014-12-09
申请人： Cesar Fernandez , Gary Neil
设计人： Cesar Fernandez , Gary Neil
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10.发明申请Method of adjusting printing resolution to avoid conditions of poor pen performance in an inkjet printing system, and systems 有权调整打印分辨率以避免在喷墨打印系统和系统中笔性能差的条件的方法公开(公告)号：US20060170716A1
公开(公告)日：2006-08-03
申请号：US11047075
申请日：2005-01-31
申请人： Santiago Reyero , Cesar Fernandez , Robert Little
发明人： Santiago Reyero , Cesar Fernandez , Robert Little
IPC分类号： B41J2/21
CPC分类号： G06K15/02 , B41J2/5056
摘要： Exemplary embodiments of the invention include methods of adjusting the print resolution of an inkjet printhead having a region of poor performance such that printing occurs outside the region of poor performance. Exemplary embodiments also include systems utilizing the methods.
摘要翻译： 本发明的示例性实施例包括调整具有差性能区域的喷墨打印头的打印分辨率的方法，使得在不良性能区域之外进行打印。 示例性实施例还包括利用该方法的系统。
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