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1. 发明公开

EP2340309A2 NEUTRAL NANOTRANSPORTERS 审中-公开
标题翻译： NEUTRALE NANOTRANSPORTER
公开(公告)号：EP2340309A2
公开(公告)日：2011-07-06
申请号：EP09789352.3
申请日：2009-09-22
申请人： Rxi Pharmaceuticals Corporation , Khvorova, Anastasia , Salomon, William , Kamens, Joanne , Samarsky, Dmitry , Woolf, Tod M. , Miller, Michelle , Bulock, Karen G.
发明人： KHVOROVA, Anastasia , SALOMON, William , KAMENS, Joanne , SAMARSKY, Dmitry , WOOLF, Tod, M. , MILLER, Michelle , BULOCK, Karen, G.
IPC分类号： C12N15/113 , A61K31/7088
CPC分类号： C12N15/1136 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/3341 , C12N2310/3515 , C12N2310/3519 , C12N2310/3521 , C12N2320/32 , C12N2320/51 , C12N2320/53
摘要： The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.
摘要翻译：本发明涉及具有最小双链区域的RNAi构建体及其在基因沉默中的用途。与本发明相关的RNAi构建体包括8-14个核苷酸的双链区域和各种化学修饰，并且在基因沉默中是非常有效的。

2. 发明公开

EP2342340A1 RNA INTERFERENCE IN SKIN INDICATIONS 审中-公开
标题翻译： RNA-INTERFERENZ BEI HAUTINDIKATIONEN
公开(公告)号：EP2342340A1
公开(公告)日：2011-07-13
申请号：EP09789350.7
申请日：2009-09-22
申请人： Rxi Pharmaceuticals Corporation , Khvorova, Anastasia , Salomon, William , Kamens, Joanne , Samarsky, Dmitry , Woolf, Tod M. , Pavco, Pamela A.
发明人： KHVOROVA, Anastasia , SALOMON, William , KAMENS, Joanne , SAMARSKY, Dmitry , WOOLF, Tod, M. , PAVCO, Pamela, A.
IPC分类号： C12N15/113 , A61K31/713
CPC分类号： C12N15/1136 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/3341 , C12N2310/3515 , C12N2310/3519 , C12N2310/3521 , C12N2320/32 , C12N2320/51 , C12N2320/53
摘要： The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.
摘要翻译：本发明涉及具有最小双链区域的RNAi构建体及其在基因沉默中的用途。与本发明相关的RNAi构建体包括8-14个核苷酸的双链区域和各种化学修饰，并且在基因沉默中是非常有效的。

3. 发明公开

EP2340310A2 REDUCED SIZE SELF-DELIVERING RNAI COMPOUNDS 有权转让
标题翻译：自RNAi化合物缩小尺寸
公开(公告)号：EP2340310A2
公开(公告)日：2011-07-06
申请号：EP09789351.5
申请日：2009-09-22
申请人： Rxi Pharmaceuticals Corporation , Khvorova, Anastasia , Salomon, William , Kamens, Joanne , Samarsky, Dmitry , Woolf, Tod M. , Cardia, James
发明人： KHVOROVA, Anastasia , SALOMON, William , KAMENS, Joanne , SAMARSKY, Dmitry , WOOLF, Tod, M. , CARDIA, James
IPC分类号： C12N15/113 , A61K31/713
CPC分类号： C12N15/1136 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/3341 , C12N2310/3515 , C12N2310/3519 , C12N2310/3521 , C12N2320/32 , C12N2320/51 , C12N2320/53
摘要： The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.

4. 发明申请

WO2011119871A1 RNA INTERFERENCE IN OCULAR INDICATIONS 审中-公开
标题翻译： RNA干扰在眼睛适应症
公开(公告)号：WO2011119871A1
公开(公告)日：2011-09-29
申请号：PCT/US2011/029849
申请日：2011-03-24
申请人： RXI PHRMACEUTICALS CORPORATION , LIBERTINE, Lyn , KHVOROVA, Anastasia , SALOMON, William , KAMENS, Joanne , SAMARSKY, Dmitry , WOOLF, Tod, M. , CARDIA, James
发明人： LIBERTINE, Lyn , KHVOROVA, Anastasia , SALOMON, William , KAMENS, Joanne , SAMARSKY, Dmitry , WOOLF, Tod, M. , CARDIA, James
IPC分类号： A61K31/713 , C07H21/02
CPC分类号： C12N15/1136 , A61K9/0048 , A61K9/0051 , A61K31/713 , A61K45/06 , A61K47/554 , C12N2310/14 , C12N2310/313 , C12N2310/321 , C12N2310/322 , C12N2310/3515 , C12N2320/31 , C12N2320/32 , A61K2300/00
摘要： The present invention relates to ocular administration of sd-rxRNA and rxRNAori molecules.
摘要翻译：本发明涉及sd-rxRNA和rxRNAori分子的眼部给药。

5. 发明申请

WO2010059226A3 INHIBITION OF MAP4K4 THROUGH RNAI 审中-公开
标题翻译：通过RNAi抑制MAP4K4
公开(公告)号：WO2010059226A3
公开(公告)日：2010-07-15
申请号：PCT/US2009006211
申请日：2009-11-19
申请人： RXI PHARMACEUTICALS CORP , WOOLF TOD M , KAMENS JOANNE , KHVOROVA ANASTASIA , SALOMON WILLIAM
发明人： WOOLF TOD M , KAMENS JOANNE , KHVOROVA ANASTASIA , SALOMON WILLIAM
IPC分类号： C07H21/02 , A61K31/7088
CPC分类号： C12N15/1137 , C12N2310/14 , C12N2310/321 , C12N2320/11 , C12N2320/30 , C12Y207/01037
摘要： RNAi constructs directed to MAP4K4 that demonstrate unexpectedly high gene silencing activities, and uses thereof are disclosed. The blunt-ended constructs have a double-stranded region of 19-49 nucleotides. The constructs have selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the strands may be modified (e g., one or both ends of the sense strand is modified by 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, the antisense strand may also be modified by a 2'-O-methyl group at the penultimate 5'-end nucleotide to greatly reduce off- target silencing.
摘要翻译：公开了针对表达意想不到的高基因沉默活性的MAP4K4的RNAi构建体及其用途。平端构建体具有19-49个核苷酸的双链区域。该构建体具有选择性的最小修饰以赋予生物活性，毒性，稳定性和靶基因特异性的最佳平衡。例如，可以修饰链（例如，有义链的一个或两个末端被2'-O-甲基修饰），使得构建体不被Dicer或其他RNA酶III切割，反义链也可以在倒数第二个5'-末端核苷酸处被2'-O-甲基修饰，以大大减少脱靶沉默。

6. 发明申请

WO2010033247A3 REDUCED SIZE SELF-DELIVERING RNAI COMPOUNDS 审中-公开
标题翻译：减少尺寸自交RNAi化合物
公开(公告)号：WO2010033247A3
公开(公告)日：2010-06-03
申请号：PCT/US2009005247
申请日：2009-09-22
申请人： RXI PHARMACEUTICALS CORP , KHVOROVA ANASTASIA , SALOMON WILLIAM , KAMENS JOANNE , SAMARSKY DMITRY , WOOLF TOD M , CARDIA JAMES
发明人： KHVOROVA ANASTASIA , SALOMON WILLIAM , KAMENS JOANNE , SAMARSKY DMITRY , WOOLF TOD M , CARDIA JAMES
IPC分类号： C12N15/113 , A61K31/713
CPC分类号： C12N15/1136 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/3341 , C12N2310/3515 , C12N2310/3519 , C12N2320/32 , C12N2320/51 , C12N2310/3521
摘要： The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.
摘要翻译：本发明涉及具有最小双链区的RNAi构建体及其在基因沉默中的应用。与本发明相关的RNAi构建体包括8-14个核苷酸的双链区域和各种化学修饰，并且在基因沉默中是非常有效的。

7. 发明申请

WO2010059226A2 INHIBITION OF MAP4K4 THROUGH RNAI 审中-公开
标题翻译：通过RNAi抑制MAP4K4
公开(公告)号：WO2010059226A2
公开(公告)日：2010-05-27
申请号：PCT/US2009/006211
申请日：2009-11-19
申请人： RXI PHARMACEUTICALS CORPORATION , WOOLF, Tod, M. , KAMENS, Joanne , KHVOROVA, Anastasia , SALOMON, William
发明人： WOOLF, Tod, M. , KAMENS, Joanne , KHVOROVA, Anastasia , SALOMON, William
IPC分类号： A61M5/31
CPC分类号： C12N15/1137 , C12N2310/14 , C12N2310/321 , C12N2320/11 , C12N2320/30 , C12Y207/01037
摘要： The invention relates to various MAP4K4 RNAi constructs with unexpectedly high gene silencing activities, and uses thereof. The construct has a double-stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified ( e.g ., one or both ends of the sense strand is/are modified by four 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2'-O-methyl group at the 2nd 5'-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.
摘要翻译：本发明涉及具有意想不到的高基因沉默活性的各种MAP4K4 RNAi构建体及其用途。该构建体具有19-49个核苷酸，优选25,26或27个核苷酸的双链区域，并且优选是平端的。该构建体具有选择性的最小修饰以赋予生物活性，毒性，稳定性和靶基因特异性的最佳平衡。例如，有义链可以被修饰（例如，有义链的一个或两个末端被四个2'-O-甲基修饰），使得该构建体不被Dicer或其他RNA酶III切割，以及反义链的整个长度被加载到RISC中。此外，反义链也可以通过2'-O-甲基在第二个5'-末端核苷酸修饰，以大大减少脱靶沉默。本发明的构建体大大避免了哺乳动物细胞中的干扰素反应和序列无关的凋亡，表现出更好的血清稳定性和增强的靶特异性。

8. 发明申请

WO2010011346A9 RNAI CONSTRUCTS AND USES THEROF 审中-公开
公开(公告)号：WO2010011346A9
公开(公告)日：2010-01-28
申请号：PCT/US2009/004326
申请日：2009-07-23
申请人： RXI PHARMACEUTICALS CORPORATION , SAMARSKY, Dmitry , WOOLF, Tod , SALOMON, William , KAMENS, Joanne , KHVOROVA, Anastasia , PAVCO, Pamela, A.
发明人： SAMARSKY, Dmitry , WOOLF, Tod , SALOMON, William , KAMENS, Joanne , KHVOROVA, Anastasia , PAVCO, Pamela, A.
IPC分类号： C12N15/11 , A61K31/713 , A61K31/712
摘要： The invention relates to improved double-stranded RNAi constructs (sometimes referred to as "solo-rxRNA") and uses thereof. The construct comprises a structure formed in some aspects of the invention by two identical single-stranded polynucleotides, with the structure having two double-stranded stem regions (each having less than 21 base pairs) and a loop or bulge having about 4 to 11 nucleotides on each strand. The construct is resistant to cleavage by Dicer or other Dicer-like RNase III enzymes and is capable of being loaded into a RISC complex to effect RNA interference. In addition, the nucleotides of the present hairpin constructs may be modified to greatly enhance functionality, such as stability and specificity.

9. 发明申请

WO2009045457A3 TRIPARTITE RNAI CONSTRUCTS 审中-公开
公开(公告)号：WO2009045457A3
公开(公告)日：2009-04-09
申请号：PCT/US2008/011394
申请日：2008-10-02
申请人： RXI PHARMACEUTICALS CORP. , WOOLF, Tod, M. , WAGNER, Rick , PAVCO, Pam , SALOMON, William , USMAN, Nassim , SAMARSKY, Dmitry
发明人： WOOLF, Tod, M. , WAGNER, Rick , PAVCO, Pam , SALOMON, William , USMAN, Nassim , SAMARSKY, Dmitry
IPC分类号： C12N15/11 , C07H21/00 , A61K31/713 , C12P19/34 , C07H21/02 , C07H21/04 , A01N43/04
摘要： The present invention provides compositions and methods for inhibiting expression of a target gene in a cell. The process comprises introduction of double-stranded tripartite RNAi constructs into the cells and reducing the expression of the corresponding messenger RNA in the cells. The constructs, which may be packaged in or delivered as sequestered RNAi constructs, differ from the canonical siRNA in that they comprise a tripartite structure which follows the general formula of having (1) an RNAi core (either native or abbreviated), (2) one or more terminal moieties attached to the RNAi core and optionally (3) a linker between the RNAi core and the terminal moiety. Once packaged into sequestration vehicles, the constructs are activated for gene regulation by the application of certain forms of energy.

10. 发明申请

WO2009102427A2 MODIFIED RNAI POLYNUCLEOTIDES AND USES THEREOF 审中-公开
标题翻译：改良的RNAi多核苷酸及其用途
公开(公告)号：WO2009102427A2
公开(公告)日：2009-08-20
申请号：PCT/US2009/000852
申请日：2009-02-11
申请人： RXI PHARMACEUTICALS CORP. , PAVCO, Pamela, A. , KAMENS, Joanne , WOOLF, Tod, M. , SALOMON, William , KHVOROVA, Anastasia
发明人： PAVCO, Pamela, A. , KAMENS, Joanne , WOOLF, Tod, M. , SALOMON, William , KHVOROVA, Anastasia
IPC分类号： C12N15/11 , C07H21/02 , A61K31/713
CPC分类号： C12N15/111 , C12N15/113 , C12N15/1136 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2320/51 , C12N2320/53 , C12N2310/3521
摘要： The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2'-O-methyl group at the 2nd 5'-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence- independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.
摘要翻译：本发明涉及改进的RNAi构建体及其用途。该构建体具有19-49个核苷酸，优选25,26或27个核苷酸的双链区域，并且优选是平端的。该构建体具有选择性的最小修饰以赋予生物活性，毒性，稳定性和靶基因特异性的最佳平衡。例如，有义链可以被修饰（例如，有义链的一个或两个末端被四个2'-O-甲基修饰），使得该构建体不被Dicer或其他RNA酶III切割，以及反义链的整个长度被加载到RISC中。此外，反义链也可以通过2'-O-甲基在第二个5'-末端核苷酸修饰，以大大减少脱靶沉默。本发明的构建体大大避免了哺乳动物细胞中的干扰素反应和序列无关的凋亡，表现出更好的血清稳定性和增强的靶特异性。

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