公开(公告)号：US09347089B2

公开(公告)日：2016-05-24

申请号：US13063155

申请日：2009-09-18

申请人： Judy Lieberman ,  Ashish Lal ,  Dipanjan Chowdhury

发明人： Judy Lieberman ,  Ashish Lal ,  Dipanjan Chowdhury

IPC分类号： C12Q1/68 ,  A61B5/00 ,  A61P35/00 ,  C12N15/11 ,  C12N15/113

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/11 ,  C12Q1/6806 ,  C12Q1/6809

摘要： The present invention encompasses the finding that microRNAs (miRNAs) regulate certain key proteins involved in DNA repair. In some embodiments, a miRNA suppresses levels and/or activity of one or more DNA repair proteins. In some such embodiments, such suppression renders cells hypersensitive to certain DNA damage agents (e.g., γ-irradiation and genotoxic drugs, among others). The present invention provides various reagents and methods associated with these findings including, among other things, strategies for treating cell proliferative disorders, certain diagnostic systems, etc.

摘要翻译： 本发明包括微RNA（miRNA）调节涉及DNA修复的某些关键蛋白的发现。 在一些实施方案中，miRNA抑制一种或多种DNA修复蛋白的水平和/或活性。 在一些这样的实施方案中，这种抑制使细胞对某些DNA损伤剂（例如γ-照射和遗传毒性药物等）过敏。 本发明提供了与这些发现相关的各种试剂和方法，其中包括治疗细胞增殖性疾病，某些诊断系统等的策略

公开(公告)号：US20120087973A1

公开(公告)日：2012-04-12

申请号：US13069589

申请日：2011-03-23

申请人： Judy Lieberman ,  Deborah Palliser ,  David Knipe

发明人： Judy Lieberman ,  Deborah Palliser ,  David Knipe

IPC分类号： A61K31/7105 ,  C12N5/071 ,  A61P31/14 ,  A61P31/12 ,  A61P31/22 ,  A61P31/20 ,  C12N5/00 ,  A61K9/127

CPC分类号： C12N15/1133 ,  A61K48/00 ,  C12N15/1131 ,  C12N2310/14

摘要： The invention provides a microbicidal composition comprising at least one siRNA. The siRNA is an RNA duplex made of one or two molecules. A portion of the siRNA is identical to a target sequence in an essential gene of a virus. The virus may be a herpesvirus, for example, HSV-1 or HSV-2. Preferably, the herpesvirus is HSV-2. The microbicidal composition further comprises a pharmaceutically acceptable carrier. Also included in the invention are methods to prevent and treat viral infections by administration of the microbicidal composition. Preferably, the microbicidal composition is administered transmucosally.

摘要翻译： 本发明提供包含至少一种siRNA的杀微生物组合物。 siRNA是由一个或两个分子制成的RNA双链体。 siRNA的一部分与病毒的必需基因中的靶序列相同。 病毒可以是疱疹病毒，例如HSV-1或HSV-2。 优选地，疱疹病毒是HSV-2。 杀微生物组合物还包含药学上可接受的载体。 本发明还包括通过施用杀微生物剂组合物预防和治疗病毒感染的方法。 优选地，所述杀微生物组合物经粘膜给药。

公开(公告)号：US20120059043A1

公开(公告)日：2012-03-08

申请号：US13063155

申请日：2009-09-18

申请人： Judy Lieberman ,  Ashish Lal ,  Dipanjan Chowdhury

发明人： Judy Lieberman ,  Ashish Lal ,  Dipanjan Chowdhury

IPC分类号： A61K31/7105 ,  A61P37/00 ,  A61P37/06 ,  C12N5/071 ,  A61P35/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/11 ,  C12Q1/6806 ,  C12Q1/6809

摘要： The present invention encompasses the finding that microRNAs (miRNAs) regulate certain key proteins involved in DNA repair. In some embodiments, a miRNA suppresses levels and/or activity of one or more DNA repair proteins. In some such embodiments, such suppression renders cells hypersensitive to certain DNA damage agents (e.g., γ-irradiation and genotoxic drugs, among others). The present invention provides various reagents and methods associated with these findings including, among other things, strategies for treating cell proliferative disorders, certain diagnostic systems, etc.

摘要翻译： 本发明包括微RNA（miRNA）调节涉及DNA修复的某些关键蛋白的发现。 在一些实施方案中，miRNA抑制一种或多种DNA修复蛋白的水平和/或活性。 在一些这样的实施方案中，这种抑制使细胞对某些DNA损伤剂（例如γ-照射和遗传毒性药物等）过敏。 本发明提供了与这些发现相关的各种试剂和方法，其中包括治疗细胞增殖性疾病，某些诊断系统等的策略

公开(公告)号：US20100310583A1

公开(公告)日：2010-12-09

申请号：US12525020

申请日：2008-01-31

申请人： Judy Lieberman ,  Erwei Song ,  Fengyan Yu ,  Xiaoqu Hu

发明人： Judy Lieberman ,  Erwei Song ,  Fengyan Yu ,  Xiaoqu Hu

IPC分类号： A61K31/713 ,  A61K31/7088 ,  A61K38/16 ,  A61K39/395 ,  A61K38/22 ,  A61P35/00

CPC分类号： A61K31/7105 ,  A61K31/7088 ,  A61K45/06 ,  A61K47/6807 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/141

摘要： The present invention relates to methods to treat or prevent cancers in a subject, in particular the present invention relates to a method of treating and/or preventing cancer comprising targeting cancer stem cells by administering miRNAs which have reduced expression or are lacking in the cancer stem cells. In some embodiments, the miRNAs that are reduced or lacking in cancer stem cells are let-7 miRNAs. In alternative embodiments, the present invention relates to a method of treating and/or preventing cancer comprising targeting cancer stem cells by administering miRNAs which have increased expression levels in the cancer stem cells. Another aspect of the present invention relates to methods to enrich for a cancer stem cell population. Another aspect of the present invention relates to methods to identify miRNAs which contribute to the self-renewal capacity of cancer stem cells.

摘要翻译： 本发明涉及治疗或预防受试者癌症的方法，特别是本发明涉及治疗和/或预防癌症的方法，其包括通过施用降低表达或缺乏癌症干细胞的miRNA来靶向癌症干细胞 细胞。 在一些实施方案中，减少或缺乏癌干细胞的miRNA是let-7 miRNA。 在替代实施方案中，本发明涉及治疗和/或预防癌症的方法，包括通过施用在癌症干细胞中具有增加的表达水平的miRNA来靶向癌症干细胞。 本发明的另一方面涉及富集癌症干细胞群体的方法。 本发明的另一方面涉及鉴定有助于癌症干细胞的自我更新能力的miRNA的方法。

公开(公告)号：US20090022783A1

公开(公告)日：2009-01-22

申请号：US11916334

申请日：2006-06-05

申请人： Judy Lieberman ,  Deborah Palliser ,  David Knipe

发明人： Judy Lieberman ,  Deborah Palliser ,  David Knipe

IPC分类号： A61K9/127 ,  A61K31/7105 ,  A61P31/00 ,  C12N5/06

CPC分类号： C12N15/1133 ,  A61K48/00 ,  C12N15/1131 ,  C12N2310/14

摘要： The invention provides a microbicidal composition comprising at least one siRNA. The siRNA is an RNA duplex made of one or two molecules. A portion of the siRNA is identical to a target sequence in an essential gene of a virus. The virus may be a herpesvirus, for example, HSV-1 or HSV-2. Preferably, the herpesvirus is HSV-2. The microbicidal composition further comprises a pharmaceutically acceptable carrier. Also included in the invention are methods to prevent and treat viral infections by administration of the microbicidal composition. Preferably, the microbicidal composition is administered transmucosally.

摘要翻译： 本发明提供包含至少一种siRNA的杀微生物组合物。 siRNA是由一个或两个分子制成的RNA双链体。 siRNA的一部分与病毒的必需基因中的靶序列相同。 病毒可以是疱疹病毒，例如HSV-1或HSV-2。 优选地，疱疹病毒是HSV-2。 杀微生物组合物还包含药学上可接受的载体。 本发明还包括通过施用杀微生物剂组合物预防和治疗病毒感染的方法。 优选地，所述杀微生物组合物经粘膜给药。

公开(公告)号：US09689040B2

公开(公告)日：2017-06-27

申请号：US14003021

申请日：2012-03-02

申请人： Judy Lieberman ,  Fabio Petrocca

发明人： Judy Lieberman ,  Fabio Petrocca

IPC分类号： C12Q1/68 ,  G01N33/574 ,  A61K31/165 ,  A61K31/167 ,  A61K31/713 ,  A61K38/05

CPC分类号： C12Q1/6886 ,  A61K31/165 ,  A61K31/167 ,  A61K31/713 ,  A61K38/05 ,  C12Q2600/158 ,  G01N33/57415 ,  G01N2500/10 ,  G01N2800/52 ,  G01N2800/56

摘要： Described herein are novel malignancy associated gene signature biomarkers, and assays and methods thereof, to classify prognosis or malignant potential of a cancer and identify cancer-initiating cells. The malignancy associated gene signature biomarkers, assays and methods described herein provide, in part, new methodologies to screen for novel drugs for treating cancers and tumors, such as, for example, triple-negative breast tumors. Using the assays and methods described herein proteasome inhibitors, histone deacetylase inhibitors, and glycolysis inhibitors, were identified as being highly effective in altering gene expression signatures specifically in malignant or cancer-initiating cells.

公开(公告)号：US20140155332A1

公开(公告)日：2014-06-05

申请号：US14003021

申请日：2012-03-02

申请人： Judy Lieberman ,  Fabio Petrocca

发明人： Judy Lieberman ,  Fabio Petrocca

IPC分类号： C12Q1/68 ,  A61K31/167 ,  A61K31/165 ,  A61K31/713 ,  A61K38/05

CPC分类号： C12Q1/6886 ,  A61K31/165 ,  A61K31/167 ,  A61K31/713 ,  A61K38/05 ,  C12Q2600/158 ,  G01N33/57415 ,  G01N2500/10 ,  G01N2800/52 ,  G01N2800/56

摘要： Described herein are novel malignancy associated gene signature biomarkers, and assays and methods thereof, to classify prognosis or malignant potential of a cancer and identify cancer-initiating cells. The malignancy associated gene signature biomarkers, assays and methods described herein provide, in part, new methodologies to screen for novel drugs for treating cancers and tumors, such as, for example, triple-negative breast tumors. Using the assays and methods described herein proteasome inhibitors, histone deacetylase inhibitors, and glycolysis inhibitors, were identified as being highly effective in altering gene expression signatures specifically in malignant or cancer-initiating cells.

摘要翻译： 本文描述了新型恶性肿瘤相关基因标签生物标志物及其测定及方法，用于分类癌症的预后或恶性潜能，并鉴定癌症起始细胞。 本文描述的恶性肿瘤相关基因特征生物标志物，测定和方法部分地提供了筛选用于治疗癌症和肿瘤的新型药物的新方法，例如三阴性乳腺肿瘤。 使用本文所述的测定和方法，蛋白酶体抑制剂，组蛋白脱乙酰酶抑制剂和糖酵解抑制剂被鉴定为在恶性或致癌细胞中特异性改变基因表达特征方面非常有效。

公开(公告)号：US20130129752A1

公开(公告)日：2013-05-23

申请号：US12298361

申请日：2007-04-25

申请人： Dan Peer ,  Motomu Shimaoka ,  Judy Lieberman

发明人： Dan Peer ,  Motomu Shimaoka ,  Judy Lieberman

IPC分类号： A61K39/395 ,  C12N5/06 ,  A61K35/12 ,  C07K16/18

CPC分类号： C12N15/87 ,  A61K2039/55555 ,  C12N15/111 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2320/32

摘要： Disclosed herein are is a leukocyte-selective delivery agent comprising, a targeting moiety that selectively binds LFA-I, a protein carrier moiety covalently linked to the targeting moiety, and a therapeutic agent associated with the carrier moiety. The delivery agent may be further selective for activated leukocytes, wherein the targeting moiety selectively binds LFA-I in its activated conformation. The targeting moiety comprises an antibody or functional fragment thereof, such as an scFV. Examples of antibodies or fragments thereof which selectively bind LFA-I activated conformation bind to the locked open I domain of LFA-I, or binds to the leg domain of the β2 subunit of LFA-I ((ILP2)—The antibody or functional fragment thereof may alternatively bind non-selectively to both low affinity and high affinity LFA-I. Examples of a non-protein carrier are a basic polypeptide such as protamine or a functional fragment thereof. One such fragment is RSQSRSRYYRQRQRSRRRRRRS. The therapeutic agent may comprise one or more of a nucleic acid, a small molecule, a polypeptide, and an antibody or functional fragment thereof. An example of a nucleic acid delivery agent comprises an RNA interference molecule. Examples of RNA interference molecules are siRNA, dsRNA, StRNA, shRNA, miRNA, and combinations thereof. Specific siRNAs are provided. Other examples of a nucleic acid delivery agent are a small RNA, an antagomir, an LNA, and an antisense oligonucleotide. Methods for leukocyte-selective delivery, or activated leukocyte-selective delivery in vivo, in vitro and ex vivo are also provided.

摘要翻译： 本文公开的是白细胞选择性递送剂，其包含选择性结合LFA-1的靶向部分，与靶向部分共价连接的蛋白质载体部分和与载体部分相关联的治疗剂。 递送剂可以对活化的白细胞进一步选择性，其中靶向部分选择性地结合其活化构象中的LFA-1。 靶向部分包含抗体或其功能片段，例如scFV。 选择性结合LFA-1激活的构象的抗体或其片段的实例与LFA-1的锁定的开放I结构域结合，或与LFA-1（（ILP2））的β2亚基的腿结构域结合 - 抗体或功能片段 非蛋白质载体的实例可以是碱性多肽，例如鱼精蛋白或其功能片段，一个这样的片段是RSQSRSRYYRQRQRSRRRRRRS，治疗剂可以包含一种 核酸分子的实例包括RNA干扰分子，RNA干扰分子的实例是siRNA，dsRNA，StRNA，shRNA， miRNA及其组合提供特异性siRNA，核酸递送剂的其它实例是小RNA，antagomir，LNA和反义寡核苷酸。白细胞选择方法 还提供体外和离体的活性递送或活化的白细胞选择性递送。

公开(公告)号：US20110142854A1

公开(公告)日：2011-06-16

申请号：US12992797

申请日：2009-05-18

申请人： Nan Yan ,  Alan Engelman ,  Judy Lieberman

发明人： Nan Yan ,  Alan Engelman ,  Judy Lieberman

IPC分类号： A61K39/42 ,  C12Q1/68 ,  C12N5/02 ,  A61K38/00 ,  A61K31/7088 ,  A61P31/18

CPC分类号： A61K31/00 ,  A61K31/7105 ,  C12N2740/16011

摘要： Described herein are methods and compositions for the inhibition of retroviral integration and replication. The methods and compositions inhibit the activity of one or more components of the SET complex or base excision repair enzymes and induce autointegration of retroviral double-stranded nucleic acid.

摘要翻译： 本文描述了用于抑制逆转录病毒整合和复制的方法和组合物。 方法和组合物抑制SET复合物或碱基切除修复酶的一种或多种组分的活性并诱导逆转录病毒双链核酸的自动整合。

公开(公告)号：US20100113560A1

公开(公告)日：2010-05-06

申请号：US12524524

申请日：2008-01-25

申请人： Judy Lieberman ,  Francisco Navarro

发明人： Judy Lieberman ,  Francisco Navarro

IPC分类号： A61K31/7088 ,  C07H21/04 ,  C12N5/00 ,  A61P35/00

CPC分类号： C12N15/1135 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/141 ,  C12Y207/11022

摘要： Described herein are compositions and methods for the prevention and treatment of hematopoietic malignancies. The compositions are miRNAs and associated nucleic acids.

摘要翻译： 本文描述了用于预防和治疗造血恶性肿瘤的组合物和方法。 组合物是miRNA和相关核酸。