公开(公告)号：US08603995B2

公开(公告)日：2013-12-10

申请号：US13359129

申请日：2012-01-26

申请人： Mark Aron Labow ,  Larry Alexander Gaither ,  Jason Borawski

发明人： Mark Aron Labow ,  Larry Alexander Gaither ,  Jason Borawski

IPC分类号： C12N15/113 ,  C07H21/04

CPC分类号： C12N15/1137 ,  A61K31/713 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3233 ,  C12N2310/3515 ,  C12N2310/531 ,  Y02A50/385 ,  C12N2310/3521

摘要： The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propogation of positive stranded RNA viruses in and between cells.

公开(公告)号：US20120129913A1

公开(公告)日：2012-05-24

申请号：US13359129

申请日：2012-01-26

申请人： Mark Aron LABOW ,  Larry Alexander GAITHER ,  Jason BORAWSKI

发明人： Mark Aron LABOW ,  Larry Alexander GAITHER ,  Jason BORAWSKI

IPC分类号： A61K31/713 ,  A61P31/14 ,  C12N15/63 ,  C12N5/10 ,  C07H21/02 ,  C12N5/071

CPC分类号： C12N15/1137 ,  A61K31/713 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3233 ,  C12N2310/3515 ,  C12N2310/531 ,  Y02A50/385 ,  C12N2310/3521

摘要： The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propogation of positive stranded RNA viruses in and between cells.

摘要翻译： 本发明涉及靶向磷脂酰肌醇4-激酶（PI4K）的基因表达的双链核糖核酸（dsRNA），特别是人磷脂酰肌醇4-激酶，催化的β多肽（PIK4CB）或人磷脂酰肌醇4-激酶，催化的α多肽 （PIK4CA），以及它们用于治疗由正链RNA病毒如丙型肝炎病毒（HCV）感染的用途。 每个dsRNA包含具有长度小于30个核苷酸的核苷酸序列的反义链，其长度通常为19-25个核苷酸，并且其与至少一部分PIK4CB或PIK4CA靶mRNA基本上互补。 可以使用多种这样的dsRNA来提供治疗益处。 本发明还涉及包含dsRNA与药学上可接受的载体的药物组合物，并且包括递送方式如完全包封的脂质体或脂质复合物。 本发明还包括使用药物组合物治疗由正链RNA病毒感染引起的疾病的方法; 以及用于抑制细胞内和细胞内的正链RNA病毒传播的方法。

公开(公告)号：US20100183613A1

公开(公告)日：2010-07-22

申请号：US12582242

申请日：2009-10-20

申请人： Jason BORAWSKI ,  Larry Alexander Gaither ,  Mark Aron Labow

发明人： Jason BORAWSKI ,  Larry Alexander Gaither ,  Mark Aron Labow

IPC分类号： A61K39/395 ,  A61K31/713 ,  A61K38/02 ,  A61K31/357 ,  A61K31/7088 ,  A61P31/14

CPC分类号： C12N9/88 ,  C12N15/1137 ,  C12N2310/14 ,  C12Y401/01033

摘要： The present invention provides novel methods of reducing Flavivirus viral replication and/or infection, e.g., Dengue virus. The invention employs mevalonate decarboxylase (MVD) antagonists to inhibit the cholesterol biosynthesis pathway, thereby inhibiting viral replication/infection.

摘要翻译： 本发明提供了减少黄病毒病毒复制和/或感染的新方法，例如登革热病毒。 本发明使用甲羟戊酸脱羧酶（MVD）拮抗剂抑制胆固醇生物合成途径，从而抑制病毒复制/感染。

公开(公告)号：US20090202565A1

公开(公告)日：2009-08-13

申请号：US11577961

申请日：2005-10-24

申请人： Mark Aron Labow ,  Mark Bittinger

发明人： Mark Aron Labow ,  Mark Bittinger

IPC分类号： A61K39/395 ,  C12Q1/68 ,  C12Q1/48 ,  C12Q1/02 ,  G01N33/566 ,  A61K38/02 ,  A61K31/7105 ,  A61K31/7088

CPC分类号： C07K14/4705 ,  A61K38/00 ,  G01N33/5008 ,  G01N33/5035 ,  G01N33/5091 ,  G01N2333/4706

摘要： The present invention relates to a broad range of methods that utilize a transducer of regulated CREB (TORC)-related polynucleotide, polypeptide, or TORC-specific antibody. In addition the invention relates to TORC-related polynucleotide, polypeptide, or TORC-specific antibody compositions, including variants of TORC wild-type sequences. Exemplary methods include a method of stimulating a TORC related process in a cell as well as a method of inhibiting a TORC-related process in a cell, and a method of inhibiting TORC-related processes in a cell. The invention additionally discloses therapeutic methods of substantially inhibiting the development of, treating, or ameliorating a disease or pathological condition in a subject related to an abnormal level of a TORC-activated process in a cell that includes administering one or more therapeutically effective doses to the subject of either a substance that modulates accumulation of a TORC polypeptide in a subcellular region of the cell, or of a substance that inhibits expression of a TORC polypeptide in the cell. In an additional aspect a method of identifying an agent that modulates the activity of a TORC-related process in a cell is disclosed. In still a further aspect the invention relates to a method of detecting the presence or quantifying the amount of a TORC polypeptide in a sample. In a further aspect, a method is disclosed of determining whether the amount of a TORC polypeptide in a sample differs from the amount of the TORC polypeptide in a reference. An additional aspect relates to a method of contributing to the diagnosis or prognosis of, or to developing a therapeutic strategy for, a disease or pathology in a first subject, wherein the subcellular localization of a TORC polypeptide in the pathology is known to differ from the subcellular localization of the TORC polypeptide in a nonpathological state.

摘要翻译： 本发明涉及利用经调节的CREB（TORC）相关多核苷酸，多肽或TORC特异性抗体的转导体的广泛范围的方法。 此外，本发明涉及TORC相关多核苷酸，多肽或TORC特异性抗体组合物，包括TORC野生型序列的变体。 示例性方法包括刺激细胞中TORC相关过程的方法以及抑制细胞中TORC相关过程的方法，以及抑制细胞中TORC相关过程的方法。 本发明另外公开了基本上抑制发展，治疗或改善受试者与细胞中TORC活化过程的异常水平相关的疾病或病理状况的治疗方法，其包括向所述细胞施用一种或多种治疗有效剂量 调节细胞亚细胞区域中TORC多肽的积累的物质或抑制细胞中TORC多肽表达的物质的受试者。 在另一方面，公开了一种识别调节细胞中TORC相关过程的活性的试剂的方法。 在另一方面，本发明涉及一种检测样品中TORC多肽的存在或定量的方法。 在另一方面，公开了确定样品中TORC多肽的量是否与参考文献中TORC多肽的量不同的方法。 另外一个方面涉及有助于第一受试者的疾病或病理学的诊断或预后或制定治疗策略的方法，其中TORC多肽在病理学中的亚细胞定位已知不同于 TORC多肽在非病理状态下的亚细胞定位。

公开(公告)号：US20090136506A1

公开(公告)日：2009-05-28

申请号：US12089005

申请日：2006-10-02

申请人： Mark Bittinger ,  Christine Chow ,  Danilo Guerini ,  Mark Aron Labow ,  Brian Jude Latario ,  Zhao-Hui Xiong

发明人： Mark Bittinger ,  Christine Chow ,  Danilo Guerini ,  Mark Aron Labow ,  Brian Jude Latario ,  Zhao-Hui Xiong

IPC分类号： A61K39/395 ,  C07K14/00 ,  C07K16/00 ,  C07H21/00 ,  A61K31/7088 ,  A61P25/00 ,  G01N33/53 ,  C12N15/74 ,  C12N5/10 ,  C12P21/00

CPC分类号： C07K14/47 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2310/53

摘要： The invention discloses the first known function and biological activity of the hypothetical protein MGC14327, now designated cMAC, which is herein identified as an important controller of T-cell activation. It is contemplated herein that cMAC is a suitable drug target for the development of new therapeutics to treat cMAC-associated disorders. The invention relates to methods to treat said pathological conditions and to pharmaceutical compositions therefore. The pharmaceutical compositions comprise modulators with inhibitory or agonist effect on cMAC protein activity and/or cMAC gene expression. The invention also relates to methods to identify compounds with therapeutic usefulness to treat said pathological conditions, comprising identifying compounds that can inhibit or agonize cMAC protein activity and/or cMAC gene expression.

摘要翻译： 本发明公开了现在称为cMAC的假想蛋白质MGC14327的第一已知功能和生物活性，其被鉴定为T细胞活化的重要控制剂。 本文预期cMAC是用于开发用于治疗cMAC相关疾病的新治疗剂的合适的药物靶标。 本发明涉及治疗所述病理状态的方法和药物组合物。 药物组合物包含对cMAC蛋白活性和/或cMAC基因表达具有抑制或激动作用的调节剂。 本发明还涉及鉴定具有治疗所述病理状况的治疗有用性的化合物的方法，其包括鉴定可抑制或激动cMAC蛋白活性和/或cMAC基因表达的化合物。

公开(公告)号：US20140057965A1

公开(公告)日：2014-02-27

申请号：US14069642

申请日：2013-11-01

申请人： Mark Aron LABOW ,  Larry Alexander GAITHER ,  Jason BORAWSKI

发明人： Mark Aron LABOW ,  Larry Alexander GAITHER ,  Jason BORAWSKI

IPC分类号： C12N15/113 ,  A61K31/713

CPC分类号： C12N15/1137 ,  A61K31/713 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3233 ,  C12N2310/3515 ,  C12N2310/531 ,  Y02A50/385 ,  C12N2310/3521

摘要： The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propogation of positive stranded RNA viruses in and between cells.

摘要翻译： 本发明涉及靶向磷脂酰肌醇4-激酶（PI4K）的基因表达的双链核糖核酸（dsRNA），特别是人磷脂酰肌醇4-激酶，催化的β多肽（PIK4CB）或人磷脂酰肌醇4-激酶，催化的α多肽 （PIK4CA），以及它们用于治疗由正链RNA病毒如丙型肝炎病毒（HCV）感染的用途。 每个dsRNA包含具有长度小于30个核苷酸的核苷酸序列的反义链，其长度通常为19-25个核苷酸，并且其与至少一部分PIK4CB或PIK4CA靶mRNA基本上互补。 可以使用多种这样的dsRNA来提供治疗益处。 本发明还涉及包含dsRNA与药学上可接受的载体的药物组合物，并且包括递送方式如完全包封的脂质体或脂质复合物。 本发明还包括使用药物组合物治疗由正链RNA病毒感染引起的疾病的方法; 以及用于抑制细胞内和细胞内的正链RNA病毒传播的方法。

公开(公告)号：US20100183704A1

公开(公告)日：2010-07-22

申请号：US12562349

申请日：2009-09-18

申请人： Jason Borawski ,  Larry Alexander Gaither ,  Mark Aron Labow

发明人： Jason Borawski ,  Larry Alexander Gaither ,  Mark Aron Labow

IPC分类号： A61K9/127 ,  C12N5/00 ,  C12N5/02 ,  C12N15/63 ,  A61P31/14 ,  A61K31/7088 ,  C07H21/02 ,  A61P31/20

CPC分类号： C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3515 ,  C12N2310/3521

摘要： The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the CAD target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propagation of positive stranded RNA viruses in and between cells.

摘要翻译： 本发明涉及靶向基因表达氨基甲酰磷酸合成酶2，天冬氨酸转氨甲酰酶和二氢激酶（CAD）的双链核糖核酸（dsRNA）及其用于治疗由正链RNA病毒如丙型肝炎病毒（HCV）感染的用途。 每个dsRNA包含具有长度小于30个核苷酸的核苷酸序列的反义链，其长度通常为19-25个核苷酸，并且其与至少一部分CAD靶mRNA基本互补。 可以使用多种这样的dsRNA来提供治疗益处。 本发明还涉及包含dsRNA与药学上可接受的载体的药物组合物，并且包括递送方式如完全包封的脂质体或脂质复合物。 本发明还包括使用药物组合物治疗由正链RNA病毒感染引起的疾病的方法; 以及用于抑制细胞内和细胞之间的正链RNA病毒繁殖的方法。

公开(公告)号：US20100316573A1

公开(公告)日：2010-12-16

申请号：US12446430

申请日：2007-10-17

申请人： Larry Alexander Gaither ,  Vadim Iourgenko ,  Mark Aron Labow ,  Dale Alan Porter ,  Christopher Sean Straub ,  Yao Yao ,  Leigh Zawel

发明人： Larry Alexander Gaither ,  Vadim Iourgenko ,  Mark Aron Labow ,  Dale Alan Porter ,  Christopher Sean Straub ,  Yao Yao ,  Leigh Zawel

IPC分类号： A61K49/00 ,  A61K31/4439 ,  C07D401/02 ,  A61P9/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00

CPC分类号： G01N33/574 ,  G01N33/6869 ,  G01N2333/525

摘要： A method to predict which patients will respond to a IAP inhibiting compound comprising: a) administering an IAP inhibitor compound to a patient, and b) measuring TNF-α or IL-β levels.

摘要翻译： 一种预测哪些患者将对IAP抑制化合物作出反应的方法，包括：a）向患者施用IAP抑制剂化合物，和b）测量TNF-α或IL- 水平。

公开(公告)号：US20100184823A1

公开(公告)日：2010-07-22

申请号：US12667631

申请日：2008-07-04

申请人： Mark Aron Labow ,  Larry Alexander Gaither ,  Jason Borawski

发明人： Mark Aron Labow ,  Larry Alexander Gaither ,  Jason Borawski

IPC分类号： A61K31/7088 ,  C07H21/02 ,  C12N5/10 ,  A61K9/127 ,  C12N5/02

CPC分类号： C12N15/1137 ,  A61K31/713 ,  C12N2310/14 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3233 ,  C12N2310/3515 ,  C12N2310/531 ,  Y02A50/385 ,  C12N2310/3521

摘要： The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propagation of positive stranded RNA viruses in and between cells.

摘要翻译： 本发明涉及靶向磷脂酰肌醇4-激酶（PI4K）的基因表达的双链核糖核酸（dsRNA），特别是人磷脂酰肌醇4-激酶，催化的β多肽（PIK4CB）或人磷脂酰肌醇4-激酶，催化的α多肽 （PIK4CA），以及它们用于治疗由正链RNA病毒如丙型肝炎病毒（HCV）感染的用途。 每个dsRNA包含具有长度小于30个核苷酸的核苷酸序列的反义链，其长度通常为19-25个核苷酸，并且其与至少一部分PIK4CB或PIK4CA靶mRNA基本上互补。 可以使用多种这样的dsRNA来提供治疗益处。 本发明还涉及包含dsRNA与药学上可接受的载体的药物组合物，并且包括递送方式如完全包封的脂质体或脂质复合物。 本发明还包括使用药物组合物治疗由正链RNA病毒感染引起的疾病的方法; 以及用于抑制细胞内和细胞之间的正链RNA病毒繁殖的方法。