公开(公告)号：US10166300B2

公开(公告)日：2019-01-01

申请号：US14895556

申请日：2014-06-04

Applicant: Virginia Commonwealth University ,  The Johns Hopkins University

Inventor： Paul B. Fisher ,  Swadesh K. Das ,  Mitchell E. Menezes ,  Devanand Sarkar ,  Martin G. Pomper

IPC: A61K51/00 ,  A61K9/14 ,  C12N15/63 ,  C07H21/04 ,  A61K48/00 ,  A61K41/00 ,  A61K49/00 ,  A61K51/04 ,  C12Q1/6897 ,  A61K9/00 ,  C12N15/86 ,  A61K38/20 ,  C12N7/00 ,  C12N15/87 ,  A61K51/12

Abstract: The presently disclosed subject matter generally relates to genetic constructs and methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols. In particular, the presently disclosed subject matter relates to tripartite cancer theranostic nucleic acid constructs that permit simultaneous cancer specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.

公开(公告)号：US20180305429A1

公开(公告)日：2018-10-25

申请号：US15956409

申请日：2018-04-18

Applicant: Virginia Commonwealth University

Inventor： Paul B. Fisher ,  Praveen Bhoopathi ,  Swadesh K. Das ,  Luni Emdad ,  Devanand Sarkar ,  Upneet Sokhi

IPC: C07K14/54 ,  A61K38/00

CPC classification number: C07K14/5428 ,  A61K38/00 ,  C07K14/54 ,  C07K2319/055

Abstract: Recombinant therapeutic cytokines (“therakines”) for the treatment of cancer are provided. The recombinant therakines include a truncated region of MDA-7/TL-24 (“M4”) not normally found in nature that has anti-cancer activity and a secretory signal which causes secretion of the therakine from plasmid/virus transduced normal and cancer cells and interaction of the therakine to MDA-7/IL-24 receptors on adjacent, neighboring and distant cancer cells. Therakine interaction results in bystander killing of the target cancer cell as well as adjacent, neighboring and distant cancer cells.

公开(公告)号：US09951114B2

公开(公告)日：2018-04-24

申请号：US14895138

申请日：2014-06-04

Applicant: Virginia Commonwealth University

Inventor： Paul B. Fisher ,  Praveen Bhoopathi ,  Swadesh K. Das ,  Luni Emdad ,  Devanand Sarkar ,  Upneet Sokhi

IPC: A61K38/00 ,  C07K14/00 ,  C07K14/54

CPC classification number: C07K14/5428 ,  A61K38/00 ,  C07K14/54 ,  C07K2319/055

Abstract: Recombinant therapeutic cytokines (“therakines”) for the treatment of cancer are provided. The recombinant therakines include a truncated region of MDA-7/TL-24 (“M4”) not normally found in nature that has anti-cancer activity and a secretory signal which causes secretion of the therakine from plasmid/virus transduced normal and cancer cells and interaction of the therakine to MDA-7/IL-24 receptors on adjacent, neighboring and distant cancer cells. Therakine interaction results in bystander killing of the target cancer cell as well as adjacent, neighboring and distant cancer cells.

公开(公告)号：US09701985B2

公开(公告)日：2017-07-11

申请号：US14895579

申请日：2014-06-04

Applicant: Virginia Commonwealth University

Inventor： Paul B. Fisher ,  Swadesh K. Das ,  Mitchell E. Menezes ,  Devanand Sarkar

IPC: C12N15/00 ,  C12N15/86 ,  G01N33/574 ,  A61K49/00 ,  C07K14/47 ,  C12N15/85 ,  G01N33/50

CPC classification number: C12N15/86 ,  A61K49/0008 ,  C07K14/47 ,  C12N15/85 ,  C12N15/8509 ,  C12N2710/10331 ,  C12N2710/10345 ,  C12N2830/008 ,  C12N2830/85 ,  G01N33/5088 ,  G01N33/57492

Abstract: Recombinant vectors in which expression of one or more elements (e.g. gene required for viral replication, detectable imaging agents, therapeutic agents, etc.) is driven by an mda-9/syntenin (mda-9) cancer selective promoter are provided, as are cells and transgenic animals that contain such vectors. The vectors are used in cancer therapy and/or diagnostics, especially to visualize (image) and treat metastasis (including in rapid in vitro assays), and the transgenic mice are used to monitor cancer progression and/or the efficacy of candidate therapeutic agents in screening assays.

公开(公告)号：US20160108101A1

公开(公告)日：2016-04-21

申请号：US14895138

申请日：2014-06-04

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Paul B. Fisher ,  Praveen Bhoopathi ,  Swadesh K. Das ,  Luni Emdad ,  Devanand Sarkar ,  Upneet Sokhi

IPC: C07K14/54

CPC classification number: C07K14/5428 ,  A61K38/00 ,  C07K14/54 ,  C07K2319/055

Abstract: Recombinant therapeutic cytokines (“therakines”) for the treatment of cancer are provided. The recombinant therakines include a truncated region of MDA-7/TL-24 (“M4”) not normally found in nature that has anti-cancer activity and a secretory signal which causes secretion of the therakine from plasmid/virus transduced normal and cancer cells and interaction of the therakine to MDA-7/IL-24 receptors on adjacent, neighboring and distant cancer cells. Therakine interaction results in bystander killing of the target cancer cell as well as adjacent, neighboring and distant cancer cells.

Abstract translation: 提供了用于治疗癌症的重组治疗细胞因子（“治疗”）。 重组酶包括自然界中通常没有发现具有抗癌活性的MDA-7 / TL-24（“M4”）的截短区域，以及导致质粒/病毒转导的正常和癌细胞分泌的热分解信号 以及相邻的，相邻的和远处的癌细胞上的热激蛋白与MDA-7 / IL-24受体的相互作用。 治疗相互作用导致旁观者杀死靶癌细胞以及相邻，相邻和远处的癌细胞。

公开(公告)号：US20210147502A1

公开(公告)日：2021-05-20

申请号：US17082523

申请日：2020-10-28

Applicant: Virginia Commonwealth University

Inventor： Paul B. Fisher ,  Praveen Bhoopathi ,  Swadesh K. Das ,  Luni Emdad ,  Devanand Sarkar ,  Upneet Sokhi

IPC: C07K14/54

Abstract: Recombinant therapeutic cytokines (“therakines”) for the treatment of cancer are provided. The recombinant therakines include a truncated region of MDA-7/TL-24 (“M4”) not normally found in nature that has anti-cancer activity and a secretory signal which causes secretion of the therakine from plasmid/virus transduced normal and cancer cells and interaction of the therakine to MDA-7/IL-24 receptors on adjacent, neighboring and distant cancer cells. Therakine interaction results in bystander killing of the target cancer cell as well as adjacent, neighboring and distant cancer cells.

公开(公告)号：US10314870B2

公开(公告)日：2019-06-11

申请号：US14650775

申请日：2013-12-10

Applicant: Virginia Commonwealth University

Inventor： Paul Fisher ,  Devanand Sarkar ,  Paul Dent

IPC: A61K35/768 ,  A61K39/00 ,  C12N15/86 ,  A61K31/166 ,  A61K31/404 ,  A61K45/06 ,  C12N7/00

Abstract: A tropism modified cancer terminator virus (Ad.5/3-CTV; Ad.5/3-CTV-M7) has been found to have infectivity that is Coxsackie Adenoviral Receptor (CAR) independent. The Ad.5/3-CTV (Ad.5/3-CTV-M7) may be used alone or in combination with other therapeutic agents such as agents that augment reactive oxygen (ROS) production, HDAC inhibitors, MCL-1 inhibitors and Bcl-2 inhibitors to treat a variety of cancers particularly including malignant glioma (GBM), renal cancer, prostate cancer, and colorectal cancer.

公开(公告)号：US20160106866A1

公开(公告)日：2016-04-21

申请号：US14895556

申请日：2014-06-04

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Paul B. FISHER ,  Swadesh K. Das ,  Mitchell E. MENEZES ,  Devanand Sarkar ,  Martin G. Pomper

IPC: A61K48/00 ,  A61K51/00 ,  C12N15/87 ,  A61K49/00 ,  A61K41/00 ,  A61K38/20 ,  C12N7/00

CPC classification number: A61K48/0058 ,  A61K9/0019 ,  A61K38/20 ,  A61K41/0028 ,  A61K41/0033 ,  A61K49/0013 ,  A61K49/0045 ,  A61K49/0054 ,  A61K51/00 ,  A61K51/0491 ,  A61K51/12 ,  C07H21/04 ,  C12N7/00 ,  C12N15/86 ,  C12N15/87 ,  C12N2710/10043 ,  C12N2710/10343 ,  C12N2710/16143 ,  C12N2710/16171 ,  C12N2830/008 ,  C12Q1/6897

Abstract: The presently disclosed subject matter generally relates to genetic constructs and methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols. In particular, the presently disclosed subject matter relates to tripartite cancer theranostic nucleic acid constructs that permit simultaneous cancer specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.

Abstract translation: 目前公开的主题通常涉及其用于癌症成像，癌症治疗和组合成像和治疗方案中的遗传构建体和方法。 特别地，目前公开的主题涉及允许同时进行癌症特异性病毒复制，诊断基因产物的表达和治疗基因表达的三方式癌症核糖核酸构建体。

公开(公告)号：US20160101193A1

公开(公告)日：2016-04-14

申请号：US14895247

申请日：2014-06-04

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Paul B. Fisher ,  Swadesh K. Das ,  Rupesh Dash ,  Devanand Sarkar ,  Siddik Sarkar ,  Jolene Windle

IPC: A61K48/00 ,  A61K49/00 ,  C12N15/86

CPC classification number: A61K48/0058 ,  A01K67/0275 ,  A01K2207/12 ,  A01K2217/052 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0393 ,  A61K35/761 ,  A61K49/0008 ,  A61K49/005 ,  C12N15/86 ,  C12N2015/8536 ,  C12N2015/8572 ,  C12N2710/10332 ,  C12N2830/008 ,  C12N2830/34

Abstract: Recombinant vectors in which expression of one or more elements (e.g. genes required for viral replication, detectable imaging agents, therapeutic agents, etc.) is driven by a truncated CCN 1 cancer selective promoter (tCCN1-Prom) are provided, as are cells and transgenic animals that contain such vectors. The vectors are used in cancer therapy and/or diagnostics, and the transgenic mice are used to monitor cancer progression, e.g. in screening assays.

Abstract translation: 提供其中一种或多种元件的表达（例如病毒复制所需的基因，可检测的成像剂，治疗剂等）由截短的CCN 1癌选择性启动子（tCCN1-Prom）驱动的重组载体，细胞和 含有这些载体的转基因动物。 这些载体用于癌症治疗和/或诊断，并且转基因小鼠用于监测癌症进展。 在筛选试验中。

公开(公告)号：US10744172B2

公开(公告)日：2020-08-18

申请号：US16369886

申请日：2019-03-29

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Paul Fisher ,  Devanand Sarkar ,  Paul Dent

IPC: A61K35/768 ,  A61K39/00 ,  C12N15/86 ,  A61K31/166 ,  A61K31/404 ,  A61K45/06 ,  C12N7/00

Abstract: A tropism modified cancer terminator virus (Ad.5/3-CTV; Ad.5/3-CTV-M7) has been found to have infectivity that is Coxsackie Adenoviral Receptor (CAR) independent. The Ad.5/3-CTV (Ad.5/3-CTV-M7) may be used alone or in combination with other therapeutic agents such as agents that augment reactive oxygen (ROS) production, HDAC inhibitors, MCL-1 inhibitors and Bcl-2 inhibitors to treat a variety of cancers particularly including malignant glioma (GBM), renal cancer, prostate cancer, and colorectal cancer.