公开(公告)号：US20130345295A1

公开(公告)日：2013-12-26

申请号：US14016149

申请日：2013-09-02

Applicant: Beijing Bio-Targeting Therapeutics Technology Inc.

Inventor： Yaohe WANG ,  Guozhong JIANG ,  Pengju WANG ,  Dongling GAO ,  Nick LEMOINE

IPC: A61K31/711

CPC classification number: A61K31/711 ,  A61K35/761 ,  A61K38/00 ,  C07K14/5434 ,  C12N15/86 ,  C12N2710/10332 ,  C12N2710/10343

Abstract: An oncolytic adenovirus vector and its potential application in cancer treatment and vaccination. The inventive vector (named Ad-TD-hIL12) is derived from the human adenovirus group C type 5, more particularly including deletion of three adenovirus genes E1A-CR2, E1B19K and E3gp-19K, and a fused cDNA sequence of p35 and p40 subunit of human IL12 placed under the control of the E3gp-19K promoter. The invention also includes a method to construct the triple gene-deleted vector (Ad-TD). The Ad-TD-hIL12 and Ad-TD-shIL12 (with a short p40 sequence of human IL 12) vectors can be used as targeted, genetically engineered agents for treatment of various solid tumors, via not only intratumoral injection, and also in intraperitoneal injection, without causing significant side effects, showing a superior antitumor efficacy and safety.

Abstract translation: 一种溶瘤腺病毒载体及其在癌症治疗和疫苗接种中的潜在应用。 本发明的载体（命名为Ad-TD-hIL12）来源于C型5型人腺病毒组，更具体地包括三种腺病毒基因E1A-CR2，E1B19K和E3gp-19K的缺失以及p35和p40亚基的融合cDNA序列 的人IL12置于E3gp-19K启动子的控制下。 本发明还包括构建三重基因缺失载体（Ad-TD）的方法。 Ad-TD-hIL12和Ad-TD-shIL12（具有短的p40序列的人IL12）载体可以用作靶向的基因工程化剂，用于治疗各种实体瘤，不仅通过瘤内注射，还可以用于腹膜内 注射，不引起显着的副作用，显示出优异的抗肿瘤功效和安全性。

公开(公告)号：US20140088180A1

公开(公告)日：2014-03-27

申请号：US14093078

申请日：2013-11-29

Applicant: Beijing Bio-Targeting Therapeutics Technology Inc.

Inventor： Yaohe WANG ,  Guozhong JIANG ,  Hanshi WONG ,  Fengyu CAO ,  Nick LEMOINE

IPC: C12N15/86

CPC classification number: C12N15/86 ,  A61K35/761 ,  C12N7/00 ,  C12N2710/10321 ,  C12N2710/10332 ,  C12N2710/10343

Abstract: A method for constructing a subgroup B recombinant human adenovirus vector Ad11-5EP. The method includes substituting a 365 bp fragment including an enhancer and a promoter of an upstream coding sequence of Ad5 E1A for a corresponding region of a serotype Ad11 of the subgroup B human adenovirus vector by homologous recombination to construct the subgroup B recombinant human adenovirus vector Ad11-5EP. A subgroup B recombinant human adenovirus vector Ad11-5EP constructed by the method and the use thereof for treatment of tumors are also provided.

Abstract translation: 一种构建亚组B重组人腺病毒载体Ad11-5EP的方法。 该方法包括通过同源重组将包含增强子的365bp片段和Ad5 E1A上游编码序列的启动子替换为亚组B人腺病毒载体的血清型Ad11的相应区域，以构建亚组B重组人腺病毒载体Ad11 -5EP。 还提供了通过该方法构建的亚组B重组人腺病毒载体Ad11-5EP及其用于治疗肿瘤的用途。

公开(公告)号：US20180187214A1

公开(公告)日：2018-07-05

申请号：US15904408

申请日：2018-02-25

Applicant: Beijing Bio-Targeting Therapeutics Technology Inc.

Inventor： Yaohe WANG ,  Guozhong JIANG ,  Hanshi WONG ,  Fengyu CAO ,  Nick LEMOINE

IPC: C12N15/86 ,  A61K35/761 ,  C12N7/00

CPC classification number: C12N15/86 ,  A61K35/761 ,  C12N7/00 ,  C12N2710/10321 ,  C12N2710/10332 ,  C12N2710/10343

Abstract: A subgroup B recombinant human adenovirus vector Ad11-5EP (SEQ ID NO: 1), which is constructed by a method including: substituting a 365 bp fragment containing an enhancer and a promoter of an upstream coding sequence of Ad5 E1A (SEQ ID NO: 2) for a corresponding region of a serotype Ad11 (SEQ ID NO: 3) of a subgroup B human adenovirus vector by homologous recombination to construct the subgroup B recombinant human adenovirus vector Ad11-5EP (SEQ ID NO: 1).

公开(公告)号：US20160222413A1

公开(公告)日：2016-08-04

申请号：US15098342

申请日：2016-04-14

Applicant: Beijing Bio-Targeting Therapeutics Technology Inc.

Inventor： Yaohe WANG ,  Guozhong JIANG ,  Hanshi WONG ,  Fengyu CAO ,  Nick LEMOINE

IPC: C12N15/86 ,  C12N7/00

CPC classification number: C12N15/86 ,  A61K35/761 ,  C12N7/00 ,  C12N2710/10321 ,  C12N2710/10332 ,  C12N2710/10343

Abstract: A method for reconstructing a replication-selective oncolytic adenovirus using a subgroup B recombinant human adenovirus vector Ad11-5EP. The method includes: 1) deleting E1A CR2 gene and/or anti-apoptotic gene E1B 21K that is necessary for viability of an adenovirus in normal cells but not necessary in tumor cells; 2) inserting a tumor-specific promoter to drive the expression of E1A gene; 3) re-directing a cellular tropism of Ad11-5EP according to receptors on a tumor cell surface; or 4) allowing adenovirus to selectively replicate in tumor cells.

Abstract translation: 使用亚组B重组人腺病毒载体Ad11-5EP重建复制选择性溶瘤腺病毒的方法。 该方法包括：1）删除正常细胞中腺病毒存活所必需的E1A CR2基因和/或抗凋亡基因E1B 21K，但在肿瘤细胞中不是必需的; 2）插入肿瘤特异性启动子以驱动E1A基因的表达; 3）根据肿瘤细胞表面上的受体重新导向Ad11-5EP的细胞向性; 或4）允许腺病毒在肿瘤细胞中选择性复制。