公开(公告)号：US20220213161A1

公开(公告)日：2022-07-07

申请号：US17700991

申请日：2022-03-22

Applicant: BEIJING BIO-TARGETING THERAPEUTICS TECHNOLOGY INC.

Inventor： Yaohe Wang ,  Pengju Wang ,  Lemoine Nick ,  Dongling GAO

IPC: C07K14/54 ,  A61K48/00 ,  C12N15/863 ,  C12N15/861 ,  C12N15/869 ,  A61K38/20 ,  A61P35/00 ,  A61K35/761 ,  C12N15/86

Abstract: The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent antitumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

公开(公告)号：US20190010200A1

公开(公告)日：2019-01-10

申请号：US15758853

申请日：2016-09-09

Applicant: BEIJING BIO-TARGETING THERAPEUTICS TECHNOLOGY INC. ,  Zhengzhou University

Inventor： Yaohe Wang ,  Pengju Wang ,  Lemoine Nick ,  Dongling GAO

IPC: C07K14/54 ,  C12N15/86 ,  A61K35/761 ,  A61P35/00

Abstract: The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent antitumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

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。