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：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：US11306129B2

公开(公告)日：2022-04-19

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: A61K35/76 ,  A61K35/761 ,  A61K35/768 ,  C07K14/54 ,  A61K48/00 ,  C12N15/863 ,  C12N15/861 ,  C12N15/869 ,  A61K38/20 ,  A61P35/00 ,  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 anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

公开(公告)号：US09932606B2

公开(公告)日：2018-04-03

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: C12N15/64 ,  C12N15/86 ,  A61K48/00 ,  A61P35/00 ,  A61K35/761 ,  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.

公开(公告)号：US11345732B2

公开(公告)日：2022-05-31

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: A61K35/76 ,  A61K35/761 ,  A61K35/768 ,  C07K14/54 ,  A61K48/00 ,  C12N15/863 ,  C12N15/861 ,  C12N15/869 ,  A61K38/20 ,  A61P35/00 ,  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 anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

公开(公告)号：US10294493B2

公开(公告)日：2019-05-21

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: A61K35/761 ,  C12N15/86 ,  C12N15/861 ,  C12N7/00

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：US09315827B2

公开(公告)日：2016-04-19

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: C12N15/64 ,  C12N15/66 ,  C12N15/86 ,  A61K35/761

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。