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公开(公告)号：US11345732B2
公开(公告)日：2022-05-31
申请号：US15758853
申请日：2016-09-09
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.
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2.发明授权公开(公告)号：US10294493B2
公开(公告)日：2019-05-21
申请号：US15904408
申请日：2018-02-25
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).
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3.发明授权Subgroup B recombinant human adenovirus vector, and methods for constructing and for using the same 有权亚组B重组人腺病毒载体，以及构建和使用它们的方法公开(公告)号：US09315827B2
公开(公告)日：2016-04-19
申请号：US14093078
申请日：2013-11-29
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。
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公开(公告)号：US20220213161A1
公开(公告)日：2022-07-07
申请号：US17700991
申请日：2022-03-22
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.
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公开(公告)号：US11306129B2
公开(公告)日：2022-04-19
申请号：US15758853
申请日：2016-09-09
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.
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Patent Agency Ranking
6.发明申请公开(公告)号：US20180187214A1
公开(公告)日：2018-07-05
申请号：US15904408
申请日：2018-02-25
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).
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7.发明授权公开(公告)号：US09932606B2
公开(公告)日：2018-04-03
申请号：US15098342
申请日：2016-04-14
Inventor： Yaohe Wang , Guozhong Jiang , Hanshi Wong , Fengyu Cao , Nick Lemoine
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.
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8.发明申请公开(公告)号：US20160222413A1
公开(公告)日：2016-08-04
申请号：US15098342
申请日：2016-04-14
Inventor： Yaohe WANG , Guozhong JIANG , Hanshi WONG , Fengyu CAO , Nick LEMOINE
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。
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9.发明申请TARGETED ONCOLYTIC ADENOVIRUS FOR TREATMENT OF HUMAN TUMORS, CONSTRCUTION METHOD AND APPLICATION THEREOF 审中-公开用于治疗人类肿瘤的靶向治疗性腺病毒，其解决方法及其应用公开(公告)号：US20130345295A1
公开(公告)日：2013-12-26
申请号：US14016149
申请日：2013-09-02
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。
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公开(公告)号：US20190010200A1
公开(公告)日：2019-01-10
申请号：US15758853
申请日：2016-09-09
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.
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