# US 11,234,968 B2 · Use of VCP inhibitor and oncolytic virus in the preparation of an anti-tumor drug > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,234,968 B2 - Document ID: US11234968B2 - Status: Granted - Kind: B2 - Application number: 16/325,960 - Filed: 2017-08-18 - Published: 2019-06-06 - Granted: 2022-02-01 - Earliest claimed: 2016-08-18 - Assignees: Guangzhou Virotech Pharmaceutical Co., Ltd. - Applicants: Guangzhou Virotech Pharmaceutical Co., Ltd. - Inventors: Guangmei Yan; Haipeng Zhang; Yuan Lin; Suizhen Lin; Jing Cai; Shoufang Gong; Jun Hu; Xiao Xiao; Kai Li; Jiankai Liang; Yaqian Tan; Wenbo Zhu; Wei Yin - Web page: https://patentgrep.com/patent/US11234968B2 ## CPC - A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)} - A61K 9/7023: {Transdermal patches and similar drug-containing composite devices, e.g. cataplasms (galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006)} - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766 - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - A61P 35/00: Antineoplastic agents - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links - A61K 31/713: Double-stranded nucleic acids or oligonucleotides - A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)} - C12N 2770/36132: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present invention belongs to the field of biomedicine and relates to use of VCP (valosin-containing protein, VCP) inhibitor and oncolytic virus in the preparation of an anti-tumor drug. The present invention firstly discovers that VCP inhibitor can be used in the preparation of an anti-tumor synergist for oncolytic virus. Meanwhile, the present invention relates to a pharmaceutical composition comprising VCP inhibitor and oncolytic virus, a pharmaceutical kit comprising VCP inhibitor and oncolytic virus, and use of VCP inhibitor and oncolytic virus for treating tumor, especially a tumor that is not sensitive to oncolytic virus. The present invention also relates to an anti-tumor administration system, characterized in that, comprising oncolytic virus and a reagent for detecting the expression level of VCP. ## Claims ### Claim 1 A pharmaceutical composition or a kit, comprising: at least one Valosin containing protein (VCP) inhibitor; and at least one oncolytic virus, wherein the oncolytic virus is Alphavirus M1 (M1 virus) and the Valosin containing protein (VCP) inhibitor is selected from the group consisting of Eeyarestatin I, NMS-873, CB-5083, RNA interference fragment of VCP (siRNA) and a combination thereof. ### Claim 2 (depends on 1) The pharmaceutical composition or the kit according to claim 1, wherein said tumor is a solid tumor or a blood tumor. ### Claim 3 (depends on 1) The pharmaceutical composition or the kit according to claim 1, wherein the ratio of Eeyarestatin I, NMS-873, CB-5083 or RNA interference fragment of VCP (siRNA) with said M1 virus is 0.01˜200 mg: 103˜109 PFU. ### Claim 4 (depends on 1) The pharmaceutical composition or the kit according to claim 1, wherein said pharmaceutical composition or the kit further comprises a pharmaceutically acceptable carrier. ### Claim 5 A method for treating a subject with a tumor, comprising: administering to the subject at least one oncolytic virus; and enhancing an anti-tumor effect of said oncolytic virus comprising administering to the subject in need thereof at least one VCP inhibitor, wherein the oncolytic virus is Alphavirus M1 (M1 virus) and the Valosin containing protein (VCP) inhibitor is selected from the group consisting of Eeyarestatin I, NMS-873, CB-5083, RNA interference fragment of VCP (siRNA) and a combination thereof. ### Claim 6 (depends on 5) The method of claim 5, wherein the tumor is a solid tumor or a blood tumor. ### Claim 7 (depends on 1) The pharmaceutical composition or the kit according to claim 1, wherein said solid tumor is liver cancer, colorectal cancer, bladder cancer, breast cancer, cervical cancer, prostate cancer, glioma, melanoma, pancreatic cancer, nasopharyngeal carcinoma, lung cancer, or gastric cancer; or said tumor is a tumor that is not sensitive to oncolytic virus; or said tumor is a tumor with high expression of VCP. ### Claim 8 (depends on 5) The method of claim 5, wherein said tumor is liver cancer, colorectal cancer, bladder cancer, breast cancer, cervical cancer, prostate cancer, glioma, melanoma, pancreatic cancer, nasopharyngeal carcinoma, lung cancer, or gastric cancer; or said tumor is a tumor that is not sensitive to oncolytic virus. ### Claim 9 (depends on 1) The pharmaceutical composition or the kit according to claim 1, wherein said M1 virus has a genome as described in Genbank Accession No. EF011023, or has a genome that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, identical to the genomic nucleotide sequence set forth in Genbank Accession No. EF011023; or has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% nucleotide sequence identity to the genome of the M1 virus deposited under Accession No. CCTCC V201423. ### Claim 10 (depends on 1) The pharmaceutical composition or the kit according to claim 1, wherein the VCP inhibitor is Eeyarestatin I. ### Claim 11 (depends on 5) The method of claim 5, wherein the VCP inhibitor is Eeyarestatin I. ### Claim 12 (depends on 5) The method of claim 5, wherein said M1 virus has a genome as described in Genbank Accession No. EF011023, or has a genome that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, identical to the genomic nucleotide sequence set forth in Genbank Accession No. EF011023; or has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% nucleotide sequence identity to the genome of the M1 virus deposited under Accession No. CCTCC V201423.