# US 11,439,679 B2 · Construction of oncolytic herpes simplex viruses (oHSV) obligate vector and constructs for cancer therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,679 B2 - Document ID: US11439679B2 - Status: Granted - Kind: B2 - Application number: 17/020,666 - Filed: 2020-09-14 - Published: 2020-12-31 - Granted: 2022-09-13 - Earliest claimed: 2020-09-14 - Assignees: Immvira Co., Limited - Applicants: Immvira Co., Limited - Inventors: Grace Guoying Zhou; Xiaoqing Chen; Xianjie Liu - Web page: https://patentgrep.com/patent/US11439679B2 ## CPC - A61K 35/763: Herpes virus - A61P 35/00: Antineoplastic agents - C07K 14/5434: {IL-12} - C07K 16/2818: {against CD28 or CD152} - C12N 15/86: Viral vectors - C07K 2317/622: Single chain antibody (scFv) - C12N 2710/16621: Viruses as such, e.g. new isolates, mutants or their genomic sequences - C12N 2710/16632: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent - C12N 2710/16643: viral genome or elements thereof as genetic vector - 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 - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract An obligate oHSV vector comprising modified viral DNA genome is provided. A recombinant oHSV-1 construct comprising the obligate oHSV vector and a heterologous nucleic acid sequence encoding an immunostimulatory and/or immunotherapeutic agent is also provided. Compositions comprising the recombinant oHSV-1 construct can be used for treating cancers. ## Claims ### Claim 1 A pharmaceutical composition for treating or alleviating cancer in a subject, comprising a pharmaceutically acceptable carrier and a recombinant oncolytic Herpes Simplex Virus type 1 (HSV-1), wherein the recombinant oncolytic HSV-1 has a deletion modification in a wild-type HSV-1 genome and comprises: (i) sequences required for expression of all single-copy open reading frames (ORFs) in the genome, comprising the ORFs themselves and regulating sequences necessary for expression of each ORF, wherein the regulating sequences include promoters which are kept intact; (ii) only one copy of each of all double-copy genes in the genome; (iii) only one copy of duplicated non-coding sequences in the genome; and (iv) a heterologous nucleic acid sequence encoding IL-12 and an anti-PD-1 agent, wherein the heterologous nucleic acid sequence encoding IL-12 is inserted into the deleted region of the modified HSV-1 genome, and the heterologous nucleic acid sequence encoding the anti-PD-1 agent is inserted between UL3 and UL4 genes in the UL component of the modified HSV-1 genome, and wherein the incorporation of the heterologous nucleic acid sequence does not interfere the expression of the wild-type HSV-1 genes. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the double-copy genes comprise genes encoding ICP0, ICP4, ICP34.5, ORF P and ORF O. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the HSV-1 has a genome isomer of prototype (P). ### Claim 4 (depends on 1) The pharmaceutical composition of claim 1, wherein the HSV-1 is selected from the group consisting of strains F, KOS, and 17. ### Claim 5 (depends on 4) The pharmaceutical composition of claim 4, wherein the deletion causes excision of nucleotide positions 117005 to 132096 in the genome of F strain. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the deletion modification comprises a deletion starting from the promoter of the last gene in the UL component to the first gene in the Us component in case of an IL isomer of HSV-1 genome. ### Claim 7 (depends on 6) The pharmaceutical composition of claim 6, wherein the last known gene in the UL component is UL1 in case of the IL isomer. ### Claim 8 (depends on 6) The pharmaceutical composition of claim 6, wherein the first known gene in the Us component is Us1 in case of the IL isomer. ### Claim 9 (depends on 1) The pharmaceutical composition of claim 1, wherein the duplicated non-coding sequences include introns of ICP0, LAT domain and “a” sequence. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1, wherein the subject is a human being. ### Claim 11 (depends on 1) The pharmaceutical composition of claim 1, wherein the cancer is selected from the group consisting of esophageal cancer, lung cancer, prostate cancer, and bladder cancer. ### Claim 12 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for intra-tumor injection.