# US 12,214,035 B2 · Herpesvirus compositions and related methods > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,214,035 B2 - Document ID: US12214035B2 - Status: Granted - Kind: B2 - Application number: 17/576,021 - Filed: 2022-01-14 - Published: 2022-05-05 - Granted: 2025-02-04 - Earliest claimed: 2012-05-21 - Assignees: Sanofi Pasteur Limited - Applicants: Sanofi Pasteur Limited; Sanofi Pasteur Inc. - Inventors: Stephen Anderson; Simon Delagrave; John Hamberger; Qinglian Li; Sophia Mundle; Nausheen Rahman - Web page: https://patentgrep.com/patent/US12214035B2 ## CPC - A61K 39/245: Herpetoviridae, e.g. herpes simplex virus - 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 39/12: Viral antigens - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 31/22: for herpes viruses - A61P 37/04: Immunostimulants - 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 2039/5254: {avirulent or attenuated} - C12N 2710/16034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2710/16611: Simplexvirus, e.g. human herpesvirus 1, 2 - C12N 2710/16634: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2710/16651: Methods of production or purification of viral material - 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 disclosure relates to liquid and dried compositions comprising a live, attenuated or genetically modified herpesvirus and methods of preparing such compositions, in one aspect, the composition comprises at least two or more pharmaceutically acceptable excepients, at least one of which is histidine and at least one of which is a sugar or sugar alcohol. The compostions retain a sufficiently high infectious titre following storage or large-scale manufacturing steps, such as lyophilization. ## Claims ### Claim 1 A method of manufacturing a dried composition comprising a live, attenuated or genetically modified herpesvirus, the method comprising: (i) admixing the live, attenuated or genetically modified herpesvirus with histidine or glutamine and sucrose or trehalose; and (ii) drying the admixture, to form a dried composition, wherein the dried composition consists of: a live, attenuated or genetically modified herpes simplex virus type-2 (HSV-2) or herpes simplex virus type-1 (HSV-1), 1 mM to 50 mM histidine or glutamine, sucrose or trehalose, sodium chloride, and glutamate, and has a pH of about 6.5 to 7.5. ### Claim 2 (depends on 1) The method of claim 1, wherein the admixture is dried by means of a method selected from the group consisting of freeze-drying, foam-drying, and spray-drying. ### Claim 3 (depends on 1) The method of claim 1, wherein the HSV-2 or the HSV-1 is a replication-defective herpes simplex virus. ### Claim 4 (depends on 1) The method of claim 1, wherein viral titres of the live, attenuated or genetically modified herpesvirus are between 107 to 105 pfu/mL before drying. ### Claim 5 (depends on 1) The method of claim 1, wherein the glutamate is selected from the group consisting of potassium glutamate, mono sodium glutamate, and sodium glutamate. ### Claim 6 (depends on 1) The method of claim 1, wherein the glutamate is present in an amount of 1 mM to 100 mM. ### Claim 7 (depends on 1) The method of claim 1, wherein the histidine is present in an amount of 5 mM to 20 mM and the sucrose is present in an amount of 5% to 10% w/v. ### Claim 8 (depends on 1) The method of claim 1, wherein the glutamate is selected from the group consisting of 1 mM to 100 mM potassium glutamate, 1 mM to 100 mM mono sodium glutamate, and 1 mM to 100 mM sodium glutamate. ### Claim 9 (depends on 1) The method of claim 1, wherein the live, attenuated or genetically modified herpesvirus is a HSV-2. ### Claim 10 (depends on 9) The method of claim 9, wherein the HSV-2 is a replication defective HSV-529 strain. ### Claim 11 (depends on 1) The method of claim 1, wherein the HSV-1 or HSV-2 contains less than 10 ng of host cell DNA per 1×107 pfu/mL. ### Claim 12 (depends on 1) The method of claim 1, wherein the residual moisture content of the dried composition is 6% or less. ### Claim 13 (depends on 1) The method of claim 1, wherein the histidine is present in an amount of 5 mM to 20 mM histidine, the sucrose is present in an amount of 5% to 10% w/v, and the glutamate comprises potassium glutamate and the potassium glutamate is present in an amount of 25 mM to 75 mM. ### Claim 14 (depends on 13) The method of claim 13, wherein the sodium chloride is present in an amount of 80 to 160 mM. ### Claim 15 (depends on 1) The method of claim 1, wherein the sodium chloride is present in an amount of 10 to 200 mM. ### Claim 16 A method of manufacturing a dried composition comprising a live, attenuated or genetically modified herpesvirus, the method comprising: (i) admixing the live, attenuated or genetically modified herpesvirus with histidine, sucrose or trehalose, sodium chloride, and glutamate; and (ii) drying the admixture, wherein the dried composition consists of: a live, attenuated or genetically modified herpes simplex virus type-2 (HSV-2) or herpes simplex virus type-1 (HSV-1), about 10 mM 1 mM, about 10% w/v sucrose or trehalose, sodium chloride, and about 50 mM glutamate, and has a pH of about 6.5 to 7.5.