# US 11,110,163 B2 · Heat stable vaccines > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,110,163 B2 - Document ID: US11110163B2 - Status: Granted - Kind: B2 - Application number: 16/571,702 - Filed: 2019-09-16 - Published: 2020-01-09 - Granted: 2021-09-07 - Earliest claimed: 2017-02-14 - Assignees: Inventprise, LLC - Applicants: Inventprise, LLC - Inventors: Subhash V. Kapre; Ivan A. Olave - Web page: https://patentgrep.com/patent/US11110163B2 ## CPC - A61K 9/10: Dispersions; Emulsions - A61K 39/15: Reoviridae, e.g. calf diarrhea virus - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)} - 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 39/12: Viral antigens - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - 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 31/14: for RNA viruses - 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 2720/12321: Viruses as such, e.g. new isolates, mutants or their genomic sequences - C12N 2720/12334: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - 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 invention is directed to an oral vaccine composed of a micronized freeze-dried rotavirus particle suspension with buffering excipients in a non-aqueous liquid. This IVT-06 formulation has imparted heat stability by protecting the virus at temperatures of 30° C. and 40° C. for at least twelve months. Extrapolations from the 12-month stability data indicate a shelf life of more than two years at 30° C., and six months at 50° C. In addition, for ease of administration, the formulated dose has a volume of 0.5 mL. ## Claims ### Claim 1 An immunogenic composition comprising: an attenuated strain of a rotavirus at a titer of about 105.9 FFU/mL or higher; arginine and sucrose at a ratio of from about 1:1.1-2.5; less than or equal to about 1.2% moisture; an approximate uniform particle size of about 5 μm or less; a buffering agent; and medium-chain triglyceride (MCT). ### Claim 2 (depends on 1) The composition of claim 1, wherein the rotavirus includes one or more serotypes of rotavirus. ### Claim 3 (depends on 1) The composition of claim 1, which comprises approximately 2-4% arginine (w/v). ### Claim 4 (depends on 1) The composition of claim 1, which comprises approximately 4-6% arginine (w/v). ### Claim 5 (depends on 1) The composition of claim 1, which comprises approximately 6-8% sucrose (w/v). ### Claim 6 (depends on 1) The composition of claim 1, which comprises approximately 8-10% sucrose (w/v). ### Claim 7 (depends on 1) The composition of claim 1, wherein the ratio of from about 1:1.1-2.0. ### Claim 8 (depends on 1) The composition of claim 1, wherein the ratio of from about 1:1.1-1.75. ### Claim 9 (depends on 1) The composition of claim 1, wherein the buffering agent comprises a mix of citrate and calcium carbonate, Tris, Hepes, phosphates, histidine, or a combination thereof. ### Claim 10 (depends on 1) The composition of claim 1, wherein the buffering agent maintains the composition at a pH of about 7.0-8.0. ### Claim 11 (depends on 1) The composition of claim 1, which is lyophilized. ### Claim 12 (depends on 1) The composition of claim 1, which as a glass transition temperature of about 70° C. or higher. ### Claim 13 (depends on 1) The composition of claim 1, which as a glass transition temperature of about 75° C. or higher. ### Claim 14 (depends on 1) The composition of claim 1, which as a glass transition temperature of about 80° C. or higher. ### Claim 15 (depends on 1) The composition of claim 1, which, when stored at about room temperature or higher for at least about twelve months, has no significant loss of efficacy. ### Claim 16 (depends on 1) The composition of claim 1, which, when stored at about 30° C. or higher for at least about two years, has no significant loss of efficacy. ### Claim 17 (depends on 1) The composition of claim 1, which, when stored at about 50° C. or higher for at least about six months, has no significant loss of efficacy. ### Claim 18 (depends on 1) The composition of claim 1, which, when stored at about 50° C. or higher for at least about twelve months, has no significant loss of efficacy. ### Claim 19 An immunogenic composition comprising: an attenuated strain of a rotavirus at a titer of about 105.9 FFU/mL or higher; less than or equal to about 1.2% moisture; an approximate uniform particle size of about 5 μm or less; a buffering agent; and medium-chain triglyceride (MCT), wherein the composition has a glass transition temperature of about 60° C. or higher. ### Claim 20 (depends on 19) The composition of claim 19, wherein the rotavirus includes one or more serotypes of rotavirus. ### Claim 21 (depends on 19) The composition of claim 19, which comprises approximately 2-4% arginine (w/v). ### Claim 22 (depends on 19) The composition of claim 19, which comprises approximately 4-6% arginine (w/v). ### Claim 23 (depends on 19) The composition of claim 19, which comprises approximately 6-8% sucrose (w/v). ### Claim 24 (depends on 19) The composition of claim 19, which comprises approximately 8-10% sucrose (w/v). ### Claim 25 (depends on 19) The composition of claim 19, arginine and sucrose at a ratio of from about 1:1.1-2.5. ### Claim 26 (depends on 25) The composition of claim 25, wherein the ratio of from about 1:1.1-1.75. ### Claim 27 (depends on 19) The composition of claim 19, wherein the buffering agent comprises a mix of citrate and calcium carbonate, Tris, Hepes, phosphates, histidine, or a combination thereof. ### Claim 28 (depends on 19) The composition of claim 19, wherein the buffering agent maintains the composition at a pH of about 7.0-8.0. ### Claim 29 (depends on 19) The composition of claim 19, which is lyophilized. ### Claim 30 (depends on 19) The composition of claim 19, which as a glass transition temperature of about 70° C. or higher. ### Claim 31 (depends on 19) The composition of claim 19, which as a glass transition temperature of about 75° C. or higher. ### Claim 32 (depends on 19) The composition of claim 19, which as a glass transition temperature of about 80° C. or higher. ### Claim 33 (depends on 19) The composition of claim 19, which, when stored at about room temperature or higher for at least about twelve months, has no significant loss of efficacy. ### Claim 34 (depends on 19) The composition of claim 19, which, when stored at about 30° C. or higher for at least about two years, has no significant loss of efficacy. ### Claim 35 (depends on 19) The composition of claim 19, which, when stored at about 50° C. or higher for at least about six months, has no significant loss of efficacy. ### Claim 36 (depends on 19) The composition of claim 19, which, when stored at about 50° C. or higher for at least about twelve months, has no significant loss of efficacy.