# US 2013/0156733 A1 · Influenza virus populations, methods of use and methods of making thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0156733 A1 - Document ID: US20130156733A1 - Status: Published application - Kind: A1 - Application number: 13/721,787 - Filed: 2012-12-20 - Published: 2013-06-20 - Earliest claimed: 2011-12-20 - Inventors: Philip I. Marcus; John M. Ngunjiri; Margaret J. Sekellick; Chang-Won Lee - Web page: https://patentgrep.com/patent/US20130156733A1 ## CPC - A61K 35/76: Viruses; Subviral particles; Bacteriophages - A61K 38/21: Interferons {[IFN]} - A61K 39/12: Viral antigens - A61K 39/145: Orthomyxoviridae, e.g. influenza virus - C07K 14/005: from 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) - C12Q 1/701: {Specific hybridization probes} - A61K 2039/5254: {avirulent or attenuated} - A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2} - C12N 2760/16121: Viruses as such, e.g. new isolates, mutants or their genomic sequences - C12N 2760/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2760/16132: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent - C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2760/16171: Demonstrated in vivo effect - C12N 2999/002: Adverse teaching - 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) - 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) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract Disclosed herein are live attenuated influenza virus compositions for inducing interferon comprising quantified subpopulations of interferon-inducing particles and defective-interfering particles. The live attenuated influenza virus compositions are particularly useful to induce interferon in an individual having or suspected of having a viral infection. Further, by infecting mammalian and avian cells with the live attenuated influenza virus compositions, the compositions optimized for mammalian or avian species can be selected based on the ratio of defective-interfering particles to interferon-inducing particles. ## Claims ### Claim 1 A live attenuated influenza virus composition for inducing interferon, comprising a subpopulation of interferon inducing particles that contain a delNS1 gene, and a subpopulation of defective-interfering particles, wherein the ratio of defective-interfering particles to interferon-inducing particles is greater than 10:1, wherein the subpopulation of interferon-inducing particles, the subpopulation of defective-interfering particles, or both, is UV irradiated at 254±20 nm, at 500 to 2,500 ergs/mm2, and wherein the live attenuated influenza virus composition has hyper interferon-inducing capacity which exceeds by 10 fold or higher the basal levels induced by wild type influenza viruses. ### Claim 2 (depends on 1) The composition of claim 1, wherein the subpopulation of interferon-inducing particles and the subpopulation of defective-interfering particles are isolated from the same virus population and are irradiated together. ### Claim 3 (depends on 1) The composition of claim 1, wherein the subpopulation of defective-interfering particles are isolated and UV-irradiated followed by mixing with the subpopulation of interferon-inducing particles. ### Claim 4 (depends on 1) The composition of claim 1, wherein the subpopulation of defective-interfering particles is prepared from a defective influenza virus that contains an RNA with a deletion such that the virus is non-infectious. ### Claim 5 (depends on 1) The composition of claim 1, wherein the influenza virus is an avian or mammalian influenza virus. ### Claim 6 (depends on 5) The composition of claim 5, wherein the influenza virus is an avian influenza virus with a delNS1 gene encoding a delNS1 protein is selected from SEQ IDMO. 5, SEQ ID NO. 6, SEQ ID NO. 7, and SEQ ID NO. 8. ### Claim 7 A method of inducing interferon in an individual having or suspected of having a viral infection, comprising administering to the individual a live attenuated influenza virus composition comprising a subpopulation of interferon inducing particles that contain a delNS1 gene, or a subpopulation of interferon inducing particles that contain a full size NS1 gene, and a subpopulation of defective-interfering particles, wherein the ratio of defective-interfering particles to interferon-inducing particles is greater than 10, and wherein the subpopulation of interferon-inducing particles, the subpopulation of defective-interfering particles, or both, is UV irradiated at 254±20 nm and at 500 to 2,500 ergs/mm2. ### Claim 8 (depends on 7) The method of claim 7, wherein the subpopulation of interferon-inducing particles and the subpopulation of defective-interfering particles are isolated from the same viral stock or population and are UV irradiated at 254±20 nm and at 500 to 2,500 ergs/mm2together. ### Claim 9 (depends on 7) The method of claim 7, wherein the subpopulation of defective-interfering particles are isolated and UV irradiated at 254±20 nm and at 500 to 2,500 ergs/mm2 followed by mixing with the subpopulation of interferon-inducing particles. ### Claim 10 (depends on 7) The method of claim 7, wherein the subpopulation of defective-interfering particles are prepared from a defective influenza virus that contains an RNA with a deletion such that the virus is non-infectious. ### Claim 11 (depends on 7) The method of claim 7, wherein the influenza virus is an avian or mammalian influenza virus. ### Claim 12 (depends on 7) The method of claim 7, wherein the individual is a mammal and the ratio of defective-interfering particles to interferon-inducing particles is greater than 10:1 in mammalian cells infected with the live attenuated influenza virus. ### Claim 13 (depends on 7) The method of claim 7, wherein the individual is a chicken and the ratio of defective-interfering particles to interferon-inducing particles is greater than 10 1 in avian cells infected with the live attenuated influenza virus. ### Claim 14 (depends on 7) The method of claim 7, wherein administration is intranasal administration. ### Claim 15 (depends on 7) The method of claim 7, wherein administration is independent of influenza virus subtype. ### Claim 16 (depends on 7) The method of claim 7, further comprising peroral administration of interferon. ### Claim 17 A method of screening an influenza virus preparation for hyper interferon-inducing capacity which exceeds by 10 fold or higher the basal levels induced by wild type influenza viruses, comprising preparing an influenza virus preparation from an influenza virus with a delNS1 gene or a full-size NS1 gene that expresses an NS1 protein lacking the capacity to suppress interferon induction, wherein the preparation contains interferon-inducing particles and defective-interfering particles, and quantifying the ratio of defective-interfering particles to interferon-inducing particles in mammalian cells, and determining that the influenza virus preparation is suitable for treating mammalian species when the ratio of defective-interfering particles to interferon-inducing particles in the influenza virus preparation is greater than 10:1 in mammalian cells, or quantifying the ratio of defective-interfering particles to interferon-inducing particles in avian cells, and determining that the influenza virus preparation is suitable for treating avian species when the ratio of defective-interfering particles to interferon-inducing particles in the influenza virus preparation is greater than 10 in avian cells. ### Claim 18 (depends on 17) The method of claim 17, wherein the influenza virus preparation is from an influenza virus with a delNS1 gene.