# US 11,028,409 B2 · Replication-deficient RNA viruses as vaccines > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,028,409 B2 - Document ID: US11028409B2 - Status: Granted - Kind: B2 - Application number: 15/605,568 - Filed: 2017-05-25 - Published: 2018-05-24 - Granted: 2021-06-08 - Earliest claimed: 2005-02-11 - Assignees: Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V. - Applicants: Max-Plank Gesellschaft Zur Forderung Der Wissenschaften E.V. - Inventors: Wolfgang J. Neubert; Sascha Bossow; Sabine Schlecht - Web page: https://patentgrep.com/patent/US11028409B2 ## CPC - C12N 15/86: Viral vectors - A61P 31/12: Antivirals - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression - C12N 2510/00: Genetically modified cells - C12N 2760/18811: Sendai virus - C12N 2770/36143: viral genome or elements thereof as genetic vector - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract A genome-replication-deficient and transcription/competent negative/strand RNA virus, which can be used for the expression of transgenes and in particular for the area of vaccine development. In particular, a recombinant Sendia virus containing a viral genome with a mutation in the gene P, which leads to loss of capacity for replication without loss of capacity for secondary transcription, and at least one sequence coding for a heterologous gene product. Furthermore, a nucleocapsid of the Sendai virus, a genome of the Sendai virus, a DNA molecule that codes for the genome and/or antigenome of the Sendai virus. One aspect is a pharmaceutical composition containing the Sendai virus, the nucleocapsid, or the viral genome as active substance, and a medical use thereof, especially as a vaccine. ## Claims ### Claim 1 A recombinant Sendai virus, containing a viral genome with a deletion of amino acids 2-77 of the protein encoded by gene P, which leads to loss of capacity for replication without loss of capacity for secondary transcription, and at least one sequence coding for a heterologous gene product, wherein the heterologous gene product is a viral antigen. ### Claim 2 (depends on 1) The Sendai virus as claimed in claim 1, characterized in that the viral genome codes for several heterologous antigens from the same or different viruses. ### Claim 3 (depends on 1) The Sendai virus as claimed in claim 1, characterized in that the sequence coding for at least one heterologous gene product is inserted in the viral genome and/or replaces sequences coding for a homologous gene product. ### Claim 4 (depends on 1) The Sendai virus as claimed in claim 1, characterized in that the virus has a capacity for transcription that is reduced by at most a factor of 20 relative to the wild-type virus. ### Claim 5 (depends on 1) A nucleocapsid of the Sendai virus as claimed in claim 1. ### Claim 6 (depends on 1) A genome of the Sendai virus as claimed in claim 1. ### Claim 7 (depends on 1) A DNA molecule that codes for the genome and/or antigenome of the Sendai virus as claimed in claim 1. ### Claim 8 (depends on 7) The DNA molecule as claimed in claim 7, characterized in that it is linked operationally with a transcription signal. ### Claim 9 (depends on 8) The DNA molecule as claimed in claim 8, characterized in that the transcription signal is a bacteriophage promoter, preferably, a T7 or SP6 promoter. ### Claim 10 (depends on 1, 5, 6, 7) A cell that contains the Sendai virus as claimed in claim 1, the nucleocapsid as claimed in claim 5, the genome as claimed in claim 6 or the DNA molecule as claimed in claim 7. ### Claim 11 (depends on 10) The cell as claimed in claim 10, characterized in that it is a vector multiplying cell. ### Claim 12 (depends on 10) The cell as claimed in claim 10, characterized in that it is a virus producing cell. ### Claim 13 (depends on 10) The cell as claimed in claim 10, characterized in that it further contains a DNA molecule coding for a heterologous DNA-dependent RNA polymerase, which effects the transcription of the DNA molecule coding for the recombinant Sendai virus. ### Claim 14 (depends on 10) The cell as claimed in claim 10, characterized in that it is a virus multiplying cell. ### Claim 15 (depends on 1) An in vitro method of production of the recombinant Sendai virus as claimed in claim 1, comprising the steps: (a) preparation of a cell that is transfected with a DNA molecule that codes for the genome of the recombinant Sendai virus, containing a mutation in gene P and said mutated gene P encodes for a P protein having deletion of amino acid 2-77 of the P protein, wherein said mutant P protein leads to loss of the capacity for viral genome replication without loss of the capacity for secondary transcription, and optionally at least one sequence coding for a heterologous gene product, and (b) cultivation of the cell under conditions such that a transcription of the DNA according to (a) takes place and the recombinant Sendai virus is formed. ### Claim 16 (depends on 15) The method as claimed in claim 15, further comprising the obtaining of the nucleocapsid or of the viral genome from the recombinant Sendai virus. ### Claim 17 (depends on 1, 5, 6) A pharmaceutical composition, characterized in that it contains the recombinant Sendai virus as claimed in claim 1, the nucleocapsid as claimed in claim 5 or the viral genome as claimed in claim 6 as active substance and optionally pharmaceutically acceptable vehicles and/or excipients. ### Claim 18 (depends on 17) The pharmaceutical composition as claimed in claim 17 as vaccine. ### Claim 19 (depends on 18) The pharmaceutical composition as claimed in claim 18 as a monovalent or polyvalent vaccine. ### Claim 20 (depends on 18) The pharmaceutical composition as claimed in claim 18 as a vaccine against viral infections, including as a vaccine against infections with pathogenic negative-strand RNA viruses. ### Claim 21 (depends on 17) The pharmaceutical composition as claimed in claim 17 as an antitumor agent. ### Claim 22 (depends on 17) The pharmaceutical composition as claimed in claim 17, comprising the nucleocapsid in the native viral envelope. ### Claim 23 (depends on 1) The Sendai virus as claimed in claim 1, characterized in that the viral antigen is an antigen of human parainfluenza virus type 3 (hPIV3) or respiratory syncytial virus (RSV). ### Claim 24 (depends on 1) The Sendai virus as claimed in claim 1, characterized in that the at least one sequence coding for a heterologous gene product is selected from SEQ ID No.27 and 28.