# US 10,363,293 B2 · Vaccine composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,363,293 B2 - Document ID: US10363293B2 - Status: Granted - Kind: B2 - Application number: 14/769,035 - Filed: 2014-02-20 - Published: 2016-04-21 - Granted: 2019-07-30 - Earliest claimed: 2013-02-21 - Assignees: Turnstone Limited Partnership - Applicants: Turnstone Limited Partnership - Inventors: David F. Stojdl; John Cameron Bell; Brian Lichty; Jonathan Pol - Web page: https://patentgrep.com/patent/US10363293B2 ## CPC - A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)} - A61K 35/766: Rhabdovirus, e.g. vesicular stomatitis virus - A61K 39/0011: {Cancer antigens} - A61K 39/001184: {Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE} - A61K 39/001186: {MAGE} - A61K 39/12: Viral antigens - A61P 35/00: Antineoplastic agents - A61P 37/04: Immunostimulants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - C12N 15/86: Viral vectors - A61K 2039/5254: {avirulent or attenuated} - A61K 2039/5256: {expressing foreign proteins} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants} - A61K 2039/572: {cytotoxic response} - A61K 2039/585: {wherein the target is cancer} - C07K 2319/00: Fusion polypeptide - C07K 2319/50: containing protease site - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2710/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2710/20034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2740/15043: viral genome or elements thereof as genetic vector - C12N 2760/20223: Virus like particles [VLP] - C12N 2760/20232: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent - C12N 2760/20242: virus or viral particle as vehicle, e.g. encapsulating small organic molecule - C12N 2760/20243: 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 - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) ## Abstract There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus. ## Claims ### Claim 1 A method for treating a patient having a cancer, said method comprising: a) a first virus, said first virus comprising a nucleic acid that is capable of expressing a MAGEA3 protein, said MAGEA3 protein comprising an amino acid sequence that is at least 70% identical to SEQ ID NO: 1, and includes at least one MAGEA3 tumor-associated epitope selected from the group consisting of: FLWGPRALV (SEQ ID NO: 27), KVAELVHFL (SEQ ID NO: 28), EGDCAPEEK (SEQ ID NO: 35), KKLLTQHFVQENYLEY (SEQ ID NO: 36), and RKVAELVHFLLLKYR (SEQ ID NO: 37), wherein said MAGEA3 protein is capable of inducing an immune response in a patient in a heterologous prime-boost format, and b) a second virus, said second virus being a Maraba MG1 virus comprising a nucleic acid that is capable of expressing a MAGEA3 protein, said MAGEA3 protein comprising an amino acid sequence that is at least 70% identical to SEQ ID NO: 1, and includes at least one MAGEA3 tumor-associated epitope selected from the group consisting of: FLWGPRALV (SEQ ID NO: 27), KVAELVHFL (SEQ ID NO: 28), EGDCAPEEK (SEQ ID NO: 35), KKLLTQHFVQENYLEY (SEQ ID NO: 36), and RKVAELVHFLLLKYR (SEQ ID NO: 37), wherein said Maraba MG1 virus is formulated for use in providing a therapeutic oncolytic effect in said patient; wherein: said first virus is immunologically distinct from said second virus; said first virus is a priming virus and administered before said second virus; and wherein said second virus is a boost virus and is administered at least twice after administration of said priming virus. ### Claim 2 (depends on 1) The method of claim 1, wherein a) said first virus is a negative strand RNA virus and includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2; b) said first virus is a DNA virus or a positive sense RNA virus and includes a transgene comprising a nucleotide sequence of SEQ ID NO: 2; c) said second virus includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2; or d) (i) said first virus is a negative strand RNA virus and includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2 and said second virus includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2; or (ii) said first virus is a DNA virus or a positive sense RNA virus and includes a transgene comprising a nucleotide sequence of SEQ ID NO: 2 and said second virus includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2. ### Claim 3 (depends on 1) The method of claim 1, wherein a) said first virus is a negative strand RNA virus and includes a reverse complement and RNA version of a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3; or b) said first virus is a DNA virus or a positive sense RNA virus and includes a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3; or c) said second virus includes a reverse complement and RNA version of a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3; or d) (i) said first virus is a negative strand RNA virus and includes a reverse complement and RNA version of a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3 and said second virus includes a reverse complement and RNA version of a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3, or (ii) said first virus is a DNA virus or a positive sense RNA virus and includes a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3 and said second virus includes a reverse complement and RNA version of a codon optimized transgene comprising a nucleotide sequence of SEQ ID NO: 3. ### Claim 4 (depends on 1) The method of claim 1, wherein at least one of said MAGEA3 proteins comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 1. ### Claim 5 (depends on 4) The method of claim 4, wherein at least one of said MAGEA3 proteins comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 1. ### Claim 6 (depends on 5) The method of claim 5, wherein at least one of said MAGEA3 proteins comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 1. ### Claim 7 (depends on 6) The method of claim 6, wherein at least one of said MAGEA3 proteins comprises an amino acid sequence that is SEQ ID NO: 1. ### Claim 8 (depends on 1) The method of claim 1, wherein at least one of said MAGEA3 proteins comprises an amino acid sequence that is SEQ ID NO: 4. ### Claim 9 (depends on 1) The method of claim 1, wherein at least one of said MAGEA3 proteins comprises an amino acid sequence that is encoded by the nucleotide sequence of SEQ ID NO: 5. ### Claim 10 (depends on 1) The method of claim 1, wherein a) said first virus is a negative sense RNA virus and includes a reverse complement and RNA version of a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 4 and said second virus includes a reverse complement and RNA version of a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 1; b) said first virus is a negative sense RNA virus and includes a reverse complement and RNA version of a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 1 and said second virus includes a reverse complement and RNA version of a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 4; c) said first virus is a DNA or RNA virus and includes a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 4 and said second virus includes a reverse complement and RNA version of a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 1; or d) said first virus is a DNA or RNA virus and includes a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 1 and said second virus includes a reverse complement and RNA version of a nucleotide sequence encoding the MAGEA3 protein of SEQ ID NO: 4. ### Claim 11 (depends on 1) The method of claim 1, wherein the sequence of said MAGEA3 protein that is expressed by said first virus and the sequence of said MAGEA3 protein that is expressed by said second virus, are identical. ### Claim 12 (depends on 1) The method of claim 1, wherein at least one of said first virus and said second virus comprises a nucleic acid that is capable of expressing the MAGEA3 protein of SEQ ID NO: 1, and at least one of said first virus and said second virus comprises a nucleic acid that is capable of expressing the MAGEA3 protein of SEQ ID NO: 4. ### Claim 13 (depends on 1) The method of claim 1, wherein said first virus is an adenovirus. ### Claim 14 (depends on 1) The method of claim 1, wherein said second virus is first administered about 24 hours after the administration of said first virus. ### Claim 15 (depends on 1) The method of claim 1, wherein said second virus is first administered about 2-4 days after the administration of said first virus. ### Claim 16 (depends on 1) The method of claim 1, wherein said second virus is first administered about 1 week after the administration of said first virus. ### Claim 17 (depends on 1) The method of claim 1, wherein said second virus is first administered about 2 weeks after the administration of said first virus. ### Claim 18 (depends on 1) The method of claim 1, wherein said second virus is administered about 3 days after the first administration of said second virus. ### Claim 19 (depends on 1) The method of claim 1, wherein said first virus is administered intramuscularly. ### Claim 20 (depends on 1) The method of claim 1, wherein said second virus is administered intravenously. ### Claim 21 (depends on 1) The method of claim 1, wherein: a) said first virus is an adenovirus; and b) said first virus comprises a nucleic acid that is capable of expressing the MAGEA3 protein of SEQ ID NO: 1, and said second virus comprises a nucleic acid that is capable of expressing the MAGEA3 protein of SEQ ID NO: 1; wherein: said second virus is administered intravenously first about 2 weeks after an intramuscular administration of said first virus; and wherein said second virus is administered intravenously about 3 days after said first intravenous administration of said second virus.