# US 8,784,836 B2 · Microorganisms for therapy

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,784,836 B2
- Document ID: US8784836B2
- Status: Granted
- Kind: B2
- Application number: 13/507,572
- Filed: 2012-07-10
- Published: 2012-11-01
- Granted: 2014-07-22
- Earliest claimed: 2003-06-18
- Assignees: Genelux Corporation
- Applicants: Aladar A. Szalay; Tatyana Timiryasova; Yong A. Yu; Qian Zhang
- Inventors: Aladar A. Szalay; Tatyana Timiryasova; Yong A. Yu; Qian Zhang
- Web page: https://patentgrep.com/patent/US8784836B2

## CPC

- A61K 39/285: Vaccinia virus or variola 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 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00)
- A61K 35/744: Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/30: from tumour cells
- C07K 16/40: against enzymes
- 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
- C12P 19/34: Polynucleotides, e.g. nucleic acids, oligoribonucleotides
- C12P 21/02: having a known sequence of two or more amino acids, e.g. glutathione
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2710/24132: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2710/24134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2710/24143: viral genome or elements thereof as genetic vector
- C12N 2710/24161: Methods of inactivation or attenuation
- 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
- 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)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}

## Abstract

Therapeutic methods and vaccinia virus therefor are provided. The viruses are designed so that they accumulate in immunoprivileged tissues and cells, such as in tumors and other proliferating tissue and in inflamed tissues, compared to other tissues, cells and organs, so that they exhibit relatively low toxicity to host organisms. Combinations of the viruses and anti-cancer agents and uses thereof for treating cancer also are provided.

## Claims

### Claim 1

A recombinant vaccinia virus, comprising a modified thymidine kinase (TK) gene and a modified hemagglutinin (HA) gene, and an insertion, deletion or mutation in the gene or locus designated F3, wherein:
each of the TK, HA and F3 gene or locus is inactivated; and
the F3 locus occurs on the HindIII-F fragment of the vaccinia virus between open reading frames F14L and F15L.

### Claim 2 (depends on 1)

The recombinant vaccinia virus of claim 1, wherein heterologous nucleic acid is inserted into the TK and HA genes to inactivate them, and heterologous nucleic acid is inserted into the F3 locus.

### Claim 3 (depends on 1)

The recombinant vaccinia virus of claim 1, wherein the vaccinia virus is a strain selected from among Western Reserve (WR), Copenhagen, Tashkent, Tian Tan, Lister, Wyeth, IHD-J, and IHD-W, Ankara, MVA, Dairen I, L-IPV, LC16M8, LC16MO, LIVP, WR 65-16, Connaught and New York City Board of Health.

### Claim 4 (depends on 1)

The recombinant vaccinia virus of claim 1, wherein the insertion in the F3 locus is at a site corresponding to the unique NotI or position 1475 of the LIVP strain inside of the HindIII-F fragment of the LIVP strain of vaccinia virus.

### Claim 5 (depends on 1)

The recombinant vaccinia virus of claim 1, wherein at least one of the TK, HA gene and F3 locus comprises an insertion of heterologous nucleic acid that encodes a protein.

### Claim 6 (depends on 5)

The recombinant vaccinia virus of claim 5, wherein the protein is an antibody or antigen-binding fragment thereof.

### Claim 7 (depends on 5)

The recombinant vaccinia virus of claim 5, wherein the protein is a solute carrier protein (sic), a superoxide dismutase (sod), a colony stimulating factor (csf), monocyte chemotactic protein-1 (mcp-1), a nonmetastatic protein (nm), a neurogenin protein (ngn), erythropoietin (epo), bmp2, bmp2a, bmp4, tyre 1, tyrp2 or aim 1.

### Claim 8 (depends on 7)

The recombinant vaccinia virus of claim 7, wherein the protein is an slc selected from among solute carrier 5 (slc5) and solute carrier 6 (slc6) transporter protein families.

### Claim 9 (depends on 8)

The recombinant vaccinia virus of claim 8, wherein the transporter protein is a norepinephrine transporter (net) or is a sodium-iodide symporter (nis).

### Claim 10 (depends on 5)

The recombinant vaccinia virus of claim 5, wherein the heterologous nucleic acid is operatively linked to a regulatory sequence.

### Claim 11 (depends on 10)

The recombinant vaccinia virus of claim 10, wherein the regulatory sequence comprises a promoter.

### Claim 12 (depends on 10)

The recombinant vaccinia virus of claim 10, wherein the regulatory sequence comprises the vaccinia virus early/late promoter p7.5.

### Claim 13 (depends on 10)

The recombinant vaccinia virus of claim 10, wherein the regulatory sequence comprises an early/late vaccinia pE/L promoter.

### Claim 14 (depends on 5)

The recombinant vaccinia virus of claim 5, wherein heterologous nucleic acid encodes a detectable protein or a protein capable of inducing a detectable signal.

### Claim 15 (depends on 5)

The recombinant vaccinia virus of claim 5, wherein the encoded protein is an anti-tumor agent or an anti-metastatic agent.

### Claim 16 (depends on 1)

A pharmaceutical composition, comprising the virus of claim 1.

### Claim 17 (depends on 16)

The pharmaceutical composition of claim 16 that is formulated for systemic administration.

### Claim 18 (depends on 16)

The pharmaceutical composition of claim 16 that is formulated for intravenous administration.

### Claim 19 (depends on 1)

A combination, comprising:
a recombinant vaccinia virus of claim 1; and
a chemotherapeutic or anti-tumor agent.