# US 12,227,755 B2 · Replication-defective arenavirus vectors

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- Number: US 12,227,755 B2
- Document ID: US12227755B2
- Status: Granted
- Kind: B2
- Application number: 17/846,817
- Filed: 2022-06-22
- Published: 2022-10-06
- Granted: 2025-02-18
- Earliest claimed: 2007-12-27
- Assignees: UniversitäT ZüRich
- Applicants: UniversitäT ZüRich
- Inventors: Daniel D. Pinschewer; Lukas Flatz; Andreas Bergthaler; Rolf Zinkernagel
- Web page: https://patentgrep.com/patent/US12227755B2

## CPC

- C12N 15/86: Viral vectors
- A61K 35/76: Viruses; Subviral particles; Bacteriophages
- A61K 39/12: Viral antigens
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61P 25/32: Alcohol-abuse
- A61P 25/34: Tobacco-abuse
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/06: for tuberculosis
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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)
- A61K 2039/525: {Virus}
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2760/10032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2760/10034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/10043: viral genome or elements thereof as genetic vector
- C12N 2760/10061: Methods of inactivation or attenuation
- C12N 2830/008: cell type or tissue specific enhancer/promoter combination
- C12N 2840/203: having an IRES
- C12N 2840/206: having multiple IRES
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention relates to an infectious arenavirus particle that is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells. One or more of the four arenavirus open reading frames glycoprotein (GP), nucleoprotein (NP), matrix protein Z and RNA-dependent RNA polymerase L are removed or mutated to prevent replication in normal cells but still allowing gene expression in arenavirus vector-infected cells, and foreign genes coding for an antigen or other protein of interest or nucleic acids modulating host gene expression are expressed under control of the arenavirus promoters, internal ribosome entry sites or under control of regulatory elements that can be read by the viral RNA-dependent RNA polymerase, cellular RNA polymerase I, RNA polymerase II or RNA polymerase III. The modified arenaviruses are useful as vaccines and therapeutic agents for a variety of diseases.

## Claims

### Claim 1

A method of making a recombinant cell comprising transfecting a cell with plasmids encoding for intracellular expression of transacting factors (TF-plasmids), and plasmids encoding arenavirus vector genome segments (GS-plasmids),
wherein the GS-plasmid encodes a large segment of the arenavirus genome (L segment) or a small segment of the arenavirus genome (S segment),
wherein the GS-plasmid encoding the S segment comprises an arenavirus open reading frame wherein a sequence encoding for glycoprotein (GP) is removed and replaced by a foreign ribonucleic acid sequence,
wherein the foreign ribonucleic acid sequence encodes for (a) a viral antigen selected from a hepatitis B antigen, a respiratory syncytial virus antigen, a human immunodeficiency virus antigen, an influenza antigen, a hepatitis C virus antigen, a varicella zoster virus antigen, a herpes simplex virus antigen, or a cytomegalovirus antigen; (b) a bacterial antigen selected from a Haemophilus spp. antigen, a Pneumoccoccus spp. antigen, or a Mycobacterium tuberculosis antigen; (c) a parasite antigen selected from the group consisting of a plasmodia antigen, an amebia antigen, and a philaria antigen; or (d) a tumor antigen.

### Claim 2 (depends on 1)

The method of claim 1, wherein the TF plasmid encodes for intracellular expression of a viral trans-acting factor.

### Claim 3 (depends on 2)

The method of claim 2, wherein the viral trans-acting factor is a nucleoprotein (NP) or an RNA-dependent RNA polymerase (L protein).

### Claim 4 (depends on 3)

The method of claim 3, wherein the cell is transfected with a TF-plasmid comprising an open reading frame encoding for intracellular expression of NP, a TF-plasmid comprising an open reading frame encoding for intracellular expression of L protein, or both.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cell is further transfected with a complementing plasmid (C-plasmid) encoding for intracellular expression of glycoprotein (GP).

### Claim 6 (depends on 1)

The method of claim 1, wherein the cell is a complementing cell and stably expresses the glycoprotein (GP).

### Claim 7 (depends on 1)

The method of claim 1, wherein the cell is transfected with a GS-plasmid encoding the L segment, a GS-plasmid encoding the S segment, or both.