# US 2025/0073267 A1 · Cytomegalovirus vectors and methods of use

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- Number: US 2025/0073267 A1
- Document ID: US20250073267A1
- Status: Published application
- Kind: A1
- Application number: 18/726,619
- Filed: 2023-01-04
- Published: 2025-03-06
- Earliest claimed: 2022-01-07
- Assignees: Mayo Foundation for Medical Education and Research
- Applicants: Mayo Foundation for Medical Education and Research
- Inventors: Haifei Jiang; Stephen James Russell
- Web page: https://patentgrep.com/patent/US20250073267A1

## CPC

- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4211: {CD19 or B4}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- C07K 14/005: from viruses
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 15/86: Viral vectors
- C12N 2710/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/16143: viral genome or elements thereof as genetic vector
- C12N 2710/16144: Chimeric viral vector comprising heterologous viral elements for production of another viral vector
- C12N 2740/13022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2740/16043: viral genome or elements thereof as genetic vector
- C12N 2760/20222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2800/30: Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
- 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)

## Abstract

This document relates to methods and materials involved in treating a mammal (e.g., a human) having cancer and/or an infectious disease. For example, this document provides recombinant human cytomegalovirus (hCMV) vectors that include (e.g., are designed to include) nucleic acid encoding a viral gene transfer vector genome (e.g., a heterologous viral gene transfer vector genome) and one or more nucleic acids encoding a packaging polypeptide such that a cell of a mammal that is infected with the hCMV vector can produce and release the viral vector (e.g., an infectious lentiviral vector) which can then infect cells (e.g., immune cells) in vivo and can, optionally, drive expression of an exogenous polypeptide (e.g., a therapeutic polypeptide or an antigen receptor such as a chimeric antigen receptor (CAR)) in the infected immune cells within a mammal (e.g., a human) to induce an immune response within the mammal are provided.

## Claims

### Claim 1

A recombinant human cytomegalovirus (hCMV) vector capable of infecting a cell of a mammal, wherein said hCMV vector comprises heterologous nucleic acid encoding (i) a heterologous viral gene transfer vector genome and (ii) one or more helper polypeptides for amplifying and packaging said heterologous viral gene transfer vector genome into infectious vector particles, wherein said cell infected with said hCMV vector produces and releases said infectious vector particles comprising said gene transfer vector genome.

### Claim 2 (depends on 1)

The hCMV vector of claim 1, wherein said hCMV vector is replication-competent in said cell.

### Claim 3 (depends on 1)

The hCMV vector of claim 1, wherein said hCMV vector lacks nucleic acid encoding a UL138 polypeptide, a UL144 polypeptide, a UL146 polypeptide, a UL147 polypeptide, or a miR-UL148D.

### Claim 4 (depends on 1)

The hCMV vector of claim 1, wherein said hCMV vector lacks a UL138 polypeptide, a UL144 polypeptide, a UL146 polypeptide, a UL147 polypeptide, or a miR-UL148D.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The hCMV vector of claim 1, wherein said hCMV vector lacks nucleic acid encoding a UL23 polypeptide, a US1 polypeptide, a US2 polypeptide, a US3 polypeptide, a US4 polypeptide, a US5 polypeptide, a US6 polypeptide, a US7 polypeptide, a US8 polypeptide, a US9 polypeptide, a US10 polypeptide, a US11 polypeptide, a US14 polypeptide, a US15 polypeptide, a US16 polypeptide, a US17 polypeptide, a US18 polypeptide, a US19 polypeptide, a US20 polypeptide, a US21 polypeptide, a US22 polypeptide, a US30 polypeptide, a UL82 polypeptide, or a UL83 polypeptide.

### Claim 7 (depends on 1)

The hCMV vector of claim 1, wherein said hCMV vector lacks a UL23 polypeptide, a US1 polypeptide, a US2 polypeptide, a US3 polypeptide, a US4 polypeptide, a US5 polypeptide, a US6 polypeptide, a US7 polypeptide, a US8 polypeptide, a US9 polypeptide, a US10 polypeptide, a US11 polypeptide, a US14 polypeptide, a US15 polypeptide, a US16 polypeptide, a US17 polypeptide, a US18 polypeptide, a US19 polypeptide, a US20 polypeptide, a US21 polypeptide, a US22 polypeptide, a US30 polypeptide, a UL82 polypeptide, or a UL83 polypeptide.

### Claim 8 (depends on 1)

The hCMV vector of claim 1, wherein said cell is a fibroblast, an epithelial cell, an endothelial cell, a monocyte, or a glial cell.

### Claim 9 (depends on 1)

The hCMV vector of claim 1, wherein said viral gene transfer vector genome is a lentiviral vector genome, a retroviral vector genome, an adeno-associated virus (AAV) vector genome, a picornavirus vector genome, a rhabdovirus vector genome, or a coronavirus vector genome.

### Claim 10 (depends on 1)

The hCMV vector of claim 1, wherein said viral gene transfer vector genome comprises a nucleic acid sequence encoding a therapeutic polypeptide or an antigen receptor polypeptide, wherein said infectious vector particles comprising said gene transfer vector genome can infect an immune cell within said mammal, and wherein the infected immune cell directs expression of said therapeutic polypeptide or said antigen receptor polypeptide.

### Claim 11 (depends on 10)

The hCMV vector of claim 10, wherein said viral gene transfer vector genome comprises a nucleic acid sequence encoding said therapeutic polypeptide.

### Claim 12

(canceled)

### Claim 13 (depends on 10)

The hCMV vector of claim 10, wherein said viral gene transfer vector genome comprises a nucleic acid sequence encoding said antigen receptor polypeptide.

### Claim at position 14

14-15. (canceled)

### Claim 16 (depends on 10)

The hCMV vector of claim 10, wherein said immune cell is a T cell, a natural killer (NK) cell, or a natural killer T (NKT) cell.

### Claim 17 (depends on 10)

The hCMV vector of claim 10, wherein said viral gene transfer vector is replication-defective in said infected immune cell.

### Claim 18 (depends on 1)

The hCMV vector of claim 1, wherein said viral gene transfer vector genome comprises one or more packaging elements selected from the group consisting of a 5′ long terminal repeat (LTR), a 3′ LTR, a psi (Ψ) element, a Rev response element (RRE), and a central polypurine tract/central termination sequence (cPPT/CTS).

### Claim 19 (depends on 1)

The hCMV vector of claim 1, wherein said nucleic acid encoding one or more helper polypeptides comprises nucleic acid encoding an envelope polypeptide selected from the group consisting of a vesicular stomatitis virus G (VSV G) polypeptide and a murine leukemia virus (MLV) 4070A polypeptide.

### Claim 20 (depends on 19)

The hCMV vector of claim 19, wherein said released viral gene transfer vector comprises said envelope polypeptide.

### Claim 21

A method for treating a mammal having cancer, wherein said method comprises administering a recombinant hCMV vector to said mammal, wherein said hCMV vector is capable of infecting a cell of said mammal, wherein said hCMV comprises heterologous nucleic acid encoding (i) a heterologous viral gene transfer vector genome comprising a nucleic acid sequence encoding an antigen receptor polypeptide targeting a cancer antigen of said cancer and (ii) one or more helper polypeptides for amplifying and packaging said heterologous viral gene transfer vector genome into infectious vector particles, wherein said cell infected with said hCMV produces and releases said infectious vector particles comprising said gene transfer vector genome, and wherein said released infectious vector particles are capable of infecting an immune cell within said mammal and directing expression of said antigen receptor polypeptide by said infected immune cell, and wherein said infected immune cell expressing said antigen receptor reduces the number of cancer cells within said mammal.

### Claim 22 (depends on 21)

The method of claim 21, wherein said mammal is a human.

### Claim at position 22

23-35. (canceled)

### Claim 36

A method for treating a mammal having an infectious disease, wherein said method comprises administering a recombinant hCMV vector to said mammal, wherein said hCMV vector is capable of infecting a cell of said mammal, wherein said hCMV vector comprises heterologous nucleic acid encoding (i) a heterologous viral gene transfer vector genome derived from a virus causing the infectious disease and (ii) one or more helper polypeptides for amplifying and packaging said heterologous viral gene transfer vector genome into infectious vector particles, wherein said cell infected with said hCMV vector produces and releases said infectious vector particles comprising said gene transfer vector genome, and wherein said infectious vector particles are recognized by an antigen presenting cell (APC) within said mammal such that said APC presents an antigen from said viral gene transfer vector to a T cell within said mammal, and wherein said T cell recognizes and destroys the virus causing the infectious disease within said mammal.

### Claim 37 (depends on 36)

The method of claim 36, wherein said mammal is a human.

### Claim at position 25

38-52. (canceled)
