# US 11,541,113 B2 · Human cytomegalovirus vaccine

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- Number: US 11,541,113 B2
- Document ID: US11541113B2
- Status: Granted
- Kind: B2
- Application number: 17/548,172
- Filed: 2021-12-10
- Published: 2022-03-31
- Granted: 2023-01-03
- Earliest claimed: 2016-10-21
- Assignees: ModernaTX, Inc.
- Applicants: ModernaTX, Inc.
- Inventors: Giuseppe Ciaramella; Shinu John
- Web page: https://patentgrep.com/patent/US11541113B2

## CPC

- A61K 39/12: Viral antigens
- A61K 39/245: Herpetoviridae, e.g. herpes simplex virus
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/7115: Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
- A61P 31/22: for herpes 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 2039/53: {DNA (RNA) vaccination}
- A61K 2039/6018: {Lipids, e.g. in lipopeptides}
- C12N 2710/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2710/16171: Demonstrated in vivo effect
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The disclosure relates to HCMV ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

## Claims

### Claim 1

A method of treating an immunocompromised organ transplant recipient subject having a cytomegalovirus (CMV) infection, comprising administering to the subject a therapeutically effective amount of:
(i) an HCMV vaccine comprising an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide pp65, and
(ii) an HCMV vaccine comprising at least one RNA polynucleotide having one or more open reading frames encoding HCMV antigenic polypeptides gH, gL, UL128, UL130, and/or UL131A; and an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gB;
wherein the HCMV vaccine of (i) and the HCMV vaccine of (ii) are formulated within cationic lipid nanoparticles, and wherein the lipid nanoparticles comprise a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pp65 polypeptide contains a deletion of amino acids 435-438.

### Claim 3 (depends on 1)

The method of claim 1, wherein the HCMV vaccine of (ii) comprises: an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gH; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gL; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide UL128; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide UL130; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide UL131A; and an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gB.

### Claim 4 (depends on 1)

The method of claim 1, wherein the one or more of the RNA polynucleotides in the HCMV vaccine of (i) and/or the HCMV vaccine of (ii) are messenger ribonucleotide polynucleotides (mRNA), and wherein each mRNA polynucleotide contains a 5′ terminal CAP structure, a 5′ untranslated region (UTR), an open reading frame (ORF), a 3′ untranslated region (UTR) and a 3′ terminal poly-A tail.

### Claim 5 (depends on 1)

The method of claim 1, wherein one or more of the RNA polynucleotides in the HCMV vaccine of (i) and/or the HCMV vaccine of (ii) are codon optimized.

### Claim 6 (depends on 1)

The method of claim 1, wherein at least one of the RNA polynucleotides encodes an antigenic polypeptide having at least 90% identity to any of the amino acid sequences of SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 71, SEQ ID NO: 73, SEQ ID NO: 77, and SEQ ID NOs: 80-83.

### Claim 7 (depends on 1)

The method of claim 1, wherein the HCMV vaccine of (i) and/or the HCMV vaccine of (ii) further comprises a pharmaceutically acceptable carrier or excipient.

### Claim 8 (depends on 1)

The method of claim 1, wherein the transplant recipient is a hematopoietic cell transplant recipient.

### Claim 9 (depends on 1)

The method of claim 1, wherein the transplant recipient is a solid organ transplant recipient.

### Claim 10 (depends on 1)

The method of claim 1, wherein at least one RNA polynucleotide further comprises a 5′ terminal cap, 7mG(5′)ppp(5′)NlmpNp.

### Claim 11 (depends on 1)

The method of claim 1, wherein at least 80% of the uracil in the open reading frame of (i)-(ii) have a chemical modification selected from 1-methyl-pseudouridine or 1-ethyl-pseudouridine.

### Claim 12 (depends on 10)

The method of claim 10, wherein the chemical modification is in the carbon-5 position of the uracil.

### Claim 13 (depends on 1)

The method of claim 1, wherein the ionizable cationic lipid comprises the following compound:

### Claim 14 (depends on 1)

The method of claim 1, wherein the RNA polynucleotides are not self-replicating RNA.

### Claim 15 (depends on 1)

The method of claim 1, wherein the HCMV vaccine of (i) is administered at a dose of between 10 μg and 400 μg.

### Claim 16 (depends on 1)

The method of claim 1, wherein the HCMV vaccine of (ii) is administered at a dose of between 10 μg and 400 μg.

### Claim 17 (depends on 1)

The method of claim 1, wherein the vaccine of i) and the vaccine of ii) are administered to the individual via a route selected from the group consisting of intramuscular administration, intradermal administration and subcutaneous administration.