# US 2024/0199705 A1 · Chimeric newcastle disease virus expressing apmv hn and f proteins

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- Number: US 2024/0199705 A1
- Document ID: US20240199705A1
- Status: Published application
- Kind: A1
- Application number: 18/556,458
- Filed: 2022-04-25
- Published: 2024-06-20
- Earliest claimed: 2021-04-26
- Assignees: Icahn School of Medicine at Mount Sinai
- Applicants: Icahn School of Medicine At Mount Sinai
- Inventors: Adolfo GARCIA-SASTRE; Ignacio MENA; Peter PALESE; Florian KRAMMER; Weina SUN
- Web page: https://patentgrep.com/patent/US20240199705A1

## CPC

- A61K 39/12: Viral antigens
- C07K 14/005: from viruses
- A61K 39/17: Newcastle disease virus
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 35/00: Antineoplastic agents
- C12N 15/86: Viral vectors
- A61K 2039/525: {Virus}
- C12N 2760/18122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/18134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18143: 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)
- 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)
- 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)

## Abstract

In one aspect, described herein are recombinant Newcastle disease virus (“NDV”) comprising a packaged genome, wherein the packaged genome comprises a nucleotide sequence of a Newcastle disease virus genome in which the nucleotide sequence encoding the NDV HN protein has been replaced with a nucleotide sequence encoding the HN protein of an avian paramyxovirus (APMV) other than NDV or a variant of the non-NDV-APMV HN protein, and the nucleotide sequence encoding the NDV F protein has been replaced with a nucleotide sequence encoding the F protein of an APMV other than NDV or a variant of the non-NDV-APMV F protein. In some embodiments, the packaged genome further comprises a transgene comprising a nucleotide sequence encoding an antigen. Also described herein are compositions comprising such recombinant NDV and the use of such recombinant NDV to induce an immune response in a subject.

## Claims

### Claim 1

A nucleic acid sequence comprising a nucleotide sequence of a Newcastle disease virus genome in which (1) the nucleotide sequence encoding the NDV HN protein has been replaced with a nucleotide sequence encoding a non-NDV APMV HN protein, wherein NDV intergenic regions are before and after the non-NDV APMV HN protein coding sequence; and (2) the nucleotide sequence encoding the NDV F protein has been replaced with a nucleotide sequence encoding a non-NDV APMV F protein, wherein NDV intergenic regions are before and after the non-NDV APMV F protein coding sequence, and wherein the non-NDV APMV HN protein and non-NDV APMV F protein are not NDV HN protein and F proteins, respectively.

### Claim 2 (depends on 1)

The nucleic acid sequence of claim 1, wherein the non-NDV APMV F protein and non-NDV APMV HN protein are immunologically distinct from the NDF F protein and NDV HN protein, respectively.

### Claim 3 (depends on 1)

The nucleic acid sequence of claim 1, wherein the non-NDV APMV HN is the HN protein of APMV4/duck/Hongkong/D3/75, APMV17/Antarctica/107/13, APMV9/duck/New York/22/78, APMV7/Dove/Tennessee/4/75, APMV21/pigeon/Taiwan/AHRI128/17, APMV6/duck/HongKong/18/199/77, APMV11/common_snipe/France/100212/10, APMV15/calidris_fuscicollis/Brazil/RS-1177/12, APMV8/Goose/Delaware/1053/76, APMV2/Chicken/California/Yucaipa/56, APMV3/Turkey/Wisconsin/68, APMV12/Wigeon/Italy/3920_1/05, APMV5/budgerigar/Japan/TI/75, or APMV10/penguin/Falkland Islands/324/07.

### Claim 4 (depends on 1, 3)

The nucleic acid sequence of claim 1 or 3, wherein the non-NDV APMV F is the F protein of APMV4/duck/Hongkong/D3/75, APMV17/Antarctica/107/13, APMV9/duck/New York/22/78, APMV7/Dove/Tennessee/4/75, APMV21/pigeon/Taiwan/AHRI128/17, APMV6/duck/HongKong/18/199/77, APMV11/common_snipe/France/100212/10, APMV15/calidris_fuscicollis/Brazil/RS-1177/12, APMV8/Goose/Delaware/1053/76, APMV2/Chicken/California/Yucaipa/56, APMV3/Turkey/Wisconsin/68, APMV12/Wigeon/Italy/3920_1/05, APMV5/budgerigar/Japan/TI/75, or APMV10/penguin/Falkland Islands/324/07.

### Claim 5 (depends on 1)

The nucleic acid sequence of claim 1, wherein the non-NDV APMV HN protein is an HN protein from the subfamily Avulavirinae and the genus orthoavulavirus, metaavulavirus, or paraavulavirus.

### Claim 6 (depends on 1, 5)

The nucleic acid sequence of claim 1 or 5, wherein the non-NDV APMV F protein is an F protein from the subfamily Avulavirinae and the genus orthoavulavirus, metaavulavirus, or paraavulavirus.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The nucleic acid sequence of any one of claims 1 to 6, wherein the NDV genome comprises the NP gene, P gene, M gene, and L gene of NDV LaSota strain.

### Claim 8

A nucleic acid sequence comprising: (1) a transcription unit encoding a NDV nucleocapsid (N) protein, (2) a transcription unit encoding a NDV phosphoprotein (P), (3) a transcription unit encoding a NDV matrix (M) protein, (4) a transcription unit encoding a NDV large polymerase (L), and (5) the nucleotide sequence of any one of SEQ ID NOS:1-14, or a nucleotide sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to the nucleotide sequence of any one of SEQ ID NOS:1-14.

### Claim 9 (depends on 8)

The nucleic acid sequence of claim 8, wherein the NDV nucleocapsid protein, NDV phosphoprotein, NDV matrix protein, and NDV large polymerase are of the NDV LaSota strain.

### Claim 10

A nucleic acid sequence comprising the nucleotide sequence of SEQ ID NO:44, or SEQ ID NO:44 without the GFP coding sequence.

### Claim 11

A nucleic acid sequence comprising a nucleotide sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to the nucleotide sequence of SEQ ID NO:44, or SEQ ID NO:44 without the GFP coding sequence.

### Claim 12

A nucleic acid sequence comprising the nucleotide sequence of SEQ ID NO:45, or SEQ ID NO:45 without the GFP coding sequence.

### Claim 13

A nucleic acid sequence comprising a nucleotide sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to the nucleotide sequence of SEQ ID NO:45, or SEQ ID NO:45 without the GFP coding sequence.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)

The nucleic acid sequence of any one of claims 1 to 13, which further comprises a transgene.

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)

The nucleic acid sequence of any one of claims 1 to 13, which further comprises a transgene encoding an antigen.

### Claim 16 (depends on 14)

The nucleic acid sequence of claim 14, wherein the antigen is viral, bacterial, fungal or protozoan antigen.

### Claim 17 (depends on 14)

The nucleic acid sequence of claim 14, wherein the antigen comprises a SARS-CoV-2 spike protein or a fragment thereof.

### Claim 18 (depends on 17)

The nucleic acid sequence of claim 17, wherein the fragment comprises the receptor binding domain of the SARS-CoV-2 spike protein.

### Claim 19 (depends on 17)

The nucleic acid sequence of claim 17, wherein the fragment comprises the ectodomain of the SARS-CoV-2 spike protein.

### Claim 20 (depends on 15)

The nucleic acid sequence of claim 15, wherein the antigen is a MERS-CoV antigen, respiratory syncytial virus antigen, human metapneumovirus antigen, a Lassa virus antigen, Ebola virus antigen, or Nipah virus antigen.

### Claim 21 (depends on 15)

The nucleic acid sequence of claim 15, wherein the antigen is a cancer or tumor antigen.

### Claim 22

A recombinant Newcastle disease virus (NDV) comprising a packaged genome, wherein the packaged genome comprises a nucleotide sequence of a Newcastle disease virus genome in which (1) the nucleotide sequence encoding the NDV HN protein has been replaced with a nucleotide sequence encoding a non-NDV APMV HN protein, wherein NDV intergenic regions are before and after the non-NDV AMPV HN protein coding sequence; and (2) the nucleotide sequence encoding the NDV F protein has been replaced with a nucleotide sequence encoding a non-NDV APMV F protein, wherein NDV intergenic regions are before and after the non-NDV AMPV F protein coding sequence, and wherein the non-NDV APMV HN protein and non-NDV APMV F protein are not NDV HN protein and F proteins, respectively.

### Claim 23 (depends on 22)

The recombinant NDV of claim 22, wherein the non-NDV APMV F protein and non-NDV APMV HN protein are immunologically distinct from the NDF F protein and NDV HN protein, respectively.

### Claim 24 (depends on 22)

The recombinant NDV of claim 22, wherein the non-NDV APMV HN protein is an HN protein from the subfamily Avulavirinae and the genus orthoavulavirus, metaavulavirus, or paraavulavirus.

### Claim 25 (depends on 22, 23)

The recombinant NDV of claim 22 or 23, wherein the non-NDV APMV F protein is an F protein from the subfamily Avulavirinae and the genus orthoavulavirus, metaavulavirus, or paraavulavirus.

### Claim 26 (depends on 22)

The recombinant NDV of claim 22, wherein the non-NDV APMV HN is the HN protein of APMV4/duck/Hongkong/D3/75, APMV17/Antarctica/107/13, APMV9/duck/New York/22/78, APMV7/Dove/Tennessee/4/75, APMV21/pigeon/Taiwan/AHRI128/17, APMV6/duck/HongKong/18/199/77, APMV11/common_snipe/France/100212/10, APMV15/calidris_fuscicollis/Brazil/RS-1177/12, APMV8/Goose/Delaware/1053/76, APMV2/Chicken/California/Yucaipa/56, APMV3/Turkey/Wisconsin/68, APMV12/Wigeon/Italy/3920_1/05, APMV5/budgerigar/Japan/TI/75, or APMV10/penguin/Falkland Islands/324/07.

### Claim 27 (depends on 22, 26)

The recombinant NDV of claim 22 or 26, wherein the non-NDV APMV F is the F protein of APMV4/duck/Hongkong/D3/75, APMV17/Antarctica/107/13, APMV9/duck/New York/22/78, APMV7/Dove/Tennessee/4/75, APMV21/pigeon/Taiwan/AHRI128/17, APMV6/duck/HongKong/18/199/77, APMV11/common_snipe/France/100212/10, APMV15/calidris_fuscicollis/Brazil/RS-1177/12, APMV8/Goose/Delaware/1053/76, APMV2/Chicken/California/Yucaipa/56, APMV3/Turkey/Wisconsin/68, APMV12/Wigeon/Italy/3920_1/05, APMV5/budgerigar/Japan/TI/75, or APMV10/penguin/Falkland Islands/324/07.

### Claim 28

A recombinant Newcastle disease virus (NDV) comprising a packaged genome, wherein the packaged genome comprises a nucleotide sequence of a Newcastle disease virus genome in which the nucleotide sequences encoding the NDV HN protein and NDV F protein are replaced with a nucleotide sequence comprising a negative sense RNA sequence transcribed from the cDNA sequence set forth in any one of SEQ ID NOs:1-14.

### Claim 29

A recombinant Newcastle disease virus (NDV) comprising a packaged genome, wherein the packaged genome comprises a nucleotide sequence of a Newcastle disease virus genome in which the nucleotide sequences encoding the NDV HN protein and NDV F protein are replaced with a nucleotide sequence comprising a negative sense RNA sequence transcribed from a nucleotide sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to the nucleotide sequence of any one of SEQ ID NOS:1-14.

### Claim 30 (depends on 22, 23, 24, 25, 26, 27, 28, 29)

The recombinant NDV of any one of claims 22 to 29, wherein the NDV genome comprises the NP gene, P gene, M gene, and L gene of NDV LaSota.

### Claim 31 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30)

The recombinant NDV of any one of claims 22 to 30, wherein the packaged genome further comprises a transgene.

### Claim 32 (depends on 31)

The recombinant NDV of claim 31, wherein the transgene comprises a nucleotide sequence encoding a viral, bacterial, fungal or protozoan antigen.

### Claim 33 (depends on 31)

The recombinant NDV of claim 31, wherein the transgene comprises a nucleotide sequence encoding a SARS-CoV-2 antigen.

### Claim 34 (depends on 33)

The recombinant NDV of claim 33, wherein the SARS-CoV-2 antigen comprises the SARS-CoV-2 spike protein or a fragment thereof.

### Claim 35 (depends on 34)

The recombinant NDV of claim 34, wherein the fragment comprises the receptor binding domain of the SARS-CoV-2 spike protein.

### Claim 36 (depends on 31)

The recombinant NDV of claim 31, wherein the transgene comprises a nucleotide sequence encoding a MERS-CoV antigen.

### Claim 37 (depends on 31)

The recombinant NDV of claim 31, wherein the transgene comprises a nucleotide sequence encoding a respiratory syncytial virus antigen or human metapneumovirus antigen.

### Claim 38 (depends on 31)

The recombinant NDV of claim 31, wherein the transgene comprises a nucleotide sequence encoding a Lassa virus antigen, Ebola virus antigen or Nipah virus antigen.

### Claim 39 (depends on 31)

The recombinant NDV of claim 31, wherein the transgene comprises a nucleotide sequence encoding a cancer or tumor antigen.

### Claim 40 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

An immunogenic composition comprising a first recombinant NDV, which is the recombinant NDV of any one of claims 22 to 31.

### Claim 41 (depends on 32, 33, 34, 35, 36, 37, 38)

An immunogenic composition comprising a first recombinant NDV, which is the recombinant NDV of any one of claims 32 to 38.

### Claim 42 (depends on 39)

An immunogenic composition comprising a first recombinant NDV, which is the recombinant NDV of claim 39.

### Claim 43 (depends on 40, 41)

A method for inducing an immune response to an antigen, comprising administering the immunogenic composition of claim 40, 41, or 42 to a subject.

### Claim 44 (depends on 40, 41)

A method for preventing an infectious disease, comprising administering the immunogenic composition of claim 40 or 41 to a subject.

### Claim 45 (depends on 40, 41)

A method for immunizing a subject against an infectious disease, comprising administering the immunogenic composition of claim 40 or 41 the subject.

### Claim 46 (depends on 40, 42)

A method for treating cancer, comprising administering the immunogenic composition of claim 40 or 42 to a subject.

### Claim 47 (depends on 43, 44, 45, 46)

The method of any one of claim 43 to 46, wherein the composition is administered to the subject intranasally.

### Claim 48 (depends on 43, 44, 45, 46, 47)

The method of any one of claims 43 to 47, wherein the method further comprises administering a second recombinant NDV comprising a packaged genome, wherein the packaged genome of the second recombinant NDV comprises a nucleotide sequence of a Newcastle disease virus genome in which (1) the nucleotide sequence encoding the NDV HN protein has been replaced with a nucleotide sequence encoding a non-NDV APMV HN protein, wherein NDV intergenic regions are before and after the non-NDV AMPV HN protein coding sequence; and (2) the nucleotide sequence encoding the NDV F protein has been replaced with a nucleotide sequence encoding a non-NDV APMV F protein, wherein NDV intergenic regions are before and after the non-NDV AMPV F protein coding sequence, and wherein the second recombinant NDV is immunologically distinct than the first recombinant NDV.

### Claim 49 (depends on 43, 44, 45, 46, 47, 48)

The method of any one of claims 43 to 48, wherein the subject is a human.

### Claim 50 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39)

A kit comprising the recombinant NDV of any one of claims 22 to 39.

### Claim 51 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)

A kit comprising the nucleic acid sequence of any one of claims 1 to 21.

### Claim 52 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39)

An in vitro or ex vivo cell comprising the recombinant NDV of any one of claims 22 to 39.

### Claim 53 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39)

A cell line or chicken embryonated egg comprising the recombinant NDV of any one of claims 22 to 39.

### Claim 54 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 52, 53)

A method for propagating the recombinant NDV of any one of claims 22 to 39, the method comprising culturing the cell or embryonated egg of claim 52 or 53.

### Claim 55 (depends on 54)

The method of claim 54, wherein the method further comprises isolating the recombinant NDV from the cell or embryonated egg.