# US 11,407,790 B2 · HPV vaccines

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- Number: US 11,407,790 B2
- Document ID: US11407790B2
- Status: Granted
- Kind: B2
- Application number: 16/863,456
- Filed: 2020-04-30
- Published: 2021-01-28
- Granted: 2022-08-09
- Earliest claimed: 2015-06-10
- Assignees: Hookipa Biotech GmbH
- Applicants: Hookipa Biotech GmbH
- Inventors: Klaus Orlinger; Thomas Monath; Anders Lilja; Sarah Schmidt; Ursula Berka; Michael Schwendinger; Elizabeth Watson; Bettina Kiefmann; Julia Hinteramskogler; Gerhard Fuhrmann; Andreas Aspöck; Katherine Cohen
- Web page: https://patentgrep.com/patent/US11407790B2

## CPC

- C07K 14/005: from viruses
- A61K 39/12: Viral antigens
- A61P 35/00: Antineoplastic agents
- C07K 14/025: Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2710/20034: 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 2760/10051: Methods of production or purification of viral material
- 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
- 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)
- 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

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

## Claims

### Claim 1

A method of generating a tri-segmented arenavirus viral vector comprising one L segment and two S segments and a nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 10, wherein the method comprises:
a. transfecting into a host cell one or more complementary deoxyribonucleic acid (cDNA) of the one L segment and two S segments;
b. maintaining the host cell under conditions suitable for virus formation; and
c. harvesting the tri-segmented arenavirus viral vector,
wherein one of the two S segments is selected from the group consisting of:
(i) an S segment wherein the ORF encoding the NP is under control of an arenavirus 5′ UTR,
(ii) an S segment wherein the ORF encoding the Z protein is under control of an arenavirus 5′ UTR,
(iii) an S segment wherein the ORF encoding the L protein is under control of an arenavirus 5′ UTR,
(iv) an S segment wherein the ORF encoding the GP is under control of an arenavirus 3′ UTR,
(v) an S segment wherein the ORF encoding the L protein is under control of an arenavirus 3′ UTR, and
(vi) an S segment wherein the ORF encoding the Z protein is under control of an arenavirus 3′ UTR.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method further comprises transcribing the one or more cDNAs of the one L segment and two S segments using a promoter.

### Claim 3 (depends on 2)

The method of claim 2, wherein the promoter is a bidirectional promoter.

### Claim 4 (depends on 1)

The method of claim 1, wherein the method further comprises transfecting into the host cell one or more nucleic acids encoding an arenavirus polymerase.

### Claim 5 (depends on 4)

The method of claim 4, wherein the arenavirus polymerase is the L protein.

### Claim 6 (depends on 1)

The method of claim 1, wherein the method further comprises transfecting into the host cell one or more nucleic acids encoding the NP protein.

### Claim 7 (depends on 2)

The method of claim 2, wherein the promoter is selected from the group consisting of:
an RNA polymerase I promoter;
(ii) an RNA polymerase II promoter; and
(iii) a T7 promoter.

### Claim 8 (depends on 1)

The method of claim 1, wherein the tri-segmented arenavirus viral vector is derived from a lymphocytic choriomeningitis virus (LCMV) or a Pichinde virus.

### Claim 9 (depends on 8)

The method of claim 8, wherein the LCMV is MP strain, WE strain, Armstrong strain, or Armstrong Clone 13 strain.

### Claim 10 (depends on 1)

The method of claim 1, wherein the tri-segmented arenavirus viral vector comprises all four arenavirus ORFs, and wherein the tri-segmented arenavirus viral vector is infectious and replication competent.

### Claim 11 (depends on 1)

The method of claim 1, wherein the tri-segmented arenavirus viral vector is attenuated.

### Claim 12 (depends on 1)

The method of claim 1, wherein one of the two S segments comprises a nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 10.

### Claim 13 (depends on 1)

The method of claim 1, wherein one of the two S segments comprises a nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is 100% identical to SEQ ID NO: 10.

### Claim 14 (depends on 1)

The method of claim 1, wherein the two S segments each comprise a nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 10.

### Claim 15 (depends on 1)

The method of claim 1, wherein the two S segments each comprise a nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is 100% identical to SEQ ID NO: 10.

### Claim 16 (depends on 1)

The method of claim 1, wherein inter-segmental recombination of the two S segments, uniting two arenavirus ORFs on only one instead of two separate S segments, abrogates viral promoter activity.

### Claim 17

A method of generating a tri-segmented arenavirus viral vector comprising one L segment and two S segments, wherein the method comprises:
a. transfecting into a host cell one or more complementary deoxyribonucleic acid (cDNA) of the one L segment and two S segments;
b. maintaining the host cell under conditions suitable for virus formation; and
c. harvesting the tri-segmented arenavirus viral vector,
wherein a first S segment of the two S segments is engineered to carry an ORF encoding GP in a position under control of an arenavirus 3′ UTR and an ORF encoding a polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 10 in a position under control of an arenavirus 5′ UTR and a second S segment of the two S segments is engineered to carry an ORF encoding NP in a position under control of an arenavirus 3′ UTR and an ORF encoding a polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 10 in a position under control of an arenavirus 5′ UTR, wherein the arenavirus 3′ UTR is a 3′ UTR of an arenavirus S segment and the arenavirus 5′ UTR is a 5′ UTR of an arenavirus S segment.

### Claim 18 (depends on 17)

The method of claim 17, wherein the tri-segmented arenavirus viral vector is attenuated.

### Claim 19 (depends on 17)

The method of claim 17, wherein the tri-segmented arenavirus viral vector is derived from a LCMV or a Pichinde virus.

### Claim 20 (depends on 17)

The method of claim 17, wherein the polypeptide encoded on the first S segment and the polypeptide encoded on the second S segment each comprise an amino acid sequence that is 100% identical to SEQ ID NO: 10.
