# US 2019/0314481 A1 · Novel vaccines against hpv and hpv-related diseases

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- Number: US 2019/0314481 A1
- Document ID: US20190314481A1
- Status: Published application
- Kind: A1
- Application number: 16/397,214
- Filed: 2019-04-29
- Published: 2019-10-17
- Earliest claimed: 2014-01-13
- Assignees: Baylor Research Institute
- Applicants: Baylor Research Institute
- Inventors: SangKon OH; Sandra ZURAWSKI; Gerard ZURAWSKI
- Web page: https://patentgrep.com/patent/US20190314481A1

## CPC

- A61K 39/12: Viral antigens
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 39/39541: {against normal tissues, cells}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- C07K 14/005: from viruses
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- 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 2039/505: {comprising antibodies}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55511: {Organic adjuvants}
- A61K 2039/585: {wherein the target is cancer}
- A61K 2039/6056: {Antibodies}
- A61K 2039/70: {Multivalent vaccine}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2319/00: Fusion polypeptide
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- C07K 2319/91: containing a motif for glycosylation
- C12N 2710/20022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/20034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Embodiments relate to novel vaccines against human papillomavirus (HPV) and HPV-related diseases, including multiple types of cancers. The HPV vaccines are composed of anti-human dendritic cell (DC) surface receptor antibodies, including CD40, and E6/7 proteins of HPV16 and 18. The technology described is not limited to making vaccines against HPV16- and HPV18-related diseases and can be applied to making vaccines carrying E6/7 from any type of HPV. The HPV vaccines described can target DCs, major and professional antigen presenting cells (APCs), and can induce and activate potent HPV E6/7-specific and strong CD4+ and CD8+ T cell responses. The HPV vaccines can be used for the prevention of HPV infection and HPV-related diseases as well as for the treatment of HPV-related diseases, including cancers.

## Claims

### Claim at position 1

1-134. (canceled)

### Claim 135

One or more nucleic acids encoding a fusion protein comprising an anti-CD40 antibody or fragment thereof, comprising at least three complementarity determining regions from each of a heavy and light chain variable region of an anti-CD40 antibody, at least one peptide linker and at least one human papillomavirus (HPV) E6 or E7 antigen, wherein the E6 or E7 antigen or antigens are HPV type 16 or HPV type 18 antigens.

### Claim 136 (depends on 135)

The one or more nucleic acids of claim 135, wherein the at least one HPV E6 or E7 antigen comprises a peptide comprising the amino acid sequence of at least one of SEQ ID Nos: 1, 3 and 4.

### Claim 137 (depends on 135)

The one or more nucleic acids of claim 135, wherein the anti-CD40 antibody or fragment thereof is humanized.

### Claim 138 (depends on 135)

The one or more nucleic acids of claim 135, wherein the peptide linker or linkers comprise one or more glycosylation sites.

### Claim 139 (depends on 135)

The one or more nucleic acids of claim 135, wherein the peptide linker comprises one or both of Flexv1 (SEQ ID NO:5) and f1 (SEQ ID NO:6).

### Claim 140 (depends on 136)

The one or more nucleic acids of claim 136, wherein the fusion protein comprises one HPV E6 antigen of SEQ ID NO: 1 or 3 and one HPV E7 antigen of SEQ ID NO:2 or 4.

### Claim 141 (depends on 135)

The one or more nucleic acids of claim 135, wherein at least one nucleic acid comprises the sequence of SEQ ID NO:18.

### Claim 142 (depends on 135)

The one or more nucleic acids of claim 135, wherein at least one nucleic acid comprises the sequence of SEQ ID NO:20 or 22.

### Claim 143 (depends on 135)

The one or more nucleic acids of claim 135, wherein at least one HPV E6 antigen is an HPV type 16 antigen and at least one HPV E7 antigen is an HPV type 16 antigen.

### Claim 144 (depends on 135)

The one or more nucleic acids of claim 135, wherein at least one HPV E6 antigen is an HPV type 18 antigen and at least one HPV E7 antigen is an HPV type 18 antigen.

### Claim 145 (depends on 135)

The one or more nucleic acids of claim 135, wherein at least one HPV E6 antigen is an HPV type 16 antigen and at least one HPV E7 antigen is an HPV type 18 antigen or wherein and at least one HPV E6 antigen is an HPV type 18 antigen and at least one HPV E7 antigen is an HPV type 16 antigen.

### Claim 146 (depends on 135)

The one or more nucleic acids of claim 135, wherein the fusion protein comprises the amino acid sequences of at least SEQ ID NOs:11-13 and/or SEQ ID NOs:14-16.

### Claim 147 (depends on 135)

The one or more nucleic acids of claim 135, wherein the fusion protein comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3 of SEQ ID Nos: 14-16, respectively, and a light chain variable region comprising CDR1, CDR2, and CDR3 SEQ ID Nos: 11-13, respectively.

### Claim 148 (depends on 135)

A vector comprising the one or more nucleic acids of claim 135.

### Claim 149 (depends on 135)

A host cell comprising the one or more nucleic acids of claim 135.

### Claim 150

A host cell comprising a nucleic acid encoding an anti-CD40 heavy chain variable region comprising at least three complementarity determining regions, at least one peptide linker and at least one human papillomavirus (HPV) type 16 or type 18 E6 or E7 antigen, wherein the at least one HPV E6 or E7 antigen comprises a peptide comprising the amino acid sequence of at least one of SEQ ID Nos: 1, 3 and 4.

### Claim 151 (depends on 150)

The cell of claim 150, wherein the cell further comprises a nucleic acid encoding an anti-CD40 light chain variable region comprising at least three complementarity determining regions.

### Claim 152

A host cell comprising:
i.) a nucleic acid comprising a sequence of SEQ ID NO:20, a nucleic acid that encodes a polypeptide of SEQ ID NO: 19, a nucleic acid comprising a sequence with at least 80% identity to SEQ ID NO:20, a nucleic acid that encodes a polypeptide with at least 80% identity to SEQ ID NO:19, a nucleic acid comprising a sequence of SEQ ID NO:22, a nucleic acid that encodes a polypeptide of SEQ ID NO:21, a nucleic acid comprising a sequence with at least 80% identity to SEQ ID NO:22, or a nucleic acid that encodes a polypeptide with at least 80% identity to SEQ ID NO:21; and
ii.) a nucleic acid comprising a sequence of SEQ ID NO:18, a nucleic acid that encodes a polypeptide of SEQ ID NO: 17, a nucleic acid comprising a sequence with at least 80% identity to SEQ ID NO: 18, a nucleic acid that encodes a polypeptide with at least 80% identity to SEQ ID NO:17.

### Claim 153 (depends on 135)

A method of making a fusion protein comprising expressing the one or more nucleic acids of claim 135 in a host cell and isolating the fusion protein.

### Claim 154 (depends on 151)

A method of making a fusion protein comprising incubating the host cell of claim 151 and isolating the fusion protein.
