# US 2019/0167813 A1 · Compositions and methods of replication deficient adenoviral vectors for vaccine applications

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- Number: US 2019/0167813 A1
- Document ID: US20190167813A1
- Status: Published application
- Kind: A1
- Application number: 16/322,139
- Filed: 2017-07-21
- Published: 2019-06-06
- Earliest claimed: 2016-08-01
- Assignees: The Wistar Institute of Anatomy and Biology
- Applicants: The Wistar Institute of Anatomy and Biology
- Inventors: Hildegund C.J. ERTL; Xiang Yang ZHOU
- Web page: https://patentgrep.com/patent/US20190167813A1

## CPC

- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 39/12: Viral antigens
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 48/0008: {characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition}
- A61K 48/0091: {Purification or manufacturing processes for gene therapy compositions}
- A61P 31/18: for HIV
- C07K 14/005: from viruses
- C12N 15/86: Viral vectors
- A61K 2039/525: {Virus}
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- C12N 2740/16234: 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

The invention includes compositions and methods of generating a chimpanzee-derived adenovirus AdC6 or AdC7 vector vaccine comprising a deletion of E1, a deletion of E3 ORF3, ORF4, ORF5, ORF6, and ORF7 and a sequence encoding HIV protein gp140, gp160 or Gag, methods of treating and/or preventing or immunizing against HIV and methods of inducing an effector T cell, memory T cell and B cell immune response in a mammal administered the composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a mammal as well as a protein expression system.

## Claims

### Claim 1

A composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein the early gene E1 is deleted, the ORF3, ORF4, ORF5, ORF6, and ORF7 from the early gene E3 are deleted, and wherein the nucleic acid sequence further comprises a promoter sequence linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140, gp160 and Gag.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the promoter is a constitutive promoter.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the promoter is a cytomegalovirus immediate early promoter (CMV).

### Claim 4 (depends on 1)

The composition of claim 1, wherein the nucleic acid sequence is selected from the group consisting of SEQ ID NOs: 1-8.

### Claim 5 (depends on 1)

A protein expression system comprising the composition of claim 1, wherein the nucleic acid sequence is selected from the group consisting of SEQ ID NOs: 1-8.

### Claim 6 (depends on 1)

A protein expression system comprising the composition of claim 1, wherein the nucleic acid sequence encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 9-16.

### Claim 7

A method of eliciting an immune response in a mammal against a heterologous protein, the method comprising administering to the mammal a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein the early gene E1 is deleted, the ORF3, ORF4, ORF5, ORF6, and ORF7 from the early gene E3 are deleted, and wherein the nucleic acid sequence further comprises a promoter sequence linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140, gp160 and Gag.

### Claim 8 (depends on 7)

The method of claim 7, wherein the nucleic acid sequence is selected from the group consisting of SEQ ID NOs: 1-8.

### Claim 9

A method of treating and/or preventing HIV in a mammal, the method comprising administering a therapeutically effective amount of a composition encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-8.

### Claim 10 (depends on 1)

A method of vaccinating a mammal against HIV infection, the method comprising administering to the mammal a pharmaceutically acceptable amount of the composition of claim 1, wherein administration of the composition elicits an immune response in the mammal.

### Claim 11 (depends on 10)

The method of claim 10, wherein the composition is administered prophylactically to the mammal.

### Claim 12 (depends on 10)

The method of claim 10, wherein the composition is administered therapeutically to the mammal.

### Claim 13 (depends on 10)

The method of claim 10, wherein the composition is administered in combination with an adjuvant.

### Claim 14 (depends on 1)

A method of generating a effector and memory T cell immune response to a heterologous protein in a mammal, the method comprising the steps of: (a) administering the composition of claim 1 to a mammal in an amount effective to elicit an immune response in the mammal; (b) administering a second effective amount of the chimpanzee-derived adenovirus vector of claim 1 at a second, subsequent time period, wherein T memory cells directed against the heterologous protein are reactivated in the mammal.

### Claim 15 (depends on 14)

The method of claim 14, wherein the composition administered first in (a) and second in (b) comprises a same or a different HIV heterologous protein selected from the group consisting of gp140, gp160 and Gag.

### Claim 16 (depends on 14)

The method of claim 14, wherein the composition administered first in (a) and in (b) has a same or a different serotype selected from the group consisting of AdC6 and AdC7.

### Claim 17 (depends on 1)

A method of generating an adaptive B cell immune response to a heterologous protein in a mammal, the method comprising the steps of: (a) administering the composition of claim 1 to a mammal in an amount effective to elicit an immune response in the mammal; (b) administering a second effective amount of the composition of claim 1 at a second, subsequent time period, wherein B memory cells directed against the heterologous protein are reactivated in the mammal.

### Claim 18 (depends on 7)

The methods of claim 7, wherein the mammal is a human.
