# US 8,540,979 B2 · Methods of generating immune responses with compositions comprising an adenoviral expression vector comprising a CD40L fusion protein

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- Number: US 8,540,979 B2
- Document ID: US8540979B2
- Status: Granted
- Kind: B2
- Application number: 13/549,581
- Filed: 2012-07-16
- Published: 2012-11-01
- Granted: 2013-09-24
- Earliest claimed: 2002-11-12
- Assignees: VAXum, LLC
- Applicants: Albert B. Deisseroth; Lixin Zhang
- Inventors: Albert B. Deisseroth; Lixin Zhang
- Web page: https://patentgrep.com/patent/US8540979B2

## CPC

- A61K 39/12: Viral antigens
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C12N 15/86: Viral vectors
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/575: {humoral response}
- C07K 2319/02: containing a signal sequence
- C07K 2319/40: containing a tag for immunodetection, or an epitope for immunisation
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- C12N 2710/10371: Demonstrated in vivo effect
- 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
- C12N 2710/20071: Demonstrated in vivo effect
- 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

Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.

## Claims

### Claim 1

A method of generating an immune response in an individual with cancer against cells expressing a tumor antigen, comprising administering an effective amount of an adenoviral expression vector, said vector comprising a transcription unit encoding a polypeptide, said polypeptide comprising from the amino terminus a secretory signal sequence, a tumor antigen, and a CD40 ligand wherein said tumor antigen is different from said CD40 ligand and wherein said CD40 ligand is missing all or substantially all of the transmembrane domain rendering the CD40 ligand secretable, and wherein said polypeptide is adapted to elicit Class I restricted cellular immunity, and whereby the generation of said immune response is achieved by injection of the vector directly into tumor nodules of the individual, expressing the tumor antigen.

### Claim 2 (depends on 1)

A method of generating an immune response in an individual according to claim 1, wherein said polypeptide is adapted to additionally elicit Class II humoral immunity.

### Claim 3 (depends on 1)

The method of generating an immune response in an individual according to claim 1, wherein the direct injection of the vector into the tumor nodules is repeated at least once.

### Claim 4

A method of generating an immune response in an individual with cancer against cells expressing a tumor antigen, comprising administering an effective amount of an adenoviral expression vector, said vector comprising a transcription unit encoding a polypeptide, said polypeptide comprising from the amino terminus a secretory signal sequence, a tumor antigen, and a CD40 ligand wherein said tumor antigen is different from said CD40 ligand and wherein said CD40 ligand is missing all or substantially all of the transmembrane domain rendering the CD40 ligand secretable, and wherein said polypeptide is adapted to elicit Class I restricted cellular immunity, and whereby the generation of said immune response is achieved by injection of the individual's dendritic cells infected with the vector directly into tumor nodules of the individual, expressing the tumor antigen.

### Claim 5 (depends on 4)

The method of generating an immune response in an individual according to claim 4, wherein said polypeptide is adapted to additionally elicit Class II humoral immunity.

### Claim 6 (depends on 4)

The method of generating an immune response in an individual according to claim 4, wherein the injection of the dendritic cells infected with the vector directly into the tumor nodules is administered multiple times.