# US 2019/0167690 A1 · Immuno-Gene Combination Therapy

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- Number: US 2019/0167690 A1
- Document ID: US20190167690A1
- Status: Published application
- Kind: A1
- Application number: 16/268,548
- Filed: 2019-02-06
- Published: 2019-06-06
- Earliest claimed: 2016-03-06
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Daniel STERMAN; Steven Albelda
- Web page: https://patentgrep.com/patent/US20190167690A1

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/415: 1,2-Diazoles
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 33/243: Platinum; Compounds thereof
- A61K 35/761: Adenovirus
- A61K 38/21: Interferons {[IFN]}
- A61K 38/212: {IFN-alpha}
- A61K 39/12: Viral antigens
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 14/4703: {Inhibitors; Suppressors}
- C12N 15/86: Viral vectors
- C12N 2710/10343: 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)
- 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

“In situ vaccination” using immuno-gene therapy has the ability to induce polyclonal anti-tumor responses directed by the patient's immune system. Patients with unresectable MPM received two intrapleural doses of a replication-defective adenoviral vector containing the human interferon-alpha (hIFN-α2b) gene (Ad.IFN) concomitant with a 14-day course of a cyclooxygenase-2 inhibitor (celecoxib), followed by standard first- or second-line cytotoxic chemotherapy. Forty subjects, ECOG PS 0 or 1, were treated: 18 received first-line pemetrexed-based chemotherapy with platinum, 22 received second-line chemotherapy with pemetrexed (n=7) or a gemcitabine-based regimen (n=15). Overall survival rate was significantly higher than historical controls in the second-line group.

## Claims

### Claim 1

A method of treating a human patient comprising:
a. diagnosing in said patient cancer; and then
b. treating said patient with a first-line treatment regimen; and then
c. diagnosing in said patient cancer resistant to or recurrent after said first-line treatment regimen; and then
d. treating said patient with an agent which induces the expression of interferon, in an amount effective to induce interferon expression in a human; and
e. treating said patient with a second-line treatment regimen comprising treatment selected from the group consisting of: pemetrexed, gemcitabine, cisplatin and carboplatin.

### Claim 2 (depends on 1)

The method of claim 1, wherein the second-line treatment regimen comprises pemetrexed.

### Claim 3 (depends on 1)

The method of claim 1, wherein the second-line treatment regimen comprises gemcitabine.

### Claim 4 (depends on 1)

The method of claim 1, wherein the agent which induces the expression of interferon comprises antigen.

### Claim 5 (depends on 4)

The method of claim 4, wherein the antigen comprises viral antigen.

### Claim 6 (depends on 5)

The method of claim 5, where the viral antigen comprises antigenic virus.

### Claim 7 (depends on 6)

The method of claim 6, where the antigenic virus comprises a transgene encoding human interferon.

### Claim 8 (depends on 7)

The method of claim 7, where said antigenic virus comprises rAd.IFN.

### Claim 9 (depends on 8)

The method of claim 8, where said rAd.IFN is provided in a dose of about 3×1011 viral particles, delivered intrapleurally.

### Claim 10 (depends on 1)

The method of claim 1, said second line treatment regimen further comprising treatment selected from the group consisting of: bevacizumab; a programmed cell death-1 (PD-1) inhibitor; a programmed cell death ligand-1 (PD-L1) inhibitor; and a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor.

### Claim 11 (depends on 1)

The method of claim 1, said second line treatment regimen further comprising treatment with celecoxib.

### Claim 12 (depends on 1)

The method of claim 1, wherein said cancer resistant to or recurrent after said first-line treatment regimen comprises epithelioid cancer.

### Claim 13 (depends on 1)

The method of claim 1, wherein said cancer resistant to or recurrent after said first-line treatment regimen is selected from the group consisting of: malignant pleural mesothelioma, non-small cell cancer and bladder cancer.