# US 11,027,017 B2 · PCI method for generating immune respose to antigenic molecule using checkpoint inhibitor and TLR3 ligand

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- Number: US 11,027,017 B2
- Document ID: US11027017B2
- Status: Granted
- Kind: B2
- Application number: 15/555,205
- Filed: 2016-03-04
- Published: 2018-02-22
- Granted: 2021-06-08
- Earliest claimed: 2015-03-05
- Assignees: PCI Biotech AS
- Applicants: PCI Biotech AS
- Inventors: Anders Høgset
- Web page: https://patentgrep.com/patent/US11027017B2

## CPC

- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61K 41/0071: {PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines}
- 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 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 39/0011: {Cancer antigens}
- A61K 39/12: Viral antigens
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/39541: {against normal tissues, cells}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 41/00: Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations}
- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2818: {against CD28 or CD152}
- C12N 5/0639: {Dendritic cells, e.g. Langherhans cells in the epidermis}
- C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- A61K 2039/5158: {Antigen-pulsed cells, e.g. T-cells}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/575: {humoral response}
- A61K 2039/585: {wherein the target is cancer}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2501/50: Cell markers; Cell surface determinants
- C12N 2501/599: with CD designations not provided for elsewhere
- C12N 2502/1114: T cells
- 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
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination. The invention also provides related methods, compositions, cells, uses, products and kits.

## Claims

### Claim 1

A method of generating an immune response in a subject, comprising administering to a subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor and a TLR3 ligand, and irradiating said subject with light of a wavelength effective to activate said photosensitizing agent, wherein an immune response is thereby generated, wherein
the antigenic molecule is a peptide,
the checkpoint inhibitor is an anti-CTLA4 antibody, an anti-PD-1 antibody, or both an anti-CTLA4 antibody and an anti-PD-1 antibody, and
the TLR3 ligand is a double stranded RNA molecule.

### Claim 2 (depends on 1)

The method as claimed in claim 1 wherein the checkpoint inhibitor is a monoclonal antibody.

### Claim 3 (depends on 1)

The method as claimed in claim 1 wherein the checkpoint inhibitor is (i) an anti-CTLA4 antibody and an anti-PD-1 antibody or (ii) an anti-CTLA4 antibody.

### Claim 4 (depends on 1)

The method as claimed in claim 1 wherein said double stranded RNA molecule is Poly(I:C).

### Claim 5 (depends on 1)

The method as claimed in claim 1 wherein the antigenic molecule is a molecule capable of stimulating an immune response, preferably a vaccine antigen or vaccine component and preferably comprises more than one antigen.

### Claim 6 (depends on 1)

The method as claimed in claim 1 wherein the photosensitising agent is selected from TPCS2a, AlPcS2a, TPPS4 and TPBS2a, preferably TPCS2a.

### Claim 7 (depends on 1)

The method as claimed in claim 1 wherein the antigenic molecule is a melanoma peptide or Human Papillomavirus (HPV) peptide.

### Claim 8 (depends on 1)

The method as claimed in claim 1 wherein said method is a method of vaccination.

### Claim 9 (depends on 1)

The method as claimed in claim 1 wherein a disease, disorder or infection is treated or prevented when said immune response is generated, and wherein said disease, disorder or infection is preferably cancer, preferably melanoma or a cancer associated with a papillomavirus.

### Claim 10 (depends on 1)

The method as claimed in claim 1 wherein said subject is a mammal, preferably a cat, dog, horse, donkey, sheep, pig, goat, cow, mouse, rat, rabbit or guinea pig, most preferably the subject is a human.

### Claim 11 (depends on 1)

The method as claimed in claim 1 wherein said antigenic molecule, photosensitising agent, checkpoint inhibitor and TLR3 ligand are administered to said subject simultaneously, separately or sequentially.
