# US 10,478,480 B2 · Peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers

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- Number: US 10,478,480 B2
- Document ID: US10478480B2
- Status: Granted
- Kind: B2
- Application number: 16/385,225
- Filed: 2019-04-16
- Published: 2019-08-08
- Granted: 2019-11-19
- Earliest claimed: 2015-08-05
- Assignees: Immatics Biotechnologies GmbH
- Applicants: Immatics Biotechnologies GmbH
- Inventors: Andrea Mahr; Toni Weinschenk; Oliver Schoor; Jens Fritsche; Harpreet Singh; Phillip Mueller; Julia Leibold; Valentina Goldfinger
- Web page: https://patentgrep.com/patent/US10478480B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- A61K 39/0011: {Cancer antigens}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/47: from mammals
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 16/30: from tumour cells
- C12N 5/0636: {T lymphocytes}
- C12N 5/0639: {Dendritic cells, e.g. Langherhans cells in the epidermis}
- C12N 9/6445: {Kallikreins (3.4.21.34; 3.4.21.35)}
- C12N 15/115: Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/57575: {involving oncogenic proteins}
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/5158: {Antigen-pulsed cells, e.g. T-cells}
- A61K 2039/572: {cytotoxic response}
- C07K 2319/00: Fusion polypeptide
- C12N 2310/16: Aptamers
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- C12Q 2600/16: Primer sets for multiplex assays
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- G01N 2570/00: Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

## Claims

### Claim 1

A method of eliciting an immune response in a patient who has cancer, comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of GYLQGLVSF (SEQ ID NO: 27),
wherein said cancer is selected from liver cancer, benign prostate hyperplasia, and prostate cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the T cells are autologous to the patient.

### Claim 3 (depends on 1)

The method of claim 1, wherein the T cells are obtained from a healthy donor.

### Claim 4 (depends on 1)

The method of claim 1, wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the activated T cells are expanded in vitro.

### Claim 6 (depends on 1)

The method of claim 1, wherein the population of activated T cells are administered in the form of a composition.

### Claim 7 (depends on 6)

The method of claim 6, wherein the composition further comprises an adjuvant.

### Claim 8 (depends on 7)

The method of claim 7, wherein the adjuvant is selected from anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

### Claim 9 (depends on 1)

The method of claim 1, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that presents the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

### Claim 10 (depends on 9)

The method of claim 9, wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.

### Claim 11 (depends on 10)

The method of claim 10, wherein the antigen presenting cell is a dendritic cell or a macrophage.

### Claim 12 (depends on 5)

The method of claim 5, wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.

### Claim 13 (depends on 1)

The method of claim 1, wherein the population of activated T cells comprises CD8-positive cells.

### Claim 14 (depends on 9)

The method of claim 9, wherein the contacting is in vitro.

### Claim 15 (depends on 1)

The method of claim 1, wherein the cancer cells present the peptide at a level at least 1.2-fold of that present in normal tissue.

### Claim 16 (depends on 1)

The method of claim 1, wherein the immune response is capable of killing cancer cells that present a peptide consisting of the amino acid sequence of GYLQGLVSF (SEQ ID NO: 27).

### Claim 17

A method of eliciting an immune response in a patient who has liver cancer, benign prostate hyperplasia, or prostate cancer, comprising administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, wherein said peptide consists of the amino acid sequence of GYLQGLVSF (SEQ ID NO: 27), thereby inducing a T-cell response to the liver cancer, benign prostate hyperplasia, or prostate cancer.

### Claim 18 (depends on 17)

The method of claim 17, wherein the T cell response comprises a cytotoxic T cell response.

### Claim 19 (depends on 17)

The method of claim 17, wherein the immune response is capable of killing cancer cells that present a peptide consisting of the amino acid sequence of GYLQGLVSF (SEQ ID NO: 27).

### Claim 20 (depends on 1)

The method of claim 1, wherein the cancer is prostate cancer.