# US 10,479,823 B2 · Peptides and combination of peptides for use in immunotherapy against various tumors

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- Number: US 10,479,823 B2
- Document ID: US10479823B2
- Status: Granted
- Kind: B2
- Application number: 16/152,122
- Filed: 2018-10-04
- Published: 2019-01-24
- Granted: 2019-11-19
- Earliest claimed: 2015-03-27
- Assignees: Immatics Biotechnologies GmbH
- Applicants: Immatics Biotechnologies GmbH
- Inventors: Andrea Mahr; Toni Weinschenk; Oliver Schoor; Jens Fritsche; Harpreet Singh; Lea Stevermann
- Web page: https://patentgrep.com/patent/US10479823B2

## CPC

- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- A01N 37/46: N-acyl derivatives
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 38/06: Tripeptides
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- A61K 39/0011: {Cancer antigens}
- A61K 39/001102: {Receptors, cell surface antigens or cell surface determinants}
- A61K 39/001103: {Receptors for growth factors}
- A61K 39/001148: {Regulators of development}
- A61K 39/001152: {Transcription factors, e.g. SOX or c-MYC}
- A61K 39/001154: {Enzymes}
- A61K 39/001159: {Matrix metalloproteinases [MMP]}
- A61K 39/001162: {Kinases, e.g. Raf or Src}
- A61K 39/001184: {Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE}
- 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
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/04: Immunostimulants
- A61P 39/00: General protective or antinoxious agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/02: Linear peptides containing at least one abnormal peptide link
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/001: {by chemical synthesis}
- C07K 14/47: from mammals
- C07K 14/4702: {Regulators; Modulating activity}
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 16/18: against material from animals or humans
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/30: from tumour cells
- C12N 5/0093: {Purging against cancer cells}
- C12N 5/0636: {T lymphocytes}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- C12N 5/0646: {Natural killers cells [NK], NKT cells}
- C12N 5/0693: {Tumour cells; Cancer cells}
- C12N 9/6491: {Matrix metalloproteases [MMP's], e.g. interstitial collagenase (3.4.24.7); Stromelysins (3.4.24.17; 3.2.1.22); Matrilysin (3.4.24.23)}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/505: {involving T-cells}
- G01N 33/5088: {of vertebrates}
- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- G01N 33/56972: {White blood cells}
- G01N 33/56977: {HLA or MHC typing}
- 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 2039/54: {characterised by the route of administration}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/585: {wherein the target is cancer}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2319/00: Fusion polypeptide
- C07K 2319/40: containing a tag for immunodetection, or an epitope for immunisation
- C07K 2319/55: containing a fusion with a toxin, e.g. diphteria toxin
- C07K 2319/60: containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
- C12N 2501/998: Proteins not provided for elsewhere
- C12N 2502/11: blood or immune system cells
- C12N 2510/00: Genetically modified cells
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- C12Y 304/24: Metalloendopeptidases (3.4.24)
- G01N 2333/04: Varicella-zoster virus
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2333/70503: Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N 2333/7051: T-cell receptor (TcR)-CD3 complex
- G01N 2333/70539: MHC-molecules, e.g. HLA-molecules
- G01N 2500/10: involving cells
- 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)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- 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)
- C12Y: ENZYMES

## 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 selectively recognize cells that aberrantly express a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 6, SEQ ID NO: 17, SEQ ID NO: 27, and SEQ ID NO: 77;
wherein said cancer is selected from the group consisting of hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), chronic lymphocytic leukemia (CLL), small cell lung cancer (SCLC), Non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC).

### 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 the group consisting of 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 expresses the peptide in a complex with an MEW 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 activated T cells release a cytokine.

### 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 selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 6, SEQ ID NO: 17, SEQ ID NO: 27, and SEQ ID NO: 77.

### Claim 17

A method of treating a patient who has cancer, comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly express a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 6, SEQ ID NO: 17, SEQ ID NO: 27, and SEQ ID NO: 77;
wherein said cancer is selected from the group consisting of hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (QC), melanoma, breast cancer (BRCA), chronic lymphocytic leukemia (CLL), small cell lung cancer (SCLC), Non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC).

### Claim 18 (depends on 1)

The method of claim 1, wherein the immune response is a cytotoxic T cell response.

### Claim 19 (depends on 17)

The method of claim 17, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses 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 20 (depends on 19)

The method of claim 19, wherein the contacting is in vitro.

### Claim 21 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.

### Claim 22 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 6.

### Claim 23 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 17.

### Claim 24 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 27.

### Claim 25 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 77.