# US 10,765,730 B2 · Peptides and combination of peptides for use in immunotherapy against various cancers

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- Number: US 10,765,730 B2
- Document ID: US10765730B2
- Status: Granted
- Kind: B2
- Application number: 16/554,139
- Filed: 2019-08-28
- Published: 2020-01-02
- Granted: 2020-09-08
- Earliest claimed: 2015-12-11
- Assignees: Immatics Biotechnologies GmbH
- Applicants: Immatics Biotechnologies GmbH
- Inventors: Andrea Mahr; Toni Weinschenk; Colette Song; Oliver Schoor; Jens Fritsche; Harpreet Singh
- Web page: https://patentgrep.com/patent/US10765730B2

## CPC

- A61K 39/0011: {Cancer antigens}
- 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 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
- A61P 37/04: Immunostimulants
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/47: from mammals
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/71: for growth factors; for growth regulators
- C07K 14/721: {Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor}
- C07K 14/8135: {Kazal type inhibitors, e.g. pancreatic secretory inhibitor, ovomucoid}
- C07K 16/18: against material from animals or humans
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)}
- C07K 16/30: from tumour cells
- C07K 16/38: against protease inhibitors of peptide structure
- C07K 16/40: against enzymes
- C12N 5/0636: {T lymphocytes}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- C12N 9/0091: {oxidizing metal ions (1.16)}
- C12N 9/1264: {DNA nucleotidylexotransferase (2.7.7.31), i.e. terminal nucleotidyl transferase}
- 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)
- C12Y 116/01: with NAD+ or NADP+ as acceptor (1.16.1)
- C12Y 207/07031: DNA nucleotidylexotransferase (2.7.7.31), i.e. terminal deoxynucleotidyl transferase
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B 25/00: ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation
- 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 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/40: containing a tag for immunodetection, or an epitope for immunisation
- C12N 2310/16: Aptamers
- C12N 2502/11: blood or immune system cells
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- 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)
- 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
- C12Y: ENZYMES
- 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)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## 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 producing an antibody specifically binding to an MHC class I molecule complexed with an antigen consisting of the amino acid sequence of VQLDSIEDLEV (SEO ID NO: 32), comprising
immunizing a genetically engineered non-human mammal comprising cells expressing said human major histocompatibility complex (MHC) class I molecule with a soluble form of an MHC class I molecule complexed with an antigen consisting of the amino acid sequence of VQLDSIEDLEV (SEO ID NO: 32);
isolating mRNA molecules from antibody producing cells of said non-human mammal;
producing a phage display library displaying protein molecules encoded by said mRNA molecules; and
isolating at least one phage from said phage display library, wherein said at least one phage displays said antibody specifically binding to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of VQLDSIEDLEV (SEO ID NO: 32).

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody is a monoclonal antibody.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antibody binds to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of SEQ ID NO: 32 with a binding affinity of below 20 nanomolar.

### Claim 4 (depends on 1)

The method of claim 1, further comprising humanizing the antibody.

### Claim 5 (depends on 1)

The method of claim 1, further comprising conjugating the antibody is conjugated with a toxin.

### Claim 6 (depends on 1)

The method of claim 1, further comprising conjugating the antibody with an immune stimulating domain.

### Claim 7 (depends on 1)

The method of claim 1, further comprising modifying the antibody in the form of a bi-specific antibody.

### Claim 8 (depends on 1)

The method of claim 1, further comprising modifying the antibody in the form of a chimeric antibody.

### Claim 9 (depends on 1)

The method of claim 1, wherein the non-human mammal is mouse.

### Claim 10 (depends on 1)

The method of claim 1, wherein the MHC class I molecule is HLA-A*02.

### Claim 11 (depends on 1)

The method of claim 1, further comprising labeling the antibody with a radionucleotide.

### Claim 12 (depends on 11)

The method of claim 11, wherein the radionucleotide is selected from the group consisting of 111In, 99Tc, 14C, 131I, 3H, 32P, and 35S.

### Claim 13 (depends on 1)

The method of claim 1, wherein the antibody has an affinity value (Kd) of less than 1×10 μM.

### Claim 14 (depends on 1)

The method of claim 1, further comprising modifying the antibody in the form of an Fv.

### Claim 15 (depends on 1)

The method of claim 1, further comprising modifying the antibody in the form of an Fab.

### Claim 16 (depends on 1)

The method of claim 1, further comprising modifying the antibody in the form of an Fab′.

### Claim 17 (depends on 1)

The method of claim 1, wherein the antibody binds to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of SEQ ID NO: 32 with a binding affinity of below 10 nanomolar.