# US 12,180,265 B2 · Citrullinated peptides that bind to types of MHC class II and their use on diagnosis and treatment

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- Number: US 12,180,265 B2
- Document ID: US12180265B2
- Status: Granted
- Kind: B2
- Application number: 16/879,706
- Filed: 2020-05-20
- Published: 2020-09-03
- Granted: 2024-12-31
- Earliest claimed: 2011-04-05
- Assignees: Curara AB
- Applicants: Curara AB
- Inventors: Lars Klareskog; Vivianne Malmstström
- Web page: https://patentgrep.com/patent/US12180265B2

## CPC

- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- A61K 38/014: {from connective tissue peptides, e.g. gelatin, collagen}
- A61K 39/0008: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 39/001: {Preparations to induce tolerance to non-self, e.g. prior to transplantation}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- C07K 14/47: from mammals
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C12N 9/88: Lyases (4.)
- C12Y 402/01011: Phosphopyruvate hydratase (4.2.1.11), i.e. enolase
- G01N 33/564: for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9}
- 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 2035/122: {for inducing tolerance or supression of immune responses}
- G01N 2333/525: Tumor necrosis factor [TNF]
- G01N 2333/54: Interleukins [IL]
- G01N 2333/57: IFN-gamma
- G01N 2333/7051: T-cell receptor (TcR)-CD3 complex
- G01N 2333/70514: CD4
- G01N 2333/70539: MHC-molecules, e.g. HLA-molecules
- G01N 2333/70575: NGF/TNF-superfamily, e.g. CD70, CD95L, CD153 or CD154
- G01N 2333/988: Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
- G01N 2800/102: Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
- G01N 2800/24: Immunology or allergic disorders
- 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)
- 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)

## Abstract

A pharmaceutical composition comprises (a) a peptide of 8 to 20 amino acids comprising at least one citrulline residue and 13, 14 or 15 consecutive amino acids residues with a sequence present in SEQ ID NO 22 or a complex of said peptide and a human recombinant MHC class II protein, and (b) an immunologic adjuvant.

## Claims

### Claim 1

A pharmaceutical composition comprising (a) a peptide epitope of up to 20 amino acids comprising 13, 14 or 15 consecutive amino acid residues with a sequence present in SEQ ID NO 22, and having a citrulline residue within the consecutive amino acid residues, or a complex of said peptide epitope and a human recombinant MHC class II protein, and (b) an immunologic adjuvant.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein the peptide epitope consists of the sequence of SEQ ID NO 22.

### Claim 3 (depends on 1)

The composition according to claim 1, wherein the immunologic adjuvant is an aluminum salt.

### Claim 4 (depends on 1)

The composition according to claim 1, further comprising a micelle component for delivery of the peptide epitope.

### Claim 5

An assay for analysis of T-cells of a patient, comprising
1) contacting a sample comprising T cells obtained from a patient with a peptide epitope of up to 20 amino acids and comprising 13, 14 or 15 consecutive amino acid residues with a sequence present in SEQ ID NO 22, and having a citrulline residue within the consecutive amino acid residues, or a complex of said peptide epitope and a human recombinant MHC class II protein; and
2) detecting the ability of the T-cells to become activated by the peptide epitope or complex.

### Claim 6

A method of detecting T-cell binding in a sample, the method comprising contacting a sample comprising T-cells obtained from a patient with a peptide epitope of up to 20 amino acids and comprising 13, 14 or 15 consecutive amino acid residues with a sequence present in SEQ ID NO 22, and having a citrulline residue within the consecutive amino acid residues, or with a complex of said peptide epitope and a human recombinant MHC class II protein, and detecting binding of T-cells in the sample to the peptide epitope or the complex.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the peptide epitope consists of the sequence of SEQ ID NO 22.

### Claim 8

A method of detecting a T-cell marker produced by T-cell binding in a sample, the method comprising contacting a sample comprising T-cells obtained from a patient with a peptide epitope of up to 20 amino acids and comprising 13, 14 or 15 consecutive amino acid residues with a sequence present in SEQ ID NO 22, and having a citrulline residue within the consecutive amino acid residues, or a complex of said peptide epitope and a human recombinant MHC class II protein, and detecting a T-cell marker produced from binding of T-cells in the sample to the peptide epitope or the complex.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the peptide epitope consists of the sequence of SEQ ID NO 22.

### Claim 10

A pharmaceutical composition, comprising (a) a peptide comprising SEQ ID NO: 22, and (b) an immunologic adjuvant.