# US 2026/0092091 A1 · Cxc receptor ligands

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- Number: US 2026/0092091 A1
- Document ID: US20260092091A1
- Status: Published application
- Kind: A1
- Application number: 19/120,219
- Filed: 2023-10-11
- Published: 2026-04-02
- Earliest claimed: 2022-10-11
- Applicants: Queen Mary University of London; The University of Manchester
- Inventors: Nikolaos KOUVATSOS; Anthony DAY; Francesco DELL'ACCIO; Sara CAXARIA
- Web page: https://patentgrep.com/patent/US20260092091A1

## CPC

- C07K 14/521: {Chemokines}
- C12N 15/00: Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor (mutants or genetically engineered microorganisms, per se C12N1/00, C12N5/00, C12N7/00; new plants per se A01H; plant reproduction by tissue culture techniques A01H4/00; new animals per se A01K67/00; use of medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases, gene therapy A61K48/00)
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- C07K 14/52: Cytokines; Lymphokines; Interferons
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention relates to novel polypeptide ligands of CXCR1 and/or CXCR2 which are derived from GCP2. The invention also concerns polynucleotides encoding the polypeptide ligands, uses of the polypeptide ligands and compositions comprising the polypeptide ligands.

## Claims

### Claim 1

A polypeptide ligand of chemokine receptor CXCR1 and/or CXCR2, which:
a. has an ability to activate CXCR1 and/or CXCR2; and
b. has a reduced ability to bind to glycosaminoglycans (GAGs) as compared to GCP2 of SEQ ID NO: 1;
wherein said polypeptide comprises or consists of the sequence of SEQ ID NO: 1 in which at least one positively charged amino acid has been substituted for a negatively charged or neutral amino acid, or in which at least one positively charged amino acid has been chemically modified to neutralise the positive charge.

### Claim 2 (depends on 1)

A polypeptide ligand according to claim 1 which has a reduced ability to attract inflammatory cells as compared to GCP2 of SEQ ID NO: 1.

### Claim 3 (depends on 1)

A polypeptide ligand according to claim 1, wherein said at least one positively charged amino acid is:
a. not within a CXC motif of GCP2; and/or
b not within an ELR motif of GCP2.

### Claim 4 (depends on 1)

A polypeptide ligand according to claim 1, wherein said at least one positively charged amino acid is lysine or arginine.

### Claim 5 (depends on 1)

A polypeptide ligand according to claim 1, wherein said negatively charged or neutral amino acid is glycine, alanine, valine, leucine, isoleucine, histidine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartic acid or glutamic acid, and/or wherein said chemical modification is succinylation, PEGylation or treatment with DEPC or p-Hydroxyphenylglyoxal.

### Claim 6 (depends on 1)

A polypeptide ligand according to claim 1,
wherein said positively charged amino acid is at:
(i) any one of K100, K101 or K105;
(ii) any two of K100, K101 or K105 (that is K100 and K101; K100 and K105; or K101 and K105); or
(iii) all three of K100 and K101 and K105.

### Claim 7 (depends on 6)

A polypeptide ligand according to claim 6, wherein at least one of the substitutions in (i), (ii) or (iii) is with E.

### Claim 8 (depends on 7)

A polypeptide according to claim 7, which comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 12 to 18.

### Claim 9 (depends on 1)

A polynucleotide which encodes a polypeptide ligand according to claim 1.

### Claim 10 (depends on 1)

A composition comprising the polypeptide ligand according to claim 1, which comprises at least one pharmaceutically acceptable diluent, carrier, preservative or excipient.

### Claim 11 (depends on 1)

A method of treating or preventing a disease or condition in a subject, the method comprising administering to the subject the polypeptide ligand according to claim 1.

### Claim 12 (depends on 11)

A method of treating or preventing a disease condition in a subject according to claim 11, wherein the disease or condition is characterised by degeneration of cartilage, damage to cartilage, or a need for cartilage regeneration.

### Claim 13 (depends on 11)

A method according to claim 11, wherein the disease is characterised by pain or stiffness, optionally wherein the pain is nociceptive and/or neuropathic pain.

### Claim 14 (depends on 11)

A method according to claim 11, wherein the disease is further characterised by hypertrophic differentiation, chondrocyte hypertrophy, calcification, and/or bone formation.

### Claim 15 (depends on 11)

A method according to claim 11, wherein the disease is osteoarthritis.
