# US 12,110,316 B2 · Cleavable activators of CXCR3 and methods of use

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- Number: US 12,110,316 B2
- Document ID: US12110316B2
- Status: Granted
- Kind: B2
- Application number: 17/287,480
- Filed: 2019-10-18
- Published: 2021-12-16
- Granted: 2024-10-08
- Earliest claimed: 2018-10-22
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Alan H. Wells
- Web page: https://patentgrep.com/patent/US12110316B2

## CPC

- C07K 14/522: {Alpha-chemokines, e.g. NAP-2, ENA-78, GRO-alpha/MGSA/NAP-3, GRO-beta/MIP-2alpha, GRO-gamma/MIP-2beta, IP-10, GCP-2, MIG, PBSF, PF-4, KC}
- 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)}
- 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 2319/50: containing protease site
- 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)
- 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

Recombinant C-X-C motif chemokine ligand (CXCL) peptides modified to introduce a cleavage site for a protease, such as a protease activated during an inflammatory response, are described. The CXCL peptides have the capacity to activate CXCR3 until being cleaved by the protease. Proteolytic cleavage of the CXCL peptide minimizes the pro-inflammatory response and inhibits the development of fibrosis.

## Claims

### Claim 1

A recombinant C-X-C motif chemokine ligand (CXCL) peptide, comprising a modification relative to a wild-type CXCL amino acid sequence, wherein the modification is a cleavage site for a protease and wherein the amino acid sequence of the peptide comprises SEQ ID NO: 2.

### Claim 2 (depends on 1)

The recombinant CXCL peptide of claim 1, wherein the protease is cathepsin G or neutrophil elastase.

### Claim 3 (depends on 1)

The recombinant CXCL peptide of claim 1, wherein the peptide further comprises at least one chemical modification.

### Claim 4 (depends on 3)

The recombinant CXCL peptide of claim 3, wherein the at least one chemical modification comprises a modification at the N-terminus of the peptide, a modification at the C-terminus of the peptide, or both.

### Claim 5 (depends on 4)

The recombinant CXCL peptide of claim 4, wherein the modification at the N-terminus comprises formylation, acetylation, propionylation, pyroglutamate formation, myristoylation, palmitylation, S-palmitoylation, mono-methylation, di-methylation, tri-methylation, or any combination thereof.

### Claim 6 (depends on 4)

The recombinant CXCL peptide of claim 4, wherein the modification at the C-terminus comprises methylation, alpha-amidation, or a combination thereof.

### Claim 7 (depends on 1)

The recombinant CXCL peptide of claim 1 in a slow release formulation.

### Claim 8 (depends on 1)

A composition comprising the recombinant CXCL peptide of claim 1 and a pharmaceutically acceptable carrier.

### Claim 9

A recombinant C-X-C motif chemokine ligand (CXCL) peptide, comprising a modification relative to a wild-type CXCL amino acid sequence, wherein the modification is a cleavage site for a protease, and wherein the amino acid sequence of the peptide consists of SEQ ID NO: 2.