# US 2014/0154249 A1 · Novel chemokine binding polypeptides capable of inhibiting the course of autoimmunity, inflammation and cancer

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- Number: US 2014/0154249 A1
- Document ID: US20140154249A1
- Status: Published application
- Kind: A1
- Application number: 14/178,301
- Filed: 2014-02-12
- Published: 2014-06-05
- Earliest claimed: 2009-06-15
- Assignees: Biokine Therapeutics Ltd.
- Applicants: Biokine Therapeutics Ltd.
- Inventors: Michal ABRAHAM; Orly Eizenberg; Amnon Peled
- Web page: https://patentgrep.com/patent/US20140154249A1

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 47/6813: {the drug being a peptidic cytokine, e.g. an interleukin or interferon}
- A61K 47/6835: {the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/7158: {for chemokines}
- C07K 16/24: against cytokines, lymphokines or 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)
- A61K 38/195: {Chemokines, e.g. RANTES}
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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

## Abstract

Novel polypeptides comprising a chemokine-binding peptide and an Fc fragment are disclosed. The polypeptides are capable of binding to certain chemokines so as to modulate their activity. These polypeptides can be used to modulate in vivo chemokine-dependent processes such as inflammation and autoimmunity, and to treat associated conditions.

## Claims

### Claim 1

An isolated polypeptide comprising at least one chemokine-binding peptide attached to an Fc domain or a fragment of said Fc domain, wherein said chemokine-binding peptide has the amino acid sequence as set forth in SEQ ID NO: 76.

### Claim 2 (depends on 1)

The polypeptide of claim 1, further comprising a linker.

### Claim 3 (depends on 1)

The polypeptide of claim 1, wherein said linker is an amino acid linker.

### Claim 4 (depends on 1)

The polypeptide of claim 1, wherein the isolated polypeptide further comprises a signal peptide.

### Claim 5 (depends on 4)

The polypeptide of claim 4, wherein said signal peptide comprises an IL-6 signal peptide.

### Claim 6 (depends on 1)

The polypeptide of claim 1, as set forth in SEQ ID NO: 159.

### Claim 7 (depends on 1)

The polypeptide of claim 1, wherein said polypeptide inhibits binding of at least one chemokine to a chemokine receptor.

### Claim 8 (depends on 1)

The polypeptide of claim 1, wherein said polypeptide inhibits eotaxin-dependent T cell adhesion.

### Claim 9

An isolated polypeptide having the formula:
W—X—Y—Z
wherein:
W is a signal peptide;
X is a chemokine-binding peptide as set forth in SEQ ID NO: 76;
Y is a linker; and
Z is an Fc domain or fragment thereof.

### Claim 10 (depends on 9)

The polypeptide of claim 9, wherein said linker is an amino acid linker.

### Claim 11 (depends on 9)

The polypeptide of claim 9, wherein said signal peptide comprises an IL-6 signal peptide.

### Claim 12 (depends on 9)

The polypeptide of claim 9, as set forth in SEQ ID NO: 159.

### Claim 13 (depends on 9)

The polypeptide of claim 9, wherein said polypeptide inhibits binding of at least one chemokine to a chemokine receptor.

### Claim 14 (depends on 9)

The polypeptide of claim 9, wherein said polypeptide inhibits eotaxin-dependent T cell adhesion.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising the polypeptide of claim 1, and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 9)

A pharmaceutical composition comprising the polypeptide of claim 9, and a pharmaceutically acceptable carrier.

### Claim 17 (depends on 1)

A method of treating a condition selected from the group consisting of an inflammation, an allergy, delayed type hypersensitivity, a non-optimal immune response, abnormal cell migration, an autoimmune reaction, rheumatoid arthritis, systemic lupus erythematosis, multiple sclerosis, an allograft rejection, diabetes, sepsis, cancer, cancer metastasis, a malignant cell growth, a bacterial infection, a viral infection, arthritis, colitis, psoriasis, atherosclerosis, hypertension, myasthenia gravis and reperfusion ischemia, the method comprising administering the polypeptide of claim 1 to a subject in need thereof, thereby treating the condition.

### Claim 18 (depends on 9)

A method of treating a condition selected from the group consisting of an inflammation, an allergy, delayed type hypersensitivity, a non-optimal immune response, abnormal cell migration, an autoimmune reaction, rheumatoid arthritis, systemic lupus erythematosis, multiple sclerosis, an allograft rejection, diabetes, sepsis, cancer, cancer metastasis, a malignant cell growth, a bacterial infection, a viral infection, arthritis, colitis, psoriasis, atherosclerosis, hypertension, myasthenia gravis and reperfusion ischemia, the method comprising administering the polypeptide of claim 9 to a subject in need thereof, thereby treating the condition.

### Claim 19 (depends on 1)

A conjugate comprising the polypeptide of claim 1 attached to a water-soluble polymer.

### Claim 20 (depends on 9)

A conjugate comprising the polypeptide of claim 9 attached to a water-soluble polymer.