# US 10,479,830 B2 · Anti eotaxin-2 antibodies that recognize additional CCR3-binding chemokines

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- Number: US 10,479,830 B2
- Document ID: US10479830B2
- Status: Granted
- Kind: B2
- Application number: 16/270,231
- Filed: 2019-02-07
- Published: 2019-05-23
- Granted: 2019-11-19
- Earliest claimed: 2014-03-04
- Assignees: Chemomab Ltd.
- Applicants: Chemomab Ltd.
- Inventors: Adi Mor
- Web page: https://patentgrep.com/patent/US10479830B2

## CPC

- C07K 16/24: against cytokines, lymphokines or interferons
- A61P 1/10: Laxatives
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- 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
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- 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 invention concerns isolated polyspecific antibodies directed to a unique epitope in the chemokine eotaxin 2, whereby the antibodies bind additional CCR3-binding chemokines. The invention further concerns use of these antibodies for attenuating the migration of various cells and for treating fibrotic diseases, autoimmune inflammatory disorders, monocyte related disorders or allergic atopic disorders.

## Claims

### Claim 1

An isolated antibody that binds a conformational epitope in the N-loop region of a CCR3-binding chemokine, wherein said conformational epitope is characterized by a relatively high concentration of positive amino acid residues located between amino acid positions 14 and 24 in the amino acid sequence of said CCR3-binding chemokine as denoted by SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 14 and wherein said antibody is a fully humanized antibody comprising a heavy chain variable region comprising:
a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 5;
b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 6; and
c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 7; and
a light chain variable region comprising
d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 8;
e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 9; and
f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 10.

### Claim 2 (depends on 1)

The isolated antibody of claim 1, wherein said conformational epitope comprises at least three positive amino acid residues between amino acid positions 14 and 24 in the amino acid sequence of said CCR3-binding chemokine as denoted by SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 14.

### Claim 3 (depends on 1)

The isolated antibody of claim 1, wherein said positive amino acid residues are selected from the group consisting of Arg, Lys and His.

### Claim 4 (depends on 1)

The isolated antibody of claim 1, wherein the conformational epitope comprises an amino acid sequence selected from: the amino acid sequences denoted by SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18 or SEQ ID NO: 19.

### Claim 5 (depends on 1)

The isolated antibody of claim 1, wherein said antibody is a polyspecific antibody, or any antigen-binding fragment thereof, that binds to at least two CCR3-binding chemokines.

### Claim 6 (depends on 5)

The isolated antibody of claim 5, wherein said antigen-binding fragment thereof is selected from the group consisting of Fv, single chain Fv (scFv), heavy chain variable region capable of binding the antigen, light chain variable region capable of binding the antigen, Fab, F(ab)2′ and any combination thereof.

### Claim 7 (depends on 5)

The isolated antibody of claim 5, wherein said antibody binds Eotaxin 1, Eotaxin-2, Rantes and MCP-3.

### Claim 8 (depends on 5)

The isolated antibody of claim 5, wherein said antibody attenuates the migratory properties of CCR3, CCR1, CCR2 and CCR5 expressing cells.

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

The isolated antibody of claim 1, wherein said antibody is a fully humanized antibody comprising the heavy chain variable region denoted by SEQ ID NO:3 and the light chain variable region denoted by SEQ ID NO: 4.

### Claim 11

An isolated fully humanized antibody comprising a heavy chain variable region comprising:
a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 5;
b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 6; and
c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 7; and
a light chain variable region comprising
d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 8;
e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 9; and
f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 10, wherein said antibody binds Eotaxin 1, Eotaxin-2, Rantes and/or MCP-3.

### Claim 12

An isolated fully humanized antibody comprising the heavy chain variable region denoted by SEQ ID NO:3 and the light chain variable region denoted by SEQ ID NO: 4, wherein said antibody binds Eotaxin 1, Eotaxin-2, Rantes and/or MCP-3.