# US 12,180,288 B2 · Antibodies to canine interleukin-4 receptor alpha

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- Number: US 12,180,288 B2
- Document ID: US12180288B2
- Status: Granted
- Kind: B2
- Application number: 17/081,188
- Filed: 2020-10-27
- Published: 2021-02-11
- Granted: 2024-12-31
- Earliest claimed: 2015-04-02
- Assignees: Intervet Inc.
- Applicants: Intervet Inc.
- Inventors: Mohamad Morsey; Yuanzheng Zhang
- Web page: https://patentgrep.com/patent/US12180288B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 11/06: Antiasthmatics
- 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 37/06: 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 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/53: Hinge
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/71: Decreased effector function due to an Fc-modification
- 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

## Abstract

The present invention discloses antibodies and blocking antibodies to canine IL-4 receptor alpha that have specific sequences and a high binding affinity for canine IL-4 receptor α. The present invention also discloses the use of the antibodies of the present invention in the treatment of atopic dermatitis in dogs. The present invention further discloses unique epitopes that bind to the antibodies to canine IL-4 receptor alpha.

## Claims

### Claim 1

An antibody or antigen binding fragment thereof that binds to canine interleukin-4 receptor α (IL-4Rα), wherein the antibody or antigen binding fragment thereof comprises:
(i) a light chain variable region (VL) comprising a VL complementarity determining region (CDR) 1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO:120; and
(ii) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO:118.

### Claim 2 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises:
(a) a VL comprising: a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 129, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:134, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:137; and
(b) a VH comprising: a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 140, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:146, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:151.

### Claim 3 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 120.

### Claim 4 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:120.

### Claim 5 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 118.

### Claim 6 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:118.

### Claim 7 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 120; and a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:118.

### Claim 8 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:120; and a VH comprising the amino acid sequence of SEQ ID NO: 118.

### Claim 9 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment is a caninized antibody or a caninized antigen binding fragment.

### Claim 10 (depends on 9)

The antibody or antigen binding fragment thereof of claim 9, wherein the antibody or antigen binding fragment thereof comprises a hinge region selected from a canine IgGA hinge region, a canine IgGB hinge region, a canine IgGC hinge region, and a canine IgGD hinge region.

### Claim 11 (depends on 9)

The antibody or antigen binding fragment thereof of claim 9, wherein the antibody or antigen binding fragment thereof comprises a hinge region comprising the amino acid sequence of SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, and SEQ ID NO: 104.

### Claim 12 (depends on 9)

The antibody or antigen binding fragment thereof of claim 9, wherein the antibody or antigen binding fragment thereof comprises a canine fragment crystallizable (cFc) region selected from a canine IgGA Fc region, a canine IgGB Fc region, a canine IgGC Fc region, and a canine IgGD Fc region.

### Claim 13 (depends on 12)

The antibody or antigen binding fragment thereof of claim 12, wherein the cFc region is selected from a genetically modified canine IgGA Fc region, a genetically modified canine IgGB Fc region, a genetically modified canine IgGC Fc region, and a genetically modified canine IgGD Fc region.

### Claim 14 (depends on 13)

The antibody or antigen binding fragment thereof of claim 13, wherein the cFc region is a genetically modified canine IgGB Fc region comprising one or more of the amino acid substitution selected from P4A, D31A, N63A, G64P, T65A, A93G, and P95A in the native canine IgGB Fc region.

### Claim 15 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein when bound to canine IL-4Rα, binds to at least one amino acid residue within the amino acid sequence of SEQ ID NO:125, or at least one amino acid residue within the amino acid sequence of SEQ ID NO:126, or any combination thereof.

### Claim 16 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein when bound to canine IL-4Rα, blocks the binding of canine IL-4Rα to one or more of canine interleukin-4 and canine interleukin-13.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier or diluent.