# US 8,785,153 B2 · Antibodies against human IL33R and uses thereof

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- Number: US 8,785,153 B2
- Document ID: US8785153B2
- Status: Granted
- Kind: B2
- Application number: 13/402,399
- Filed: 2012-02-22
- Published: 2012-08-23
- Granted: 2014-07-22
- Earliest claimed: 2011-02-23
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Georg Fertig; Jens Fischer; Guy Georges; Klaus Kaluza; Valeria Lifke; Joerg Moelleken; Sonja Offner; Achal Pashine; Stefan Seeber
- Inventors: Georg Fertig; Jens Fischer; Guy Georges; Klaus Kaluza; Valeria Lifke; Joerg Moelleken; Sonja Offner; Achal Pashine; Stefan Seeber
- Web page: https://patentgrep.com/patent/US8785153B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 11/06: Antiasthmatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- 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
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/30: characterized by aspects of specificity or valency
- 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

An antibody binding to IL33R characterized in that the heavy chain variable domain comprises a CDR3 region of SEQ ID NO:1, a CDR2 region of SEQ ID NO:2 and a CDR1 region of SEQ ID NO:3 and in that the light chain variable domain comprises a CDR3 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5 and a CDR1 region of SEQ ID NO:6 or a chimeric, humanized or T cell epitope depleted antibody variant thereof has advantageous properties for the treatment of inflammatory diseases.

## Claims

### Claim 1

An anti-human IL33R antibody, wherein said antibody has a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31.

### Claim 2 (depends on 1)

The antibody according to claim 1, wherein the heavy chain variable domain comprises SEQ ID NO:21.

### Claim 3 (depends on 2)

The antibody according to claim 2, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30.

### Claim 4 (depends on 1)

The antibody according to claim 1, which is a chimeric antibody, a humanized antibody or a T cell epitope-depleted antibody.

### Claim 5

An anti-human IL33R antibody having a human IgG1 or IgG4 isotype but modified in the hinge region at one or more amino acid position between 216-240, and/or in the second inter-domain region at one or more amino acid position between 327-331 between CH2 and CH3, wherein said antibody is selected from:
a) An anti-human IL33R antibody comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31;
b) An anti-human IL33R antibody, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30; or
c) An anti-human IL33R antibody according to a) or b), which is a chimeric antibody, a humanized antibody or a T cell epitope-depleted antibody.

### Claim 6 (depends on 5)

An anti-human IL33R antibody according to claim 5, wherein said hinge region is modified by replacing the amino acid at position 234 and the amino acid at position 235 with alanine.

### Claim 7 (depends on 5)

An anti-human IL33R antibody according to claim 5, wherein said hinge region is modified by replacing the amino acid at position 235 and the amino acid at position 228 with glutamic acid and proline, respectively.

### Claim 8

A pharmaceutical composition comprising an anti-human IL33R antibody, wherein said antibody is selected from:
a) An anti-human IL33R antibody comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31;
b) An anti-human IL33R antibody, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30; or
c) An anti-human IL33R antibody according to a) or b) having a human IgG1 or IgG4 isotype but modified in the hinge region at one or more amino acid position between 216-240, and/or in the second inter-domain region at one or more amino acid position between 327-331 between CH2 and CH3;
d) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 234 and the amino acid at position 235 with alanine; or
e) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 235 and the amino acid at position 228 with glutamic acid and proline, respectively;
and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 3, 8)

A pharmaceutical composition according to claim 8, wherein the antibody binds to the same IL33R epitope to which the antibody according to claim 3 binds.

### Claim 10

A nucleic acid encoding a heavy chain of an antibody binding to IL33R, wherein said antibody comprises a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprises a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31.

### Claim 11

An expression vector comprising a nucleic acid encoding an anti-human IL33R antibody or antigen binding fragment thereof selected from:
a) An anti-human IL33R antibody comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31;
b) An anti-human IL33R antibody, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30;
c) An anti-human IL33R antibody according to a) or b) having a human IgG1 or IgG4 isotype but modified in the hinge region at one or more amino acid position between 216-240, and/or in the second inter-domain region at one or more amino acid position between 327-331 between CH2 and CH3;
d) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 234 and the amino acid at position 235 with alanine; or
e) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 235 and the amino acid at position 228 with glutamic acid and proline, respectively.

### Claim 12 (depends on 11)

The vector according to claim 11, wherein the vector is capable of expressing the anti-human IL33R antibody or antigen binding fragment thereof in a host cell.

### Claim 13 (depends on 11)

A host cell comprising a vector according to claim 11.

### Claim 14 (depends on 13)

The host cell of claim 13 wherein the host cell is a prokaryotic cell.

### Claim 15 (depends on 13)

The host cell of claim 13 wherein the host cell is a eukaryotic cell.

### Claim 16 (depends on 13)

A method for producing a recombinant anti-human IL33R antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31, said method comprising culturing a host cell according to claim 13 and recovering said antibody from said cell or the cell culture supernatant.