# US 11,897,960 B2 · Anti-IL-4R antibody and use thereof

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- Number: US 11,897,960 B2
- Document ID: US11897960B2
- Status: Granted
- Kind: B2
- Application number: 17/049,288
- Filed: 2018-08-13
- Published: 2022-03-17
- Granted: 2024-02-13
- Earliest claimed: 2018-04-20
- Assignees: Beijing Wisdomab Biotechnology Co., Ltd; Genrix (Shanghai) Biopharmaceutical Co. Ltd.; Chongqing Genrix Biopharmaceutical Co., Ltd.
- Applicants: Beijing Wisdomab Biotechnology Co., Ltd; Genrix (Shanghai) Biopharmaceutical Co. Ltd.; Chongqing Genrix Biopharmaceutical Co., Ltd.
- Inventors: Zhigang Liu; Yulan Liu; Xiaobo Hao; Lei Jiang; Jingjing Guo
- Web page: https://patentgrep.com/patent/US11897960B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- 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)
- 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

Disclosed in the present application are an antibody or an antigen-binding portion thereof binding to human IL-4R, a polynucleotide encoding the antibody or antigen-binding portion thereof, a vector comprising the polynucleotide, a host cell comprising the polynucleotide or vector, a method for preparing and purifying the antibody, and the use of the antibody or antigen-binding portion thereof.

## Claims

### Claim 1

An antibody that binds to human IL-4R comprising a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 and a light chain variable region comprising LCDR1, LCDR2 and LCDR, wherein
the HCDR1 has the sequence of GFTFSSYAMS (SEQ ID NO: 33), the HCDR2 has the sequence of SITGGGGGIYYADSVKG (SEQ ID NO: 34), the HCDR3 has the sequence of DRISITIRPRYFGLDF (SEQ ID NO: 35), the LCDR1 has the sequence of RSSQSLLYSIGYNYLD (SEQ ID NO: 36), the LCDR2 has the sequence of LGSNRAS (SEQ ID NO: 37), and the LCDR3 has the sequence of MQSFKAPYT (SEQ ID NO: 38); or
the HCDR1 has the sequence of GFTFSSYAMS (SEQ ID NO: 33), the HCDR2 has the sequence of SITGGGGGIYYADSVKG (SEQ ID NO: 34), the HCDR3 has the sequence of DRISITIRPRYFGLDF (SEQ ID NO: 35), the LCDR1 has the sequence of RSSRNVIYGNGYNYLD (SEQ ID NO: 39), the LCDR2 has the sequence of LGNNVAA (SEQ ID NO: 40), and the LCDR3 has the sequence of MQSLQAPYT (SEQ ID NO: 41); or
the HCDR1 has the sequence of GFTFSSYAMS (SEQ ID NO: 33), the HCDR2 has the sequence of SITGGGGGIYYADSVKG (SEQ ID NO: 34), the HCDR3 has the sequence of DRISITIRPRYFGLDF (SEQ ID NO: 35), the LCDR1 has the sequence of RSSQNVYGNGYNYLD (SEQ ID NO: 42), the LCDR2 has the sequence of LGTNVAA (SEQ ID NO: 43), and the LCDR3 has the sequence of MQSLQAPYT (SEQ ID NO: 41); or
the HCDR1 has the sequence of GFTFSSYAMS (SEQ ID NO: 33), the HCDR2 has the sequence of SITGGGGGIYYADSVKG (SEQ ID NO: 34), the HCDR3 has the sequence of DRISITIRPRYFGLDF (SEQ ID NO: 35), the LCDR1 has the sequence of RSSQNVYGNGYNYLD (SEQ ID NO: 42), the LCDR2 has the sequence of LGNNVAA (SEQ ID NO: 40), and the LCDR3 has the sequence of MQSLKAPYT (SEQ ID NO: 44); or
the HCDR1 has the sequence of GFTFSSYAMS (SEQ ID NO: 33), the HCDR2 has the sequence of SITGGGGGIYYADSVKG (SEQ ID NO: 34), the HCDR3 has the sequence of DRISITIRPRYFGLDF (SEQ ID NO: 35), the LCDR1 has the sequence of RSSHNLLYSNGYNYLD (SEQ ID NO: 45), the LCDR2 has the sequence of LGSNRAY (SEQ ID NO: 46), and the LCDR3 has the sequence of MQALQSPYT (SEQ ID NO: 47);
the HCDR1 has the sequence of GFTFSSYAMS (SEQ ID NO: 33), the HCDR2 has the sequence of SITGGGGGIYYADSVKG (SEQ ID NO: 34), the HCDR3 has the sequence of DRISITIRPRYFGLDF (SEQ ID NO: 35), the LCDR1 has the sequence of RSSQSLLYSNGYNYLD (SEQ ID NO: 48), the LCDR2 has the sequence of LGSNRAS (SEQ ID NO: 37), and the LCDR3 has the sequence of MQALETPYA (SEQ ID NO: 49);
wherein the HCDR and LCDR are defined according to Kabat.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 26, 27, 28, 29, 30, or 31.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein
the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18, and the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 26; or
the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18, and the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 27; or
the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18, and the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 28; or
the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18, and the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 29; or
the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18, and the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 30; or
the heavy chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 18, and the light chain variable region of the antibody has the amino acid sequence of SEQ ID NO: 31.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein
the antibody is capable of binding to recombinant human IL4R (SEQ ID NO: 1) and recombinant monkey IL4R (SEQ ID NO: 3) and has a KD of less than 1 nM when binding to recombinant human IL4R.

### Claim 6 (depends on 1)

The antibody of claim 1, wherein the antibody is capable of inhibiting the activation of HEK-Blue IL-4/IL-13 cells by recombinant IL4 (SEQ ID NO: 4) with an IC50 value below 100 pM.

### Claim 7 (depends on 1)

The antibody of claim 1, wherein the antibody is capable of inhibiting the activation of HEK-Blue IL-4/IL-13 cells by recombinant IL13 (SEQ ID NO: 32) with an IC50 value below 50 pM.

### Claim 8 (depends on 1)

The antibody of claim 1, wherein the antibody is capable of inhibiting the proliferation of TF-1 cells induced by recombinant IL4 (SEQ ID NO: 4) with an IC50 value below 200 pM.

### Claim 9 (depends on 1)

The antibody of claim 1, wherein the antibody is an intact antibody, a Fab fragment, a F(ab′)2 fragment or a single chain Fv fragment (scFv).

### Claim 10 (depends on 1)

The antibody of claim 1, wherein the antibody further comprises a heavy chain constant region of an IgG1 subtype, an IgG2 subtype or an IgG4 subtype and/or a light chain constant region of a κ subtype or a λ subtype.

### Claim 11 (depends on 1)

The antibody of claim 1, wherein the antibody is a monoclonal antibody.

### Claim 12 (depends on 1)

The antibody of claim 1, wherein the antibody binds to and neutralizes human IL4R, thereby blocking IL4-IL4R and IL13-IL4R signaling pathways.

### Claim 13 (depends on 1)

A nucleic acid molecule encoding the antibody of claim 1.

### Claim 14 (depends on 1)

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

### Claim 15 (depends on 1)

A method of treating an IL-4R-mediated disease comprising administering to a subject in need thereof the antibody of claim 1.

### Claim 16 (depends on 15)

The method of claim 15, wherein the IL-4R-mediated disease is an autoimmune disease.

### Claim 17 (depends on 15)

The method of claim 15, wherein the IL-4R-mediated disease is asthma or allergic dermatitis.

### Claim 18 (depends on 1)

The antibody of claim 1, wherein the antibody is a fully human antibody.