# US 11,891,441 B2 · Human interleukin-4 receptor alpha antibodies

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,891,441 B2
- Document ID: US11891441B2
- Status: Granted
- Kind: B2
- Application number: 17/817,754
- Filed: 2022-08-05
- Published: 2023-03-02
- Granted: 2024-02-06
- Earliest claimed: 2021-08-05
- Assignees: Eli Lilly and Company
- Applicants: Eli Lilly and Company
- Inventors: Shane Krummen Atwell; Yiqing Feng; Maya Rachel Karta; Donmienne Leung; Songqing Na; Diana Isabel Ruiz; David John Stokell; Laura Anne Pelletier
- Web page: https://patentgrep.com/patent/US11891441B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 35/00: Antineoplastic agents
- C07K 16/06: from serum
- C07K 16/247: {IL-4}
- C07K 2317/21: from primates, e.g. man
- 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 2317/52: Constant or Fc region; Isotype
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- 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
- C12N 2015/8518: {expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles}
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure relates to antibodies that specifically bind human IL-4Rα, compositions comprising such IL-4Rα antibodies, and methods of using such IL-4Rα antibodies.

## Claims

### Claim 1

An antibody or antigen binding fragment thereof that specifically binds human IL-4Rα, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the VL comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein:
the HCDR1 comprises SEQ ID NO: 1;
the HCDR2 comprises SEQ ID NO: 2;
the HCDR3 comprises SEQ ID NO: 3;
the LCDR1 comprises SEQ ID NO: 4;
the LCDR2 comprises SEQ ID NO: 5; and
the LCDR3 comprises SEQ ID NO: 6.

### Claim 2 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the VH comprises SEQ ID NO: 7 and the VL comprises SEQ ID NO: 8.

### Claim 3

An antibody or antigen binding fragment thereof that specifically binds human IL-4Rα, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the VL comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein:
the HCDR1 comprises SEQ ID NO: 42;
the HCDR2 comprises SEQ ID NO: 2;
the HCDR3 comprises SEQ ID NO: 3;
the LCDR1 comprises SEQ ID NO: 22;
the LCDR2 comprises SEQ ID NO: 5; and
the LCDR3 comprises SEQ ID NO: 6.

### Claim 4 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the VH comprises SEQ ID NO: 44 and the VL comprises SEQ ID NO: 45.

### Claim 5 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody comprises:
i. a heavy chain (HC) comprising SEQ ID NO: 33 and a light chain (LC) comprising SEQ ID NO: 10;
ii. a heavy chain (HC) comprising SEQ ID NO: 35 and a light chain (LC) comprising SEQ ID NO: 10;
iii. a heavy chain (HC) comprising SEQ ID NO: 9 and a light chain (LC) comprising SEQ ID NO: 10;
iv. a heavy chain (HC) comprising SEQ ID NO: 13 and a light chain (LC) comprising SEQ ID NO: 10;
v. a heavy chain (HC) comprising SEQ ID NO: 31 and a light chain (LC) comprising SEQ ID NO: 10;
vi. a heavy chain (HC) comprising SEQ ID NO: 37 and a light chain (LC) comprising SEQ ID NO: 10;
vii. a heavy chain (HC) comprising SEQ ID NO: 52 and a light chain (LC) comprising SEQ ID NO: 10; or
viii. a heavy chain (HC) comprising SEQ ID NO: 50 and a light chain (LC) comprising SEQ ID NO: 10.

### Claim 6 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the antibody comprises a HC comprising SEQ ID NO: 46 and a LC comprising SEQ ID NO: 47.

### Claim 7 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody comprises a human IgG1 isotype.

### Claim 8 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the antibody comprises a human IgG1 isotype.

### Claim 9 (depends on 7)

The antibody or antigen binding fragment thereof of claim 7, wherein the antibody comprises an alanine at amino acid residue 322 (EU numbering).

### Claim 10 (depends on 8)

The antibody or antigen binding fragment thereof of claim 8, wherein the antibody comprises an alanine at amino acid residue 322 (EU numbering).

### Claim 11 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody comprises a human IgG4 isotype.

### Claim 12 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the antibody comprises a human IgG4 isotype.

### Claim 13 (depends on 11)

The antibody or antigen binding fragment thereof of claim 11, wherein the antibody comprises one or more of the following: a glycine at amino acid residue 137 (EU numbering); an asparagine at amino acid residue 203 (EU numbering); a lysine at amino acid residue 274 (EU numbering); an arginine at amino acid residue 355 (EU numbering); or a glutamine at amino acid residue 419 (EU numbering).

### Claim 14 (depends on 12)

The antibody or antigen binding fragment thereof of claim 12, wherein the antibody comprises one or more of the following: a glycine at amino acid residue 137 (EU numbering); an asparagine at amino acid residue 203 (EU numbering); a lysine at amino acid residue 274 (EU numbering); an arginine at amino acid residue 355 (EU numbering); or a glutamine at amino acid residue 419 (EU numbering).

### Claim 15 (depends on 11)

The antibody or antigen binding fragment thereof of claim 11, wherein the antibody comprises:
a lysine at amino acid residue 274 (EU numbering), an arginine at amino acid residue 355, and a glutamine at amino acid residue 419 (EU numbering).

### Claim 16 (depends on 12)

The antibody or antigen binding fragment thereof of claim 12, wherein the antibody comprises:
a lysine at amino acid residue 274 (EU numbering), an arginine at amino acid residue 355, and a glutamine at amino acid residue 419 (EU numbering).

### Claim 17 (depends on 11)

The antibody or antigen binding fragment thereof of claim 11, wherein the antibody comprises:
a glycine at amino acid residue 137 (EU numbering), an asparagine at amino acid residue 203 (EU numbering), a lysine at amino acid residue 274 (EU numbering), an arginine at amino acid residue 355, and a glutamine at amino acid residue 419 (EU numbering).

### Claim 18 (depends on 12)

The antibody or antigen binding fragment thereof of claim 12, wherein the antibody comprises:
a glycine at amino acid residue 137 (EU numbering), an asparagine at amino acid residue 203 (EU numbering), a lysine at amino acid residue 274 (EU numbering), an arginine at amino acid residue 355, and a glutamine at amino acid residue 419 (EU numbering).

### Claim 19

An antibody or antigen binding fragment thereof that specifically binds human IL-4Rα, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the VL comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein:
the HCDR1 comprises SEQ ID NO: 19;
the HCDR2 comprises SEQ ID NO: 20;
the HCDR3 comprises SEQ ID NO: 3;
the LCDR1 comprises SEQ ID NO: 22;
the LCDR2 comprises SEQ ID NO: 5; and
the LCDR3 comprises SEQ ID NO: 24.

### Claim 20 (depends on 19)

The antibody or antigen binding fragment thereof of claim 19, wherein the VH comprises SEQ ID NO: 25 and the VL comprises SEQ ID NO: 26.

### Claim 21 (depends on 19)

The antibody or antigen binding fragment thereof of claim 19, wherein the antibody comprises a HC comprising SEQ ID NO: 27 and a LC comprising SEQ ID NO: 28.

### Claim 22 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody comprises:
a cysteine at amino acid residue 124 (EU numbering);
a cysteine at amino acid residue 378 (EU numbering); or
a cysteine at amino acid residue 124 (EU numbering) and cysteine at amino acid residue 378 (EU numbering).

### Claim 23 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the antibody comprises:
a cysteine at amino acid residue 124 (EU numbering);
a cysteine at amino acid residue 378 (EU numbering); or
a cysteine at amino acid residue 124 (EU numbering) and cysteine at amino acid residue 378 (EU numbering).

### Claim 24 (depends on 19)

The antibody or antigen binding fragment thereof of claim 19, wherein the antibody comprises:
a cysteine at amino acid residue 124 (EU numbering);
a cysteine at amino acid residue 378 (EU numbering); or
a cysteine at amino acid residue 124 (EU numbering) and cysteine at amino acid residue 378 (EU numbering).

### Claim 25 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody inhibits binding of human IL-4 to human IL-4Rα.

### Claim 26 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the antibody inhibits binding of human IL-4 to human IL-4Rα.

### Claim 27 (depends on 19)

The antibody or antigen binding fragment thereof of claim 19, wherein the antibody inhibits binding of human IL-4 to human IL-4Rα.

### Claim 28 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein the antibody inhibits binding of human IL-13 to human IL-4Rα.

### Claim 29 (depends on 3)

The antibody or antigen binding fragment thereof of claim 3, wherein the antibody inhibits binding of human IL-13 to human IL-4Rα.

### Claim 30 (depends on 19)

The antibody or antigen binding fragment thereof of claim 19, wherein the antibody inhibits binding of human IL-13 to human IL-4Rα.

### Claim 31

A nucleic acid comprising a sequence encoding SEQ ID NO: 9, 10, 13, 27, 28, 31, 33, 35, 37, 46, 47, 50, or 52.

### Claim 32 (depends on 31)

A vector comprising the nucleic acid of claim 31.

### Claim 33 (depends on 32)

The vector of claim 32, wherein the vector comprises a first nucleic acid sequence encoding SEQ ID NO: 9, 13, 31, 33, 35, 37, 46, 50, or 52 and a second nucleic acid sequence encoding SEQ ID NO: 10 or 47.

### Claim 34 (depends on 32)

The vector of claim 32, wherein the vector comprises a first nucleic acid sequence encoding SEQ ID NO: 27, and a second nucleic acid sequence encoding SEQ ID NO: 28.

### Claim 35

A composition comprising a first vector comprising a nucleic acid sequence encoding SEQ ID NO: 9, 13, 31, 33, 35, 37, 46, 50, or 52 and a second vector comprising a nucleic acid sequence encoding SEQ ID NO: 10 or 47.

### Claim 36

A composition comprising a first vector comprising a nucleic acid sequence encoding SEQ ID NO: 27, and a second vector comprising a nucleic acid sequence encoding SEQ ID NO: 28.

### Claim 37 (depends on 32)

A cell comprising the vector of claim 32.

### Claim 38 (depends on 33)

A cell comprising the vector of claim 33.

### Claim 39 (depends on 34)

A cell comprising the vector of claim 34.

### Claim 40 (depends on 37)

The cell of claim 37, wherein the cell is a mammalian cell.

### Claim 41 (depends on 38)

The cell of claim 38, wherein the cell is a mammalian cell.

### Claim 42 (depends on 39)

The cell of claim 39, wherein the cell is a mammalian cell.

### Claim 43 (depends on 37)

A process of producing an antibody or antigen binding fragment thereof comprising culturing the cell of claim 37, under conditions such that the antibody is expressed and recovering the expressed antibody from the culture medium.

### Claim 44 (depends on 38)

A process of producing an antibody or antigen binding fragment thereof comprising culturing the cell of claim 38, under conditions such that the antibody is expressed and recovering the expressed antibody from the culture medium.

### Claim 45 (depends on 39)

A process of producing an antibody or antigen binding fragment thereof comprising culturing the cell of claim 39, under conditions such that the antibody is expressed and recovering the expressed antibody from the culture medium.

### Claim 46 (depends on 43)

An antibody or antigen binding fragment thereof produced by the process of claim 43.

### Claim 47 (depends on 44)

An antibody or antigen binding fragment thereof produced by the process of claim 44.

### Claim 48 (depends on 45)

An antibody or antigen binding fragment thereof produced by the process of claim 45.

### Claim 49 (depends on 1)

An antibody drug conjugate comprising the antibody of claim 1.

### Claim 50 (depends on 3)

An antibody drug conjugate comprising the antibody of claim 3.

### Claim 51 (depends on 19)

An antibody drug conjugate comprising the antibody of claim 19.

### Claim 52 (depends on 1)

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

### Claim 53 (depends on 3)

A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 3, and a pharmaceutically acceptable excipient, diluent, or carrier.

### Claim 54 (depends on 19)

A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 19, and a pharmaceutically acceptable excipient, diluent, or carrier.

### Claim 55 (depends on 1)

A method of treating an IL-4R associated disorder, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of claim 1.

### Claim 56 (depends on 3)

A method of treating an IL-4R associated disorder, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of claim 3.

### Claim 57 (depends on 19)

A method of treating an IL-4R associated disorder, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of claim 19.

### Claim 58 (depends on 55)

The method of claim 55, wherein IL-4R associated disorder is an immune inflammatory disorder.

### Claim 59 (depends on 56)

The method of claim 56, wherein IL-4R associated disorder is an immune inflammatory disorder.

### Claim 60 (depends on 57)

The method of claim 57, wherein IL-4R associated disorder is an immune inflammatory disorder.

### Claim 61 (depends on 58)

The method of claim 58, wherein the immune inflammatory disorder is a Type 2 inflammatory disorder.

### Claim 62 (depends on 59)

The method of claim 59, wherein the immune inflammatory disorder is a Type 2 inflammatory disorder.

### Claim 63 (depends on 60)

The method of claim 60, wherein the immune inflammatory disorder is a Type 2 inflammatory disorder.

### Claim 64 (depends on 61)

The method of claim 61, wherein the Type 2 inflammatory disorder is selected from atopic dermatitis, eosinophilic esophagitis, nasal polyposis, asthma, chronic rhinosinusitis (CRS), allergic disease, chronic obstructive pulmonary disease (COPD), or chronic spontaneous urticaria (CSU).

### Claim 65 (depends on 62)

The method of claim 62, wherein the Type 2 inflammatory disorder is selected from atopic dermatitis, eosinophilic esophagitis, nasal polyposis, asthma, chronic rhinosinusitis (CRS), allergic disease, chronic obstructive pulmonary disease (COPD), or chronic spontaneous urticaria (CSU).

### Claim 66 (depends on 63)

The method of claim 63, wherein the Type 2 inflammatory disorder is selected from atopic dermatitis, eosinophilic esophagitis, nasal polyposis, asthma, chronic rhinosinusitis (CRS), allergic disease, chronic obstructive pulmonary disease (COPD), or chronic spontaneous urticaria (CSU).

### Claim 67 (depends on 55)

The method of claim 55, wherein the IL-4R associated disorder is cancer.

### Claim 68 (depends on 56)

The method of claim 56, wherein the IL-4R associated disorder is cancer.

### Claim 69 (depends on 57)

The method of claim 57, wherein the IL-4R associated disorder is cancer.