# US 2013/0157313 A1 · High affinity antibodies to human il-6 receptor

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- Number: US 2013/0157313 A1
- Document ID: US20130157313A1
- Status: Published application
- Kind: A1
- Application number: 13/450,011
- Filed: 2012-04-18
- Published: 2013-06-20
- Earliest claimed: 2006-06-02
- Assignees: Regeneron Pharmaceuticals, Inc.
- Inventors: Sean Stevens; Tammy T. Huang; Joel H. Martin; Jeanette L. Fairhurst; Ashique Rafique; Eric Smith; Kevin J. Pobursky; Nicholas J. Papadopoulos; James P. Fandl; Gang Chen; Margaret Karow
- Web page: https://patentgrep.com/patent/US20130157313A1

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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 37/02: Immunomodulators
- A61K 2039/505: {comprising antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/21: from primates, e.g. man
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- 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

A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a KD of about 500 pM or less and blocks IL-6 activity with an IC50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.

## Claims

### Claim 1

An isolated nucleic acid molecule encoding an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody or antibody fragment comprises three heavy chain complementarity determining region (CDR) sequences and three light chain CDR sequences, wherein the three heavy chain CDR sequences comprise a combination selected from the group consisting of SEQ ID NO:149, 151 and 153; SEQ ID NO:5, 7 and 9; and SEQ ID NO:181, 183 and 185; and wherein the three light chain CDR sequences comprise a combination selected from the group consisting of SEQ ID NO:157, 159 and 161; SEQ ID NO:13, 15 and 17; and SEQ ID NO:189, 191 and 193.

### Claim 2 (depends on 1)

The nucleic acid molecule of claim 1, wherein the antibody or antibody fragment comprises a CDR sequence combination selected from the group consisting of SEQ ID NO:149, 151, 153, 157, 159 and 161; SEQ ID NO:5, 7, 9, 13, 15 and 17; and SEQ ID NO:181, 183, 185, 189, 191 and 193.

### Claim 3 (depends on 1)

The nucleic acid molecule of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:147, 3 or 179.

### Claim 4 (depends on 1)

The nucleic acid molecule of claim 1, wherein the antibody or antibody fragment comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:155, 11 or 187.

### Claim 5 (depends on 1)

A recombinant expression vector comprising the nucleic acid molecule of claim 1.

### Claim 6 (depends on 5)

An isolated host cell comprising the expression vector of claim 5.

### Claim 7 (depends on 6)

The host cell of claim 6 being a prokaryotic cell or an eukaryotic cell.

### Claim 8 (depends on 7)

The host cell of claim 7, wherein the prokaryotic cell is an E. coli cell and the eukaryotic cell is a CHO cell.

### Claim 9 (depends on 6)

A method of producing an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), comprising growing the host cell of claim 6 under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced.

### Claim 10

An isolated nucleic acid molecule encoding an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody or antibody fragment comprises a heavy chain variable region (HCVR) comprising SEQ ID NO:147, 3 or 179.

### Claim 11 (depends on 10)

The nucleic acid molecule of claim 10, comprising the nucleotide sequence of SEQ ID NO:146, or 178.

### Claim 12 (depends on 10)

The nucleic acid molecule of claim 10, wherein the antibody or antibody fragment further comprises a light chain variable region (LCVR) comprising SEQ ID NO:155, 11 or 187.

### Claim 13 (depends on 12)

The nucleic acid molecule of claim 12, wherein the antibody or antibody fragment comprises a HCVR/LCVR pair selected from the group consisting of SEQ ID NO:147/155, 3/11 and 179/187.

### Claim 14 (depends on 13)

A recombinant expression vector comprising the nucleic acid molecule of claim 13.

### Claim 15 (depends on 14)

An isolated host cell comprising the expression vector of claim 14.

### Claim 16 (depends on 15)

The host cell of claim 15 being a prokaryotic cell or an eukaryotic cell.

### Claim 17 (depends on 16)

The host cell of claim 16, wherein the prokaryotic cell is an E. coli cell and the eukaryotic cell is a CHO cell.

### Claim 18 (depends on 15)

A method of producing an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), comprising growing the host cell of claim 15 under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced.

### Claim 19

An isolated nucleic acid molecule encoding an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody or antibody fragment comprises a light chain variable region (LCVR) comprising SEQ ID NO:155, 11 or 187.

### Claim 20 (depends on 19)

The nucleic acid molecule of claim 19, comprising the nucleotide sequence of SEQ ID NO:154, or 186.
