# US 8,540,993 B2 · Methods of treatment using IL-18 receptor antigen binding proteins

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- Number: US 8,540,993 B2
- Document ID: US8540993B2
- Status: Granted
- Kind: B2
- Application number: 13/589,984
- Filed: 2012-08-20
- Published: 2013-02-07
- Granted: 2013-09-24
- Earliest claimed: 2007-07-24
- Assignees: Amgen Inc.
- Applicants: Dirk E. Smith; John E. Sims; Jeffrey T. McGrew; Marek Z. Kubin; Duncan Cochrane; Louise Conroy
- Inventors: Dirk E. Smith; John E. Sims; Jeffrey T. McGrew; Marek Z. Kubin; Duncan Cochrane; Louise Conroy
- Web page: https://patentgrep.com/patent/US8540993B2

## 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 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/02: Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/18: for HIV
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- 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 2317/76: 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

Provided herein are IL-18 receptor antigen binding proteins and polynucleotides encoding the same. Expression vectors and host cells comprising the same for production of the antigen binding proteins are also provided. In addition, provided are compositions and methods for diagnosing and treating diseases mediated by IL-18 receptor.

## Claims

### Claim 1

A method for treating a condition associated with IL-18 receptor in a patient, comprising administering to a patient in need thereof a pharmaceutical composition comprising an antigen binding protein that binds the IL-18 receptor, wherein said antigen binding protein comprises:
an antibody heavy chain comprising (a) a CDRH1 of SEQ ID NO:104; (b) a CDRH2 of SEQ ID NO:105; and (c) a CDRH3 of SEQ ID NO:106; and
an antibody light chain comprising (a) a CDRL1 of SEQ ID NO:173; (b) a CDRL2 of SEQ ID NO:174; and (c) a CDRL3 of SEQ ID NO:175.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody heavy chain comprises SEQ ID NO:6.

### Claim 3 (depends on 2)

The method of claim 2, wherein the antibody heavy chain comprises SEQ ID NO:73.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antibody light chain comprises SEQ ID NO:29.

### Claim 5 (depends on 4)

The method of claim 4, wherein the antibody light chain comprises SEQ ID NO:75.

### Claim 6 (depends on 1)

The method of claim 1, wherein the antibody heavy chain comprises SEQ ID NO:6 and the antibody light chain comprises SEQ ID NO:29.

### Claim 7 (depends on 1)

The method of claim 1, wherein the antibody heavy chain comprises SEQ ID NO:73 and the antibody light chain comprises SEQ ID NO:75.

### Claim 8 (depends on 1)

The method of claim 1 wherein the condition is selected from the group consisting of an autoimmune disease, a hepatic disease, a pancreatic disease, pulmonary disease, and a cardiovascular disease.

### Claim 9 (depends on 8)

The method of claim 8, wherein said autoimmune disease is selected from the group consisting of psoriasis, rheumatoid arthritis, lupus, Type I diabetes, Crohn's disease, inflammatory bowel disease, multiple sclerosis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, and sarcoidosis.

### Claim 10 (depends on 8)

The method of claim 8, wherein said hepatic disease is hepatitis.

### Claim 11 (depends on 8)

The method of claim 8, wherein said pancreatic disease is chronic pancreatitis or acute pancreatitis.

### Claim 12 (depends on 8)

The method of claim 8, wherein said cardiovascular disease is selected from the group consisting of heart disease including acute heart attacks, atheromatous plaque rupture, post-ischemic heart failure, reperfusion injury, vascular inflammation, and atherogenesis.

### Claim 13 (depends on 8)

The method of claim 8, wherein the pulmonary disease is selected from the group consisting of chronic obstructed pulmonary disease, chronic severe asthma, and acute respiratory distress syndrome.

### Claim 14

A method of inhibiting the binding of IL-18 to IL-18 receptor comprising contacting an IL-18 receptor with an antigen binding protein comprising:
an antibody heavy chain comprising (a) a CDRH1 of SEQ ID NO:104; (b) a CDRH2 of SEQ ID NO:105; and (c) a CDRH3 of SEQ ID NO:106; and
an antibody light chain comprising (a) a CDRL1 of SEQ ID NO:173; (b) a CDRL2 of SEQ ID NO:174; and (c) a CDRL3 of SEQ ID NO:175,
wherein said antigen binding protein binds said IL-18 receptor and prevents binding of said IL-18 receptor to IL-18.