Methods for treating or preventing asthma by administering an IL-4R antagonist

Patent metadata

Field	Value
Publication number	US-9574004-B2
Application number	US-201313971334-A
Country	US
Kind code	B2
Filing date	Aug 20, 2013
Priority date	Aug 21, 2012
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

The present invention provides methods for treating or preventing asthma and associated conditions in a patient. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody.

First claim

What is claimed is:

1. A method for the treatment of persistent asthma that reduces the incidence of asthma exacerbations or improves one or more asthma-associated parameter(s) in a subject with persistent asthma comprising sequentially administering to the subject a single initial dose of a pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof specifically binds an interleukin-4 receptor (IL-4R), and wherein administration of the single initial dose is followed by one or more secondary doses of the pharmaceutical composition comprising the antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises heavy chain and light chain complementarity determining region (CDR) sequences from a heavy chain variable region (HCVR)/light chain variable region (LCVR) sequence pair of SEQ ID NOs: 162/164.

2. The method of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain comprising heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150, and 152, respectively, and a light chain comprising light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158, and 160, respectively.

3. The method of claim 1 , wherein each of the initial dose and the secondary doses comprise 75 mg to 600 mg of the antibody or antigen-binding fragment thereof.

4. The method of claim 1 , wherein the pharmaceutical composition is administered to the subject systemically, subcutaneously, intravenously, or intranasally.

5. The method of claim 1 , wherein the pharmaceutical composition comprising an antibody or antigen-binding fragment thereof is an add-on treatment to medium-to-high dose inhaled corticosteroid (ICS) and a second controller medication.

6. The method of claim 5 , wherein the second controller medication is selected from the group consisting of: a Tumor Necrosis Factor (TNF) inhibitor, an interleukin-1 (IL-1) inhibitor, an interleukin 5 (IL-5) inhibitor, an interleukin-1 (IL-8) inhibitor, an immunoglobulin E (IgE) inhibitor, a leukotriene inhibitor, a corticosteroid, a methylxanthine, a non-steroidal anti-inflammatory drug (NSAID), nedocromil sodium, cromolyn sodium, a long-acting beta2 agonist (LABA), an anti-fungal agent, and a combination thereof.

7. The method of claim 1 , wherein each secondary dose is administered 1 to 8 weeks after the immediately preceding dose.

8. The method of claim 1 , wherein at least 8 secondary doses of the antibody or antigen-binding fragment thereof that specifically binds an interleukin-4 receptor (IL-4R) are administered to the subject, and wherein each secondary dose is administered 1 week after the immediately preceding dose.

9. The method of claim 1 , wherein the expression level of one or more gene products selected from the group consisting of thymus and activation-regulated chemokine (TARC), IgE, eotaxin-3, periostin, carcinoembryonic antigen (CEA), and YKL-40 is reduced in the subject relative to baseline expression.

10. A method for the treatment of persistent asthma that reduces or eliminates an asthma patient's dependence on inhaled corticosteroids (ICS) and/or long-acting beta-agonists (LABA) for the treatment of one or more asthma exacerbations comprising:
(a) selecting a patient with persistent asthma who has moderate-to-severe asthma that is uncontrolled with a background asthma therapy comprising an ICS, a LAB A, or a combination thereof;
(b) administering to the patient a defined dose of an antibody or antigen-binding fragment thereof that specifically binds to an Interleukin-4 receptor (IL-4R) at a defined frequency for an initial treatment period while maintaining the patient's background asthma therapy for the initial treatment period; and
(c) gradually reducing or eliminating the dosage of ICS and/or LABA administered to the patient over the course of a subsequent treatment period while continuing to administer the antibody or antigen-binding fragment thereof at the defined frequency and dose used during the initial treatment period,
wherein the antibody or antigen-binding fragment thereof comprises heavy chain and light chain complementarity determining region (CDR) sequences from a heavy chain variable region (HCVR)/light chain variable region (LCVR) sequence pair of SEQ ID NOs: 162/164.

11. The method of claim 10 , wherein the ICS is fluticasone, budesonide, or mometasone.

12. The method of claim 10 , wherein the LABA is salmeterol or formoterol.

13. The method of claim 10 , wherein the ICS/LAB A combination is fluticasone/salmeterol, budesonide/formoterol, or mometasone/formoterol.

14. The method of claim 10 , wherein the dosage of LABA is eliminated at the end of the initial treatment period.

15. The method of claim 10 , wherein the dosage of LABA and/or ICS is gradually reduced or eliminated over the course of 2 to 8 weeks.

16. The method of claim 10 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain comprising heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150, and 152, respectively, and a light chain comprising light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158, and 160, respectively.

17. The method of claim 10 , wherein each of the doses comprises 75 mg to 600 mg of the antibody or antigen-binding fragment thereof.

18. The method of claim 10 , wherein the pharmaceutical composition is administered to the subject systemically, subcutaneously, intravenously, or intranasally.

19. The method of claim 10 , wherein the expression level of one or more gene products selected from the group consisting of thymus and activation-regulated chemokine (TARC), IgE, eotaxin-3, periostin, carcinoembryonic antigen (CEA), and YKL-40 is reduced in the subject relative to baseline expression.

Assignees

• Sanofi Sa
• Regeneron Pharma
• Sanofi Biotechnology

Inventors

• Ardeleanu Marius
• Gandhi Namita A
• Graham Neil
• Kirkesseli Stephanie C
• Kundu Sudeep
• Rocklin Ross E
• Radin Allen
• Weinstein Steven P
• Hamilton Jennifer Davidson
• Ming Jeffrey

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/10

  Antimycotics · CPC title