Methods and compositions for treating asthma using anti-il-13 antibodies

Abstract

The invention provides methods and compositions for treating asthma, e.g., mild or moderate asthma, in a subject using an anti-IL-13 antibody, or antigen-binding portion thereof.

1 . An isolated composition comprising an anti-IL-13 antibody, or antigen-binding portion thereof, wherein, when administered intravenously to a subject at a dose of about 0.3 mg/kg, the antibody, or antigen-binding portion thereof, is capable of exhibiting:
 (a) an area under the curve (AUC) of between about 1,500 and about 2,700 μgh/ml;   (b) a volume of distribution of between about 65 and 125 mL/kg;   (c) a peak concentration (C max ) of between about 5 and about 8 μg/ml; and   (d) a clearance rate of between about 0.1 and about 0.2 ml/h/kg.   
     
     
         2 . An isolated composition comprising an anti-IL-13 antibody, or antigen-binding portion thereof, wherein, when administered intravenously to a subject at a dose of about 3 mg/kg, the antibody, or antigen-binding portion thereof, is capable of exhibiting:
 (a) an area under the curve (AUC) of between about 21,000 and about 33,500 μgh/ml;   (b) a volume of distribution of between about 55 and about 100 mL/kg;   (c) a peak concentration (C max ) of between about 55 and about 90 μg/ml; and   (d) a clearance rate of between about 0.08 and about 0.15 ml/h/kg.   
     
     
         3 . An isolated composition comprising an anti-IL-13 antibody, or antigen-binding portion thereof, wherein, when administered intravenously to a subject at a dose of about 10 mg/kg, the antibody, or antigen-binding portion thereof, is capable of exhibiting:
 (a) an area under the curve (AUC) of between about 75 and about 100 μgh/ml;   (b) a volume of distribution of between about 90 and about 130 mL/kg;   (c) a peak concentration (C max ) of between about 185 and about 250 μg/ml; and   (d) a clearance rate of between about 0.1 and about 0.15 ml/h/kg.   
     
     
         4 . An isolated composition comprising an anti-IL-13 antibody, or antigen-binding portion thereof, wherein, when administered subcutaneously to a subject at a dose of about 0.3 mg/kg, the antibody, or antigen-binding portion thereof, is capable of exhibiting:
 (a) an area under the curve (AUC) of between about 125 and about 800 μgh/ml; and   (b) a peak concentration (C max ) of between about 1.0 and about 6.0 μg/ml.   
     
     
         5 . An isolated composition comprising an anti-IL-13 antibody, or antigen-binding portion thereof, wherein, when administered subcutaneously to a subject at a dose of about 3 mg/kg, the antibody, or antigen-binding portion thereof, is capable of exhibiting:
 (a) an area under the curve (AUC) of between about 1,100 and about 8,500 μgh/ml; and   (b) a peak concentration (C max ) of between about 12 and about 60 μg/ml.   
     
     
         6 .- 7 . (canceled) 
     
     
         8 . A method of treating or preventing asthma in a subject comprising administering the composition of any one of  claims 1 - 5  to the subject, thereby treating or preventing asthma in said subject. 
     
     
         9 .- 14 . (canceled) 
     
     
         15 . A method of treating asthma in a subject comprising intravenously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a maximum serum concentration (C max ) of between about 5 and about 235 μg/mL, and   (b) an area under the serum concentration-time curve (AUC) of between about 1,500 and about 98,000 μgh/mL,   
       is achieved following administration of the antibody, or antigen-binding portion thereof to said subject. 
     
     
         16 . The method of  claim 15 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 0.3 mg/kg, optionally
 wherein the C max  is between about 5 and about 10 μg/mL, or   wherein the AUC is between about 1,500 and about 2,700 μgh/mL.   
     
     
         17 .- 18 . (canceled) 
     
     
         19 . The method of  claim 15 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 3 mg/kg, optionally
 wherein the C max  is between about 55 and about 90 μg/mL, or   wherein the AUC is between about 20,000 and about 34,000 μgh/mL.   
     
     
         20 .- 21 . (canceled) 
     
     
         22 . The method of  claim 15 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 10 mg/kg, optionally
 wherein the C max  is between about 190 and about 235 μg/mL, or   wherein the AUC is between about 75,000 and about 100,000 μgh/mL.   
     
     
         23 .- 26 . (canceled) 
     
     
         27 . A method of treating asthma in a subject comprising subcutaneously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a maximum serum concentration (C max ) of between about 1 and about 60 μg/mL, and   (b) an area under the serum concentration-time curve (AUC) of between about 125 and about 8,100 μgh/mL,   
       is achieved following administration of the antibody, or antigen-binding portion thereof to said subject. 
     
     
         28 . The method of  claim 27 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 0.3 mg/kg, optionally
 wherein the C max  is between about 1 and about 6 μg/mL, or   wherein the AUC is between about 100 and about 800 μgh/mL.   
     
     
         29 .- 30 . (canceled) 
     
     
         31 . The method of  claim 27 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 3 mg/kg, optionally
 wherein the C max  is between about 12 and about 60 μg/mL, or   wherein the AUC is between about 1,100 and about 8,100 μgh/mL.   
     
     
         32 .- 40 . (canceled) 
     
     
         41 . A method of treating asthma in a subject comprising subcutaneously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, at a dose of about 0.3 mg/kg, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a half-life of between about 24 and 31 days;   (b) a T max  of between about 3 and about 5 days; and   (c) a bioavailability of at least about 60%,   
       is achieved following administration of the antibody, or antigen-binding portion thereof to said subject. 
     
     
         42 . (canceled) 
     
     
         43 . A method of treating asthma in a subject comprising subcutaneously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, at a dose of about 3 mg/kg, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a half-life of between about 23 and 26 days;   (b) a T max  of less than or equal to about 5 days; and   (c) a bioavailability of at least about 60%,   
       is achieved following administration of the antibody, or antigen-binding portion thereof to said subject. 
     
     
         44 . (canceled) 
     
     
         45 . A method of treating asthma in a subject comprising intravenously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, at a dose of about 0.3 mg/kg, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a clearance rate of between about 0.11 to about 0.19 mL/hr/kg; and   (b) a volume of distribution of between about 70 to about 130 mL/kg is achieved following administration of the antibody, or antigen-binding portion thereof to said subject.   
     
     
         46 . A method of treating asthma in a subject comprising intravenously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, at a dose of about 3 mg/kg, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a clearance rate of between about 0.08 to about 0.14 mL/hr/kg; and   (b) a volume of distribution of between about 55 to about 100 mL/kg is achieved following administration of the antibody, or antigen-binding portion thereof to said subject.   
     
     
         47 . A method of treating asthma in a subject comprising intravenously administering to the subject an anti-IL-13 antibody, or antigen-binding portion thereof, at a dose of about 10 mg/kg, wherein at least one pharmacokinetic characteristic selected from the group consisting of:
 (a) a clearance rate of between about 0.09 to about 0.13 mL/hr/kg; and   (b) a volume of distribution of between about 85 to about 130 mL/kg is achieved following administration of the antibody, or antigen-binding portion thereof to said subject.   
     
     
         48 . The composition of  claim 1  or the method of  claim 41 , wherein the anti-IL-13 antibody, or antigen-binding portion thereof, is 13C5.5, or an antigen-binding portion thereof. 
     
     
         49 . The method of  claim 41 , wherein the anti-IL-13 antibody, or antigen-binding portion thereof, is administered once. 
     
     
         50 . The method of  claim 41 , wherein the anti-IL-13 antibody, or antigen-binding portion thereof, is administered weekly, optionally wherein the antibody, or antigen-binding portion thereof, is administered for 3 weeks. 
     
     
         51 .- 52 . (canceled) 
     
     
         53 . The method of  claim 41 , further comprising administering an additional agent to said subject, optionally wherein said additional agent is selected from the group consisting of: a therapeutic agent, an imaging agent, a cytotoxic agent, an angiogenesis inhibitor, a kinase inhibitor, a co-stimulation molecule blocker, an adhesion molecule blocker, an anti-cytokine antibody or functional fragment thereof; methotrexate, a cyclosporin, a rapamycin, an FK506, a detectable label or reporter, a TNF antagonist, an anti-rheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteroid, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an oral steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist. 
     
     
         54 . (canceled) 
     
     
         55 . The composition  claim 1  or the method of  claim 15 ,
 wherein said subject is a human, or 
 wherein the asthma is mild to moderate asthma. 
 
     
     
         56 .- 59 . (canceled)