Methods of selectively treating asthma using il-13 antagonists

Abstract

The disclosure is directed to novel predictive methods and personalized therapies for treating asthma. Specifically, this disclosure relates to methods of treating a patient having asthma by selectively administering an IL-13 antagonist, on the basis of that patient being genetically predisposed to have a favorable response to treatment with the IL-13 antagonist. Also disclosed herein are transmittable forms of information, diagnostic methods, and kits useful in predicting the likelihood that a patient having asthma will respond to treatment with an IL-13 antagonist.

1 .- 22 . (canceled) 
     
     
         23 . A method of selectively treating a patient having asthma, comprising
 i. identifying a patient having at least one AIR marker selected from the group consisting of AIR marker-1, 2, 3, 4, 5, 6, 7, 8, and 9,   ii. determining whether the patient is homozygous or heterozygous for said AIR marker, and   iii. selectively administering a therapeutically effective amount of an IL-13 antagonist to the patient that is
 a. homozygous for one of AIR marker 3 and AIR marker 7 and heterozygous at the other; 
 b. homozygous for both AIR marker 3 and AIR marker 7; or 
 c. homozygous for AIR marker 3, and 
   thereafter administering a therapeutically effective amount of the IL-13 antagonist to the patient.   
     
     
         24 . The method according to  claim 23 , wherein said identification comprises assaying a biological sample from the patient for the presence of at least one AIR marker selected from said group. 
     
     
         25 . The method according to  claim 24 , wherein the step of assaying comprises assaying the biological sample for a nucleic acid product of the at least one AIR marker, or a polypeptide product of the at least one AIR marker. 
     
     
         26 . The method according to  claim 24 , wherein the step of assaying comprises assaying the biological sample for a genomic sequence of the at least one AIR marker. 
     
     
         27 . The method according to  claim 24 , wherein the biological sample is selected from the group consisting of blood, serum, feces, plasma, urine, tear, saliva, and a tissue sample. 
     
     
         28 . The method according to  claim 24 , wherein the step of assaying comprises a technique selected from the group consisting of Northern blot analysis, polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), TaqMan-based assays, direct sequencing, dynamic allele-specific hybridization, high-density oligonucleotide SNP arrays, restriction fragment length polymorphism (RFLP) assays, primer extension assays, oligonucleotide ligase assays, analysis of single strand conformation polymorphism, temperature gradient gel electrophoresis (TGGE), denaturing high performance liquid chromatography, high-resolution melting analysis, DNA mismatch-binding protein assays, SNPLex®, capillary electrophoresis, Southern Blot, immunoassays, immunohistochemistry, ELISA, flow cytometry, Western blot, HPLC, and mass spectrometry. 
     
     
         29 . The method according to  claim 23 , wherein said IL-13 antagonist competes with antibody 01951/G12 (SEQ ID NO:14 and 16) for binding to IL-13 under conditions that promotes said competition. 
     
     
         30 . The method according to  claim 23 , wherein said IL-13 antagonist is a polypeptide or a fragment thereof, an antibody or an antigen binding fragment thereof, a Fab, an ScFv. 
     
     
         31 . The method according to  claim 23 , wherein said IL-13 antagonist is an antibody or a fragment thereof that binds to an epitope of IL-13 comprising residues FCPHKV (SEQ ID NO: 67) set forth as residues 103 to 108 of SEQ ID NO: 1. 
     
     
         32 . The method according to  claim 23 , wherein said IL-13 antagonist is an antibody comprising a heavy chain as set forth in SEQ ID NO: 20 and a light chain as recited in SEQ ID NO: 18. 
     
     
         33 . The method according to  claim 23 , wherein said IL-13 antagonist is an antibody administered at a dose of about 50-1000mg i.v. administered every 4 weeks. 
     
     
         34 . The method according to  claim 23 , wherein the IL-13 antagonist has a K D  of about 100-200 pM. 
     
     
         35 . The method according to  claim 23 , wherein the IL-13 antagonist has an in vivo half-life of about 21 days. 
     
     
         36 . The method according to  claim 23 , wherein the IL-13 antagonist is an antibody selected from the group consisting of
 i. an antibody comprising one or more of the CDRs selected from the list consisting of: (a) the V H  CDR1s shown in SEQ ID NOs: 2 or 5 (b) the V H  CDR2s shown in SEQ ID NOs: 3 or 6, (c) the V H  CDR3s shown in SEQ ID NOs: 4 or 7 (d) the V L  CDR1s shown in SEQ ID NOs: 8 or 11, (e) the V L  CDR2s shown in SEQ ID NOs:   9 or 12, (f) the V L  CDR3s shown in SEQ ID NOs: 10 or 13;   ii. an antibody comprising a heavy chain variable region CDR1 of SEQ ID NO: 2; a heavy chain variable region CDR2 of SEQ ID NO: 3; a heavy chain variable region CDR3 of SEQ ID NO: 4; a light chain variable region CDR1 of SEQ ID NO: 8; a light chain variable region CDR2 of SEQ ID NO: 9; and a light chain variable region CDR3 of SEQ ID NO: 10;   iii. an antibody comprising a heavy chain variable region CDR1 of SEQ ID NO: 5; a heavy chain variable region CDR2 of SEQ ID NO: 6; a heavy chain variable region CDR3 of SEQ ID NO: 7; a light chain variable region CDR1 of SEQ ID NO: 11; a light chain variable region CDR2 of SEQ ID NO: 12; and a light chain variable region CDR3 of SEQ ID NO: 13,   iv. an antibody comprising a heavy chain variable region as recited in SEQ ID NO: 14 and a light chain variable region as recited in SEQ ID NO: 16,   v. an antibody comprising a heavy chain as recited in SEQ ID NO: 20 and a light chain as recited in SEQ ID NO: 18.   
     
     
         37 . A method of selectively treating a patient having asthma , comprising
 i. assaying a biological sample from the patient for the presence or absence of at least one AIR marker selected from said group consisting of AIR marker-1, 2, 3, 4, 5, 6, 7, 8, and 9,   ii. detecting the presence of at least one AIR marker selected from said group in said sample and thereby determining that the patient is positive for said AIR marker,   iii. determining whether the patient is homozygous or heterozygous for said AIR marker, and   iv. selectively administering a therapeutically effective amount of an IL-13 antagonist to the patient that is
 a. homozygous for one of AIR marker 3 and AIR marker 7 and heterozygous at the other; 
 b. homozygous for both AIR marker 3 and AIR marker 7; or homozygous for AIR marker 3, and 
 v. selectively administering a therapeutically effective amount of an IL-13 antagonist to the patient that is positive.