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 . A method of selectively treating a patient having asthma, comprising
 i) measuring AIR marker selected from the group consisting of AIR marker-1, 2, 3, 4, 5, 6, 7, 8, and 9, and   ii) thereafter administering a therapeutically effective amount of an IL-13 antagonist to the patient.   
     
     
         2 . The method according to  claim 1 , wherein
 said identification comprises assaying a biological sample from the patient for the presence of at least one AIR marker selected from said group.   
     
     
         3 . A method of predicting the likelihood that a patient having asthma will respond to treatment with an IL-13 antagonist, comprising the step of assaying a biological sample from the patient for the presence or absence of at least one AIR marker selected from the group consisting of AIR marker-1, 2, 3, 4, 5, 6, 7, 8, and 9, wherein:
 a) the presence of the at least one AIR marker is indicative of an increased likelihood that the patient will respond to treatment with the IL-13 antagonist; and   b) the absence of the at least one AIR marker is indicative of a decreased likelihood that the patient will respond to treatment with the IL-13 antagonist.   
     
     
         4 . A method of predicting the likelihood that a patient having asthma will respond to treatment with an IL-13 antagonist, comprising the steps of:
 a) assaying a biological sample from the patient for the presence or absence of at least one AIR marker, and   b) determining whether said AIR marker is present in homozygous or heterozygous form, wherein   
       the presence of the at least one AIR marker in homozygous form is indicative of an increased likelihood that the patient will respond to treatment with the IL-13 antagonist, wherein said at least one AIR marker is selected from the group consisting of:
 i) AIR marker 3 and AIR marker 7 each present in homozygous form, 
 ii) AIR marker 3 present in homozygous form and AIR marker 7 in heterozygous form,
 a. AIR marker 7 present in homozygous form and AIR marker 3 in heterozygous form, and 
 b. AIR marker 3 in homozygous form. 
 
 
     
     
         5 . The method according to  claim 2 , 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. 
     
     
         6 . The method according to  claim 2 , wherein the step of assaying comprises assaying the biological sample for a genomic sequence of the at least one AIR marker. 
     
     
         7 . The method according to  claim 2 , wherein the biological sample is selected from the group consisting of blood, serum, feces, plasma, urine, tear, saliva, and a tissue sample. 
     
     
         8 . The method according to  claim 2 , 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), Taq Man-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, capillary electrophoresis, Southern Blot, immunoassays, immunohistochemistry, ELISA, flow cytometry, Western blot, HPLC, and mass spectrometry. 
     
     
         9 . The method according to  claim 1 , wherein said IL-13 antagonist is a polypeptide or a fragment thereof, an antibody or an antigen binding fragment thereof, a Fab, or an ScFv. 
     
     
         10 . The method according to  claim 1 , 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 107 of SEQID NO: 1. 
     
     
         11 . The method according to  claim 1 , 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. 
     
     
         12 . The method according to  claim 1 , wherein said IL-13 antagonist is an antibody administered at a dose of about 50-1000 mg i.v. administered every 4 weeks. 
     
     
         13 . The method according to  claim 1 , wherein the IL-13 antagonist has a K D  of about 100-200 pM. 
     
     
         14 . The method according to  claim 1 , wherein the IL-13 antagonist has an in vivo half-life of about 21 days. 
     
     
         15 . The method according to  claim 1 , 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, and   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.