Uses of a dual v region antibody-like protein

Abstract

Uses of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region.

1 . A maximal safe therapeutic dose of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 to a human subject having an area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to real time (AUC last ) from about 433 ug·h/ml to about 14200 ug·h/ml. 
     
     
         2 . A maximal safe therapeutic dose of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 to a human subject having an area under the plasma concentration versus time curve extrapolated to infinity (AUC) from about 459 ug·h/ml to about 670014500 ug·h/ml. 
     
     
         3 . A maximal safe therapeutic dose of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 to a human subject having a maximum plasma concentration observed (C max ) from about 0.717 ug/ml to about 28.7 ug/ml. 
     
     
         4 . A maximal safe therapeutic dose of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 to a human subject having a first time to reach a maximum plasma concentration (t max ) from about 96 hr to about 168 hr. 
     
     
         5 . A method monitoring whether a therapeutic dose of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 administered to a human subject is safe, said method comprising:
 (a) administering said therapeutic dose of said dual V region antibody-like protein or a fragment of a dual V region antibody-like region to said human subject;   (b) measuring one or more events selected from the group consisting of intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions, alanine aminotransferase (ALT) >3×upper limit of normal range (ULN) associated with total bilirubin >2×ULN, asymptomatic ALT increase >10×ULN, development of drug dependency or drug abuse, ALT increase ≥2×ULN, hsCRP >10 mg/L for ≥72 hours, cardiac troponin I (cTnI) >2×ULN, a ventricular depolarization and repolariztion time (QT) on an electrocardiogram (ECG) machine wherein the QT is automatically corrected by the ECG machine (QTc) that is QTc ≥500 ms and severe skin reactions local to the site of IP injection; and   (c) determining one or more said events as measured in (b) has occurred wherein said therapeutic dose is identified as not safe and the therapeutic dose is discontinued or lowered.   
     
     
         6 . A method of selecting a safe therapeutic dose or of monitoring the safe use of a therapeutic dose of dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 to a human subject, said method comprising:
 (a) administering a dose of said dual V region antibody-like protein or a fragment of a dual V region antibody-like region to said human subject;   (b) measuring a level of C-reactive protein (CRP) in a blood sample from said human subject; and   (c) determining said level of C-reactive protein (CRP) is less than 20 mg/L as measured in (b)
 wherein said dose is selected as said safe therapeutic dose to be administered to said human subject. 
   
     
     
         7 . A method of selecting a safe therapeutic dose or of monitoring the safe use of a therapeutic dose of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region that specifically binds to IL-4 and IL-13 to a human subject, said method comprising:
 (a) administering a dose of said dual V region antibody-like protein or a fragment of a dual V region antibody-like region to said human subject;   (b) measuring a ventricular depolarization and repolariztion time (QT) on an electrocardiogram (ECG) machine wherein the QT is automatically corrected by the ECG machine (QTc) of said human subject; and   (c) determining said QTC is less than 500 ms as measured in (b)   wherein said dose is selected as said safe therapeutic dose to be administered to said human subject.   
     
     
         8 . The method of any one of the preceding claims, wherein the dual V region antibody-like protein or the fragment of a dual V region antibody-like region comprises a variable light chain comprising amino acid sequences SEQ ID NO:1 and SEQ ID NO: 3 and a variable heavy chain comprising amino acid sequences SEQ ID NO:2 and SEQ ID NO: 4. 
     
     
         9 . The method of any one of the preceding claims, wherein the dual V region antibody-like protein or the fragment of a dual V region antibody-like region comprises a peptide linker such that SEQ ID NO:1 and SEQ ID NO:3 are linked together with the peptide linker and SEQ ID NO:2 and SEQ ID NO:4 are linked together with the peptide linker. 
     
     
         10 . The method of any one of the preceding claims, wherein the peptide linker consists of SEQ ID NO: 6. 
     
     
         11 . The method of any one of the preceding claims, wherein the therapeutic dose is equal to or less than about 300 mg. 
     
     
         12 . The method of any one of the preceding claims, wherein the therapeutic dose is selected from the group consisting of 10 mg, 20 mg, 40 mg, 80 mg, 150 mg and 300 mg.