Antibodies that bind il-4 and/or il-13 and their uses

Abstract

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

1 - 49 . (canceled) 
     
     
         50 . A bispecific antibody or bispecific antibody fragment thereof that specifically binds to IL-13 and IL-4,
 wherein the bispecific antibody or bispecific antibody fragment thereof comprises two light chains and two heavy chains;   wherein the light chains comprise an outer variable light chain domain linked to an inner variable light chain domain which is linked to a constant light chain domain (CL), and the heavy chains comprise an outer variable heavy chain domain linked to an inner variable heavy chain domain which is linked to a constant heavy chain domain (CH1); and   wherein:   (a) the outer variable light chain domain comprises the amino acid sequence of SEQ ID NO: 1, the inner variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the outer variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2 and the inner variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 4;   (b) the outer variable light chain domain comprises the amino acid sequence of SEQ ID NO: 1 the inner variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the outer variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2, and the inner variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 5;   (c) the outer variable light chain domain comprises the amino acid sequences RASESVDSYGQSYMH (SEQ ID NO: 8), LASNLES (SEQ ID NO: 9), and QQNAEDSRT SEQ ID NO: 10 the inner variable light chain domain comprises the amino acid sequences HASQNIDVWLS (SEQ ID NO: 14), KASNLHTG (SEQ ID NO: 15), and QQAHSYPFT (SEQ ID NO: 16), the outer variable heavy chain domain comprises the amino acid sequences GFSLTDSSIN (SEQ ID NO: 11), DGRID (SEQ ID NO: 12), and DGYFPYAMDF (SEQ ID NO: 13), and the inner variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (SEQ ID NO: 17), IDPSDGETR (SEQ ID NO: 18), and LKEYGNYDSFYFDV (SEQ ID NO: 19); or   (d) the outer variable light chain domain comprises the amino acid sequences RASESVDSYGQSYMH (SEQ ID NO: 8), LASNLES (SEQ ID NO: 9), and QQNAEDSRT (SEQ ID NO: 10) the inner variable light chain domain comprises the amino acid sequences HASQNIDVWLS (SEQ ID NO: 14), KASNLHTG (SEQ ID NO: 15), and QQAHSYPFT (SEQ ID NO: 16), the outer variable heavy chain domain comprises the amino acid sequences GFSLTDSSIN (SEQ ID NO: 11), DGRID (SEQ ID NO: 12), and DGYFPYAMDF (SEQ ID NO: 13), and the inner variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (SEQ ID NO: 20), IDASDGETR (SEQ ID NO: 21), and LKEYGNYDSFYFDV (SEQ ID NO: 22).   
     
     
         51 - 54 . (canceled) 
     
     
         55 . The bispecific antibody or bispecific antibody fragment thereof of  claim 50  that further comprises additional constant region domains. 
     
     
         56 . The bispecific antibody or bispecific antibody fragment thereof of  claim 55 , wherein the additional constant region domains are C H2  and C H3 . 
     
     
         57 . A pharmaceutical composition comprising the bispecific antibody or bispecific antibody fragment thereof of  claim 50  and a pharmaceutically acceptable carrier. 
     
     
         58 . The bispecific antibody or bispecific antibody fragment thereof of  claim 50  that is further conjugated to an effector molecule. 
     
     
         59 . The bispecific antibody or bispecific antibody fragment thereof of  claim 58 , wherein the effector molecule is selected from the group consisting of heterologous polypeptides, drugs, radionucleotides, and toxins. 
     
     
         60 - 67 . (canceled) 
     
     
         68 . The bispecific antibody or bispecific antibody fragment thereof of  claim 50  comprising a label, wherein the label is a radiolabel, a fluorophore, a chromophore, an imaging agent, or a metal ion. 
     
     
         69 . (canceled) 
     
     
         70 . The bispecific antibody or bispecific antibody fragment thereof of  claim 50 , wherein a peptide linker links the outer variable light chain domain to the inner variable light chain domain, and a peptide linker links the outer variable heavy chain domain to the inner variable heavy chain domain. 
     
     
         71 . The bispecific antibody or bispecific antibody fragment thereof of  claim 70 , wherein the peptide linker consists of the amino acid sequence of SEQ ID NO: 6.