ANTIBODIES THAT BIND IL-4 AND/OR IL-13 AND THEIR USES
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.