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 two different antigens, wherein one of the antigens is IL-4, wherein the bispecific antibody or bispecific antibody fragment thereof comprises a first pair of polypeptides and a second pair of polypeptides;
wherein the first pair of polypeptides comprise an outer (N-terminal) variable light chain domain linked to an inner (C-terminal) variable light chain domain which is linked to a constant light chain domain (CL), and the second pair of polypeptides comprise an outer (N-terminal) variable heavy chain domain linked to an inner (C-terminal) variable heavy chain domain which is linked to a constant heavy chain domain (CH1); and wherein:
(a) the outer (N-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, and the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 4;
(b) the outer (N-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, and the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 5;
(c) the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 4;
(d) the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 5;
(e) the outer (N-terminal) variable light chain domain comprises the amino acid sequences of HASQNIDVWLS (SEQ ID NO: 14), KASNLHTG (SEQ ID NO: 15), and QQAHSYPFT (SEQ ID NO: 16), and the outer (N-terminal) 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);
(f) the outer (N-terminal) variable light chain domain comprises the amino acid sequences of HASQNIDVWLS (SEQ ID NO: 14), KASNLHTG (SEQ ID NO: 15), and QQAHSYPFT (SEQ ID NO: 16), and the outer (N-terminal) 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);
(g) the inner (C-terminal) variable light chain domain comprises the amino acid sequences of HASQNIDVWLS (SEQ ID NO: 14), KASNLHTG (SEQ ID NO: 15), and QQAHSYPFT (SEQ ID NO: 16 and the inner (C-terminal variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (SEQ ID NO: 18), and LKEYGNYDSFYFDV (SEQ ID NO: 19); or
(h) the inner (C-terminal) variable light chain domain comprises the amino acid sequences of HASQNIDVWLS (SEQ ID NO: 14), KASNLHTG (SEQ ID NO: 15), and QQAHSYPFT (SEQ ID NO: 16 and the inner (C-terminal variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (SEQ ID NO: 21), and LKEYGNYDSFYFDV SE ID NO: 22).
51 . The bispecific antibody or bispecific antibody fragment thereof of claim 50 that further comprises additional constant region domains.
52 . The bispecific antibody or bispecific antibody fragment thereof of claim 51 , wherein the additional constant region domains consist of C H2 and C H3 .
53 . The bispecific antibody or bispecific antibody fragment thereof of claim 50 that further comprises a label, wherein the label is a radiolabel, fluorophore, chromophore, imaging agent, or metal ion.
54 . The bispecific antibody or bispecific antibody fragment thereof of claim 50 that is further conjugated to an effector molecule.
55 . The bispecific antibody or bispecific antibody fragment thereof of claim 54 , wherein the effector molecule is a heterologous polypeptide, drug, radionucleotide, or toxin.
56 . The bispecific antibody or bispecific antibody fragment thereof of claim 50 , wherein the bispecific antibody or bispecific antibody fragment thereof neutralizes IL-4 activity and preferably neutralizes IL-4 mediated cell proliferation in TF-1 cells.
57 . A nucleic acid molecule encoding the bispecific antibody or bispecific antibody fragment thereof of claim 50 .
58 . A vector comprising the nucleic acid molecule of claim 57 .
59 . A host cell comprising the vector of claim 58 .
60 . A pharmaceutical composition comprising the bispecific antibody or bispecific antibody fragment thereof of claim 50 and a pharmaceutically acceptable carrier.
61 . A method of manufacturing the bispecific antibody or bispecific antibody fragment thereof of claim 50 comprising expressing a nucleic acid molecule encoding the bispecific antibody or bispecific antibody fragment thereof in a suitable host cell.
62 . A kit comprising the bispecific antibody or bispecific antibody fragment thereof of claim 50 and instructions for use.