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 method of treating an IL-4 and/or IL-13 mediated disease in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a bispecific antibody or bispecific antibody fragment that specifically binds to IL-13 and 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 an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4;
(b) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is that are at least 95% identical to the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 5;
(c) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2; or
(d) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 5, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.
51 . The method of claim 50 , wherein the IL-4 and/or IL-13 mediated disease is an allergic disease, cancer, asthma, a disease associated with abnormal production of IL-4 and/or IL-13, an autoimmune disease, scleroderma, or idiopathic pulmonary fibrosis.
52 . A method of suppressing a TH-2 mediated response in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a bispecific antibody or bispecific antibody fragment that specifically binds to IL-13 and 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 an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4;
(b) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is that are at least 95% identical to the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 5;
(c) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2; or
(d) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 5, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.