NOVEL ANTI-IL13 ANTIBODIES AND USES THEREOF
The present invention relates to anti-IL13 antibodies that bind specifically and with high affinity to both glycosylated and non-glycosylated human IL13, does not bind mouse IL13, and neutralize human IL13 activity at an approximate molar ratio of 1:2 (MAb:IL13). The invention also relates to the use of these antibodies in the treatment of IL13-mediated diseases, such as allergic disease, including asthma, allergic asthma, non-allergic (intrinsic) asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, eczema, urticaria, food allergies, chronic obstructive pulmonary disease, ulcerative colitis, RSV infection, uveitis, scleroderma, and osteoporosis.
1 - 61 . (canceled)
62 . An antibody that binds human IL-13, wherein said antibody binds to an epitope comprising the sequence ESLINVSG (SEQ ID NO: 18) or YCAALESLINVS (SEQ ID NO:19).
63 . The antibody of claim 62 , wherein the antibody comprises CDRH1, CDRH2 and CDRH3 with the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively.
64 . The antibody of claim 62 , wherein the antibody comprises CDRL1, CDRL2 and CDRL3 with the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
65 . The antibody of claim 63 , wherein the antibody comprises CDRL1, CDRL2 and CDRL3 with the sequences of SEQ ID NO: 99, SEQ ID NO: 104 and SEQ ID NO: 115, respectively.
66 . The antibody of claim 62 , wherein said antibody comprises:
(1) a CDRH1 having the amino acid sequence of SEQ ID NO: 117, 118, 119, 120, 121 or 122;
(2) a CDRH2 having the amino acid sequence of SEQ ID NO: 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133 or 134; and
(3) a CDRH3 having the amino acid sequence of SEQ ID NO: 135, 136, 137, 138, 139, 140 or 141.
67 . The antibody of claim 62 , wherein said antibody comprises the amino acid sequence of SEQ ID NO: 4, 143, 145, 146, 147, 148 or 149.
68 . The antibody of claim 62 , wherein said antibody comprises:
(1) a CDRL1 having the amino acid sequence of SEQ ID NO: 99, 100, 101, 102, or 103;
(2) a CDRL2 having the amino acid sequence of SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, or 114; and
(3) a CDRL3 having the amino acid sequence of SEQ ID NO: 115 or 116.
69 . The antibody of claim 62 , wherein said antibody comprises the amino acid sequence of SEQ ID NO: 3, 142, 144 or 150.
70 . The antibody of claim 62 , wherein said antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 3, 142, 144 or 150; and said antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 4, 143, 145, 146, 147, 148 or 149.
71 . The antibody of claim 62 , wherein the antibody is an IgG antibody.
72 . The antibody of claim 71 , wherein the antibody is an IgG1, an IgG2, an IgG3 or an IgG4 antibody.
73 . The antibody of claim 62 , wherein the antibody is humanized.
74 . The antibody of claim 62 , wherein the antibody is an antibody fragment.
75 . The antibody of claim 62 , wherein the antibody is a single chain antibody or a single domain antibody.
76 . A method for treating asthma in a patient, comprising administering to a patient in need thereof an effective amount of the antibody of claim 62 .
77 . A method for treating an inflammatory disease in a patient, comprising administering to a patient in need thereof an effective amount of the antibody of claim 62 .
78 . The method of claim 76 , wherein the antibody is humanized.
79 . The method of claim 77 , wherein the antibody is humanized.
80 . The method of claim 76 , wherein the effective amount is between 0.1 mg/kg and 20 mg/kg.
81 . The method of claim 77 , wherein the effective amount is between 0.1 mg/kg and 20 mg/kg.
82 . A pharmaceutical composition comprising the antibody of claim 62 .
83 . A pharmaceutical composition comprising the antibody of claim 73 .
84 . The antibody of claim 62 , wherein said antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 142, and a heavy chain comprising the amino acid sequence of SEQ ID NO: 143.
85 . A hybridoma cell line that produces the antibody of claim 62 .
86 . A DNA sequence encoding a heavy chain of an antibody or a fragment thereof that binds human IL-13, wherein said antibody binds to an epitope comprising the sequence ESLINVSG (SEQ ID NO: 18) or YCAALESLINVS (SEQ ID NO:19).
87 . A DNA sequence encoding a light chain of an antibody or a fragment thereof that binds human IL-13, wherein said antibody binds to an epitope comprising the sequence ESLINVSG (SEQ ID NO: 18) or YCAALESLINVS (SEQ ID NO:19).
88 . The DNA sequence of claim 86 which encodes a heavy chain or a fragment thereof comprising:
(1) a CDRH1 having the amino acid sequence of SEQ ID NO: 117, 118, 119, 120, 121 or 122;
(2) a CDRH2 having the amino acid sequence of SEQ ID NO: 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133 or 134; and
(3) a CDRH3 having the amino acid sequence of SEQ ID NO: 135, 136, 137, 138, 139, 140 or 141.
89 . The DNA sequence of claim 87 which encodes a light chain or a fragment thereof comprising:
(1) a CDRL1 having the amino acid sequence of SEQ ID NO: 99, 100, 101, 102, or 103;
(2) a CDRL2 having the amino acid sequence of SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, or 114; and
(3) a CDRL3 having the amino acid sequence of SEQ ID NO: 115 or 116.
90 . The DNA sequence of claim 86 which encodes a heavy chain or a fragment thereof comprising the amino acid sequence of SEQ ID NO: 4, 143, 145, 146, 147, 148 or 149.
91 . The DNA sequence of claim 87 which encodes a light chain or a fragment thereof comprising the amino acid sequence of SEQ ID NO: 3, 142, 144 or 150.
92 . A vector comprising the DNA sequence of claim 86 .
93 . A host cell comprising the vector of claim 92 .
94 . A vector comprising the DNA sequence of claim 87 .
95 . A host cell comprising the vector of claim 94 .