Novel anti-il13 antibodies and uses thereof

Abstract

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 .